Virus World

Versiti’s blood tests screen for antibodies that may make typical clot treatments harmful to help healthcare providers choose alternative therapies.  Following international probes into rare blood clots among recipients of Johnson & Johnson and AstraZeneca’s COVID-19 vaccines, blood testing company Versiti has put forward a suite of antibody tests to help identify patients that may be at risk. While these cases only number in the dozens among the millions of shots administered worldwide, one of the more dangerous aspects of these potentially severe clots—known as cerebral venous sinus thrombosis—is that the typical anticoagulation treatment can make matters worse. The blood thinner heparin is often used to treat blood clots, but in patients carrying certain platelet-activating antibodies, heparin can trigger harmful drops in platelet counts that could lead to spontaneous bleeding, worsening of their original clots and other complications, according to the Centers for Disease Control and Prevention (CDC).  

Versiti’s blood tests screen for these antibodies, to help healthcare providers choose alternative anticoagulation therapies.  They include an ELISA diagnostic for the PF4, heparin-dependent antibody, followed by additional heparin-induced thrombocytopenia testing or serotonin release assays, depending on the initial result.  The company also offers antibody identification panels if the patient shows low platelet counts in a standard blood draw. The American Society of Hematology recommends testing for PF4 antibodies ahead of treatment for vaccine-induced thrombotic thrombocytopenia, which it describes as an evolving disorder based on limited data.  After a 10-day pause on the use of the J&J vaccine in the U.S.—while the FDA and other agencies reviewed safety data, including the deaths of three recipients—a CDC advisory panel last week recommended restarting nationwide distribution. The shot, like AstraZeneca’s, will carry warnings about rare and severe blood clots and guidance for proper treatment. Both use adenovirus-based vectors to deliver the vaccine’s instructions into human cells.

Versiti's Press Release (April 27, 2021):

https://www.versiti.org/newsroom/news-releases/versiti-unveils-new-testing-options-for-vaccine-in 

Background: Several cases of unusual thrombotic events and thrombocytopenia have developed after vaccination with the recombinant adenoviral vector encoding the spike protein antigen of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (ChAdOx1 nCov-19, AstraZeneca). More data were needed on the pathogenesis of this unusual clotting disorder.

Methods: We assessed the clinical and laboratory features of 11 patients in Germany and Austria in whom thrombosis or thrombocytopenia had developed after vaccination with ChAdOx1 nCov-19. We used a standard enzyme-linked immunosorbent assay to detect platelet factor 4 (PF4)–heparin antibodies and a modified (PF4-enhanced) platelet-activation test to detect platelet-activating antibodies under various reaction conditions. Included in this testing were samples from patients who had blood samples referred for investigation of vaccine-associated thrombotic events, with 28 testing positive on a screening PF4–heparin immunoassay.

Results: Of the 11 original patients, 9 were women, with a median age of 36 years (range, 22 to 49). Beginning 5 to 16 days after vaccination, the patients presented with one or more thrombotic events, with the exception of 1 patient, who presented with fatal intracranial hemorrhage. Of the patients with one or more thrombotic events, 9 had cerebral venous thrombosis, 3 had splanchnic-vein thrombosis, 3 had pulmonary embolism, and 4 had other thromboses; of these patients, 6 died. Five patients had disseminated intravascular coagulation. None of the patients had received heparin before symptom onset. All 28 patients who tested positive for antibodies against PF4–heparin tested positive on the platelet-activation assay in the presence of PF4 independent of heparin. Platelet activation was inhibited by high levels of heparin, Fc receptor–blocking monoclonal antibody, and immune globulin (10 mg per milliliter). Additional studies with PF4 or PF4–heparin affinity purified antibodies in 2 patients confirmed PF4-dependent platelet activation.

Conclusions: Vaccination with ChAdOx1 nCov-19 can result in the rare development of immune thrombotic thrombocytopenia mediated by platelet-activating antibodies against PF4, which clinically mimics autoimmune heparin-induced thrombocytopenia. (Funded by the German Research Foundation.)

Published in NEJM (April 9, 2021):

https://doi.org/10.1056/NEJMoa2104840

See also in NEJM:

https://doi.org/10.1056/NEJMoa2104882