AZD-1222

Author Information

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

A 49-year-old man developed acute arterial clot formation following administration of AZD-1222 for immunisation against COVID-19.

The man who was fit and well previously, presented with a 4 day history of cramping left leg pain with progressive paraesthesia and pallor. He did not had any history of recreational drug use, smoking and alcohol consumption. Moreover, his family history was also non-significant. Subsequently, it was reported that, 14 days previously, he had received his first dose of the AZD-1222 [ChAdOx1 nCov-19 vaccination; route and dosage not stated]. Subsequently, at current presentation, he was admitted. Thereafter, examination confirmed left lower acute limb ischemia of Rutherford Class IIa. Blood laboratory findings showed mild thrombocytopenia and elevated D-dimer. Subsequent, CT lower limb angiogram revealed focal acute thrombus (clot) just above the left iliac bifurcation and an acute occlusion of the midpopliteal artery which extended into the proximal segments of the crural arteries.

Thereafter, it was decided to perform an urgent pharmaco-mechanical thrombectomy of man. Fluoroscopic angiogram confirmed occlusion of the popliteal artery without any distal run-off. It was concluded that, the absence of filling defects in the iliac arteries on angiogram was deemed likely secondary to distal clot embolisation. Subsequently, he received thrombectomy and afterwards, thrombolysis with alteplase. It was revealed that, initial therapy restored in line flow to the ankle along with residual filling defects in the infra-popliteal arteries. For overnight thrombolysis, he received a multi-side hole infusion catheter up to the anterior tibial artery (ATA) along with alteplase and heparin. Thereafter, for a total of 24 hours, he remained on thrombolysis meanwhile, subsequent checking of angiograms was done. During the first check angiogram, to reduce the clot burden, further thrombectomy was performed in the ATA, however, it failed to restore the flow. Since, there was a concern of further clot formation by heparin. It was stopped and to maintain access sheath patency and thrombolysis he received sodium-chloride [saline] with continued treatment with alteplase. Subsequently, final angiogram showed resolution of the popliteal and tibial thrombus with only a short segment residual filling defect in the common plantar artery. Thereafter, to treat suspected vaccine-induced immune thrombotic thrombocytopenia, he started to receive anticoagulation with argatroban with a target activated partial thromboplastin time (APTT) range of 1.5−3.0 of normal control. Following clinical and symptomatic improvement, on discharge, his treatment with argatroban was switched to warfarin and it was continued for a period of 6 months. Afterwards, thrombophilia screen showed a normal activity of protein C and S activity and negative assays for prothrombin and factor V Leiden mutation. On admission, he was detected with lupus anticoagulant. However, at 6 months follow up, this was negative; excluding it as a cause for the thrombosis. Rapid heparin induced thrombocytopenia (HIT) screen test was negative. However, conversely, testing with Stago-Asserachrom HPIA ELISA' was positive for anti-PF4 antibodies, hence, a diagnosis of vaccine-induced immune thrombotic thrombocytopenia (VIITT) was confirmed. Since, there was an absence of any identifiable cause of arterial clot formation and timing of the presentation following vaccination. The clinical and diagnostic suspicion for a vaccine related phenomenon increased. Subsequently ELISA PF4 antibodies revealed a positive results hence, eventually, the development of arterial clot formation which was followed by acute arterial occlusion was attributed to AZD-1222.