Thrombotic disorders

This video explores the complex and evolving topic of thrombophilia workup, with Marc Carrier, MD highlighting that while advances in genetic testing and risk stratification have improved the ability to assess thrombophilia disorders, the decision of when and how to test remains controversial and nuanced. Marc Carrier, MD emphasizes that testing should not be done routinely but can be considered for certain patients, provided there is a clear rationale and understanding of how the results might change patient management. The presentation delves into the interpretation of ASH guidelines, discussing recurrence risk thresholds for provoked and unprovoked venous thromboembolism (VTE) and challenging some recommendations based on actual recurrence data. It covers considerations for testing in pregnancy, optimal timing of testing, and approaches for unusual site thrombosis.

Key Learning Points:

• Thrombophilia testing is a controversial area with limited definitive data; decisions on testing should be nuanced
• Testing should not be routine; a clear rationale is needed, understanding how results will impact patient management
• A thrombophilia diagnosis can have significant negative implications, including insurance issues and risks of over-diagnosis or overtreatment
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This video features a discussion between Christoph Licht, MD and Taha Bat, MD about atypical Hemolytic Uremic Syndrome (aHUS), a rare but challenging disease caused by the disregulation of the alternative complement pathway. They cover the advancements in understanding and managing aHUS over the past decade, emphasizing the efficacy of C5 blockade as a cornerstone therapy. The discussion provides a comprehensive overview of aHUS, detailing its characteristic triad of anemia, thrombocytopenia, and impaired kidney function. The speakers elaborate on the diagnostic approach for TMA and aHUS, genetic and autoimmune factors, and treatment strategies including C5 inhibitors like eculizumab and ravulizumab. The evolving therapeutic landscape includes new treatments and the importance of early intervention for optimal outcomes.

Key Learning Points:

• Atypical Hemolytic Uremic Syndrome (aHUS) results from disregulation of the alternative complement pathway, presenting with anemia, thrombocytopenia, and kidney impairment
• Diagnosis of primary complement-driven TMA is by exclusion, involving confirmation of MAHA and ruling out other TMAs like E.coli-HUS and TTP
• Genetic mutations in complement regulators (Factor H, Factor I, MCP/CD46) and autoantibodies (anti-Factor H) are key causes
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In the session, Marc Carrier, MD provides a comprehensive overview of cancer-associated thrombosis (CAT), using patient case studies to discuss the topic. He defines CAT as a form of venous thromboembolic disease, including DVT and pulmonary embolism, and clarifies the definition of "active cancer" in this context. Marc Carrier, MD highlights the Khorana Risk Score as a simple and widely used tool for assessing a patient's risk of developing CAT. He also discusses clinical guidelines for primary prophylaxis, noting that direct oral anticoagulants (DOACs) can reduce the risk of VTE in high-risk patients. For treating established CAT, he states his preference for a DOAC, based on trial data showing a lower risk of recurrent VTE compared to low-molecular-weight heparin (LMWH), although he acknowledges situations where LMWH may be a better choice due to bleeding risks. Finally, Marc Carrier, MD touches on future directions, including the need for new anticoagulation agents with a better safety profile and fewer drug interactions, mentioning Factor XI/XIa inhibitors as a promising new therapy.

Key Learning Points:

• Cancer-associated thrombosis (CAT) is a form of venous thromboembolic disease, which includes DVT and pulmonary embolism, that occurs in patients with active cancer.
• The Khorana Risk Score is a widely used tool for stratifying a patient's risk of developing CAT based on factors like tumor type and blood count results.
• For high-risk patients, prophylactic anticoagulation with direct oral anticoagulants (DOACs) can help reduce the risk of VTE.
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In this session, Spero Cataland, MD and Taha Bat, MD discuss thrombotic thrombocytopenic purpura (TTP), emphasizing the pathogenesis via ADAMTS13 deficiency, clinical presentation, and evolving treatments. The session underscores how timely recognition and therapy are lifesaving in this microangiopathic disease.

Key Learning Points:

• TTP is caused by severe ADAMTS13 deficiency (usually via autoantibody), leading to accumulation of ultra-large von Willebrand factor multimers and microvascular platelet-rich thrombi.
• Clinically, patients may present with thrombocytopenia, microangiopathic hemolysis (schistocytes), neurologic symptoms (e.g. confusion, seizures), renal dysfunction, and fever.
• Laboratory clues include elevated LDH, low haptoglobin, indirect hyperbilirubinemia, and schistocytes on peripheral smear.
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