Incidence of obstetrical thrombotic thrombocytopenic purpura in a retrospective study within thrombocytopenic pregnant women. A difficult diagnosis and a treatable disease

BMC Pregnancy and Childbirth

Christian Combe⁶  Paul Coppo¹  Jacques Horovitz⁶  Agnès Veyradier¹  Pierre Boisseau³  Dominique Carles⁶  Fanny Pelluard⁶  Anne Ryman⁴  Pierre Chabanier⁵  Sébastien Helou⁶  Yahsou Delmas² 

[1] Centre de Référence des Microangiopathies Thrombotiques, Paris, France;Centre de Compétence des Microangiopathies Thrombotiques, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France;Service de Génétique Médicale, Centre Hospitalier Universitaire de Nantes Hôtel Dieu, Nantes, France;Service d’Hémostase Spécialisée, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France;Pôle Gynécologie-Obstétrique-et Médecine Foetale, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France;Université Bordeaux Segalen, Bordeaux, France

关键词: Upshaw-Schulman syndrome;    Thrombotic Thrombocytopenic Purpura;    ADAMTS-13 deficiency;    HELLP syndrome;    Thrombocytopenia;    Pregnancy;   

Others  :  1215951
DOI  :  10.1186/s12884-015-0557-5

 received in 2014-10-05, accepted in 2015-05-15,  发布年份 2015

【 摘 要 】

Background

Thrombotic thrombocytopenic Purpura (TTP) defined as ADAMTS-13 (A Disintegrin And Metalloprotease with ThromboSpondin type 1 domain 13) activity <10 % is a rare aetiology of thrombocytopenia during pregnancy, although the precise incidence is unknown. During pregnancy, the diagnosis of TTP is crucial as it has high feto-maternal morbidity-mortality and requires urgent plasma exchange. The purpose of this study was to assess the incidence of TTP retrospectively and to describe case presentations and follow-up.

Methods

A monocentric retrospective study (2008–2009) was conducted among pregnant women followed in a tertiary care obstetrical unit who experienced at least one episode of severe thrombocytopenia (platelets ≤75 G/L) during 2008 and 2009. In cases of uncertain aetiology of thrombocytopenia, ADAMTS-13 activity was assessed by the full length technique.

Results

Among 8,908 deliveries over the 2 year period, 79 women had a platelet count nadir ≤75 G/L. Eighteen had a known aetiology of thrombocytopenia and 11 were lost to follow-up. Among 50 remaining patients, ADAMTS-13 activity was undetectable (<5 %) in 4, consistent with the diagnosis of TTP. Platelet count spontaneously normalized in 3 patients after delivery. None presented focal cerebral involvement. Three of the four, who were primipara patients, had a sustained severe deficiency in the absence of anti-ADAMTS-13 antibodies, and ADAMTS-13 gene sequencing indicated a constitutive deficiency. The fourth, a multipara patient, had an acquired, auto-immune TTP. Placental pathology in the three primipara patients showed severe and non-specific ischemic lesions. Two patients lost their babies shortly after birth. In subsequent pregnancies in these two patients, prophylactic plasma infusion initiated early with increasing volume throughout pregnancy prevented TTP relapse, improved placental pathology, and led to normal delivery.

Conclusions

The prevalence of TTP among thrombocytopenic pregnant women is high, up to 5 % in a tertiary unit. Platelet count normalization after delivery does not eliminate TTP. Clinicians should be aware of TTP during pregnancy, and, even if assessed retrospectively, ADAMTS-13 assessment is of particular importance for identifying patients with congenital TTP. In these patients, preventive plasma infusion and/or exchange can dramatically improve foetal prognosis, resulting in successful childbirth.

【 授权许可】

   
2015 Delmas et al.; licensee BioMed Central.

【 图 表 】

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【 参考文献 】

• [1]George JN, Nester CM. Syndromes of thrombotic microangiopathy. N Engl J Med. 2014; 371(7):654-66.
• [2]Benhamou Y, Assie C, Boelle PY, Buffet M, Grillberger R, Malot S et al.. Development and validation of a predictive model for death in acquired severe ADAMTS13 deficiency-associated idiopathic thrombotic thrombocytopenic purpura: the French TMA Reference Center experience. Haematologica. 2012; 97(8):1181-6.
• [3]Mannucci PM, Canciani MT, Forza I, Lussana F, Lattuada A, Rossi E. Changes in health and disease of the metalloprotease that cleaves von Willebrand factor. Blood. 2001; 98(9):2730-5.
• [4]Sanchez-Luceros A, Farias CE, Amaral MM, Kempfer AC, Votta R, Marchese C et al.. von Willebrand factor-cleaving protease (ADAMTS13) activity in normal non-pregnant women, pregnant and post-delivery women. Thromb Haemost. 2004; 92(6):1320-6.
• [5]Veyradier A, Stepanian A, Coppo P. ADAMTS13, Thrombotic Thrombocytopenic Purpura and Pregnancy. Hereditary Gen. 2012; S1:002(2161-1041):1-6.
• [6]Sibai BM. Imitators of severe pre-eclampsia. Semin Perinatol. 2009; 33(3):196-205.
• [7]McCrae KR. Thrombocytopenia in pregnancy. Hematology Am Soc Hematol Educ Program. 2010; 2010:397-402.
• [8]Raman R, Yang S, Wu HM, Cataland SR. ADAMTS13 activity and the risk of thrombotic thrombocytopenic purpura relapse in pregnancy. Br J Haematol. 2011; 153(2):277-9.
• [9]Richter J, Strandberg K, Lindblom A, Strevens H, Karpman D, Wide-Swensson D. Successful management of a planned pregnancy in severe congenital thrombotic thrombocytopaenic purpura: the Upshaw-Schulman syndrome. Transfus Med. 2011; 21(3):211-3.
• [10]Scully M, Starke R, Lee R, Mackie I, Machin S, Cohen H. Successful management of pregnancy in women with a history of thrombotic thrombocytopaenic purpura. Blood Coagul Fibrinolysis. 2006; 17(6):459-63.
• [11]Martin JN, Bailey AP, Rehberg JF, Owens MT, Keiser SD, May WL. Thrombotic thrombocytopenic purpura in 166 pregnancies: 1955-2006. Am J Obstet Gynecol. 2008; 199(2):98-104.
• [12]Terrell DR, Williams LA, Vesely SK, Lammle B, Hovinga JA, George JN. The incidence of thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: all patients, idiopathic patients, and patients with severe ADAMTS-13 deficiency. J Thromb Haemost. 2005; 3(7):1432-6.
• [13]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(5 Pt 1):662-8.
• [14]Lattuada A, Rossi E, Calzarossa C, Candolfi R, Mannucci PM. Mild to moderate reduction of a von Willebrand factor cleaving protease (ADAMTS-13) in pregnant women with HELLP microangiopathic syndrome. Haematologica. 2003; 88(9):1029-34.
• [15]Fujimura Y, Matsumoto M, Kokame K, Isonishi A, Soejima K, Akiyama N 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(5):742-54.
• [16]Coppo P, Schwarzinger M, Buffet M, Wynckel A, Clabault K, Presne C et al.. Predictive features of severe acquired ADAMTS13 deficiency in idiopathic thrombotic microangiopathies: the French TMA reference center experience. PLoS One. 2010; 5(4): Article ID e10208
• [17]Harambat J, Lamireau D, Delmas Y, Ryman A, Llanas B, Brissaud O. Successful treatment with rituximab for acute refractory thrombotic thrombocytopenic purpura related to acquired ADAMTS13 deficiency: a pediatric report and literature review. Pediatr Crit Care Med. 2011; 12(2):e90-3.
• [18]Moatti-Cohen M, Garrec C, Wolf M, Boisseau P, Galicier L, Azoulay E et al.. Unexpected frequency of Upshaw-Schulman syndrome in pregnancy-onset thrombotic thrombocytopenic purpura. Blood. 2012; 119(24):5888-97.
• [19]Mamelle N, David S, Lombrail P, Roze JC. [Indicators and evaluation tools for perinatal care networks]. J Gynecol Obstet Biol Reprod. 2001; 30(7 Pt 1):641-55.
• [20]Keiser SD, Boyd KW, Rehberg JF, Elkins S, Owens MY, Sunesara I et al.. A high LDH to AST ratio helps to differentiate pregnancy-associated thrombotic thrombocytopenic purpura (TTP) from HELLP syndrome. J Matern Fetal Neonatal Med. 2012; 25(7):1059-63.
• [21]Camilleri RS, Cohen H, Mackie IJ, Scully M, Starke RD, Crawley JT et al.. Prevalence of the ADAMTS-13 missense mutation R1060W in late onset adult thrombotic thrombocytopenic purpura. J Thromb Haemost. 2008; 6(2):331-8.
• [22]Plaimauer B, Fuhrmann J, Mohr G, Wernhart W, Bruno K, Ferrari S et al.. Modulation of ADAMTS13 secretion and specific activity by a combination of common amino acid polymorphisms and a missense mutation. Blood. 2006; 107(1):118-25.
• [23]Hunt BJ, Thomas-Dewing RR, Bramham K, Lucas SB. Preventing maternal deaths due to acquired thrombotic thrombocytopenic purpura. J Obstet Gynaecol Res. 2013; 39(1):347-50.
• [24]Imanirad I, Rajasekhar A, Zumberg M. A case series of atypical presentations of thrombotic thrombocytopenic purpura. J Clin Apher. 2012; 27(4):221-6.
• [25]Ducloy-Bouthors AS, Caron C, Subtil D, Provot F, Tournoys A, Wibau B et al.. Thrombotic thrombocytopenic purpura: medical and biological monitoring of six pregnancies. Eur J Obstet Gynecol Reprod Biol. 2003; 111(2):146-52.
• [26]Scully M, Hunt BJ, Benjamin S, Liesner R, Rose P, Peyvandi F et al.. Guidelines on the diagnosis and management of thrombotic thrombocytopenic purpura and other thrombotic microangiopathies. Br J Haematol. 2012; 158(3):323-35.
• [27]Kentouche K, Voigt A, Schleussner E, Schneppenheim R, Budde U, Beck JF et al.. Pregnancy in Upshaw-Schulman syndrome. Hamostaseologie. 2013; 33(2):144-8.
• [28]Gernsheimer T, James AH, Stasi R. How I treat thrombocytopenia in pregnancy. Blood. 2013; 121(1):38-47.
• [29]Shamseddine A, Chehal A, Usta I, Salem Z, El-Saghir N, Taher A. Thrombotic thrombocytopenic purpura and pregnancy: report of four cases and literature review. J Clin Apher. 2004; 19(1):5-10.
• [30]Rehberg JF, Briery CM, Hudson WT, Bofill JA, Martin JN. Thrombotic thrombocytopenic purpura masquerading as hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome in late pregnancy. Obstet Gynecol. 2006; 108(3 Pt 2):817-20.
• [31]Tanaka H, Tenkumo C, Mori N, Kokame K, Fujimura Y, Hata T. Case of maternal and fetal deaths due to severe congenital thrombotic thrombocytopenic purpura (Upshaw-Schulman syndrome) during pregnancy. J Obstet Gynaecol Res. 2014; 40(1):247-9.