Cryptic conspirators: a conversation about thrombocytopenia and antiphospholipid syndrome

Abstract

Purpose of review: Although antiphospholipid syndrome (APS) is best known for conveying increased risk of thrombotic events and pregnancy morbidity, thrombocytopenia is also recognized as a common association. In this review, we will explore the relationship between thrombocytopenia and APS, highlighting our evolving understanding - and persistent knowledge gaps - through clinically oriented questions and answers.

Recent findings: A history of thrombocytopenia likely portends a more severe APS phenotype (including increased risk of thrombosis). Although the pathophysiology underlying thrombocytopenia in APS has yet to be definitively revealed, mechanisms that play a role (at least in subsets of patients) include: immune thrombocytopenic purpura/ITP-like autoantibodies against platelet glycoproteins; antiphospholipid antibody (aPL)-mediated platelet activation and consumption; and potentially life threatening thrombotic microangiopathy. Although thrombocytopenia is often 'mild' in APS (and therefore, may not require specific therapy), there are causes of acute-onset thrombocytopenia that mandate emergent work-up and treatment. When APS-related thrombocytopenia does require therapy, the approach must be individualized (requiring an understanding of pathophysiology in the particular APS patient). For patients with ITP-like disease, rituximab is emerging as a popular approach to treatment; in contrast, there are hints that thrombopoietin mimetics may be associated with elevated thrombotic risk.

Summary: Thrombocytopenia is common in APS, and is likely associated with more severe disease. Improved understanding of thrombocytopenia in APS has the potential to improve risk stratification, reveal novel aspects of APS pathophysiology, and lead to treatments that are more individualized and holistic.

Box 1

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FIGURE 1

Proposed algorithm for a pathogenesis-directed approach to managing thrombocytopenia in antiphospholipid syndrome patients. The yellow path consists of the majority of APS patients with thrombocytopenia, in which no specific therapy is required. The green path highlights a combination of mechanisms of thrombocytopenia, including drug-related causes and immune-mediated pathogenesis. The red/orange path emphasizes acute, life-threatening thrombotic microangiopathies (which may or may not be associated with microangiopathic hemolytic anemia). APS, antiphospholipid syndrome; HIT, heparin-induced thrombocytopenia; BM, bone marrow; ITP, immune thrombocytopenic purpura, TPO, thrombopoietin; CAPS, catastrophic APS; TTP, thrombotic thrombocytopenic purpura.