key: cord-0701166-vgkfrd59
authors: Vercruysse, Kobe; Devreese, Katrien M. J.
title: Laboratory testing for post ChAdOx1 nCOV‐19 vaccination VITT: A challenge. Comment on: Recommendations for the clinical and laboratory diagnosis of VITT against COVID‐19: Communication from the ISTH SSC Subcommittee on Platelet Immunology
date: 2021-07-27
journal: J Thromb Haemost
DOI: 10.1111/jth.15457
sha: d7dea51dd1ad56eff710a8aff81cf709f5868a87
doc_id: 701166
cord_uid: vgkfrd59

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ity and clinical implications of the PF4 antibodies in VITT are still unclear. The recommendation of the ISTH SSC Subcommittee on Platelet Immunology concerning the clinical and laboratory diagnosis of VITT against COVID-19 provides case definitions and includes a test strategy for laboratories. The authors propose a methodology similar to HIT testing, in which the platelet-activating properties of PF4 antibodies detected by a PF4/heparin ELISA need to be confirmed with a functional HIT assay. 6 Thereby, the HemosIL AcuStar HIT IgG chemiluminescence immunoassay and other rapid immunoassays are not recommended to detect PF4/heparin antibodies because of a high rate of false-negative results. Indeed, Platton et al. concluded that the HemosIL AcuStar HIT IgG may not be of use in VITT testing because 31 of the 33 tested sera of suspected patients were negative on this platform, with the two remaining sera only showing borderline reaction. 3 Positive PF4/heparin ELISA sera or plasma samples may be confirmed by different functional assays, in which a positive result strongly suggests VITT. 6 However, the circumstances or patterns at which a sample may be confirmed as VITT are not stated. Multiple groups have shown that PF4 antibody-related platelet activation in VITT occurs in a heparin-independent manner, with platelet activation observed both in presence and absence of heparin (e.g., buffer solution). 1, 2, 4 Moreover, functional test methods are being adapted to include platelet incubation with PF4, which seem to enhance platelet activation in some sera. 2, 5 Still, it is known that VITT sera are quite heterogeneous with respect to their activation profile. Another aspect is that laboratory features of VITT patients resemble those of patients previously described with autoimmune HIT. The term "autoimmune HIT" comprises several distinct disorders, including some triggered by heparin (e.g., delayed-onset HIT, refractory HIT) but also some not triggered by heparin (e.g., post-knee replacement HIT syndrome) called "spontaneous HIT." 7 These syndromes might pass the proposed test strategy and lead to wrong recognition and diagnosis of VITT, and could contribute to an overestimation of the vaccine-related severe side effect of thrombocytopenia/thrombosis. We have to take care that reporting "false" VITT does not contribute to public anxiety against vaccination and we have to avoid unnecessary therapeutic action.

To illustrate the resemblances between VITT and autoimmune/ spontaneous HIT, we selected two cases suspected for VITT, as well as two autoimmune HIT and two confirmed HIT patients from the pre-SARS-CoV-2 era. Both VITT patients, one woman and one man, presented with thrombocytopenia and altered coagulation parameters (e.g., low fibrinogen, high D-dimers), although thrombosis was only objectified in the male patient at the mo- The ISTH-SSC recommendation does not define positivity thresholds or patterns for VITT testing, neither does it state test conditions. Many different assay formats and conditions are currently being used. This lack of standardization combined with the heterogeneity of the activation profile in VITT samples makes that the diagnosis of VITT remains a challenge for laboratories. Moreover, because clinical and ELISA laboratory characteristics of VITT seem similar to HIT, a functional assay is mandatory to differentiate both syndromes. In this short correspondence with selected cases by way of example, we illustrate that the laboratory findings in VITT might resemble those of patients previously described with spontaneous or autoimmune HIT, which also are syndromes that can be provoked independent of heparin. Although it is challenging to be able to reach strong conclusions based on a limited number of samples, we want to raise clinical awareness of the existence of these heparin-independent platelet-activating syndromes, and highlighted the resemblance with VITT. We suggest a possible diagnostic tool for differentiation that might be of relevance for future updates on laboratory diagnosis of VITT.

The study had no funding.

Both authors declare that they have no conflict of interest. 

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Thrombotic thrombocytopenia after ChAdOx1 nCov-19 vaccination

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Thrombosis and thrombocytopenia after ChAdOx1 nCoV-19 vaccination

A Flow cytometric assay to detect platelet activating antibodies in VITT after ChAdOx1 nCov-19 vaccination

Recommendations for the clinical and laboratory diagnosis of VITT against COVID-19: communication from the ISTH SSC subcommittee on platelet immunology

Autoimmune heparin-induced thrombocytopenia

A clinical-laboratory approach contributing to a rapid and reliable diagnosis of heparininduced thrombocytopenia

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