Sheep anti Human Antithrombin polyclonal antibody [FITC]

Background: Acute unprovoked idiopathic fatal pulmonary embolism (IFPE) causes sudden death without an identifiable thrombogenic risk. We aimed to investigate the underlying genomic risks of IFPE through whole exome sequencing (WES). Methods: We reviewed 14 years of consecutive out-of-hospital fatal pulmonary embolism records (n = 1478) fromthe ethnically diverse population of New York City. We selected 68 qualifying IFPE cases for WES. We compared the WES data of IFPE cases to those of 9332 controls to determine if there is an excess of rare damaging variants in the genome using ethnicity-matched controls in collapsing analyses. Findings: We found nine of the 68 decedents (13.2%) who died of IFPE had at least one pathogenic or likely pathogenic variant in one of the three anti-coagulant genes: SERPINC1 (Antithrombin III), PROC, and PROS1. The odds ratio of developing IFPE as a variant carrier for SERPINC1 is 144.2 (95% CI, 26.3-779.4; P=1.7 x 10(-7)), for PROC is 85.6 (95% CI, 13.0-448.9; P= 2.0 x 10(-5)), and for PROS1 is 56.4 (95% CI, 5.3-351.1; P=0.001). The average age-at-death of anti-coagulant gene variant carriers is significantly younger than that of non-carriers (28.56 years versus 38.02 years; P = 0.01). Interpretation: This study showed the important role of severe thrombophilia due to natural anti-coagulant deficiency in IFPE. Evaluating severe thrombophilia in out-of-hospital fatal PE beyond IFPE is warranted. (C) 2017 The Authors. Published by Elsevier B.V.

Introduction: Antithrombin (AT) deficiency is associated with an increasing risk of thrombosis. Materials and methods: 15 unrelated patients with AT deficiency defined by thrombophilic assays were recruited and detailed clinical information about patients, focusing on the personal and family history of thromboembolism (TE), were recorded. Mutation analysis was performed by direct sequencing of an AT gene (SERPINC1) in the patients and their family members. Results: A total of 15 heterozygous causative mutations, each being identified in one family, were identified. Five mutations (33.3%) were reported here for the first time, including three null mutations (Ser36X, Lys70X and Try307X) and two missense mutations (Phe123Cys and Leu340Phe) probably impairing the structural integrity and stability of protein based on the AT structural analysis. Of the 15 patients, 33.3% (5/15) had additional risk factors and only one patient presented with additional genetic alteration causing an early onset of thrombosis. Fourteen patients (93.9%) suffered from multisite recurrent thrombotic episodes after a first episode of thrombosis. 93.3% of the patients experienced deep vein thrombosis (DVT) and 40.0% presented with mesenteric venous thrombosis (MVT). In addition, both venous and arterial thrombosis was present in two unrelated patients. 51.0% subjects with AT deficiency in the 15 unrelated pedigrees experienced TE events. Conclusions: Prophylactic anticoagulation may be suggested in AT-deficient patients to avoid the recurrent and multisite thrombosis. The association of primary MVT and AT deficiency is highlighted. (C) 2013 Elsevier Ltd. All rights reserved.