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Hematologic changes in pregnancy Author Kenneth A Bauer, MD
Section Editor Charles J Lockwood, MD, MHCM
Deputy Editors Deputy Kristen Eckler, MD, FACOG Jennifer S Tirnauer, MD
All topics topics are are updated updated as new new eviden evidence ce become becomes s availab available le and and our our peer review process process is complete. Literature review current through: Nov 2015. | This topic last updated: Mar 14, 2014. INTRODUCTION INTRODUCTION — Normal pregnancy is characterized by profound changes in almost every organ system to accommodate the demands of the fetoplacental unit. The h ematologic system must adapt in a number of ways, such as provision of vitamins and mi nerals nerals for fetal hematopoiesis (iron, vitamin B12, B12, folic acid), acid), which can exacerbate maternal anemia, and preparation for bleeding at delivery, which requires enhanced hemostatic function. While these changes facilitate healthy pregnancy, they also increase the risks of some conditions (eg, venous thromboembolism). In addition, additio n, physiologic changes in blood cell counts must be distinguished from pregnancy complications that require specific treatments. This topic discusses physiologic changes in blood cells and hemostasis during pregn anc ancy. Hematologic complications of pregnancy are discussed in separate topic reviews. OVERVIEW OVERVIEW — The most significant hematological changes during pregnancy include the following ( table 1): 1): ● Physiologic anemia ● Neutrophilia ● Mild thrombocytopenia ● Increased procoagulant factors ● Diminished fibrinolysis PLASMA VOLUME VOLUME — Plasma volume increases by 10 to 15 percent at 6 to 12 weeks of gestation [ 11-3 3], expands rapidly until 30 to 34 weeks, after which there is only a modest rise ( figure 1). 1). The total gain at term averages 1100 to 1600 mL and results in a plasma volume of 4700 to 5200 mL, 30 to 50 percent above that found in nonpregnant women [ 1,4 1,4]. ]. During pregnancy, plasma renin activity tends to be increased and atrial natriuretic peptide levels are slightly reduced. This suggests that the rise in plasma volume is in response to an underfilled vascular system caused by systemic vasodilatation and the rise in vascular capacit ance. If expansion expansi on of blood volume was the initial event, renal and atrial volume sensors would respond, leading to the opposite hormonal profile (low plasma renin activity, elevated atrial natriuretic natriu retic peptide) [5,6 [ 5,6]. ]. This hypothesis hypothesis is also supported supported by the observation that increasing increasing sodium intake intake does not not lead to further volume volume expansion expansion [7 [ 7]. Postpartum, plasma volume decreases immediately after delivery, then increases again two to five days later, possibly because of a rise in aldosterone secretion, which occurs at this time. Plasma volume then decreases; it is still elevated by 10 10 to 15 percent percent above nonpregnant levels at three weeks postpartum, but is usually at normal nonpregnant levels at six weeks postpartum. RED BLOOD CELLS CELLS — Red blood cell (RBC) mass begins to increase at 8 to 10 weeks of gestation and steadily rises by 20 to 30 percent (250 to 450 mL) above nonpregnant levels by the end of pregnancy in women taking iron supplements [4,8-11 [ 4,8-11]. ]. Among women not on iron supplements, the red cell mass may only increase by 15 to 20 percent [ 12 12]. ]. RBC life span is slightly decreased during normal pregnancy [ 13 13]. ]. The major mediator of increased RBC mass is an increase in levels of erythropoietin, which stimulates RBC production. Erythropoietin levels increase by 50 percent in normal pregnancies and vary according to the presence of pregnancy complications [ 14 14]. ]. The resulting increased RBC mass partially supports the higher
metabolic requirement for oxygen during pregnancy [ 15 15]. ]. In women not taking iron supplements, mean corpuscular volume (MCV) decreases during pregnancy and averages 80 to 84 fL in the third trimester [ 16 16]. ]. However, MCV increases approximately 4 fL in healthy pregnant women and those with only mild iron deficiency [ 17 17]. ]. Levels of RBC 2,3 bisphosphoglycerate (2,3-BPG, also called 2,3-diphosphoglycerate [2,3-DPG]) remain elevated during pregnancy, which leads to a decrease in oxygen affinity of maternal RBCs ( figure 2) 2) [18 18]. ]. This lower oxygen affinity, affinity , comb c ombined ined with low pCO 2 of the maternal maternal blood blood due due to increased increased minute minute ventilation, facilitates transport of oxygen across the placenta. Anemia Anemia — Healthy pregnancy is associated with a modest decrease in hemoglobin levels (ie, physiological or dilutional anemia of pregnancy). This decrease is due to a greater expansion of plasma volume relative to the increase in RBC mass. The greatest disproportion between the rates at which plasma and RBCs are added to the maternal circulation occurs during the late second to early third trimester (lowest hemoglobin is typically measured at 28 to 36 weeks [ 16 16]). ]). Nearer to term, hemoglobin concentration increases due to cessation of plasma expansion and continuing increase in hemoglobin mass ( figure 1). 1). Conversely, the absence of physiologic anemia appears to be a risk factor for stillbirth [ 19 19]. ]. Determining a precise definition of anemia in pregnant women is not straightforward, given the pregnancy associated changes in plasma volume and RBC mass, ethnic variation between white and black women, and the frequent use of iron supplementation in pregnancy. ● The Centers for Disease Control and Prevention (CDC) has defined anemia as hemoglobin levels of less than 11 g/dL (hematocrit less than 33 percent) in the first and third trimesters and less than 10.5 g/dL (hematocrit less than 32 percent) in the second trimester [ 20 20]. ]. Since hemoglobin and hematocrit levels are lower in African-American adults, the Institute of Medicine recommends lowering the hemoglobin cutoff level by 0.8 g/dL in this population [ 21 21]. ]. ● The World Health Organization Organization (WHO) defines anemia in pregnant women as hemoglobin <110 g/L (11 g/dL) or hematocrit <6.83 mmol/L or 0.33 L/L (33 percent) [ 22 22]. ]. Severe anemia in pregnancy is defined as hemoglobin <70 g/L (7 g/dL) and requires medical treatment. Very severe anaemia is defined as hemoglobin <40 g/L (4 g/dL) and is a medical emergency due to the risk of congestive heart failure. Women with hemoglobin values below these levels can be considered anemic and should undergo a standard evaluation (eg, complete blood count, review of peripheral smear, reticulocyte count, serum Fe/TIBC, and ferritin) [23 [23]. ]. Sixteen to 29 percent of pregnant women in the United States become anemic in the third trimester [24 [24]. ]. If the evaluation is negative, a hemoglobin as low as 10 g/dL can be attributed to physiologic anemia since a wide variety of factors affects the normal level of hemoglobin in a specific individual. (See "Approach to the adult patient with anemia" and "Causes and diagnosis of iron deficiency anemia in the adult", section on 'Pregnancy' .) Chronic severe anemia is most common in women in developing countries. Maternal hemoglobin below 6 g/dL has been associated with reduced amniotic fluid volume, fetal cerebral vasodilation, and nonreassuring fetal heart rate patterns [25 [ 25]. ]. Increased risks of prematurity, spontaneous abortion, low birth weight, and fetal death have also been reported [ 26 26]. ]. In addition, severe anemia (hemoglobin less than 7 g/dL) increases the risk of maternal mortality [27 [ 27]. ]. There is no evidence that maternal anemia increases the risk of congenital anomalies in offspring. Chronic severe anemia is usually related to (1) inadequate iron stores due to nutritional deficiency and intestinal helminthic infections, (2) folate deficiency due to inadequate intake, and (3) chronic hemolytic states, such as malaria. Ideally, severe anemia could be prevented and pregnancy outcome improved with nutritional supplementation and infection control measures [ 28,29 28,29]. ]. As an example, a randomized trial in rural China found an iron-folic iron-folic acid acid supplement (60 mg iron plus 400 mcg folic acid) was associated with higher maternal hemoglobin levels, fewer births before 34 weeks of gestation, and fewer early neonatal deaths than folate alone [ 29 29]. ]. However, 40 percent of women were still anemic in the third trimester. A similar trial found that an ironfolic acid supplement given to pregnant Nepalese women in an area where iron deficiency was common appeared to be associated with improvement in some aspects of intellectual and motor function in offspring
evaluated at age 7 to 9 years [30 [ 30]. ]. Where safe blood transfusion is available, it is probably prudent to treat severe anemia aggressively, as with red cell transfusion, if there are signs suggestive of fetal hypoxemia [ 23 23]. ]. Physiologic anemia of pregnancy should resolve by six weeks postpartum since plasma volume has returned to normal by that time. (See 'Plasma volume' volume' above.) Iron requirements requirements — In a typical singleton gestation, maternal iron requirements average close to 1000 mg over the course of pregnancy: approximately 300 mg for the fetus and placenta and approximately 500 mg, if available, for the expansion of the maternal hemoglobin mass. Two hundred milligrams is shed through the gut, urine, and skin. Since most women do not have adequate iron stores to handle the demands of pregnancy, iron is commonly prescribed as part of a prenatal multivitamin or as a separate supplement. In general, women taking iron supplements have a mean hemoglobin concentration that is 1 g/dL greater than that of women not taking supplements. Reference ranges for iron indices in pregnancy are listed in the table ( table 2). 2). (See "Nutrition in pregnancy", section on 'Iron' .) A detaile detailed d discussion on the diagn diagnosis, osis, preve prevention ntion,, and and manag manageme ement nt of iron iron deficiency deficiency anemia anemia in preg pregna nant nt women can be found separately. (See "Causes and diagnosis of iron deficiency anemia in the adult", section on 'Pregnancy' 'Pregnancy' and "Causes and diagnosis of iron deficiency anemia in the adult", section on 'Prevention' and and "Treatment of the adult with iron deficiency anemia", section on 'Pregnancy' .) Folate requirements requirements — In nonpregnant individuals, the daily folic acid acid requirement is 50 to 100 mcg. The increase in RBC production during pregnancy necessitates an increase in the folic acid requirement, but this is more than met by the increased daily intake (400 to 800 mcg) already recommended for prevention of neural tube defects. (See "Folic acid supplementation in pregnancy" and "Nutrition in pregnancy".) pregnancy" .) WHITE BLOOD CELLS — CELLS — Pregnancy is associated with leukocytosis, primarily related to increased circulation of neutrophils. The neutrophil count begins to increase in the second month of pregnancy and plateaus in the second or third trimester, at which time the total white blood cell counts range from 9000 to 15,000 cells/microL [31 [ 31]. ]. Data from two series reported mean white blood cell counts in laboring patients of 10,000 to 16,000 cells/microL, with an upper level as high as 29,000 cells/microL [ 32,33 32,33]; ]; the mean count increased linearly with the duration of elapsed labor [ 33 33]. ]. The white blood cell count falls to the normal nonpregnant range by the sixth day postpartum. Normal pregnant women can have a small number of myelocytes or metamyelocytes in the peripheral circulation. Some studies have observed an increase in the percent of bands as pregnancy advances [ 34-36 34-36]. ]. Dohle bodies (blue staining cytoplasmic inclusions in granulocytes) are a normal finding in pregnant women. (See "Evaluation of the peripheral blood smear", section on 'Neutrophil series' and "Evaluation of the peripheral blood smear", section on 'Granulation' .) In healthy women with normal pregnancies, there is no change in the absolute lymphocyte count and no significant changes in the relative numbers of T and B lymphocytes [ 37 37]. ]. The monocyte count is generally stable, the basophil count may slightly decrease and the eosinophil count may slightly increase. PLATELETS AND COAGULATION SYSTEM SYSTEM — Hemostasis involves complex interactions between the coagulation system (figure (figure 3), 3), platelets, and the vascular endothelium. The fibrinolytic system has a complementary role in preventing excessive coagulation, via removal of fibrin and clot dissolution ( table 3 and and figure 4). 4). These processes interact to ensure that the circulating blood flows freely in the vascular bed and that bleeding is quickly arrested following trauma. (See "Overview of hemostasis".) hemostasis" .) In pregnancy, however, the demands on the hemostatic and fibrinolytic systems change in order to prevent excessive hemorrhage during placental separation. A relative hypercoagulable state compared with nonpregnant individuals is caused by a marked increase in some coagulation factors, reduced fibrinolysis, and increased platelet activity. Changes in vascular tone that enhance uteroplacental blood flow also occur. These changes are due to a variety of factors (eg, nitric oxide, endothelin, renin-angiotensin, estrogen, progesterone, prostacyclin).
Platelets Platelets — Although platelet counts remain in the normal nonpregnant range in most women during uncomplicated pregnancies [38 [ 38], ], mean platelet counts of pregnant women may be slightly lower than in healthy nonpregnant women (table ( table 2) 2) [39 39]. ]. Serial platelet counts during uncomplicated pregnancies may [ 40 40]] or may not [ 41 41]] decrease, but the mean values in groups of women do not necessarily reflect changes in individual women [ 42 42]. ]. Mild decreases in platelet count occur in about 5 percent of pregnancies (ie, gestational thrombocytopenia, incidental thrombocytopenia of pregnancy). Gestational thrombocytopenia is characterized by mild asymptomatic thrombocytopenia occurring in the third trimester in a patient without any history of thrombocytopenia (other than in a prior pregnancy). It is not associated with maternal, fetal, or neonatal sequelae and spontaneously resolves postpartum [ 43-45 43-45]. ]. Platelet counts are typically >70,000/microL, with about two-thirds being 130,000 to 150,000/microL. Diagnosis and management of gestational thrombocytopenia are discussed in detail separately. (See "Thrombocytopenia in pregnancy", section on 'Gestational thrombocytopenia' .) It is important to distinguish gestational thrombocytopenia from other causes of thrombocytopenia, including severe preeclampsia, hemolysis elevated elevated liver function tests and low platelets (HELLP) syndrome, thrombotic thrombocytopenic purpura (TTP), immune thrombocytopenia (ITP), antiphospholipid syndrome, and druginduced thrombocytopenia. Most of these conditions are associated with more severe thrombocytopenia and/or other hematologic changes. These other conditions are discussed in detail separately. (See "Thrombocytopenia in pregnancy".) pregnancy" .) The platelet count begins to rise soon after delivery and continues to increase for three to four weeks before returning to baseline. In one study of 50 presumably normal pregnant/postpartum women followed with serial platelet counts, the mean platelet count predelivery and 3, 7, 15, 25, and 42 days after delivery was 219,000; 267,000; 349,000; 363,000; 279,000; and 254,000 per microL, respectively [ 46 46]. ]. Coagulation and fibrinolysis fibrinolysis — Normal pregnancy is a prothrombotic state [47-57 [ 47-57]. ]. A variety variety of chang changes es occur in proco procoag agula ulant nt and and anticoag anticoagula ulant nt pathways, pathways, which on balan balance ce increase increase coagula coagulation tion potential on a background of reduced anticoagulation and fibrinolysis. The following changes occur in circulating levels of coagulation factors, inhibitors, and fibrinolytic markers (table 2): 2): ● The physiological anticoagulant protein S decreases (measured as total protein S, free protein S, and protein S activity). ● Procoagulant factors fibrinogen, factors II, VII, VIII, X, XII, and XIII increase by 20 to 200 percent [ 57,58 57,58]. ]. ● The pro-hemostatic factor von Willebrand factor increases. ● Activity Activit y of fibrinolytic fibrinolytic inhibito inhibitors rs increase increases, s, including including thrombin thrombin activatable activatable fibrinolytic fibrinolytic inhibito inhibitorr (TAFI), (TAFI), plasminogen activator inhibitor-1 (PAI-1), and PAI-2 [ 59 59]. ]. PAI-1 levels increase markedly derived from the placenta and decidua. ● Thrombin cleavage products increase, suggesting ongoing coagulation. Changes include increases in fibrin D-dimer, fibrin monomers, and fibrinopeptides A and B [ 60-67 60-67]. ]. Products of fibrinolysis also increase, including plasminogen and tissue type plasminogen activator [ 68 68]. ]. ● Other anticoagulant and procoagulant proteins (eg, antithrombin, protein C, factor V and factor IX) remain unchanged or increase slightly [ 57,69 57,69]. ]. ● Resistance to activated protein C (a biochemical test used to diagnose the prothrombotic factor V Leiden mutation) increases in the second and third trimesters when evaluated by a test using plasma that is not factor V deficient; however, this type of “first generation” test is rarely performed clinically and is primarily of historical interest. (See "Factor V Leiden and activated protein C resistance: Clinical manifestations and diagnosis", section on 'Diagnostic testing' .) The net effect of these changes is to increase the tendency for thrombus formation and extension, which,
along with myometrial contractions and high levels of decidual tissue factor expression, protect the mother from excessive bleeding at the time of placental separation and delivery. These changes also increase the risk of venous thromboembolism during pregnancy and especially the postpartum period. Laboratory tests of coagulation are not routinely done (or required) during pregnancy. In a study of 117 normal pregnant women, the activated partial thromboplastin time (aPTT) remained in the normal range during pregnancy, but decreased slightly near term [ 70 70]. ]. The prothrombin time (PT) shortened in some. (See "Clinical use of coagulation tests".) tests" .) The D-dimer lacks utility to evaluate the likelihood of venous thromboembolism during pregnancy, due to changes in this parameter and a lack of normal reference ranges during pregnancy. (See "Pulmonary embolism in pregnancy: Epidemiology, pathogenesis, and diagnosis", section on 'Laboratory studies' .) Postpartum, normalization of coagulation parameters and factor levels varies depending on the factor, but all should return to baseline by six to eight weeks after delivery [ 46 46]. ]. Hemostasis probably should not be evaluated earlier than three months following delivery and after terminating lactation to exclude pregnancyrelated effects [57 [ 57]. ]. The effects of acquired and inherited thrombophilias on pregnancy outcome are controversial and active areas of investigation. These effects are discussed separately. (See "Inherited thrombophilias in pregnancy" .) POSTPARTUM POSTPARTUM — Pregnancy-related hematological changes return to baseline by six to eight weeks after delivery [46 [ 46]. ]. Within this range, the rate and pattern of resolution of pregnancy-related changes of specific hematological parameters vary and are described above in the section on each parameter. SUMMARY AND RECOMMENDATIONS ● The major hematological changes during pregnancy are physiologic anemia, neutrophilia, mild thrombocytopenia, increased procoagulant factors, and diminished fibrinolysis ( table 1). 1). (See 'Introduction' above.) ● Plasma volume increases by 10 to 15 percent at 6 to 12 weeks of gestation, and then expands rapidly until 30 to 34 weeks, after which there is only a modest rise ( figure 1). 1). (See 'Plasma volume' volume' above.) ● Red blood cell mass begins to increase at 8 to 10 weeks of gestation and steadily rises by 20 to 30 percent (250 to 450 mL) above nonpregnant levels by the end of pregnancy. A greater expansion of plasma volume relative to the increase in hemoglobin mass and erythrocyte volume is responsible for the modest fall in hemoglobin levels (ie, physiological or dilutional anemia of pregnancy) observed in healthy pregnant women. The Centers for Disease Control and Prevention (CDC) has defined anemia as hemoglobin levels of less than 11 g/dL in the first and third trimesters and less than 10.5 g/dL in the second trimester. (See 'Red blood cells' cells' above.) ● The neutrophil count begins to increase in the second month of pregnancy and plateaus in the second or third trimester, at which time the total white blood cell counts range from 9000 to 15,000 cells/microL. There is no change in the absolute lymphocyte count. (See 'White blood cells' cells' above.) ● The circulating levels of several coagulation factors change during pregnancy ( table 2), 2), resulting in a relative prothrombotic state. (See 'Coagulation and fibrinolysis' above.) ● Mean platelet counts of pregnant women may be slightly lower than in healthy nonpregnant women, but most pregnant women have normal platelet counts ( table 2). 2). (See 'Platelets' 'Platelets' above.) Use of UpToDate is subject to the Subscription and License Agreement . REFERENCES 1. Lund CJ, Donovan JC. Blood volume during pregnancy. Significance of plasma and red cell volumes. Am J Ob Obstet stet Gyne Gynecol col 19 1967 67;; 98 98:39 :394. 4. 2. Bernstein IM, Ziegler W, Badger GJ. Plasma volume expansion in early pregnancy. Obstet Gynecol
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58. Esmon CT. Molecular events that control the protein C anticoagulant pathway. Thromb Haemost 1993; 70:29. 59. Ku DH, Arkel YS, Paidas MP, Lockwood CJ. Circulating levels of inflammatory cytokines (IL-1 beta and TNF-alpha), resistance to activated protein C, thrombin and fibrin generation in uncomplicated pregnancies. Thromb Haemost 2003; 90:1074. 60. Francalanci I, Comeglio P, Alessandrello Liotta A, et al. D-dimer plasma levels during normal pregnancy measured by specific ELISA. Int J Clin Lab Res 1997; 27:65. 61. Senent M, Bellart J, Zuazu-Jausoro I, et al. [Markers of hypercoagulability during pregnancy: thrombinantithrombin-III complexes and D dimer]. Sangre (Barc) 1991; 36:21. 62. van Wersch JW, Ubachs JM. Blood coagulation and fibrinolysis during normal pregnancy. Eur J Clin Chem Clin Biochem 1991; 29:45. 63. Mercelina-Roumans PE, Ubachs JM, van Wersch JW. Coagulation and fibrinolysis in smoking and nonsmoking pregnant women. Br J Obstet Gynaecol 1996; 103:789. 64. Bremme K, Ostlund E, Almqvist I, et al. Enhanced thrombin generation and fibrinolytic activity in normal pregnancy and the puerperium. Obstet Gynecol 1992; 80:132. 65. Bellart J, Gilabert R, Fontcuberta J, et al. Fibrinolysis changes in normal pregnancy. J Perinat Med 1997; 25:368. 66. Chabloz P, Reber G, Boehlen F, et al. TAFI antigen and D-dimer levels during normal pregnancy and at delivery. Br J Haematol 2001; 115:150. 67. Kline JA, Williams GW, Hernandez-Nino J. D-dimer concentrations in normal pregnancy: new diagnostic thresholds are needed. Clin Chem 2005; 51:825. 68. Bonnar J, McNicol GP, Douglas AS. Fibrinolytic enzyme system and pregnancy. Br Med J 1969; 3:387. 69. Clark P, Brennand J, Conkie JA, et al. Activated protein C sensitivity, protein C, protein S and coagulation in normal pregnancy. Thromb Haemost 1998; 79:1166. 70. Cerneca F, Ricci G, Simeone R, et al. Coagulation and fibrinolysis changes in normal pregnancy. Increased levels of procoagulants and reduced levels of inhibitors during pregnancy induce a hypercoagulable state, combined with a reactive fibrinolysis. Eur J Obstet Gynecol Reprod Biol 1997; 73:31. Topic 429 Version 15.0
GRAPHICS
Summary of hematological changes associated with normal pregnancy Plasma volume
In creases 3 0 to 50 percent
Red blood cell mass
In creases 2 0 to 30 percent
Hemoglobin con centration
Decreases
Red cell lifespan
Sligh tly decreased
Eryth ropoietin
In creases
Mean corpusc uscula ular volume ume (MCV)
Incr ncreases slightl htly
Platelet coun t
No ch an ge to slight decrease
White blood cell coun t
In creases (neutrophilia)
Lymphocyte cou nt
No ch an ge
Monocyte cou nt
No ch an ge
Basoph il coun t
No ch an ge to slight decrease
Eosin ophil coun t
No ch an ge to slight in crease
Proth rombin time
Sligh t decrease
Bleedin g time
No ch an ge
Total protein S antigen, free protein S antigen,
Decreases
protein S activity Resistance nce to activated protein C
Incr ncreases
Fibrino Fibrinoge gen, n, factors factors II, VII, VII, VIII, VIII, X, XII, XII, XIII XIII
Increas Increases es 20 to 200 perc percent ent
Antithrombi Antithrombin, n, protein protein C, factor factor V, factor factor IX
No change change to slig slight ht increas increase e
Von Willebran d factor
In creases
Thrombin activatable fibrinolytic inhibitor
Increases
(TAFI), PAI-1, PAI-2 D-dimer Graphic 89214 Version 2.0
In creases
Total blood volume, plasma volume and red cell volume in normal pregnancy
Data from Shnider SM, Levinson G. Anesthesia for Obstetrics, 3rd ed, Williams & Wilkins, Baltimore, p. 8. Graphic 61948 Version 2.0
Oxyhemoglobin dissociation curve
Depicted here is the oxyhemoglobin dissociation curve for normal adult hemoglobin (Hemoglobin A, solid line). Note that hemoglobin is 50 percent saturated with oxygen at a partial pressure of 27 mmHg (ie, the P50 is 27 mmHg) mmHg) and is 100 100 percent percent saturated saturated at a PaO 2 of approximately 100 100 mmHg. Depicted here are curves that are "left-shifted" (blue line, representing increased oxygen affinity) and "right-shifted" (red line, decreased oxygen affinity). The effect of right- or left-shifting of the curve is most pronounced at low oxygen partial pressures. In the examples shown, the left-shifted curve means that hemoglobin can deliver approximately 70 percent percent of its attached oxygen at a PaO 2 of 27 mmHg. mmHg. In In contrast, contrast, the the right-shifted hemoglobin can deliver only about 35 percent of its attached oxygen at this PaO 2 . A high proport proportion ion of fetal f etal hemoglobin, which which has high high oxygen affinity, shifts this curve to the left in newborns. Graphic 81216 Version 5.0
Normal reference ranges in pregnant women Nonpregnant
First
Second
Third
adult*
trimester
trimester
trimester
4-27
1 2-25
8-67
1 4-2 22
1 -3
Ferritin ¶ (ng/mL)
10 -15 0 Δ
6 -1 30
2-23 0
0 -11 6
1 -8
Folate, red blood cell
15 0-4 50
1 37 -58 9
94 -8 28
1 09-66 3
6, 9,
Folate, serum (ng/mL)
5.4 -1 8.0
2 .6-15 .0
0.8-24.0
1 .4-20 .7
1, 6,
Haptoglobin (mg/mL)
25 -25 0
1 30 +/- 4 3
11 5 +/- 5 0
1 35 +/- 6 5
93
Hemoglobin ¶ (g/dL)
12 -15 .8 Δ
1 1.6 -1 3.9
9.7-14.8
9 .5-15 .0
2, 3,
Hematocrit ¶ (percent)
35 .4-44 .4
3 1.0 -4 1.0
30 .0 -39 .0
2 8.0 -4 0.0
1, 2,
Re
Hematology Erythropoietin ¶ (units/L)
(ng/mL)
15 Iron, total binding
25 1-4 06
2 78 -40 3
Not reported
3 59-60 9
7
Iron , seru m ¶ (mcg/dL)
41 -14 1
7 2-143
44 -1 78
3 0-1 93
2, 7
Mean corpuscular
27 -32
3 0-32
30 -3 3
2 9-3 2
5
79 -93
8 1-96
82 -9 7
8 1-9 9
5, 6,
16 5-4 15
1 74 -39 1
15 5-40 9
1 46-42 9
5, 6,
capacity capacity¶ (mcg/dL) (mcg/dL)
hemoglobin (pg/cell) Mean corpuscular volume volume (xm (xm 3 ) Platelet (x10 9/L)
17 Mean platelet volume
6.4 -1 1.0
7 .7-10 .3
7.8-10.2
8 .2-10 .4
5
4.0 0-5.2 0 Δ
3 .42 -4 .55
2.81 -4.49
2 .71 -4 .43
5, 6,
<1 4.5
1 2.5 -1 4.1
13 .4 -13 .6
1 2.7 -1 5.3
5
3.5 -9 .1
5 .7-13 .6
5.6-14.8
5 .9-16 .9
5, 6,
(mcm mcm 3) Red blood cell count (x10 x10 6/mm 3 ) Red cell distribution width (percent) White blood cell count (x10 x10 3/mm 3 ) Neutrophils
18 1.4-4.6
3.6-10.1
3.8-12.3
3 . 9- 1 3 . 1
5, 1
0.7-4.6
1.1-3.6
0.9-3.9
1.0-3.6
5, 1
0.1-0.7
0.1-1.1
0.1-1.1
0.1-1.4
5, 1
0-0.6
0 -0 . 6
0-0.6
0-0.6
1 4,
0-0.2
0 -0 . 1
0-0.1
0-0.1
1 4,
Tran sferrin (mg/dL)
20 0-4 00
2 54 -34 4
22 0-44 1
2 88-53 0
4, 5
Transferrin, saturation
22 -46 ¶
Not reported
10 -4 4
5 -37
3
(x10 (x10 3/mm /mm 3) Lymphocytes (x10 (x10 3/mm /mm 3) Monocytes (x10 (x10 3/mm /mm 3) Eosinophils (x10 (x10 3/mm /mm 3) Bas o phils (x10 3/m m 3)
without iron (percent)
22 -46 ¶
Not reported
18 -9 2
9 -98
3
70 -13 0
8 9-114
78 -1 26
8 2-1 16
1 7,
D-dimer (mcg/mL)
0.2 2-0.7 4
0 .05 -0 .95
0.32 -1.29
0 .13 -1 .7
1 7,
Factor V (percen t)
50 -15 0
7 5-95
72 -9 6
6 0-8 8
25
Factor VII (percen t)
50 -15 0
1 00 -14 6
95 -1 53
1 49-21 1
17
Factor VIII (percen t)
50 -15 0
9 0-210
97 -3 12
1 43-35 3
1 7,
Factor IX (percent)
50 -15 0
1 03 -17 2
15 4-21 7
1 64-23 5
17
Factor XI (percent)
50 -15 0
8 0-127
82 -1 44
6 5-1 23
17
Factor XII (percen t)
50 -15 0
7 8-124
90 -1 51
1 29-19 4
17
Fibrinogen (mg/dL)
21 1-4 96
2 44 -51 0
29 1-53 8
3 01-69 6
5, 1
Transferrin, saturation with iron (percent) Coagulation Antithrombin, functional (percent)
23, Homocystein e (mmol/L)
4.4 -1 0.8
3 .34 -1 1
2.0-26.9
3 .2-21 .4
6, 9,
International
0.9 -1 .04 ◊
0 .86 -1 .08
0.83 -1.02
0 .80 -1 .09
1 9,
26 .3-39 .4
2 3.0 -3 8.9
22 .9 -38 .1
2 2.6 -3 5.0
5, 1
17. 17.3 +/– 5.7 5.7
17. 17.7 +/– 1.9 1.9
Not reported ted
66. 66.4 +/– 4.9 4.9
87
9.3 +/– 1.9
9 .0 +/– 0 .8
Not reported
3 1.4 +/– 3.0
87
Proth rombin time (sec)
12 .7-15 .4
9 .7-13 .5
9.5-13.4
9 .6-12 .9
5, 1
Protein C, functional
70 -13 0
7 8-121
83 -1 33
6 7-1 35
1 9,
70 -14 0
3 9-105
27 -1 01
3 3-1 01
1 7,
Protein S, free (percent)
70 -14 0
3 4-133
19 -1 13
2 0-6 5
2 5,
Protein S, functional
65 -14 0
5 7-95
42 -6 8
1 6-4 2
25
1.6 -1 3 §
1 .8-6.0
2.36 -6.6
3 .34 -9 .20
1 7,
4-43
1 6-33
36 -5 5
6 7-9 2
17
75 -12 5
6 2-318
90 -2 47
8 4-4 22
2 0,
40 -17 0 ￥
4 0-160
22 -1 35
3 8-1 05
2 0,
Normalized Ratio Partial thromboplastin time, activated (sec) Plasminogen activator inhibitor-1 (PAI-1) antigen (pg/mL) Plasminogen activator inhibitor-1 (PAI-1) activity (arbitrary units)
(percent) Protein S, total (percent)
activity (percent) Tissue plasminogen activator (ng/mL) Tissue plasminogen activator inhibitor-1 (ng/mL) von Willebrand measurements von Willebrand factor antigen (percent) ADAMTS-13, von Willebrand cleaving protease
Blood chemical constituents Alanine transaminase
7-41
3 -3 0
2-33
2 -25
4, 5,
Albu min (g/dL)
4.1 -5 .3 Δ
3 .1-5.1
2.6-4.5
2 .3-4.2
2 9-
Alkaline phosphatase
33 -96
1 7-88
25 -1 26
3 8-2 29
4, 5,
10 0-2 00
2 25 -32 3
27 3-39 1
3 27-48 7
5
—
—
Approximately
Approximately
95
130-400
130-590
(units/L)
(units/L) Alpha-1 antitrypsin (mg/dL) Alpha-fetoprotein (ng/mL) Ammon ia (microM)
31 +/- 3 .2
—
—
2 7.3 +/- 1 .6
94
Amylase (un its/L)
20 -96
2 4-83
16 -7 3
1 5-8 1
4, 5,
An ion gap (mmol/L)
7-16
1 3-17
12 -1 6
1 2-1 6
5
Aspartate transaminase
12 -38
3 -2 3
3-33
4 -32
4, 5,
Bicarbonate (mmol/L)
22 2 2 -30
2 0-24
20 -2 4
2 0-2 4
5
Biliru bin , total (mg/dL)
0.3 -1 .3
0 .1-0.4
0.1-0.8
0 .1-1.1
4, 2
Bilirubin, unconjugated
0.2 -0 .9
0 .1-0.5
0.1-0.4
0 .1-0.5
5, 2
0.1 -0 .4
0 -0 .1
0-0.1
0 -0.1
29
Bile acids (mmol/L)
0.3 -4 .8 ‡
0 -4 .9
0-9.1
0 -11 .3
2 9,
CA-125 antigen
7.2 -2 7.0
2 /2 -26 8
12 -2 5.1
1 6.8 -4 3.8
8 8,
4.5 -5 .3
4 .5-5.1
4.4-5.0
4 .4-5.3
5, 3
8.7 -1 0.2
8 .8-10 .6
8.2-9.0
8 .2-9.7
4, 5,
(units/L)
(mg/dL) Bilirubin, conjugated (mg/dL)
(units/mL) Calcium, ionized (mg/dL) Calcium, total (mg/dL)
36Ceru loplasmin (mg/dL)
25 -63
3 0-49
40 -5 3
4 3-7 8
5, 3
Ch loride (mE q/L)
10 2-1 09
1 01 -10 5
97 -1 09
9 7-1 09
4, 5,
Creatin ine (mg/dL)
0.5 -0 .9 Δ
0 .4-0.7
0.4-0.8
0 .4-0.9
4, 5,
Gamma-glutamyl
9-58
2 -2 3
4-22
3 -26
4, 5,
11 5-2 21
7 8-433
80 -4 47
8 2-5 24
4, 5,
Lipase (un its/L)
3-43
2 1-76
26 -1 00
4 1-1 12
33
Magn esium (mg/dL)
1.5 -2 .3
1 .6-2.2
1.5-2.2
1 .1-2.2
4, 5,
transpeptidase (units/L) Lactate dehydrogenase (units/L)
36, Osmolality (mOsm/kg
27 5-2 95
2 75 -28 0
27 6-28 9
2 78-28 0
3 8,
2.5 -4 .3
3 .1-4.6
2.5-4.6
2 .8-4.6
4, 5,
H20) Ph osph ate (mg/dL)
42 Potassiu m (mEq/L)
3.5 -5 .0
3 .6-5.0
3.3-5.0
3 .3-5.1
4, 5,
32, Prealbu min (mg/dL)
17 -34
1 5-27
20 -2 7
1 4-2 3
5
Protein , total (g/dL)
6.7 -8 .6
6 .2-7.6
5.7-6.9
5 .6-6.7
5, 3
Sodium (mEq/L)
13 6-1 46
1 33 -14 8
12 9-14 8
1 30-14 8
4, 5, 32,
Urea nitrogen (mg/dL)
77-20
7 -1 2
3-13
3 -11
4, 5,
Uric acid (mg/dL)
2.5 -5 .6 Δ
2 .0-4.2
2.4-4.9
3 .1-6.3
4, 5,
Metabolic and endocrine tests Aldosteron e (ng/dL)
2-9
6 -1 04
9-10 4
1 5-1 01
4 3,
Angiotensin converting
9-67
1 -3 8
1-36
1 -39
3 9,
0-8.5
Not reported
50 -4 25
5 0-5 90
8 4,
Cortisol (mcg/dL)
0-25
7 -1 9
10 -4 2
1 2-5 0
5, 4
Hemoglobin A 1C (percent)
4-6
4 -6
4-6
4 -7
3 6,
Parathyroid hormone
8-51
1 0-15
18 -2 5
9 -26
30
<1 .3 †
0 .7-0.9
1.8-2.2
2 .5-2.8
30
0.3 -9 .0 †
Not reported
7.5-54.0
5 .9-58 .8
4 0,
0.3 4-4.2 5
0 .60 -3 .40
0.37 -3.60
0 .38 -4 .04
4, 5,
0 .1-2.5
0.2-3.0
0 .3-3.0
85
1.3 -3 .0
1 .8-3.2
2.8-4.0
2 .6-4.2
5
Th yroxine, free (ng/dL)
0.8 -1 .7
0 .8-1.2
0.6-1.0
0 .5-0.8
5, 4
Thyroxine, total
5.4 -1 1.7
6 .5-10 .1
7.5-10.3
6 .3-9.7
5, 3
2.4 -4 .2
4 .1-4.4
4.0-4.2
Not reported
49
77 -13 5
9 7-149
11 7-16 9
1 23-16 2
5
Copper (mcg/dL)
70 -14 0
1 12 -19 9
16 5-22 1
1 30-24 0
5 0,
Seleniu m (mcg/L)
63 -16 0
1 16 -14 6
75 -1 45
7 1-1 33
5, 5
Vitamin A (retinol)
20 -10 0
3 2-47
35 -4 4
2 9-4 2
5
27 9-9 66
1 18 -43 8
13 0-65 6
9 9-5 26
6, 1
enzyme (units/L) Alpha-fetoprotein (ng/mL)
(pg/mL) Parathyroid hormonerelated protein (pmol/L) Renin, plasma activity (ng/mL/hour) Thyroid-stimulating hormone (milli-int. units/mL) [American Thyroid Association recommendation]** Thyroxine-binding globulin (mg/dL)
(mcg/dL) Triiodothyronine, free (pg/mL) Triiodothyronine, total (ng/dL) Vitamins and minerals
(mcg/dL) Vitamin B12 (pg/mL)
Vitamin C (ascorbic acid)
0.4 -1 .0
Not reported
No N ot reported
0 .9-1.3
52
25 -45
2 0-65
72 -1 60
6 0-1 19
3 0,
0.5 -5 .0 †
1 .2-1.8
1.1-1.5
0 .7-0.9
53
14 -80
1 8-27
10 -2 2
1 0-1 8
3 0,
5-18
7 -1 3
10 -1 6
1 3-2 3
5
75 -12 0
5 7-88
51 -8 0
5 0-7 7
5, 1
(mg/dL) Vitamin D, 1,25dihydroxy (pg/mL) Vitamin D, 24,25dihydroxy (ng/mL) Vitamin D, 25-hydroxy (ng/mL) Vitamin E (α-tocopherol) (mcg/mL) Zinc (mcg/dL)
Autoimmune and inflammatory mediators C3 complement (mg/dL)
83 -17 7
6 2-98
73 -1 03
7 7-1 11
5
C4 complement (mg/dL)
16 -47
1 8-36
18 -3 4
2 2-3 2
5
C-reactive protein
0.2 -3 .0
Not reported
0.4-20.3
0 .4-8.1
54
0-20 Δ
4 -5 7
7-47
1 3-7 0
55
70 -35 0
9 5-243
99 -2 37
1 12-25 0
5
70 0-1 70 0
9 81 -12 67
81 3-11 31
6 78-99 0
5
50 -30 0
7 8-232
74 -2 18
8 5-2 69
5
1.3 -6 .8 †
2 .0-16 .5
0.9-7.8
0 .8-6.5
56
Estradiol (pg/mL)
<2 0-44 3 Δ,¶¶
1 88 -24 97
12 78 -7 19 2
6 137 -3 46 0
5 6,
Progesterone (n g/mL)
<1 -2 0 Δ
8 -4 8
9 9-3 42
5 6,
Prolactin (ng/mL)
0-20
3 6-213
11 0-33 0
1 37-37 2
3 0,
Sex hormone binding
18 -11 4 Δ
3 9-131
21 4-71 7
2 16-72 4
5 6,
Testosterone (n g/dL)
6-86 Δ
2 5.7 -2 11 .4
34 .3 -24 2.9
6 2.9 -3 08.6
56
17-
0.6 -1 0.6 Δ ,†
5 .2-28 .5
5.2-28.5
1 5.5 -8 4
56
<2 0 0
1 41 -21 0
17 6-29 9
2 19-34 9
5, 6
40-60
40-78
52 -8 7
48 -8 7
5, 6
<100
60-153
77-184
101-224
5, 6
(mg/L) Erythrocyte sedimentation rate (mm/hour) Immunoglobulin A (mg/dL) Immunoglobulin G (mg/dL) Immunoglobulin M (mg/dL) Sex hormones Dehydroepiandrosterone sulfate (mmol/L)
globulin (nmol/L)
hydroxyprogesterone (nmol/L) Lipids Cholesterol, total (mg/dL) High-density lipoprotein c holesterol holesterol (mg/dL) Low-density lipoprotein cholesterol (mg/dL)
6-40 †
10-18
13 -2 3
21 -3 6
62
Triglycerides (mg/dL)
<1 5 0
4 0-159
75 -3 82
1 31-45 3
4, 5,
Apolipoprotein A-I
11 9-2 40
1 11 -15 0
14 2-25 3
1 45-26 2
4, 4
52 -16 3
5 8-81
66 -1 88
8 5-2 38
4, 4
4.8 -6 .8
5 .6-9.7
5.5-9.9
4 .8-8.7
6 4,
Very-low-density lipoprotein c holesterol holesterol (mg/dL)
(mg/dL) Apolipoprotein B (mg/dL) Cardiac function Cardiac ou tpu t (L/min )
68 Cardiac index
2.6 -4 .2
3 .2-4.6
3.1-4.7
2 .5-4.4
6 5,
79 -90
7 7.5 -1 07 .6
70 .3 -10 7.6
5 4-9 9
6 5,
4 6-62
39 -6 2
3 0-4 2
65
70 0-1 60 0
7 47 -14 85
69 2-12 01
1 034 -1 20 1
6 5,
0.7 -0 .9
0 .63 -0 .83
0.65 -0.85
0 .66 -0 .9
6 8,
(L/min/ (L/min/m m 2) Stroke volume (mL) Stroke index (mL/m 2) Systemic vascular resistance resistance (dyns/cm (dyns/cm 5 ) Echocardiography Intraventricular septal septal dimension (cm) Posterior ventricular
92 0.7 5-0.9
0 .56 -0 .8
0.59 -0.9
0 .59 -0 .9
wall dimension (cm) Left ventricular mass
6 8, 92
11 6-1 43
1 08 -16 7
11 5-15 0
1 28-16 2
6 8,
40 -78
5 3-79
58 -8 2
6 0-8 8
6 8,
E/A ratio
1.4 -1 .75
1 .6
1.4
1 .3
6 8,
Left ventricular diastolic
4.3 -4 .8
4 .3-4.6
4.4-4.9
5 .1
6 9,
2.8 -3 .1
2 .8-2.9
2.8-3.4
2 .8-3.3
6 9,
35 -36
3 5-37
3.5
3 5-3 6
6 9,
60 -73
6 1-75
61 -6 3
6 0-7 3
6 9,
Not reported
Not reported
28 .1 .1 -7 -70 .1 .1
Not reported
73
B-type natriuretic
<167 (age- and
1 8.4
13 .5 -29 .5
1 5.5 -4 6
7 1,
peptide (pg/mL)
gender-specific)
Creatine kinase
39 -23 8 Δ
2 7-83
25 -7 5
1 3-1 01
5, 7
<6 ΔΔ
—
—
1 .8-2.4
74 74
(g) Left ventricular mass index
diameter (cm) Left ventricular systolic diameter (cm) Left vent, fractional shortening (percent) Left vent ejection fraction (percent) Cardiac function (blood tests) Atrial natriuretic peptide (pg/mL)
(units/L) Creatine kinase-MB (units/L)
N-terminal pro-brain
50 +/- 2 6
6 0 +/- 45
60 +/- 40
4 3 +/- 34
96
0-0.0 8
Not reported
Not reported
0 -0.06 4
75,
natriuretic peptide (pg/mL) Troponin I (n g/mL)
(intrapartum) Blood gas pH
7.3 8-7.4 2
7.36-7.52
7.40-7.52
7.41-7.53
(arterial)
(venous)
(venous)
(venous)
31,
7.39-7.45 (arterial) PO 2 (mmHg)
90 -10 0
9 3-100
90 -9 8
9 2-1 07
7 7,
PCO 2 (mmHg)
38 -42
Not reported
Not reported
2 5-3 3
77
Bica Bicarb rbona onate te (HCO (HCO3 –)
22 -26
Not reported
Not reported
1 6-2 2
77
49 2-6 96 Δ ,†
6 96 -98 5
61 2-11 70
5 95-94 5
7 9,
10 6-1 32 Δ
1 31 -16 6
13 5-17 0
1 17-18 2
7 9,
16 .9-24 .7 ◊ ◊
1 4.7 -2 1.6
14 .3 -21 .9
1 7.1 -2 5.1
7 9,
50 0-8 00
3 26 -97 5
27 8-10 66
2 38-10 34
82
<3 0
5 -1 5
4-18
3 -22
8 2,
<7 .5 †
1 .6-5.2
0.3-6.9
0 .8-4.2
15
91 -13 0
6 9-140
55 -1 36
5 0-1 66
1 5,
8.8 -1 4 †
1 0.6 -1 1.6
10 .3 -11 .5
1 0.2 -1 1.4
82
25 -10 0 †
1 7-33
10 -3 8
1 1-3 5
15
<1 5 0
1 9-141
47 -1 86
4 6-1 85
83
10 0-2 60 †
5 3-215
34 -2 13
3 7-1 49
1 5,
(mEq/L) Renal function tests Effective renal plasma flow (mL/min) Glomerular filtration rate (GFR) (mL/min) Filtration fraction (percent) Osmolarity, urine (mOsm/kg) 24-h albumin excretion (mg/24 hours) 24-h calcium excretion (mmol/24 hours) 24-h creatinine clearance (mL/min) 24-h creatinine excretion (mmol/24 hours) 24-h potassium excretion (mmol/24 hours) 24-h protein excretion (mg/24 hours) 24-h sodium excretion (mmol/24 hours) * Unless otherwise specified, all normal reference values are from the seventeenth edition of
Harrison's Principles of Internal Medicine [84] . ¶ Range includes references with and without iron supplementation. Δ Normal reference range is specific range for females. ◊ Reference values are from Cerneca et al: Coagulation and fibrinolysis changes in normal pregnancy
increased levels of procoagulants and reduced levels of inhibitors during pregnancy induce a
hypercoagulab hypercoagulable le state, combined combined with a reactive reactive fibrinolysi fibrinolysis s[19] . § References values are from Cerneca et al and Choi et al: Tissue plasminogen activator levels change with with plas plasma ma fibr fibrino inoge gen n conce concentra ntratio tions ns during during preg pregnanc nancy y[17,19] . ￥ Reference values are from Mannuci et al: Changes in health and disease of the metalloprotease that cleav cleaves es von Willeb Willebrand rand factor factor[28] . ‡ Reference values are from Bacq Y et al: Liver function tests in normal pregnancy: a prospective study of 102 preg pregnant nant women and 102 matched matched controls controls[29] . † Reference values are from the fifteenth edition of
Harrison's Principles of Internal Medicine [85] .
** The American Thyroid Association recommends these TSH ranges if individual laboratories do not determine their own trimester-specific reference ranges. ¶¶ Range is for premenopausal females and varies by menstrual cycle phase. ΔΔ Reference values are from Leiserowitz GS et al: Creatine kinase and its MB isoenzyme in the third trimester trimester and the perip peripartum artum perio period d [74] . ◊◊ Reference values are from Dunlop W: Serial changes in renal haemodynamics during normal huma human pregnanc nancy y [79] .
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84. 84 . Kratz A, Pesce MA, Basner RC, Einstein Ein stein AJ. Appendix: Appendix: Laboratory values of clinical clinical importance. In: Longo DL, Fauci AS, Kasper DL, et al (Eds). Harrison's Principles of Internal Medicine, 18th ed, McGraw-Hill, New York 2012. Appendix 1, p A-1. 85. 85 . Stagnaro-Green A, Abalovich Abalovich M, Alexander E, et al. al. Guidelines of of the American Thyroid Associatio Association n for the th e diagnosis diagnosis and an d management man agement of thyroid th yroid disease disease during pregnancy pregnancy and postpartum. postpartum. Thyroid 2011; 201 1; 21:1081. 21:10 81. 86. 86 . Leek AE, Ruoss CF, Kitau Kitau MJ, Chard T. Magernal Magernal plasma alphafetoprotein alphafetoprotein levels in the th e second half of normal pregnancy: Relationship to fetal weight, and maternal age and parity. BJOG 1975; 82:669. 87. 87 . Hale SA, Sobel B, Benvenuto Benvenu to A, et al. al. Coagulation Coagulation and fibrinolytic system protein profiles in women with normal pregnancies and pregnancies complicated by hypertension. Pregnancy Hypertens 2012; 2:152. 88. Spitzer Spitzer M, Kaushal N, Benjamin F. Maternal CA-125 CA-125 levels in in pregnancy and the puerperium. J Reprod Med 1998; 43:387. 89. Aslam Aslam N, Ong C, Woelfer Woelfer B, et al. Serum CA-125 CA-125 at 11-14 weeks of gestation gestation in women with w ith morphologically normal ovaries. BJOG 2000; 107:689. 90. 90 . Jacobs IJ, Fay TN, Stabile Stabile I, et al. The The distribution of CA 125 in the th e reproductive tract of pregnant pregnant and non-pre n on-pregnant gnant women. Br J Obstet Obstet Gynaecol 1988; 198 8; 95:1190. 95:11 90. 91. 91 . Savu O, Jurcuţ R, Giuşcă S, et al. Morphological Morphological and functional function al adaptation adaptation of the th e maternal heart during pregnancy. Circ Cardiovasc Imaging 2012; 5:289. 92. 92 . Vitarelli A, Capotosto L. Role Role of echocardiography in the assessment and an d management managemen t of adult adult congenital heart disease in pregnancy. Int J Cardiovasc Imaging 2011; 27:843. 93. Haram K, Augensen K, Elsayed Elsayed S. Serum Serum protein pattern in n ormal pregnancy pregnancy with special special reference to acute-phase reactants. BJOG 1983; 90:139. 94. 94 . Jozwik M, Jozwik M, Pierzycki K, K, et al. Maternal Matern al and fetal blood blood ammonia concentrations concent rations in normal term human pregnancies. Biol Neonate 2005; 87:38. 95. 95 . Leek AE, Ruoss CF, Kitau Kitau MG, et al. Maternal Matern al plasma plasma alphafetoprotein levels in the second half of normal pregnancy: relationship to fetal weight and maternal age and parity. BJOG 1975; 82:669. 96. 96 . Burlingame Burlin game J, J, Hyeong JA, Tang WHW. Changes in cardiovascular cardiovascular biomarkers biomarkers throughout throu ghout pregnancy pregnancy and the t he remote postpartum postpartum period. period. Am J Obstet Gynecol 2013; 201 3; 208:S97. 208 :S97. Modified and reproduced with permission from: Abbassi-Ghanavati M, Greer LG. Reference Table of Normal Laboratory Values in Uncomplicated Pregnancies. In: Cunningham FG, Leveno KJ, Bloom S, Hauth JC, Rouse DJ, Spong CY. Williams Obstetrics, 23rd Edition. New York: McGraw-Hill, 2010. Copyright © 2010 The McGraw-Hill Companies, Inc. Graphic 81137 Version 40.0
Coagulation cascade overview
This schematic shows a revised version of the coagulation cascade that emphasizes the importance of pathways for hemostasis in vivo. Tissue factor exposed at a wound interacts with factor VIIa and initiates clotting by two pathways: (1) activaton of factor X to Xa (ie, the extrinsic ten-ase complex) and (2) conversion of factor IX to IXa, which activates factor X to Xa (ie, the intrinsic ten-ase complex). Pathways 1 and 2 are equally important. In a third pathway (3), thrombin also activates factor XI to XIa, which can lead to further generation of factor IXa; this is required during severe hemostatic challenges. Coagulation factors are shown as Roman numerals. Only the activated forms (with the suffix "a") are shown in this diagram for simplicity. Thrombin is also known as factor IIa. Graphic 90873 Version 4.0
Components of the plasma fibrinolytic system Molecular weight (d)
Activity
Plasminogen
88,000 (sing (single le chain) chain)
Proenzyme Proenzyme form form of fibrinol fibrinolytic ytic enzyme
Plasmin
88,000 (two (two chain) chain)
Activ Active e fibr fibrino inoly lytic tic enzyme enzyme
TPA
70,00 0 (one/two (one/two
Enzyme present in tissues that coverts plasminogen
chain)
to plasmin
UPA
54,000 (two chain) chain)
Plasmino Plasminoge gen n activato activatorr (diff (differe erent nt from from tPA)
α2PI
70,000 (singl (single e chain) chain)
Speci Specific fic fast-a fast-acting cting inhibitor inhibitor in plasma plasma
PAI-1
40,00 0 (single (single chain)
Fast-acting Fast-acting inhibitor of tPA (and UPA) secreted secreted by endothelial cells)
d: Daltons; TPA: tissue plasminogen activator; UPA: urokinase-like plasminogen activator; α2PI: alpha-2 plasmin inhibitor; PAI-1: plasminogen activator inhibitor-1. Graphic 70156 Version 3.0
Regulation of fibrinolysis by plasminogen activator inhibitor-1 (PAI-1), α2-antiplasmin, and thrombinactivatable fibrinolysis inhibitor (TAFI)
PAI-1 inhibits plasmin formation by inhibiting tissue-type plasminogen activator (t-PA). α2-antiplasmin inhibits the activity of plasmin, thereby inhibiting fibrinolysis. TAFI circulates in plasma as a zymogen. It is activated by thrombin when thrombin is bound on endothelial thrombomodulin, and therefore represents a link between blood coagulation and fibrinolysis. During fibrinolysis, plasmin cleaves intact fibrin at lysine residues, initially yielding large, insoluble fibrin fragments with lysine residues at their carboxyl termini. Plasminogen binds avidly to C-terminal lysine residues within the partially degraded fibrin clot and assumes a conformation that is susceptible to activation by t-PA, thereby promoting plasmin formation, continued fibrinolysis ("rapid lysis by plasmin"), and generation of smaller, soluble fibrin fragments that are dispersed by flowing blood. Activated TAFI (TAF (TAFIIa ) is a carb ca rboxypeptidase oxypeptidase that removes removes lysi ne residues from the carboxy (C) termini of partially degraded fibrin fragments. By removing C-terminal lysine residues from large fibrin fragments in the partially degraded clot, TAFI inhibits recruitment of plasminogen to the clot, thereby slowing fibrinolysis ("slow lysis by plasmin").
Diagram supplied by William P Fay, MD. Graphic 81428 Version 5.0
Disclosures Kenneth A Bauer, MD Consultant/Advisory Boards: Janssen Pharmaceuticals [Anticoagulation (Rivaroxaban)]; Daiichi Sankyo [Anticoagulation (Edoxaban)]; Portola Pharmaceuticals Pharmaceuticals [Anticoagulati [Anticoagulation on rever sal, anticoagulation anticoagulation (Andexanet, betrixaban)]; Instrumentation Instrumentation Laboratory [Coagulation instruments/reagents (ACL TOP instruments and reagents)]. Charles J Lockwood, MD, MHCM Consultant/Advisory Consultant/Advisory Boards: Celula [Aneuploidy [Aneuploidy sc reening (Prenatal and cancer DNA screening tests in development)]. Kristen Eckler, MD, FACOG Nothing to disclose. Jennifer S Tirnauer, MD Nothing to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Disclosures:
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