Use of tociluzumab in the thrombocytopenic COVID-19 patient: A challenge in the therapeutic approach

Coronavirus disease (COVID-19) is an infectious disease caused by the SARS-CoV-2 virus. So far, approximately 615 million COVID-19–positive cases have been detected all over the world. Unfortunately, about five million of them resulted in death [1]. Most people who get COVID-19 show mild to moderate symptoms and recover without the need for special treatment. But some of them become seriously ill and need medical attention. Hypercytocinemia–associated macrophage activation syndrome (MAS) may typically develop in severe COVID-19. In patients who develop MAS, SARS-CoV-2 infection causes strong inflammation in the lungs, resulting in respiratory and systemic organ failure [2].

A 60-year-old male patient, who had a bone marrow transplant due to multiple myeloma a year ago and was followed up in the pandemic service with the diagnosis of COVID-19 pneumonia, was admitted to the COVID-19 intensive care unit due to severe respiratory distress and a decrease in SpO2.In the medical history of the patient, it was learned that the COVID-19 swab was positive.The mutation was negative 20 days previously, and he was discharged from the pandemic service on the 7th day after medical treatment without any problem. On the 20th day of his positivity, the patient started to have respiratory distress; he was hospitalised again, and it was determined that he was COVID-19 delta variant–positive in the reapplied COVID-PCR test. His respiratory rate was 35 per minute; PaO2/FiO2 ratio was 62; C-reactive protein (CRP) was 69 mg/L (<5 mg/L); Ferritin was 15301 ng/ml(20-300 ng/ml); fibrinogen was 2.39 g/L(1.8-3.5 g/L); D-dimer was 3050 mcg/L(0-500 mcg/L); lactate dehydrogenase (LDH) was 1179 U/L (120-246 U/L); and platelet count was 39.46*10³ per microliter. There were bilateral diffuse ground glass infiltrates on thorax computed tomography. Despite high flow oxygen therapy, the patient’s hypoxia continued, and progression of infiltrates was observed on direct chest radiography.Since the patient had thromb ocytopenia, the haematology clinic was consulted for the indication of tocilizumab, and it was decided to administer tocilizumab with platelet replacement (platelet count >30000/L). Tocilizumab 8 mg/day was administered two consecutive days with thrombocyte replacement. During this period, the patient was carefully followed up for haemorrhagic complications. On the 5thday of tocilizumab, inflammation markers declined, the patient’s respiratory symptoms resolved, and the PaO2/ FiO2 ratio increased to 250. No bleeding disorder was encountered during this period, and the patient was successfully discharged to the ward on the 6thday after intensive care admission.

Specific antiviral treatment that will provide adequate improvement in the treatment of the disease has not been developed yet. For patients with MAS due to COVID-19, the physiological and pathological aspects are not well known, but current studies demonstrate the effectiveness of anti-cytokine therapy. Tocilizumab is a recombinant humanised monoclonal antibody, used as an anti-cytokine agent that acts as an interleukin (IL)-6 receptor antagonist [3]. Indications for administration of tocilizumab in COVID-19 patients are hypoxia, lung infiltrates on chest radiograph, and high inflammatory biomarkers (CRP>3 g/ dl or ferritin>400 ng/ml).Contraindications are confirmed or suspected bacterial orofungalinfections, platelet count <100000/mm3, neutrophil count <2000/mm3, and alanine aminotransferase (ALT) or aspartate aminotransferase (AST) values higher than the upper limit of the normal range (50 U/L for ALT and 40 for AST U/L) [4].

Although thrombocytopenia developed due to tocilizumab treatment, no bleeding event was reported in patients with thrombocytopenia [5]. In the light of this literature information, we decided to apply tocilizumab treatment in a patient with thrombocytopenia andwe did not encounter any bleeding complications.

In conclusion, in the presence of thrombocytopenia in COVID-19 patients with MAS, tocilizumab can be administered under intensive care conditions with great care and very strict clinical follow-up. However, we think that more clinical experience and published data are needed on this subject.