Discussion:
Despite serval studies on Direct anticoagulant (DOAC), warfarin remained the gold standard therapy for patient with mechanical valve. The use of DOAC in patients with mechanical heart valves was associated with increased rates of thromboembolic and bleeding complications compared to warfarin and showed no benefit but an excess risk [4]. The river trial showed a non-inferiority to warfarin with bioprosthetic mitral valve in case of atrial fibrillation [5]. The use of DOAC with mild thrombocytopenia is an option but as shown in this case patient has both severe thrombocytopenia and a mechanical valve [6]. Per ESC guidelines 2017 bridging is recommended in case of a metallic mitral valve with UFH or LMWH when VKA is interrupted. Targeted INR in case of medium to high thrombogenicity and atrial fibrillation must be between 2,5 and 3,5 [7]. But in our case, using heparin with severe thrombocytopenia was risky.
On the other hand, Fondaparinux a factor Xa inhibitor used for venous thromboembolism prevention and treatment [1] has low affinity for platelet factor 4, making it an alternative agent to unfractionated heparin (UFH) and low-molecular weight heparin (LMWH) and a plausible consideration for patients with a history of heparin-induced thrombocytopenia (HIT) with decreased platelets and hypercoagulable state [2]. The use of fondaparinux as a bridging therapy in patients with mitral mechanical heart valve replacement and severe thrombocytopenia due to chemotherapy has never been discussed before in the literature but this case was like a HIT situation where balance between bleeding and thrombosis was needed.
While both unfractionated heparin and low-molecular weight heparin are also options but carries a risk for HIT when binding to platelets and endothelial cells, therefore, both UFH and LMWH are most often avoided in this case. Fondaparinux binds specifically to antithrombin and has minimal affinity for platelet factor 4, making it an alternative agent to UFH and LMWH. However, the use of fondaparinux in patients with mechanical heart valve replacement and a thrombocytopenia induced by chemotherapy has never been reported in the literature.
Furthermore, thrombocytopenia by itself may increase bleeding risk, but it does not protect against venous thromboembolic events or stroke that was very risky in this patient with a high CHADVASC score and HASBLED score and on chemotherapy for cancer. Thus, caring for patients with both thrombocytopenia and an indication for anticoagulation can be challenging. It is generally when platelet counts <50,000/microL that severe spontaneous bleeding is most likely as in this case [8]. However, there is not a good linear correlation between the platelet count and bleeding risks in these situations. In addition, the risk of VTE is greatest in the setting of a strongly prothrombotic risk as active chemotherapy [9].
There are no randomized trials comparing different approaches to reducing the risks of VTE, stroke and mechanical valve thrombosis in people with cancer and thrombocytopenia and mortality from VTE and other thromboembolic events may be greater than mortality from bleeding in most populations. That is why we need to shed the light on these issues and further studies need to be done so that new guidelines would take into consideration this subpopulation.