Hematology in the post-COVID era: spotlight on vaccine-induced immune thrombotic thrombocytopenia and a conceptual framework (the 4P’s) for anti-PF4 diseases

ABSTRACT

Introduction

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a life-threatening prothrombotic disorder first identified following the introduction of adenoviral vector vaccines for COVID-19. The condition is characterized by anti-PF4 antibodies and clinically presents with thrombocytopenia and thrombosis often in unusual anatomical sites.

Areas covered

In this review, we discuss the clinical presentation, diagnostic testing, and treatment of VITT. We also review VITT-like syndromes that have been described in patients without previous vaccination. We propose a conceptual framework for the mechanism of anti-PF4 diseases that includes sufficiently high levels of PF4, the presence of a Polyanion that can form immune complexes with PF4, a Pro-inflammatory milieu, and an immunological Predisposition – the 4Ps.

Expert opinion

Significant progress has been made in understanding the characteristics of the VITT antibody and in testing methods that can confirm that diagnosis. Future work should be directed at understanding long-term outcomes, mechanisms of thrombosis, and individual risk factors for this rare but dangerous immune-thrombotic disease.

KEYWORDS:

• VITT
• anti-PF4 antibodies
• long VITT
• platelet activation assays
• anti-PF4 antibody assays
• VITT treatment
• VITT-like syndromes

Article highlights

• VITT is characterized by atypical thrombi, with a high incidence of CVST.

• Rapid immunoassays continue to show both poor sensitivity and specificity and are not recommended in VITT diagnostic testing.

• As VITT is a pro-thrombotic disorder, the frontline treatment includes anticoagulation.

• While it appears that heparin is not harmful in VITT, non-heparin anticoagulation is advised if available.

• High-dose IVIG has been shown to be effective in the management of VITT and is recommended in the frontline treatment of this condition.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

Funding support for this work was provided by a grant from the Public Health Agency of Canada (to DM Arnold and I Nazy) and by a grant from the Heart and Stroke Foundation of Canada (HSFC#G-23-0035035, to I Nazy and DM Arnold).