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Purpose of Review: Laboratory criteria for the classification of antiphospholipid syndrome include the detection of a lupus anticoagulant and/or anticardiolipin and anti-β2-glycoprotein I antibodies. However, the majority of patients who test positive in these assays do not have thrombosis. Current risk-stratification tools are largely limited to the antiphospholipid antibody profile and traditional thrombotic risk factors., Recent Findings: Novel biomarkers that correlate with disease activity and potentially provide insight into future clinical events include domain 1 specific anti-β 2 GPI antibodies, antibodies to other phospholipids or phospholipid/protein antigens (such as anti-PS/PT), and functional/biological assays such as thrombin generation, complement activation, levels of circulating microparticles, and annexin A5 resistance. Clinical risk scores may also have value in predicting clinical events. Biomarkers that predict thrombosis risk in patients with antiphospholipid antibodies have been long sought, and several biomarkers have been proposed. Ultimately, integration of biomarkers with established assays and clinical characteristics may offer the best chance of identifying patients at highest risk of APS-related complications.

The antiphospholipid syndrome (APS) is characterized by venous and/or arterial thrombosis, or recurrent fetal loss, in the presence of antiphospholipid antibodies (APL). The pathogenesis of APS is multifaceted and involves numerous mechanisms including activation of endothelial cells, monocytes, and/or platelets; inhibition of natural anticoagulant pathways such as protein C, tissue factor inhibitor, and annexin A5; activation of the complement system; and impairment of the fibrinolytic system. Fibrinolysis--the process by which fibrin thrombi are remodeled and degraded--involves the conversion of plasminogen to plasmin by tissue plasminogen activator (tPA) or urokinase-type plasminogen activator, and is tightly regulated. Although the role of altered fibrinolysis in patients with APS is relatively understudied, several reports suggest that deficient fibrinolytic activity may contribute to the pathogenesis of disease in these patients. This article discusses the function of the fibrinolytic system and reviews studies that have reported alterations in fibrinolytic pathways that may contribute to thrombosis in patients with APL. Some of these mechanisms include elevations in plasminogen activator inhibitor-1 levels, inhibitory antibodies against tPA or other components of the fibrinolytic system, antibodies against annexin A2, and finally, antibodies to beta(2)-glycoprotein-I (beta(2)GPI) that block the ability of beta(2)GPI to stimulate tPA-mediated plasminogen activation.

Immune thrombocytopenic purpura (ITP) is an uncommon disorder but a relatively frequent cause of isolated thrombocytopenia. The pathogenesis of ITP involves enhanced platelet clearance, primarily in the spleen, caused by antiplatelet glycoprotein antibodies. Most patients with ITP respond transiently to an initial course of corticosteroids, although only 20% of adult patients achieve a durable remission after such therapy. Classically, patients who fail corticosteroid therapy undergo splenectomy, with approximately two thirds of these individuals maintaining partial remissions 5 years later. However, due to evidence suggesting a continuous relapse rate in splenectomized patients with ITP, in addition to the emergence of newer agents associated with durable remissions in ITP patients with intact spleens, the therapeutic approach to ITP is evolving. This article reviews the role of splenectomy in patients with ITP and reviews new approaches to management of ITP in patients who fail an initial trial of corticosteroids.