Sex: M
Vaccine: COVID19
Symptoms: Haemoglobin, Haptoglobin, Immune thrombocytopenia, International normalised ratio, Laboratory test
Clinical narrative: Developed bleeding from ITP 2 weeks after receiving the second dose of the Pfizer SARS-CoV-2 vaccine; This is a literature report for the following literature source(s):  A male patient in his 20's received BNT162b2 (BNT162B2), as dose number 2, single (Batch/Lot number: unknown) for covid-19 immunisation. The patient's relevant medical history included: "obesity" (unspecified if ongoing), notes: presented after a cat scratch to the right arm with persistent bleeding; "right arm with persistent bleeding" (unspecified if ongoing); "cat scratch" (unspecified if ongoing); "gum bleeding" (unspecified if ongoing), notes: over the past 1week. The patient's family history included: "refractory ITP" (unspecified if ongoing), notes: Family history is notable for refractory ITP in his mother. The patient's concomitant medications were not reported. Vaccination history included: Bnt162b2 (DOSE 1), for COVID-19 immunisation. The following information was reported: IMMUNE THROMBOCYTOPENIA (hospitalization, medically significant, life threatening), 2 weeks after the suspect product(s) administration, outcome "recovered", described as "Developed bleeding from ITP 2 weeks after receiving the second dose of the Pfizer SARS-CoV-2 vaccine". The patient underwent the following laboratory tests and procedures: ADAMTS13 activity assay: normal; ADAMTS13 activity assay (normal high range >=70): 90 %; Antibody test: Negative; Antinuclear antibody: Negative; Biopsy bone marrow: was performed and showed increased, notes: iron storage and hypocellular marrow; Blood fibrinogen (197-448): 284 mg/dl; Blood immunoglobulin A: Negative; Blood immunoglobulin G: Negative; Blood immunoglobulin M: Negative; Blood lactate dehydrogenase: normal; Blood lactic acid (0.5-2.2): 21.5 mmol/L; Blood smear test: showed absent platelets without, notes: schistocytes or blasts; Blood thromboplastin: normal; Blood thromboplastin (26.2-37.2): 30 seconds; Body mass index: 30.2, notes: Unit: kg/m2; DNA antibody (normal high range <=4): <1 IU/ml; Fibrin D dimer (normal high range <=500): 287 ng/ml; Haemoglobin: normal; Throughout hospitalisation, his haemoglobin, notes: was steadily trending down; Haemoglobin (12.6-16.7): 23 g/l; Haptoglobin: normal; International normalised ratio: 1.3; laboratory test: The patient met five out of nine diagnostic, notes: criteria for HLH including fever, splenomegaly, elevated ferritin, hypertriglyceridaemia, anaemia and thrombocytopenia; Occult blood: positive; Pathology test: revealed diffuse white pulp depletion, consistent, notes: with ITP; Physical examination: revealed a generalised petechial rash and, notes: bleeding from the scratch site; Platelet count: 1000 uL, notes: On the fourth day of hospitalisation, platelet count remained low; less than 1000, notes: On the 11th day of hospitalisation, the platelet count remained less than 1000uL despite daily steroid therapy; remained between 1000 and 2000; remained less than 1000, notes: On hospital day 25, despite being on steroids and ciclosporin, and the patient was restarted on IVIG for 8days; failed to improve beyond 2000-7000, notes: Ultimately, ciclosporin and romiplostim were discontinued, platelet counts failed to improve beyond 2000-7000uL, and the patient underwent an elective splenectomy on hospital day 40; 300000 uL, notes: Platelet counts began to slowly improve and eventually reached 300000uL 16 days after the splenectomy; Platelet count (139000-361000): less than 1000; Platelet count: remained low, notes: and romiplostim was restarted on hospital day 31; Prothrombin time (9.5-13.3): 14.9 seconds, notes: elevated; Reticulocyte percentage (0.50-2.20): 2.49 %, notes: increased; Serology negative: negative; Serum ferritin: normal; elevated; Vital signs measurement: normal; White blood cell count: normal. Therapeutic measures were taken as a result of immune thrombocytopenia. Clinical course: He received three units of platelets without significant elevation in platelet count. The patient was suspected to have ITP and was started on high-dose intravenous steroids and IVIG for 2 days. On the fourth day of hospitalisation, platelet count remained low at 1000 µL and the patient was started on weekly rituximab, an immunosuppressive agent. A bone marrow biopsy was performed and showed increased iron storage and hypocellular marrow. On the 11th day of hospitalisation, the platelet count remained less than 1000 µL despite daily steroid therapy. The patient was started on daily eltrombopag, a thrombopoietin receptor agonist, and received a second dose of rituximab. Throughout hospitalisation, his haemoglobin was steadily trending down. On the 15th day of hospitalisation, the patient became encephalopathic requiring intubation for airway protection and transfer to the intensive care unit. Haemoglobin was found to be 23 g/L (12.616.7 g/dL) despite receiving a total of four units of packed red blood cells in the previous days, and massive transfusion protocol was initiated. Faecal occult blood test was positive and gastroenterology was consulted for suspected gastrointestinal bleed. However, endoscopy could not be performed as platelet counts remained between 1000 and 2000 µL. The patient required vasopressor support and bicarbonate infusion for severe metabolic acidosis with a lactate of 21.5 mmol/L (0.52.2 mmol/L) secondary to suspected haemorrhagic shock. Eltrombopag was discontinued and the patient was started on romiplostim, another bone marrow stimulating agent. On the 16th day of hospitalisation, the patient was started on plasmapheresis for a total of 5 days for persistent thrombocytopenia although the suspicion for thrombotic thrombocytopenic purpura was low and ADAMTS13 was normal. The patient was extubated after 9 days. At this point, there was concern that the patient may have haemophagocytic lymphohistiocytosis (HLH) as he failed to respond to multiple ITP treatments. The patient met five out of nine diagnostic criteria for HLH including fever, splenomegaly, elevated ferritin, hypertriglyceridaemia, anaemia and thrombocytopenia. Romiplostim was discontinued and the patient was started on ciclosporin, an immunosuppressive agent, for possible HLH. On hospital day 25, the platelet counts remained less than 1000 µL despite being on steroids and ciclosporin, and the patient was restarted on IVIG for 8 days. The platelet counts remained low and romiplostim was restarted on hospital day 31. Ultimately, ciclosporin and romiplostim were discontinued, platelet counts failed to improve beyond 20007000 µL, and the patient underwent an elective splenectomy on hospital day 40. Spleen pathology revealed diffuse white pulp depletion, consistent with ITP. Platelet counts began to slowly improve and eventually reached 300 000 µL 16 days after the splenectomy. The patient was discharged to inpatient rehab on a steroid taper. Throughout his hospital stay, the patient received a total of 77 units of platelets. Follow-up attempts are completed. No further information is expected.; Sender's Comments: Based on the information provided, the event of Immune thrombocytopenia is assessed as possibly related to the suspect drug BNT162B2 based on temporal association, but consider also possible contributory effects from patient's medical history including familial history notable for refractory ITP from his mother.  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.