Authors: James N George, MD, Jennifer J McIntosh, DO, MS
Section Editors: Lawrence LK Leung, MD, Charles J Lockwood, MD, MHCM
Literature review current through: Apr 2020. | This topic last updated: Jan 06, 2020.
Тромбоцитопения – это состояние, сопровождающееся уменьшением количества тромбоцитов ниже 150х109/л. Продолжительность жизни клеток при этом не меняется и составляет 8-9 дней.
При физиологическом течении беременности, к третьему триместру в результате гемодилюции уровень тромбоцитов снижается на 10% от исходного.
Частота тромбоцитопений у беременных составляет 5-10% и является самым распространенным гематологическим состоянием (после анемии), которое выявляется во время гестациии.
Наиболее частыми причинами снижения уровня тромбоцитов у беременных являются гестационная тромбоцитопения (75%), вторичная тромбоцитопения на фоне преэклампсии и эклампсии (15%), иммунная тромбоцитопения (6%) и симптоматические состояния (на фоне системной красной волчанки, АФС, миелопролиферативных неоплазий, ДВС). Кроме того, причинами тромбоцитопении могут быть дефицит фолиевой кислоты и витамина В12, гемолитико-уремический синдром, ВИЧ-инфекция и применение ряда лекарственных средств (ампициллин, пенициллин, аспирин, парацетамол, индометацин, вальпроевая кислота, карбамазепин, метилдопа, гепарит, ранитидин, циклоспорин, циметидин, фуросемид).
По степени выраженности тромбоцитопения классифицируется на:
- легкую – количество тромбоцитов 100-150х109/л;
- умеренную – количество тромбоцитов 50-100х109/л;
- тяжелую (выраженную) – количество тромбоцитов менее 50х109/л.
Гестационная тромбоцитопения, или связанная с беременностью тромбоцитопения, это доброкачественное заболевание, которое не требует проведения дополнительных лечебных мероприятий. Это наиболее частая причина развития тромбоцитопении во время гестации и не ассоциируется с риском развития акушерских осложнений.
Общими характеристиками гестационной тромбоцитопении являются:
Иммунная тромбоцитопения (ИТ) – это аутоиммунное заболевание, при котором в организме женщины образуются антитела к гликопротеину плазматической мембраны тромбоцитов (чаще к GPIIb/IIa и Ib/IX), приводящие к их разрушению. Тромбоциты с антителами на своей поверхности распознаются и разрушаются клетками ретикулоэндотелиальной системы, преимущественно в селезенке.
Иммунная тромбоцитопения встречается с частотой 1-3 случая на 10.000 беременностей, или 3-5% всех тромбоцитопений. ИТ может развиваться в любом триместре беременности, а также вторично на фоне бактериальных инфекций, СКВ и АФС. Клинически течение ИТ обычно бессимптомно или сопровождается развитием незначительных петехиальных кровоизлияний.
В каждом четвертом случае (около 5%) в связи с трансплацентарным проникновением анти-тромбоцитарных IgG у плода развивается тромбоцитопения, внутримозговые кровоизлияния, а у новорожденных диагностируется пурпура и экхимозы (подкожных кровоизлияний диаметром более 3 мм).
Тромботическая тромбоцитопеническая пурпура (ТТП) – это острое угрожающее жизни заболевание, клинический синдром, который характеризуется тромбоцитопенией, микроангиопатической гемолитической анемией, микроваскулярным тромбозом концевых артериол и капилляров, множественной дисфункцией органов. Основу болезни составляет резкое повышение агрегации тромбоцитов с образованием тромбоцитарных (или гиалиновых) тромбов, состоящих из тромбоцитов и фактора фон Виллебранда. В первую очередь поражается головной мозг, почки и сердце. Было установлено, что у больных имеется дефект металлопротеиназы ADAMTS-13 (A Disintegrin And Metalloproteinase with ThromboSpondin type 1 modif 13), на фоне чего нарушается расщепление мультимеров фактора фон Виллебранда и увеличивается агрегазия тромбоцитов.
Классической пентатой призанков ТТП являются:
- развивается на поздних сроках беременности или перед родами;
- умеренное снижение уровня тромбоцитов в пределах 100-150х109/л;
- не повышен риск развития кровотечений;
- нет других изменений в клиническом анализе крови;
- не вызывает развития фетальной и неонатальной тромбоцитопении.
Иммунная тромбоцитопения (ИТ) – это аутоиммунное заболевание, при котором в организме женщины образуются антитела к гликопротеину плазматической мембраны тромбоцитов (чаще к GPIIb/IIa и Ib/IX), приводящие к их разрушению. Тромбоциты с антителами на своей поверхности распознаются и разрушаются клетками ретикулоэндотелиальной системы, преимущественно в селезенке.
Иммунная тромбоцитопения встречается с частотой 1-3 случая на 10.000 беременностей, или 3-5% всех тромбоцитопений. ИТ может развиваться в любом триместре беременности, а также вторично на фоне бактериальных инфекций, СКВ и АФС. Клинически течение ИТ обычно бессимптомно или сопровождается развитием незначительных петехиальных кровоизлияний.
В каждом четвертом случае (около 5%) в связи с трансплацентарным проникновением анти-тромбоцитарных IgG у плода развивается тромбоцитопения, внутримозговые кровоизлияния, а у новорожденных диагностируется пурпура и экхимозы (подкожных кровоизлияний диаметром более 3 мм).
Тромботическая тромбоцитопеническая пурпура (ТТП) – это острое угрожающее жизни заболевание, клинический синдром, который характеризуется тромбоцитопенией, микроангиопатической гемолитической анемией, микроваскулярным тромбозом концевых артериол и капилляров, множественной дисфункцией органов. Основу болезни составляет резкое повышение агрегации тромбоцитов с образованием тромбоцитарных (или гиалиновых) тромбов, состоящих из тромбоцитов и фактора фон Виллебранда. В первую очередь поражается головной мозг, почки и сердце. Было установлено, что у больных имеется дефект металлопротеиназы ADAMTS-13 (A Disintegrin And Metalloproteinase with ThromboSpondin type 1 modif 13), на фоне чего нарушается расщепление мультимеров фактора фон Виллебранда и увеличивается агрегазия тромбоцитов.
Классической пентатой призанков ТТП являются:
- Тромбоцитопения
- Микроангиопатическая гемолитическая анемия
- Неврологические нарушения (нарушение сознания)
- Поражение почек (микрогематурия, протеинурия, повышение уровня креатинина)
- Лихорадка
Таблица. Критерии диагностики причин тромбоцитопении у беременных
Литература:
1. Reese JA, Peck JD, Deschamps DR, et al. Platelet Counts during Pregnancy. N Engl J Med 2018; 379:32.
2. Segal JB, Moliterno AR. Platelet counts differ by sex, ethnicity, and age in the United States. Ann Epidemiol 2006; 16:123.
3. Myers B. Diagnosis and management of maternal thrombocytopenia in pregnancy. Br J Haematol 2012; 158:3.
4. Gernsheimer T, James AH, Stasi R. How I treat thrombocytopenia in pregnancy. Blood 2013; 121:38.
5. Parnas M, Sheiner E, Shoham-Vardi I, et al. Moderate to severe thrombocytopenia during pregnancy. Eur J Obstet Gynecol Reprod Biol 2006; 128:163.
6. Aster RH. "Gestational" thrombocytopenia: a plea for conservative management. N Engl J Med 1990; 323:264.
7. Jaschevatzky OE, David H, Bivas M, et al. Outcome of pregnancies associated with marked gestational thrombocytopenia. J Perinat Med 1994; 22:351.
8. 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.
9. Sainio S, Kekomäki R, Riikonen S, Teramo K. Maternal thrombocytopenia at term: a population-based study. Acta Obstet Gynecol Scand 2000; 79:744.
10. Burrows RF, Kelton JG. Fetal thrombocytopenia and its relation to maternal thrombocytopenia. N Engl J Med 1993; 329:1463.
11. http://www.hematology.org/Clinicians/Guidelines-Quality/Quick-Ref/530.aspx.
12. Reese JA, Peck JD, Yu Z, et al. Platelet sequestration and consumption in the placental intervillous space contribute to lower platelet counts during pregnancy. Am J Hematol 2019; 94:E8.
13. Care A, Pavord S, Knight M, Alfirevic Z. Severe primary autoimmune thrombocytopenia in pregnancy: a national cohort study. BJOG 2018; 125:604.
14. Terrell DR, Beebe LA, Vesely SK, et al. The incidence of immune thrombocytopenic purpura in children and adults: A critical review of published reports. Am J Hematol 2010; 85:174.
15. Loustau V, Debouverie O, Canoui-Poitrine F, et al. Effect of pregnancy on the course of immune thrombocytopenia: a retrospective study of 118 pregnancies in 82 women. Br J Haematol 2014; 166:929.
16. Webert KE, Mittal R, Sigouin C, et al. A retrospective 11-year analysis of obstetric patients with idiopathic thrombocytopenic purpura. Blood 2003; 102:4306.
17. ACOG Practice Bulletin No. 202: Gestational Hypertension and Preeclampsia. Obstet Gynecol 2019; 133:e1.
18. McMinn JR, George JN. Evaluation of women with clinically suspected thrombotic thrombocytopenic purpura-hemolytic uremic syndrome during pregnancy. J Clin Apher 2001; 16:202.
19. 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.
20. Jiang Y, McIntosh JJ, Reese JA, et al. Pregnancy outcomes following recovery from acquired thrombotic thrombocytopenic purpura. Blood 2014; 123:1674.
21. 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.
22. Amorosi EL, Ultmann JE. Thrombotic thrombocytopenic purpura: Report of 16 cases and review of the literature. Medicine (Baltimore) 1966; 45:139.
23. Scully M, Thomas M, Underwood M, et al. Thrombotic thrombocytopenic purpura and pregnancy: presentation, management, and subsequent pregnancy outcomes. Blood 2014; 124:211.
24. Martin JN Jr, Bailey AP, Rehberg JF, et al. Thrombotic thrombocytopenic purpura in 166 pregnancies: 1955-2006. Am J Obstet Gynecol 2008; 199:98.
25. Mannucci PM, Canciani MT, Forza I, et al. Changes in health and disease of the metalloprotease that cleaves von Willebrand factor. Blood 2001; 98:2730.
26. Gupta M, Govindappagari S, Burwick RM. Pregnancy-Associated Atypical Hemolytic Uremic Syndrome: A Systematic Review. Obstet Gynecol 2020; 135:46.
27. Provan D, Stasi R, Newland AC, et al. International consensus report on the investigation and management of primary immune thrombocytopenia. Blood 2010; 115:168.
28. 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.
29. https://www.hematology.org/Clinicians/Guidelines-Quality/Quick-Ref/526.aspx.
30. www.ouhsc.edu/platelets (Accessed on March 01, 2011).
31. George JN, Nester CM, McIntosh JJ. Syndromes of thrombotic microangiopathy associated with pregnancy. Hematology Am Soc Hematol Educ Program 2015; 2015:644.
32. ACOG Practice Bulletin No. 207: Thrombocytopenia in Pregnancy. Obstet Gynecol 2019; 133:e181.
33. 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.
34. 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.
35. Martí-Carvajal AJ, Peña-Martí GE, Comunián-Carrasco G. Medical treatments for idiopathic thrombocytopenic purpura during pregnancy. Cochrane Database Syst Rev 2009; :CD007722.
36. 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.
37. Sun D, Shehata N, Ye XY, et al. Corticosteroids compared with intravenous immunoglobulin for the treatment of immune thrombocytopenia in pregnancy. Blood 2016; 128:1329.
38. van Runnard Heimel PJ, Schobben AF, Huisjes AJ, et al. The transplacental passage of prednisolone in pregnancies complicated by early-onset HELLP syndrome. Placenta 2005; 26:842.
39. Rodeghiero F, Stasi R, Gernsheimer T, et al. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood 2009; 113:2386.
40. Bussel JB, Berkowitz RL, Lynch L, et al. Antenatal management of alloimmune thrombocytopenia with intravenous gamma-globulin: a randomized trial of the addition of low-dose steroid to intravenous gamma-globulin. Am J Obstet Gynecol 1996; 174:1414.
41. Berkowitz RL, Kolb EA, McFarland JG, et al. Parallel randomized trials of risk-based therapy for fetal alloimmune thrombocytopenia. Obstet Gynecol 2006; 107:91.
42. Palmeira P, Quinello C, Silveira-Lessa AL, et al. IgG placental transfer in healthy and pathological pregnancies. Clin Dev Immunol 2012; 2012:985646.
43. DeSesso JM, Williams AL, Ahuja A, et al. The placenta, transfer of immunoglobulins, and safety assessment of biopharmaceuticals in pregnancy. Crit Rev Toxicol 2012; 42:185.
44. Chakravarty EF, Murray ER, Kelman A, Farmer P. Pregnancy outcomes after maternal exposure to rituximab. Blood 2011; 117:1499.
45. Kong Z, Qin P, Xiao S, et al. A novel recombinant human thrombopoietin therapy for the management of immune thrombocytopenia in pregnancy. Blood 2017; 130:1097.
46. 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.
47. Bernstein J, Hua B, Kahana M, et al. Neuraxial Anesthesia in Parturients with Low Platelet Counts. Anesth Analg 2016; 123:165.
48. Goodier CG, Lu JT, Hebbar L, et al. Neuraxial Anesthesia in Parturients with Thrombocytopenia: A Multisite Retrospective Cohort Study. Anesth Analg 2015; 121:988.
49. van Veen JJ, Nokes TJ, Makris M. The risk of spinal haematoma following neuraxial anaesthesia or lumbar puncture in thrombocytopenic individuals. Br J Haematol 2010; 148:15.
50. Ruggeri M, Schiavotto C, Castaman G, et al. Gestational thrombocytopenia: a prospective study. Haematologica 1997; 82:341.
51. 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.
52. 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.
53. Iyori H, Fujisawa K, Akatsuka J. Thrombocytopenia in neonates born to women with autoimmune thrombocytopenic purpura. Pediatr Hematol Oncol 1997; 14:367.
54. 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.
55. 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.
56. 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.
57. 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.
58. Cook RL, Miller RC, Katz VL, Cefalo RC. Immune thrombocytopenic purpura in pregnancy: a reappraisal of management. Obstet Gynecol 1991; 78:578.
59. 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.
60. 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.
61. 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.
62. Paidas MJ, Berkowitz RL, Lynch L, et al. Alloimmune thrombocytopenia: fetal and neonatal losses related to cordocentesis. Am J Obstet Gynecol 1995; 172:475.
63. Anteby E, Shalev O. Clinical relevance of gestational thrombocytopenia of < 100,000/microliters. Am J Hematol 1994; 47:118.
64. 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.
1. Reese JA, Peck JD, Deschamps DR, et al. Platelet Counts during Pregnancy. N Engl J Med 2018; 379:32.
2. Segal JB, Moliterno AR. Platelet counts differ by sex, ethnicity, and age in the United States. Ann Epidemiol 2006; 16:123.
3. Myers B. Diagnosis and management of maternal thrombocytopenia in pregnancy. Br J Haematol 2012; 158:3.
4. Gernsheimer T, James AH, Stasi R. How I treat thrombocytopenia in pregnancy. Blood 2013; 121:38.
5. Parnas M, Sheiner E, Shoham-Vardi I, et al. Moderate to severe thrombocytopenia during pregnancy. Eur J Obstet Gynecol Reprod Biol 2006; 128:163.
6. Aster RH. "Gestational" thrombocytopenia: a plea for conservative management. N Engl J Med 1990; 323:264.
7. Jaschevatzky OE, David H, Bivas M, et al. Outcome of pregnancies associated with marked gestational thrombocytopenia. J Perinat Med 1994; 22:351.
8. 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.
9. Sainio S, Kekomäki R, Riikonen S, Teramo K. Maternal thrombocytopenia at term: a population-based study. Acta Obstet Gynecol Scand 2000; 79:744.
10. Burrows RF, Kelton JG. Fetal thrombocytopenia and its relation to maternal thrombocytopenia. N Engl J Med 1993; 329:1463.
11. http://www.hematology.org/Clinicians/Guidelines-Quality/Quick-Ref/530.aspx.
12. Reese JA, Peck JD, Yu Z, et al. Platelet sequestration and consumption in the placental intervillous space contribute to lower platelet counts during pregnancy. Am J Hematol 2019; 94:E8.
13. Care A, Pavord S, Knight M, Alfirevic Z. Severe primary autoimmune thrombocytopenia in pregnancy: a national cohort study. BJOG 2018; 125:604.
14. Terrell DR, Beebe LA, Vesely SK, et al. The incidence of immune thrombocytopenic purpura in children and adults: A critical review of published reports. Am J Hematol 2010; 85:174.
15. Loustau V, Debouverie O, Canoui-Poitrine F, et al. Effect of pregnancy on the course of immune thrombocytopenia: a retrospective study of 118 pregnancies in 82 women. Br J Haematol 2014; 166:929.
16. Webert KE, Mittal R, Sigouin C, et al. A retrospective 11-year analysis of obstetric patients with idiopathic thrombocytopenic purpura. Blood 2003; 102:4306.
17. ACOG Practice Bulletin No. 202: Gestational Hypertension and Preeclampsia. Obstet Gynecol 2019; 133:e1.
18. McMinn JR, George JN. Evaluation of women with clinically suspected thrombotic thrombocytopenic purpura-hemolytic uremic syndrome during pregnancy. J Clin Apher 2001; 16:202.
19. 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.
20. Jiang Y, McIntosh JJ, Reese JA, et al. Pregnancy outcomes following recovery from acquired thrombotic thrombocytopenic purpura. Blood 2014; 123:1674.
21. 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.
22. Amorosi EL, Ultmann JE. Thrombotic thrombocytopenic purpura: Report of 16 cases and review of the literature. Medicine (Baltimore) 1966; 45:139.
23. Scully M, Thomas M, Underwood M, et al. Thrombotic thrombocytopenic purpura and pregnancy: presentation, management, and subsequent pregnancy outcomes. Blood 2014; 124:211.
24. Martin JN Jr, Bailey AP, Rehberg JF, et al. Thrombotic thrombocytopenic purpura in 166 pregnancies: 1955-2006. Am J Obstet Gynecol 2008; 199:98.
25. Mannucci PM, Canciani MT, Forza I, et al. Changes in health and disease of the metalloprotease that cleaves von Willebrand factor. Blood 2001; 98:2730.
26. Gupta M, Govindappagari S, Burwick RM. Pregnancy-Associated Atypical Hemolytic Uremic Syndrome: A Systematic Review. Obstet Gynecol 2020; 135:46.
27. Provan D, Stasi R, Newland AC, et al. International consensus report on the investigation and management of primary immune thrombocytopenia. Blood 2010; 115:168.
28. 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.
29. https://www.hematology.org/Clinicians/Guidelines-Quality/Quick-Ref/526.aspx.
30. www.ouhsc.edu/platelets (Accessed on March 01, 2011).
31. George JN, Nester CM, McIntosh JJ. Syndromes of thrombotic microangiopathy associated with pregnancy. Hematology Am Soc Hematol Educ Program 2015; 2015:644.
32. ACOG Practice Bulletin No. 207: Thrombocytopenia in Pregnancy. Obstet Gynecol 2019; 133:e181.
33. 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.
34. 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.
35. Martí-Carvajal AJ, Peña-Martí GE, Comunián-Carrasco G. Medical treatments for idiopathic thrombocytopenic purpura during pregnancy. Cochrane Database Syst Rev 2009; :CD007722.
36. 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.
37. Sun D, Shehata N, Ye XY, et al. Corticosteroids compared with intravenous immunoglobulin for the treatment of immune thrombocytopenia in pregnancy. Blood 2016; 128:1329.
38. van Runnard Heimel PJ, Schobben AF, Huisjes AJ, et al. The transplacental passage of prednisolone in pregnancies complicated by early-onset HELLP syndrome. Placenta 2005; 26:842.
39. Rodeghiero F, Stasi R, Gernsheimer T, et al. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood 2009; 113:2386.
40. Bussel JB, Berkowitz RL, Lynch L, et al. Antenatal management of alloimmune thrombocytopenia with intravenous gamma-globulin: a randomized trial of the addition of low-dose steroid to intravenous gamma-globulin. Am J Obstet Gynecol 1996; 174:1414.
41. Berkowitz RL, Kolb EA, McFarland JG, et al. Parallel randomized trials of risk-based therapy for fetal alloimmune thrombocytopenia. Obstet Gynecol 2006; 107:91.
42. Palmeira P, Quinello C, Silveira-Lessa AL, et al. IgG placental transfer in healthy and pathological pregnancies. Clin Dev Immunol 2012; 2012:985646.
43. DeSesso JM, Williams AL, Ahuja A, et al. The placenta, transfer of immunoglobulins, and safety assessment of biopharmaceuticals in pregnancy. Crit Rev Toxicol 2012; 42:185.
44. Chakravarty EF, Murray ER, Kelman A, Farmer P. Pregnancy outcomes after maternal exposure to rituximab. Blood 2011; 117:1499.
45. Kong Z, Qin P, Xiao S, et al. A novel recombinant human thrombopoietin therapy for the management of immune thrombocytopenia in pregnancy. Blood 2017; 130:1097.
46. 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.
47. Bernstein J, Hua B, Kahana M, et al. Neuraxial Anesthesia in Parturients with Low Platelet Counts. Anesth Analg 2016; 123:165.
48. Goodier CG, Lu JT, Hebbar L, et al. Neuraxial Anesthesia in Parturients with Thrombocytopenia: A Multisite Retrospective Cohort Study. Anesth Analg 2015; 121:988.
49. van Veen JJ, Nokes TJ, Makris M. The risk of spinal haematoma following neuraxial anaesthesia or lumbar puncture in thrombocytopenic individuals. Br J Haematol 2010; 148:15.
50. Ruggeri M, Schiavotto C, Castaman G, et al. Gestational thrombocytopenia: a prospective study. Haematologica 1997; 82:341.
51. 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.
52. 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.
53. Iyori H, Fujisawa K, Akatsuka J. Thrombocytopenia in neonates born to women with autoimmune thrombocytopenic purpura. Pediatr Hematol Oncol 1997; 14:367.
54. 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.
55. 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.
56. 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.
57. 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.
58. Cook RL, Miller RC, Katz VL, Cefalo RC. Immune thrombocytopenic purpura in pregnancy: a reappraisal of management. Obstet Gynecol 1991; 78:578.
59. 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.
60. 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.
61. 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.
62. Paidas MJ, Berkowitz RL, Lynch L, et al. Alloimmune thrombocytopenia: fetal and neonatal losses related to cordocentesis. Am J Obstet Gynecol 1995; 172:475.
63. Anteby E, Shalev O. Clinical relevance of gestational thrombocytopenia of < 100,000/microliters. Am J Hematol 1994; 47:118.
64. 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.
