ワクチン接種由来の免疫性血小板減少症の分析

//Background//---
 Vaccine-induced immune thrombotic thrombocytopenia(VITT) is a rare but serious adverse effect of SARS-CoV-2 adenoviral vector vaccine(1 case of 100,000~1,000,000)(2-4)1-3. This side effect makes arterial and/or venous thrombi in unusual location evolve(2-4). Despite of no heparin exposure(6,7)6,7, this side effect develop thrombocytopenia. Heparin induces thrombocytopenia associated with platelet-activating antibody against platelet factor 4(PF4)(5)4.
 In this situation, Angela Huynh, John G Kelton, Donald M Arnold, Mercy Daka & Ishac Nazy investigate platelet-activation mechanism by anti-PF4 antibody from patients (n=5) with VITT(1).
 
//Condition//---
Patient received a single dose of ChAdOx1 nCoV-19 vaccine.
Mean age: 44 years (35-72)
2/5 persons is female.
Collection period: 14 to 40 days after vaccination
All VITT samples had antibodies against PF4
 
//Brief result(1)//---
 VITT anti-PF4 antibodies had a strong binding response against PF4 and PF4/heparin complexes than HIT antibodies in a similar manner of heparin. This induces FcγRⅡa-dependent platelet activation through PF4 tetramer and immune complex formation. Additionally, they clarify the binding cite through structural analysis and compare VITT to HIT(heparin-induced thrombocytopenia. We can evaluate the overlapped binding sites of anti-PF4 antibodies and heparin(Epitope: R22, H23, K46 and K66 are corresponded.)(See Fig.1).
 
(Reference)
(1)
Angela Huynh, John G Kelton, Donald M Arnold, Mercy Daka & Ishac Nazy
Antibody epitopes in vaccine-induced immune thrombotic thrombocytopenia
Nature (2021)
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Author information
Affiliations
Department of Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada
Angela Huynh, John G Kelton, Donald M Arnold & Ishac Nazy
McMaster Centre for Transfusion Research, Hamilton, Ontario, Canada
John G Kelton, Donald M Arnold & Ishac Nazy
Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada
Mercy Daka
(2)
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Thrombotic Thrombocytopenia after ChAdOx1 nCov-19 Vaccination.
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(3)
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Thrombosis and Thrombocytopenia after ChAdOx1 nCoV-19 Vaccination.
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Pathologic Antibodies to Platelet Factor 4 after ChAdOx1 nCoV-19 Vaccination.
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(5)
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(6)
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Am J Med 121, 632-636, https://doi.org/10.1016/j.amjmed.2008.03.012 (2008).
(7)
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Cerebral venous sinus thrombosis associated with spontaneous heparin-induced thrombocytopenia syndrome after total knee arthroplasty.
Platelets, 1-5, https://doi.org/10.1080/09537104.2020.1828574 (2020).