Sex: M
Vaccine: COVID19
Symptoms: ADAMTS13 activity assay, Activated partial thromboplastin time, Alanine aminotransferase, Antibody test, Aspartate aminotransferase
Clinical narrative: Thrombotic thrombocytopenic purpura; This is a literature report from the , 2021, DOI: 10.1007/s12185-021-03190-y entitled Thrombotic thrombocytopenic purpura: a new menace after COVID bnt162b2 vaccine.   A 69-year-old male with a known medical history of hypertension, chronic kidney disease, HIV on anti-retroviral therapy (ART), chronic hepatitis B, two prior episodes of deep vein thrombosis managed with daily oral warfarin, presented to the emergency department with primary complaints of severe fatigue and new onset of shortness of breath for past three days. The shortness of breath was progressive, limiting his ability to walk and even talk in complete sentences without stopping to catch his breath. He denied any inciting event. There was no association with fever, chills, night sweats, weight loss, headaches, vision changes, cough, sputum chest pain, abdominal pain, rash, bleeding, bruising, edema, focal weakness, or changes in bowel or urinary habits. The patient received a second dose of BNT162b2 mRNA vaccine one week before the onset of concerning symptoms. On examination, the patient was afebrile and hemodynamically stable with oxygen saturation of 96% at room air. The patient appeared frail and tired but in no apparent distress. A thorough examination was unremarkable with no neurological deficits. An initial baseline laboratory workup was sent (Laboratory results of the patient on presentation with component/reference range/labs 1 month prior to presentation/patient's labs at day 1 of presentation: WBC (4.50-10.90 K/uL): 4.7 and 8.25; HGB (14.0-18.0 g/dL): 15 and 9.3; HCT (42.0-52.0%): 46 and 29.5; MCV (78.0-95.0 fL): 92 and 89.4; Platelet count (130-400 K/uL): 374 and 22; Sodium (136-146 mmol/L): 138 and 139; Potassium (3.5-5.0 mmol/L): 4.2 and 4.1; Chloride (98-106 mmol/L): 101 and 102; CO2 (24-31 mmol/L): 25 and 26; BUN (8.0-23.0 mg/dL): 18 and 29.0; Creatinine (0.70-1.20 mg/dL): 1.98 and 2.01; Calcium (8.8-10.2 mg/dL): 9.1 and 9.0; Albumin (3.3-6.1 g/dL): 4.0 and 4.4; Total Protein (6.4-8.3 g/dL): 7.4 and 8.3; Total Bilirubin (0.0-1.2 mg/dL): 0.2 and 1.8; Alkaline Phosphatase (35-145 U/L): 23 and 110; ALT (SGPT) (0-41 U/L): 19 and 22; AST (SGOT) (10-50 U/L): 26 and 35), which revealed anemia, thrombocytopenia, and elevated bilirubin. Of note, patient had a normal hemoglobin and platelet count with no evidence of hemolysis on the labs prior to admission. Von Willebrand factor assay was not sent during the workup of TTP. The CD4 T-cell count of the patient was 354 with undetectable viral load, showing compliance of the patient to ART medications. Further blood workup (Table 2: Hematological parameters: Components/Reference Range/Presentation Day/Day 1*/Day 2*/Day 3*/Day 4*/Day 5*: Prothrombin Time (PT) 9.4-12.5 s/69.5/51.0/15.2/14.6/14.8/-; INR 0.8-1.2 ratio/ 6.0/4.3/1.3/1.2/1.2/-; Platelet's count 130-400 K/uL/22/19/61/133/164/199; activated partial; thromboplastin time (aPTT) 25-37 s/41/25/24/-/24/-/; Lactate Dehydrogenase (LDH) 135-225 U/L/1229/1333/652/394/316/262/d-Dimer 0-243 ng/mL 136/225/985/629/-/-/; Fibrinogen (200-393 mg/dL) 509/318/287/485/-/-/; Total Bilirubin 0.0-1.2 mg/dL 1.8/1.5/1.2/0.6/0.7/0.9) showed elevated reticulocyte count of 2.8% (Reference: 0.5-1%), elevated lactate dehydrogenase, low haptoglobin level of 10 (Reference: 50-220 mg/dL) and indirect bilirubin of 1.4 mg/dL. Peripheral smear was remarkable for normocytic, normochromic red blood cells with polychromasia, an ample number of spherocytes and schistocytes, along with a decreased number of platelets without any evidence of clumping. All these findings were consistent with the hemolytic phenomenon. Henceforth, a tentative diagnosis of Thrombotic Thrombocytopenic Purpura (TTP) was made. Of note, computed tomography of the chest with contrast was performed for pulmonary embolism concerns, which was normal. The PLASMIC score for estimating ADAMTS13 deficiency was seven, indicating a high risk of severe deficiency. An urgent decision was made to initiate plasma exchange therapy. Since the patient's HIV status is stable with a CD4 count above 200, the trigger of TTP was presumed to be recent vaccination. The patient received five plasmapheresis sessions along with daily trending of hematological profile. Pulse prednisone of 1 mg/kg (60 mg) IV was also given along the plasmapheresis sessions. ADAMTS13 activity was below 2% and anti-ADAMTS13 antibodies (titer>90 UI/ml) were detected, hence confirming acquired TTP. The platelet count was considerably improved by the fifth session. After that, the author started prednisone taper. The patient got discharged after the first dose of rituximab infusion and the next four doses scheduled in the out-patient infusion center. TTP is a rare disorder characterized by microangiopathic hemolytic anemia and thrombocytopenia, often with or without neurological or renal abnormalities with the complete pentad seen in only one-third of the patients. Generally, thrombocytopenia is attributed to infection, bone marrow suppression, lack of nutrition, genetic causes, or autoimmune processes, for instance, immune thrombotic thrombocytopenia, thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, or disseminated vascular coagulation however, the patient's characteristic symptoms and peripheral blood smear point to a very diagnosis of TTP. TTP is classified into two types: congenital and acquired. Congenital or primary TTP mainly occurs due to a mutation or autoantibodies directed to the ADAMTS13 gene. In contrast, acquired TTP is associated with autoimmune diseases, such as systemic lupus erythematosus and scleroderma, pregnancy, transplantation, neoplasms, or antineoplastic drugs. Vaccines, like infections, activate the defensive immunity of a person by mediating an immune response which could eventually trigger the development of an autoimmune disorder like immune thrombocytopenic purpura (ITP) or thrombotic thrombocytopenic purpura (TTP) or Guillain-Barre syndrome. Previous cases have been recorded in the medical literature giving rise to the terminology of vaccine-induced prothrombotic immune thrombocytopenia (VIPIT) or vaccine induced thrombosis with thrombocytopenia (VITT) which is a rare disorder that affects one individual in 1 million people around the world. Studies suggest a possible presence of vaccinal antigens against ADAMTS13 specific gene, responsible for creating a robust immune response. In the elderly population post-pneumococcal vaccination, cases of thrombocytopenic purpura have been registered with an indication of antigens present in the vaccine against the ADAMTS 13 gene. Antibodies against platelet-factor 4 (PF4) have been found in VIPIT like the heparin complexes formed in heparin-induced thrombocytopenic purpura, hinting at analogous immune mechanisms. However, being a novel disease, literature on the adverse effects of the SARSCoV2 (COVID-19) vaccination is still scarce. Reported women with co-morbidities in a similar age group as the patient presenting with similar symptoms within a month of administration of the Ad26.COV2.S and BNT162b2 mRNA vaccines respectively, indicating the presence of a possible diagnosis of VIPIT that was treated efficiently with plasmapheresis in both cases. Of note, in the latter case involving BNT162b2, the patient suffered from relapse precisely six days after the second dosage of COVID vaccine, just as in the case-although the patient never had TTP before. TTP is commonly treated with plasmapheresis, chemotherapeutics, for example, vincristine and corticosteroids with splenectomy kept as a last resort in case of refractory disease. Further studies are, however, needed to verify possible associations between microangiopathic, thrombocytopenic thrombotic disorders and the administration of vaccines against COVID-19, so the menace can be nipped in the bud before the presumptive rewarding efforts go in vain.; Sender's Comments: Based on available information and  plausible drug-event temporal association, a possibility contributory role of the suspect product BNT162B2 COVID Vaccine to the reported event cannot be ruled out. This case will be re-assessed should additional information becomes available.  The impact of this report on the benefit/risk profile of the product is evaluated as part of Pfizer procedures for safety evaluation, including the review and analysis of aggregate data for adverse events. Any safety concerns identified as part of this review, as well as any appropriate actions in response, will be promptly notified to Regulatory Authorities, Ethics Committees and Investigators, as appropriate.