Thrombocytopenia in pregnancy
- James N George, MD
James N George, MD
- Professor of Medicine
- University of Oklahoma Health Sciences Center
- Eric J Knudtson, MD
Eric J Knudtson, MD
- Associate Professor, Maternal Fetal Medicine
- University of Oklahoma
- Section Editors
- Lawrence LK Leung, MD
Lawrence LK Leung, MD
- Editor-in-Chief — Hematology
- Section Editor — Disorders of Hemostasis and Coagulation
- Professor of Medicine
- Stanford University School of Medicine
- 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
- Deputy Editors
- Jennifer S Tirnauer, MD
Jennifer S Tirnauer, MD
- Deputy Editor — Hematology
- Vanessa A Barss, MD, FACOG
Vanessa A Barss, MD, FACOG
- Senior Deputy Editor — UpToDate
- Deputy Editor — Obstetrics, Gynecology and Women's Health
- Associate Clinical Professor of Obstetrics, Gynecology and Reproductive Biology
- Harvard Medical School
Thrombocytopenia occurring during pregnancy is a common diagnostic and management problem and may have many causes (table 1) The most common of these, along with their manifestations, are shown in the table (table 2). Asymptomatic thrombocytopenia is observed near term in about 5 percent of normal pregnancies, and thrombocytopenia, sometimes severe, develops in about 15 percent of women with preeclampsia , which itself occurs in about 3 to 4 percent of pregnancies in the United States (table 3) . The diagnosis and management of thrombocytopenia in pregnancy will be discussed here . This discussion will focus on two issues:
●Thrombocytopenia discovered incidentally during a normal pregnancy and its distinction from immune thrombocytopenia (ITP)
●Thrombocytopenia associated with preeclampsia/eclampsia and the HELLP syndrome and their distinction from thrombotic thrombocytopenic purpura (TTP)
An overall approach to the patient with thrombocytopenia is discussed separately. (See "Approach to the adult with unexplained thrombocytopenia".)
Platelet counts are within the normal range of 150,000 to 450,000/microL in the vast majority of women during normal pregnancies, however they may be slightly lower, on average, than in healthy, non-pregnant women [4-6].
- Burrows RF, Kelton JG. Fetal thrombocytopenia and its relation to maternal thrombocytopenia. N Engl J Med 1993; 329:1463.
- Saftlas AF, Olson DR, Franks AL, et al. Epidemiology of preeclampsia and eclampsia in the United States, 1979-1986. Am J Obstet Gynecol 1990; 163:460.
- Myers B. Diagnosis and management of maternal thrombocytopenia in pregnancy. Br J Haematol 2012; 158:3.
- 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.
- Boehlen F, Hohlfeld P, Extermann P, et al. Platelet count at term pregnancy: a reappraisal of the threshold. Obstet Gynecol 2000; 95:29.
- Fenton V, Saunders K, Cavill I. The platelet count in pregnancy. J Clin Pathol 1977; 30:68.
- Stirling Y, Woolf L, North WR, et al. Haemostasis in normal pregnancy. Thromb Haemost 1984; 52:176.
- Sill PR, Lind T, Walker W. Platelet values during normal pregnancy. Br J Obstet Gynaecol 1985; 92:480.
- Tygart SG, McRoyan DK, Spinnato JA, et al. Longitudinal study of platelet indices during normal pregnancy. Am J Obstet Gynecol 1986; 154:883.
- 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.
- Sejeny SA, Eastham RD, Baker SR. Platelet counts during normal pregnancy. J Clin Pathol 1975; 28:812.
- Fay RA, Hughes AO, Farron NT. Platelets in pregnancy: hyperdestruction in pregnancy. Obstet Gynecol 1983; 61:238.
- Verdy E, Bessous V, Dreyfus M, et al. Longitudinal analysis of platelet count and volume in normal pregnancy. Thromb Haemost 1997; 77:806.
- Tsunoda T, Ohkuchi A, Izumi A, et al. Antithrombin III activity and platelet count are more likely to decrease in twin pregnancies than in singleton pregnancies. Acta Obstet Gynecol Scand 2002; 81:840.
- 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.
- Burrows RF, Kelton JG. Platelets and pregnancy. In: Current Obstetric Medicine, Lee RV (Ed), Mosby-Year Book, St Louis 1993. Vol 2, p.83.
- Ballem PJ. Diagnosis and management of thrombocytopenia in obstetric syndromes. In: Obstetric Transfusion Practice, Sacher RA, Brecher ME (Eds), American Association of Blood Banks, Bethesda 1993. p.49.
- Anteby E, Shalev O. Clinical relevance of gestational thrombocytopenia of < 100,000/microliters. Am J Hematol 1994; 47:118.
- Letsky EA, Greaves M. Guidelines on the investigation and management of thrombocytopenia in pregnancy and neonatal alloimmune thrombocytopenia. Maternal and Neonatal Haemostasis Working Party of the Haemostasis and Thrombosis Task Force of the British Society for Haematology. Br J Haematol 1996; 95:21.
- Lescale KB, Eddleman KA, Cines DB, et al. Antiplatelet antibody testing in thrombocytopenic pregnant women. Am J Obstet Gynecol 1996; 174:1014.
- Ajzenberg N, Dreyfus M, Kaplan C, et al. Pregnancy-associated thrombocytopenia revisited: assessment and follow-up of 50 cases. Blood 1998; 92:4573.
- Moise KJ Jr. Autoimmune thrombocytopenic purpura in pregnancy. Clin Obstet Gynecol 1991; 34:51.
- Burrows RF, Kelton JG. Pregnancy in patients with idiopathic thrombocytopenic purpura: assessing the risks for the infant at delivery. Obstet Gynecol Surv 1993; 48:781.
- Payne SD, Resnik R, Moore TR, et al. Maternal characteristics and risk of severe neonatal thrombocytopenia and intracranial hemorrhage in pregnancies complicated by autoimmune thrombocytopenia. Am J Obstet Gynecol 1997; 177:149.
- Valat AS, Caulier MT, Devos P, et al. Relationships between severe neonatal thrombocytopenia and maternal characteristics in pregnancies associated with autoimmune thrombocytopenia. Br J Haematol 1998; 103:397.
- Silver RM, Branch DW, Scott JR. Maternal thrombocytopenia in pregnancy: time for a reassessment. Am J Obstet Gynecol 1995; 173:479.
- Shalev O, Anteby E. Epidural anesthesia can be safely performed in gestational thrombocytopenia of >50,000/uL (abstract). Blood 1996; 88:62a.
- Webert KE, Mittal R, Sigouin C, et al. A retrospective 11-year analysis of obstetric patients with idiopathic thrombocytopenic purpura. Blood 2003; 102:4306.
- Allford SL, Hunt BJ, Rose P, et al. Guidelines on the diagnosis and management of the thrombotic microangiopathic haemolytic anaemias. Br J Haematol 2003; 120:556.
- Provan D, Stasi R, Newland AC, et al. International consensus report on the investigation and management of primary immune thrombocytopenia. Blood 2010; 115:168.
- Neunert C, Lim W, Crowther M, et al. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood 2011; 117:4190.
- Simon L, Santi TM, Sacquin P, Hamza J. Pre-anaesthetic assessment of coagulation abnormalities in obstetric patients: usefulness, timing and clinical implications. Br J Anaesth 1997; 78:678.
- Ruggeri M, Schiavotto C, Castaman G, et al. Gestational thrombocytopenia: a prospective study. Haematologica 1997; 82:341.
- Gill KK, Kelton JG. Management of idiopathic thrombocytopenic purpura in pregnancy. Semin Hematol 2000; 37:275.
- Christiaens GC, Nieuwenhuis HK, von dem Borne AE, et al. Idiopathic thrombocytopenic purpura in pregnancy: a randomized trial on the effect of antenatal low dose corticosteroids on neonatal platelet count. Br J Obstet Gynaecol 1990; 97:893.
- Martí-Carvajal AJ, Peña-Martí GE, Comunián-Carrasco G. Medical treatments for idiopathic thrombocytopenic purpura during pregnancy. Cochrane Database Syst Rev 2009; :CD007722.
- Chakravarty EF, Murray ER, Kelman A, Farmer P. Pregnancy outcomes after maternal exposure to rituximab. Blood 2011; 117:1499.
- Yamada H, Kato EH, Kishida T, et al. Risk factors for neonatal thrombocytopenia in pregnancy complicated by idiopathic thrombocytopenic purpura. Ann Hematol 1998; 76:211.
- Asano T, Sawa R, Araki T, Yamamoto M. Incidence of thrombocytopenia in infants born to mothers with idiopathic thrombocytopenic purpura. Acta Paediatr Jpn 1998; 40:112.
- Iyori H, Fujisawa K, Akatsuka J. Thrombocytopenia in neonates born to women with autoimmune thrombocytopenic purpura. Pediatr Hematol Oncol 1997; 14:367.
- Christiaens GC, Nieuwenhuis HK, Bussel JB. Comparison of platelet counts in first and second newborns of mothers with immune thrombocytopenic purpura. Obstet Gynecol 1997; 90:546.
- Cook RL, Miller RC, Katz VL, Cefalo RC. Immune thrombocytopenic purpura in pregnancy: a reappraisal of management. Obstet Gynecol 1991; 78:578.
- Veneri D, Franchini M, Raffaelli R, et al. Idiopathic thrombocytopenic purpura in pregnancy: Analysis of 43 consecutive cases followed at a single Italian institution. Ann Hematol 2006; 85:552.
- Paidas MJ, Berkowitz RL, Lynch L, et al. Alloimmune thrombocytopenia: fetal and neonatal losses related to cordocentesis. Am J Obstet Gynecol 1995; 172:475.
- Fujimura K, Harada Y, Fujimoto T, et al. Nationwide study of idiopathic thrombocytopenic purpura in pregnant women and the clinical influence on neonates. Int J Hematol 2002; 75:426.
- Koyama S, Tomimatsu T, Kanagawa T, et al. Reliable predictors of neonatal immune thrombocytopenia in pregnant women with idiopathic thrombocytopenic purpura. Am J Hematol 2012; 87:15.
- Samuels P, Bussel JB, Braitman LE, et al. Estimation of the risk of thrombocytopenia in the offspring of pregnant women with presumed immune thrombocytopenic purpura. N Engl J Med 1990; 323:229.
- Cines DB. ITP and pregnancy (editorial). Blood 2003; 102:4250.
- Cunningham FG, Lindheimer MD. Hypertension in pregnancy. N Engl J Med 1992; 326:927.
- Mushambi MC, Halligan AW, Williamson K. Recent developments in the pathophysiology and management of pre-eclampsia. Br J Anaesth 1996; 76:133.
- Leitch CR, Cameron AD, Walker JJ. The changing pattern of eclampsia over a 60-year period. Br J Obstet Gynaecol 1997; 104:917.
- Thomas SV. Neurological aspects of eclampsia. J Neurol Sci 1998; 155:37.
- Sibai BM, Ramadan MK, Chari RS, Friedman SA. Pregnancies complicated by HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets): subsequent pregnancy outcome and long-term prognosis. Am J Obstet Gynecol 1995; 172:125.
- Weiner CP. Thrombotic microangiopathy in pregnancy and the postpartum period. Semin Hematol 1987; 24:119.
- Martin JN Jr, Bailey AP, Rehberg JF, et al. Thrombotic thrombocytopenic purpura in 166 pregnancies: 1955-2006. Am J Obstet Gynecol 2008; 199:98.
- McMinn JR, George JN. Evaluation of women with clinically suspected thrombotic thrombocytopenic purpura-hemolytic uremic syndrome during pregnancy. J Clin Apher 2001; 16:202.
- Ibdah JA, Bennett MJ, Rinaldo P, et al. A fetal fatty-acid oxidation disorder as a cause of liver disease in pregnant women. N Engl J Med 1999; 340:1723.
- Lam C, Lim KH, Karumanchi SA. Circulating angiogenic factors in the pathogenesis and prediction of preeclampsia. Hypertension 2005; 46:1077.
- Young B, Levine RJ, Salahuddin S, et al. The use of angiogenic biomarkers to differentiate non-HELLP related thrombocytopenia from HELLP syndrome. J Matern Fetal Neonatal Med 2010; 23:366.
- Martin JN Jr, Blake PG, Perry KG Jr, et al. The natural history of HELLP syndrome: patterns of disease progression and regression. Am J Obstet Gynecol 1991; 164:1500.
- Martin JN Jr, Files JC, Blake PG, et al. Postpartum plasma exchange for atypical preeclampsia-eclampsia as HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome. Am J Obstet Gynecol 1995; 172:1107.
- Amorosi EL, Ultmann JE. Thrombotic thrombocytopenic purpura: Report of 16 cases and review of the literature. Medicine (Baltimore) 1966; 45:139.
- Ezra Y, Rose M, Eldor A. Therapy and prevention of thrombotic thrombocytopenic purpura during pregnancy: a clinical study of 16 pregnancies. Am J Hematol 1996; 51:1.
- George JN. The association of pregnancy with thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Curr Opin Hematol 2003; 10:339.
- Dashe JS, Ramin SM, Cunningham FG. The long-term consequences of thrombotic microangiopathy (thrombotic thrombocytopenic purpura and hemolytic uremic syndrome) in pregnancy. Obstet Gynecol 1998; 91:662.
- Fakhouri F, Roumenina L, Provot F, et al. Pregnancy-associated hemolytic uremic syndrome revisited in the era of complement gene mutations. J Am Soc Nephrol 2010; 21:859.
- Mokrzycki MH, Rickles FR, Kaplan AA, Kohn OF. Thrombotic thrombocytopenic purpura in pregnancy: successful treatment with plasma exchange. Case report and review of the literature. Blood Purif 1995; 13:271.
- Scully M, Thomas M, Underwood M, et al. Thrombotic thrombocytopenic purpura and pregnancy: presentation, management, and subsequent pregnancy outcomes. Blood 2014; 124:211.
- Moatti-Cohen M, Garrec C, Wolf M, et al. Unexpected frequency of Upshaw-Schulman syndrome in pregnancy-onset thrombotic thrombocytopenic purpura. Blood 2012; 119:5888.
- McCrae KR, Cines DB. Thrombotic microangiopathy during pregnancy. Semin Hematol 1997; 34:148.
- Natelson EA, White D. Recurrent thrombotic thrombocytopenic purpura in early pregnancy: effect of uterine evacuation. Obstet Gynecol 1985; 66:54S.
- Egerman RS, Witlin AG, Friedman SA, Sibai BM. Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome in pregnancy: review of 11 cases. Am J Obstet Gynecol 1996; 175:950.
- Bell WR, Braine HG, Ness PM, Kickler TS. Improved survival in thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Clinical experience in 108 patients. N Engl J Med 1991; 325:398.
- Wurzei JM. TTP lesions in placenta but not fetus. N Engl J Med 1979; 301:503.
- Fujimura Y, Matsumoto M, Kokame K, et al. Pregnancy-induced thrombocytopenia and TTP, and the risk of fetal death, in Upshaw-Schulman syndrome: a series of 15 pregnancies in 9 genotyped patients. Br J Haematol 2009; 144:742.
- Scully M, Starke R, Lee R, et al. Successful management of pregnancy in women with a history of thrombotic thrombocytopaenic purpura. Blood Coagul Fibrinolysis 2006; 17:459.
- Nguyen L, Terrell DR, Duvall D, et al. Complications of plasma exchange in patients treated for thrombotic thrombocytopenic purpura. IV. An additional study of 43 consecutive patients, 2005 to 2008. Transfusion 2009; 49:392.
- Vesely SK, Li X, McMinn JR, et al. Pregnancy outcomes after recovery from thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Transfusion 2004; 44:1149.
- Ananth CV, Keyes KM, Wapner RJ. Pre-eclampsia rates in the United States, 1980-2010: age-period-cohort analysis. BMJ 2013; 347:f6564.
- www.ouhsc.edu/platelets (Accessed on March 01, 2011).
- NORMAL PREGNANCY
- GESTATIONAL THROMBOCYTOPENIA
- Differential diagnosis
- Platelet count monitoring
- Course and prognosis
- IMMUNE THROMBOCYTOPENIA (ITP)
- Maternal management issues
- - Early pregnancy
- - Neuraxial anesthesia
- - Delivery and postpartum
- Fetal/neonatal management issues
- PREECLAMPSIA AND HELLP SYNDROME
- Definitions and prevalence
- Degree of thrombocytopenia
- Differential diagnosis
- - Use of dexamethasone for HELLP syndrome
- Incidence and timing
- Hereditary versus acquired syndromes
- Evaluation and diagnosis
- Recurrence in subsequent pregnancies
- HEPARIN-INDUCED THROMBOCYTOPENIA (HIT)
- ADDITIONAL INFORMATION
- SUMMARY AND RECOMMENDATIONS