Antiphospholipid antibodies: Update on detection, pathophysiology, and treatment

Current Opinion in Hematology

Volumn 11, Issue 3, 2004, Pages 165-169

  De Groot, Philip G ^a   Derksen, Ronald H W M ^a  

^a UNIVERSITY MEDICAL CENTER UTRECHT   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

ACETYLSALICYLIC ACID; ANTITHROMBOCYTIC AGENT; BETA2 GLYCOPROTEIN 1; LUPUS ANTICOAGULANT; PHOSPHOLIPID ANTIBODY; WARFARIN;

ANTIBODY DETECTION; ANTIPHOSPHOLIPID SYNDROME; CEREBROVASCULAR ACCIDENT; CLINICAL TRIAL; HEMOSTASIS; HIGH RISK PATIENT; HUMAN; INTERNATIONAL STANDARD UNIT; LOW DRUG DOSE; PATHOPHYSIOLOGY; PRIORITY JOURNAL; PROPHYLAXIS; REGULATORY MECHANISM; REVIEW; SEROLOGY; THROMBOSIS; VEIN THROMBOSIS;

ANTIBODIES, ANTIPHOSPHOLIPID; ANTICOAGULANTS; ANTIPHOSPHOLIPID SYNDROME; FEMALE; HUMANS; PREGNANCY; PREGNANCY COMPLICATIONS, HEMATOLOGIC; THROMBOPHILIA; THROMBOSIS; VENOUS THROMBOSIS;

EID: 3242671255     PISSN: 10656251     EISSN: None     Source Type: Journal    
DOI: 10.1097/01.moh.0000130313.95291.4a     Document Type: Review

References (35)

1. Arnout J, Vermylen J: Current status and implications of autoimmune antiphospholipid antibodies in relation to thrombotic complications. J Thromb Haemost 2003, 1:931-942. An excellent review that outlines the various mechanisms whereby the antibodies can induce thromboembolic complications.
2. 2GPI and prothrombin.
3. Petri M: Evidence-based management of thrombosis in the antiphospholipid antibody syndrome. Curr Rheumatol Rep 2003, 5:370-373. A comprehensive review on treatment of APS patients.
4. Galli M, Luciani D, Bertolini G, Barbui T: Lupus anticoagulants are stronger risk factors for thrombosis than anticardiolipin antibodies in the antiphospholipid syndrome: a systematic review of the literature. Blood 2003, 101:1827-1832. Meta-analysis that analyzes the correlation between different tests to detect aPLs and thromboembolic complications. The analysis clearly showed the superiority of the LAC assay.
5. Galli M, Luciani D, Bertolini G, Barbui T: Anti-β2-glycoprotein I, antiprothrombin antibodies, and the risk of thrombosis in the antiphospholipid syndrome. Blood 2003, 102:2717-2723. Meta-analysis that showed the low association of assays that detect the presence of antiprothrombin antibodies and anti-β2GPI antibodies and thromboembolic complications.
6. Simmelink MJA, de Groot PhG, Derksen RHWM: A study on associations between antiprothrombin antibodies, antiplasminogen antibodies and thrombosis. J Thromb Haemost 2003, 1:735-739. A study that did not show clinical relevance of antiprothrombin antibodies.
7. Zanon E, Saggiorato G, Ramon R, et al.: Anti-prothrombin antibodies as a potential risk factor of recurrent venous thromboembolism. Thromb Haemost 2004, 91:255-258. A study that showed clinical relevance of antiprothrombin antibodies.
8. von Landenberg P, Matthias T, Zaech J, et al.: Antiprothrombin antibodies are associated with pregnancy loss in patients with the antiphospholipid syndrome. Am J Reprod Immunol 2003, 49:51-56. A study that showed clinical relevance of antiprothrombin antibodies.
9. 2-glycoprotein I- and prothrombin- dependent lupus anticoagulants. J Thromb Haemost 2003, 1:740-747. In this assay cardiolipin is used as neutralizing agent in the LAC assay to pick up an LAC caused by anti-β2GPI antibodies.
10. 2+ concentrations are used as neutralizing agent in the LAC assay to pick up an LAC caused by anti-β2GPI antibodies.
11. Shoenfeld Y, Krause I, Kvapil F, et al.: Prevalence and clinical correlations of antibodies against six beta2-glycoprotein-I-related peptides in the antiphospholipid syndrome. J Clin Immunol 2003, 23:377-383. Characterization of antibodies against peptide derived from β2GPI. No information on whether these antipeptide antibodies recognize β2GPI.
12. Giles IP, Isenberg DA, Latchman DS, et al.: How do antiphospholipid antibodies bind beta2-glycoprotein I? Arthritis Rheum 2003, 48:2111-2121. Among others, epitope mapping of anti-β2GPI antibodies.
13. Iverson GM, Reddel S, Victoria EJ, et al.: Use of single point mutations in domain 1 of beta 2-glycoprotein I to determine fine antigenic specificity of antiphospholipid autoantibodies. J Immunol 2002, 169:7097-7103.
14. Simmelink MJA, Horbach DA, Derksen RHWM, et al.: Complexes of antiprothrombin-antibodies and prothrombin cause LAC activity by competing with the binding of clotting factors for catalytic phospholipid surfaces. Br J Haematol 2001, 113:621-629.
15. Cugno M, Cabibbe M, Galli M, et al.: Antibodies to tissue-type plasminogen activator (tPA) in patients with antiphospholipid syndrome: evidence of interaction between the antibodies and the catalytic domain of tPA in 2 patients. Blood 2004, 103:2121-2126. Strong evidence that antibodies directed against tPA are of clinical relevance.
16. Yasuda S, Atsumi T, Ieko M, et al.: Nicked beta2-glycoprotein I: a marker of cerebral infarct and a novel role in the negative feedback pathway of extrinsic fibrinolysis. Blood 2004, 103:3766-3772 This article described elegantly how β2GPI can act as a negative regulator of fibrinolysis.
17. 2-Giycoprotein I is proteolytically cleaved in vivo upon activation of fibrinolysis. Thromb Haemost 1999, 81:87-95.
18. Guerin J, Sheng Y, Reddel S, et al.: Heparin inhibits the binding of beta 2-glycoprotein I to phospholipids and promotes the plasmin-mediated inactivation of this blood protein: elucidation of the consequences of the two biological events in patients with the anti-phospholipid syndrome. J Biol Chem 2002, 277:2644-2649.
19. Merten M, Motamedy S, Ramamurthy S, et al.: Sulfatides: targets for antiphospholipid antibodies. Circulation 2003, 108:2082-2087. This article shows the specificity of aPLs for other negatively charged macromolecular structures.
20. Riboldi P, Gerosa M, Raschi E, et al.: Endothelium as a target for antiphospholipid antibodies. Immunobiology 2003, 207:29-36. A review on the interaction of aPLs with endothelium.
21. Raschi E, Testoni C, Bosisio D, et al.: Role of the MyD88 transduction signaling pathway in endothelial activation by antiphospholipid antibodies. Blood 2003, 101:3495-3500. The best study till now on the effects of β2GPI on endothelial cells.
22. Ma K, Simantov R, Zhang JC, et al.: High affinity binding of beta 2-glycoprotein I to human endothelial cells is mediated by annexin II. J Biol Chem 2000, 275:15541-15548.
23. Zhou H, Roubey RAS: Annexin A2 and the upregulation of monocyte tissue factor activity by aPL [abstract]. Lupus 2002, 11:543.
24. 2-glycoprotein I increase platelet deposition to collagen via interaction with phospholipids and the apolipoprotein E receptor 2′. J Biol Chem 2003, 278:33831-33838. Interesting study on how anti-β2GPI antibodies can activate platelets.
25. Forastiero R, Martinuzzo M, Carreras LO, Maclouf J: Anti-beta2 glycoprotein I antibodies and platelet activation in patients with antiphospholipid antibodies: association with increased excretion of platelet-derived thromboxane urinary metabolites. Thromb Haemost 1998, 79:42-45.
26. Boucher P, Gotthardt M, Li WP, et al.: LRP: role in vascular wall integrity and protection from atherosclerosis. Science 2003, 300:329-332. A review on LRP-receptor family and atherosclerosis.
27. Merrill JT: The antiphospholipid syndrome and atherosclerosis: clue to pathogenesis. Curr Rheumatol Rep 2003, 5:401-406. One of the many articles suggesting a relation between atherosclerosis and aPLs.
28. Nicolo D, Goldman BI, Monestier M: Reduction of atherosclerosis in low-density lipoprotein receptor-deficient mice by passive administration of antiphospholipid antibody. Arthritis Rheum 2003, 48:2974-2978. An unexpected finding: aPLs were thought to accelerate atherosclerosis.
29. Levine JS, Branch DW, Rauch J: The antiphospholipid syndrome. N Engl J Med 2002, 346:752-763.
30. Erkan D, Yazici Y, Harrison M, et al.: APLASA study: primary thrombosis prevention in asymptomatic antiphospholipid antibody (aPL) patients with low-dose aspirin. Lupus 2004, 11:573. Unique study because of the inclusion of a placebo group.
31. Cooper C, Choy E: The blossoming of evidence-based clinical rheumatology: the Arthritis Research Campaign's Clinical Trials Collaboration in association with the MRC Clinical Trials Unit, BSR and BOA. Rheumatology 2003, 42:713-715. An editorial from the Arthritis Research Campaign's Clinical Trials Collaboration mentioning the current ALIWAPAS study.
32. Crowther MA, Ginsberg JS, Julian J, et al.: A comparison of two intensities of warfarin for the prevention of recurrent thrombosis in patients with the antiphospholipid antibody syndrome. N Engl J Med 2003, 349:1133-1138. Erratum in N Engl J Med 2003, 349:2577. Very important prospective study that shows that high, intensive anticoagulation with oral anticoagulants is not necessary for patients with APS.
33. Derksen RH, de Groot PG, Kappelle U: Low dose aspirin after ischemic stroke associated with antiphospholipid syndrome. Neurology 2003, 61:111-114. Observational study showing the effectiveness of aspirin.
34. Levine SR, Brey RL, Tilley BC, et al. and the APSSS Study Group: aPL and stroke study (APASS) [abstract]. Lupus 2003, 11:559. Study included also low-liter antibodies. In contradiction to the official criteria, aPLs were only measured once.
35. Derksen RH, Khamashta M, Branch DW: Management of the obstetric antiphospholipid syndrome. Arthritis Rheum 2004, 50:1028-1039. Overview of the literature with suggestions for treatments.