Immunology · Year 2 · from Immunology
Case 5: Vaccine-Induced Immune Thrombocytopenia and Thrombosis (VITT)
Clinical Image
Source: Wikipedia - Cerebral venous sinus thrombosis - CC BY-SA 4.0
Case Presentation
A 34-year-old female presents to the emergency department with 3 days of progressively worsening thunderclap headache, photophobia, nausea, and vomiting beginning 11 days after receiving her first dose of an adenoviral vector COVID-19 vaccine (Ad26.COV2.S). She has no prior history of heparin exposure, thrombophilia, or oral contraceptive use. On examination, she is alert but appears uncomfortable, with papilledema on fundoscopic examination and no focal neurological deficits initially. Vital signs show HR 96 bpm, BP 148/92 mmHg, and temperature 37.2C. Initial laboratory results reveal platelet count 38 x 10^9/L (normal 150-400), D-dimer >35 mcg/mL FEU (markedly elevated), fibrinogen 120 mg/dL (low-normal), PT/INR and aPTT mildly prolonged. CT head without contrast shows a hyperdense superior sagittal sinus. CT venography confirms extensive thrombosis of the superior sagittal sinus and left transverse sinus with surrounding cerebral edema. An anti-PF4 ELISA is sent and returns strongly positive (OD 3.2), with confirmatory positive PF4-dependent platelet activation assay (functional HIPA test). Heparin is strictly avoided. She is started on argatroban IV infusion (non-heparin anticoagulant) titrated to aPTT 1.5-3x baseline, and receives IVIG 1 g/kg daily for 2 days. Platelet count recovers to 124 x 10^9/L by day 5. She is transitioned to oral rivaroxaban 15 mg twice daily for 3 weeks followed by 20 mg daily. Serial imaging at 3 months shows partial recanalization.
Key Learning Points
- VITT is caused by adenoviral vector vaccine components (or adenoviral DNA-PF4 complexes) triggering formation of high-titer IgG antibodies against platelet factor 4 (PF4) that activate platelets via FcgammaRIIA receptors, mechanistically analogous to autoimmune heparin-induced thrombocytopenia (aHIT) but occurring without prior heparin exposure
- The classic VITT presentation occurs 4-28 days post-vaccination with thrombosis at unusual sites (cerebral venous sinuses, splanchnic veins, adrenal veins) combined with thrombocytopenia, markedly elevated D-dimer, and low-to-normal fibrinogen
- Heparin must be strictly avoided in VITT because anti-PF4 antibodies can be further activated by heparin-PF4 complexes; alternative anticoagulants include argatroban (direct thrombin inhibitor), fondaparinux, or direct oral anticoagulants
- IVIG at 1 g/kg for 2 days blocks FcgammaRIIA-mediated platelet activation by saturating Fc receptors and is a critical adjunctive therapy alongside non-heparin anticoagulation