Vaccine Induced Thrombosis and Thrombocytopenia (VITT): Pathogenesis and Clinical Findings
Current leading theory: COVID-19 viral vector vaccines (Johnson and Johnson and AstraZeneca) contain an anionic molecule (currently unspecified), which binds to the cationic platelet factor 4 (PF4) molecule in the bloodstream, forming vaccine/PF4 complexes
Authors: Brooke Fallis Reviewers: Yan Yu* Katie Lin* * MD at time of publication
Spleen macrophages remove antibody/platelet complexes from circulation
Fewer unbound platelets in circulation detected on complete blood count (CBC)
Thrombocytopenia: Platelets <150x!"#/L ↓ plateletsà↓ ability to form platelet plugs at sites of blood vessel ruptureà↑ bleeding, particularly under the skin Petechial rash Thrombi in arteries block blood flow in susceptible areas (ex. brain and extremities) leading to ischemia Immune system recognizes the vaccine/PF4 complex as an antigen Widespread immune response against PF4/vaccine complex is triggered through complex physiological mechanisms (e.g. certain anti-PF4 antibodies induce platelet activation), with various end-results: IgG antibodies are produced against the vaccine/PF4 complexes Heparin induced thrombocytopenia (HIT) produces similar IgG antibodies. Enzyme linked immunosorbant assay (ELISA) test for HIT can be used to identify if the specific IgG against the vaccine/PF4 complexes is present ELISA positive for HIT Monocyte activation ↑ Tissue Factor (TF) expression starts coagulation cascade Endothelial activation Platelet activation Neutrophil activation Activated neutrophils create sticky webs of extracellular DNA called Neutrophil Extracellular Traps (NETs) which trap platelets and red blood cells ↑ blood clotting Vaccine-induced thrombosis Thrombi in ophthalmic vein block blood drainage causing congestion that damages surrounding tissues and nerves ↑ fibrinogen breakdown as body Positive D-dimer reacts to reduce blood clots Thrombi in splanchnic veins of the abdomen block blood flow, increasing intra-vascular pressure, activating nociceptors which can refer pain to adjacent skin, such as the skin of the abdomen, chest, and back Abdominal, chest and back pain Thrombi in cerebral venous sinus prevents blood drainage causing swelling and damage to brain tissue Thrombi in adrenal vein prevents blood drainage and increases upstream pressure causing rupture of vessels in adrenal glands Adrenal hemorrhage, leading to adrenal failure Critically low serum cortisol (life threatening) Ischemic stroke Limb ischemia Vision changes/loss Eye pain Headaches Focal neurological findings Seizures Mental status changes Extreme muscle weakness Extreme low blood pressure Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published July 13, 2021 on www.thecalgaryguide.com