• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of annrheumdAnnals of the Rheumatic DiseasesView this articleSubmit a manuscriptReceive email alertsContact usBMJ
Ann Rheum Dis. Feb 2005; 64(2): 273–278.
PMCID: PMC1755358

The HELLP syndrome in the antiphospholipid syndrome: retrospective study of 16 cases in 15 women


Objective: To study the characteristics of the haemolysis, elevated liver enzymes, low platelets (HELLP) syndrome in the antiphospholipid syndrome (APS) and its influence on the subsequent pregnancies.

Methods: This was a retrospective analysis of 16 episodes of HELLP complicating APS in 15 women.

Results: HELLP was complete in 10 cases and partial in six. It occurred during the second trimester in seven cases (the earliest at 18 weeks' gestation), the third trimester in seven cases, and the day following delivery in two cases. Pre-eclampsia was present in six cases and eclampsia in five. Outcome of pregnancies was: live birth (n = 8), stillbirth (n = 2) and fetal death (n = 6). APS was primary in nine women and secondary to systemic lupus erythematosus (SLE) in six. HELLP revealed primary APS in six cases. Seven women were not treated. Low dose aspirin was empirically prescribed in one woman whose APS had been undiagnosed despite a history of two fetal deaths. In the other women, therapy consisted of aspirin (n = 8), low molecular weight heparin with a dose varying between 3000 and 12 000 U daily (n = 5), and high dose immunoglobulin every 4 weeks (n = 2), hydroxychloroquine (n = 4), and prednisone (n = 6). Six women had seven subsequent pregnancies, 3–6 years after the complicated pregnancy. HELLP recurred at 33 weeks' gestation in one woman with SLE treated with prednisone, hydroxychloroquine, aspirin, and enoxaparin, and pregnancy ended in live birth. One woman became pregnant after in vitro fertilisation and embryo transfer, but pregnancy ended in fetal death despite prednisone, hydroxychloroquine, and enoxaparin. Four women had five uneventful pregnancies with 100 mg daily aspirin and heparin.

Conclusions: APS may be revealed by HELLP. In APS, HELLP is associated with pre-eclampsia/eclampsia in most cases and seems to occur earlier than in the general population. Heparin plus aspirin may prevent obstetric complications in the subsequent pregnancies.

Full Text

The Full Text of this article is available as a PDF (244K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Sibai BM, Ramadan MK, Usta I, Salama M, Mercer BM, Friedman SA. Maternal morbidity and mortality in 442 pregnancies with hemolysis, elevated liver enzymes, and low platelets (HELLP syndrome) Am J Obstet Gynecol. 1993 Oct;169(4):1000–1006. [PubMed]
  • Wilson WA, Gharavi AE, Koike T, Lockshin MD, Branch DW, Piette JC, Brey R, Derksen R, Harris EN, Hughes GR, et al. International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome: report of an international workshop. Arthritis Rheum. 1999 Jul;42(7):1309–1311. [PubMed]
  • Audibert F, Friedman SA, Frangieh AY, Sibai BM. Clinical utility of strict diagnostic criteria for the HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome. Am J Obstet Gynecol. 1996 Aug;175(2):460–464. [PubMed]
  • Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1997 Sep;40(9):1725–1725. [PubMed]
  • Branch DW. Antiphospholipid antibodies and reproductive outcome: the current state of affairs. J Reprod Immunol. 1998 Apr;38(1):75–87. [PubMed]
  • Martin JN, Jr, Rinehart BK, May WL, Magann EF, Terrone DA, Blake PG. The spectrum of severe preeclampsia: comparative analysis by HELLP (hemolysis, elevated liver enzyme levels, and low platelet count) syndrome classification. Am J Obstet Gynecol. 1999 Jun;180(6 Pt 1):1373–1384. [PubMed]
  • Queyrel V, Ducloy-Bouthors A-S, Michon-Pasturel U, Hachulla E, Dubucquoi S, Caron C, Vallat A-S, Subtil D, Dufour P, Lambert M, et al. Anticorps antiphospholipides au cours du syndrome HELLP: étude clinique et biologique à partir de 68 patientes. Rev Med Interne. 2003 Mar;24(3):158–164. [PubMed]
  • Kinoshita K. Hepatic infarction during pregnancy complicated by antiphospholipid syndrome. Am J Obstet Gynecol. 1993 Jul;169(1):199–202. [PubMed]
  • Hochfeld M, Druzin ML, Maia D, Wright J, Lambert RE, McGuire J. Pregnancy complicated by primary antiphospholipid antibody syndrome. Obstet Gynecol. 1994 May;83(5 Pt 2):804–805. [PubMed]
  • Ornstein MH, Rand JH. An association between refractory HELLP syndrome and antiphospholipid antibodies during pregnancy; a report of 2 cases. J Rheumatol. 1994 Jul;21(7):1360–1364. [PubMed]
  • Ilbery M, Jones AR, Sampson J. Lupus anticoagulant and HELLP syndrome complicated by placental abruption, hepatic, dermal and adrenal infarction. Aust N Z J Obstet Gynaecol. 1995 May;35(2):215–217. [PubMed]
  • Alsulyman OM, Castro MA, Zuckerman E, McGehee W, Goodwin TM. Preeclampsia and liver infarction in early pregnancy associated with the antiphospholipid syndrome. Obstet Gynecol. 1996 Oct;88(4 Pt 2):644–646. [PubMed]
  • Segal S, Shenhav S, Segal O, Zohav E, Gemer O. Budd-Chiari syndrome complicating severe preeclampsia in a parturient with primary antiphospholipid syndrome. Eur J Obstet Gynecol Reprod Biol. 1996 Sep;68(1-2):227–229. [PubMed]
  • Amant F, Spitz B, Arnout J, Van Assche FA. Hepatic necrosis and haemorrhage in pregnant patients with antiphospholipid antibodies. Lupus. 1997;6(6):552–555. [PubMed]
  • Nagayama K, Izumi N, Miyasaka Y, Saito K, Ono K, Noguchi O, Hoshino Y, Uchihara M, Miyake S, Enomoto N, et al. Hemolysis, elevated liver enzymes, and low platelets syndrome associated with primary anti-phospholipid antibody syndrome. Intern Med. 1997 Sep;36(9):661–666. [PubMed]
  • Neuwelt CM, Daikh DI, Linfoot JA, Pfister DA, Young RG, Webb RL, London SS, Asherson RA. Catastrophic antiphospholipid syndrome: response to repeated plasmapheresis over three years. Arthritis Rheum. 1997 Aug;40(8):1534–1539. [PubMed]
  • McMahon LP, Smith J. The HELLP syndrome at 16 weeks gestation: possible association with the antiphospholipid syndrome. Aust N Z J Obstet Gynaecol. 1997 Aug;37(3):313–314. [PubMed]
  • Fehr T, Cathomas G, Weber C, Fontana A, Schaffner A. Foetal loss, liver necrosis and acute lupus erythematosus in a patient with antiphospholipid antibody syndrome. Lupus. 2001;10(8):576–579. [PubMed]
  • Sinha Jayashree, Chowdhry Iftikhar, Sedan Sarah, Barland Peter. Bone marrow necrosis and refractory HELLP syndrome in a patient with catastrophic antiphospholipid antibody syndrome. J Rheumatol. 2002 Jan;29(1):195–197. [PubMed]
  • Pauzner R, Dulitzky M, Carp H, Mayan H, Kenett R, Farfel Z, Many A. Hepatic infarctions during pregnancy are associated with the antiphospholipid syndrome and in addition with complete or incomplete HELLP syndrome. J Thromb Haemost. 2003 Aug;1(8):1758–1763. [PubMed]
  • Haram Kjell, Trovik Jone, Sandset Per Morten, Hordnes Knut. 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 Jul;82(7):679–680. [PubMed]
  • Roberts G, Gordon MM, Porter D, Jardine AG, Gibson IW. Acute renal failure complicating HELLP syndrome, SLE and anti-phospholipid syndrome: successful outcome using plasma exchange therapy. Lupus. 2003;12(4):251–257. [PubMed]
  • Huong DL, Wechsler B, Bletry O, Vauthier-Brouzes D, Lefebvre G, Piette JC. A study of 75 pregnancies in patients with antiphospholipid syndrome. J Rheumatol. 2001 Sep;28(9):2025–2030. [PubMed]
  • Backos M, Rai R, Baxter N, Chilcott IT, Cohen H, Regan L. Pregnancy complications in women with recurrent miscarriage associated with antiphospholipid antibodies treated with low dose aspirin and heparin. Br J Obstet Gynaecol. 1999 Feb;106(2):102–107. [PubMed]
  • Branch DW, Peaceman AM, Druzin M, Silver RK, El-Sayed Y, Silver RM, Esplin MS, Spinnato J, Harger J. A multicenter, placebo-controlled pilot study of intravenous immune globulin treatment of antiphospholipid syndrome during pregnancy. The Pregnancy Loss Study Group. Am J Obstet Gynecol. 2000 Jan;182(1 Pt 1):122–127. [PubMed]
  • Kutteh WH. Antiphospholipid antibody-associated recurrent pregnancy loss: treatment with heparin and low-dose aspirin is superior to low-dose aspirin alone. Am J Obstet Gynecol. 1996 May;174(5):1584–1589. [PubMed]
  • Lima F, Khamashta MA, Buchanan NM, Kerslake S, Hunt BJ, Hughes GR. A study of sixty pregnancies in patients with the antiphospholipid syndrome. Clin Exp Rheumatol. 1996 Mar-Apr;14(2):131–136. [PubMed]
  • Rai RS, Clifford K, Cohen H, Regan L. High prospective fetal loss rate in untreated pregnancies of women with recurrent miscarriage and antiphospholipid antibodies. Hum Reprod. 1995 Dec;10(12):3301–3304. [PubMed]
  • Rosove MH, Tabsh K, Wasserstrum N, Howard P, Hahn BH, Kalunian KC. Heparin therapy for pregnant women with lupus anticoagulant or anticardiolipin antibodies. Obstet Gynecol. 1990 Apr;75(4):630–634. [PubMed]
  • Ruffatti A, Orsini A, Di Lenardo L, Nardelli GB, Patrassi GM, Truscia D, Brigato G, Grella P, Todesco S. A prospective study of fifty-three consecutive calcium heparin treated pregnancies in patients with antiphospholipid antibody-related fetal loss. Clin Exp Rheumatol. 1997 Sep-Oct;15(5):499–505. [PubMed]
  • Silveira LH, Hubble CL, Jara LJ, Saway S, Martínez-Osuna P, Seleznick MJ, Angel J, O'Brien W, Espinoza LR. Prevention of anticardiolipin antibody-related pregnancy losses with prednisone and aspirin. Am J Med. 1992 Oct;93(4):403–411. [PubMed]
  • Silver RK, MacGregor SN, Sholl JS, Hobart JM, Neerhof MG, Ragin A. Comparative trial of prednisone plus aspirin versus aspirin alone in the treatment of anticardiolipin antibody-positive obstetric patients. Am J Obstet Gynecol. 1993 Dec;169(6):1411–1417. [PubMed]
  • Balasch J, Carmona F, López-Soto A, Font J, Creus M, Fábregues F, Ingelmo M, Vanrell JA. Low-dose aspirin for prevention of pregnancy losses in women with primary antiphospholipid syndrome. Hum Reprod. 1993 Dec;8(12):2234–2239. [PubMed]
  • Cowchock FS, Reece EA, Balaban D, Branch DW, Plouffe L. Repeated fetal losses associated with antiphospholipid antibodies: a collaborative randomized trial comparing prednisone with low-dose heparin treatment. Am J Obstet Gynecol. 1992 May;166(5):1318–1323. [PubMed]
  • Hasegawa I, Takakuwa K, Goto S, Yamada K, Sekizuka N, Kanazawa K, Tanaka K. Effectiveness of prednisolone/aspirin therapy for recurrent aborters with antiphospholipid antibody. Hum Reprod. 1992 Feb;7(2):203–207. [PubMed]
  • Branch DW, Silver RM, Blackwell JL, Reading JC, Scott JR. Outcome of treated pregnancies in women with antiphospholipid syndrome: an update of the Utah experience. Obstet Gynecol. 1992 Oct;80(4):614–620. [PubMed]
  • von Tempelhoff GF, Heilmann L, Spanuth E, Kunzmann E, Hommel G. Incidence of the factor V Leiden-mutation, coagulation inhibitor deficiency, and elevated antiphospholipid-antibodies in patients with preeclampsia or HELLP-syndrome. Hemolysis, elevated liver-enzymes, low platelets. Thromb Res. 2000 Nov 15;100(4):363–365. [PubMed]
  • Asherson RA, Cervera R, Piette JC, Shoenfeld Y, Espinosa G, Petri MA, Lim E, Lau TC, Gurjal A, Jedryka-Góral A, et al. Catastrophic antiphospholipid syndrome: clues to the pathogenesis from a series of 80 patients. Medicine (Baltimore) 2001 Nov;80(6):355–377. [PubMed]
  • Isler CM, Barrilleaux PS, Magann EF, Bass JD, Martin JN., Jr A prospective, randomized trial comparing the efficacy of dexamethasone and betamethasone for the treatment of antepartum HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome. Am J Obstet Gynecol. 2001 Jun;184(7):1332–1339. [PubMed]

Figures and Tables

Figure 1
 Date of HELLP onset in APS.

Articles from Annals of the Rheumatic Diseases are provided here courtesy of BMJ Group


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...