What can labs do to assess vaccine-induced blood clots with low platelets?

Vaccines from AstraZeneca and Janssen Pharmaceuticals are possibly associated with a risk of a rare and severe blood clot occurring with low platelets.

This is something labs should be prepared for – although the likelihood of being called on to assist in one of these cases is probably minimal.

The issue first arose in the United Kingdom earlier this year when health officials noted cases of the rare blood clots in people who had received the AstraZeneca vaccine (now known as Vaxzevria, which is not authorized for use in the United States). Both the Medicines and Healthcare products Regulatory Agency (MHRA) in the United Kingdom and the European Medicines Agency (EMA) reviewed the cases, decided the benefits of the vaccine outweighed the risks, and vaccinations continued.

The issue arose again this spring with the COVID-19 vaccine from Janssen Pharmaceuticals, a division of Johnson & Johnson. In this case, the U.S. Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention (CDC) recommended a pause in the use of the vaccine while the agencies weighed the evidence. The EMA followed a similar course. In these cases, the organizations also concluded that the benefits of the vaccine outweighed the risk, and the use of the Johnson & Johnson COVID-19 vaccine has resumed.

The cases in question involve severe blood clots that occur mostly at unusual sites, such as in veins in the brain (cerebral venous sinus thrombosis, CVST), the abdomen (splanchnic vein thrombosis), and in arteries. The cases are usually accompanied with low levels of blood platelets, or thrombocytopenia, according to the EMA.

The EMA also said one explanation for the combination of blood clots and low blood platelets could be an immune response, leading to a condition similar to one that happens sometimes in patients treated with heparin, called heparin induced thrombocytopenia (HIT).

When the FDA and CDC initiated the pause in the use of the Johnson & Johnson vaccine, they said they wanted time to warn providers about the potential for this serious side effect and the unique treatment required for the condition, also known as thrombosis-thrombocytopenia syndrome (TTS). The typical treatment for blood clots, an anticoagulation medicine, can make the situation worse – even deadly.

What should clinicians and laboratorians do if they suspect a case of blood clots combined with low platelets in a patient after the administration of Johnson & Johnson’s COVID-19 vaccine?

The CDC recommends that they obtain platelet counts and screen for evidence of immune thrombotic thrombocytopenia. They also should evaluate the patient with a screening PF4 enzyme-linked immunosorbent (ELISA) assay – just as they would for a suspected case of autoimmune HIT. If HIT testing is positive, or if it cannot be performed, the CDC recommends the use of non-heparin anticoagulants and high-dose intravenous immune globulin. The American Society of Hematology adds that tests to measure the levels of fibrinogen and D-dimer in blood also are indicated. And, of course, a hematologist should be involved from the beginning.

Some of the symptoms, which typically occur within 3 weeks of vaccination, include a severe headache, new neurological symptoms, abdominal pain, leg pain, back pain, and shortness of breath, the CDC said.

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