Thrombocytopenic syndromes during pregnancy
The authors carried out a systematic analysis of data on the etiology and pathogenesis of thrombocytopenia-associated conditions during pregnancy. The review includes foreign and Russian articles published over the past 10 years and found in eLibrary and PubMed on this topic. It analyzes data on the most studied and common diseases accompanied by thrombocytopenia during gestation: gestational thrombocytopenia (thrombocytopenia during pregnancy, pseudo-idiopathic thrombocytopenic purpura), immune-mediated thrombocytopenic purpura, preeclampsia, HELLP syndrome, thrombotic thrombocytopenic purpura (Moschcowitz disease), atypical hemolytic uremic syndrome, acute fatty liver of pregnancy, heparin-induced thrombocytopenia, antiphospholipid syndrome, and virus-induced thrombocytopenia. The information obtained will assist in more carefully making a differential diagnosis of the causes of thrombocytopenia in pregnant women and in timely prescribing etiotropic treatment.Grandone E., Mingalimov M.A., Grigoryeva K.N., Bitsadze V.O., Shkoda A.S., Khizroeva D.Kh., Vorobyev A.V., Makatsariya A.D.
Keywords
gestational thrombocytopenia
pseudo-idiopathic thrombocytopenic purpura
idiopathic thrombocytopenic purpura
preeclampsia
HELLP-syndrome
thrombotic thrombocytopenic purpura
atypical hemolytic-uremic syndrome
acute fatty liver of pregnancy
heparin-induced thrombocytopenia
antiphospholipid syndrome
virus-induced thrombocytopenia
References
- Cines D.B., Levine L.D. Thrombocytopenia in pregnancy. Blood. 2017; 130(21): 2271-7. https://doi.org/10.1182/blood-2017-05-781971
- Fogerty A.E. Thrombocytopenia in pregnancy: mechanisms and management. Transfusion medicine reviews. 2018; 32(4): 225-9. doi:10.1016/ j.tmrv.2018.08.004.
- Chaturvedi S., McCrae K.R. Thrombocytopenia in pregnancy. Platelets in Thrombotic and Non-Thrombotic Disorders: Pathophysiology, Pharmacology and Therapeutics: an Update. Springer International Publishing. 2017; 813-823.https://doi.org/10.1007/978-3-319-47462-5_54
- Parnas M., et al. Moderate to severe thrombocytopenia during pregnancy. Eur J Obstet Gynecol Reprod Biol. 2006; 128(1-2):163-8. DOI:10,1016/ j.ejogrb.2005.12.031
- Valera M.C., Parant O., et.al. Physiologic and pathologic changes of platelets in pregnancy. Platelets. 2010; 21(8): 587-95. DOI:10,3109/ 09537104.2010.509828
- Palta A., Dhiman P. Thrombocytopenia in pregnancy. Journal of Obstetrics and gynecology. 2016; 36(2): 146-52. https://doi.org/10.3109/01443615.2015.1041893
- Webert K.E., Mittal R., Sigouin C., Heddle N.M., Kelton J.G. A retrospective 11-year analysis of obstetric patients with idiopathic thrombocytopenic purpura. Blood. 2003; 102(13): 4306-11. DOI:10,1182 / Blood-2002-10-3317
- 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(4): 426-33. PMID:12041677
- 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(6): 929-35. DOI: 10,1111 / bjh.12976
- Lefkou E., Hunt B.J. Bleeding disorders in pregnancy. Obstetrics, Gynaecology and Reproductive medicine. 2018; 28(7):189-195. DOI: 10.1016/j.ogrm.2018.06.002
- Karim R., Sacher R.A. Thrombocytopenia in pregnancy. Curr Hematol Rep. 2004; 3(2):128-33. PMID: 14965489
- Neunert C., Lim W., Crowther M., et al. The American society of hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood. 2011; 117(16): 4190-207. doi:10.1182 / blood-2010-08-302984
- Provan D., Stasi R, Newland A.C., et al. International consensus report on the investigation and management of primary immune thrombocytopenia. Blood. 2010;115(2):168-86. doi: 10.1182 / blood-2009-06-225565.
- British Committee for standards in Haematology General Haematology Task Force. Guidelines for the investigation and management of idiopathic thrombocytopenic purpura in adults, children and in pregnancy. Br J Haematol. 2011; 120(4): 574-96.
- Mizutani H., Furubayashi T., Imai Y., Kashiwagi H., Honda S., Take H., Kurata Y., Yonezawa T., Tarui S., Ikehara S. Mechanisms of corticosteroid action in immune thrombocytopenic purpura (ITP): experimental studies using ITP-prone mice, (NZW x BXSB) F1. Blood. 1992; 79(4): 942-7.PMID: 1737103
- Jin F., Balthasar J.P. Mechanisms of intravenous immunoglobulin action in immune thrombocytopenic purpura. Hum Immunol. 2005; 66(4): 403-10. https://dx.doi.org/10.1016/j.humimm.2005.01.029
- Sun D. Shehata N., Ye XY, Gregorovich S., De France B., Arnold D.M., et al. Corticosteroids compared with intravenous immunoglobulin for the treatment of immune thrombocytopenia in pregnancy. Blood. 2016; 128(10): 1329-35. doi: 10.1182/blood-2016-04-710285
- Hviid A and Molgaard-Nielsen D. Corticosteroid use during pregnancy and risk of orofacial clefs. CM AJ. 2011; 183(7): 796-804. DOI: https://doi.org/10.1503/cmaj.101063
- Park-Wyllie, Mazzotta P, Pastuszak A., et al. Birth defects after maternal exposure to corticosteroids: progressive cohort study and meta-analysis of epidemiological studies. Teratology. 2000; 62(6): 385-92. PMID: 11091360
- Wang X., Xu Y., Luo W., Feng H., Luo Y., Wang Y. et al. Thrombocytopenia in pregnancy with different diagnoses. Differential clinical features, treatments, outcomes. Medicine. 2017; 96(29): е7561. http://dx.doi.org/10.1097/MD.0000000000007561
- Abalos E., Cuesta C., Grosso A.L., et al. Global and regional estimates of preeclampsia and eclampsia : a systematic review. Eur J Obstet Gynecol Reprod Biol. 2013;170(1):1-7. doi: 10.1016/j.ejogrb.2013.05.005
- Ananth C.V., Keyes K.M., Wabner R.J. Pre-eclampsia rates in the United States, 1980-2010: age-period-cohort analysis. BMJ. 2013; 347:f6564. doi: 10.1136/bmj.f6564
- Daley L. The global impact of pre-eclampsia and eclampsia. Semin Perinatol. 2009; 33(3):130-7. doi: 10.1053/j.semperi.2009.02.010
- ACOG. Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists task force on hypertension in pregnancy. Obstet Gynecol. 2013; 122(5):1122-31. doi: 10.1097/01.AOG.0000437382.03963.88
- Bartsch E., Medcalf K.E., Park A.L., Ray J.G. Clinical risk factors for preeclampsia determined in early pregnancy: systematic review and meta-analysis of large cohort studies. BMJ. 2016; 353: i1753. doi: 10.1136/bmj.i1753
- McCrae K.R. Thrombocytopenia in pregnancy: differential diagnosis, pathogenesis, and management. Blood Rev. 2003; 17(1): 7-14. PMID: 12490206
- Макацария А.Д., Акиньшина С.В., Бицадзе В.О. Преэклампсия и HELLP-синдром как проявление тромботической микроангиопатии. Акушерство и гинекология. 2014; 4: 4-10.[Makatsariya A.D., Akinshina S.V., Bitsadze V.O. Preeclampsia and HELLP syndrome as a manifestation of thrombotic microangiopathy. Akusherstvo i Ginekologiya/ Obstetrics and gynecology. 2014; 4: 4-10.(In Russian)].
- Rinehart B.K., Terrone D.A., May W.L., Magann E.F., Isler C.M., Martin J.N. Jr. Change in platelet count predicts eventual maternal outcome with syndrome of hemolysis, elevated liver enzymes and low platelet count. J Matern Fetal Med. 2001;10(1): 28-34. PMID: 11332416
- Kirkpatrick C.A. The HELLP-syndrome. Acta Clin Belg. 2010; 65(2): 91-7. DOI: 10.1179/acb.2010.020
- Mao M., Chen C. Corticosteroid therapy for management of hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome: a meta-analysis. Med Sci Monit. 2015; 21: 3777-3783. DOI: 10.12659/msm.895220
- Rose C.H., Thigpen B.D., Bofill J.A., Cushman J., May W.L., Martin J.N. Jr. Obstetric implications of antepartum corticosteroid therapy for HELLP syndrome. Obstet Gynecol. 2004; 104(5 Pt 1): 1011-4. DOI: 10.1097/01.AOG.0000143262.85124.e8
- Barrilleaux P.S., Martin Jr J.N., Klauser C.K., et al. Postpartum intravenosus dexamethasone for severely preeclamptic patients without HELLP-syndrome: a randomized trial. Obstet Gynecol. 2005; 105(4): 843-8. DOI: 10.1097/01.AOG.0000154887.57440.d1
- Katz L., de Amorim M.M., Figueiroa J.N., et al. Postpartum dexamethasone for women with (HELLP) syndrome: a double-blind, placebo-controlled, randomized clinical trial. Am J Obstet Gynecol. 2008; 198(3): 283.e1-8. DOI: 10.1016/j.ajog.2005.07.037
- Kentouche K., Voigt A., Schleussner E., Schneppenheim R., Budde U., Beck J.F., Stefańska-Windyga E., Windyga J. Pregnancy in Upshaw-Schulman syndrome. Hamostaseologie. 2013; 33(2): 144-8. DOI: 10.5482/HAMO-13-04-0025
- Sadler J.E. Pathophysiology of thrombotic thrombocytopenic purpura. Blood. 2017; 130(10): 1181-8. DOI: 10.1182/blood-2017-04-636431
- Tsai H.M. Pathophysiology of thrombotic thrombocytopenic purpura. Int J Hematol. 2010; 91(1): 1-19. doi:10.1007/s12185-009-0476-1
- McMinn J.R., George J.N. Evaluation of women with clinically suspected thrombotic thrombocytopenic purpura-hemolytic uremic syndrome during pregnancy. J Clin Apher. 2001;16(4):202-9.PMID: 11835417
- Martin J.N. Jr, Bailey A.P., Rehberg J.F., Owens M.T., Keiser S.D., May W.L. Thrombotic thrombocytopenic purpura in 166 pregnancies: 1955-2006. Am J Obstet Gynecol. 2008 Aug; 199(2): 98-104. DOI:10.1016/j.ajog.2008.03.011
- George J.N., Nester C.M., Mclntosh J.J. Syndromes of thrombotic microangiopathy associated with pregnancy. Hematology Am Soc Hematol Educ Program. 2015; 2015: 644-8. DOI: 10.1182/asheducation-2015.1.644
- Vesely S.K., Li X., McMinn J.R., Terrell D.R., George JN. Pregnancy outcomes after recovery from thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Transfusion. 2004; 44(8):1149-58. DOI: 10.1111/j.1537-2995.2004.03422.x
- Moatti-Cohen M., Garrec C., Wolf M., et al. French Reference Center for Thrombotic Microangiopathies. Unexpected frequency of Upshaw-Schulman syndrome in pregnancy-onset thrombotic thrombocytopenic purpura. Blood. 2012; 119(24): 5888-97. doi: 10.1182/blood-2012-02-408914
- Scully M., Thomas M., Underwood M., et al. Collaborators of the UK TTP registry. Thrombotic thrombocytopenic purpura and pregnancy: presentation, management, and subsequent pregnancy outcomes. Blood. 2014; 124(2): 211-9. doi: 10.1182/blood-2014-02-553131.
- Scully M. Thrombotic thrombocytopenic purpura and atypical hemolytic uremic syndrome microangiopathy in pregnancy. Semin Thromb Hemost. 2016; 42(7): 774-779. DOI: 10.1055/s-0036-1587683
- Saad A., Roman J., Wyble A., Pacheco L. D. Pregnancy-associated atypical hemolytic-uremic syndrome. AJP Rep. 2016; 6(1): e125-e128. doi: 10.1055/s-0036-1579539.
- Laurence J., et al. Atypical hemolytic uremic syndrome (aHUS): essential aspects of an accurate diagnosis. Clin Adv Hematol Oncol. 2016.; 14 Suppl 11(11): 2-15. PMID: 27930620
- Caprioli J., Noris M., Brioschi S., et al. Genetics of HUS: the impact of MCP, CFH, and IF mutations on clinical presentation, response to treatment, and outcome. Blood. 2006. 15; 108(4): 1267-79. DOI: 10.1182/blood-2005-10-007252
- 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(5): 859-67. doi: 10.1681/ASN.2009070706
- Andries G., Karass M., Linder K., et al. Atypical hemolytic uremic syndrome in first trimester pregnancy successfully treated with eculizumab. Experimental hematology and oncology. 2017; 6: 4. https://doi.org/10.1186/s40164-017-0064-7
- Fesenmeier M.F., Coppage K.H., Lambera D.S., et al. Acute fatty liver of pregnancy in 3 tertiary care centers. Am J Obstet Gynecol. 2005; 192(5): 1416-9. DOI: 10.1016/j.ajog.2004.12.035
- Mauermann E., Vokt C., Tsakiris D.A., Tobler D., Girard T. Heparin-induced thrombocytopenia in pregnancy: an interdisciplinary challenge – a case report and literature review. International Journal of Obstetric Anesthesia. 2016; 26: 79-82. DOI: 10.1016/j.ijoa.2015.11.009
- Greinacher A. Heparin-induced thrombocytopenia. N Engl J Med. 2015; 373(19):1883-4. doi: 10.1056/NEJMc1510993
- Warkentin T.E., Heddle N.M. Laboratory diagnosis of immune heparin-induced thrombocytopenia. Curr Hematol Rep. 2003; 2(2):148-57.
- Cuker A., Arepally G., Crowther M.A., et al. The HIT Expert Probability (HEP) Score: a novel pre-test probability model for heparin-induced thrombocytopenia based on broad expert opinion. J Thromb Haemost. 2010; 8(12): 2642-50.doi: 10.1111/j.1538-7836.2010.04059.x.
- Joseph L., Gomes MP., Al Solaiman F., et al. External validation of the HIT Expert Probability (HEP) score. Thromb Haemost. 2015;113(3): 633-40. DOI: 10.1160/TH14-05-0472
- Warkentin T.E., Aird W.C., Rand J.H. Platelet-endothelial interactions: sepsis, HIT, and antiphospholipid syndrome. Hematology Am Soc Hematol Educ Program. 2003: 497-519. PMID: 14633796
- Fausett M.B., Vogtlander M., Beyer-Westendorf J., et al. Heparin-induced thrombocytopenia is rare in pregnancy. Am J Obstet Gynecol. 2001; 185(1):148-52. http://dx.doi.org/10.1067/mob.2001.114690
- Elsaigh E., Thachil J., Nash M.J., et al. The use of fondaparinux in pregnancy. Br J Haematol. 2015;168(5):762-4. http://dx.doi.org/10.1111/bjh.1314
- Li Z., Nardi M.A., Karpatkin S. Role of molecular mimicry to HIV-1 peptides in HIV-1-related immunologic thrombocytopenia. Blood. 2005;106(2): 572-576. DOI: 10.1182/blood-2005-01-0243
- Zhang W., Nardi M.A., Borkowsky W., Li Z., Karpatkin S. Role of molecular mimicry of hepatitis С virus protein with platelet GPIIIa in hepatitis C-related immunologic thrombocytopenia. Blood. 2009;113(17): 4086-93. doi: 10.1182/blood-2008-09-181073
- Khamashta M.A., Harris E.N., Gharavi A.E., Derue G., Gil A., Vázquez J.J., Hughes G.R. Immune mediated mechanism for thrombosis: antiphospholipid antibody binding to platelet membranes. Ann Rheum Dis. 1988; 47(10): 849-54. DOI: 10.1136/ard.47.10.849
- Vazquez-Mellado J., Liorente L., Richaud-Patin Y., Alarcon-Segovia D. Exposure of anionic phospholipids upon platelet activation permits binding b2-glycoprotein-I and through it IgG antiphospholipid antibodies. Studies in platelets from patients with antiphospholipid syndrome and normal subjects. J Autoimmun. 1994; 7(3): 335-48.
- Godeau B., Piette J.C., Fromont P., Intrator L., Schaeffer A., Bierling P. Specific antiplatelet glycoprotein autoantibodies are associated with the thrombocytopenia of primary antiphospholipid syndrome. Br J Haematol. 1997; 98(4): 873-9. DOI: 10.1046/j.1365-2141.1997.3063123.x
- Gernsheimer T., McCrae K.R. Immune thrombocytopenic purpura in pregnancy. Curr Opin Hematol. 2007; 14(5): 574-80. DOI:10.1097/MOH.0b013e3282bf6dc2
Received 03.09.2019
Accepted 04.10.2019
About the Authors
Elvira Grandone, MD, PhD, Head of Unit Clinical and Research In Thrombosis and Haemostasis IRCCS Ospedale Casa Sollievo della Sofferenza, professor of the Department of Obstetrics and Gynecology, The First I.M. Sechenov Moscow State Medical University; email: grandoneelvira@gmail.comMarat A. Mingalimov, student of paediatric faculty of The First I.M. Sechenov Moscow State Medical University; e-mail: ya.mingalimov2017@yandex.ru
Kristina N. Grigorieva, student of paediatric faculty of The First I.M. Sechenov Moscow State Medical University; email: grigkristik96@gmail.com
Viktoria O. Bitsadze, MD, PhD, Professor of the Russian Academy of Sciences, Professor of the Department of Obstetrics and Gynecology, The First I.M. Sechenov Moscow State Medical University; e-mail: gemostasis@mail.ru
Andrei S. Skoda, MD, professor, chief physician of the City Clinical Hospital No. 67 named after L.A. Vorokhobov, Moscow Department of Health. Tel .: +7 (495) 530-30-71; e-mail: 67gkb@mail.ru; 123423, Russia, Moscow, ul. Salam Adil, d. 2/44.
Jamilya Kh. Khizroeva, MD, PhD, Professor of the Department of Obstetrics and Gynecology, The First I.M. Sechenov Moscow State Medical University; E-mail: gemostasis@mail.ru
Alexander V. Vorobev, MD, PhD, Associate Professor of the Department of Obstetrics and Gynecology, The First I.M. Sechenov Moscow State Medical University;
E-mail: alvorobev@gmail.com
Aleksander D. Makatsariya, MD, PhD, corresponding member of the Russian Academy of Sciences, Professor, Head of the Department of Obstetrics and Gynecology,
The First I.M. Sechenov Moscow State Medical University; E-mail: gemostasis@mail.ru
For citation: Grandone E., Mingalimov M.A, Grigoryeva K.N. Bitsadze V.O., Shkoda A.S., Khizroeva D.Kh., Vorobyev A.V., Makatsariya A.D. Thrombocytopenic syndromes during pregnancy.
Akusherstvo i Ginekologiya/ Obstetrics and gynecology. 2019; 10: 5-12. (In Russian).
https://dx.doi.org/10.18565/aig.2019.10.5-12