Sex: F
Vaccine: COVID19
Symptoms: Hepatitis B surface antigen, Hepatitis C antibody, Hepatitis viral test, Immune thrombocytopenia, International normalised ratio
Clinical narrative: Immune thrombocytopenia; petechial rash; fatigue; muscle aches;   The case we present, of severe ITP after exposure to the BNT162b2 mRNA COVID-19 vaccine, is an important addition to the safety profile of this novel vaccine. A 39-year-old woman received the second dose of the BNT162b2 mRNA COVID-19 vaccine at a community hospital; 3 days later, she presented to the same institution with a petechial rash. Approximately 12 h after her vaccination, she had experienced fatigue and muscle aches. She did not have fever, cough, runny nose, a change in taste or smell, or any other associated symptoms. Her medical history included polycystic ovary syndrome, for which she took norgestimate- ethinyl estradiol. She had no pertinent family or travel history and no history of use of tobacco or alcohol or of substance abuse. The patient had a complete blood count (CBC) and differential 5 months before, during a routine health examination, which was entirely within normal limits. At that time, she also was tested for COVID-19 antibodies; the results were negative. The patient did not have any illnesses or known COVID-19 exposures before the incident reported here. On presentation, the patient had a heart rate of 109 bpm, blood pressure of 127/80 mm Hg, respiratory rate of 18 breaths/min, and a temperature of 36.6 degree Celsius. Physical examination revealed petechiae on her legs, abdomen, chest, and arms which extended to the base of her neck. A CBC revealed a platelet count of 1000/uL (Table 1). She had an elevated erythrocyte sedimentation rate of 75 mm/h and normal coagulation studies (Table 2). A peripheral smear showed profound, isolated thrombocytopenia that was consistent with immune thrombocytopenia (ITP) with no schistocytes, blasts, microspherocytes, or agglutination. An ultrasound of the spleen was normal. The patient was not tested for COVID-19. Tests for viral hepatitis, HIV, and Helicobacter pylori were negative. An antinuclear antibody test also was negative. The results of investigatory tests are summarized in Table 3. On the day of her admission, the patient received a transfusion of 1 unit of platelets and 1000 mg of i.v. methylprednisolone. Approximately 6 h after initial treatment, her platelet count improved to 16 000/uL. The following day, her platelets decreased to 4000/uL. She was treated with a second platelet transfusion and started on i.v. immunoglobulin (IVIG). On her second and third hospital days, she received 70 mg of IVIG. After discussion among the vaccination clinic, primary care team, and hematologist, the team determined that the most likely cause of the patient's ITP was vaccination. The event was then reported through the Vaccine Adverse Event Reporting System. After 3 days of hospitalization and approximately 6 days after vaccination, the patient was discharged with no major bleeding events. Her platelet count on discharge was 92 000/uL. When the patient followed up with her primary care physician the day after discharge, her platelets had further increased to 243 000/uL. Her recovery was uncomplicated. She tested negative for antiplatelet antibodies (APAs) after her discharge and treatment. This case highlights a potential consequence of the BNT162b2 mRNA COVID-19 vaccine that has implications for monitoring after vaccination. Considerations for other causes of ITP were viral hepatitis, HIV, and H. pylori. Tests for these conditions were negative. The isolated thrombocytopenia on peripheral smear and normal reticulocytes, lactate dehydrogenase, and bilirubin (Table 3) ruled out Evans syndrome. The patient was up to date on age-appropriate cancer screening. She had not received any other vaccinations or new medications, nor had she experienced any illness in the preceding months that may have caused the ITP. Her only medication was norgestimateethinyl estradiol. Given the geography and her lack of travel, she was not tested for tropical illnesses that can cause thrombocytopenia. The main limitation is that the diagnosis of ITP is one of exclusion. The patient was not tested for COVID-19, which can cause ITP. Another limitation is the delay in testing of APAs after her recovery. Causally linking the vaccine and ITP with certainty poses challenges. Because of the lack of medications or conditions that could have caused ITP in our patient, we feel that this outcome was most likely due to the BNT162b2 mRNA COVID-19 vaccine. The established relationship between ITP and COVID-19 and ITP and other immunizations further supports this hypothesis. We feel that this case provides insight into a potential new AE for which monitoring should be performed after vaccination. Further investigations are required to determine the risk and frequency of this association.  Table 1. Complete blood count and differential. Variable; Results; Reference range White blood cells (thousands/uL); 3.7; 4.5-10.5 Red blood cells (millions/uL); 4.79; 3.9-5.0 Hemoglobin (g/dL); 14.9; 12.0-15.5 Hematocrit (%); 45; 35-45 MCV (fL); 94.8; 80.0-100.0 MCH (pg); 31.1; 27-34 MCHC (g/dL); 32.8; 31.0-35.0 RDW (%); 12.4; 12.0-16.0 Platelets (thousands/uL); 1; 150-400 Neutrophils%; 40.8; 46-78 Lymphocytes%; 38.8; 20-45 Monocytes%; 16.4; 5.0-13.0 Eosinophils%; 2.4; 0.0-7.0 Basophils%; 1.1; 0.0-2.0 Immature granulocytes%; 0.5; 0.0-1.0 MCH - mean cell hemoglobin; MCHC - mean cell hemoglobin concentration; MCV - mean cell volume; RDW - red cell distribution width. Table 2. Hematology and coagulation studies. Variable; Results; Reference range Reticulocytes (thousand/uL); 103; 44-106 Haptoglobin (mg/dL); 144; 30-200 Fibrinogen (mg/dL); 229; 204-408 Erythrocyte sedimentation rate (mm/h); 75; 0.0-20.0 PT (s); 11.6; 10.3-13.5 INR; 1.0; PTT (s); 28.1; 26.6-38.2 INR - international normalized ratio; PT - prothrombin time; PTT - partial thromboplastin time. Table 3. Chemistry studies. Variable; Results; Reference range Random glucose (mg/dL); 142; 80-200 Sodium (mEq/L); 138; 136-145 Potassium (mEq/L); 4.7; 3.5-5.1 Chloride (mEq/L); 103; 98-107 Carbon dioxide (mEq/L); 22.5; 22.0-29.0 BUN (mg/dL); 8.00; 6.0-20.0 Creatinine (mg/dL); 0.6; 0.5-0.9 Calcium (mg/dL); 9.4; 8.6-10.2 Bilirubin-total (mg/dL); 0.26; 0.00-1.20 Alkaline phosphatase (U/L); 70.0; 35.0-104.0 Aspartate aminotransferase (U/L); 20.0; 0.0-31.0 Alanine aminotransferase (U/L); 12.0; 0.0-32.0 B12 (pg/mL); 319; 211-946 TSH (mIU/L); 1.70; 0.27-4.20 Lactate dehydrogenase (U/L); 194.00; 135.0-214.0 Hepatitis A virus antibody, IgM; Negative Hepatitis B virus core antibody, IgM; Negative Hepatitis B virus surface antigen; Negative Hepatitis C virus antibody; Negative Antinuclear antibody; Negative HIV-1,2 screen; Negative HIV-1 P24 antigen; Negative HIV-1 antibody; Negative HIV-2 antibody; Negative C-reactive protein (mg/dL); 0.37; 0.00-4.99 Heliobacter pylori breath test; Negative BUN - blood urea nitrogen; TSH - thyroid-stimulating hormone.; Sender's Comments: Based on the information currently provided (plausible time association), it cannot be fully excluded that the BNT162b2 might have played a contributory role in triggering the occurrence of Immune thrombocytopenia.   The impact of this report on the benefit/risk profile of the Pfizer product is evaluated as part of Pfizer procedures for safety evaluation, including the review and analysis of aggregate data for adverse events. Any safety concern identified as part of this review, as well as any appropriate action in response, will be promptly notified to Regulatory Authorities, Ethics Committees and Investigators, as appropriate.