Blood Res 2021; 56(3): 201-202  https://doi.org/10.5045/br.2021.2020245
Ruxolitinib-induced extreme thrombocytosis in a COVID-19 patient
Víctor Manuel Anguiano-Álvarez1, José Antonio Maza-Larrea2, Francisco Javier Rosado-Hernández2, Gustavo Rojas-Velasco3, Raúl Izaguirre-Ávila1
Departments of 1Hematology, 2Pharmacovigilance, and 3Intensive Care Unit, National Institute of Cardiology Ignacio Chávez, Mexico City, Mexico
Correspondence to: Víctor Manuel Anguiano-Álvarez
Department of Hematology, National Institute of Cardiology Ignacio Chávez, Calle Juan Badiano 1, Col. Sección XVI, Tlalpan, 14080 Ciudad de México, Mexico
E-mail: vanguiano@comunidad.unam.mx
Received: September 29, 2020; Revised: March 2, 2021; Accepted: July 8, 2021; Published online: August 12, 2021.
© The Korean Journal of Hematology. All rights reserved.

cc This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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TO THE EDITOR: The SARS-CoV-2 pandemic is a global health crisis. Currently, there is still no specific treatment for coronavirus disease 2019 (COVID-19), but ruxolitinib has been used in treating COVID-19 [1, 2]. In fact, the clinical effectiveness and safety profile, which includes adverse events of ruxolitinib, is still being studied in patients with COVID-19. Ruxolitinib is a JAK-2 and JAK-1 inhibitor approved for myelofibrosis, including primary myelofibrosis, post-polycythemia vera myelofibrosis, post-essential thrombocythemia myelofibrosis, polycythemia vera, and for patients who have had an inadequate response to hydroxyurea and steroid-refractory acute graft-versus-host disease [3-6].

A 52-year-old healthy and non-obese (BMI 24.09) man started having fever (39.5°C), odynophagia, asthenia, adynamia, and cough five days prior to his arrival at the emergency department. Three days later, he developed tachypnea and dyspnea with an oxygen saturation of 82% at room air, which made him require oxygen supplementation. During his initial intrahospital hours, the patient was transferred to the intensive care unit (ICU), diagnosed with severe pneumonia due to SARS-CoV-2, which was confirmed by nasal swab RT-PCR test and tomography thorax score CO-RADS category 5, and initiated on standard therapy. Twenty-four hours later in the ICU, persistent deterioration required mechanical ventilation (MV), and lopinavir/ritonavir (LPV/r) 200/50 mg BID was started. The patient was included in a ruxolitinib (10 mg BID) clinical trial; therefore, LPV/r was suspended due to possible interactions. During follow-up, we identified a progressive platelet count increase (Fig. 1), which was assessed at the pharmacovigilance institutional center as a suspected adverse drug reaction related to ruxolitinib, based on the temporality of the platelet count rise and the duration of the ruxolitinib effect. After stopping ruxolitinib, the platelet count decreased and normalized, and interleukin-6 levels decreased until they were undetectable on day 13 after ruxolitinib, without relevant changes in the rest of the inflammatory markers. We administered an anticoagulation treatment with enoxaparin 80 mg SC BID, maintaining anti-Xa therapeutic levels, and the patient was discharged without clinical complications.

Figure 1. Platelet count (yellow bars), ruxolitinib treatment period (green bar), anticoagulant and Anti-Xa levels (red colors), IL-6 levels (blue arrows).
Abbreviations: ER, emergency Room; MV, mechanical ventilation; ND, non-detectable; OR, oral route; SC, subcutaneous.

In controlled clinical trials, thrombocytosis has not been reported as an adverse effect in the context of myeloproliferative diseases or graft-versus-host disease. In addition, there are only isolated case reports, and it is not included as an expected adverse effect in commercial pharmaceutical information. This phenomenon is possibly due to multifactorial causes, such as reduction in phagocytic activity, reduction of splenic sequestration, incomplete JAK-2 inhibition, or activation of kinases not yet described with megakaryopoiesis dysregulation [3-7]. To our knowledge, this is the first case of ruxolitinib-induced extreme thrombocytosis in the context of COVID-19 in a patient without hematological disease, and should be considered as an extraordinarily rare side effect, which may increase the risk of fatal thromboembolic events.

Authors’ Disclosures of Potential Conflicts of Interest

No potential conflicts of interest relevant to this article were reported.

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