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COVID‐19‐associated immune thrombocytopenia

2020; Wiley; Volume: 190; Issue: 2 Linguagem: Inglês

10.1111/bjh.16850

1365-2141

Gienke Bomhof, Pim Mutsaers, Frank W.G. Leebeek, Peter te Boekhorst, Johannes Hofland, F. Nanne Croles, A.J. Gerard Jansen,

Blood properties and coagulation

Thrombocytopenia is a risk factor for increased morbidity and mortality in patients infected with the new severe acute respiratory syndrome coronavirus 2, SARS-CoV-2 (COVID-19 infection).1 Thrombocytopenia in COVID-19 patients may be caused by disseminated intravascular coagulation (DIC), sepsis or be drug-induced. Recently a single case report suggested immune thrombocytopenia (ITP) may be associated with COVID-19 infection.2 ITP is a rare autoimmune disease characterised by a platelet count <100 × 109/l, leading to an increased risk of bleeding.3 Several risk factors have been described for ITP including environmental (e.g. infection, malignancy and drugs) and genetic predisposition.4 We report here the first case series of three patients with ITP associated with COVID-19 infection. Patient 1 is a 59-year-old man, known for 10 years with a stage IV neuroendocrine tumour (NET) of the small bowel, who presented with oral mucosal petechiae and spontaneous skin haematomas. He also experienced symptoms of coughing and fever 10 days before presentation and his partner had a documented COVID-19 infection. Full blood counts showed an isolated thrombocytopenia ( 40 × 109/l. Unfortunately, he did not have increments on platelet transfusions and died of an intracerebral bleeding within 24 h. Based on the course of platelet counts and exclusion of other causes we consider the thrombocytopenia as COVID-19-associated ITP. Viral infections are associated with ITP.4 Here we describe the first case series of three patients with COVID-19-associated ITP. The ITP occurred not only during active COVID-19 infection, but also up to 10 days after the clinical COVID-19 symptoms subsided. Diagnosis of COVID-19-associated ITP may be difficult because of several other potential causes, for instance the coagulation activation by COVID-19 infection leading to DIC and subsequent thrombocytopenia. Also, treatments for COVID-19, including heparin, azithromycin and hydroxychloroquine, may lead to thrombocytopenia.1 The goal of ITP treatment is preventing severe bleeding by providing a safe platelet count.3 Treatment for COVID-19-associated ITP may pose several issues. Commonly used treatments include IVIG, glucocorticoids or thrombopoietin receptor agonists (TPO-RAs).3 IVIG are generally reserved for ITP patients who require a rapid increase in platelet count. A disadvantage of IVIG is that they are not curative and often poorly tolerated.3 As IVIG inhibit the phagocytic capabilities of macrophages,4 treatment with IVIG in an early stage of COVID-19 may be successful.5 Additionally, some COVID-19 patients who suffered deterioration of clinical symptoms have been salvaged by IVIG treatment.6 IVIG was chosen in patient 1 because of active bleeding and the relative contraindication of glucocorticoid treatment, which may interfere with the somatostatin analogue therapy for the NET, and in patient 2 because of failure of dexamethasone treatment. Glucocorticoids comprise the primary treatment of ITP.3 However, glucocorticoids are considered harmful for patients with COVID-19 infection as they inhibit immune responses and clearance of the SARS-COV-2 virus.7 Patient 2 received treatment with dexamethasone because she had no symptoms of the COVID-19 infection for over a week. She received a short course of high-dose dexamethasone rather than a longer period of prednisone which is associated with significant toxicities and a longer time to response.8 COVID-19 infection may be accompanied by thrombocytopenia as a result of DIC, which is associated with a strongly increased risk of thromboembolism reported in 30% of the patients.9 As treatment with TPO-RA has shown in selected cases to increase the risk of venous thromboembolism,10 it should be used with caution in COVID-19 infection. In conclusion, this is the first case series of three patients with a COVID-19-associated ITP. It is important to be aware of this severe complication of a COVID-19 infection and should be diagnosed and treated immediately. Failure to recognise it on time may ultimately lead to fatal complications, as shown in one of our patients. Choice of treatment of ITP should be based on balancing the risk of bleeding due to ITP versus potential deterioration of COVID-19 infection due to immunosuppressive therapy. FNC and AJGJ designed the project. GB, FNC, FWGL and AJGJ analysed the data and wrote the manuscript. GB, PGNJM, FWGL, PAWB and JH interpreted the data, commented, provided essential clinical input and reviewed the manuscript. All authors approved the final version of the manuscript. The authors declare that there are no conflicts of interest in carrying out this study. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.