To provide an update of recent insights into the pathogenesis, diagnosis and treatment of antiphospholipid syndrome (APS) from current literature.
β2GPI was recently implicated in the pathogenesis of thrombosis. High titres of anti-β2GPI antibodies are present in patients with triple positivity which highlight its importance. Consensus guidelines have been published to standardise diagnostic assays and once implemented may yield more accurate diagnoses of APS. An 'aPL score' has been formulated to improve the detection and outcomes of patients. New oral anticoagulants, statins and concomitant therapy with warfarin and aspirin have been identified as potential novel therapeutic interventions for thrombotic APS. Advances in the pathogenesis of obstetric APS have occurred, such as the concept of redefining the syndrome as inflammatory and clearer identification of the roles of complement, β2GPI and annexin 5. Independent risk factors for pregnancy failure have been recognised and when combined with clinical and laboratory features may improve patient outcomes. Interventions involving adjusted doses of low molecular weight heparin in combination with aspirin have shown promising results from initial studies.
Recent insights into the pathogenesis of APS have unveiled novel areas for treatment intervention. Diagnostic criteria and recommendations have been revised and formulated to provide consensus and standardisation for diagnosis.
"Treatment guidelines suggest combining therapies of low-dose aspirin and heparin for all APS patients during pregnancy (Table 1). Depending on the patient's history of thrombosis, miscarriage, or other pregnancy complications, the medication may be extended to anticoagulation with full therapeutic dose [41, 42]. "
[Show abstract][Hide abstract] ABSTRACT: Preeclampsia, the onset of hypertension and proteinuria during pregnancy, is a common medical disorder with high maternal and fetal mortality and morbidity. The underlying pathology remains poorly understood and includes inflammation, endothelial dysfunction, and an unbalanced thromboxane A2/prostacyclin ratio. For women with systemic lupus erythematosus (SLE), particularly those with preexisting renal disease or with active lupus, the risk of developing preeclampsia is up to 14% higher than it is among healthy individuals. The mechanism is still unknown and the data for preventing preeclampsia in lupus pregnancies are rare. Modulating the impaired thromboxane A2/prostacyclin ratio by administration of low-dose aspirin appears to be the current best option for the prevention of preeclampsia. After providing an overview of the pathogenesis of preeclampsia, preeclampsia in lupus pregnancies, and previous trials for prevention of preeclampsia with aspirin treatment, we recommend low-dose aspirin administration for all lupus patients starting prior to 16 weeks of gestation. Patients with SLE and antiphospholipid syndrome should receive treatment with heparin and low-dose aspirin during pregnancy.
"The antiphospholipid syndrome (APS) is an autoimmune disease characterized by vascular thrombosis and obstetrical complications, and serologically by the presence of antiphospholipid antibodies . Other clinical symptoms that can be prominently present are kidney-faillure, livedo reticularis and neurological signs, though these have not been accepted as official criteria due to specificity reasons . "
[Show abstract][Hide abstract] ABSTRACT: β(2)glycoprotein I (β(2)GPI) is the major antigen in the antiphospholipid syndrome. It has been shown that β(2)GPI can adapt to different conformations, a circular, a S-shaped and a J-shaped conformation. In literature anticoagulant properties of β(2)GPI have been indicated, though there is no consensus on how β(2)GPI exerts a certain action. This article will first review existing data on the conformation of β(2)GPI. In addition, we will investigate whether the conformation of β(2)GPI plays a role in in the proposed anticoagulant activity of β(2)GPI. We investigated the effect of native β(2)GPI and phospholipid-bound β(2)GPI on thrombin generation (TG). Native β(2)GPI was found to have no significant effect on the TG regardless of the concentration of tissue factor. On the contrary, β(2)GPI preincubated with phospholipids significantly inhibited TG triggered with low TF concentration, suggesting an effect on the intrinsic pathway. This indicates that native β(2)GPI in circulation obtains its anticoagulant activity in the presence of anionic phospholipids such as activated blood cells thereby serving as an inhibitory modulator in hemostasis.
"Here we provide new evidence that the binding site for VWF is located within domain I of b 2 GPI, a conclusion supported both by functional inhibition experiments and direct evidence for a high affinity bimolecular interaction between b 2 GPI domain I and VWF A1 domain. b 2 GPI is known from its role in the antiphospholipid syndrome (APS), an autoimmune disease in which patients suffer from thrombosis and pregnancy loss (Wijetilleka et al, 2012). Besides a thrombotic phenotype, APS patients have more similarities with TTP patients, such as thrombocytopenia . "
[Show abstract][Hide abstract] ABSTRACT: It has been shown that β(2) -glycoprotein I (β(2) GPI) interacts with von Willebrand factor (VWF) in a glycoprotein (GP)Ib binding state. Given the presence of active VWF multimers in thrombotic thrombocytopenic purpura (TTP), we speculated that β(2) GPI might play a role in TTP. We found that β(2) GPI plasma levels were significantly lower in acute and remission TTP patients than in normal controls, showing a direct correlation with ADAMTS 13 levels and an inverse correlation with the extent of VWF activation. In vitro flow experiments demonstrated that β(2) GPI can block platelet adhesion to endothelial cell-derived VWF strings. We confirmed the direct binding of β(2) GPI to VWF by surface plasmon resonance, and determined that domain I of β(2) GPI is the binding site of VWF A1 domain. Adhesion of β(2) GPI to erythrocytes and platelets was increased in the presence of active VWF, indicating that β(2) GPI may be cleared from the circulation during TTP episodes together with blood cells. Our findings suggest that β(2) GPI may protect from the effects of hyper-functional VWF by inhibiting its interaction with platelets.
British Journal of Haematology 08/2012; 159(1):94-103. DOI:10.1111/bjh.12004 · 4.71 Impact Factor
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