Thrombocytopenia as an initial manifestation of COVID‐19; case series and literature review

Abstract

COVID-19 has been declared as a global pandemic, affecting more than a hundred countries in a matter of weeks and claiming many lives up until now. The clinical spectrum ranges from asymptomatic carriers to symptomatic patients with mild symptoms and patients requiring intensive care unit (ICU) admission at the other extreme. Variable clinical presentations have been reported, most commonly involving the chest with shortness of breath being most common. Less commonly it has also been reported with gastrointestinal and neurological manifestations. Haematological manifestations in symptomatic COVID-19 patients include severe leukopenia with lymphopenia and mild thrombocytopenia with platelet counts ranging between 100–150 × 109/l.1-4 We hereby report a case series of three patients; the first two patients presented with severe thrombocytopenia and were subsequently found to be COVID-19positive. The third case emphasises the presentation of severe thrombocytopenia as a marker of severity and poor prognosis in symptomatic COVID-19 patients. A 50-year-old male with no known prior comorbidities presented to the emergency department with epistaxis and a generalised petechial rash. He was self-isolating at his home after being in contact with his brother who was found to be COVID-19positive. He was otherwise asymptomatic and had no chest symptoms. On presentation, he was apyrexial, with a pulse of 78 beats/min, respiratory rate of 16 breaths/min and 98% saturation on room air. Clinical examination revealed petechiae and oral blisters, systemic examination was unremarkable. He was swabbed for COVID-19 and all baseline tests were sent for, along with viral serology and a baseline autoimmune profile. Laboratory results revealed Hb 132 g/l, WBC 4 × 109/l, neutrophils of 3·2 × 109/l and a platelet count of 0 × 109/l. Peripheral film revealed isolated thrombocytopenia without any fragments or platelet clumps with reactive lymphocytes and normal neutrophils and red blood cells (RBCs), suggestive of idiopathic thrombocytopenic purpura (ITP). Urea and electrolytes (U+E), liver function tests (LFT), haemolysis screen and coagulation profile all came back normal. Extended viral serology (including hepatitis B, C and HIV) was negative. C-reactive protein (CRP) was 14. However, his throat swab was positive for SARS-CoV-2 RNA detected by reverse transcript polymerase chain reaction (RT-PCR). His chest X-ray (CXR) was normal. He was started on intravenous immunoglobulin (IVIG) at 1 g/kg for two doses, along with tranexamic acid and nasal packing to support his local epistaxis. The full blood count (FBC) was repeated the next day and showed a platelet count of 11 × 109/l, further increasing to 25 × 109/l in the next 24 h. His bleeding settled and he was discharged home with an appointment for follow-up in two weeks for repeat FBC, which further showed a platelet count of 103 × 109/l. A 49-year-old female with no known prior comorbidities presented to the surgery of her general practitioner with generalised bruises and gum bleed for the past three days. She was a massage therapist by profession and had attended an Italian client two weeks before her hospital admission. She had no chest symptoms and was vitally stable. General physical examination revealed generalised bruises. However, systemic examination was unremarkable. Baseline laboratory tests were sent, the results of which revealed Hb 134 g/l, WBC of 5·3 × 109/l, neutrophils of 4 × 109/l and a platelet count of 4 × 109/l with peripheral blood film findings being consistent with isolated thrombocytopenia, suggestive of ITP. She was swabbed for COVID-19. The other results, including U + E, LFTs, coagulation profile, viral serology and autoimmune profile came back normal. CRP was 9. Surprisingly her swab came back positive for SARS-CoV-2 RNA detected by RT-PCR which stayed positive on repeat swab at 24 h. CXR was normal. She was given IVIG at 1 g/kg for a single dose. Her repeat FBC 48 h later revealed a platelet count increment from 4 × 109/l to 18 × 109/l to 52 × 109/l over 48 h and she was discharged home with an appointment for follow-up in the clinic in two weeks for repeat FBC. A 96-year-old female with multiple comorbidities including atrial fibrillation, ischaemic heart disease and chronic kidney disease (CKD) presented to the Emergency department with shortness of breath. She was vitally stable, clinical examination revealed bilateral coarse crepitations in chest. Baseline labs were sent including a COVID-19 swab and CXR was requested. CXR revealed bilateral patchy consolidation, a non-specific finding for COVID-19. FBC revealed Hb 114 g/l, WBC 3·7 × 109/l, with neutrophils of 2 × 109/l and a platelet count of 109 × 109/l. Renal fuction tests showed an estimated glomerular filtration rate of 31 which was consistent with her baseline CKD status. LFTs, coagulation profile and bone profile were normal. Viral serology was negative. Her swab was positive for SARS-CoV-2 RNA detected by RT-PCR. She was admitted and during the course of admission over the next five days, she deteriorated further with increasing oxygen requirements and worsening platelet counts reaching a nadir of 3 × 109/l. She was started on IVIG at 0.4 mg/kg for five days and her platelet count started improving to 16 × 109/l. However, clinically she deteriorated further with increasing oxygen requirements and ultimately she passed away (Fig 1). Thrombocytopenia is a common manifestation in critically ill patients and is usually representative of physiological decompensation rather than an underlying haematological cause. The aetiology of thrombocytopenia in COVID-19 is likely multifactorial. It could be due to a direct effect of SARS-CoV-2 on haematopoietic cells and bone marrow stromal cells leading to haematopoietic dysfunction and bone marrow growth inhibition or a cytokine storm which in turn leads to the destruction of bone marrow progenitor cells, both of which result in decreased platelet production.5 The other factor by which SARS-CoV-2 causes thrombocytopenia and the likely cause of thrombocytopenia in our first two patients is that it increases the levels of antibodies and immune complexes as a consequence of which platelet destruction is augmented.6 As seen in patient 3, it can also increase platelet consumption by infection and inflammation which causes damage to lung tissues and pulmonary endothelial cells, resulting in platelet activation in lungs and aggregation and formation of microthrombi leading to increased platelet consumption. Hence, as the literature suggests, severe thrombocytopenia is a poor prognostic marker in symptomatic COVID-19 patients.7 To the best of our knowledge, this is the only case series which highlights thrombocytopenia as an initial presentation of this novel virus without any other symptoms. Both of our patients presented with haemorrhagic manifestation and severe thrombocytopenia responding to IVIG fairly quickly with a sustained response over weeks. IVIG exerts immunomodulatory effects which lead to neutralisation of antiplatelet antibodies, stimulation of Fcγ receptor IIB expression and inhibition of Fcγ receptor-mediated platelet destruction.8 Immunoglobulins are also known to be beneficial in the treatment of infections by improving the ability of an individual to make antibodies by its immunomodulatory effects, resulting in limited infection. Its role in COVID-19 has not been established yet but it may provide a protective effect against this lethal virus.9 We recommend any new-onset cytopenias should be screened for COVID-19 in the current situation and IVIG may have a protective role against this deadly virus.

Topics & Concepts