Severe thrombocytopenia resulting in intrauterine exitus in pregnancy and review of the literature

Öz

Objective: We aimed to present a pregnancy accompanied by severe thrombocytopenia and intrauterine exitus fetus and its management by reviewing the literature. Case report: A 21-year-old patient with a 24-week singleton pregnancy was admitted with the complaints of nausea, vomiting and epistaxis. TA: 110/70 mmHg, heart rate: 85/min. Severe thrombocytopenia (plt: 9000/uL) was found in the patient who did not have any obstetric pathology. Hb: 13 g/dl, ALT: 12 U/ L, AST: 40 U/ L, Albumin: 2.47 g/dl, creatinine: 0.83 mg/dl, total bilirubin: 0.27 mg/dl, and with the preliminary diagnosis of immune thrombocytopenia, 1 U apheresis and 1 U pooled platelet transfusion and 32 mg/day prednol treatment were applied; control plt was 36000/uL. At the patient's follow-up 10 days later, plt: 6000/uL and fetal heart rate were not observed, so termination was decided. Vital signs: TA: 130/80, heart rate: 98/min, fever: 36 0C. Hb: 6.7 g/ dl, plt: 6000/ uL, total bilirubin 0.88 mg/ dl, ALT: 28 U/ L, AST: 70 U/ L, LDH: 2297 U/L, Haptoglobin <10 mg/ dl, INR: 0.94, Albumin: 2.47 g/dl, creatinine: 0.83 mg/dl, direct coombs:-, indirect coombs:-, urinary analysis: protein 4+. With the diagnosis of microangioptic hemolytic anemia, the patient was administered 4 U apheresis platelets, 3 U ES, 30 g IVIG, 120 mg prednol. When plt: 59000 /uL, labor induction was started. During induction, plasmapheresis was applied and vaginal delivery occurred 6 hours later. Conclusion: The differential diagnosis of patients with severe thrombocytopenia during pregnancy should be made as soon as possible. Immediate termination of pregnancy may be required due to the risk of maternal mortality. In complex and critical cases, more effective results can be obtained by using a multidisciplinary team approach.

Anahtar Kelimeler

• thrombocytopenia
• TTP
• pregnancy
• ADAMTS13

Gebelikte intrauterin exitusla sonuçlanan şiddetli trombositopeni ve literatürün gözden geçirilmesi

Öz

Amaç: Şiddetli trombositopeni ve intrauterin exitus fetusun eşlik ettiği bir gebeliği ve bunun yönetimini literatürü gözden geçirerek sunmayı amaçladık Olgu sunumu: 21 yaşında, 24 hafta tekil gebeliği olan hasta, bulantı, kusma, burun kanaması şikayeti ile başvurdu. TA: 110/ 70 mmHg, nabız: 85/ dk idi. Herhangi bir obstetrik patoloji saptanmayan hastada, şiddetli trombositopeni (plt: 9000/ uL) saptandı. Hb: 13 g/ dl, ALT: 12 U/ L, AST: 40 U/ L, Albumin: 2,47 g/ dl, kreatinin: 0,83 mg/dl, total biluribin: 0,27 mg/dl idi ve immün trombositopeni ön tanısı ile, 1 Ü aferez ve 1 Ü havuzlanmış trombosit transfüzyonu ve 32 mg/gün prednol tedavisi uygulandı; kontrol plt: 36000/ uL idi. Hastanın 10 gün sonraki kontrolünde, plt: 6000/ uL ve fetal kalp atımı izlenmemesi üzerine, terminasyon kararı verildi. Vital bulgular: TA: 130/ 80, nabız: 98/ dk, ateş: 36 0C idi. Hb:6,7 g/ dl, plt: 6000/ uL, total biluribin 0,88 mg/ dl, ALT: 28 U/ L, AST: 70 U/ L, LDH: 2297 U/L, Haptoglobin <10 mg/dl, INR: 0,94, Albumin: 2,47 g/dl, kreatinin: 0,83 mg/dl, direct coombs:-, indirect coombs:-, TİT: protein 4+ idi. Hastaya mikroanjioptik hemolitik anemi tanısıyla, 4 Ü aferez trombosit, 3 Ü ES, 30 gr İVİG, 120 mg prednol uygulandı. Plt: 59000 /uL olduğunda, doğum indüksiyonuna başlandı. İndüksiyon sırasında, plazmaferez uygulandı ve 6 saat sonra vajinal yolla doğum gerçekleşti. Sonuç: Gebelikte şiddetli trombositopeni saptanan hastaların, nedene yönelik ayırıcı tanısı en kısa sürede yapılmalıdır. Maternal mortalite riski nedeniyle gebeliğin acil sonlandırılması gerekebilir. Karmaşık ve kritik vakalarda, multidisipliner bir ekip yaklaşımının kullanılması ile daha etkili sonuç alınabilir.

Anahtar Kelimeler

• trombositopeni
• TTP
• gebelik
• ADAMTS13

Kaynakça

1. 1. Gupta M, Feinberg BB, Burwick RM. Thrombotic microangiopathies of pregnancy: Differential diagnosis. Pregnancy Hypertens. 2018;12:29-34.
2. 2. 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.
3. 3. Tsai HM, Kuo E. From Gestational Hypertension and Preeclampsia to Atypical Hemolytic Uremic Syndrome. Obstet Gynecol. 2016;127(5):907-10.
4. 4. Scully M, Goodship T. How I treat thrombotic thrombocytopenic purpura and atypical haemolytic uraemic syndrome. Br J Haematol. 2014;164(6):759-66.
5. 5. Weinstein L. Syndrome of hemolysis, elevated liver enzymes, and low platelet count: a severe consequence of hypertension in pregnancy. Am J Obstet Gynecol. 1982;142(2):159-67.
6. 6. Sibai BM, Taslimi MM, el-Nazer A, Amon E, Mabie BC, Ryan GM. Maternal-perinatal outcome associated with the syndrome of hemolysis, elevated liver enzymes, and low platelets in severe preeclampsia-eclampsia. Am J Obstet Gynecol. 1986;155(3):501-9.
7. 7. Haram K, Mortensen JH, Mastrolia SA, Erez O. Disseminated intravascular coagulation in the HELLP syndrome: how much do we really know? J Matern Fetal Neonatal Med. 2017;30(7):779-88.
8. 8. Sibai BM. The HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets): much ado about nothing? Am J Obstet Gynecol. 1990;162(2):311-6.

9. 9. Vigil-De Gracia P. Acute fatty liver and HELLP syndrome: two distinct pregnancy disorders. Int J Gynaecol Obstet. 2001;73(3):215-20.
10. 10. Chaplin H, Jr., Cohen R, Bloomberg G, Kaplan HJ, Moore JA, Dorner I. Pregnancy and idiopathic autoimmune haemolytic anaemia: a prospective study during 6 months gestation and 3 months post-partum. Br J Haematol. 1973;24(2):219-29.
11. 11. Siegler RL, Pavia AT, Hansen FL, Christofferson RD, Cook JB. Atypical hemolytic-uremic syndrome: a comparison with postdiarrheal disease. J Pediatr. 1996;128(4):505-11.
12. 12. Fakhouri F, Hourmant M, Campistol JM, Cataland SR, Espinosa M, Gaber AO, et al. Terminal Complement Inhibitor Eculizumab in Adult Patients With Atypical Hemolytic Uremic Syndrome: A Single-Arm, Open-Label Trial. Am J Kidney Dis. 2016;68(1):84-93.
13. 13. Fremeaux-Bacchi V, Fakhouri F, Garnier A, Bienaimé F, Dragon-Durey MA, Ngo S, et al. Genetics and outcome of atypical hemolytic uremic syndrome: a nationwide French series comparing children and adults. Clin J Am Soc Nephrol. 2013;8(4):554-62.
14. 14. Józsi M, Licht C, Strobel S, Zipfel SL, Richter H, Heinen S, et al. Factor H autoantibodies in atypical hemolytic uremic syndrome correlate with CFHR1/CFHR3 deficiency. Blood. 2008;111(3):1512-4.
15. 15. Song D, Yu XJ, Wang FM, Xu BN, He YD, Chen Q, et al. Overactivation of Complement Alternative Pathway in Postpartum Atypical Hemolytic Uremic Syndrome Patients with Renal Involvement. Am J Reprod Immunol. 2015;74(4):345-56.
16. 16. Kozlovskaya NL, Korotchaeva YV, Bobrova LA. Adverse outcomes in obstetric-atypical haemolytic uraemic syndrome: a case series analysis. J Matern Fetal Neonatal Med. 2019;32(17):2853-9.
17. 17. Asif A, Nayer A, Haas CS. Atypical hemolytic uremic syndrome in the setting of complement-amplifying conditions: case reports and a review of the evidence for treatment with eculizumab. J Nephrol. 2017;30(3):347-62.
18. 18. Mwita JC, Vento S, Benti T. Thrombotic Thrombocytopenic Purpura-Haemolytic Uremic Syndrome and pregnancy. Pan Afr Med J. 2014;17:255.
19. 19. Dixit S, Tiwari AK, Pandey PK, Raina V. Successful outcome of therapeutic plasma exchange in post-partum haemolytic-uraemic syndrome: a case report. Blood Transfus. 2012;10(4):533-5.
20. 20. Zschiedrich S, Prager EP, Kuehn EW. Successful treatment of the postpartum atypical hemolytic uremic syndrome with eculizumab. Ann Intern Med. 2013;159(1):76.
21. 21. Scully M, Cataland S, Coppo P, de la Rubia J, Friedman KD, Kremer Hovinga J, et al. Consensus on the standardization of terminology in thrombotic thrombocytopenic purpura and related thrombotic microangiopathies. J Thromb Haemost. 2017;15(2):312-22.
22. 22. Elayoubi J, Donthireddy K, Nemakayala DR. Microangiopathies in pregnancy. BMJ Case Rep. 2018;2018.
23. 23. Bendapudi PK, Hurwitz S, Fry A, Marques MB, Waldo SW, Li A, et al. Derivation and external validation of the PLASMIC score for rapid assessment of adults with thrombotic microangiopathies: a cohort study. Lancet Haematol. 2017;4(4):e157-e64.