One of the attractions of the Johnson & Johnson (J&J) vaccine throughout the pandemic has been the fact that it only requires a single shot, but now the CDC has explicitly recommended the mRNA vaccines over the J&J vaccine, mainly because of the risk of blood clots that can result after the J&J vaccine. We cover the essential points you and your patients need to know about the CDC’s new recommendations.

Until last week, the CDC did not preferentially recommend any Covid vaccine over another. However, after the CDC’s Advisory Committee on Immunization Practices voted 15 to 0 for the new guidance, the agency formally recommended that Americans get the Pfizer or Moderna mRNA vaccines instead of J&J unless J&J is the only one available. The CDC cited two reasons for the change: the mRNA vaccines appear more effective than the J&J one, and, even more importantly, the J&J vaccine has continued to cause cases of a rare blood clotting condition that comes along with an increase in platelets.

The condition, called thrombosis with thrombocytopenia syndrome (TTS), remains rare, occurring at different rates in different populations. The highest risk group in the CDC data was women aged 30 to 49, who experienced TTS at a rate of approximately 1 per 100,000 doses. Rates among men ranged from 1 in 250,000 doses in ages 40 to 49 or 1 in 500,000 doses for other age groups under 65. Although middle-aged women are at the highest risk for TTS after J&J vaccination, men and women in all age groups have experienced clots. The overall rate has been approximately 4 cases per 1 million doses.

However, with millions of people getting vaccinated, those numbers add up. The agency reported knowledge of 54 cases out of 17 million vaccinations, including 36 requiring intensive care. In addition, nine confirmed deaths from the blood clots caused by J&J vaccinations have also been confirmed. Since these are only the confirmed numbers, there have likely been other cases that have not been identified or reported.  

TTS is problematic because it involves blood clotting along with thrombocytopenia, which is counterintuitive. Typically, you would expect to see a higher platelet count in someone with clotting problems, but TTS is similar to heparin-induced thrombocytopenia (HIT), which means the most common first-line treatment for blood clots, heparin, is the worst treatment for TTS. In addition, if clinicians don’t adequately screen for a recent J&J vaccination before treating a suspected or confirmed blood clot, the condition could worsen if the patient receives heparin.

The American Society of Hematology provides an excellent overview of the diagnostic criteria, incidence, and treatment recommendations for TTS.  

Signs and Symptoms

The following symptoms, occurring 4 to 42 days after vaccination, indicate the need for urgent evaluation for TTS:

• Severe headache.

• Visual changes.

• Abdominal pain.

• Nausea and vomiting.

• Back pain.

• Shortness of breath.

• Leg pain or swelling.

• Petechiae, easy bruising, or bleeding.

Diagnosis

A TTS diagnosis requires all five of the following criteria:

• Covid vaccine four to 42 days before symptom onset.

• Any venous or arterial thrombosis (often cerebral or abdominal).

• Thrombocytopenia (platelet count < 150 x 109/L), though someone with a normal platelet count post-vaccination might be in the early stage of TTS and require ongoing monitoring.

• Positive PF4 “HIT” (heparin-induced thrombocytopenia) ELISA.

• Markedly elevated D-dimer (> four times the upper limit of normal).

Treatment

Treatment includes the following:

• Heparin should not be given to the patient until TTS has been ruled out or another plausible alternative diagnosis has been made.

• Work-up requires an immediate CBC with platelet count and peripheral smear, imaging for thrombosis based on signs and symptoms, a PF4-ELISA (HIT assay), and fibrinogen and D-dimer counts.

• Identification of thrombosis necessitates urgent consultation from a hematologist with expertise in hemostasis.

• Treatment should begin while awaiting PF4 ELISA results if a confirmed thrombosis exists and the patient has low platelets and/or a markedly elevated D-dimer.

• Therapy consists of intravenous immunoglobulin and non-heparin anticoagulation.

• If PF4 ELISA is negative, indicating no thrombocytopenia, the patient should receive standard treatment for typical venous thromboembolism.

• If the patient has thrombocytopenia and very high D-dimer but no confirmed thrombosis, especially if the patient has a headache, check PF4 ELISA and consider treatment.

• If the patient has thrombocytopenia but no confirmed thrombosis and a negative PF4 ELISA, the diagnosis is likely immune thrombocytopenic purpura (ITP).