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1. Injury of the nerve passing with anterior bial artery causes what of the following: a- loss of planter flexion of the foot b- foot drop c- loss of sensations at the foot and leg d- loss of sensations at the sole 2. One of the following structures crosses the bifurcation of common carotid artery:a- common facial vein b- vagus nerve c- hypoglossal nerve d- recurrent laryngeal nerve
The common facial vein branch of the internal jugular vein marks the site of the carotid bifurcation. After dividing the facial vein, the internal jugular vein is retracted posteriorly to expose the carotid bifurcation. The hypoglossal nerve crosses the vessels superior to the bifurcation.
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3. One of the following muscles present at the deep posterior group of the leg: a- soleus b- gastrocnemius c- popliteus d- tibialis anterior 4. One of the following muscles present at the superfascial posterior group of the leg:a-soleus b- Flexor digitorum c- tibialis posterior d- popliteus
Muscles of the Posterior Fascial Compartment of the Leg Superficial Group Gastrocnemius
Plantaris
Soleus
Deep Group Popliteus
Flexor digitorum longus Flexor hallucis longus
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Tibialis posterior
5. One of the structures that present during exposure of the subclavian artery at supraclavicular approach:a- scalenus posterior muscle b- recurrent laryngeal nerve c- phrenic nerve d- hypoglossal nerve
Branches of Subclavian artery •1st part 1. The vertebral artery 2. The thyrocervical trunk: (a) inferior thyroid artery (b) transverse cervical artery (c) suprascapular artery 3. The internal thoracic artery •2nd part :- the costocervical trunk (supplying deep structures of the neck via its deep cervical branch, and the superior intercostal artery, which gives off the 1st and 2nd posterior intercostal arteries). •3rd part gives no constant branch.
Branches of Axillary artery 1st part: 2nd part: 3rd part:
1. superior thoracic artery 1. acromiothoracic artery 2. lateral thoracic artery 1. subscapular artery 2. anterior circumflex humeral artery 3. posterior circumflex humeral artery
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6. The vertebral artery is divided into V1, V2, V3, and V4, V4 passes through a- intracranial b- from the origin ll C6 c- from C6 ll C2 d- from C1 to the dura
Vertebral Artery
Internal Carotid Artery
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7. Which of the following is a branch from axillary artery:a- vertebral artery b- thoraco-acromial artery c- costocervical trunck d- superior thyroid 8. The commonest vein anomaly is in:a- right renal vein b- left renal vein c- SVC d- IVC Left renal vein anomalies or variants:circumaortic and retroaortic IVC anomalies:duplication, left IVC and absent hepatic portion The left vertebral artery is usually larger and carries more blood.
9. The most common site for embolus impaction is in:a- common femoral artery b- popliteal artery c- iliac bifurcation d- aortic bifurcation 10. The most common site for peripheral aneurysm is:a- external iliac artery b- common femoral artery c- superficial femoral artery d- popliteal artery 11. ABI is more than 1 in the following disease:a- Burger disease b- Raynaud,s disease c- Diabetes patient d- Cardiac patient 12. Liga on of left renal vein during AAA repair can cause:a- frequently asymptomatic b- 20% renal failure c- 5% renal dysfunc on d- should be avided
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13. Valves of the lower limb veins are composed of :a- 3 leaflets b- intima only c- intima and media d- intima, media and adventitia
Risk Factors for AAA
A type I endoleak (periprosthetic) occurs at the proximal or distal attachment zones (or at both). A type II endoleak is caused by retrograde flow from patent lumbar or inferior mesenteric arteries. A type III endoleak arises from a defect in the graft fabric, an inadequate seal, or disconnection of modular graft components. A type IV endoleak is due to graft fabric porosity, which often results in a generalized mild blush of contrast material within the aneurysm sac. -٧-
14. in AAA incidence in first degree rela ves:a- 5 – 15% b- 3 – 5% c- 10 – 20% d- more than 20% (NB in Rutherford 15 – 25%) N.B. Although popliteal aneurysms are the most common aneurysms of the lower extremity and account for 70% of all lower extremity aneurysms, they are rela vely uncommon. Popliteal artery aneurysm is almost exclusively a disease of men. Contralateral aneurysms were found in 50% and aor c aneurysms in 36%.
Takayasu arteritis can be divided into the following 6 types based on angiographic involvement : Type I - Branches of the aortic arch Type IIa - Ascending aorta, aortic arch, and its branches Type IIb - Type IIa region plus thoracic descending aorta Type III - Thoracic descending aorta, abdominal aorta, renal arteries, or a combination Type IV - Abdominal aorta, renal arteries, or both Type V - Entire aorta and its branches Classification criteria The American College of Rheumatology has established classification criteria for Takayasu arteri s (3 of 6 criteria are necessary). The presence of any 3 or more criteria yields a sensi vity of 90.5% and a specificity of 97.8%. The criteria are as follows: • • • • • •
Age of 40 years or younger at disease onset Claudication of the extremities Decreased pulsa on of 1 or both brachial arteries Difference of at least 10 mm Hg in systolic blood pressure between arms Bruit over 1 or both subclavian arteries or the abdominal aorta Arteriographic narrowing or occlusion of the entire aorta, its primary branches, or large arteries in the upper or lower extremities that is not due to arteriosclerosis, fibromuscular dysplasia, or other causes.
Patterns of disease have also been described by geographic region. Stenotic lesions are thought to be more common in Japan, whereas aneurysmal disease is more frequent in India,Thailand, and Mexico. Cardiac manifestations of TA are common. Coronary artery involvement occurs in 6% to 16% of patients with TA and may lead to ischemic symptoms or congestive heart failure. Hypertension is one of the most common presenting signs in patients with TA and occurs in 33% to 60% of pa ents. Bilateral stenosis of the subclavian arteries occurs in up to 92% of patients with TA and can mask hypertension. Blood pressure measurements of both upper and lower extremities should be performed in any patient suspected of having TA. Congestive heart failure is the most common cause of death in patients with TA.
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Classification of Takayasu’s Arteritis
15. The least presentation of AAA is:a- colonic obstruction b- hematuria and hydronephrosis c- vomiting of bile d- massive GIT bleeding 16. Warfarin's anticoagulant effect is inhibited by one of these drugs a- ciprofloxacin b- metronidazole c- rifampicin d- propranolol N.B. The commonest cause of renal fistula is kidney biopsy.
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Statins Statins decrease hepatic cholesterol synthesis, leading to the upregulation of LDL receptors on the surface of hepatocytes. This increase in hepatocyte LDL receptors results in increased clearance of LDL cholesterol particles from the serum, ultimately lowering total serum LDL cholesterol levels.
Adverse Effects a. 1.4% incidence of elevated hepa c transaminases, Dose-dependent phenomenon that is usually reversible b. Myopathy (myalgias, myositis, rhabdomyolysis) c. Incident diabetes d. Neuropathies e.Hemmorhagic stroke f. memory loss When the FDA approved the first sta ns in the late 1980s, doctors were told to do periodic blood tests on anyone taking a statin to look for early signs of liver trouble. Millions of statin users later, it’s clear that liver damage is extremely rare. It also can’t be predicted by checking liver tests every few months. The FDA now says that you should have a liver function test soon after starting to take a statin or after switching to a new one. If everything is fine, no further blood test is needed unless a problem arises. 16. One of the following concerned to sta ns a- the pa ent must check for liver func ons at 3,6,9 months b- follow up for GB function c- can cause myopathy
Angiotensin Converting Enzyme Inhibitors Adverse Effects Hypotension Renal Insufficiency (if bilateral renal artery stenosis) Hyperkalemia – special group of patients (Na restricted, on K-sparing diuretic, COX inhibitors) Cough (20 %) Angioedema With captopril especially: neutropenia, nephrotic syndrome, skin rash, taste disturbances (SH group- related).
Therapeutic Uses Anti-hypertensive Prevent or reverse LVH Protect against sudden death and second myocardial infarction after acute MI Improve survival and hemodynamics in patients with congestive heart failure Protect against progression of diabetic and non-diabetic nephropathy
Additional Beneficial Effects of ACE Inhibitors:Cardioprotective Reduce incidence of second heart attack Reduce cardiovascular complications in patients with risk factors Reduce incidence of diabetes in high risk patients Reduce complications in diabetic patients - ١٠ -
17. ACE inhibitors are effective treatment in patients with PVD, in all except:a- good control of hypertension b- control of CHF c- improve renal function in renal artery stenosis d- decreases risk of MI 18. Self expanding stents, All are correct except:a- precise placement site b- used in tortuous arteries c- foreshortening on deployment d- overriding 19. During excision of carotid body tumor more than 5 cm, to decrease intra-operative bleeding do:a- preoperative radiotherapy b- balloon in CCA c- preoperative embolization of ECA 20. Caro d duplex for heterogenous plaques, can show all except:a- hemorrhage b- necrosis c- calcification d- ulceration 21. Smoking affect bleeding profile through:a- increase of blood viscosity b- decrease in bleeding time c- increase in coagulation time d- increase in platelet function and platelet aggregation POPLITEAL ARTERY ENTRAPMENT SYNDROME This is a rare disorder with an es mated prevalence of 0.16% that occurs with a male-to female ra o of 15:1. Concomitant popliteal vein impingement occurs in up to 30%. Twenty-five percent of cases are bilateral. Five types of anatomic entrapment have been defined:I Popliteal artery is displaced medially around a normal medial head of the gastrocnemius II Medial head of gastrocnemius, which arises lateral to popliteal artery III Popliteal artery is compressed by an accessory slip of muscle form the medial head IV Entrapment by a deeper popliteus muscle V Any of the above plus popliteal vein VI Functional entrapment Noninvasive studies with ankle-brachial indices should be performed with the knee extended and the foot in a neutral, forced plantar, and dorsiflexed position. A drop in pressure of 50% or greater or dampening of the plethysmographic waveforms in plantar or dorsiflexion is a classic finding. Although CT and MRI have been used, angiography remains the most widely used test. Angiography performed with the foot in a neutral position may demonstrate classical medial deviation of the popliteal artery or normal anatomic positioning. Coexisting abnormalities may include stenosis, luminal irregularity, delayed flow, aneurysm, or complete occlusion. Diagnostic accuracy is increased with the use of ankle stress view–active plantar flexion and passive dorsiflexion. The treatment of popliteal artery entrapment consists of surgical decompression of the impinged artery with possible arterial reconstruction.
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Range of diameters of normal arteries in adults.
Aneurysms in children are uncommon, tend to be congenital, and usually involve the aorta. They are associated with a variety of anomalies, such as tuberous sclerosis, aortic coarctation, and Marfan’s syndrome. Aneurysms due to Developmental Anomalies:1. persistent scia c arteries 2. aberrant right subclavian artery and an associated Kommerell diver culum. Common femoral artery aneurysms are most commonly pseudoaneurysms that occur after percutaneous arterial puncture. Popliteal aneurysms are the most common peripheral aneurysms. Visceral Aneurysms The most common of the visceral artery aneurysms is renal, and they represent 0.3% of aneurysm repairs overall in our series versus 0.1% for the other visceral vessels. Renal artery aneurysms are associated with fibromuscular dysplasia, arteritis, and dissections, although they are most commonly “degenerative.”
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The splenic and mesenteric arteries are most commonly affected by aneurysm, followed by the hepatic and celiac vessels. Visceral aneurysms can also occur in association with diseases such as polyarteritis nodosa. Splanchnic artery aneurysms splenic artery, 60% hepa c artery, 20%; SMA, 6%; celiac artery, 4%. Splenic artery aneurysms, the most common type of splanchnic aneurysm, occur predominantly in women during the sixth decade of life. Infected aneurysms
Infected aortoiliac aneurysms
The most prevalent form of infected aneurysm was a post-traumatic infected false aneurysm, the predominant infec ng organism has been S. aureus (30%). The predominant microorganisms associated with microbial arteritis leading to aneurysms are Escherichia coli and Salmonella and Staphylococcus species.
Incidence of Cranial Nerve Dysfunction after Carotid Endarterectomy
22. 50% stenosis of an artery deno ng reduc on of the cross-sectional area of the artery by:- a- 50% b- 75% c- 90% d- 25%
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Estimation of Internal Carotid Artery Stenosis. A PSV of 125 cm/sec recorded from a proximal diseased ICA segment is the threshold for greater than or less than 50% stenosis.
Artery Diameters and Peak Systolic Velocities in Healthy Subjects
Duplex Classification of Peripheral Artery Occlusive Disease
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23.The following test does not need to be checked before conven onal angiography:a- bleeding time b- PTT c- PT d- platelet count
Aspirin Aspirin irreversibly acetylates the active site of cyclooxygenase, which is required for the produc on of thromboxane A2, a powerful promoter of platelet aggrega on. An platelet therapy, principally with aspirin, reduced stroke by about 25%. Antiplatelet therapy, principally with aspirin, increases the absolute risk of hemorrhagic stroke by 3 per 10,000 treated pa ents. Additive Benefits of Aspirin and Statins in Secondary Prevention of CVD. Aspirin reduces risk of a first myocardial infarction by about 1/3 but un l then any decision to use aspirin in primary prevention should be an individual clinical judgement by the healthcare provider. Aspirin and clopidogrel are not licensed for primary prevention. For Secondary Prevention of CVD Clopidogrel monotherapy should not be used first-line, but can be considered for patients with aspirin hypersensitivity. Possible Additional Beneficial Mechanisms of Action of Higher Doses of Aspirin on CVD Enhance nitric oxide formation,Decrease inflammation and Stabilize enadothelial function. New data show that when clopidogrel and omeprazole are taken together, the effectiveness of clopidogrel is reduced. Patients at risk for heart attacks or strokes who use clopidogrel to prevent blood clots will not get the full effect of this medicine if they are also taking omeprazole. - ١٥ -
Platelet activation leads to platelet aggregation. Various classes of antiplatelet therapies act by disparate mechanisms to reduce platelet activation and clot formation. Aspirin inhibits platelet aggrega on by inhibi ng the produc on of thromboxane A2. The thienopyridines, clopidogrel and ticlopidine, bind and inhibit adenosine diphosphate (ADP) receptors on platelets thereby inhibiting glycoprotein IIb/IIIa-receptor activation and preventing platelet aggregation. Dipyridamole interferes with platelet stimulating factors like collagen through various mechanisms including the inhibition of phosphodiesterase and inhibition of cellular uptake of adenosine. Dipyridamole may also cause vasodilation. Dipyridamole is currently available in two forms: An immediate-release form, usually given as 50 to 100 mg three mes per day A proprietary formula on containing both aspirin (25 mg) plus extended-release dipyridamole (200 mg), given two mes per day. Headache is a well known side effect of dipyridamole and also may cause Gastric upset and/or diarrhea. American College of Cardiology/American Heart Association guideline for the management of patients with chronic stable angina recommend avoidance of dipyridamole in patients with stable angina.
Glycoprotein IIb/IIa inhibitors directly interfere with platelet binding of fibrinogen, the final step in platelet aggregation. The thienopyridines, clopidogrel and ticlopidine, selec vely and irreversibly bind P2Y12, one of the adenosine diphosphate (ADP) receptors on platelets. This binding inhibits ADPinduced platelet glycoprotein IIb/IIIa-receptor activation and prevents platelet aggregation. Side effects of ticlopidine : The most serious complication of ticlopidine therapy is severe neutropenia, which occurs in approximately 1 percent of pa ents. Thus, for the first three months of treatment, patients must undergo biweekly complete blood counts. This side effect limits the utility of ticlopidine. Other common side effects, which occur more frequently with ticlopidine than aspirin, are rash and diarrhea.
Cilostazol
The antiplatelet agent cilostazol is a phosphodiesterase 3 inhibitor that is
used mainly for intermittent claudication in patients with peripheral artery disease and also significantly reduced the risk of stroke . 24. Mechanism of ac on of Clopidogrel is :a- inhibits AMP b- inhibition of phosphodiesterase c- inhibition of cyclooxygenase d- inhibits ADP-induced platelet glycoprotein IIb/IIIa-receptor activation 25. Classifica on used in caro d body tumor:a- Charlls classification b- Debakey classification c- Shamblin classification d- Levels classification
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26. For the pa ent with the following angiography, the procedure of choice is:-
a- carotid-subclavian bypass b- aorta-subclavian bypass c- subclavian endarterectomy d- Percutaneous angioplasty and stenting
Subclavian steal syndrome The term "subclavian steal" refers to a phenomenon of flow reversal in the vertebral artery ipsilateral to a hemodynamically significant stenosis or occlusion of the subclavian artery. In most cases, subclavian steal is asymptomatic, does not warrant invasive evaluation or treatment, and represents an appropriate physiological response to proximal arterial disease. Subclavian steal syndrome implies the presence of significant symptoms due to arterial insufficiency in the brain (ie, vertebrobasilar insufficiency) or upper extremity which are supplied by the subclavian artery.
Coronary-subclavian steal A coronary-subclavian steal phenomenon has been described in patients who have undergone prior coronary artery bypass surgery (CABG) utilizing the internal mammary artery (IMA). In the presence of a hemodynamically significant subclavian artery stenosis proximal to the origin of the ipsilateral IMA, flow through the internal mammary artery may reverse and "steal" flow from the coronary circulation during upper extremity exercise. Coronary and graft angiography demonstrate retrograde flow in the involved IMA during selective catheterization of the grafted coronary artery. Simultaneous coronary and cerebrovascular ischemia have also been reported. Identification of a significant subclavian artery stenosis prior to CABG can prevent this important problem. Those patients with a high-grade subclavian artery stenosis should be treated (percutaneously or surgically) prior to CABG.
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ETIOLOGY Atherosclerosis is the most common cause of subclavian steal syndrome which is more common on the left side, possibly due to a more acute origin of the left subclavian artery, resulting in accelerated atherosclerosis from increased turbulence. Other cause Takayasu arteritis Extra-anatomic revascularization (eg, carotid-subclavian bypass, carotid transposition) is the most common form of surgical correction for symptomatic subclavian artery stenosis. The approach to therapy of subclavian steal associated with symptoms varies with the clinical setting. In many patients, symptoms improve over time without treatment. Interventional treatment is not usually warranted in patients with asymptomatic subclavian stenosis/occlusion. Symptomatic patients with proximal subclavian artery ulcerative occlusive disease complicated by embolization, in the absence of other significant cerebrovascular disease, can be successfully treated by surgical removal or exclusion of the proximal subclavian lesion. Percutaneous angioplasty and stenting (with embolic protection) for embolism related to proximal subclavian artery is appropriate for patients with short stenosis/occlusion at the origin of the subclavian artery.
AAA Rupture risk is directly related to aneurysm size. Acute expansion is considered an immediate precursor of rupture. A triad of chronic abdominal pain, weight loss, and elevated erythrocyte sedimentation rate in a patient with an AAA is highly suggestive of an inflammatory aneurysm, occur predominantly in males in the 5th and 6th decades of life. The diagnosis is made preopera vely on abdominal CT scan in approximately 50% of pa ents. The treatment of IAAA is resection and grafting. Ureterolysis is fraught with danger and seldom indicated. Administration of beta-blocking medications may offer the first effective nonsurgical therapy for AAA. The classic triad of abdominal pain, cardiovascular collapse and a pulsatile abdominal mass may often be present in patients with ruptured AAA.
Stent Characteristics
Ballon- expandable stents are the preferred choice for eccentric, heavily calcified lesions. Self- expanding stents may require postdilation, not for ostial lesions but can be used for tortuous arteries.
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Carotid body tumor The carotid body is a collection of chemoreceptor cells in the adventitia of carotid bifurcation for control of Ph, and is supplied by ascending pharyngeal artery from ECA and Glossopharyngeal nerve .The commonest type of cervical paraganglionoma, derived from neural crest ectoderm, occurs in the fourth and fifth decades. Caro d body tumor occurs more in femals, 5% bilateral, 5% locally malignant 5% systema cally malignant, 10% familial, 1% of neck tumors. The risk of malignancy is greatest in young patients with familial tumors.
Diagnostic Evaluation Carotid body tumors are usually detected by clinical examination, and the diagnosis is confirmed by basic imaging. Diagnostic biopsy is avoided because paragangliomas are so highly vascular, rarely malignant, and easily diagnosed with routine imaging modalities. Ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI) are all effective for diagnosis; bilateral imaging is advocated to rule out multicentricity. On ultrasound examination, carotid body tumors usually appear as solid, well-defined, hypoechoic, hypervascular masses that characteristically splay the carotid bifurcation. The tumor itself may exhibit a very active mixed signal pattern representing the extensive vascularity of the tumor. MRI and CT show a hypervascular tumor that does not invade the carotid. Positron emission tomography is being used to diagnose paragangliomas with a diameter of less than 1 cm and may be helpful in diagnosing small or mul centric tumors.
Selective carotid angiogram demonstrating the classic characteristics of a carotid body tumor. The bifurcation is widened by the tumor; note the contrast density of the “tumor blush,” which illustrates the highly vascular nature of these tumors. N.B. Glomus vagale causes splaying of ICA and ECA.
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Shamblin’s classification of carotid body tumors based on the degree of difficulty of resection. Type I tumors are localized and easily resected. Type II tumors include tumors adherent to or partially surrounding vessels. Type III tumors intimately surround or encase the vessels and nerves. ECA, external carotid artery; ICA, internal carotid artery.
Treatment Resection in subadventitial plane Conservative in old age with small lesion Preoperative embolization of ECA or covered stent within the first few centimeters of ECA Recurrence 5%.
Risk Factors for AAA rupture Available data suggest that, For a given sized AAA, female gender, hypertension, COPD, current smoking status, and wall stress seem to be independent risk factors for rupture. Family history for AAA and rapid expansion are probably risk factors for rupture, whereas the influence of thrombus content and diameter ratio are less certain. Other factors:-DM eccentric or saccular aneurysms. Large AAA diameter and hypertension should increase wall tension and rupture risk. maximum Transverse diameter remains the standard method of risk assessment for aneurysm rupture. - ٢٠ -
GRADING OF CAROTID DISEASE B-mode imaging is the most appropriate method to evaluate the degree of narrowing, if the degree of lumen diameter reduc on is less than 50%. In the ECST trial, the degree of stenosis was measured by comparing the residual lumen diameter with the estimated diameter of the carotid bulb, whereas the NASCET trial compared the residual lumen diameter with the diameter of the normal distal ICA.
The percentage diameter reduction can be estimated from diameter measurements as follows:
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Classification of lower extremity arterial stenosis
Classification of renal artery stenosis
Bypass Graft Failure 1. 2. 3. 4.
<30 days technical error, hypercoagulable state, or inadequate outflow 1- 6 months residual lesion 6 -24 months myoin mal hyperplasia >24 months progression of atherosclerosis
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Observable characteristics of venous thrombus
27. Pa ent with aorto-iliac occlusive disease, angiography revealed bilateral external iliac and inferior mesenteric occlusion, the procedure of choice is :a- aorto- bifemoral bypass graft, end of graft to side of aorta b- aorto- bifemoral bypass graft, end of graft to end of aorta c- axillo-bifemaral bypass
Aorto- bifemoral bypass For most patients, an end-to-end aortic anastomosis is preferred for several reasons. First, because all blood flows through the graft, there is less chance of competitive flow through the native aortoiliac vessels that may potentially increase the incidence of graft limb thrombosis. Second, an end-to-end anastomosis is theoretically a hemodynamically superior configuration. It is associated with less perianastomotic turbulence and therefore a smaller likelihood of developing recurrent atheroma or an anastomotic aneurysm. In addition, the end-to-end anastomosis is less likely to cause distal atheromatous embolization and is easier to cover with retroperitoneal tissue after implantation than the end-to-side anastomosis, which tends to protrude anteriorly off the aorta. This consideration may reduce the potential for late graft-enteric fistula formation. End-to-Side Aortic Anastomosis in patients with either a sizable accessory renal artery arising from the infrarenal aorta or a large, patent inferior mesenteric artery. Although these branch vessels may be preserved by reimplanting them into the body of an end-to-end graft, it is clearly easier to achieve this objective with the end-to-side aortic anastomosis that maintains the native antegrade aortic blood flow. More commonly, an end-to-side is used in patients in whom most of their occlusive disease is located in the external iliac arteries. An end-to-side graft configuration that maintains antegrade pelvic circulation via the hypogastric systems is clearly desirable in these circumstances. 28. For stenting of SFA after balloon angioplasty, the following is true:a- indicated if there is a small dissection. b- stenting is done every time after PTA c- if there is a remaining stenosis more than 30%
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29. 9 months aUer femoro-popliteal bypass by saphenous vein graft, the most important cause of graft failure is :a- intimal hyperplasia b- technical defect c- progression of the underlying cause d- residual lesion 30. Type I endoleak after EVAR is: a- leak occurs at the proximal or distal attachment zones (or at both). b- caused by retrograde flow from patent lumbar or inferior mesenteric arteries c- leak from defect in graft fabric d- endoleak is due to graft fabric porosity 31. Type II endoleak aUer EVAR is caused by:a- leak occurs at the proximal or distal attachment zones (or at both). b- leak from defect in graft fabric c- leak from collateras d- endoleak is due to graft fabric porosity 32. Duplex findings in caro d body tumor include the following except:a- deviation of both ICA and ECA b- hypoechoic lesion c- intra tumor thrombus d- hypervascular lesion 33. In angiography for proximal subclavian artery stenosis, loss of dye in vertebral artery means :a- improper collaterals from innominate artery b- incomplete circle of Willis c- occluded vertebral artery d- Flow reversal in vertebral artery 34. Sclerosing agents that may cause skin necrosis:a- Sodium tetradecyl sulphate b- Polidocanol c- Sodium morrhuate d- Ethanolamine oleate 35. For good resolu on during angiography and angioplasty for distal lesions :a- increase the rate of dye injection b- increase the dye concentration c- increase sequence d- use of ???? 36. The skin lesion in Lymphangiosarcoma after cancer breast surgery is :a- skin pigmentation b- blue skin nodules c- skin ulceration
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37. In patients with superficial venous reflux, the following is true :a-venous stripping can worse the patient if there is deep venous reflux b- GSF stripping to just below the knee can improve the patient c- Trendelenberg operation is the operation of choice 38. One of the following is concerning the saphenous nerve:a- leaves the GSV at the knee b- enter the saphenous opening with the GSV c- accompanies GSV all through its course till saphenous opening d-supply ankle and foot 39. The most common complica on of long standing lymphedema is:a- Angiosarcoma b- deep venous insufficiency c- pitting edema 40. Male pa ent, 45 years, heavy smoker is showing the following picture, the most possible diagnosis is:-
a- Reynaud's disease b- Burger's disease c- Scleroderma d- Takayasu disease 41. Male pa ent, 50 years, heavy smoker is showing the following angiography
a- Marfan syndrome c- Burger's disease
b- Takayasu disease d- popliteal entrapment - ٢٥ -
42. The most common disease causes congenital aneurysm is:a- Marfan syndrome b- Takayasu disease c- Fibromuscular dysplasia 43. The most common artery affected by Fibromuscular dysplasia is:a- renal artery b- internal carotid artery c- retinal artery d- external iliac artery 44. Clinical picture of Pseudoxanthom elasticum include all except:a- GIT bleeding b- hematuria c- constrictive pericarditis d- ischemic heart disease 45. Absence of pedal pulse on knee flexion occurs in :a- popliteal entrapment b- Burger's disease c- popliteal cystic adventitial disease N.B. Angiography in popliteal cystic adventitial disease Scimitar sign 46. in polytrauma pa ent with vascular injury, the following item mandates direct push to O.R. without investigations:a- palpable thrill at the groin b- history of massive bleeding at scene c- weak pulse if compared to contralateral extremity d- Peripheral nerve deficit 47. Pa ent with gunshot injury at the leg , but there is palpable pulse, the following investigation is needed to exclude vascular injury:a- CT Angiography b- Conventional angiography c- MRA d- Duplex
48. Pa ent with chronic L.L. ischemia operated with synthetic graft for bypass, he can take first generation cephalosporin during:a- as long as IV cannula is present b- during the operation only c- the first 24 hours post-operative
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49. The most common risk factors for AAA rupture, includes all except:a- hypertension b-positive family history for AAA c- male gender d- COPD
50. male pa ent with severe blunt chest trauma with fracture ribs, the following angiography was done , what is the diagnosis?
a- type A aortic dissection b- type B aortic dissection c- descending aortic aneurysm
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51. male pa ent with severe blunt chest trauma, the following angiography was done , what is the diagnosis?
a- Coincedental thoracic aortic aneurysm b- aortic disruption at the aortic isthmus c-injury and leak in right subclavian artery d- injury and leak in innominate artery 52. What is the second most common cause of synthetic graft failure in renal dialysis patients:a- pseudoaneurysm b- infection c- arterial steal d- Thrombosis
Vascular Access Associated Steal Syndrome Constructing vascular access for hemodialysis causes changes in blood flow to the extremity, which can lead to distal ischemia. Ischemic steal syndrome is manifested by pain; weakness; pallor; and, in severe cases, ulceration and tissue loss. Severe ischemia, requiring reintervention, has an incidence of 5%, although some degree of ischemia causing pain or parasthesias occurs in 10% to 20% of pa ents following access construc on. Pathophysiology may be on the basis of inadequate arterial collateral inflow due to occlusive disease, particularly involving the mediumsized vessels, or high flow in a fistula exceeding the inflow capacity in the absence of intrinsic occlusive disease of the inflow arteries. Predicting steal remains difficult, although certain patient characteristics and preoperative techniques can help identify those patients in whom arteriovenous fistulas have an increased risk of causing steal. Patients with - ٢٨ -
diabetes, multiple access procedures, and constructions based on proximal arteries are more prone to ischemia. Operative techniques for correcting steal include arteriovenous fistula ligation, percutaneous transluminal angioplasty, banding or restrictive procedures, and distal revascularization interval ligation or modifications of this technique. Operative intervention for ischemic steal syndrome successfully resolves ischemia in 80% to 95% of pa ents.Some pa ents can have persistent pain despite healing of ulceration. Blood flow can reverse in the distal vascular bed so that retrograde flow will be present in the artery just distal to the fistula in 80% to 90% of all AV fistulas. Reversal of distal arterial flow usually occurs when the diameter of the fistula opening exceeds the diameter of the inflow artery. Distal pulses are frequently diminished or absent. Despite these physiological changes, clinically evident ischemia may not be present. AV grafts typically develop steal immediately following surgery. Ischemia caused by autologous fistulas presents later as the vein matures and dilates, allowing increased blood flow. Compression of the shunt often relieves symptoms temporarily and augments the distal pulse.
Classification of Steal Symptoms in Patients with Arteriovenous Shunts
Treatment 1. DRIL 2. Revision using distal inflow (RUDI). 3. Proximalization of the arterial inflow. 4. Simple ligation of the brachial artery without revascularization. Blood flow distal to the ligation was maintained by collateral blood vessels. 5. Simple arterial bypass graft from the artery just proximal to the fistulas to a site just distal to the fistula (without arterial ligation). Banding, partial suturing, application of a clip, or other methods to restrict shunt diameter remain accepted procedures for reducing blood flow in the graft, although one must be careful because thrombosis frequently complicates this approach.
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53. Cys c medial necrosis (CMN) is associated with :a- Marfan's syndrome b- Turner syndrome c- Dawn syndrome Cystic medial necrosis (CMN) is a disorder of large arteries, in particular the aorta, characterized by an accumulation of basophilic ground substance in the media with cystlike lesions. CMN is known to occur in certain connective tissue diseases such as Marfan syndrome, Ehlers-Danlos syndrome, and annuloaortic ectasia, which usually result from degenerative changes in the aortic wall. The relationships between CMN and congenital heart defects as well as other disorders have been evidenced. 54. Heterogenous caro d plaques by duplex, means all except:a- hemorrhage b- necrosis c- calcification d- ulceration
55. The best management of retrohepa c IVC injuries is :a- IVC ligation b- liver resection and repair c-extensive mobilization of the liver and repair d- perihepatic packing and observation
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IVC Injuries The IVC is the most commonly injured abdominal vessel and accounts for about 25% of abdominal vascular injuries. Blunt trauma is responsible for about 10% of IVC injuries, and it usually involves the retrohepatic part of the vein.
Infrarenal IVC Many injuries to the IVC, especially those involving the infrarenal IVC, present with stable hematomas. As a rule, all hematomas due to penetrating trauma should be explored. An exception to this approach is stable retrohepatic hematomas. The infrarenal and juxtarenal IVC are best exposed by mobilization and medial rotation of the right colon, the hepatic flexure of the colon, and the duodenum. Exposure of the retrohepatic IVC is technically challenging and usually requires extensive mobilization of the liver by dividing its ligaments and extending the incision to include a right subcostal incision, right thoracotomy, or sternotomy. In our experience, a subcostal incision provides excellent exposure and is preferred. A median sternotomy is performed if an atriocaval shunt is anticipated. These additional incisions should be considered only if perihepatic packing is not effective in controlling the hemorrhage. In cases in which packing is not effective and the additional incisions are not sufficient for adequate visualization and repair of the IVC or hepatic veins, other more radical maneuvers may be considered. Such maneuvers include hepatic vascular isolation, an atriocaval shunt, or division of the liver. Hepatic Vascular Isolation. Hepatic vascular isolation involves cross-clamping the infradiaphragmatic aorta, suprahepatic IVC, infrahepatic IVC above the renal veins, and portal triad. 56. Evaluation of carotid shunt function during CEA to ensure that antegrade flow is present :a- carotid stump pressure b- EEG c- Transcranial Doppler d-application of a hand held Doppler probe to the shunt tubing
Interactions of Warfarin with Drugs and Food Many drugs and foods interact with warfarin, including antibiotics, drugs affecting the central nervous system, and cardiac medications. Many of these drug interactions increase warfarin's anticoagulant effect. Warfarin's anticoagulant effect was potentiated by 6 an bio cs (cotrimoxazole, erythromycin, fluconazole, isoniazid, metronidazole, and miconazole); 5 cardiac drugs (amiodarone, clofibrate, propafenone, propranolol, and sulfinpyrazone); phenylbutazone; piroxicam; alcohol (only with concomitant liver disease); cimetidine; and omeprazole. Three patients had a hemorrhage at the time of a potentiating interaction (caused by alcohol, isoniazid, and phenylbutazone). Warfarin's anticoagulant effect was inhibited by 3 an bio cs (griseofulvin, rifampin, and nafcillin); 3 drugs ac ve on the central nervous system (barbiturates, carbamazepine, and chlordiazepoxide); cholestyramine; sucralfate; foods high in vitamin K; and large amounts of avocado. Alcohol increases the metabolism of Warfarin (decreases the effect).
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COAGULATION Antithrombin Antithrombin is a serine protease inhibitor of thrombin and also inhibits factors IXa, Xa, XIa, and XIIa. Thrombin is irreversibly bound by antithrombin and prevents thrombin’s action on fibrinogen, on factors V, VIII, and XIII, and on platelets. This anticoagulant is synthesized in the liver and endothelial cells, and has a half-life of 2.8 days.
Protein C, S and Z Protein C is a vitamin K dependent anticoagulant protein that, once activated by thrombin, will inactivate factors Va and VIIIa, thereby inhibiting the generation of thrombin. Additionally, activated protein C stimulates the release of t-PA. It is produced in the liver and is the dominant endogenous anticoagulant with an eight-hour half-life. Protein S is also a vitamin K dependent anticoagulant protein that is a cofactor to activated protein C. Additionally, protein S appears to have independent anticoagulant function by directly inhibiting procoagulant enzyme complexes. Protein Z Mediates thrombin adhesion to phospholipids and stimulates degradation of factor X by ZPI (Protein Z-related protease inhibitor). Coagulation begins almost instantly after an injury to the blood vessel has damaged the endothelium (lining of the vessel). Exposure of the blood to proteins such as tissue factor initiates changes to blood platelets and the plasma protein fibrinogen, a clotting factor. Platelets immediately form a plug at the site of injury; this is called primary hemostasis. Secondary hemostasis occurs simultaneously: Proteins in the blood plasma, called coagulation factors or clotting factors, respond in a complex cascade to form fibrin strands, which strengthen the platelet plug. It is now known that the primary pathway for the initiation of blood coagulation is the tissue factor pathway. The pathways are a series of reactions, in which a zymogen(inactive enzyme precursor) of a serine protease and its glycoprotein co-factor are activated to become active components that then catalyze the next reaction in the cascade, ultimately resulting in cross-linked fibrin.
Tissue factor pathway (extrinsic)
Following damage to the blood vessel, FVII leaves the circulation and comes into contact with tissue factor (TF which was formerly known as factor III or Thromboplastin) forming an activated complex (TF-FVIIa). TF-FVIIa activates FIX and FX. FVII is itself activated by thrombin, FXIa, FXII and FXa. The activation of FXa by TF-FVIIa is almost immediately inhibited by tissue factor pathway inhibitor (TFPI). FXa and its co-factor FVa form the prothrombinase complex, which activates prothrombin to thrombin. Thrombin then activates other components of the coagulation cascade, including FV and FVIII.
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Contact activation pathway (intrinsic) The contact activation pathway begins with formation of the primary complex on collagen by high-molecular-weight kininogen (HMWK), prekallikrein, and FXII (Hageman factor). Prekallikrein is converted to kallikrein and FXII becomes FXIIa. FXIIa converts FXI into FXIa. Factor XIa activates FIX, which with its co-factor FVIIIa form the tenase complex, which activates FX to FXa. The minor role that the contact activation pathway has in initiating clot formation can be illustrated by the fact that patients with severe deficiencies of FXII, HMWK, and prekallikrein do not have a bleeding disorder. Instead, contact activation system seems to be more involved in inflammation. Patients without FXII (Hageman factor) suffer from constant infections.
Final common pathway Thrombin has a large array of functions. Its primary role is the conversion of fibrinogen to fibrin, the building block of a hemostatic plug.
Cofactors
Calcium Phospholipid Vitamin K
Regulators
Protein C Antithrombin Tissue factor pathway inhibitor (TFPI). Plasmin Prostacyclin (inhibits platelets activation)
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Laboratory Tests of Thrombosis
Hypercoagulable Disorders
Nonlipid Lowering Effects of Statins
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57. Female pa ent with thigh superficial thrombophlebi s, the most proper management:a- surgery b- venous duplex c- antibiotic, anti-inflammatory and compression d- anticoagulation with Warfarin 58. Male pa ent with a venous ulcer of 3 years dura on, duplex revealed incompetent saphenous vein, the treatment should be:a- GSV stripping b- GSV endovenous ablation c- compression d-skin graft
Percutaneous Transluminal Angioplasty in femoropopliteal artery disease Despite the higher immediate success, routine stenting was not associated with a significant reduction in the rate of restenosis or target vessel revascularization (TVR). Current data do not support use of routine stenting as the primary endovascular treatment for short SFPA lesions. TASC II recommends PTA as the initial preferred option for endovascular treatment of symptomatic SFPA lesions, reserving provisional stenting for salvage therapy after a suboptimal or failed result from balloon dilation. Endovascular stenting avoids the problems of early elastic recoil, residual stenosis, and flow-limiting dissection after balloon angioplasty and can thus be used for the treatment of long and calcified lesions. In contrast, SFPA is subject to longitudinal stretching, external compression, torsion, and flexion, which may lead to stent fractures and eventually to restenosis. Immediate technical success after PTA was defined as residual stenosis less than 30% without flow-limiting dissection. PTA with provisional stenting should remain the preferred endovascular therapy for patients with SFPA disease.
Iliac Artery Angioplasty Percutaneous angioplasty is widely used for the treatment of iliac artery occlusive disease. Stent placement is used in lesions not amenable to balloon angioplasty, in complications, and recurrences. Evidence suggests that balloon angioplasty is the procedure of choice for iliac artery occlusive lesions. Stent placement should be reserved for angioplasty failures. However, primary stent placement is indicated in total occlusions. Lesion morphology is an important determinant of immediate success and long-term patency. TASC lesions type A and B are best treated with angioplasty and stenting, while TASC lesions type C and D show better results with surgical treatment. The technical success of the intervention is judged not only by the angiographic appearance, but most importantly by measurement of the pressure gradient across the lesion. Less than 20% residual stenosis and < 10 mm Hg systolic pressure gradient is considered a technical success. When in doubt, the pressures are measured following vasodilator injection distal to the lesion (200 mg of nitroglycerin or 15-25 mg of tolazoline) : more than 15mmHg systolic pressure gradient represents a technical failure. The decision for successful PTA should be based on the translesional pressure gradient measurement ; angiographic criteria are not reliable. - ٣٥ -
Stent placement is indicated to address a technical failure, or a complication of PTA ; heavily calcified and eccentric lesions do not respond to PTA alone. Elastic recoil is another cause of PTA failure. Recurrent stenosis after PTA and flow-limiting dissection are indications for stenting. Primary stenting is the practice of using stents as the initial treatment modality instead of trying to achieve successful results with PTA alone. Chronic occlusions are best managed by primary stenting. In the case of lesions suspected as sources of emboli, stenting is indicated to trap embolic material between the arterial wall and the stent mesh. Nevertheless, the efficacy of this practice still remains unproven.
CEAP Classification of Lower Extremity Chronic Venous Disease
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Historic and New Anatomic Terms of Lower Extremity Veins
Anatomy of the superficial veins of the lower extremity
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Risk Factors for Varicose Veins
Pathophysiology of CVI There are three basic mechanisms that lead to raised AVP and the symptoms and signs of CVI: (1) muscle pump dysfunc on, (2) valvular reflux, and (3) venous obstruc on. Reflux is present in more than 90% of pa ents with CVI; 5% to 10% have isolated deep, 30% to 50% isolated superficial, and 50% to 60% combined. In general, superficial reflux has a better prognosis than deep reflux (especially when the latter is postphlebitic), and proximal reflux has a better prognosis than distal reflux. 59. During supraclavicular approach of the subclavian artery, one of the following structures is not found:a- scalenus anterior b- vagus nerve c- phrenic nerve d- vertebral artery 60. During distal exposure of ICA, which of the following structures is divided:a- internal jugular vein b- lingual artery c- posterior belly of digastrics muscle d- hypoglossal nerve 61. The lowest infec on rate occurs in:a- carotid endarterectomy with patch closure b- fem-fem bypass c- Axillo-bifemoral bypass d- aorto-bifemoral bypass
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62. Patient with stab wound in the zone I of the neck, the next step in management is:a- immediate exploration b- observation c- Angiography d- duplex US 63. Patient with a stab wound in a limb with external bleeding, the best treatment is:a- tourniquet b- external compression followed by wound exploration at OR c- Extension of the wound d- control of bleeding at ER 64. The most common organism found in synthetic graft infection is:a- Staphylococcus aureus b- Pseudomonas aeruginosa c- Staphylococcus epidermidis d- Escherichia coli
Vascular Graft Infections Early-appearing graU infec ons occur within the first 4 months following vascular bypass surgery and are associated with virulent pathogens. Patients present with classic signs of graft sepsis, such as fever, leukocytosis, and bacteremia. The pathogens are easily identified by cultures of blood or perigraft tissues. S. aureus continues is the most prevalent pathogen. Gram-negative bacteria are also implicated in early graft infection. Pseudomonas aeruginosa infection is most commonly associated with anastomotic bleeding. Graft healing complications, such as graft-enteric erosion or fistula, typically involve infection with gram-negative enteric bacteria and can develop in both the early and late postoperative periods. Late-appearing infections are most frequently the result of graft colonization by Staphylococcus epidermidis or other coagulase-negative staphylococci. These indolent infections manifest themselves months to years after implantation and have replaced early graft infections as the most common presentation in vascular patients
Zones of the Neck
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The widely accepted prac ce is that zone 2 injuries are explored in the operating room, whereas zone 1 and 3 injuries require angiography. Hard signs of vascular injury (active bleeding, expanding hematoma, bruit/thrill, pulse deficit, central neurologic deficit). Patients with zone 2 penetra ng neck wounds can be safely and accurately evaluated by physical examination alone to confirm or exclude vascular injury. Preoperative arteriography is recommended in all patients with zone 1 penetra on if they are hemodynamically stable and do not have evidence of active hemorrhage. It is recommended because these injuries are frequently clinically occult and their exposure technically challenging. Angiography appears to be essen al in zone 3 neck wounds because of the potential inaccessibility of distal vascular injuries. Ultrasonography has been used for penetrating neck trauma, but its utility is limited to zone II neck injuries. In addition, subcutaneous air, fragments, and hematomas make ultrasound less reliable.
Angiosarcoma (Lymphangiosarcoma) Stewart-Treves syndrome is a rare, deadly cutaneous angiosarcoma that develops in longstanding chronic lymphedema. Most commonly, this tumor is a result of lymphedema induced by radical or conservative mastectomy to treat breast cancer. Chronic lymphedema from other causes may also be associated with Stewart-Treves syndrome. The skin in patients with Stewart-Treves syndrome tends to become atrophic and eventually pachydermatous, with prominent wrinkle lines. At times, hyperkeratoses and telangiectasias can be observed. AUer an interval of 1-30 years, a purplish patch appears that then develops into a plaque or nodule in the area of chronic lymphedema. Other initial lesions of Stewart-Treves syndrome may include a palpable subcutaneous mass or a poorly healing eschar with recurrent bleeding and oozing. The lesions of Stewart-Treves syndrome typically appear as multiple reddish blue macules or nodules that may become polypoid. Around these nodules, small satellite areas can develop and become confluent, forming an enlarging lesion. Sometimes, a bullous component may be seen. Thus, the morphology may be heterogeneous, with hematomalike lesions, multiple bluish-reddish nodules, and asymptomatic nodules. As the angiosarcoma continues to grow and expand, the overlying atrophic epidermis may ulcerate, producing recurrent episodes of bleeding and infection. Necrosis may be evident in advanced cutaneous tumors. Ultimately, extensive cutaneous nodules and systemic metastases appear. These nodules most commonly occur in the lungs and cause the patient's death. Not every tumor in an area of lymphedema is an angiosarcoma. Lymphangiosarcoma is a misnomer because this malignancy seems to arise from blood vessels instead of lymphatic vessels. A more appropriate name is hemangiosarcoma. Lymphangiosarcomas are extremely aggressive tumors with a high local recurrence rate and a tendency to metastasize early to many areas. Long-term survivors are the exceptions.
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65. The Treatment of Hyperhomocysteinemia is:a- Folic acid b- Zinc c- Vit. A d- Iron N.B. oral supplementa on with the combina on of folic acid, B6-, and B12-vitmains substantially lowers circulating homocysteine levels. 66. Measurement of toe pressure is more accurate than ABPI:a- D.M. and ESRD b- PVD c- Burger's disease d-Popliteal entrapment syndrome 67. Patient presented by bilateral LL edema, scrotal swelling, hematuria. Diagnosis is:a- IVC obstruction b- Left renal artery thrombosis c- Left renal vein thrombosis d- Portal vein thrombosis N.B. IVC obstruction: The classic presentation of IVCT includes bilateral lower extremity edema with dilated, visible superficial abdominal veins.
Renal Vein Thrombosis Although renal vein thrombosis (RVT) has numerous etiologies, it occurs most commonly in patients with nephrotic syndrome (ie, >3 g/d protein loss in the urine, hypoalbuminemia, hypercholesterolemia, edema). The syndrome is responsible for a hypercoagulable state. The excessive urinary protein loss is associated with decreased antithrombin III, a relative excess of fibrinogen, and changes in other clotting factors; all lead to a propensity to clot. The renal vein may also contain thrombus after invasion by renal cell cancer. Other less common causes include renal transplantation, Behçet syndrome, hypercoagulable states, and antiphospholipid antibody syndrome. 68. Pa ent with past history of CABAG harvested both GSV, now the pa ent need Femdistal bypass, which graft can be used? a- ePTFE b- Dacron c- Upper limb veins d- Umblical vein graft 69. Usual presenta on of isolated iliac aneurysm:a- deep pelvic pain b- sepsis c- sudden pain and collapse d- distal embolization 70. Reperfusion aUer acute L.L. ischemia:a- hyperkalemia b- hypercalcemia c- hypermagnesemia d- hypernatremia 71. Management of aorto-caval fistula:a- complete separation between aorta and IVC B- shunt in IVC c- closure of the fistula from within the aneurysm sac
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Ischemia-Reperfusion Injury Ischemic effects are due to not only the lack of oxygen as seen during ischemia, but also due to the absence of whole blood with its scavenging properties.The leukocyteendothelial cell interactions appear to be a key element in the pathophysiology of I/R injury. The cellular damage and capillary leak result from oxygen free radical and neutrophil activity. Endothelium is damaged by ischemia resulting in an increase in capillary permeability. Under these conditions, white cells marginate and become activated. The superoxides and other substances so released further increase capillary permeability and can cause direct tissue damage and the condition may end in microvascular perfusion failure. There are two components to the reperfusion syndrome, which follows extremity ischemia. The local response, which follows reperfusion, consists of limb swelling with its potential for aggravating tissue injury and the systemic response, which results in multiple organ failure and death. It is apparent that skeletal muscle is the predominant tissue in the limb but also the tissue that is most vulnerable to ischemia. Physiological and anatomical studies show that irreversible muscle cell damage starts aUer 3 h of ischemia and is nearly complete at 6 h. These muscle changes are paralleled by progressive microvascular damage.
Critical tissue ischemic times
No reflow phenomenon Assessment of limb ischemia tolerance times is confused by the “no-reflow phenomenon” the observation that when muscle ischemia is advanced there is permanent closure of the nutrient vessels. As a result there is controversy as to whether the no reflow phenomenon occurs as a consequence of cell muscle death or whether the no-flow injury results in a perfusion deficit that subsequently leads to muscle death. The post ischemic no reflow is due to intravascular hemoconcentration and thrombosis, swelling of capillary endothelial cells, plugging of the capillaries by leukocytes, and increased extravascular tissue pressure caused by interstitial edema formation. Heparin anticoagulation protects the microcirculation from further thrombosis, lessens the risk of venous thromboembolism and decreases microvascular permeability and interstitial edema in the reperfused area. Moreover, heparin in adequate dosage sufficient to stop local propagating thrombus will shut down the local inflammatory response, improve collateral blood flow, and lower the level of demarcation even in limbs in which there has been irreversible damage.
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Laboratory findings in Crush syndrome Urinalysis that is dipstick positive for blood with few or no red blood cells on microscopic examination is highly suggestive of rhabdomyolysis. Urine myoglobin is usually positive and pigmented casts may be seen. Elevated serum creatine phosphokinase is the most sensitive marker of muscle damage in rhabdomyolysis. Muscle cell death also leads to hyperkalemia, hyperuricemia,acidosis and hyperphosphatemia. Hypocalcemia secondary to production of calcium phosphate salts commonly follows hyperphosphatemia.
Aorto caval fistula (the bursting heart syndrome) Spontaneous rupture of abdominal aortic aneurysm into the inferior vena cava is rare but it is the most common form of spontaneous AVF encountered. The incidence of ACF ranges from 0.2% to 1.3% of pa ents with AAAs and 3% to 4% of those with ruptured aneurysms. Patients with ACFs are predominantly male, with an average age of 65 years. The clinical presentation is highly variable, and the diagnosis can be difficult, often being made only at operation. Hematuria in association with an abdominal aortic aneurysm should raise the suspicion of an aortocaval fistula. The aortocaval fistula results in a large left-to-right shunt, which can cause cardiac failure (high output congestive cardiac failure with warm peripheries). Once the diagnosis is made, treatment is by surgical closure of the fistula and repair of the aneurysm with a graft. Diagnosis of an aortocaval fistula before operation is helpful to plan operative strategy and to prepare for blood loss caused by hemorrhage. Both ultrasonography, either Bmode or duplex, and CT scanning have been used to demonstrate the fistula. During surgery for ruptured AAA:Rarely, venous bleeding, which can be secondary to an aortocaval fistula, will continue to fill the opened aneurysm. Direct digital pressure or the use of proximal and distal sponge sticks is recommended for control of the vena cava above and below the fistula. Suture of the fistula from within the aneurysm is then performed either directly with interrupted polypropylene sutures or with a prosthetic patch. The aneurysm is then repaired with a tube or bifurcated prosthetic graft in the standard fashion. It is important to not generate an air embolism or push thrombus or other aortic debris into the vena cava during this repair. Attempts to dissect the vena cava proximally and distally will greatly increase the chance of a venous injury.
Intraoperative maneuvers used to control bleeding from an aortocaval fistula. A, Vessel loop constriction; B, digital compression; C, sponge stick compression.
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Combined Vascular Malformations (Hemolymphatic Malformations) Klippel-Trenaunay-Weber syndrome (KTWS) is characterized by a triad of: 1. port-wine stain (CM), 2. varicose veins and lymphedema (VM & LM) 3. bony and soU tissue hypertrophy involving an extremity. Parkes Weber syndrome (PWS) the triad above with the addition of arteriovenous malformation. Other Regional vascular syndromes Sturge-Weber: facial CM, intracranial CM, VM and AVM PHACE syndrome: neurocutaneous syndrome with CM in 5th Cranial N. distribution. Posterior fossa abnormalities (brain malformations) Hemangioma, Arterial anomalies, Cardiac anomalies and Coarctation of the Aorta, Eye anomalies Rendu-Osler-Weber syndrome (heriditary hemorrhagic telangiectasia), Visceral AVMs. N.B. The commonest congenital vascular defect is PDA. 72. The main blood supply of the ureter:a- aorta b- renal arteries c- iliac arteies d- gonadal arteries
Chopart Amputation (midtarsal joint amputation) - Chopart amputation removes the forefoot and midfoot, saving talus and calcaneus; - Chopart amptutations should not performed for ischemia; - this is a very unstable amputation, noting that most of the tendons which act around the ankle joint have lost their insertion into foot and the heel remains unstable.
Syme's Amputation - includes ankle disarticulation, removal of malleoli, & anchoring heel pad to the wt bearing surface) allows execellent gait with a cosmetic prosthesis; - symes amputations will not heal w/o palpable posterior artery pulse
Ray Amputation Ray resection consists of longitudinal amputation of a toe and its corresponding metatarsal head.
Lisfranc Amputation tarso-metatarsal amputation Amputations Through the Midfoot Lisfranc and Chopart amputations
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Isolated iliac aneurysms Before the era of widespread use of CT and MRI, larger isolated iliac aneurysms were more often initially found to have ruptured, with a high resultant mortality rate. Today they are often identified incidentally during abdominal imaging studies performed for other reasons. Larger aneurysms may have vague findings, typically caused by compression of adjacent pelvic structures. In symptomatic patients, the diagnosis is frequently delayed until the aneurysm is large and imaging studies finally reveal the cause of the complaint. Local compression or erosive problems that affect adjacent pelvic structures can lead to ureteral obstruction, hematuria, iliac vein thrombosis, bowel obstruction, or neurologic deficit. Surgical treatment is appropriate for aneurysms larger than 3 cm.
Critical Limb Ischemia The term critical limb ischemia should be used for all patients with chronic ischemic rest pain, ulcers or gangrene attributable to objectively proven arterial occlusive disease. The term CLI implies chronicity and is to be distinguished from acute limb ischemia. The common major manifestations of CLI are rest pain and ischemic ulceration or gangrene of the forefoot or toes, representing a reduction in distal tissue perfusion below resting metabolic requirements. The clinical diagnosis is confirmed by a fall in ankle pressure to less than 50 mm Hg, toe pressure to less than 30 mm Hg, or ABI to less than 0.40.
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Pharmacotherapy for symptoms of intermittent claudication ● A 3- to 6-month course of cilostazol (Pletal) should be firstline pharmacotherapy for the relief of claudication symptoms, as evidence shows both an improvement in treadmill exercise performance and in quality of life [A]. ● Naftidrofuryl (Praxilene) can also be considered for treatment of claudication symptoms.
Smoking
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Toe pressure Normal toe systolic pressure ranges from 90-100 mm Hg and is 80-90% of brachial systolic pressure (30 mmHg less than the ankle pressure) and a toe-brachial index of <0.70 is abnormal.
Primary lymphedema • • • • •
Congenita (onset <2 years old): sporadic Congenita (onset <2 years old): familial (Milroy’s disease) Praecox (onset 2–35 years): sporadic Praecox (onset 2–35 years): familial (Meige’s disease) Tarda (onset aUer 35 years of age)
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Ideal Characteristics of an Aneurysm for EVAR Neck length (mm) Neck diameter (mm) Aortic neck angle (°) Neck mural calcification (% circumference) Neck luminal thrombus (% circumference) Common iliac artery diameter (mm) Common iliac artery length (mm) External iliac artery diameter (mm)
>15 >18, <32 <60 <50 <50 between 8 – 20 >20 >7
Features that are severe as relative contraindications to the procedure include short (<25mm) and wide (>14mm) common iliac arteries and the presence of mural thrombus in the aneurysmal sac. Funnel-shaped necks and excessive calcification are absolute contraindications to endovascular repair.
Complications of Hemodialysis Access Fistulae and Grafts THROMBOTIC COMPLICATIONS ACCESS SITE INFECTION Infection is the most common reason for hospitalization and the second most common cause of death in hemodialysis patients. Infec on accounts for 12% of mortality in this group, exceeded only by cardiovascular causes. The vast majority of graft infections are caused by gram-positive cocci, with Staphylococcus aureus accoun ng for approximately 70% and Staphylococcus epidermidis responsible for only 10% in one series. Infection is commonly seen in patients with synthetic grafts (5%) but is an uncommon complication of autogenous fistulae.
Treatment of Infection of Dialysis AV Grafts
Treatment of Infection of Primary AV Fistulae
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HEMODYNAMIC COMPLICATIONS Arterial insufficiency or steal syndrome Venous Hypertension Congestive Heart Failure OTHER COMPLICATIONS Pseudoaneurysm Pseudoaneurysm forma on secondary to graU infec on or trauma occurs in 2 to 10% of patients and is more commonly seen in prosthetic grafts. Pseudoaneurysm formation at the arterial anastomosis is often due to local infection, with partial disruption of the suture line. This complication may lead to anastomotic disruption or graft rupture, with resultant exsanguination.
Access Aneurysm True aneurysms are more likely to occur in native AVFs.
Venous hypertension Venous hypertension is an uncommon complication of dialysis angioaccess. Two clinical syndromes may be recognized. The first occurs in the setting of a side to- side fistula and affects the extremity distal to the fistula. High-pressure arterial blood flows into the lowresistance venous bed results in venous hypertension, which is manifest as progressive extremity swelling, hyperpigmentation, induration, cyanosis, and—if allowed to progress—skin ulceration. The hand is most commonly affected. The clinical appearance is similar to that seen in chronic lower extremity venous insufficiency. Resolution is typically seen following ligation of the vein distal to the anastamosis, converting the side-to-side anastomosis to a functional side-of-artery to end-of-vein configuration. The second syndrome of venous hypertension is related to venous outflow obstruction. This more common form of venous hypertension may present acutely when an arteriovenous anastomosis is constructed distal to an unrecognized proximal venous stenosis or occlusion. More often, however, venous hypertension develops chronically in the extremity with a patent AV fistula and proximal venous obstruction. The most common site of venous obstruction is at the axillary– subclavian vein level. If the subclavian vein occlusion is located proximal to the internal mammary vein, ipsilateral breast edema may be seen. Chronic subclavian vein occlusions are more difficult to treat successfully.
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Treatment of Central Vein Stenosis
When complete subclavian or brachiocephalic occlusion is encountered in a patient whose contralateral extremity is free of any contraindications for use as an AV access site, the most reliable method to eliminate venous hypertension in the involved extremity is simple fistula ligation.
Carotid siphon stenosis CALCIFICATION of the carotid siphon or intracranial internal carotid artery occurs frequently, but significant stenosis of this segment is less common. Stenosis of the carotid siphon has been estimated to be about one-sixth as common as disease of the carotid bifurcation. Patients with carotid siphon or MCA stenosis who were treated medically had an annual stroke rate of 10%.More common in Asian patients. Patients with symptomatic intracranial vertebral artery or basilar stenosis are at a higher risk of stroke, MI, or sudden death. Symptomatic atherosclerotic intracranial stenosis is a high-risk condition. Aspirin is safer and as effective as warfarin for preventing recurrent strokes. Angioplasty and stenting cannot be justified in pa ents with < 70% stenosis. Females are at the highest risk for strokes. 30-40% of patients had subsequent ischemic events, and more than half of these events were ipsilateral to the siphon stenosis. Although carotid siphon stenosis seemed to be associated with a higher risk of late death, it did not alter the short- and long-term stroke morbidity rates after carotid endarterectomy significantly. Transcranial Doppler sonography seems to be a valuable tool for noninvasive detection of intracranial lesions of the middle cerebral artery and carotid siphon. The presence of a tandem lesion infrequently alters the surgeon's decision to perform an endarterectomy. However, the importance of detecting tandem stenoses cannot be underestimated, since they may have important implications for long-term medical management in symptomatic patients. Carotid siphon calcification was correlated with the occurrence of lacunar infarction.
Venous Leg Ulcer From 70% to 80% of ulcers healed aUer 6 months of compression therapy. Patients with chronic venous insufficiency (CVI) who have lower extremity ulceration develop have difficult conditions to treat even after ulcer healing because of the frequency of ulcer recurrence. The incidence rate of recurrent ulceration after wound healing with nonoperative techniques has been reported as 28% at 2 years, 38% at 3 years, and 57% at 4 years in various studies. The incidence rate of recurrence is markedly increased by associated deep venous insufficiency.
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Transcutaneous oxygen tension (TcpO2) measurements normal, 45 mm Hg; mild ischemia, 40-45 mm Hg; moderate ischemia, 20-39 mm Hg; severe ischemia 20 mm Hg. Skin Perfusion Pressure Chronic extremity wounds with an SPP < 30 mmHg have a low probability of healing.
Acute Mesenteric Ischemia
Nonocclusive Mesenteric Ischemia (NOMI) (Severe mesenteric vasoconstriction) NOMI accounts for more than 10% to 20% of cases of acute mesenteric ischemia. The prognosis is poor, despite the absence of organic obstruction in the principal arteries. Visceral ischemia can occur due to low-flow states, especially in conjunction with intestinal atherosclerotic disease. NOMI most commonly occurs secondary to cardiac disease, particularly severe congestive heart failure. Atrial fibrillation, commonly a cause of cardiac thrombi and visceral embolization, can also induce NOMI by reducing left ventricular function and causing low cardiac output. Other risk factors for NOMI include hypovolemia, systemic vasoconstrictors, vasoactive drugs (e.g., digoxin, α-adrenergic agents, β-receptor blocking agents, cocaine), aortic insufficiency, cardiopulmonary bypass, abdominal and cardiovascular surgery, and liver failure.
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N.B. in all cases the surgeon should proceed with revascularization before resecting any intestine unless faced with an area of frank necrosis or perforation and peritoneal soilage.
Operative exposure of the infrapancreatic superior mesenteric mesenteric artery (SMA).
SMA Embolectomy The proximal SMA is vented to allow any clot to be expelled without the use of an embolectomy catheter if possible. When necessary, catheter embolectomy is typically performed with 3 or 4 Fr balloon catheter. With extraction of the embolus, torrential and pulsatile inflow should be expected. Distally, a smaller embolectomy catheter, typically 2 or 3 Fr, is employed. Great care must be taken to avoid damage or rupture of the fragile mesenteric arteries. Difficulty passing p a catheter down multiple small branches adds to the complexity of the distal embolectomy. An alternative or adjunct to balloon embolectomy of the distal mesenteric vessels is for the surgeon to place a hand on either side of the mesentery and “milk” thrombotic material out of the vessels.
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Raynaud’s syndrome. Raynaud’s syndrome is intermittent digital ischemia occurring in response to cold or emotional stress. Most patients describe tricolor changes, with the fingers initially turning white, then blue or purple, and finally red after rewarming. The traditional division of Raynaud’s patients was into Raynaud’s phenomenon and Raynaud’s disease, where phenomenon refers to patients with a diagnosed associated disease and disease refers to those with episodic digital ischemia in the absence of a diagnosed associated disease.
Acrocyanosis
زرقة النھايات
Acrocyanosis may be confused with Raynaud’s disease but it is painless and not episodic. It tends to affect young women and the mottled cyanosis of the fingers and/or toes may be accompanied by paraesthesia and chilblains.
Livedo reticularis Livedo reticularis is a vascular condition characterized by a purplish discoloration of the skin, usually on the legs. This discoloration is described as lacy or net-like in appearance and may be aggravated by cold exposure. Most often livedo reticularis causes no symptoms and needs no treatment. But it can be associated with serious underlying disorders, such as lupus, anti-phospholipid syndrome or Sneddon's syndrome. A rare complication of chronic renal dialysis known as calciphylaxis may first present with a livedo reticularis pattern. In addition, livedo reticularis may occur as a side effect of certain medications, such as hydroxyurea.
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Clinical Features Distinguishing Primary from Secondary Raynaud’s Syndrome
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Hypothenar Hammer Syndrome
Arteriogram of the hand of a carpenter. Note the aneurysm of the ulnar artery (arrow) caused by repetitive trauma from using the hand as a hammer.
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Renal Artery Stenosis Renal Artery Stenosis more than 60% = PSV more than 180 cm/s A ra o of PSV in Renal artery to PSV in Aorta, 3.5 or more Etiology of Renal Artery Stenosis (greater than 60% luminal narrowing) Atherosclerosis (70%) Usually involves the ostium and/or proximal third (the proximal 2 cm of the main renal artery, with non-ostial lesions comprising only 10% of cases. 10-15% progress to occlusion. Fibromuscular dysplasia (30%) (Medial Fibroplasia) more in femals and younger age and usually bilateral involves distal 2/3 and branches and progression is less common. Never leads to occlusion and loss of renal function is rare.Responds well to PTA. Polyarteritis Nodosa Radiation-induced Takayasu’s arteritis • 23% of malignant hypertension is the result of renovascular causes • Not all patients with RAS are hypertensive as a result • Found in 2-5% of all cases of hypertension The majority of patients are unlikely to benefit from renal revascularization, but optimal medical therapy is appropriate for all patients. Renal stenting has become the initial technique of choice to revascularise an atherosclerotic RAS and has replaced PTA and surgery. - ٥٦ -
Indications for Renal Artery Revascularization Angiography criteria • Fibromuscular dysplasia lesion • Pressure gradient >20 mmHg • Affected/unaffected kidney renin ra o >1.5:1 Clinical criteria • Refractory or rapidly progressive hypertension • Hypertension associated with flash pulmonary edema without coronary artery disease • Rapidly progressive deterioration in renal function • Intolerance to antihypertensive medications • Chronic renal insufficiency related to bilateral renal artery occlusive disease or stenosis to a solitary functioning kidney • Dialysis-dependent renal failure in a patient with renal artery stenosis but without another definite cause of end-stage renal disease • Recurrent congestive heart failure or flash pulmonary edema not attributable to active coronary ischemia
The indications for endovascular treatment for renal artery occlusive disease include 70% or greater stenosis of one or both renal arteries and at least one of the following clinical criteria: • • • •
Inability to adequately control hypertension despite appropriate antihypertensive regimen. Chronic renal insufficiency related to bilateral renal artery occlusive disease or stenosis to a solitary functioning kidney. Dialysis-dependent renal failure in a patient with renal artery stenosis but without another definite cause of end-stage renal disease. Recurrent congestive heart failure or flash pulmonary edema not attributable to active coronary ischemia.
Choice of Conduit for Infrainguinal Bypass Grafting Autogenous vein is superior to prosthetic conduits for all infrainguinal bypasses, even in the AK position. This preference is applicable not only for the initial bypass but also for reoperative cases. For long bypasses, ipsilateral great saphenous vein (GSV), contralateral GSV, small saphenous vein, arm vein, and spliced vein are used, in decreasing order of preference.
Retroperitoneal Hematomas Particularly after blunt trauma, intact retroperitoneal hematomas are a common finding during laparotomy. If such hematomas are not bleeding actively or expanding, they should not be explored right away. Other injuries can be treated first if needed and if sufficient time is available, additional diagnostic work-up pursued. Hematomas with signs of active bleeding and those that appear to be expanding rapidly should be left intact until proximal and distal control is achieved. Because of their propensity to contain major vessel damage, it is recommended to explore most hematomas in the midline. - ٥٧ -
Lateral hematomas found after blunt injury should be left intact, but after penetrating injury, lateral hematomas should be explored because they are more often associated with major vessel damage. It is recommended, however, is to leave all nonexpanding lateral hematomas, regardless of trauma mechanism. Instead, the patient should undergo CT, IVP, or angiography to rule out major vessel injury and urinary leaks. The most common cause of pelvic hematomas after blunt trauma is pelvic fracture. Hematomas in this area should not be explored routinely. Even if the pelvic hematoma is expanding, it is often better to pack the pelvic area and continue the work-up with arteriography. For penetrating trauma, on the other hand, it is usually wise to explore pelvic hematomas after securing proximal control to exclude vessel damage.
Contrast Agents Iodinated Contrast Agents Ionic contrast agents When iodinated contrast agents dissolve, their osmolality doubles because of the presence of two ions. The osmolality of these agents ranges from 1500 to 1700 mOsm, thus making them significantly more hyperosmolar than plasma (285 mOsm). Non-ionic contrast agents Have considerably less osmolality but the osmolality remains half that of ionic contrast agents. Toxic side effects of iodinated contrast agents The toxic side effects of iodinated contrast agents are primarily thought to be due to hyperosmolality. The most common adverse symptoms are nausea, vomiting, and pain in the distribution of the specific arterial bed that is injected. Other adverse systemic effects:- urticaria, laryngeal edema or bronchospasm, cardiopulmonary arrest. Reduction in adverse reactions from 12.6% to 3.1% when using ionic, high-osmolality contrast agents as opposed to non-ionic, low-osmolality agents. Cardiac Toxicity:- The most common hemodynamic effects are a decrease in heart rate and blood pressure, usually temporary and self-limited. Use of low-osmolality agents has been shown to reduce the incidence of such adverse hemodynamic effects. Hematologic Toxicity:- inhibit multiple coagulation factors and antithrombin activity, as well as exhibit antifibrinolytic properties. There is some evidence that use of non-ionic contrast agents may reduce these adverse hematologic effects. Nephrotoxicity:- Contrast-induced nephropathy is perhaps the most commonly cited and studied adverse reaction to iodinated contrast agents and carries with it significant morbidity and mortality. It continues to be the third leading cause of acute renal failure in hospitalized patients. there is no difference in such occurrence with ionic and non-ionic contrast agents. There does, however, appear to be reduced risk with the use of lowosmolality contrast agents as opposed to those with high osmolality. Neither the type of contrast agent used nor the total volume infused seems to play a significant role in the development of this complication in patients with normal renal function. Although administering contrast agents to patients already suffering from complete renal failure may be done without fear of inducing nephropathy, these patients are at risk for hyperosmolar volume overload and should be scheduled for dialysis after the angiography procedure. The principal site of contrast-induced nephropathy is the renal tubule secondary to transient local ischemia.
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The incidence of contrast-induced nephropathy in patients with normal renal function is only 1% to 2%. This risk increases to 10% in pa ents with crea nine levels of 1.3 to 1.9 mg/dL (115 μmol/L to 168 μmol/L) and to 62% in patients with levels greater than 2 mg/dL (177 μmol/L). The incidence of contrast-induced nephropathy is high in the diabetic population. Pa ents with type 1 diabetes are more prone to the development of contrastinduced nephropathy than are pa ents with type 2 diabetes. Diabetics taking metformin (dimethylbiguanide), an oral hypoglycemic agent, require special consideration when receiving iodinated contrast material.
Carbon Dioxide Arteriography Another contrast agent with novel properties and applications is CO2. Injection of this gas with its decreased radiodensity creates radiographic contrast by transiently displacing blood from the artery being imaged. Historically, CO2 arteriography has had limited use because of poor imaging quality in comparison to conventional contrast agents. However, with improved equipment, technology, and image-processing software, coupled with the significant number of vascular patients who have compromised renal func on, use of CO2 arteriography has expanded to a wide variety of cases, and it can be used with much less reservation and hesitation than in the past.
Unfavorable Carotid Angiographic Appearance in Which Carotid Stenting Should Be Avoided:• • • • • • •
Extensive carotid calcification Polypoid or globular carotid lesions Severe tortuosity of the common carotid artery Long segment stenoses (>2 cm in length) Carotid artery occlusion Severe intraluminal thrombus (angiographic defects) Extensive middle cerebral artery atherosclerosis
Treatment of air embolism Oxygen, and left lateral decubitus in the Trendelenburg position. Because death may be due to an airlock that obstructs the pulmonary outflow tract, this maneuver keeps the air within the apex of the right ventricle.
Widened mediastinum Widened mediastinum is a mediastinum with a measured width greater than 8 cm on PA chest X-ray, A widened mediastinum can be indicative of several important pathologies:• aortic aneurysm • aortic dissection or disruption • hilar lymphadenopathy • esophageal rupture - presents usually with • mediastinal mass • cardiac tamponade • pericardial effusion • thoracic vertebrae fractures in trauma patients.
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Widened mediastinum due to Aortic Pseudoaneurysm
ANTICOAGULANTS Vitamin K antagonists These oral anticoagulants are a class of pharmaceuticals that antagonize the effects of vitamin K. Examples include warfarin. It takes at least 48 to 72 hours for the an coagulant effect to develop. Approved for clinical use in 1955 Where an immediate effect is required, heparin must be given concomitantly. These anticoagulants are used to treat patients with deep-vein thrombosis (DVT), pulmonary embolism (PE), atrial fibrillation (AF), and mechanical prosthetic heart valves. I. Coumarins – Warfarin - Approx. 6 – 8 generic forms - Best to order coumadin II. Indandiones - Phenindione - Differ slightly from the coumarins - Same Mech. of action No therapeutic advantages Warfarin inhibits hepa c synthesis of vit. K dependent coagula on factors, 2-7-9-10 and decreases synthesis of protein C and S. Adverse effects 1.Pa ents aged 80 years or more may be especially suscep ble to bleeding complica ons with a rate of 13 bleeds per 100 person-years. 2.These oral an coagulants are used widely as poisons for mammalian pests, especially rodents. 3.Deple on of vitamin K by coumadin therapy increases risk of arterial calcifica on and heart valve calcification, especially if too much vitamin D is present. 4. Warfarin skin necrosis. Heparin and derivative substances Heparin is a biological substance, usually made from pig intestines. It works by activating antithrombin III, which blocks thrombin from clotting blood. Heparin can be used in vivo (by injection), and also in vitro to prevent blood or plasma clotting in or on medical devices.
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UFH Direct and indirect (through Antithrombin) actions. Anti Xa = Anti IIa Excreted by kidneys. Heparin catalyzes the inactivation of thrombin by plasma cofactor II which acts independently of Antithrombin. Heparin suppresses platelet function and increases vascular permeability. About 1/3 of dose binds to AT III To form the AT III:Heparin:Clotting Factor Complex- requires at least18 saccharides Unique high affinity pentasaccharide heparin sequences catalyze inhibition of Xa by AT Mechanism of action Only about one third of an administered dose of heparin binds to AT, and this fraction is responsible for most of its anticoagulant effect. The remaining two thirds has minimal anticoagulant activity at therapeutic concentrations, but at concentrations greater than usually obtained clinically, both high-affinity and low-affinity heparin catalyze the AT effect of a second plasma protein, heparin cofactor II The role of heparin cofactor II is insignificant except at very high heparin concentrations. The heparin-AT complex inactivates a number of coagulation enzymes, including thrombin factor (IIa), factors Xa, IXa, XIa, and XIIa. Of these, thrombin and factor Xa are most responsive to inhibi on, and human thrombin is about 10-fold more sensitive to inhibition by the heparin-AT complex than factor Xa By inactivating thrombin, heparin not only prevents fibrin formation but also inhibits thrombin-induced activation of factor V and factor VIII. Unfractionated heparin (UFH) and LMWH also induce secretion of tissue factor pathway inhibitor by vascular endothelial cells that reduce procoagulant activity of tissue factor VIIa complex, and this could contribute to the antithrombotic action of heparin and LMWH. Heparin binds to platelets, and depending on the experimental conditions in vitro, can either induce or inhibit platelet aggregation. In addition to its anticoagulant effect, heparin increases vessel wall permeability, inhibits the proliferation of vascular smooth muscle cells, and suppresses osteoblast formation and activates osteoclasts that promote bone loss. Each of these effects is independent of its anticoagulant activity, but only the osteopenic effect is likely to be relevant clinically. Anticoagulant Properties of Heparin 1. Inhibits the thrombin-mediated conversion of fibrinogen to fibrin 2. Inhibits the aggregation of platelets by thrombin 3. Inhibits activation of fibrin stabilizing enzyme 4. Inhibits activated factors XII, XI, IX, X and II
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Heparin Dose 1. IV- 5,000 Units bolus, then 30,000-35,000 units/24 hrs 2. 80 Units/kg bolus, then 18 Units/kg/hr to maintain aPTT in therapeutic range. AUer IV the half me is 90 minutes and aUer SC the peak 4-6 hours and lasts about 12 hours. Protamin sulphate Up to 50 mg slow iv (1-2 mg per 100 IU heparin).
Low molecular weight heparin Low molecular weight heparin is a more highly processed product that is useful as it does not require monitoring of the APTT coagulation parameter (it has more predictable plasma levels) and has fewer side effects. Binds to Antithrombin with no direct action. The Anti Xa is more than the Anti IIa Less effect on platelet function. Less frequent HIT and Osteoprosis. Doesn’t change the APTT (much) – an increased APTT may signify an overdose of LMWH or some other influence on the APTT (platelet antibodies) Difficult to reverse with protamine sulfate (antidote for UFH) Cleared through the kidneys Enoxaparin (Lovenox and Clexane) twice daily. Tinzaparin (Innohep) once daily. Amp. 0.5 (10000 IU),0.7(14000 IU),0.9 ml(18000 IU) and multidose vial 20000 IU 175 IU per Kg per day Who should be monitored for LMWH? Patients with kidney problems (need to check creatinine clearance) Patients that are obese or have a very low body weight Children, burn patients How should LMWH be monitored? Monitor with an anti-Xa method, using LMWH calibrators and controls. Samples should be drawn 4 hours aUer dosing.
Synthetic pentasaccharide indirect inhibitors of factor Xa Fondaparinux (Arixtra) is a synthetic sugar composed of the five sugars (pentasaccharide) in heparin that bind to antithrombin. It is a smaller molecule than low molecular weight heparin. A synthetic analog of the antithrombin-binding pentasaccharide sequence found on heparin or LMWH. Fondaparinux binds antithrombin with high affinity. Once bound, fondaparinux evokes conformational changes in the reactive center loop of antithrombin that enhance its reactivity with factor Xa. Fondaparinux is a catalytic inhibitor; thus, after promoting the formation of the factor Xa/antithrombin complex, fondaparinux dissociates from antithrombin and is available to activate additional antithrombin molecules. - ٦٢ -
With excellent bioavailability after SC administration and a plasma half-life of 17 hours, fondaparinux is administered subcutaneously once daily. Systemic fondaparinux is excreted unchanged via the kidneys. Therefore, fondaparinux must be used with caution in patients with renal insufficiency. When given SC in fixed doses, fondaparinux produces a predictable anticoagulant response. Consequently, routine coagulation monitoring is unnecessary. If necessary, fondaparinux can be monitored with antifactor Xa levels using a chromogenic assay. Fondaparinux has no effect on routine tests of coagulation, such as the activated partial thromboplastin time or activated clotting time. Does not produce heparin associated antibodies or bind to platelets. Not associated with HIT
Arixtra SC Once daily 7.5 mg for treatment and 2.5 mg for prophylaxis.
Idraparinux A second-generation synthetic pentasaccharide, idraparinux is more negatively charged than fondaparinux . Consequently, idraparinux binds to antithrombin with an affinity higher than that of fondaparinux. Because it binds antithrombin so tightly, idraparinux has a plasma half-life similar to that of antithrombin, about 80 hours. With this long halflife, idraparinux is administered SC on a once-weekly basis. Like fondaparinux, idraparinux exhibits excellent bioavailability after SC injection and produces a predictable anticoagulant response, thereby obviating the need for routine coagulation monitoring. Its anticoagulant activity is reversible with Novo Seven (r FVIIa)
Heparinoid Danaparoid Danaparoid sodium (Orgaran) is an anticoagulant that works by inhibiting activated factor X (factor Xa). IV and SC Danaparoid is considered a "low molecular weight heparin" by some sources, but is chemically distinct from heparin and thus has little cross-reactivity in heparin-intolerant patients. It has also been described as a heparinoid. It is used to prevent deep venous clots, particularly in situations with a high risk of clot formation, such as after hip surgery. It is also used as a heparinoid substitute in heparin-induced thrombocytopenia (HIT). SIDE EFFECTS
Bleeding problems
Low platelets, due to a low level of structural similarity between danaparoid and heparin
Asthma exacerbations, due to allergies to sulfites contained within the medicine
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Direct thrombin inhibitors Another type of anticoagulant is the direct thrombin inhibitor. Current members of this class include:Hirudin (Thrombex) & Recombinant hirudins like lepirudin (Refludan)
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and bivalirudin (Angiomax). •
Argatroban (Argatroban injection or Novastan).
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Oral direct thrombin inhibitors:- dabigatran (Pradaxa) and ximelagatran (Exanta).
Ximelagatran The first oral, direct thrombin inhibitor, ximelagatran is a prodrug of melagatran , a 429dalton dipeptide that fits within the active-site cleft of thrombin and blocks the enzyme’s interactions with its substrates. Thus, melagatran is a stoichiometric inhibitor of thrombin that forms a reversible 1:1 complex with the enzyme. Melagatran exhibits poor bioavailability aUer oral administra on. Ximelagatran, which has a molecular mass of 474, was developed to overcome this problem. An oral direct thrombin inhibitor, ximelagatran (Exanta) was denied approval by the Food and Drug Administration (FDA) in September 2004 and was pulled from the market en rely in February 2006 aUer reports of severe liver damage and heart attacks.
The New Oral Anticoagulants Dabigatran (Pradaxa) Direct thrombin inhibitor Approved by FDA on 10/20/2010 The first and only new oral anticoagulant that is currently approved in the US The only FDA approved indication – prevention of stroke in atrial fibrillation (RE-LY trial) Several large phase III trials are either completed or ongoing for dabigatran in DVT prophylaxis and acute VTE treatments 75,110 and 150mg capsules. bid
Rivaroxaban (Xarelto 10mg tab.) A direct factor Xa inhibitor once daily Approved in Canada and Europe for DVT prophylaxis for after total knee and hip replacement, based on RECORD trial 1-4 Not yet approved in the US. Apixaban ( Eliques tablets) Direct factor Xa inhibitor The recommended dose is 5 mg orally twice daily.
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HIT Venous thrombosis itself is the most common complication of HIT. HIT is a thrombotic storm HIT occurs in approximately 1-5% of pa ents receiving heparin. The diagnosis of this condi on is clinical. Platelet counts drop below 100000/uL or there is more than a 50% drop of the baseline platelet count following the administra on of heparin, independent of the route of administration. The incidence of HIT may be lower with LMWHs. The morbidity and mortality rates are so high, that failure to diagnose early can result in catastrophic complications. HIT can be defined as any clinical event (or events) best explained by platelet-activating anti-platelet factor 4 (PF4)/ heparin antibodies (HIT antibodies) in a patient who is receiving, or who has recently received, heparin. Types of HIT Type I (HAT) due to direct (nonimmune) effect of heparin on platelet activation, occurs within the first two days and often normalizes with continued heparin administration. Type II (HIT-T) Characterized by formation of antibodies against the heparin-platelet factor 4 complex (immune mediated syndrome). Occurs aUer 5-10 days aUer star ng heparin. CONTRAINDICATIONS: Warfarin, Platelet Transfusions, Vena Caval Filters ALTERNATIVE NON HEPARIN ANTICOAGULANTS Five alternative nonheparin anticoagulants have a rational basis for use in managing HIT.10 Three (lepirudin, argatroban, bivalirudin) are direct thrombin inhibitors (DTIs), whereas two can be classifi ed as indirect (antithrombin [AT]-dependent) inhibitors of activated factor X (Xa), either predominantly (danaparoid) or exclusively (fondaparinux). Lepirudin and argatroban are approved by the U.S. Food and Drug Administration (FDA) for treatment of HIT, whereas danaparoid is approved for this indication in Canada and Europe (but not in the United States).
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