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A 39-year-old woman presents to her community hospital concerned about tiny blood spots that cover most of her body. She explains that she has had muscle aches and has been feeling fatigued for the past 2 days. She has no flu-like symptoms and her sense of taste and smell are normal.

The patient notes that 3 days previously, she received her second dose of Pfizer's mRNA COVID-19 at the same hospital.

Examination reveals that her heart rate is 109 bpm, blood pressure is 127/80 mm Hg, respiratory rate is 18 breaths/min, and temperature is 36.6°C; the petechiae are on her legs, abdomen, chest, and arms up to the base of her neck.

Blood results show:

• Platelet count: 1,000/μL (reference range is 150,000-400,000 /μL)

• Monocytes: 16.4% (reference range is 5.0-13.0)

• Other complete blood count (CDC) findings are within the normal range

• Erythrocyte sedimentation rate: 75 mm/h (reference range is 0.0-20.00 mm/h)

• Coagulation is normal

The patient's medical history includes being diagnosed with polycystic ovary syndrome, for which she took norgestimate-ethinyl estradiol. There is nothing unusual in her family or travel history, she has had no previous illnesses or known COVID-19 exposures, and she has no history of tobacco/alcohol/drug use.

Five months previously, a routine checkup that included a CBC and differential reported that all findings were within normal limits. She also tested negative for COVID-19 antibodies at that time.

The patient is not tested for COVID-19 upon presentation to the hospital now. A peripheral smear reveals profound, isolated thrombocytopenia consistent with immune thrombocytopenia (ITP) with no schistocytes, blasts, microspherocytes, or agglutination.

Ultrasound of the spleen returns normal results. Tests for viral hepatitis, HIV, and Helicobacter pylori are negative, as is an antinuclear antibody test. Results of the other tests are within normal range.

On the day of her admission, clinicians administer a transfusion of one unit of platelets and 1,000 mg of intravenous methylprednisolone. Six hours after beginning treatment, her platelet count has increased to 16,000/μL. By the next day, however, her platelets fall to 4,000/μL. She receives a second platelet transfusion and is started on IV immunoglobulin (IVIG).

On hospital days 2 and 3, she is given 70 mg of IVIG. The vaccination clinic clinicians, primary care team, and hematologist confer, and conclude that the ITP was probably related to her COVID-19 vaccination, and report the event on the Vaccine Adverse Event Reporting System.

Six days after receiving the vaccination, the patient has had no major hemorrhages. She is discharged, and her platelet count is 92,000/μL.

One day later, she is assessed by her primary care physician and her platelets are found to be further increased, to 243,000/μL. She recovers without complications, and follow-up tests show no evidence of antiplatelet antibodies (APAs) after her discharge and treatment.

Discussion

The clinicians presenting this of severe ITP in a patient with no risk factors for the condition 3 days after receiving her second COVID-19 vaccine state that their aim is to raise awareness of this potential new adverse effect, which has implications for post-vaccination monitoring.

Although the platelet-destroying immune response is a known complication of COVID-19 itself, with effects ranging from mild bruising to intracranial hemorrhage, it has only rarely been linked to other immunizations, particularly the flu vaccine and the measles, mumps, rubella vaccine in children. Such risk is , and cases that do occur are generally self-limiting and respond well to standard treatment, the authors note.

ITP is characterized by increased bleeding, commonly presenting with flat/non-palpable petechiae and mucosal hemorrhages, and in some patients, urogenital bleeding and increased menstrual bleeding. Many patients report exhaustion and fatigue, including depressive disorders. Some patients with ITP, however, may have no symptoms at all.

Because ITP is a diagnosis of exclusion, it is important to rule out other causes of isolated thrombocytopenia, the case authors emphasize. Typically, coagulation studies, testing for HIV, hepatitis C, and drug-induced thrombocytopenia, as well as a peripheral blood smear are considered in differential diagnosis.

This research suggests that bone marrow aspiration is rarely required, except for patients with an uncertain diagnosis, those not responding to standard therapies, and those whose blood smear shows evidence of abnormalities aside from thrombocytopenia. Measurement of platelet-associated antibodies is not helpful since such testing lacks both sensitivity and specificity.

The case authors note that their patient was tested for other causes of ITP, such as viral hepatitis, HIV, and H. pylori, with negative results. Furthermore, the team was able to rule out Evans syndrome, based on the patient's isolated thrombocytopenia on peripheral smear, normal reticulocyte count of 103 thousand/μL (reference range 44-106), lactate dehydrogenase level of 194 U/L (reference range 135.0-214.0), and bilirubin of 0.26 mg/dL (reference range 0.00-1.20).

As well, this patient had received age-appropriate cancer screening. She had not received any other vaccinations, started any new medications, or been ill in the months leading up to her ITP.

In addition, the authors explain, because she had not traveled, she was not tested for tropical illnesses that can cause thrombocytopenia. Along with the delay in testing the patient's APAs after she recovered, the main limitation in knowing for sure that her ITP was related to the COVID-19 vaccine is that the diagnosis of ITP is one of exclusion, the case authors note. "The patient was not tested for COVID-19, which can cause ITP. Causally linking the vaccine and ITP with certainty poses challenges ... and further investigations are required to determine the risk and frequency of this association."

Conclusion

Nevertheless the team concludes that ITP should be considered a severe adverse effect of the Pfizer mRNA COVID-19 vaccine, and that knowing the early signs and symptoms of ITP will become increasingly important as more of the world's population receives the vaccine. "Quick diagnosis and management are essential to avoid life-threatening bleeding," the authors caution.

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