Feasible concomitant treatment with eltrombopag and oral anticoagulation in a patient with chronic immune thrombocytopenia and severe cardiac comorbidities

• Thrombopoietin receptor agonist
• eltrombopag
• romiplostim
• immune thrombocytopenia
• platelets
• anticoagulation

To the editor,

Recently, Baldini et al. [1] and Cantoni et al. [2] reported new interesting clinical experiences with romiplostim, a thrombopoietin receptor agonist (TRA), in the context of treatment of immune thrombocytopenia (ITP) in patients with oral anticoagulation. TRAs, romiplostim and eltrombopag are new agents approved for the treatment of chronic ITP that have demonstrated high efficacy and safety in clinical trials [3–5]. Nevertheless, there are no reported cases of concomitant use of eltrombopag and anticoagulation therapy.

Here we report a case of an 84-year-old man with chronic ITP. This patient was taking a vitamin K antagonist, acenocoumarol, due to a metallic cardiac valve and chronic atrial fibrillation. In March 2011, he was admitted to our hospital because of ecchymoses and diffuse mucocutaneous purpura. Blood analysis showed severe thrombocytopenia with a platelet count of 15 × 10⁹/l, without other hematological abnormalities in his blood cell count. Coagulation panel was normal except for an international normalized ratio (INR) of 2.9. Diagnosis of ITP was confirmed according to currently accepted guidelines [6], [7]. Bone marrow analysis showed an increased number of megakaryocytes with normal erythroid and granulocytic lineages. Screening for antiplatelet antibodies was not performed. Patient was started on first line treatment with oral prednisone (1 mg/kg/d) and intravenous inmunoglobulins (IVIG) (1 g/kg/d for 2 d). Oral anticoagulation was stopped. After 2 weeks, a platelet count of 49 × 10⁹/l was observed which, nevertheless, still contraindicated oral anticoagulation restart. Prednisone tolerance was remarkably poor due to the appearance of nervousness and insomnia. After this initial response, and still under prednisone treatment, the platelet count dropped to 25 × 10⁹/l and patient showed cutaneous bleeding again. In this setting, we decided to administer IVIG as rescue therapy. Platelet count increased again until 45 × 10⁹/l, remaining stable for 3 months. However, a new platelet count decrease to 20 × 10⁹/l was observed and we decided to administer once more IVIG treatment as rescue therapy. After several cycles, totalling 6 months, IVIG were no longer effective. At this point, we decided to begin a second-line treatment to ensure the long-term control of platelet counts, in order to restore anticoagulation therapy. Splenectomy was not feasible due to the presence of severe concomitant comorbidities that increased the risk of surgical and anesthetic complications. In this setting, we decided to start a TRA. Due to patient's preference, eltrombopag was chosen. Eltrombopag starting dose was 50 mg daily. Concomitant medication at this point was beta blockers, diuretics, hydralazine and nitroglycerin (of note, no HMG CoA reductase inhibitors were used). One week later, platelet count increased to 250 × 10⁹/l and eltrombopag dose was decreased to 25 mg/d. With this dose of eltrombopag, platelet counts remained stable with an actual mean value of 100 × 10⁹/l, allowing the restart of oral anticoagulation therapy. During follow-up, no further dose adjustments were required and a stable INR was also maintained. Of note, neither bleedings nor thrombotic complications were observed during follow-up. Headache and fatigue grade 2 (Common Terminology Criteria for Adverse Events, version 3.0.) [8] appeared at an eltrombopag dose of 50 mg but were no longer observed at 25 mg/d.

To the best of our knowledge, this is the first report of the concomitant use of eltrombopag and oral anticoagulation. In our single-case experience, the combination of acenocoumarol and eltrombopag was feasible and effective for a patient that required anticoagulation for severe cardiac comorbidities. Of interest, no clinically significant drug interactions with oral anticoagulation were observed, in spite of the interaction profile of eltrombopag. Once TRAs gain widespread approval, it should be expected that the scenario described in our patient is seen quite often, given the high prevalence of patients who need anticoagulation therapy.

Although clinical trials are required to determine the safety of TRAs in patients with chronic ITP who need long-term anticoagulation, we consider that this combination is potentially feasible. Nevertheless, this specific setting needs a tailored approach, depending on the thrombotic risk profile for each patient. Our recommendation would include to perform a platelet count every 2–3 days upon start of TRA therapy until stability of platelet counts around 50 × 10⁹/l is observed. Subsequently, blood counts should be performed weekly until stable platelet counts around 100 × 10⁹/l are seen. After that threshold is achieved, either biweekly or monthly blood counts should be performed depending on the stability of platelet counts. Regarding anticoagulation therapy, we would recommend to start low-molecular-weight heparin (LMWH) when stable platelet counts around 50 × 10⁹/l are achieved, with a subsequent change to oral anticoagulation when stable platelet counts around 100 × 10⁹/l are achieved. However, once more a tailored anticoagulation approach is needed, depending on the thrombotic risk profile for each patient. Finally, clinical trials should address the question of which TRA is more adequate for this particular population.

Declaration of interest

The author(s) indicated no potential conflicts of interest.