Hematologic changes in pregnancy
- Kenneth A Bauer, MD
Kenneth A Bauer, MD
- Professor of Medicine
- Harvard Medical School
- Section Editor
- Charles J Lockwood, MD, MHCM
Charles J Lockwood, MD, MHCM
- Section Editor — Obstetrics
- Senior Vice President, USF Health
- Dean, Morsani College of Medicine
- Professor, Obstetrics and Gynecology
- University of South Florida
Normal pregnancy is characterized by profound changes in almost every organ system to accommodate the demands of the fetoplacental unit. The hematologic system must adapt in a number of ways, such as provision of vitamins and minerals for fetal hematopoiesis (iron, vitamin B12, folic 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, 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 pregnancy. Hematologic complications of pregnancy are discussed in separate topic reviews.
The most significant hematological changes during pregnancy include the following (table 1):
- Lund CJ, Donovan JC. Blood volume during pregnancy. Significance of plasma and red cell volumes. Am J Obstet Gynecol 1967; 98:394.
- Bernstein IM, Ziegler W, Badger GJ. Plasma volume expansion in early pregnancy. Obstet Gynecol 2001; 97:669.
- Whittaker PG, Lind T. The intravascular mass of albumin during human pregnancy: a serial study in normal and diabetic women. Br J Obstet Gynaecol 1993; 100:587.
- PRITCHARD JA. CHANGES IN THE BLOOD VOLUME DURING PREGNANCY AND DELIVERY. Anesthesiology 1965; 26:393.
- Schrier RW. Pathogenesis of sodium and water retention in high-output and low-output cardiac failure, nephrotic syndrome, cirrhosis, and pregnancy (2). N Engl J Med 1988; 319:1127.
- Nadel AS, Ballermann BJ, Anderson S, Brenner BM. Interrelationships among atrial peptides, renin, and blood volume in pregnant rats. Am J Physiol 1988; 254:R793.
- Lindheimer MD, Katz AI. Sodium and diuretics in pregnancy. N Engl J Med 1973; 288:891.
- Metcalfe J, Stock MK, Barron DH. Maternal physiology during gestation. In: The Physiology of Reproduction, Knobil K, Ewing L (Eds), Raven Press, New York 1988. p.2145.
- McLENNAN CE. Plasma volume late in pregnancy. Am J Obstet Gynecol 1950; 59:662.
- Campbell DM, MacGillivray I. Comparison of maternal response in first and second pregnancies in relation to baby weight. J Obstet Gynaecol Br Commonw 1972; 79:684.
- Ueland K. Maternal cardiovascular dynamics. VII. Intrapartum blood volume changes. Am J Obstet Gynecol 1976; 126:671.
- Hytten FE, Lind T. Indices of cardiovascular function. In: Diagnostic Indices in Pregnancy, Hytten FE, Lind T (Eds), Documenta Geigy, Basel 1973.
- Lurie S, Mamet Y. Red blood cell survival and kinetics during pregnancy. Eur J Obstet Gynecol Reprod Biol 2000; 93:185.
- Harstad TW, Mason RA, Cox SM. Serum erythropoietin quantitation in pregnancy using an enzyme-linked immunoassay. Am J Perinatol 1992; 9:233.
- Milman N, Graudal N, Nielsen OJ, Agger AO. Serum erythropoietin during normal pregnancy: relationship to hemoglobin and iron status markers and impact of iron supplementation in a longitudinal, placebo-controlled study on 118 women. Int J Hematol 1997; 66:159.
- Whittaker PG, Macphail S, Lind T. Serial hematologic changes and pregnancy outcome. Obstet Gynecol 1996; 88:33.
- Haram K, Nilsen ST, Ulvik RJ. Iron supplementation in pregnancy--evidence and controversies. Acta Obstet Gynecol Scand 2001; 80:683.
- Bille-Brahe NE, Rørth M. Red cell 2.3-diphosphoglycerate in pregnancy. Acta Obstet Gynecol Scand 1979; 58:19.
- Stephansson O, Dickman PW, Johansson A, Cnattingius S. Maternal hemoglobin concentration during pregnancy and risk of stillbirth. JAMA 2000; 284:2611.
- Centers for Disease Control (CDC). CDC criteria for anemia in children and childbearing-aged women. MMWR Morb Mortal Wkly Rep 1989; 38:400.
- Institute of Medicine. Iron deficiency anemia: recommended guidelines for the prevention, detection, and management among US children and women of childbearing age. 1993, Washington, DC.
- World Health Organization. Iron Deficiency Anaemia. Assessment, Prevention, and Control. A guide for programme managers. 2001. http://www.who.int/nutrition/publications/en/ida_assessment_prevention_control.pdf (Accessed on September 06, 2011).
- American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 95: anemia in pregnancy. Obstet Gynecol 2008; 112:201.
- Bailit JL, Doty E, Todia W. Repeated hematocrit measurements in low-risk pregnant women. J Reprod Med 2007; 52:619.
- Carles G, Tobal N, Raynal P, et al. Doppler assessment of the fetal cerebral hemodynamic response to moderate or severe maternal anemia. Am J Obstet Gynecol 2003; 188:794.
- Sifakis S, Pharmakides G. Anemia in pregnancy. Ann N Y Acad Sci 2000; 900:125.
- Brabin BJ, Hakimi M, Pelletier D. An analysis of anemia and pregnancy-related maternal mortality. J Nutr 2001; 131:604S.
- www.who.int/making_pregnancy_safer/publications/en/ (accessed July 15, 2008).
- Zeng L, Dibley MJ, Cheng Y, et al. Impact of micronutrient supplementation during pregnancy on birth weight, duration of gestation, and perinatal mortality in rural western China: double blind cluster randomised controlled trial. BMJ 2008; 337:a2001.
- Christian P, Murray-Kolb LE, Khatry SK, et al. Prenatal micronutrient supplementation and intellectual and motor function in early school-aged children in Nepal. JAMA 2010; 304:2716.
- KUVIN SF, BRECHER G. Differential neutrophil counts in pregnancy. N Engl J Med 1962; 266:877.
- Molberg P, Johnson C, Brown TS. Leukocytosis in labor: what are its implications? Fam Pract Res J 1994; 14:229.
- Acker DB, Johnson MP, Sachs BP, Friedman EA. The leukocyte count in labor. Am J Obstet Gynecol 1985; 153:737.
- Siegel I, Gleicher N. Peripheral white blood cell alterations in early labor. Diagn Gynecol Obstet 1981; 3:123.
- Fernández-Suárez A, Pascual VT, Gimenez MT, Hernández JF. Immature granulocyte detection by the SE-9000 haematology analyser during pregnancy. Clin Lab Haematol 2003; 25:347.
- Pramanik SS, Pramanik T, Mondal SC, Chanda R. Number, maturity and phagocytic activity of neutrophils in the three trimesters of pregnancy. East Mediterr Health J 2007; 13:862.
- Kühnert M, Strohmeier R, Stegmüller M, Halberstadt E. Changes in lymphocyte subsets during normal pregnancy. Eur J Obstet Gynecol Reprod Biol 1998; 76:147.
- Giles C, Inglis TC. Thrombocytopenia and macrothrombocytosis in gestational hypertension. Br J Obstet Gynaecol 1981; 88:1115.
- Matthews JH, Benjamin S, Gill DS, Smith NA. Pregnancy-associated thrombocytopenia: definition, incidence and natural history. Acta Haematol 1990; 84:24.
- Verdy E, Bessous V, Dreyfus M, et al. Longitudinal analysis of platelet count and volume in normal pregnancy. Thromb Haemost 1997; 77:806.
- Ahmed Y, van Iddekinge B, Paul C, et al. Retrospective analysis of platelet numbers and volumes in normal pregnancy and in pre-eclampsia. Br J Obstet Gynaecol 1993; 100:216.
- Minakami H, Kuwata T, Sato I. Gestational thrombocytopenia: is it new? Am J Obstet Gynecol 1996; 175:1676.
- Burrows RF, Kelton JG. Fetal thrombocytopenia and its relation to maternal thrombocytopenia. N Engl J Med 1993; 329:1463.
- Rouse DJ, Owen J, Goldenberg RL. Routine maternal platelet count: an assessment of a technologically driven screening practice. Am J Obstet Gynecol 1998; 179:573.
- George JN, Woolf SH, Raskob GE, et al. Idiopathic thrombocytopenic purpura: a practice guideline developed by explicit methods for the American Society of Hematology. Blood 1996; 88:3.
- Saha P, Stott D, Atalla R. Haemostatic changes in the puerperium '6 weeks postpartum' (HIP Study) - implication for maternal thromboembolism. BJOG 2009; 116:1602.
- Paidas MJ, Ku DH, Arkel YS. Screening and management of inherited thrombophilias in the setting of adverse pregnancy outcome. Clin Perinatol 2004; 31:783.
- Greer IA. Epidemiology, risk factors and prophylaxis of venous thrombo-embolism in obstetrics and gynaecology. Baillieres Clin Obstet Gynaecol 1997; 11:403.
- Greer IA. Thrombosis in pregnancy: maternal and fetal issues. Lancet 1999; 353:1258.
- Lindqvist P, Dahlbäck B, Marŝál K. Thrombotic risk during pregnancy: a population study. Obstet Gynecol 1999; 94:595.
- Andersen BS, Steffensen FH, Sørensen HT, et al. The cumulative incidence of venous thromboembolism during pregnancy and puerperium--an 11 year Danish population-based study of 63,300 pregnancies. Acta Obstet Gynecol Scand 1998; 77:170.
- Hellgren M, Blombäck M. Studies on blood coagulation and fibrinolysis in pregnancy, during delivery and in the puerperium. I. Normal condition. Gynecol Obstet Invest 1981; 12:141.
- Stirling Y, Woolf L, North WR, et al. Haemostasis in normal pregnancy. Thromb Haemost 1984; 52:176.
- Comp PC, Thurnau GR, Welsh J, Esmon CT. Functional and immunologic protein S levels are decreased during pregnancy. Blood 1986; 68:881.
- Cumming AM, Tait RC, Fildes S, et al. Development of resistance to activated protein C during pregnancy. Br J Haematol 1995; 90:725.
- Bremme KA. Haemostatic changes in pregnancy. Best Pract Res Clin Haematol 2003; 16:153.
- Hellgren M. Hemostasis during normal pregnancy and puerperium. Semin Thromb Hemost 2003; 29:125.
- James AH, Rhee E, Thames B, Philipp CS. Characterization of antithrombin levels in pregnancy. Thromb Res 2014; 134:648.
- 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.
- Dahlman T, Hellgren M, Blombäck M. Changes in blood coagulation and fibrinolysis in the normal puerperium. Gynecol Obstet Invest 1985; 20:37.
- Gerbasi FR, Bottoms S, Farag A, Mammen E. Increased intravascular coagulation associated with pregnancy. Obstet Gynecol 1990; 75:385.
- Sánchez-Luceros A, Meschengieser SS, Marchese C, et al. Factor VIII and von Willebrand factor changes during normal pregnancy and puerperium. Blood Coagul Fibrinolysis 2003; 14:647.
- Wickström K, Edelstam G, Löwbeer CH, et al. Reference intervals for plasma levels of fibronectin, von Willebrand factor, free protein S and antithrombin during third-trimester pregnancy. Scand J Clin Lab Invest 2004; 64:31.
- Esmon CT. Molecular events that control the protein C anticoagulant pathway. Thromb Haemost 1993; 70:29.
- 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.
- 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.
- Senent M, Bellart J, Zuazu-Jausoro I, et al. [Markers of hypercoagulability during pregnancy: thrombin-antithrombin-III complexes and D dimer]. Sangre (Barc) 1991; 36:21.
- van Wersch JW, Ubachs JM. Blood coagulation and fibrinolysis during normal pregnancy. Eur J Clin Chem Clin Biochem 1991; 29:45.
- Mercelina-Roumans PE, Ubachs JM, van Wersch JW. Coagulation and fibrinolysis in smoking and nonsmoking pregnant women. Br J Obstet Gynaecol 1996; 103:789.
- 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.
- Bellart J, Gilabert R, Fontcuberta J, et al. Fibrinolysis changes in normal pregnancy. J Perinat Med 1997; 25:368.
- 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.
- Kline JA, Williams GW, Hernandez-Nino J. D-dimer concentrations in normal pregnancy: new diagnostic thresholds are needed. Clin Chem 2005; 51:825.
- Bonnar J, McNicol GP, Douglas AS. Fibrinolytic enzyme system and pregnancy. Br Med J 1969; 3:387.
- 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.