Lupus Anticoagulunt Associated with Transient Severe Factor X Deficiency: A Report of Two Patients Presenting with Major Bleeding Complications

Abstract Acquired factor X (FX) deficiency is rare, but has been reported in diverse disease states, including systemic amyloidosis and respiratory infections. FX deficiency associated with lupus anticoagulant (LA) and a bleeding diathesis has not been previously reported. We report two patients both of whom presented with a severe bleeding diathesis after a preceding respiratory infection due to isolated FX deficiency associated with a LA. The FX deficiency and LA were transient. We conclude that patients with LA may rarely present with severe acquired FX deficiency. This may be another mechanism whereby patients with antiphospholipid antibodies present with bleeding complications

Case Report Monoclonal Gammopathy of Undetermined Significance (MGUS) in a Man with Fragile X-associated Tremor/Ataxia Syndrome

We report the clinical presentation and laboratory findings of a 69-year-old man with fragile X-associated tremor ataxia syndrome (FXTAS), a progressive neurodegenerative disorder, who was noted to have monoclonal gammopathy of undetermined significance (MGUS), a plasma cell proliferative disorder and a precursor disease of multiple myeloma. Both MGUS and FXTAS are associated with microRNA (miRNA) dysregulation. We speculate that individuals with FXTAS may be predisposed to MGUS and further studies are warranted regarding this association

Genetic diversity fuels gene discovery for tobacco and alcohol use

Tobacco and alcohol use are heritable behaviours associated with 15% and 5.3% of worldwide deaths, respectively, due largely to broad increased risk for disease and injury(1-4). These substances are used across the globe, yet genome-wide association studies have focused largely on individuals of European ancestries(5). Here we leveraged global genetic diversity across 3.4 million individuals from four major clines of global ancestry (approximately 21% non-European) to power the discovery and fine-mapping of genomic loci associated with tobacco and alcohol use, to inform function of these loci via ancestry-aware transcriptome-wide association studies, and to evaluate the genetic architecture and predictive power of polygenic risk within and across populations. We found that increases in sample size and genetic diversity improved locus identification and fine-mapping resolution, and that a large majority of the 3,823 associated variants (from 2,143 loci) showed consistent effect sizes across ancestry dimensions. However, polygenic risk scores developed in one ancestry performed poorly in others, highlighting the continued need to increase sample sizes of diverse ancestries to realize any potential benefit of polygenic prediction.Peer reviewe

Risk Factors for Thrombosis in Cancer Patients

Venous thromboembolism (VTE), comprised of deep vein thrombosis (DVT) and its complication, pulmonary embolism (PE), is a multifactorial disease, involving complex interactions between environmental exposures and patients, including their hemostatic system and genetic predispositions. VTE is relatively common, with an overall average age- and sex-adjusted incidence of about 1.04-1.9 per 1000 person-years that rises dramatically with increasing age [1-4]. Active malignancy accounts for almost 20% of incident VTE events occurring in the community [5], and imparts a 4- to 6.5-fold higher VTE risk compared to non-cancer patients, depending on concurrent use of anti-cancer therapy [6]. The risk of VTE also varies by cancer type and stage [7-10]. The association between VTE and malignancy has been recognized since 1861 when Trousseau, in a lecture, described thrombophlebitis as the presenting sign of visceral malignancy [11]