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A CAPtivating Debate

December 11, 2022

A page in the middle of the night wakes you. You pull up the peripheral smear on your computer and note schistocytes. Laboratory studies also show thrombocytopenia, anemia, and acute renal insufficiency. You are highly concerned for thrombotic thrombocytopenic purpura (TTP). A line is placed and plasmapheresis is promptly initiated. You inquire about administrating caplacizumab and are informed by your pharmacy colleagues that the inpatient cost is estimated to be $60,000. You want to provide your patient the highest quality of care and wonder whether or not caplacizumab is indicated.

Drs. Camila Masias and George Goshua will settle the equipoise on caplacizumab for management of TTP at the Education Spotlight Session titled Debate: Most/All Patients with Acquired (Immune) Thrombotic Thrombocytopenic Purpura Receive Caplacizumab, on Monday, December 12 (10:30 a.m.-11:45 a.m., Ernest N. Morial Convention Center, Room 295-296).

TTP, a disease that arises from deficiency of ADAMTS-13, is rare and rapidly life-threatening if untreated. The mainstay of initial treatment includes plasmapheresis, steroids, and rituximab. The newest kid on the block is caplacizumab, an immunoglobulin fragment targeting the A1 domain of von Willebrand factor (vWF) that was FDA approved in 2019 as an adjunctive therapy to standard of care in TTP. Proponents of this exciting new drug cite that it accelerates platelet recovery and even reduces the risk of TTP relapse and TTP-related mortality. “What both the HERCULES and TITAN studies have shown, as well as multiple real- life data studies,” Dr. Masias stated, “is that caplacizumab provides benefits beyond the primary endpoint [of platelet count normalization]. Equally or more important, caplacizumab reduces the risk of exacerbations and life-threatening complications, including death and refractoriness.”

Dr. Goshua of Yale University isn’t so sure about this, however, noting “pooled randomized controlled trial data and all observational studies to date have failed to show a mortality benefit for caplacizumab.” In addition to concerns about cost and a commitment to daily subcutaneous injections for a month, there is also a notable risk of bleeding. “We are seeing unprecedented rates of major bleeding with caplacizumab in idiopathic TTP, which includes a 1 to 5 percent risk of intracranial bleeding,” said Dr. Goshua. Which TTP patients are likely to benefit from this drug? Attend the discussion between Drs. Masias and Goshua on Monday.

As you step outside the front door of the hospital, another page comes through. “Consult for unprovoked pulmonary embolism (PE) and thrombophilia testing.” The patient is a young male with high body mass index (BMI) who has already been started on low molecular weight heparin (LMWH). You wonder which thrombophilia tests to send, if any, and when to send them. Suddenly, you remember there is an exciting Point/Counterpoint Spotlight Session on this very topic, presented by Dr. Stephan Moll and Dr. Deborah Siegel on Monday, December 12, from 2:45 p.m. to 4:00 p.m. (Ernest N. Morial Convention Center, Room 288-290).

Those arguing against widespread thrombophilia testing in unprovoked thrombosis therefore point out that it may not impact clinical care. Dr. Siegel reminds us of a guiding principle described by Dr. Archie Cochrane: “Before ordering a test, decide what you will do if it is 1) positive or 2) negative. If both answers are the same, don’t take the test.” Further, Dr. Siegel teaches of the potential dangers of unnecessary thrombophilia testing: “Genetic testing has important potential harms, including false reassurance by negative testing, unnecessary anxiety, insurability issues, and cost.” Dr. Moll offers the counterpoint that “one cannot be dogmatic about who should be tested, given the absence of prospective studies that show whether finding a thrombophilia and modifying the length of anticoagulation decision based on finding a thrombophilia will change clinical outcomes (e.g., venous thromboembolism [VTE] recurrence, major bleeding, quality of life).”

Thrombophilia testing does still seem to have a role in determining the length of anticoagulation in special circumstances. As Dr. Moll noted, “The purpose of thrombophilia testing is to detect a strong thrombophilia in the patient at intermediate risk for VTE recurrence that would push the patient down into the red zone of (the) ‘recurrence triangle’ and would be an argument for long-term anticoagulation.”1 In terms of therapeutic agents, currently, direct oral anticoagulants are preferentially prescribed over vitamin K antagonists in VTE given ease of administration and lack of requirement for monitoring. The notable exception is patients with triple-positive antiphospholipid antibody syndrome.

Learn all about the nuances of thrombophilia testing in this much awaited session!

  1. Moll S. New insights into treatment of venous thromboembolism. Hematology Am Soc Hematol Educ Program. 2014(1):297-305.

Dr Kumar and Dr Jeong indicated no relevant conflicts of interest.

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