Platelet transfusions and heparin therapy should be avoided in the management of suspected vaccine-induced immune thrombotic thrombocytopenia (VITT).
A UK case series of 23 patients presenting with VITT after a first dose of the AstraZeneca COVID-19 vaccine said the combination of thrombosis and an apparent consumptive coagulopathy was a dilemma with respect to the benefits and risks associated with aggressive anticoagulation.
“This dilemma is especially relevant in patients with cerebral venous thrombosis, in whom bleeding could be catastrophic but withholding anticoagulation could be equally harmful,” the study said.
The study, published in the NEJM, said avoidance of platelet transfusions was critical, because such treatment would provide a substrate for further antibody-mediated platelet activation and coagulopathy.
“The exact nature of these pathologic antibodies has not been characterised, but they appear to be of the IgG subtype, and platelet activation can be completely abrogated with an excess of heparin, as seen in classic HIT.”
“An understanding of the precise pathophysiological mechanism may allow for more targeted therapeutic interventions,” the investigators said.
They also recommended against heparin therapy, given VITT’s similarities with conventional heparin-induced thrombocytopenia (HIT).
“Although evidence does not yet suggest that the use of heparin will exacerbate this condition, pending further data, we would recommend considering anticoagulation with the use of a nonheparin anticoagulant agent, such as argatroban, danaparoid, fondaparinux, or direct oral anticoagulants.”
“Intravenous immune globulin (IVIG) has been used successfully in the treatment of patients with “spontaneous” autoimmune HIT, which is the closest comparison to this vaccine-induced syndrome, and IVIG would be expected to have direct antibody-mediated toxic effects.”
“Plasma exchange with plasma rather than albumin could also be effective in temporarily reducing levels of pathologic antibodies and providing some correction of the coagulopathy in terms of the hypofibrinogenemia.”
The study also confirmed some of the likely laboratory findings, consistent with THANZ advice and as reported in the limbic recently.
The study said all patients had a negative SARS-CoV-2 polymerase-chain-reaction assay at presentation.
The D-dimer levels, at a median 31,301 fibrinogen-equivalent units, were much higher than would be expected in patients with acute VTE. Thirteen patients had low fibrinogen levels.
An ELISA for anti-PF4 antibodies was positive in 22 of the 23 patients.
A functional HIT assay performed to confirm the ELISA result was positive in 5 of the 7 patients who were tested – confirming the presence of platelet activation similar to that seen in HIT.
“No other relevant laboratory tests were positive, including tests for thrombophilia, antinuclear antibodies, extractable nuclear antigen, and antiphospholipid antibodies.”