Primary immune thrombocytopenia (ITP) is a hematologic disorder characterized by isolated thrombocytopenia (platelet count of <100,000/uL) [1] without associated leukopenia or anemia [2] . Secondary ITP is defined as any form of ITP other than the primary kind. ITP is primarily a diagnosis of exclusion and newly diagnosed ITP usually refers to ITP diagnosed within the preceding three months. ITP is not a single disorder, but a syndrome in which thrombocytopenia may be primary or occur secondary to underlying infectious or immune processes. Vaccinations, especially the measles, mumps, and rubella (MMR) vaccine, have been implicated in the past as a possible trigger for its development [1] . Recently, a few case reports have shown a temporal relationship between receiving the coronavirus disease 2019 (COVID-19) vaccine and developing ITP of varying severity [3] .

A 54-year-old female presented with a three-week history of progressive and diffuse non-pruritic, painless, petechial rash on her lower extremities, chest, and abdomen. She reported increased mucosal bleeding and worsening ecchymosis.

The patient had received the first dose of the Pfizer COVID-19 vaccine (Pfizer, New York City, NY) one week before the onset of the rash and had received the second dose five days prior to this presentation. Routine outpatient laboratory evaluation revealed a platelet count of zero, prompting hospital admission. A review of systems was otherwise negative as the patient denied pain, pruritus, fevers, or new lymphadenopathy. Physical examination was pertinent for elevated blood pressure at 184/95 mmHg and diffuse petechiae and ecchymoses, mostly in the bilateral upper and lower extremities (Figures 1, 2). There was no hepatosplenomegaly noted on the exam.

Figure 1: Petechiae located in the left lower extremity

Figure 2: Ecchymosis of the left upper extremity

Her past medical history was significant for congenital epidermal dysplasia, hypertension, overactive bladder, mild cognitive impairment, chronic kidney disease, as well as anxiety. Her family history was insignificant except for colon cancer in her mother. The patient's home medications included amlodipine, lisinopril, pravastatin, baclofen, tizanidine, and sucralfate.

Initial laboratory findings showed a platelet count of 0/uL with an elevated D-dimer at 2.99 mg/L. Erythrocyte sedimentation rate (ESR) was elevated at 56 mm/hr, and the patient had mild transaminitis with alanine aminotransferase (ALT) of 56 U/L and aspartate aminotransferase (AST) of 45 U/L. Creatinine on presentation was 1.23 mg/dL with a baseline of 0.99 mg/dL.

CT of the head showed a right mastoid effusion with no acute intracranial hemorrhage. Serology was negative for hepatitis B virus, hepatitis C virus (HCV), Epstein-Barr virus, cytomegalovirus (CMV), or HIV infection. Additionally, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing was negative. Bone marrow biopsy revealed a hypercellular bone marrow with megakaryocytic hyperplasia. Lactate dehydrogenase (LDH) and haptoglobin were within normal limits. Flow cytometry detected no overt immunophenotypic abnormalities. Initial peripheral smear confirmed no visible platelets (Figure 3).

Figure 3: Initial peripheral smear demonstrating no visible platelets

Clinical course

Given that the patient's workup had been negative for secondary causes of thrombocytopenia, she was then started on dexamethasone as a treatment for presumptive ITP. Initial treatment consisted of three units of platelets and a 40-mg dose of IV dexamethasone with a good response. Her platelet count the following morning was 23,000/uL. An additional unit of platelets was given with further improvement in the count to 71k. Platelet counts continued to fluctuate as demonstrated in the graph below (Figure 3).

Figure 4: Graph demonstrating trends in platelet function during first and second hospitalizations

On the fifth day of hospitalization, platelet count remained low at 36,000/uL, and therapy was modified to include two doses of IV immunoglobulin (IVIG), followed by a two-day steroid taper. At the time of discharge, her platelet count was 135,000/uL. She was readmitted four days later for thrombocytopenia of 18k. She reported no additional complaints except for the emergence of new areas of ecchymosis on her forearms. At the second presentation, D-dimer and ESR/C-reactive protein (CRP) were again elevated. However, the direct Coombs test returned negative; fibrinogen, fibrinogen degradation products, haptoglobin, and LDH were within normal limits. Peripheral smear was without schistocytes, but immature platelet fraction was increased. Treatment consisted of four doses of dexamethasone with two days of IVIG treatment. During her second presentation, platelet transfusions were not administered. She was discharged four days later with a platelet count of 59k, and she has not been readmitted to date. Her laboratory test results over the course of her first and second presentation are summarized in Table 1.