Immune thrombocytopenic purpura in an elderly patient with cerebral hemorrhage after the fourth mRNA ‐1273 COVID ‐19 vaccination

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Patient: An 89-year-old man. Chief complaint: Widespread petechial hemorrhages. History: Postoperative abdominal aortic aneurysm, chronic kidney disease, Alzheimer dementia, hypertension. Current medical history: The patient attended the Department of Cardiology and Nephrology at our hospital. In August 2022, 21 days before admission, he had received the fourth dose of the mRNA-1273 COVID-19 vaccine. There were no apparent symptoms immediately after the vaccination. Seven days before admission, petechial hemorrhage was observed on the right upper arm; 3 days before, petechial hemorrhage was observed on the head, in addition to gingival hemorrhage and bloody stools. He visited our emergency department, exhibiting disordered consciousness and low platelet count (1000/μL), and was urgently admitted. Findings of physical examination at the initial visit: Height 165.0 cm, weight 58.6 kg, temperature 36.3°C, blood pressure 124/46 mmHg, pulse 61 beats/min, SpO2 99% (room air). Conscious, with anemic eyelid conjunctiva and gingival hemorrhage observed. Heart sounds: normal, no heart murmur. Respiratory sounds: normal, no rales. Abdomen flat and soft, no tenderness. No edema of the extremities. Petechial hemorrhage in the parietal region, left shoulder, right upper arm, right lateral abdomen, and left lower leg. Laboratory findings: White blood cell count 5090/μL, Hb 8.8 g/dL, platelet count 1000/μL, FDP 44.7 μg/dL, D-dimer 20.6 μg/dL. Helicobacter pylori IgG was negative. Platelet-associated IgG (PA-IgG) was high (1259.0 ng/107 cells) (Fig. 1a). Despite methylprednisolone (mPSL) 1000 mg/day started on Day 1 of admission and intravenous immunoglobulin (IVIg) 10 g/day administered for 4 days, platelet count remained below 10 000/μL. On Day 5, the patient complained of headache, and a CT scan of the head revealed cerebral hemorrhage in the right frontal lobe. Considering the risk of expansion of fatal cerebral hemorrhage while waiting for prior treatment to take effect, despite a second mPSL pulse therapy, weekly subcutaneous injection of romiplostim was started. Platelet count gradually increased, and steroid was changed to internal use on Day 12 and reduced from Day 28. Repeat head CT performed on Day 21 showed no new hemorrhage or enlargement of the previous hemorrhage. Platelet count improved to 140 000/μL, and romiplostim was discontinued after the fourth dose. Platelet count normalized to 172 000/μL on Day 34, and the patient was discharged on Day 37, in October 2022 (Fig. 1b). His platelet count has remained normal to date. The patient had received the mRNA-1273 COVID-19 vaccine, the same as received in three previous doses, 21 days before admission. As his platelet count before vaccination was consistently normal and no other apparent cause was found, we diagnosed acute de novo immune thrombocytopenic purpura (ITP) related to vaccination. Most reports of ITP after SARS-CoV-2 vaccination have occurred after the first or second vaccination,1-3 and this is the first report after the fourth vaccination. Although the cause of ITP after SARS-CoV-2 vaccination remains unclear, molecular homology between viral proteins and autologous platelets4, 5 and immunologic-enhancing effects of adjuvants have been reported.4, 5 In the present case, it is noteworthy that the immature platelet fraction (IPF) was 0.0% and showed no increase, despite the markedly decreased platelet count at the time of admission. Some reports have been skeptical regarding a direct effect of the SARS-CoV-2 vaccine, a type of inactivated vaccine, on megakaryocytes;1 however, it has been pointed out that even before the COVID-19 pandemic, antigen–antibody reaction against megakaryocytes, opsonization, and induction of apoptosis were considered possible mechanisms of post-vaccination ITP.6 The fact that IPF showed no elevation at admission in our patient, who had petechial hemorrhage 7 days prior to admission, suggests a direct effect of the vaccine on the platelet-producing capacity of megakaryocytes. In addition, it has been suggested that early introduction of a thrombopoietin receptor agonist may lead to early recovery of platelet production in patients with low IPF. A limitation of this case is that we did not measure vaccine-related anti-platelet factor 4 or heparin-induced thrombocytopenia (HIT) antibodies. As no thrombosis was observed and there was no history of heparin administration, we ruled out thrombosis due to thrombocytopenia syndrome or autoimmune HIT. However, we believe that these measurements could have provided additional information. We could not find a similar report after the fourth vaccination. Elderly people are likely to continue receiving routine vaccination because they are likely to have a complicated medical history and are at high risk of severe infection. If a decrease in platelets is observed after COVID-19 vaccination, the vaccination history should be reviewed regardless of the number of vaccine doses. The authors have no financial conflicts of interest to disclose concerning this manuscript. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

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