Sex: M
Vaccine: COVID19
Symptoms: Anti-platelet factor 4 antibody test, Deep vein thrombosis, Factor VIII activity test, Fibrin D dimer, Investigation
Clinical narrative: Idiopathic upper extremity deep venous thrombosis (DVT); This is a literature report.  A 17-year-old male patient received BNT162b2 (BNT162B2), as dose 2, single (Batch/Lot number: unknown) for covid-19 immunisation. The patient's relevant medical history and concomitant medications were not reported. Vaccination history included: Bnt162b2 (DOSE 1, SINGLE), for COVID-19 immunisation. The following information was reported: DEEP VEIN THROMBOSIS (hospitalization, medically significant, life threatening), outcome "recovered", described as "Idiopathic upper extremity deep venous thrombosis (DVT)". The patient was hospitalized for deep vein thrombosis (hospitalization duration: 5 day(s)). The Therapeutic measures were taken as a result of deep vein thrombosis.  Short Running Title: Thrombosis in Factor VII deficiency after COVID Vaccine. Background: Congenital factor VII (FVII) deficiency is a rare bleeding disorder with a heterogeneous clinical phenotype, ranging from asymptomatic to life-threatening bleeding. Paradoxically, literature reports that FVII deficiency may also present with both arterial and venous thrombotic events. These thrombotic events are usually associated with the presence of other prothrombotic risk-factors and the aggressive use of recombinant activated FVII (FVIIa). The exact mechanisms responsible for this association remain unclear. Severe thrombotic events have been described in the setting of COVID-19 infection and others occurring after administration of the SARS-COV-2 vaccine. Objective(s): Authors presented the case of an adolescent male with undiagnosed congenital FVII deficiency who presented with an idiopathic upper extremity deep venous thrombosis (DVT) following SARS-COV-2 vaccination. Design/Method: Case report. Result(s): A 17-year-old male patient water-polo player presented to the hospital for evaluation after developing significant fatigue and acute and severe generalized headache 8 days after his second Pfizer SARS-COV-2 vaccine dose. Initial brain MRI was negative, and he was started on an intravenous migraine cocktail, requiring multiple peripheral intravenous (PIV) line insertions. Neurological symptoms improved over a five-day hospitalization, and he was discharged home. On the discharge day, patient suddenly developed severe bilateral arm erythema and pain, at the sites of PIV lines. Symptoms were initially thought to be due to phlebitis and were managed with warm compresses and over-the-counter aspirin. Bilateral upper extremity Doppler ultrasounds were performed 10 days later as symptoms had worsened. Imaging revealed bilateral cephalic vein thromboses and a right axillary DVT. Laboratory studies, at that time, showed a platelet count at baseline (273 x 10 3/uL), mild leukocytosis (11.4x10 3/uL), negative anti-platelet factor 4 and a D-dimer of 0.3 ug/mL. SARS-CoV-2 antibody testing had positive IgG and negative IgM results. Thrombophilia work-up was also sent. Patient was started on rivaroxaban 15 mg PO, twice daily as acute DVT management. Regimen was subsequently changed to 20 mg PO daily. A thrombophilia workup was nondiagnostic. The patient's FVII activity level was found to be 0.44 U/mL, with a repeat of 0.34 U/mL (normal range for age 0.69 U/mL-2.0 U/mL). In light of these results, further questioning elicited a positive bleeding history within the family: menorrhagia was highly prevalent on patient's maternal side. Further work-up also revealed heterozygosity for the p.R353Q FVII gene variant. The patient completed 6 months of therapeutic anticoagulation with subsequent resolution of all thromboses. FVII genotyping results are currently pending. Brachial plexus MRI ruled out thoracic outlet syndrome. Conclusion: To authors knowledge, this is the first case reporting a patient with congenital FVII deficiency developing an acute DVT in association with the SARS-COV-2 vaccination. Despite the often-recognized increased bleeding risk in FVII deficient patients, case confirmed the need for considering FVII deficiency in the etiological assessment of patients presenting with acute thrombotic episodes. Further studies to elucidate the pathophysiology and the hemostatic impact that FVII deficiency might play in those patients receiving SARS-COV-2 vaccination or developing coronavirus-19 disease (COVID-19) acute infection are needed.; Sender's Comments: Based on the available information, the company considers that a causal relationship between "Idiopathic upper extremity deep venous thrombosis (DVT)" and BNT162b2 vaccination cannot be excluded due to plausible temporal association. 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.