LAUSR

As the vaccination program for COVID-19 progresses worldwide, rare but significant adverse events associated with vaccination are becoming a global concern. In the field of hematology, exacerbation of idiopathic thrombocytopenic purpura (ITP) or acute-onset immune thrombocytopenia occurring shortly after vaccination is attracting attention [1, 2]. Kuter et al. reported that exacerbation of ITP is observed at a significantly higher rate than would be expected, even among patients in remission with normal platelet counts [2]. However, the precise nature, incidence and appropriate management of immune thrombocytopenia after SARS-CoV-2 vaccination remains unclear. We herein report three cases of severe and acute immune thrombocytopenia following SARS-CoV-2 vaccination in two patients with chronic ITP in remission and in one healthy individual. Case 1 was a 64-year-old woman with chronic ITP managed without medication for 23 years. Her platelet count had been stable around 40 × 109/L. She visited our hospital complaining of oral mucosal bleeding and petechiae on the extremities. Two days before the visit, she received the first dose of the BNT162b2 mRNA covid-19 vaccine (Comirnaty, Pfizer) for SARS-CoV-2 (Fig. 1A). She did not take any medication or supplements before or after vaccination. Oral bleeding and generalized petechiae were observed on physical examination. Laboratory testing showed severe thrombocytopenia with 1 × 109/L platelets, while white blood cells (WBCs), red blood cells (RBCs) and hemoglobin (Hb) levels were within normal limits (Fig. 1A). The international normalized ratio of prothrombin time (PT-INR), activated partial thromboplastin time (APTT), fibrinogen, fibrin/fibrinogen degradation products (FDP), D-dimer and all blood chemistry parameters were within normal range. Clinical and laboratory findings were consistent with acute exacerbation of ITP, and thus treatment with oral prednisolone (PSL) 55 mg/day (1 mg/kg) and intravenous immunoglobulin (IVIG) 20 g/day for 5 days was started. Complete blood cell (CBC) count after two days of treatment showed effective platelet recovery to 76 × 109/L (Fig. 1A). The patient had been in good physical condition and cutaneous purpura progressively improved. CBC after 5 days of PSL treatment showed a normal platelet count of 274 × 109/L. Case 2 was a 61-year-old woman with scleroderma (SSc), Sjogren syndrome (SS) and ITP who presented with petechiae on both legs after the second dose of SARSCoV-2 vaccine. SSc and SS had been clinically stable without medication for 34 years. Eleven months earlier, she was diagnosed with ITP due to acute-onset thrombocytopenia with 1 × 109/L platelets and with widespread petechiae on extremities. Her platelet count and bleeding symptoms had effectively improved with PSL, which had been gradually tapered and discontinued 6 months prior to presentation. She had received the first and second doses of BNT162b2 mRNA covid-19 vaccine (Pfizer) 42 days and 21 days prior to the visit, respectively (Fig. 1B). She noticed subcutaneous bleeding 17 days after the second vaccination and visited the hospital 21 days after the second vaccination. Diffuse petechiae on the legs with no active bleeding were observed on physical examination. Laboratory tests showed severe thrombocytopenia with a platelet count of 1 × 109/L, but other CBC parameters, coagulation parameters including PT-INR, APTT, fibrinogen, FDP and D-dimer, and blood chemistry parameters were otherwise normal (Fig. 1B). Based on these findings, * Hideaki Nakajima [email protected]