Rivaroxaban induced Thrombocytosis

A not enough known adverse effect


(1) Department of Clinical Pharmacology, Institute of Biology, Nantes, France ; (2) Sèvre and Loire Hospital, Vertou, France and Pharmacy University, Nantes, France ; (3) Medical Director, Saint Laurent sur Sèvre Public Nursing Home, France and Hospital Practioner, Cholet Hospital, France ; (4) EA 4275 « Biostatistics, Pharmacoepidemiology and Subjective Health Measures », Medicine University, Nantes, France


Thrombocytosis is a common abnormality in clinical practice. There is no consensus on the exact defintion of thrombocytosis. It includes a very wide range of primitive and secondary etiologies spectrum. There are familial thrombocytosis, clonal thrombocytosis (including essential thrombocytosis due to myeloproliferative disease) and secondary or reactive thrombocytosis [1].

Reactive thrombocytosis are much more common than other causes of thrombocytosis and are associated with underlying conditions such as infection, inflammatory disease, anaemia due to iron deficiency, surgery (especially splenectomy), acute haemorrhage and exposure to certain drugs [1,2]. Some authors reported cases of thrombocytosis with low molecular weight heparin (LMWH) [2-6]. In june 2000, a french Pharmacovigilance study has found 51 notifications of thrombocytosis (> 500 000 platelets/mm3) associated with LMWH in the French Pharmacovigilance Database. In all cases, patients were asymptomatic and thrombocytosis was accidentally discovered. On average, patients had completed 12 days of treatment at the time of discovery of thrombocytosis. This side effect disappeared without complication in 41 cases, the outcome is unknown for the 10 other cases [7]. The pathophysiologic mechanism is not fully understood but it is established that heparin stimulates megakaryocytopoiesis. The mechanism of action involves a neutralization of inhibitory of platelet factor 4 (PF4) and transforming growth factor (TGF-β) on megakaryocyte proliferation. There is also a synergistic action with many growth factors such as interleukin 6 (IL6), GM-CSF, erythropoietin, stem cell factor but not with interleukin 3 (IL3). Finally, a potentiating action of thrombopoietin factor favouring predominantly megakaryocytopoiesis was also highlighted [2]. This risk reinforces the importance of regular monitoring of platelets during heparin therapy.

In secondary thrombocytosis, platelets are qualitatively and functionnaly normal. Complications (such as thrombotic or haemorrhagic events) do not occur normally and thrombo-haemorrhagic risk, if it existed, would be related to the underlying disease and not to thrombocytosis. The occurrence of these risks in a patient with secondary thrombocytosis must lead to a clonal component associated search. The treatment of reactive thrombocytosis is the treatment of the causal disease [1]. Whatever the cause of thrombocytosis, his supervision should never be neglected because the combination of several etiologies is possible and could increase the thrombocytosis.
To our knowledge, there is no case report of thrombocytosis with oral direct anticoagulants in the literature. We report a case of a woman treated with rivaroxaban who developed thrombocytosis.


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