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CC BY-NC-ND 4.0 · Thromb Haemost 2022; 122(08): 1352-1360
DOI: 10.1055/a-1788-5206
Cellular Haemostasis and Platelets

Assessing Clinically Meaningful Hypercoagulability after COVID-19 Vaccination: A Longitudinal Study

Elena Campello 
1   General Internal Medicine and Thrombotic and Hemorrhagic Diseases Unit, Department of Medicine, Padova University Hospital, Veneto, Italy
,
Cristiana Bulato
1   General Internal Medicine and Thrombotic and Hemorrhagic Diseases Unit, Department of Medicine, Padova University Hospital, Veneto, Italy
,
Chiara Simion
1   General Internal Medicine and Thrombotic and Hemorrhagic Diseases Unit, Department of Medicine, Padova University Hospital, Veneto, Italy
,
Luca Spiezia 
1   General Internal Medicine and Thrombotic and Hemorrhagic Diseases Unit, Department of Medicine, Padova University Hospital, Veneto, Italy
,
Claudia Maria Radu
1   General Internal Medicine and Thrombotic and Hemorrhagic Diseases Unit, Department of Medicine, Padova University Hospital, Veneto, Italy
,
Sabrina Gavasso
1   General Internal Medicine and Thrombotic and Hemorrhagic Diseases Unit, Department of Medicine, Padova University Hospital, Veneto, Italy
,
Francesca Sartorello
1   General Internal Medicine and Thrombotic and Hemorrhagic Diseases Unit, Department of Medicine, Padova University Hospital, Veneto, Italy
,
Graziella Saggiorato
1   General Internal Medicine and Thrombotic and Hemorrhagic Diseases Unit, Department of Medicine, Padova University Hospital, Veneto, Italy
,
Patrizia Zerbinati
1   General Internal Medicine and Thrombotic and Hemorrhagic Diseases Unit, Department of Medicine, Padova University Hospital, Veneto, Italy
,
Mariangela Fadin
1   General Internal Medicine and Thrombotic and Hemorrhagic Diseases Unit, Department of Medicine, Padova University Hospital, Veneto, Italy
,
Daniela Tormene
1   General Internal Medicine and Thrombotic and Hemorrhagic Diseases Unit, Department of Medicine, Padova University Hospital, Veneto, Italy
,
Paolo Simioni
1   General Internal Medicine and Thrombotic and Hemorrhagic Diseases Unit, Department of Medicine, Padova University Hospital, Veneto, Italy
› Author Affiliations Funding The study was funded by Ministry of Education, University and research (MIUR), grant DOR2147942/2021 to P.S.
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Abstract

A large number of daily requests to exclude possible prothrombotic risk factors for coronavirus disease 2019 (COVID-19) vaccines were received. Our aim was to longitudinally evaluate coagulation profiles in a series of healthy subjects who received COVID-19 vaccination and assess hypercoagulability thereafter. Volunteers awaiting a first or second dose of either the ChAdOx1 or BNT162b2 vaccine were enrolled. Venous samples were obtained at baseline (before the vaccine) and longitudinally 3 ± 2 days (T1) and 10 ± 2 days after the vaccine (T2). Global coagulation monitoring was assessed via platelet count, whole blood thromboelastometry and impedance aggregometry, plasma thrombin generation, and anti-platelet factor 4 (PF4)/heparin immunoglobulin G antibodies. One hundred and twenty-two subjects were enrolled (61 [50%] ChAdOx1 and 61 BNT162b2). The ChAdOx1 cohort showed a slight but transient increase in thrombin generation (mainly endogenous thrombin potential [ETP] with thrombomodulin and ETP ratio) at T1, which promptly decreased at T2. In addition, the second dose of either vaccine was associated with increased thrombin peak, ETP with thrombomodulin, and ETP ratio. At baseline, 3.2% of the ChAdOx1 cohort and 1.6% BNT162b2 cohort were positive for PF4/heparin antibodies with a stable titer through T1 and T2. No relevant differences were detected in platelet count and aggregation, or thromboelastometry parameters. No thrombotic or hemorrhagic events occurred. We can confirm that no clinically meaningful hypercoagulability occurred after either vaccine, albeit keeping in mind that thrombin generation may increase in the first days after the second dose of either vaccine and after the first dose of the ChAdOx1 vaccine.

Keywords

SARS-CoV-2 - thrombin generation - thrombophilia - vaccine - venous thrombosis


Publication History

Received: 20 November 2021

Accepted: 14 January 2022

Accepted Manuscript online:
04 March 2022

Article published online:
27 May 2022

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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  • References

  • 1 Greinacher A, Thiele T, Warkentin TE, Weisser K, Kyrle PA, Eichinger S. Thrombotic thrombocytopenia after ChAdOx1 nCov-19 vaccination. N Engl J Med 2021; 384 (22) 2092-2101
    Search in Google Scholar
  • 2 Schultz NH, Sørvoll IH, Michelsen AE. et al. Thrombosis and thrombocytopenia after ChAdOx1 nCoV-19 vaccination. N Engl J Med 2021; 384 (22) 2124-2130
    Search in Google Scholar
  • 3 Scully M, Singh D, Lown R. et al. Pathologic antibodies to platelet factor 4 after ChAdOx1 nCoV-19 vaccination. N Engl J Med 2021; 384 (23) 2202-2211
    Search in Google Scholar
  • 4 See I, Su JR, Lale A. et al. US case reports of cerebral venous sinus thrombosis with thrombocytopenia after Ad26.COV2.S vaccination, march 2 to April 21, 2021. JAMA 2021; 325 (24) 2448-2456
    CrossrefPubMedSearch in Google Scholar
  • 5 Ceschia N, Scheggi V, Gori AM. et al. Diffuse prothrombotic syndrome after ChAdOx1 nCoV-19 vaccine administration: a case report. J Med Case Reports 2021; 15 (01) 496
    CrossrefPubMedSearch in Google Scholar
  • 6 Klok FA, Pai M, Huisman MV, Makris M. Vaccine-induced immune thrombotic thrombocytopenia. Lancet Haematol 2022; 9 (01) e73-e80
    CrossrefPubMedSearch in Google Scholar
  • 7 Pavord S, Scully M, Hunt BJ. et al. Clinical features of vaccine-induced immune thrombocytopenia and thrombosis. N Engl J Med 2021; 385 (18) 1680-1689
    Search in Google Scholar
  • 8 Chan BTB, Bobos P, Odutayo A, Pai M. Meta-Analysis of Risk of Vaccine- Induced Immune Thrombotic Thrombocytopenia Following ChAdOx1-S Recombinant Vaccine. Accessed March 21, 2022 at: https://www.medrxiv.org/content/10.1101/2021.05.04.21256613v1
    PubMed
  • 9 Baden LR, El Sahly HM, Essink B. et al; COVE Study Group. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med 2021; 384 (05) 403-416
    Search in Google Scholar
  • 10 Uaprasert N, Panrong K, Rojnuckarin P, Chiasakul T. Thromboembolic and hemorrhagic risks after vaccination against SARS-CoV-2: a systematic review and meta-analysis of randomized controlled trials. Thromb J 2021; 19 (01) 86
    CrossrefPubMedSearch in Google Scholar
  • 11 Sangli S, Virani A, Cheronis N. et al. Thrombosis with thrombocytopenia after the messenger RNA-1273 vaccine. Ann Intern Med 2021; 174 (10) 1480-1482
    CrossrefPubMedSearch in Google Scholar
  • 12 Razai MS, Chaudhry UAR, Doerholt K, Bauld L, Majeed A. Covid-19 vaccination hesitancy. BMJ 2021; 373 (1138): n1138
    CrossrefPubMedSearch in Google Scholar
  • 13 Campello E, Simion C, Bulato C. et al. Absence of hypercoagulability after nCoV-19 vaccination: an observational pilot study. Thromb Res 2021; 205: 24-28
    CrossrefPubMedSearch in Google Scholar
  • 14 Spiezia L, Radu C, Campello E. et al. Whole blood rotation thromboelastometry (ROTEM(®)) in nine severe factor V deficient patients and evaluation of the role of intraplatelets factor V. Haemophilia 2012; 18 (03) 463-468
    CrossrefPubMedSearch in Google Scholar
  • 15 Hartmann J, Walsh M, Grisoli A. et al. Diagnosis and treatment of trauma-induced coagulopathy by viscoelastography. Semin Thromb Hemost 2020; 46 (02) 134-146
    Thieme ConnectPubMedSearch in Google Scholar
  • 16 Zanetto A, Senzolo M, Campello E. et al. Influence of hepatocellular carcinoma on platelet aggregation in cirrhosis. Cancers (Basel) 2021; 13 (05) 1150
    CrossrefPubMedSearch in Google Scholar
  • 17 Campello E, Bulato C, Spiezia L. et al. Thrombin generation in patients with COVID-19 with and without thromboprophylaxis. Clin Chem Lab Med 2021; 59 (07) 1323-1330
    CrossrefPubMedSearch in Google Scholar
  • 18 Morrow GB, Beavis J, Harper S. et al. Coagulation status of critically ill patients with and without liver disease assessed using a novel thrombin generation analyzer. J Thromb Haemost 2020; 18 (07) 1576-1585
    CrossrefPubMedSearch in Google Scholar
  • 19 Zanetto A, Rinder HM, Campello E. et al. Acute kidney injury in decompensated cirrhosis is associated with both hypo-coagulable and hyper-coagulable features. Hepatology 2020; 72 (04) 1327-1340
    CrossrefPubMedSearch in Google Scholar
  • 20 Greinacher A, Selleng K, Palankar R. et al. Insights in ChAdOx1 nCov-19 vaccine-induced immune thrombotic thrombocytopenia (VITT). Blood 2021; 138 (22) 2256-2268
    CrossrefPubMedSearch in Google Scholar
  • 21 McGonagle D, De Marco G, Bridgewood C. Mechanisms of immunothrombosis in vaccine-induced thrombotic thrombocytopenia (VITT) compared to natural SARS-CoV-2 infection. J Autoimmun 2021; 121: 102662
    CrossrefPubMedSearch in Google Scholar
  • 22 Campello E, Spiezia L, Adamo A, Simioni P. Thrombophilia, risk factors and prevention. Expert Rev Hematol 2019; 12 (03) 147-158
    CrossrefPubMedSearch in Google Scholar
  • 23 Tchaikovski SN, van Vliet HA, Thomassen MC. et al. Effect of oral contraceptives on thrombin generation measured via calibrated automated thrombography. Thromb Haemost 2007; 98 (06) 1350-1356
    Thieme ConnectPubMedSearch in Google Scholar
  • 24 Greinacher A, Holtfreter B, Krauel K. et al. Association of natural anti-platelet factor 4/heparin antibodies with periodontal disease. Blood 2011; 118 (05) 1395-1401
    CrossrefPubMedSearch in Google Scholar
  • 25 Juhl D, Eichler P, Lubenow N, Strobel U, Wessel A, Greinacher A. Incidence and clinical significance of anti-PF4/heparin antibodies of the IgG, IgM, and IgA class in 755 consecutive patient samples referred for diagnostic testing for heparin-induced thrombocytopenia. Eur J Haematol 2006; 76 (05) 420-426
    CrossrefPubMedSearch in Google Scholar
  • 26 Otis SA, Zehnder JL. Heparin-induced thrombocytopenia: current status and diagnostic challenges. Am J Hematol 2010; 85 (09) 700-706
    CrossrefPubMedSearch in Google Scholar
  • 27 Terpos E, Politou M, Ntanasis-Stathopoulos I. et al. High prevalence of anti-PF4 antibodies following ChAdOx1 nCov-19 (AZD1222) vaccination even in the absence of thrombotic events. Vaccines (Basel) 2021; 9 (07) 712
    CrossrefPubMedSearch in Google Scholar
  • 28 Thiele T, Ulm L, Holtfreter S. et al. Frequency of positive anti-PF4/polyanion antibody tests after COVID-19 vaccination with ChAdOx1 nCoV-19 and BNT162b2. Blood 2021; 138 (04) 299-303
    CrossrefPubMedSearch in Google Scholar