To the Editor:
Recently, it was reported that a physician developed petechiae 3 days after receiving the Pfizer-BioNTech Covid-19 vaccine, was diagnosed with idiopathic thrombocytopenic purpura, and ultimately died of a cerebral hemorrhage.1 Here, we report a case of idiopathic thrombocytopenic purpura in a 72-year-old woman 1 day after receiving the first dose of the Moderna COVID-19 vaccine.
The day after receiving her vaccination, the patient woke up with a rash, spontaneous oral bleeding, and headache. She denied any history of easy bruising or abnormal bleeding. Her medical history included gout, type 2 diabetes mellitus, and seasonal contact dermatitis. She denied any new medications or changes to her allopurinol and sitagliptin within the last 5 years. She denied any family history of autoimmune disorders.
On examination, she had diffuse petechiae across her arms, legs, and abdomen and hemorrhagic bullae of the gingival mucosa. Laboratory tests were notable for an initial platelet count of 12,000/μL, decreasing to 1,000/μL within 12 hours of arrival. Other laboratory tests are as shown in Table 1 . Of note, normal prothrombin time, activated partial-thromboplastin time, d-dimer, and fibrinogen ruled out disseminated intravascular coagulation. Further, normal hemoglobin, haptoglobin, lactate dehydrogenase, and peripheral smear without schistocytes were inconsistent with hemolytic uremic syndrome or thrombotic thrombocytopenic purpura. Viral studies, including hepatitis A, B, and C, Epstein-Barr virus, HIV, cytomegalovirus, influenza A and B, and SARS-CoV-2, revealed no evidence of current or prior infection. Parvovirus IgG but not IgM antibodies were present, indicating prior resolved infection. Antinuclear antibody titers were undetectable, making rheumatic etiology less likely.
Table 1.
Clinical laboratory results.
| Measure | Reference Range | Hospital Day 1 | Hospital Day 3 | Hospital Day 5 | Hospital Day 8 |
|---|---|---|---|---|---|
| Hemoglobin (g/dL) | 12.0–16.0 | 13.3 | 12.2 | 10.8∗ | 11.1∗ |
| Hematocrit (%) | 37.0–47.0 | 41.2 | 36.3∗ | 33.9∗ | 34.5∗ |
| Platelet count (per μL) | 150,000–400,000 | 12,000∗ | 9,000∗ | 11,000∗ | 1,000∗ |
| White-cell count (per μL) | 4,800–10,800 | 5,320 | 5,360 | 3,020∗ | 3,300∗ |
| Mean corpuscular volume (fL) | 80.0–99.0 | 92.6 | 90.5 | 92.6 | 92.5 |
| Mean corpuscular hemoglobin (pg) | 27.0–31.0 | 29.9 | 30.4 | 29.5 | 29.8 |
| Mean corpuscular hemoglobin concentration (g/dL) | 29.8–35.2 | 32.3 | 33.6 | 31.9 | 32.2 |
| Red-cell distribution width (%) | 12.0–15.0 | 12.3 | 12.3 | 12.0 | 12.0 |
| Differential count (per μL) | |||||
| Neutrophils | 2,100–7,600 | 3,510 | 3,630 | 1600∗ | 2,350 |
| Lymphocytes | 1,000–4,900 | 1,260 | 1,160 | 980∗ | 580∗ |
| Monocytes | 100–1,100 | 410 | 480 | 350 | 290 |
| Eosinophils | 100–400 | 110 | 60∗ | 50∗ | 80∗ |
| Basophils | 0–200 | 2 | 1 | 2 | 1 |
| Sodium (mmol/L) | 136–145 | 140 | 141 | 138 | 137 |
| Potassium (mmol/L) | 3.5–5.1 | 3.7 | 4.1 | 3.9 | 3.8 |
| Chloride (mmol/L) | 98–108 | 100 | 104 | 104 | 101 |
| Carbon dioxide (mmol/L) | 22–29 | 26 | 25 | 28 | 28 |
| Urea nitrogen (mg/dL) | 6.0–23.0 | 14 | 19 | 21 | 16 |
| Creatinine (mg/dL) | 0.50–1.20 | 0.76 | 0.68 | 0.73 | 0.76 |
| Glucose (mg/dL) | 74–110 | 103 | 105 | 102 | 112∗ |
| Calcium (mg/dL) | 8.6–10.3 | 9.3 | 9.1 | 8.9 | 9 |
| Total protein (g/dL) | 6.6–8.7 | 7.2 | 6.4∗ | — | 8.2 |
| Albumin (g/dL) | 3.5–5.2 | 4.6 | 4.0 | — | 3.7 |
| Aspartate aminotransferase (U/L) | 5–32 | 21 | 16 | — | 18 |
| Alanine aminotransferase (U/L) | 0–33 | 13 | 10 | — | 12 |
| Alkaline phosphatase (U/L) | 35–104 | 98 | 82 | — | 73 |
| Total bilirubin (mg/dL) | 0.0–1.2 | 2.8† | 2.1† | — | 1.9† |
| Direct bilirubin (mg/dL) | 0.0–0.3 | 0.4 | 0.3 | — | 0.3 |
| Magnesium (mg/dL) | 1.6–2.6 | 2.1 | 2.1 | — | 2.1 |
| Phosphorus (mg/dL) | 2.5–4.5 | 3.4 | 2.6 | 3.9 | 2.8 |
| Prothrombin time (seconds) | 10.0–13.0 | 11.8 | — | — | — |
| International normalized ratio | 1 | — | — | — | |
| Activated partial-thromboplastin time (seconds) | 25.1–36.5 | 31.7 | — | — | — |
| Fibrinogen (mg/dL) | 200–393 | 359 | — | — | — |
| D-dimer (ng/mL DDU) | 0–243 | 216 | — | — | — |
| Iron (ng/μL) | 37–145 | 45 | — | — | — |
| Unsaturated iron-binding capacity (ng/μL) | 112.0–347.0 | 275.5 | — | — | — |
| Total iron-binding capacity (ng/μL) | 220–430 | 320 | — | — | — |
| Haptoglobin (mg/dL) | 34–200 | 106 | — | — | — |
| Central venous oxygen saturation (%) | 60.0–85.0 | 78.9 | — | — | — |
| Ionized calcium (mmol/L) | 1.16–1.32 | 1.22 | — | — | — |
| Lactic acid (mmol/L) | 0.6–1.4 | 1.5† | — | — | — |
| Thyroid stimulating hormone (mlU/L) | 0.27–4.20 | 1.29 | — | — | — |
| Vitamin B12 (pg/mL) | 211–946 | 299 | — | — | — |
| SARS-CoV-2 RNA | NA | Not detected | — | — | — |
| SARS-CoV-2 antibody index | <0.99 | 0.08 | — | — | — |
| Influenza A RNA | NA | Not detected | — | — | — |
| Influenza B RNA | NA | Not detected | — | — | — |
| Hepatitis A IgM antibodies | NA | Non-reactive | — | — | — |
| Hepatitis B surface antibody | NA | Reactive | — | — | — |
| Hepatitis B surface antigen | NA | Non-reactive | — | — | — |
| Hepatitis B core IgM antibody | NA | Non-reactive | — | — | — |
| Hepatitis C RNA | NA | Not detected | — | — | — |
| HIV 1,2 antigen and antibody assay | NA | Non-reactive | — | — | — |
| Cytomegalovirus PCR | NA | Not detected | — | — | — |
| Epstein-Barr virus PCR | NA | Not detected | — | — | — |
| Parvovirus B19 IgM antibodies | NA | Negative | — | — | — |
| Parvovirus B19 IgG antibodies | NA | Positive | — | — | — |
| H. pylori stool antigen | NA | Not detected | — | — | — |
| Antinuclear antibody | NA | Negative | — | — | — |
NA, not applicable; PCR, polymerase chain reaction.
The value in this patient was below normal.
The value in this patient was above normal.
The patient received an initial 40-mg intravenous dose of dexamethasone and additional doses of 20 mg/day for 3 days thereafter. Intravenous immunoglobulin, aminocaproic acid, and rituximab were administered, and she received multiple platelet transfusions. However, her platelets continued to fluctuate between 1,000/μL and 40,000/μL. Non-contrast computed tomography of the head was without evidence of intracranial bleeding. Her course was complicated by multiple episodes of melena.
Idiopathic thrombocytopenic purpura postvaccination has been reported in the measles, mumps, and rubella vaccine2 and has been associated with the use of attenuated vaccines and vaccine adjuvants, with one review identifying 45% of drug-induced idiopathic thrombocytopenic purpura occurring postvaccination.3 While hypersensitivity reactions are a known adverse event related to mRNA COVID-19 vaccines,4 this is, to our knowledge, the second known case of acute idiopathic thrombocytopenic purpura following administration.
Acknowledgments
Drs. Julian and Mathern are co-first authors and have contributed equally to this article.
Footnotes
Funding and support: By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article as per ICMJE conflict of interest guidelines (see www.icmje.org). The authors have stated that no such relationships exist.
References
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