key: cord-0801572-y1ns8ds6
authors: AbdelMassih, Antoine; Hozaien, Rafeef; El Shershaby, Meryam; Kamel, Aya; Ismail, Habiba-Allah; Fouda, Raghda
title: Is the HIT-like syndrome associated with ChAdOx vaccine related to the vaccine itself or an autoimmune reaction to SARS-CoV-2, insights and implications from previous reports in infected cases?
date: 2021-04-23
journal: New Microbes New Infect
DOI: 10.1016/j.nmni.2021.100884
sha: db7ee70c9eb01e9323c941aef66a4b4f2d191d5e
doc_id: 801572
cord_uid: y1ns8ds6

Prothrombotic states, similar to Heparin induced thrombocytopenia (HIT) in recipients of the ChAdOx vaccine, sounded alarm bells internationally. Equivalent episodes of HIT were detailed in several case reports of Coronavirus Disease 2019 (COVID-19) patients. This suggests a common pathogenesis and warrants a shift in the management of implicated cases.

Is the HIT-like syndrome associated with ChAdOx vaccine related to the vaccine itself or an autoimmune reaction to SARS-CoV-2, insights and implications from previous reports in infected cases?

Antoine AbdelMassih (1,2), Rafeef Hozaien (3) The European Medicines Agency (EMA) stated concern for the safety of the ChAdOx vaccine.

However, Greinacher and colleagues revealed (in a preprint) the serologic profile of patients who developed this unusual set of symptoms after the ChAdOx vaccine. They concluded that the prothrombotic state in these patients is similar to Heparin-induced thrombocytopenia (HIT). All nine patients showed positive anti-platelet factor 4 antibodies (anti-PF4), frequently seen in recipients of heparin. None of these patients were on heparin before getting vaccinated. This implies that the ChAdOx vaccine can potentially induce such autoantibodies. (3) J o u r n a l P r e -p r o o f

Many reports of HIT were reported before the current vaccine rollout; these were reviewed and summarized in table 1 (4) (5) (6) (7) (8) (9) (10) (11) (12) . All the reports incriminated heparin in the development of the observed prothrombotic state. These patients received heparin due to one of three reasons:

The commonest type of thrombosis observed was venous thrombosis, mimicking the pattern of thrombosis observed in recipients of ChAdOx vaccination, males were affected more than females (84% vs. 16%), and median age was 58 years. 

These findings necessitate updating laboratory testing and treatment of COVID-19 patients, presenting with thrombosis, through the following:

The high prevalence of anti-PF4 in COVID-19 patients previously diagnosed with HIT (as mentioned in table 1) warrants screening of this antibody profile in individuals presenting with thrombotic events in COVID-19 patients and after ChAdOx vaccination.

-Presently, three non-heparin anticoagulants, namely danaparoid, lepirudin, and argatroban, are used in HIT as alternative anticoagulants; because they do not cross-react with HIT antibodies.

As such, low molecular weight heparin (LMWH) is also not to be used in COVID-19 patients J o u r n a l P r e -p r o o f and ChAdOx vaccinated individuals because of its cross-reactivity with PF4 autoantibodies.

Warfarin is also discouraged in HIT due to a paradoxical increase in the thrombotic tendency.

-On the other hand, high-dose intravenous immunoglobulins are one of the most well-established therapies for HIT.

-A final therapeutic approach of importance is using Hep-like molecules to disrupt the PF4-GAG complexes. This is considered in the treatment of HIT and could successively be regarded as a treatment for the prothrombotic state in COVID-19 patients and ChAdOx -vaccinated individuals.(14)

A final aspect learnt from the observed prothrombotic syndrome is the choice of proper COVID-19 vaccine in those receiving heparin-based anticoagulants or warfarin. Caution should be taken on administering adenovirus-mediated viral vector vaccines, such as ChAdOx, due to the ability of those medications to induce the same autoimmune complication.

Authors declare that they have no financial links with any of the suppliers of the suggestive alternative anticoagulants.

J o u r n a l P r e -p r o o f Increasing evidence suggests that SARS-CoV-2 is an independent risk factor for PF4 autoantibody development, regardless of prior heparin therapy. The reports encountered following the ChAdOx vaccination and COVID infection, advocate for this hypothesis. This information warrants clinicians to screen for specific autoantibodies in any COVID-19 patient and ChAdOx vaccinated individual presenting with a thrombotic event. It may also lead to advances in the anti-coagulant regimens and treatments used in these patients; such as avoidance of heparin based anticoagulants and the use of immunoglobulins and Hep-like molecules that can disrupt PF4-GAG complexes.

1.

Guerstein 

A Prothrombotic Thrombocytopenic Disorder Resembling Heparin-Induced Thrombocytopenia Following Coronavirus-19

Is COVID-19 an Independent Risk Factor for Heparin-Induced Thrombocytopenia?

Heparin-Induced Thrombocytopenia in a Patient With Coronavirus Disease-19

Heparin-Induced Thrombocytopenia in COVID-19

Heparin-induced thrombocytopenia and COVID-19

Heparin-induced thrombocytopenia in COVID-19 patients with severe acute respiratory distress syndrome requiring extracorporeal membrane oxygenation: two case reports

COVID-19

Incidence of heparin-induced thrombocytopenia in patients with 2019 coronavirus disease

Suspected heparin-induced thrombocytopenia in a COVID-19 patient on extracorporeal membrane oxygenation support: a case report

Adenovirus-induced thrombocytopenia: the role of von Willebrand factor and P-selectin in mediating accelerated platelet clearance

Successful Use of Alternative Anticoagulants in the Management of Heparin-induced Thrombocytopenia with Thrombotic Complications: Report of 5 cases and review of literature