Elucidating mechanisms of genetic cross-disease associations at the PROCR vascular disease locus.

Many individual genetic risk loci have been associated with multiple common human diseases. However, the molecular basis of this pleiotropy often remains unclear. We present an integrative approach to reveal the molecular mechanism underlying the PROCR locus, associated with lower coronary artery disease (CAD) risk but higher venous thromboembolism (VTE) risk.

Investigation of patients with unclassified bleeding disorder and abnormal thrombin generation for physiological coagulation inhibitors reveals multiple abnormalities and a subset of patients with increased tissue factor pathway inhibitor activity.

Introduction: We have routinely used thrombin generation to investigate patients with unclassified bleeding disorder (UBD).

Aims: To investigate haemostatic abnormalities in patients with UBD that had abnormal thrombin generation on at least one occasion.

Methods: Investigation of 13 known UBD patients with thrombin generation and detailed haemostatic testing was undertaken including TFPI assays but also thrombomodulin and fibrinogen-γ.

Hb Penang [β78(EF2)Leu→Pro, HBB: c.236T>C]: a Novel β-Globin Variant.

We report a novel hemoglobin (Hb) variant with a β chain amino acid substitution at codon 78 (CTG>CCG) (HBB: c.236T>C), detected through prenatal screening via capillary electrophoresis (CE) in an otherwise healthy and asymptomatic 38-year-old female of Southeast Asian ancestry. The variant, named Hb Penang after the proband's Malaysian city of origin, underwent further characterization through high performance liquid chromatography (HPLC), reversed phase HPLC, Sanger sequencing, isopropanol stability testing and isoelectric focusing (IEF).

Discovery and characterization of an antibody directed against exosite I of thrombin.

Unlabelled: ESSENTIALS: An IgA paraprotein with anti-thrombin activity was not associated with a severe bleeding phenotype. This observation challenges the paradigm that anticoagulant therapy necessarily increases bleeding risk. Characterization of the antibody showed that it specifically binds to thrombin exosite I.