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.