Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Aug;43(4):559-570.
doi: 10.1111/ijlh.13629. Epub 2021 Jun 17.

Laboratory testing for suspected COVID-19 vaccine-induced (immune) thrombotic thrombocytopenia

Emmanuel J Favaloro  1   2
Affiliations
Review

Laboratory testing for suspected COVID-19 vaccine-induced (immune) thrombotic thrombocytopenia

Emmanuel J Favaloro. Int J Lab Hematol. 2021 Aug.

Abstract

COVID-19 (coronavirus disease 2019) represents a pandemic, and several vaccines have been produced to prevent infection and/or severe sequelae associated with SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection. There have been several reports of infrequent post vaccine associated thrombotic events, in particular for adenovirus-based vaccines. These have variously been termed VIPIT (vaccine-induced prothrombotic immune thrombocytopenia), VITT (vaccine-induced [immune] thrombotic thrombocytopenia), VATT (vaccine-associated [immune] thrombotic thrombocytopenia), and TTS (thrombosis with thrombocytopenia syndrome). In this report, the laboratory test processes, as utilised to assess suspected VITT, are reviewed. In published reports to date, there are notable similarities and divergences in testing approaches, potentially leading to identification of slightly disparate patient cohorts. The key to appropriate identification/exclusion of VITT, and potential differentiation from heparin-induced thrombocytopenia with thrombosis (HITT), is identification of potentially differential test patterns. In summary, testing typically comprises platelet counts, D-dimer, fibrinogen, and various immunological and functional assays for platelet factor 4 (PF4) antibodies. In suspected VITT, there is a generally highly elevated level of D-dimer, thrombocytopenia, and PF4 antibodies can be identified by ELISA-based assays, but not by other immunological assays typically positive in HITT. In addition, in some functional platelet activation assays, standard doses of heparin have been identified to inhibit activation in suspected VITT, but they tend to augment activation in HITT. Conversely, it is also important to not over-diagnose VITT, given that not all cases of thrombosis post vaccination will have an immune basis and not all PF4-ELISA positive patients will be VITT.

Keywords: COVID-19; laboratory testing; platelet factor 4 antibodies; thrombosis with thrombocytopenia syndrome; vaccine-associated thrombotic thrombocytopenia; vaccine-induced (immune) thrombotic thrombocytopenia.

PubMed Disclaimer

Conflict of interest statement

The author has no competing interests.

Figures

FIGURE 1
FIGURE 1
Summary of findings in the literature in regard to age (years), presenting symptoms or hospitalisation post vaccine (days), platelet count (×109/L), D‐dimer (mg/L) (all left y‐axis) or fibrinogen level (g/L; right y‐axis). Data are from the references cited in Table 2
FIGURE 2
FIGURE 2
Summary of reported ELISA OD readings for PF4 antibodies according to the literature using case series cited in Table 2, excluding the study of Platton et al The horizontal lines indicate the median values for each group
FIGURE 3
FIGURE 3
Summary of reported ELISA OD readings for PF4 antibodies and results of rapid assays, according to the study of Platton et al For rapid assays, CLIA and LIA results given in U/mL; for PAGIA, the numbers refer to the grade of response, and, for STiC, a value of 0 represents negative and a value of 1.5 represents positive. The horizontal lines indicate the negative/positive cut‐off values
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. COVID‐19 Dashboard by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University . COVID‐19 Dashboard by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University. 2021. Available at. <https://www.arcgis.com/apps/opsdashboard/index.html#/bda7594740fd4029942...> Accessed 27th May.
    1. Lippi G, Sanchis‐Gomar F, Favaloro EJ, Lavie CJ, Henry BM. Coronavirus disease 2019‐associated coagulopathy. Mayo Clin Proc. 2021;96(1):203‐217. - PMC - PubMed
    1. Thachil J, Srivastava A. SARS‐2 coronavirus‐associated hemostatic lung abnormality in covid‐19: is it pulmonary thrombosis or pulmonary embolism? Semin Thromb Hemost. 2020;46(7):777‐780. - PMC - PubMed
    1. Schulman S. Coronavirus disease 2019, prothrombotic factors, and venous thromboembolism. Semin Thromb Hemost. 2020;46(7):772‐776. - PMC - PubMed
    1. Di Minno A, Ambrosino P, Calcaterra I, Di Minno MND. COVID‐19 and venous thromboembolism: A meta‐analysis of literature studies. Semin Thromb Hemost. 2020;46(7):763‐771. - PMC - PubMed

MeSH terms

Substances