Risk of VITT-related thrombosis declines within weeks

The risk of thrombosis in most patients who have developed vaccine-induced immune thrombotic thrombocytopenia (VITT) appears to decline within three months, indicates a German study published in the New England Journal of Medicine.

The researchers, led by Dr Linda Schönborn from the Transfusion Medicine of the University Medicine Greifswald, discovered that in more than 90% of VITT patients pathologic, platelet-activating anti-PF4 antibodies had disappeared by 12 weeks.

“Physicians had been concerned that these antibodies might persist for many months or even years,” she said. “The rapid decline of the pathogenic antibodies is a major relief for the patients and their families as the risk of thrombosis seems to disappear within weeks.”

The findings also indicate that following an occurrence of VITT, a second dose with an mRNA vaccine “appears to be safe after results of platelet-activation assays for VITT antibodies have become negative”, and the authors recommend a period of 3 months between vaccine doses to minimise the risk of subsequent, related issues.

The study involved 35 patients with serologically confirmed VITT (27 women and 8 men; median age, 53 years). The patients’ clinical symptoms started between days 5 and 18 after vaccination. All patients presented with thrombocytopenia, and 30 presented with thrombosis.

The median follow-up time after VITT diagnosis was 11 weeks, during which results of the PF4-dependent platelet-activation assay became negative in 23 of 35 patients (66%). In 14 of the 15 patients with follow-up of more than 12 weeks (93%), the assay became negative within a median of 12 weeks.

Also, the median optical density on anti–PF4–heparin IgG ELISA test significantly declined by 53% between the first and last available blood samples, but full seroreversion to a negative ELISA result was seen in only three patients. However, the authors did observe that in one patient, who experienced recurrent episodes of thrombocytopenia, PF4-dependent platelet-activating antibodies and ELISA optical density values of greater than 3.0 persisted for more than 12 weeks.

Five patients received Pfizer–BioNTech’s mRNA vaccine BNT162b2 as a second vaccination 10 to 18 weeks after their first vaccination, while still receiving anticoagulation; four had a negative platelet-activation assay result before the second dose vaccination, but clinically symptomatic new thrombotic complications or a significant rise in optical density on anti–PF4–heparin IgG ELISA did not occur in any of the patients.

“Our study indicates that anti-PF4 antibodies are transient in most patients with VITT. In a subgroup of these patients, pathogenic platelet-activating anti-PF4 antibodies may persist for more than 12 weeks [but] further studies are needed to clarify whether these patients should receive prolonged anticoagulation or additional treatment,” the authors concluded.

Dr Sue Pavord, Consultant Haematologist at Oxford University Hospitals told the limbic that the findings were important and “consistent with what we have been seeing in the UK – whilst the platelet factor 4 antibodies are persisting, their pathogenicity is declining.”

“This helps inform decisions around duration of anticoagulation and subsequent COVID-19 vaccination, albeit avoiding the adenoviral vector vaccines,” she said.

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