HELLP Syndrome Developing at 14 Weeks of Gestation: An Extremely Rare Case Report and a Literature Review

Article ID: e101023221976 Pages: 5

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Abstract

Introduction: Hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome is a disease of pregnancy that occurs very rarely before 20 weeks of gestation. We report a case of HELLP syndrome developing at 14 weeks and 2 days of gestation.

Case Presentation: A 33-year-old Asian primipara at 14 weeks and 2 days of gestation visited the emergency room with a fever and headache. Initial blood pressure was 140/70 mm Hg, temperature 38.5°C, heart rate 130 beats/min with tachycardia. Her prenatal examination has been unremarkable, and fetal ultrasonography was within normal range. The laboratory results showed low platelet count with elevated liver enzymes, D-dimer, and fibrinogen but no sign of jaundice. Her WBC differential suggested a bacterial infection. Thus, we diagnosed early HELLP syndrome and immediately started conservative treatments. One day after admission, symptoms and laboratory results showed aggravation of the disease. We performed termination, followed by dilation and curettage for retained placenta. Her general condition improved rapidly after the operation. Placental biopsy showed both acute and chronic inflammation. She also had anticardiolipin antibody IgM, and after discharge, she was referred to a rheumatology specialist to address the antiphospholipid syndrome issue.

Discussion: Although the triggers of HELLP syndrome are unclear, a recent inflammatory hypothesis suggests that placenta-derived inflammatory cytokines are involved. In our case, the anti-cardiolipin antibody may have triggered microangiopathy of the placenta. Our analysis of published HELLP cases revealed that, apart from the three diagnostic criteria, the most common abnormal laboratory finding was antiphospholipid antibodies. Therefore, despite its rarity, if a sign of inflammation is present in a patient, it is important to consider HELLP syndrome regardless of gestational age.

Graphical Abstract

[1]
Haram, K.; Svendsen, E.; Abildgaard, U. The HELLP syndrome: Clinical issues and management. BMC Pregnancy Childbirth, 2009, 9(1), 8.
[http://dx.doi.org/10.1186/1471-2393-9-8] [PMID: 19245695]
[2]
He, Y.; Yang, H. Clinical diagnosis and treatment of “atypical” HELLP syndrome. Gynecol. Obstetrics Clin. Med., 2022, 2(3), 105-108.
[http://dx.doi.org/10.1016/j.gocm.2022.08.001]
[3]
Md, L.P.M.M.; Smith, J. The HELLP syndrome at 16 weeks gestation: Possible association with the antiphospholipid syndrome. Aust. N. Z. J. Obstet. Gynaecol., 1997, 37(3), 313-314.
[http://dx.doi.org/10.1111/j.1479-828X.1997.tb02417.x] [PMID: 9325513]
[4]
Stefos, T.; Plachouras, N.; Mari, G.; Cosmi, E.; Lolis, D. A case of partial mole and atypical type I triploidy associated with severe HELLP syndrome at 18 weeks’ gestation. Ultrasound Obstet. Gynecol., 2002, 20(4), 403-404.
[http://dx.doi.org/10.1046/j.1469-0705.2002.00822.x] [PMID: 12383328]
[5]
Haram, K.; Trovik, J.; Sandset, P.M.; Hordnes, K. Severe syndrome of hemolysis, elevated liver enzymes and low platelets (HELLP) in the 18th week of pregnancy associated with the antiphospholipid-antibody syndrome. Acta Obstet. Gynecol. Scand., 2003, 82(7), 679-680.
[http://dx.doi.org/10.1034/j.1600-0412.2003.00181.x] [PMID: 12790854]
[6]
Sherer, D.; Dalloul, M.; Stimphil, R.; Hellmann, M.; Khoury-Collado, F.; Osho, J.; Fomitcheva, L.; Brennan, K.; Abulafia, O. Acute onset of severe hemolysis, elevated liver enzymes, and low platelet count syndrome in a patient with a partial hydatidiform mole at 17 weeks gestation. Am. J. Perinatol., 2006, 23(3), 163-166.
[http://dx.doi.org/10.1055/s-2006-934093] [PMID: 16586230]
[7]
Bornstein, E.; Barnhard, Y.; Atkin, R.; Divon, M.Y. HELLP syndrome. Obstet. Gynecol., 2007, 110(2), 525-527.
[http://dx.doi.org/10.1097/01.AOG.0000268512.26170.ad] [PMID: 17666652]
[8]
Berry, E.L.; Iqbal, S.N. HELLP syndrome at 17 weeks gestation: A rare and catastrophic phenomenon. J. Clin. Gynecol. Obstet., 2014, 3(4), 147-150.
[http://dx.doi.org/10.14740/jcgo297w] [PMID: 25806101]
[9]
Myer, E.; Hill, J. First trimester hemolysis, elevated liver enzymes, low platelets syndrome in a surrogate pregnancy. AJP Rep., 2015, 5(2), e212-e214.
[http://dx.doi.org/10.1055/s-0035-1563389] [PMID: 26495187]
[10]
Craig, K.; Pinette, M.G.; Blackstone, J.; Chard, R.; Cartin, A. Highly abnormal maternal inhibin and β-human chorionic gonadotropin levels along with severe HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome at 17 weeks’ gestation with triploidy. Am. J. Obstet. Gynecol., 2000, 182(3), 737-739.
[http://dx.doi.org/10.1067/mob.2000.103771] [PMID: 10739543]
[11]
Gasem, T.; Al Jama, F.E.; Burshaid, S.; Rahman, J.; Al Suleiman, S.A.; Rahman, M.S. Maternal and fetal outcome of pregnancy complicated by HELLP syndrome. J. Matern. Fetal Neonatal Med., 2009, 22(12), 1140-1143.
[http://dx.doi.org/10.3109/14767050903019627] [PMID: 19916711]
[12]
Miyakis, S.; Lockshin, M.D.; Atsumi, T.; Branch, D.W.; Brey, R.L.; Cervera, R.; Derksen, R.H.W.M.; De Groot, P.G.; Koike, T.; Meroni, P.L.; Reber, G.; Shoenfeld, Y.; Tincani, A.; Vlachoyiannopoulos, P.G.; Krilis, S.A. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J. Thromb. Haemost., 2006, 4(2), 295-306.
[http://dx.doi.org/10.1111/j.1538-7836.2006.01753.x] [PMID: 16420554]
[13]
Sibai, B.M. Diagnosis, controversies, and management of the syndrome of hemolysis, elevated liver enzymes, and low platelet count. Obstet. Gynecol., 2004, 103(5 (Part 1)), 981-991.
[http://dx.doi.org/10.1097/01.AOG.0000126245.35811.2a] [PMID: 15121574]
[14]
Wallace, K.; Harris, S.; Addison, A.; Bean, C. HELLP syndrome: Pathophysiology and current therapies. Curr. Pharm. Biotechnol., 2018, 19(10), 816-826.
[http://dx.doi.org/10.2174/1389201019666180712115215] [PMID: 29998801]
[15]
Habli, M.; Eftekhari, N.; Wiebracht, E.; Bombrys, A.; Khabbaz, M.; How, H.; Sibai, B. Long-term maternal and subsequent pregnancy outcomes 5 years after hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome. Am. J. Obstet. Gynecol., 2009, 201(4), 385.e1-385.e5.
[http://dx.doi.org/10.1016/j.ajog.2009.06.033] [PMID: 19716544]
[16]
Abildgaard, U.; Heimdal, K. Pathogenesis of the syndrome of hemolysis, elevated liver enzymes, and low platelet count (HELLP): A review. Eur. J. Obstet. Gynecol. Reprod. Biol., 2013, 166(2), 117-123.
[http://dx.doi.org/10.1016/j.ejogrb.2012.09.026] [PMID: 23107053]
[17]
Malmström, O.; Morken, N.H. HELLP syndrome, risk factors in first and second pregnancy: A population-based cohort study. Acta Obstet. Gynecol. Scand., 2018, 97(6), 709-716.
[http://dx.doi.org/10.1111/aogs.13322] [PMID: 29430625]
[18]
Petca, A.; Miron, B.C.; Pacu, I.; Dumitrașcu, M.C.; Mehedințu, C.; Șandru, F.; Petca, R.C.; Rotar, I.C. HELLP syndrome-holistic insight into pathophysiology. Medicina, 2022, 58(2), 326.
[http://dx.doi.org/10.3390/medicina58020326] [PMID: 35208649]
[19]
Landi, B.; Tranquilli, A.L. HELLP syndrome and placental inflammatory pathology. Minerva Ginecol., 2008, 60(5), 389-398.
[PMID: 18854806]
[20]
Goldstein, JA; Gallagher, K; Beck, C; Kumar, R; Gernand, AD Maternal-fetal inflammation in the placenta and the developmental origins of health and disease. Front. Immunol., 2020, 13(11), 531543.
[http://dx.doi.org/10.3389/fimmu.2020.531543]
[21]
Gardiner, C.; Tannetta, D.S.; Simms, C.A.; Harrison, P.; Redman, C.W.G.; Sargent, I.L. Syncytiotrophoblast microvesicles released from pre-eclampsia placentae exhibit increased tissue factor activity. PLoS One, 2011, 6(10), e26313.
[http://dx.doi.org/10.1371/journal.pone.0026313] [PMID: 22022598]
[22]
Bouariu, A.; Gică, N.; Ciobanu, A.M.; Scutelnicu, A.M.; Popescu, M.R.; Panaitescu, A.M. The potential benefit of hydroxychloroquine in chronic placental inflammation of unknown etiology associated with adverse pregnancy outcomes. Healthcare, 2022, 10(1), 168.
[http://dx.doi.org/10.3390/healthcare10010168] [PMID: 35052331]
[23]
Appenzeller, S.; Souza, F.H.C.; Wagner Silva de Souza, A.; Shoenfeld, Y.; de Carvalho, J.F. HELLP syndrome and its relationship with antiphospholipid syndrome and antiphospholipid antibodies. Semin. Arthritis Rheum., 2011, 41(3), 517-523.
[http://dx.doi.org/10.1016/j.semarthrit.2011.05.007] [PMID: 21868064]
[24]
Mulla, M.J.; Brosens, J.J.; Chamley, L.W.; Giles, I.; Pericleous, C.; Rahman, A.; Joyce, S.K.; Panda, B.; Paidas, M.J.; Abrahams, V.M. Antiphospholipid antibodies induce a pro-inflammatory response in first trimester trophoblast via the TLR4/MyD88 pathway. Am. J. Reprod. Immunol., 2009, 62(2), 96-111.
[http://dx.doi.org/10.1111/j.1600-0897.2009.00717.x] [PMID: 19614626]