A case of thrombocytopenia and multiple thromboses after vaccination with ChAdOx1 nCoV-19 against SARS-CoV-2

Abstract

Recently, reports of severe thromboses, thrombocytopenia, and hemorrhage in persons vaccinated with the chimpanzee adenovirus-vectored vaccine (ChAdOx1 nCoV-19, AZD1222, Vaxzevria; Oxford/AstraZeneca) against severe acute respiratory syndrome coronavirus 2 have emerged. We describe an otherwise healthy 30-year-old woman who developed thrombocytopenia, ecchymosis, portal vein thrombosis, and cerebral venous sinus thrombosis the second week after she received the ChAdOx1 nCoV-19 vaccine. Extensive diagnostic workup for thrombosis predispositions showed heterozygosity for the prothrombin mutation, but no evidence of myeloproliferative neoplasia or infectious or autoimmune diseases. Her only temporary risk factor was long-term use of oral contraceptive pills (OCPs). Although both the prothrombin mutation and use of OCPs predispose to portal and cerebral vein thrombosis, the occurrence of multiple thromboses within a short time and the associated pattern of thrombocytopenia and consumption coagulopathy are highly unusual. A maximum 4T heparin-induced thrombocytopenia (HIT) score and a positive immunoassay for anti-platelet factor 4/heparin antibodies identified autoimmune HIT as a potential pathogenic mechanism. Although causality has not been established, our case emphasizes the importance of clinical awareness. Further studies of this potentially new clinical entity have suggested that it should be regarded as a vaccine-induced immune thrombotic thrombocytopenia.

Inflammation and Platelet Activation After COVID-19 Vaccines - Possible Mechanisms Behind Vaccine-Induced Immune Thrombocytopenia and Thrombosis

“…VITT is characterized by multiple thromboses at unusual sites most often as cerebral venous sinus thrombosis (CVST) and splanchnic vein thromboses combined with thrombocytopenia, increased D-dimer and often decreased fibrinogen ( 1 , 2 , 7 – 9 , 11 ). VITT is occasionally complicated by arterial thrombosis as ischemic stroke, myocardial infarction or limb ischemia ( 3 , 12 , 13 ).…”

Vaccine-induced thrombotic thrombocytopenia following coronavirus vaccine: A narrative review

“… IVIg (1 g/kg) once a day, Dabigatran, Idarucizumab, Prednisolone once daily (1 mg/kg) with proton pump inhibitors cover Death Mehta et al [ 16 ] 32 y/o Male N/A Thunderclap headache, subsequent left-sided incoordination, and hemiparesis ChAdOx1 vaccine (AZD1222, Vaxzevria) Platelets = 30 × 10 9 /L Superior sagittal sinus and cortical vein thrombosis No treatment since the condition continued to deteriorate Death Mehta et al [ 16 ] 25 y/o Male Primary sclerosing cholangitis and migraines Photophobia, neck stiffness, visual disturbances, petechial rashes, and gum bleeding ChAdOx1 vaccine (AZD1222, Vaxzevria) Platelets = 19 × 10 9 /L Positive anti -P4 antibodies Superior sagittal sinus thrombosis with cortical veins involvement. Intravenous unfractionated heparin, platelet transfusions, IV dexamethasone, IVIG, and intravenous levetiracetam Death Xie et al [ 50 ] 23 y/o N/A Chest pain and breathlessness N/A Platelets = 73 × 10 9 /L D-dimer = 17548 μg/L Pulmonary emboli, right ventricle thrombus, and splenic vein thrombus Apixaban, intubation, ventilation, plasma exchange, IV methylprednisolone, and heparin infusion Recovered Sørensen et al [ 22 ] 33 y/o Female Migraine Headache and general malaise ChAdOx1 nCoV-19 (AstraZeneca) Platelets = 51 × 10 9 /L Anti-PF4 antibodies were positive Cerebral venous sinus thrombosis and portal vein thrombosis Tinzaparin, Fondaparinux Recovered Dias et al [ 61 ] …”

“…The exact pathophysiology behind VITT is unclear. As shown in Table 1 , most of the cases presented with thrombocytopenia, elevated D-dimer, and positive titers of IgG antibodies against platelet factor 4 (PF-4) [ [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] ]. Based on these findings, this syndrome is closely related to heparin-induced thrombocytopenia (HIT), a medical condition characterized by thrombocytopenia, and the presence of antibodies against the Heparin-PF4 complex [ 23 ].…”

Anti-PF4 VITT antibodies are oligoclonal and variably inhibited by heparin

“…Several vaccines have shown high efficacy in clinical studies and have produced salutary effects on hospitalizations and deaths 2 . Two vaccines, ChAdOx1 nCoV-19 (AstraZeneca) and Ad26.COV2.S (Janssen/Johnson & Johnson) have been associated with very rare adverse reactions variably called Vaccine-induced immune thrombotic thrombocytopenia (VITT) and Thrombosis and Thrombocytopenia syndrome (TTS), respectively [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] . In this report, both syndromes are referred to as VITT, in line with expert recommendations 18 .…”