Adjunct Immune Globulin for Vaccine-Induced Immune Thrombotic Thrombocytopenia

N Engl J Med. 2021 Aug 19;385(8):720-728. doi: 10.1056/NEJMoa2107051. Epub 2021 Jun 9.


The use of high-dose intravenous immune globulin (IVIG) plus anticoagulation is recommended for the treatment of vaccine-induced immune thrombotic thrombocytopenia (VITT), a rare side effect of adenoviral vector vaccines against coronavirus disease 2019 (Covid-19). We describe the response to IVIG therapy in three of the first patients in whom VITT was identified in Canada after the receipt of the ChAdOx1 nCoV-19 vaccine. The patients were between the ages of 63 and 72 years; one was female. At the time of this report, Canada had restricted the use of the ChAdOx1 nCoV-19 vaccine to persons who were 55 years of age or older on the basis of reports that VITT had occurred primarily in younger persons. Two of the patients in our study presented with limb-artery thrombosis; the third had cerebral venous and arterial thrombosis. Variable patterns of serum-induced platelet activation were observed in response to heparin and platelet factor 4 (PF4), indicating the heterogeneity of the manifestations of VITT in serum. After the initiation of IVIG, reduced antibody-induced platelet activation in serum was seen in all three patients. (Funded by the Canadian Institutes of Health Research.).

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • COVID-19 Vaccines / adverse effects*
  • ChAdOx1 nCoV-19
  • Female
  • Fibrin Fibrinogen Degradation Products / analysis
  • Fibrinogen / analysis
  • Heparin / pharmacology
  • Humans
  • Immunoglobulins, Intravenous*
  • Male
  • Middle Aged
  • Platelet Count
  • Platelet Factor 4 / pharmacology
  • Serotonin / blood
  • Thrombocytopenia / blood
  • Thrombocytopenia / etiology
  • Thrombocytopenia / therapy*
  • Thrombosis / etiology
  • Thrombosis / immunology
  • Thrombosis / therapy*


  • COVID-19 Vaccines
  • Fibrin Fibrinogen Degradation Products
  • Immunoglobulins, Intravenous
  • fibrin fragment D
  • Serotonin
  • Platelet Factor 4
  • Fibrinogen
  • Heparin
  • ChAdOx1 nCoV-19