Antiphospholipid Syndrome and Pre-Eclampsia

ABSTRACT

Antiphospholipid syndrome (APS) is defined as an autoimmune disorder characterized by recurrent thrombosis or obstetrical morbidity. These features are linked to the presence in blood of autoantibodies against negatively charged phospholipids or phospholipid-binding proteins. Obstetric morbidity includes recurrent abortion (early and late) and severe pre-eclampsia (P-EC)/hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome, and/or severe placental insufficiency. Criteria that define the major clinical and laboratory events were published in revised forms in the Sydney recommendations in 2006. We analyzed the blood of patients with severe P-EC according to the subgroups based on the 2006 revised criteria definition and compared these results with women after uncomplicated pregnancy and delivery. We found 20% elevated antiphospholipid antibodies (APAs) in women with severe P-EC (group I, 7.5%; group IIa, 5.0%; group IIb, 5.0%; group IIc, 2.5%). The increased APAs were observed only in women with severe P-EC (odds ratio: 2.45; 95% confidence interval, 1.01 to 4.3) and not in patients with severe P-EC at >34 weeks of gestation. According to our retrospective observation, we recommend the determination of anticardiolipin antibodies, lupus anticoagulant, and β-2 glycoprotein-1 antibodies in patients with severe P-EC at <34 weeks of gestation.

KEYWORDS

Antiphospholipid syndrome (APS) - severe P-EC - obstetric APS - Sydney criteria

REFERENCES

• 1 Bick R L. Antiphospholipid thrombosis syndromes.  Clin Appl Thromb Hemost. 2001;  7 (4) 241-258
• 2 Brown M A, Lindheimer M D, de Swiet M, Van Assche A, Moutquin J M. The classification and diagnosis of the hypertensive disorders of pregnancy: statement from the International Society for the Study of Hypertension in Pregnancy (ISSHP).  Hypertens Pregnancy. 2001;  20 (1) ix-xiv
• 3 Milne F, Redman C, Walker J et al. The pre-eclampsia community guideline (PRECOG): how to screen for and detect onset of pre-eclampsia in the community.  BMJ. 2005;  330 (7491) 576-580
• 4 Hiby S E, Walker J J, O'Shaughnessy K M et al. Combinations of maternal KIR and fetal HLA-C genes influence the risk of preeclampsia and reproductive success.  J Exp Med. 2004;  200 (8) 957-965
• 5 Sargent I L, Borzychowski A M, Redman C WG. NK cells and pre-eclampsia.  J Reprod Immunol. 2007;  76 (1–2) 40-44
• 6 Carp H JA. Antiphospholipid syndrome in pregnancy.  Curr Opin Obstet Gynecol. 2004;  16 (2) 129-135
• 7 Zhang J, Tian Z. UNK cells: their role in tissue re-modelling and preeclampsia.  Semin Immunopathol. 2007;  29 (2) 123-133
• 8 Carp H JA, Asherson R A, Shoenfeld Y. Intravenous immunoglobulin in pregnancies complicated by the antiphospholipid syndrome: what is its role?.  J Clin Rheumatol. 2001;  7 (5) 291-294
• 9 Duckitt K, Harrington D. Risk factors for pre-eclampsia at antenatal booking: systematic review of controlled studies.  BMJ. 2005;  330 (7491) 565-571
• 10 Katano K, Aoki A, Sasa H, Ogasawara M, Matsuura E, Yagami Y. β 2-Glycoprotein I-dependent anticardiolipin antibodies as a predictor of adverse pregnancy outcomes in healthy pregnant women.  Hum Reprod. 1996;  11 (3) 509-512
• 11 Nodler J, Moolamalla S R, Ledger E M, Nuwayhid B S, Mulla Z D. Elevated antiphospholipid antibody titers and adverse pregnancy outcomes: analysis of a population-based hospital dataset.  BMC Pregnancy Childbirth. 2009;  9 11
• 12 van Pampus M G, Dekker G A, Wolf H et al. High prevalence of hemostatic abnormalities in women with a history of severe preeclampsia.  Am J Obstet Gynecol. 1999;  180 (5) 1146-1150
• 13 Yamamoto T, Yoshimura S, Geshi Y et al. Measurement of antiphospholipid antibody by ELISA using purified β 2-glycoprotein I in preeclampsia.  Clin Exp Immunol. 1993;  94 (1) 196-200
• 14 Yasuda M, Takakuwa K, Tokunaga A, Tanaka K. Prospective studies of the association between anticardiolipin antibody and outcome of pregnancy.  Obstet Gynecol. 1995;  86 (4 Pt 1) 555-559
• 15 Clark E AS, Silver R M, Branch D W. Do antiphospholipid antibodies cause preeclampsia and HELLP syndrome?.  Curr Rheumatol Rep. 2007;  9 (3) 219-225
• 16 Le Thi Thuong D, Tieulié N, Costedoat N et al. The HELLP syndrome in the antiphospholipid syndrome: retrospective study of 16 cases in 15 women.  Ann Rheum Dis. 2005;  64 (2) 273-278
• 17 George D, Vasanth L, Erkan D, Bass A, Salmon J, Lockshin M D. Primary antiphospholipid syndrome presenting as HELLP syndrome: a clinical pathology conference held by the Division of Rheumatology at Hospital for Special Surgery.  HSS J. 2007;  3 (2) 216-221
• 18 Yamada H, Atsumi T, Kobashi G et al. Antiphospholipid antibodies increase the risk of pregnancy-induced hypertension and adverse pregnancy outcomes.  J Reprod Immunol. 2009;  79 (2) 188-195
• 19 Zhang J, Zeisler J, Hatch M C, Berkowitz G. Epidemiology of pregnancy-induced hypertension.  Epidemiol Rev. 1997;  19 (2) 218-232
• 20 Branch D W, Khamashta M A. Antiphospholipid syndrome: obstetric diagnosis, management, and controversies.  Obstet Gynecol. 2003;  101 (6) 1333-1344
• 21 Caruso A, De Carolis S, Di Simone N. Antiphospholipid antibodies in obstetrics: new complexities and sites of action.  Hum Reprod Update. 1999;  5 (3) 267-276
• 22 Giannakopoulos B, Passam F, Rahgozar S, Krilis S A. Current concepts on the pathogenesis of the antiphospholipid syndrome.  Blood. 2007;  109 (2) 422-430
• 23 Girardi G, Mackman N. Tissue factor in antiphospholipid antibody-induced pregnancy loss: a pro-inflammatory molecule.  Lupus. 2008;  17 (10) 931-936
• 24 Salmon J E, de Groot P G. Pathogenic role of antiphospholipid antibodies.  Lupus. 2008;  17 (5) 405-411
• 25 Bates S M, Greer I A, Hirsh J, Ginsberg J S. Use of antithrombotic agents during pregnancy: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy.  Chest. 2004;  126 (3, Suppl) 627S-644S
• 26 Wilson W A, Gharavi A E, Koike T et al. International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome: report of an international workshop.  Arthritis Rheum. 1999;  42 (7) 1309-1311
• 27 Miyakis S, Lockshin M D, Atsumi T et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS).  J Thromb Haemost. 2006;  4 (2) 295-306
• 28 Kutteh W H. 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;  174 (5) 1584-1589
• 29 Rai R, Cohen H, Dave M, Regan L. Randomised controlled trial of aspirin and aspirin plus heparin in pregnant women with recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies).  BMJ. 1997;  314 (7076) 253-257
• 30 Derksen R HWM, Khamashta M A, Branch D W. Management of the obstetric antiphospholipid syndrome.  Arthritis Rheum. 2004;  50 (4) 1028-1039
• 31 Alarcón-Segovia D, Boffa M C, Branch W et al. Prophylaxis of the antiphospholipid syndrome: a consensus report.  Lupus. 2003;  12 (7) 499-503
• 32 Cowchock S. Treatment of antiphospholipid syndrome in pregnancy.  Lupus. 1998;  7 (Suppl 2) 95-97
• 33 Huong D LT, Wechsler B, Bletry O, Vauthier-Brouzes D, Lefebvre G, Piette J-C. A study of 75 pregnancies in patients with antiphospholipid syndrome.  J Rheumatol. 2001;  28 (9) 2025-2030
• 34 Tincani A, Branch W, Levy R A et al. Treatment of pregnant patients with antiphospholipid syndrome.  Lupus. 2003;  12 (7) 524-529
• 35 Kupferminc M J, Fait G, Many A et al. Low-molecular-weight heparin for the prevention of obstetric complications in women with thrombophilias.  Hypertens Pregnancy. 2001;  20 (1) 35-44
• 36 Kalk J J, Huisjes A J, de Groot C JM et al. Recurrence rate of pre-eclampsia in women with thrombophilia influenced by low-molecular-weight heparin treatment?.  Neth J Med. 2004;  62 (3) 83-87
• 37 Brandt J T, Triplett D A, Alving B, Scharrer I. Criteria for the diagnosis of lupus anticoagulants: an update. On behalf of the Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardisation Committee of the ISTH.  Thromb Haemost. 1995;  74 (4) 1185-1190
• 38 Branch D W, Andres R, Digre K B, Rote N S, Scott J R. The association of antiphospholipid antibodies with severe preeclampsia.  Obstet Gynecol. 1989;  73 (4) 541-545
• 39 Dekker G A, de Vries J IP, Doelitzsch P M et al. Underlying disorders associated with severe early-onset preeclampsia.  Am J Obstet Gynecol. 1995;  173 (4) 1042-1048
• 40 Faden D, Tincani A, Tanzi P et al. Anti-beta 2 glycoprotein I antibodies in a general obstetric population: preliminary results on the prevalence and correlations with pregnancy outcome. Anti-beta2 glycoprotein I antibodies are associated with some obstetrical complications, mainly preeclampsia-eclampsia.  Eur J Obstet Gynecol Reprod Biol. 1997;  73 37-42
• 41 Mello G, Parretti E, Marozio L et al. Thrombophilia is significantly associated with severe preeclampsia: results of a large-scale, case-controlled study.  Hypertension. 2005;  46 (6) 1270-1274
• 42 Vashisht A, Regan L. Antiphospholipid syndrome in pregnancy-an update.  J R Coll Physicians Edinb. 2005;  35 337-339
• 43 Branch D W. Antiphospholipid antibodies and reproductive outcome: the current state of affairs.  J Reprod Immunol. 1998;  38 (1) 75-87
• 44 Lim W L, Crowther M A, Eikelboom J W. Management of antiphospholipid antibody syndrome: a systematic review.  JAMA. 2006;  295 (9) 1050-1057
• 45 Pattison N S, Chamley L W, McKay E J, Liggins G C, Butler W S. Antiphospholipid-antibodies in pregnancy: prevalence and clinical association.  BJOG. 1993;  100 909-913
• 46 Dreyfus M, Hedelin G, Kutnahorsky R et al. Antiphospholipid antibodies and preeclampsia: a case-control study.  Obstet Gynecol. 2001;  97 (1) 29-34
• 47 Branch D W, Porter T F, Rittenhouse L National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network et al. Antiphospholipid antibodies in women at risk for preeclampsia.  Am J Obstet Gynecol. 2001;  184 (5) 825-832; discussion 832–834
• 48 Sletnes K E, Wisløff F, Moe N, Dale P O. Antiphospholipid antibodies in pre-eclamptic women: relation to growth retardation and neonatal outcome.  Acta Obstet Gynecol Scand. 1992;  71 (2) 112-117
• 49 Cervera R, Piette J C, Font J Euro-Phospholipid Project Group et al. Antiphospholipid syndrome: clinical and immunologic manifestations and patterns of disease expression in a cohort of 1,000 patients.  Arthritis Rheum. 2002;  46 1019-1027
• 50 Lee R M, Brown M A, Branch D W, Ward K, Silver R M. Anticardiolipin and anti-β2-glycoprotein-I antibodies in preeclampsia.  Obstet Gynecol. 2003;  102 (2) 294-300
• 51 Lynch A, Marlar R, Murphy J et al. Antiphospholipid antibodies in predicting adverse pregnancy outcome. A prospective study.  Ann Intern Med. 1994;  120 (6) 470-475
• 52 Heilmann L, Schorch M, Hahn T et al. Pregnancy outcome in women with antiphospholipid antibodies: report on a retrospective study.  Semin Thromb Hemost. 2008;  34 (8) 794-802
• 53 Topping J, Quenby S, Farquharson R, Malia R, Greaves M. Marked variation in antiphospholipid antibodies during pregnancy: relationships to pregnancy outcome.  Hum Reprod. 1999;  14 (1) 224-228
• 54 Devreese K, Hoylaerts M F. Laboratory diagnosis of the antiphospholipid syndrome: a plethora of obstacles to overcome.  Eur J Haematol. 2009;  83 (1) 1-16