Immune thrombocytopenia secondary to COVID‐19 infection: Report of two cases

Abstract

To the Editor: Immune thrombocytopenia (ITP) is well described in childhood, affecting approximately 1.9–6.4 /100,000 children per year.1 It has been linked to vaccinations and viral infections occurring approximately 1–3 weeks earlier. Recovery time is usually less than 3 months. The suggested management is “watch and wait,” but in cases with active mucosal bleeding treatment with corticosteroids and/or intravenous immunoglobulin (IVIG) is recommended.2 Infectionwith the severe acute respiratory syndrome–corona virus2 (SARS-CoV-2) could represent a novel cause of secondary immune phenomena including thrombocytopenia.3 Although in adults cases suspicious of ITP have been reported in the setting of corona virus disease 2019 (COVID-19),4–6 similar reports in pediatric patients are scarce.7 Herein, we describe two pediatric patients with ITP, temporally and possibly causally, related to a preceding, real-time polymerase chain reaction (RT-PCR) confirmed, COVID-19 infection, presenting in two tertiary hospitals when the secondwave of the pandemic swept northern Greece in late 2020. Patient 1: A 15-year-old male presented with epistaxis, petechiae, and bruises that had commenced 7 days earlier. On admission, he was hemodynamically stable, with unremarkable physical examination apart from the bruises and petechiae. Blood tests revealed severe thrombocytopenia (platelets = 1000/μL), whereas the rest of the full blood count was normal (hemoglobin = 16 g/dl, white blood cells [WBC] = 7070/μl, N: 72.7%, L:19%, M: 7.5%). Liver and renal function and coagulation testswere normal. Serology for viruses commonly associatedwith ITP (Epstein–Barr virus [EBV], seasonal influenza, adenovirus, hepatitis C, Varicella Zoster virus [VZV], and cytomegalovirus [CMV]) was negative. His RT-PCR for SARS-CoV-2 was negative. He had no past medical or family history of autoimmunity or previously abnormal laboratory tests. Interestingly, he reported a history of an asymptomatic, RT-PCR-confirmed, COVID-19 infection 5 weeks earlier requiring no treatment or hospitalization. Due to the very low platelet count, he was treated with IVIG (1 g/kg), with a good clinical and laboratory response. He was discharged four days later with a platelet count of 49,000/μl, which gradually increased to 110,000/μl during 12weeks of follow-up. Patient 2: A 3-year-old female child was referred to the pediatric A&E because of thrombocytopenia. Disease onset was 3 days earlier, with low-grade fever for 24 h, epistaxis, and melaena (due to nasal bleeding). On admission she was hemodynamically stable and in good clinical condition. Physical examination revealed approximately 10 ecchymoses (<3 cm) in several parts of her body but was otherwise unremarkable with no organomegaly or lymphadenopathy. She had one further episode of nasal bleeding upon admission. Laboratory findings revealed moderate thrombocytopenia (platelets = 26,000/μl) with normal hemoglobin = 10.4 g/dl, WBC:6950/μl (N:46%, L: 39%, M:11%), coagulation and biochemistry. Viral infections known to trigger ITP (EBV, CMV, Herpes Simplex virus, Hepatitis C, adenovirus, seasonal influenza, and VZV) were excluded with serologic tests, whereas RT-PCR for SARS-CoV-2was negative.Of note, she had ahistory of RTPCR-confirmed COVID-19 infection 3 weeks earlier, with mild pyrexia and fatigue for 48 h, not requiring hospitalization. No medical or family history of autoimmunity or previous abnormal laboratory tests was reported. Because of the continuing epistaxis, IVIG was administered (1 g/kg), with immediate clinical and laboratory improvement. She had no further bleeding episodes, her platelet count increased to 100,000/μl and she was discharged 2 days later. During 12 weeks of follow-up, her platelet count gradually increased to 236,000/μl and remained stable. Our hypothesis is that in these patients ITP is possibly related to SARS-CoV-2 based on the serological exclusion of other viral infections, and the evidence of preceding COVID-19 infection (asymptomatic-first patient/mild-second patient), which were molecularly confirmed 3–4 weeks prior to manifestation of thrombocytopenia. There is a growing body of literature regarding the clinical and laboratory manifestations of COVID-19 infection in children. The vast majority of reports refer to the period of acute infection, when leukopenia and anemia can be present, although most children have normal counts.8 Thrombocytopenia has been reported in relation to severe disease or to the multisystem inflammatory syndrome.8 As the infection runs a mild course in children and adolescents, follow-up with blood tests or physical examination is not advised unless clinically indicated. Since the beginning of the pandemic >3.9 million pediatric cases of SARS-CoV-2 infectionhavebeen recorded in theUnited States alone,9 however no severe hematologic sequalae were reported. Up to date, only three patients<18 years old with ITP after COVID19 have been reported. All of themwere pre-adolescents/adolescents, with platelets <10,000/μl, no active bleeding, and were treated with IVIG or corticosteroids with adequate clinical/laboratory response.7,10,11 One of the patients presented herein is 3.5 years old, the youngest reported to date.