HELLP syndrome: its clinical and laboratory features and imbalance of placental angiogenic factors
Objective. To investigate the clinical and laboratory characteristics of HELLP syndrome and to compare the clinical manifestations of nephropathy in women with moderate and severe preeclampsia (PE) and HELLP syndrome, by correlating them with the blood levels of placental growth factor (PlGF) and soluble fms-like tyrosine kinase 1 (sFlt-1). Material and methods. The course and outcome of pregnancies were studied in 141 women who were divided into 4 groups: 1) HELLP syndrome; 2) severe PE; 3) moderate PE; and 4) a control group. The investigators assessed and compared main laboratory, clinical, biochemical, and immunological parameters, including imbalance of placental angiogenic factors (sFlt-1 and PlGF) and conducted instrumental studies. Results. The patients with HELLP syndrome were found to have a significantly lower sFlt-1/PLGF ratio (median value, 254±93.51 pg/ml) than those with severe (median values, 439.08±112.29 pg/ml) or moderate (306.62±164.59 pg/ml) PE. In addition to damage to the liver, the signs of involvement of other organs in the pathological process were seen in almost all the patients; at the same time renal failure was more pronounced than in those with PE (median values of serum creatinine was 110.80±20.62, 73.26±4.55, and 71.73±6.16 µmol/l in HELLP syndrome, severe PE, and moderate PE, respectively). There was a moderate direct correlation of the level of lactate dehydrogenase (LDH) with that of creatinine (r = 0.539) and total bilirubin (r = 0.606) and an inverse correlation of LDH with platelets (r = -0.384). The role of the imbalance of placental angiogenic markers in the development of clinical manifestations in HELLP syndrome was discussed. Conclusion. HELLP syndrome is unlikely to be a more severe variant of PE. HELLP syndrome is a clinically manifest variant of thrombotic microangiopathy. PE appears to be only a trigger for the development of HELLP syndrome.Kirsanova T.V., Vinogradova M.A., Kolyvanova A.I., Shmakov R.G.
Keywords
HELLP syndrome
pre-eclampsia
thrombotic microangiopathy
placental growth factor (PLGF)
soluble fms-like tyrosine kinase-1 (sFlt-1)
References
1. Sibai B.M., Ramadan M.K., Usta I., Salama M., Mercer B.M., Friedman S.A. Maternal morbidity and mortality in 442 pregnancies with hemolysis, elevated liver enzymes, and low platelets (HELLP syndrome). Am. J. Obstet. Gynecol.1993; 169(4): 1000-6.
2. Sibai B.M., Ramadan M.K., Chari R.S., Friedman S.A. 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(1, Pt 1): 125-9.
3. Sibai B.M., Ramadan M.K. Acute renal failure in pregnancies complicated by hemolysis, elevated liver enzymes, and low platelets. Am. J. Obstet. Gynecol. 1993; 168(6): 1682-7.
4. Fakhouri F., Jablonski M., Lepercq J., Blouin J., Benachi A., Hourmat M. et al. Factor H, membrane cofactor protein, and factor I mutations in patients with hemolysis, elevated liver enzymes, and low platelet count syndrome. Blood. 2008; 112(12): 4542-5.
5. Ходжаева З.С., Холин А.М., Вихляева Е.М. Ранняя и поздняя преэклампсия: парадигмы патобиологии и клиническая практика. Акушерство и гинекология. 2013; 10: 4-11. [Khodzhaeva Z.S., Kholin A.M., Vikhlyaeva E.M. Early and late preeclampsia: Pathobiology paradigms and clinical practice. Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2013; 10: 4-11. (in Russian)]
6. Carty D.M., Delles C., Dominiczak A.F. Novel biomarkers for predicting preeclampsia. Trends Cardiovasc. Med. 2008; 18(5): 186-94.
7. Redman C.W., Sargent I.L. Placental stress and preeclampsia: a revised view. Placenta. 2009; 30A: 38-42.
8. Guller S. Role of the syncytium in placenta-mediated complications of preeclampsia. Thromb. Res. 2009; 124(4): 389-92.
9. Landi B., Tranquilli A.L. HELLP syndrome and placental inflammatory pathology. Minerva Ginecol. 2008; 60(5): 389-98.
10. Tranquilli А.L., Landi B., Corradetti A., Giannubilo S.R., Sartini D., Pozzi V. et al. Inflammatory cytokines patterns in the placenta of pregnancies complicated by HELLP (hemolysis, elevated liver enzyme, and low platelet) syndrome. Cytokine. 2007; 40(2): 82-8.
11. Wallace K., Martin J.N. Jr, Tam Tam K., Wallukat G., Dechend R., Lamarca B. et al. Seeking the mechanisms of action for corticosteroids in HELLP syndrome: SMASH study. Am. J. Obstet. Gynecol. 2013; 208(5): 380. e1-8.
12. Weiner Е., Schreiber L., Grinstein E., Feldstein O., Rymer-Haskel N., Bar J., Kovo M. The placental component and obstetric outcome in severe preeclampsia with and without HELLP syndrome. Placenta. 2016; 47: 99-104.
13. Shinohara S., Ushida Y., Kasai M., Sunami R. Association between the high soluble fms-like tyrosine kinase-1 to placental growth factor ratio and adverse outcomes in asymptomatic women with early-onset fetal growth restriction. Hypertens. Pregnancy. 2017; 36(3): 269-75.
14. Stepan H., Hund M., Gencay M., Denk B., Dinkel C., Kaminski W.E. et al. A comparison of the diagnostic utility of the sFlt-1/PlGF ratio versus PlGF alone for the detection of preeclampsia/HELLP syndrome. Hypertens. Pregnancy. 2016; 35(3): 295-305.
15. Иванец Т.Ю., Алексеева М.Л., Кан Н.Е., Тютюнник В.Л., Амирасланов Э.Ю., Насонова Д.М., Фанченко Н.Д. Диагностическая значимость определения плацентарного фактора роста и растворимой FMS-подобной тирозинкиназы-1 в качестве маркеров преэклампсии. Проблемы репродукции. 2015; 21(4): 129-33. [Ivanets T.Yu., Alekseeva M.L., Kan N.E., Tyutyunnik V.L., Amiraslanov E.Yu., Nasonova D.M., Fanchenko N.D. Diagnostic significance of the determination of placental growth factor and soluble FMS-like tyrosine kinase-1 as markers of preeclampsia. Problemy reproduktsii. 2015; 21(4): 129-33. (in Russian)]
16. Козловская Н.Л., Кирсанова Т.В., Калашникова Л.А., Смирнова Т.В., Боброва Л.А., Садовников В.И., Платова Е.Н., Беляева Л.Е., Варшавский В.А., Рощупкина С.В. Поражение почек при синдроме Снеддона. Нефрология и диализ. 2011; 13(4): 408-19. [Kozlovskaya N.L., Kirsanova T.V., Kalashnikova L.A., Smirnova T.V., Bobrova L.A., Sadovnikov V.I., Platova E.N., Belyaeva L.E., Varshavsky V.A., Roshchupkina S.V. Kidney damage in Sneddon’s syndrome. Nefrologiya i dializ. 2011; 13 (4): 408-19. (in Russian)]
17. Шилов Е.М., Козловская Н.Л., Метелева Н.А., Козловская Л.В., Варшавский В.А., Мирошниченко Н.Г., Блохина Г.В., Серова А.Г., Нестерова С.Г., Смоляницкий A.Я. Клинические проявления нефропатии, связанной с антифосфолипидным синдромом, при первичном антифосфолипидном синдроме. Терапевтический архив. 2003; 75(6): 22-8. [Shilov E.M., Kozlovskaya N.L., Meteleva N.A., Kozlovskaya L.V., Varshavsky V.A., Miroshnichenko N.G., Blokhina G.V., Serova A.G., Nesterova S.G., Smolyanitsky A.Ya. Clinical manifestations of nephropathy associated with antiphospholipid syndrome, with primary antiphospholipid syndrome. Terapevticheskiy arhiv. 2003; 75 (6): 22-8. (in Russian)]
18. Ballermann B.J. Glomerular endothelial cell differentiation. Kidney Int. 2005; 67(5): 1668-71.
19. Erkılınç S., Eyi E.G.Y. Factors contributing to adverse maternal outcomes in patients with HELLP syndrome. J. Matern. Fetal Neonatal Med. 2017;Aug 8: 1-7.
20. Калашникова Л.А. Неврология антифосфолипидного синдрома. М.: Медицина; 2003. 256с. [Kalashnikova L.A. Neurology of antiphospholipid syndrome. Moscow: Meditsina; 2003. 256p. (in Russian)]
21. Takahashi H., Matsubara T., Makino S., Horie K., Matsubara S. Color vision abnormality as the sole manifestation of posterior reversible encephalopathy due to post-partum HELLP syndrome. J. Obstet. Gynaecol. Res. 2017; 43(3): 592-4.
22. Morisawa H., Makino S., Takahashi H., Sorita M., Matsubara S. Retinal detachment in hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome: Color vision abnormality as the first and predominant manifestation. J. Obstet. Gynaecol. Res. 2015; 41(11): 1835-8.
23. Trese M.G., Thanos A., Yonekawa Y., Randhawa S. Optical coherence tomography angiography of paracentral acute middle maculopathy associated with primary antiphospholipid syndrome. Ophthalmic Surg. Lasers Imaging Retina. 2017; 48(2): 175-8.
24. Giorgi D., David V., Afeltre A., Gabrieli C.B. Transient visual symptomus in systemic lupus erythematosus and antiphospholipid syndrome. Ocul. Immunol. Inflamm. 2001; 9(1): 49-57.
25. Gerber S.L., Cantor L.B. Progressive optic atrophy and the primary antiphospholipid antibody syndrome. Am. J. Ophthalmol.1990; 110(4): 443-4.
26. Bolling J.P., Brown J.C. The antiphospholipid antibody syndrome. Curr. Opin. Ophthalmol. 2000; 11(3): 211-3.
27. Castanon C., Amigo M.C., Banales J.L., Nava A., Reyes P.A. Ocular vasoocclusive disease in primary antiphospholipid syndrome. Ophthalmology. 1995; 102(2): 256-62.
28. Kleiner R.C., Najarian L.V., Schatten S., Jabs D.A., Patz A., Kaplan H.J. Vaso-occlusive retinopathy associated with an antiphospholipid antibodyes (lupus anticoagulant retinopathy). Ophthalmology. 1989; 96(6):896-904.
29. Patschan D., Witzke O., Dührsen U., Erbel R, Philipp T., Herget-Rosenthal S. Acute myocardial infarction in thrombotic microangiopathies - clinical characteristics, risk factors and outcome. Nephrol. Dial. Transplant. 2006; 21(6): 1549-54.
30. Orabona R., Vizzardi E., Sciatti E., Prefumo F., Bonadei I., Valcamonico A. et al. Maternal cardiac function after HELLP syndrome: an echocardiography study. Ultrasound Obstet. Gynecol. 2017; 50(4): 507-13.
31. Hosokawa A., Umazume T., Yamada T., Minakami H. Maternal bradycardia occurring prior to onset of HELLP syndrome in a woman with pre-eclampsia. BMJ Case Rep 2017; May 13; 2017. pii: bcr-2016-217964.
32. Hedengran K., Andersen M., Stender S., Szecsi P. Large D-dimer fluctuation in normal pregnancy: a longitudinal cohort study of 4,117 samples from 714 healthy Danish women. Obstet. Gynecol. Int. 2016; 2016: 3561675.
33. Jakobsen I.M., Helmig R.B., Stengaard-Pedersen K. Maternal and fetal outcomes in pregnant systemic lupus erythematosus patients: incident cohort from a stable referral population followed during 1990-2010. Scand. J. Rheumatol. 2015; 44(5): 377-84.
34. Servais A., Devillard N., Frémeaux-Bacchi V., Hummel A., Salomon L., Contin-Bordes C. et al. Atypical haemolytic uraemic syndrome and pregnancy: outcome with ongoing eculizumab. Nephrol. Dial. Transplant. 2016; 31(12):2122-30.
35. Woodside K.J., Knisely A.S., Strauss A.W., Gugluizza K.K., Daller J.A. Progression of hepatic damage during cold storage after procurement in a liver and kidney donor with HELLP syndrome. Transplantation. 2001;72(12): 1990-3.
36. Kitchens W.H., Adams A.B., Hughes C.B., Subramanian R.M. Diagnostic challenges in the evaluation of hepatic grafts from donors with HELLP syndrome: case report and review of the literature. Transplant. Proc. 2011; 43(10): 4010-2.
37. George J.N., Terrell D.R., Vesely S.K., Kremer Hovinga J.A., Lämmle B. Thrombotic microangiopathic syndromes associated with drugs, HIV infection, hematopoietic stem cell transplantation and cancer. Presse Med. 2012; 41(3, Pt2): e177-88.
38. Carson J.M., Newman E.D., Farber J.L., Filippone E.J. Tacrolimus-induced thrombotic microangiopathy: natural history of a severe, acute vasculopathy. Clin. Nephrol. 2012; 77(1): 79-84.
39. Duineveld C., Verhave J.C., Berger S.P., van de Kar N.C.A.J., Wetzels J.F.M. Living donor kidney transplantation in atypical hemolytic uremic syndrome: a case series. Am. J. Kidney Dis. 2017; 70(6): 770-7.
40. Andreoli L., Chighizola C.B., Banzato A., Pons-Estel G.J., Ramire de Jesus G., Erkan D. Estimated frequency of antiphospholipid antibodies in patients with pregnancy morbidity, stroke, myocardial infarction, and deep vein thrombosis: a critical review of the literature. Arthritis Care Res. (Hoboken). 2013; 65(11): 1869-73.
41. Berry E.L., Iqbal S.N. HELLP Syndrome at 17 weeks gestation: a rare and catastrophic phenomenon. J. Clin. Gynecol. Obstet. 2014;3(4): 147-50.
42. Kim J.H., Yee C., Kuk J.Y., Choi S.J., Roh C.R., Kim J.H. Hepatic infarction in a pregnant woman with antiphospholipid syndrome and triple antibody positivity: A case report focusing on catastrophic antiphospholipid syndrome. Obstet. Gynecol. Sci. 2016; 59(5): 397-402.
Received 30.11.2017
Accepted 22.12.2017
About the Authors
Tatyana V. Kirsanova, Candidate of Medical Science, Senior Researcher Department of Reproductive Hematology and Clinical Hemostasiology,National Medical Research Center of Obstetrics, Gynecology, and Perinatology named after Academician V.I. Kulakov, Ministry of Health of Russia.
117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +79262484560. E-mail: A_Tatya@mail.ru
Maria A. Vinogradova, Candidate of Medical Science, Head. Department of Reproductive Hematology and Clinical Haemostasiology, National Medical Research
Center of Obstetrics, Gynecology, and Perinatology named after Academician V.I. Kulakov, Ministry of Health of Russia.
117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +74954387135. E-mail: mary-grape@ya.ru
Alina I. Kolyvanova, clinical resident of the Department of Internal Medicine of the Faculty of Fundamental Medicine of the M.V. Lomonosov Moscow State University.
119991, Russia, Moscow, Lomonosovsky Ave, 27, bld. 1. Tel.: +79858759016. E-mail: koluvanova@gmail.com
Shmakov Roman Georgievich, MD, Ph.D. National Medical Research Center of Obstetrics, Gynecology, and Perinatology named after Academician V.I. Kulakov,
Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4
For citations: Kirsanova T.V., Vinogradova M.A., Kolyvanova A.I., Shmakov R.G. HELLP syndrome: its clinical and laboratory features and imbalance of placental angiogenic factors. Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2018; (7): 46-55. (in Russian)
https://dx.doi.org/10.18565/aig.2018.7.46-55
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