AZD-1222

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An event is serious (based on the ICH definition) when the patient outcome is:

• * death

• * life-threatening

• * hospitalisation

• * disability

• * congenital anomaly

• * other medically important event

In a report, 2 men aged 55−68 years were described, who developed vaccine-induced immune thrombotic thrombocytopenia (VITT) following vaccination with AZD-1222 against COVID-19 [routes and dosages stated].

Case 1: A 68-year-old man who had just received his first AZD-1222 [ChAdOx1 nCoV-19; Covishield] COVID-19 vaccination. After 31 days, he experienced left leg swelling and erythema. Two days later, he was presented due to left lower limb deep-vein thrombosis (DVT). His D-dimer was increased and his platelet count was reduced. He received apixaban as an outpatient. Doppler ultrasonography revealed significant DVT in the left lower limb, extending from the mid-superficial femoral vein to the popliteal vein and its trifurcation. He had received apixaban at home, without bleeding. His left leg swelling had diminished by day 37, and his D-dimer level had dropped to 6.1 mg/L. The polyspecific PF4/polyanion enzyme immunoassay (1.020 optical density) was positive, as were two immunoglobulin G (IgG)-specific EIAs (PF4/heparin [PF4/H] and PF4 alone, with >50% inhibition with high heparin (100 IU/mL); his serum stimulated serotonin release in the presence of PF4. His leg swelling had improved even more on day 39 with a D-dimer of 5.6 mg/L, and an elevated platelet count was observed. Eventually, he was diagnosed with VITT. His treatment started with immune-globulin. Subsequently, his platelet counts increased, and his D-dimer gradually decreased. On day 147, he showed no signs of pulmonary embolism or cerebral venous thrombosis symptoms. However, his mild thrombocytopenia continued with elevated D-dimer levels, even after receiving immune-globulin on day 72. Repeated serological testing post-immune-globulin revealed sustained reactivity in all three EIAs, but negative platelet activation tests.

Case 2: A 55-year-old man who had received his first AZD-1222 [ChAdOx1 nCoV-19; Covishield] COVID-19 vaccination. After 8 to 11 days, he developed a bitemporal headache (7/10 severity), which was pulsatile with no focal neurologic deficits. On day 11, he developed dyspnoea and a cough when he exerted himself; his respiratory symptoms deteriorated over the next three days. He was presented to the emergency room on day 15 because he had a small-volume haemoptysis (without any further bleeding). His platelet count was 103 x 10⁹/L and his D-dimer was >20 mg/L. His chest CT revealed pulmonary emboli on both sides with indications of embolism in the saddle. He was haemodynamically stable and had no echocardiographic signs of right heart strain. A DVT in the left lower leg was discovered on Doppler ultrasonography, with a partly occlusive thrombus in the distal superficial femoral vein spreading into the popliteal vein. A CT venography of his brain revealed no CVT. Eventually, he was hospitalised and received rivaroxaban. Following that, he was diagnosed with VITT and immune-globulin was started. The testing polyspecific PF4/polyanion EIA (2.554 OD units) was positive, as were two IgG-specific EIAs (PF4/H and PF4 alone), with >50% inhibition with high heparin; his serum stimulated serotonin release in the presence of PF4. After receiving two doses of immune-globulin, his platelet count increased quickly. He was discharged on rivaroxaban. Serial D-dimer examinations revealed a steady deterioration, although he was otherwise healthy during his last follow-up on day 138. Repeated serological testing post-immune-globulin revealed sustained reactivity in all three EIAs, but negative platelet activation tests.