How I treat the antiphospholipid syndrome

Abstract

This article discusses how we approach medical decision making in the treatment of the various facets of the antiphospholipid syndrome (APS), including secondary prophylaxis in the setting of venous and arterial thrombosis, as well as treatment for the prevention of recurrent miscarriages and fetal death. The role of primary thromboprophylaxis is also discussed in depth. Great emphasis is given to incorporating the most up-to-date and relevant evidence base both from the APS literature, and from large, recent, randomized controlled trials (RCTs) of primary and secondary thrombotic prophylaxis in the general population setting (ie, the population that has not been specifically investigated for APS). IntroductionThe antiphospholipid syndrome (APS) is characterized clinically by the occurrence of either venous or arterial thrombosis in diverse vascular beds, or recurrent miscarriages in the first trimester, or fetal death in the second or third trimesters, or severe pre-eclampsia necessitating delivery of a premature infant before 34 weeks of gestation. 1 It is an important cause of acquired thrombophilia, with the diagnosis being particularly considered and made in younger age groups relative to the average age at which thrombosis occurs in the general population. 2 Within the arterial circulation, cerebrovascular infarction is a prominent event, whereas lower limb deep venous thrombosis and pulmonary embolus are important locations in which venous pathology occurs. 2 Three prominent features of the updated APS classification criteria are (1) the incorporation of the beta 2-glycoprotein I (␤ 2 GPI) enzyme-linked immunosorbent assay (ELISA) as a diagnostic test in addition to the cardiolipin ELISA (CL-ELISA) and the lupus anticoagulant (LA) assay(s), (2) the recommendation that classification of APS requires the persistence of antibodies for at least 12 weeks, and (3) the setting of definitive cutoff values for the CL-ELISA and the ␤ 2 GPI-ELISA (see details in Miyakis et al 1 regarding a detailed description of the current APS classification criteria, including cutoff values for the ELISAs).The current classification criteria do not exclude the diagnosis of thrombotic APS being made in the presence of concurrent arterial and/or venous prothrombotic risk factors, such as the presence of atherosclerotic risk factors in the former instance. In the context of obstetric APS, the situation is distinct as the diagnosis is excluded if there is an identifiable alternate explanation for either recurrent first-trimester miscarriages or fetal death (second and third trimesters).In 2 previous review articles published in this journal we have presented evidence for considering the importance of the antibodies, in particular anti-␤ 2 GPI antibodies with LA activity as having diagnostic (ie, etiopathogenic) significance. 3,4 The concept of prognosis involves consideration of whether the detection of the autoantibodies alters the probability of thrombotic recurrence or death compared with not having the antibodies in patients who...

Chemical synthesis and characterization of wild‐type and biotinylated N‐terminal domain 1–64 of β2‐glycoprotein I

“…6,22 To date, the only treatment proven to reduce the risk of thrombosis in APS is life-long anticoagulation, which often has severe side effects. 3 Despite antithrombotic therapy, a significant proportion of patients with APS undergo rethrombosis, 41 likely because anticoagulant therapy affects only the final outcome, without interfering with the early biochemical events from which thrombotic events originate, that is production of anti-b2GpI Abs and binding to b2GpI. 19,22,42 Hence, the possibility to identify a molecule that is able to block anti-b2GpI Abs activities could disclose new therapeutic strategies in APS.…”

“…[1][2][3] APS is characterized serologically by high levels of autoantibodies (aAbs) mainly directed against b2-glycoprotein I (b2GpI), 3,4 a 54-kDa plasma glycoprotein synthesized in the liver and abundantly present in normal plasma ($0.2 mg mL À1 ). 5 b2GpI is now recognized as the major autoantigen involved in APS, 3,6 and the presence of anti-b2GpI Abs strongly correlates with the occurrence of thrombotic events in APS patients.…”

“…[1][2][3] APS is characterized serologically by high levels of autoantibodies (aAbs) mainly directed against b2-glycoprotein I (b2GpI), 3,4 a 54-kDa plasma glycoprotein synthesized in the liver and abundantly present in normal plasma ($0.2 mg mL À1 ). 5 b2GpI is now recognized as the major autoantigen involved in APS, 3,6 and the presence of anti-b2GpI Abs strongly correlates with the occurrence of thrombotic events in APS patients. 4,7 The mature sequence of human b2GpI consists of 326 amino acids with four N-linked carbohydrate chains, 8,9 localized in the third and fourth domain (see below) and accounting for about 19% of the protein mass (Fig.…”

Síndrome antifosfolípide e trombocitopenia na infância

“…Patients who are positive for aPLs but have no history of thrombosis are not candidates for prophylactic treatment with drugs; however, studies by Giannakopoulos and Krilis suggest that the use of acetylsalicylic acid may be beneficial (23) . Nonetheless, risk factors associated with thrombosis, such as hypertension, smoking, hypercholesterolemia, contraceptive Positive serologies, detection of the agent.…”

Antiphospholipid Syndrome in Pregnancy

“…Most obstetricians would consider treatment with low-dose aspirin and prophylactic dose of (low molecular weight) heparin in such cases. In women with APA antibodies, and a history of severe preeclampsia, at least low dose aspirin (75-80 mg once a day) is recommended (79) . Glucorticoids, cytotoxic agents, and intravenous immunoglobulin have no confirmed benefit and should not be used to treat pregnant women with APS (79) .…”