A Look at Versiti’s Testing System for COVID-19 Vaccine-Induced Blood Clots

A Look at Versiti’s Testing System for COVID-19 Vaccine-Induced Blood Clots

Versiti, home of the Blood Research Institute, is offering comprehensive testing options for the accurate and timely diagnosis of the rare blood clots being seen in some people after vaccination with adenoviral vector-based COVID-19 vaccines.

Blood health and research organization Versiti Inc. is offering a comprehensive diagnostic for COVID-19 vaccine-induced blood clot testing to help in the accurate and prompt diagnosis of the rare but serious blood clots being seen after some individuals are vaccinated with viral vector COVID-19 vaccines such as those from AstraZeneca and Johnson & Johnson.

Versiti’s diagnostic tool is a targeted set of assays that can help clinicians readily detect the clotting issue, called vaccine-induced thrombotic thrombocytopenia (VITT), and identify individuals at high risk of developing the condition.

Xtalks spoke to some of the experts at Versiti, Ruchika Sharma, MD, associate medical director, Hematology; and Brian Curtis, PhD, senior director, Diagnostic Hematology, to learn more about the VITT diagnostic system.

The COVID-19 vaccine-induced blood clot testing system is a set of antibody tests that includes detection of platelet-activating autoantibodies implicated in the clotting phenomenon. The testing options were unveiled at the end of April this year.

“The goal is not to advertise a vaccine side effect. It is a very, very rare side effect of the vaccines among millions of vaccines that have been administered,” Dr. Sharma says. She says the goal is prompt diagnosis with appropriate and accurate testing, allowing for quick treatment.

In people that have experienced VITT, symptoms have appeared anywhere between three to 30 days post-vaccination. Symptoms include persistent and severe headaches; dizziness; blurred vision; chest, back or abdominal pain; shortness of breath; swelling and redness in a limb; and unusual bleeding or bruising, among others.

Related: US Regulators Recommend Pause on J&J’s COVID-19 Vaccine, But Just as a Precaution

While there have only been dozens of cases of VITT among the millions of vaccine doses administered globally, the severity of the clots is of concern, making timely diagnosis and treatment critical.

The clots associated with VITT are atypical, presenting in unusual locations in the body such as the abdomen and brain — the latter is known as the serious condition called cerebral venous sinus thrombosis (CVST). Moreover, these clots cannot be treated with conventional anticoagulants like heparin because they can lead to uncontrolled bleeding, making matters worse.

Blood clots are usually diagnosed through the D-dimer test that detects a fibrinogen protein fragment released during clot breakdown. It is typically used in the diagnosis of pulmonary embolus and deep vein thrombosis. It usually reveals the occurrence of a blood clot after it has happened.

In contrast, Versiti’s COVID-19 vaccine-induced blood clot testing tool may help in the early identification of clots, and individuals at high risk for them, through the detection of specific platelet autoantibodies which can trigger clot formation in conditions like VITT.

VITT has been found to present similarly to a condition called autoimmune heparin-induced thrombocytopenia (HIT). However, in VITT, vaccination is the trigger instead of heparin.

Antibodies against PF4 sometimes develop in individuals after exposure to heparin. These PF4 autoantibodies bind to PF4-heparin complexes on platelets to cause thrombocytopenia which often leads to venous and/or arterial thrombosis (blood clots). In VITT, the PF4 autoantibodies form in the absence of heparin.

Having testing options for HIT, Versiti was well-positioned to leverage a tool for VITT.

Versiti is one of the nation’s leaders in clinical blood testing and research and is home to the world-renowned Blood Research Institute.

Being involved in some of the nation’s top research in the field of hematology and blood disorders, Dr. Sharma explains how Versiti started getting calls from physicians for consultations and advice as they began to see the appearance of VITT after administration of the Johnson & Johnson COVID-19 vaccine in the US, which is the only approved adenoviral vector-based COVID-19 vaccine in the country.

While VITT has not been seen after administration of Pfizer or Moderna’s mRNA vaccines, rare cases of severe thrombocytopenia have been reported after their administration. These cases may also be related to the generation of platelet autoantibodies which may cause the severe thrombocytopenia that can lead to serious bleeding.

COVID-19 Vaccine-Induced Blood Clot Testing

Versiti’s COVID-19 vaccine-induced blood clot testing system includes an ELISA diagnostic for the platelet factor 4 (PF4)/heparin-dependent antibody, as well as additional HIT testing or serotonin release assays (SRA), depending on the initial result.

PF4 antibody testing is the focus because almost all the initial cases seen in the UK and US had a PF4-positive ELISA result, Dr. Curtis explains.

Some VITT cases also had positive serotonin release-assay (SRA) results, which is the gold standard test for HIT that detects platelet activation by measuring the release of endogenous serotonin induced by heparin.

Dr. Curtis has been involved in the development of HIT assays and along with Dr. Sharma, oversees labs at Versiti that are focused on immune platelet and neutrophil disorders, as well as bleeding and clotting disorders.

He explains this is how they became involved with the issue of VITT because “those tests are basically being repurposed for trying to help in diagnosing it.”

For VITT, the PF4 antibody ELISA is the first line of testing. While the test is highly sensitive, it can lack specificity. For this reason, the test is often followed by the SRA test for added specificity. In addition, there is also the newer flow cytometry-based PF4-dependent P-selectin expression assay (PEA), which is used in the diagnosis of HIT and has been shown to offer higher diagnostic accuracy than SRA, lending added sensitivity.

However, “The test that’s really important is the PF4 ELISA assay. All the [VITT] patients that have been reported in places like VAERS and some of the other adverse event reporting systems, have been positive in the test, so that’s the real key test,” Dr. Curtis says.

He also says it’s important to keep in mind that this is “a fluid situation, so we learn more each day about it. We’re trying to keep up with all the new information that comes out.”

The ELISA-based tests are available commercially and Versiti’s labs helped develop one of the first tests that is still sold by EMMI Corp today.

While hospitals and clinics can order the tests, Versiti has in-house testing labs where samples can be sent for testing.

“The idea is to get awareness out there, so we know what the best diagnostic modality is, and to aid our clinicians to best diagnose, promptly diagnose and aid in appropriate therapy, which we have guidelines for now by the American Society of Hematology (ASH) and the International Society of Thrombosis and Hemostasis (ISTH),” Dr. Sharma says.

Dr. Sharma explains how Versiti has had representation on ISTH’s platelet methodology subcommittee for many years now, and of which she is one of the co-chairs. She says together, the committee got together within 48 to 72 hours to quickly act on the issue, coming up with the diagnostic offering and testing recommendations to have a way to accurately diagnose patients and initiate therapy quickly.

The current treatment guidelines for VITT patients include treatment with intravenous immunoglobulin and non-heparin anticoagulation.

“We know how to manage them. Now we know how to treat them. That should reduce vaccine anxiety as opposed to increase it,” Dr. Sharma says.