This month, Leslie J. Raffini, MD, discusses treating large venous thromboembolisms in two teenaged siblings.
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Siblings, a 19-year-old female (wild type factor V Leiden [FVL]) and a 15-year-old male (heterozygous FVL+), developed large venous thromboembolisms (VTEs) within days of each other. Neither has a travel history, use of medications or drugs that they will admit to, or provoking events. Both VTEs are extensive, involving iliac to femoral veins in the male and female; she also has bilateral pulmonary embolisms (PEs). All other workup (prothrombin gene, protein S, protein C, lupus anticoagulation) is normal. Both patients are on low-molecular-weight heparin and will be switched to a factor Xa inhibitor for six months.
Since I cannot identify a provoking event and the extent of the VTE is significant (life-threatening in the female), I am considering the possibility of lifelong anticoagulation. However, they are very young, and the events seem to be provoked by simultaneous exposure to something. Do you have any suggestions as to what it could be or any feedback on duration of treatment beyond six months? Is there another test I should perform?
What an interesting family! I agree that it is very unusual that two teenage siblings would develop VTE so closely in time, suggesting that there may have been some sort of provoking factor or exposure. However, it sounds like you have performed a careful history, and there is no obvious transient risk factor. One other acquired condition to consider in this age group is “gamer’s thrombosis.” This refers to deep vein thrombosis that develops due to prolonged immobility and venous stasis from playing hours of video games, often in the basement.1
Ultimately, even if this was “exposure” related, if you can’t identify and remove the “exposure” then it could happen again. The next relevant issues are the risk of recurrence and duration of anticoagulation therapy for each sibling:
- The 19-year-old female is homozygous for the factor V Leiden mutation, which is considered a strong risk factor for venous thrombosis. This, along with her history of unprovoked proximal VTE and PE is worrisome for a high risk of recurrence, and she would likely benefit from extended (no scheduled stop date) anticoagulation. Fortunately, the direct oral anticoagulants are much more convenient than warfarin. The adult guidelines for treatment of unprovoked VTE support extended anticoagulation for a patient with an unprovoked thrombosis and low or moderate bleeding risk, irrespective of the thrombophilia.2 The continued use of anticoagulation should be assessed annually at clinic visits.
- The 15-year-old male has a relatively weak thrombophilia but also an unprovoked proximal thrombus. Unfortunately, there is less data in the “pediatric” population regarding recurrence risk for unprovoked thrombosis. The recent American Society of Hematology (ASH) VTE Guidelines for Pediatrics recommend 6 to 12 months of anticoagulation for unprovoked VTE in children.3 I think that this would be reasonable for this patient.
Additional thrombophilia testing for rarer disorders may identify abnormalities (e.g., elevated FVIII or FIX), but would likely not alter treatment. I can’t think of anything else you are missing. Interestingly, you have now identified that both parents are heterozygotes for factor V Leiden, so it’s worth reviewing relevant risk factor avoidance and signs and symptoms of VTE for their benefit.
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NEXT MONTH'S CLINICAL DILEMMA
A 65-year-old man with Rai stage II chronic lymphocytic leukemia (CLL), splenomegaly, and no 17p deletion was asymptomatic for a few years, then developed warm autoimmune hemolytic anemia (AIHA). He responded to rituximab/prednisone, then had recurrent hemolysis about two years later and was retreated with rituximab/prednisone with another good response. The prednisone was tapered slowly over several months, but the patient started having recurrent mild hemolysis with a prednisone dose of 10 mg every other day. The dose was re-escalated to 20 mg every other day with no improvement. He is about five months from the last rituximab course. He has no other clinical CLL-related symptoms. How would you proceed with further management of AIHA? Re-treat with rituximab? Add other immune suppressive agents? Initiate CLL specific treatment? Any particular preferred regimen in this setting?
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