Sex: F
Vaccine: COVID19
Symptoms: Bradycardia, COVID-19, Ecchymosis, Epistaxis, Gastrointestinal haemorrhage
Clinical narrative: The patient presented with bleeding from multiple sites, including possible upper and lower gastrointestinal bleeds; bleeding along the urinary tract; Cardiopulmonary examination was significant for a bradycardic rate; SARS-CoV-2-associated immune thrombocytopenia (ITP); COVID-19; self-resolved epistaxis; skin examination demonstrated both petechiae and ecchymoses; skin examination demonstrated both petechiae and ecchymoses; thrombotic thrombocytopenia purpura; This case was detected in the medical literature. This spontaneous case was reported in the medical literature by a physician.  A 47-year-old female patient received BNT162b2 (BNT162B2), as dose 1, single (Batch/Lot number: unknown) for covid-19 immunisation. The patient's relevant medical history included: "migraines" (ongoing), notes: increased headaches; "lung cancer" (unspecified if ongoing), notes: She had lung cancer treated with surgical resection 2 decades prior to presentation.; "Tumor resection" (unspecified if ongoing), notes: She had lung cancer treated with surgical resection 2 decades prior to presentation. Concomitant medication(s) included: SUMATRIPTAN taken for migraine. The following information was reported: GASTROINTESTINAL HAEMORRHAGE (hospitalization, medically significant), outcome "unknown", described as "The patient presented with bleeding from multiple sites, including possible upper and lower gastrointestinal bleeds"; HAEMORRHAGE URINARY TRACT (medically significant), outcome "unknown", described as "bleeding along the urinary tract"; BRADYCARDIA (medically significant), outcome "unknown", described as "Cardiopulmonary examination was significant for a bradycardic rate"; IMMUNE THROMBOCYTOPENIA (medically significant), outcome "unknown", described as "SARS-CoV-2-associated immune thrombocytopenia (ITP)"; COVID-19 (non-serious), outcome "unknown"; EPISTAXIS (non-serious), outcome "recovered", described as "self-resolved epistaxis"; ECCHYMOSIS (non-serious), PETECHIAE (non-serious), outcome "unknown" and all described as "skin examination demonstrated both petechiae and ecchymoses"; THROMBOCYTOPENIC PURPURA (non-serious), outcome "unknown", described as "thrombotic thrombocytopenia purpura". The patient underwent the following laboratory tests and procedures: Heart rate: 58; Oxygen saturation: 97 %; Respiratory rate: 18; Skin test: petechiae. Therapeutic measures were taken as a result of gastrointestinal haemorrhage, haemorrhage urinary tract, covid-19.  Clinical course: The patient was referred to the emergency department (ED) due to bloody urine, dark tarry stools, red spots on her skin, and bruising throughout her body. Fourteen days prior to presentation, she began exhibiting intermittent fevers, headache, shortness of breath, and a dry cough, and she tested positive for SARS-CoV-2 (the virus that causes COVID-19 pneumonia). Over the 3 days prior to her ED presentation, she experienced a headache that was more intense than the headaches she had been having in the preceding 2 weeks. She reported episodes of both dark urine as well as bright red blood in her urine. In addition, she had multiple dark stools described as tar-like when asked. On the day of her ED presentation, the patient noted a red rash throughout her body. In addition, earlier in the day, she had a traumatic self-limited epistaxis. She denied any falls or head strikes, vision changes, focal weakness or numbness, shortness of breath, chest pain, abdominal pain, or peripheral swelling. The patient had anxiety and depression for which she was taking escitalopram, propranolol, and trazodone. In addition, she had a history of migraines, for which she was taking sumatriptan. She had lung cancer treated with surgical resection 2 decades prior to presentation. In the setting of recent COVID-19 infection and increased headaches, she was taking ibuprofen 800 mg three times most days for the last 2 weeks. She has no personal or family history of known coagulopathies or hematologic disorders. Approximately 1 week prior to being diagnosed with COVID-19, the patient received a SARS-Cov-2 mRNAbased vaccination (BNT162b2; Pfizer-BioNTech) for the first time. On arrival, the patient was normotensive and afebrile with a pulse of 58 beats/min, a respiratory rate of 18 breaths/min, and oxygen saturation of 97% breathing room air. She was well-appearing. Cardiopulmonary examination was significant for a bradycardic rate and regular rhythm without murmur, and breath sounds were clear to auscultation throughout all lung fields. Her abdomen was soft and nontender without organomegaly. Examination of the skin revealed scattered petechiae throughout the trunk, back, and extremities. There were areas of ecchymosis noted on her abdomen, chest, arms, and legs. Examination of the oropharynx demonstrated petechiae on the hard palate. On neurologic assessment, the patient was alert and oriented with a normal cranial nerve assessment. A complete motor, sensory, and gait assessment were also normal. Differential diagnosis: The patient presented with bleeding from multiple sites, including possible upper and lower gastrointestinal bleeds, bleeding along the urinary tract, and self-resolved epistaxis. Her skin examination demonstrated both petechiae and ecchymoses. These symptoms were in the context of both COVID-19 vaccination and subsequent infection. Author's differential diagnosis for the patient's bleeding symptoms and rash included acquired and congenital coagulopathies and infectious etiologies. Author considered thrombocytopenic disorders, including idiopathic, as well as SARS-CoV-2-associated immune thrombocytopenia (ITP) and thrombotic thrombocytopenia purpura. Recent administration of the SARS-CoV-2 vaccine raised suspicion for vaccine-induced immune thrombotic thrombocytopenia. The patient had not been exposed to heparin or other new medications, making heparin- or drug-induced thrombocytopenia unlikely. Acquired coagulopathies including acute hepatic failure in the setting of viral infection, vitamin deficiency, and disseminated intravascular coagulopathy were all considered. In the absence of diarrheal disease, hemolytic uremic syndrome associated with Escherichia coli infection was thought to be unlikely. Other viral infectious etiologies, such as hepatitis viruses and Epstein-Barr virus, were considered. Although endemic in that region, she had no known recent tick bites to suggest zoonotic disease like babesiosis or ehrlichiosis. She had not traveled to any region with risk of spotted fever transmission. Congenital coagulation factor deficiencies were deemed unlikely in the absence of familial history or prior bleeding complications in the patient. The patient's frequent use of nonsteroidal anti-inflammatory ibuprofen may have exacerbated or caused an upper gastrointestinal bleed. Given the clinical context, her hematuria was thought to be secondary to a primary hematologic process. Urinary tract infection and nephrolithiasis were considered less likely in the absence of typical symptoms. The patient had no chest pain or respiratory symptoms and was not tachycardic or hypoxic, lowering concerns for other thrombotic pathology such as acute myocardial infarction or pulmonary embolism. The change in the patient's headache raised concern for thrombotic and hemorrhagic pathology, including cerebral venous sinus thrombosis and intracranial hemorrhage, especially intraparenchymal hemorrhage in the setting of signs of bleeding and presumed coagulopathy. On arrival, the patient was hemodynamically stable and displayed no signs of ongoing bleeding that required emergent intervention prior to pursuing laboratory and imaging evaluation. Laboratory studies were notable for normal white blood cell count, a normocytic anemia with hemoglobin of 11.3 g/dL (reference range [RF] 11.6-16.5 g/dL) and mean corpuscle volume 94.3 fL (RF 80-100 fL). Platelet count was 1000/ uL (RF 150,000-450,000/ uL). Reticulocytes were measured at 1% (RF 0.7-2.5%). Blood smear did not reveal schistocytes. The prothrombin time was 12.2 s (RF 11.5-14.5 s), international normalized ratio was 0.9 (RF 0.9-1.1), and partial thromboplastin was 29.7 s (RF 23.8-36.6 s). The fibrinogen level was 430 mg/dL (RF 200-450 mg/dL), d -dimer was 1366 ng/mL (RF < 500 ng/mL), lactate dehydrogenase was 276 U/L (RF 135-225 U/L), folic acid was > 20 ng/mL (RF > 4 ng/mL), and vitamin B-12 level was 931 pg/mL (RF 232-1245 pg/mL). Electrocardiography revealed sinus bradycardia without evidence of heart block or ischemia and the high-sensitivity cardiac troponin was not elevated. Urinalysis revealed 3 + blood. A computed tomography (CT) scan of the brain was performed without evidence of bleeding and a CT venogram did not reveal any thrombosis. The patient was consented to receive blood products and the blood type and screen were obtained. Given the concern for ITP, hematology consultation was obtained. After discussion of the case and their bedside evaluation of the patient, the decision was made to treat for presumed ITP with dexamethasone 40 mg, as well as intravenous immunoglobulin (IVIG) 1 g/kg. Two units of platelets were transfused. Remainder of the patient's hospital course: After initiation of steroids, IVIG and 2 apheresis units of platelets in the ED, the platelet count rose from 1000/ uL to 6000/ uL. The patient was admitted to the hematology service, received dexamethasone 40 mg daily for 3 days, IVIG 1 g/kg daily for 2 days, and a total of 3 U transfused platelets. On the third hospital day, the patient's platelet count rose to 116,000/ uL and on follow-up after discharge 1 week after her ED presentation had reached a normal range at 252,000/ uL 1 week after presentation. Viral workup did not reveal infection other than the previously documented SARSCoV-2 infection. Testing for the anti-heparin PF4 antibodies, a proposed causative antibody in SARS-CoV-2 vaccine-induced immune thrombotic thrombocytopenia, was negative. During her hospitalization, the patient continued having headache and received i.v. magnesium and metoclopramide. Repeat neuroimaging with both CT and magnetic resonance imaging were negative for acute pathology, including hemorrhage and thrombosis.; Sender's Comments: Based on the information given in narrative, the causal relationship between the reported events  and the suspect drug BNT162B2 cannot be excluded. The impact of this report on the benefit/risk profile of the Pfizer drug 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.