Thrombotic Thrombocytopenia after Ad26.COV2.S Vaccination

U.S, 20 May 2021, Muir et al New England Journal of Medicine


A 48-year-old White woman with an unremarkable medical history presented to the emergency department with a 3-day history of malaise and abdominal pain. The initial evaluation at another hospital showed mild anemia and severe thrombocytopenia (platelet count, 13,000 per cubic millimeter [reference range, 150,000 to 400,000]). A peripheral-blood smear confirmed a marked reduction in the platelet count with occasional schistocytes. Additional studies showed a low fibrinogen level (89 mg per deciliter [reference range, 220 to 397]), a prolonged activated partial thromboplastin time (41 seconds [reference range, 25 to 37]), and a marked elevation in the d-dimer level (117.5 mg per liter [reference value, <0.5]), indicating a disseminated intravascular coagulation–like state. (A complete listing of the patient’s laboratory values is provided in the Supplementary Appendix, available with the full text of this letter at Computed tomographic (CT) imaging of the abdomen and pelvis showed extensive splanchnic-vein thrombosis.

The patient was transferred to our institution. SARS-CoV-2 RNA was not detected on reverse-transcriptase–polymerase-chain-reaction assay of a sample obtained with a nasopharyngeal swab. Head CT that was performed after a report of new-onset headache showed cerebral venous sinus thrombosis involving the right transverse and straight sinuses. The administration of unfractionated heparin was initiated, but despite this treatment, the patient had progressive thrombosis with hemorrhagic stroke evident on magnetic resonance imaging and magnetic resonance venography of the brain. Repeat CT angiography showed new thrombus involving the right hepatic and splenic veins.

On further inquiry, it was noted that the patient had received the Ad26.COV2.S vaccine 14 days before symptom onset. The screening test for antibodies against platelet factor 4 (PF4)–heparin by latex-enhanced immunoassay was negative. However, the result of enzyme-linked immunosorbent assay for antibodies against PF4–polyanion was strongly positive (2.550 optical-density units [upper limit of normal range, ≤0.399). Heparin was switched to argatroban. She also received intravenous immune globulin at a dose of 1 g per kilogram of ideal body weight (as calculated according to the actual weight [112 kg] and height [168 cm] of the patient) for 2 days. This treatment was followed by an increase in the platelet count from 30,000 to 145,000 during a 5-day period. The patient remained critically ill at the time of this report.

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Thrombotic Thrombocytopenia after Ad26.COV2.S Vaccination — Response from the Manufacturer

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