Safety of prothrombin complex concentrate in healthy subjects

Keywords: anticoagulants; prothrombin complex concentrate; thrombosis; reversal; meta-analysis; bleeding disorders

Survival and recurrent venous thromboembolism in patients with first proximal or isolated distal deep vein thrombosis and no pulmonary embolism

Essentials The long-term risk of recurrence and death after distal deep vein thrombosis (DVT) is uncertain. We included subjects with first proximal or isolated distal DVT (IDDVT) and no pulmonary embolism. The risk of symptomatic and asymptomatic recurrence is lower after IDDVT (vs. proximal). IDDVT may be associated with a lower long-term risk of death, especially after unprovoked DVT. SummaryBackground A few studies have focused on the risk of recurrence after first acute isolated distal deep vein thrombosis (IDDVT) compared with proximal DVT (PDVT), whereas the incremental risk of death has never been explored beyond the first 3 years after acute event. Methods Our single-center cohort …

c.451dupT in KLKB1 is common in Nigerians, confirming a higher prevalence of severe prekallikrein deficiency in Africans compared to Europeans

Essentials Prekallikrein (PK) deficiency is a recessive trait with isolated aPTT prolongation. KLKB1 c.451dupT is common in Nigerians (7/600 alleles) and absent in a European group (0/600). To date, all genotyped PK-deficient patients of African ancestry were homozygous for 451dupT. Diagnostics of isolated aPTT prolongation in African descendants should include PK testing. ABSTRACT: Background Severe prekallikrein deficiency (PK deficiency) is an autosomal-recessive condition thought to be very rare. Recently we reported that the previously unnoticed variant c.451dupT, p.Ser151Phefs*34 in KLKB1, which is listed in databases aggregating genome data, causes PK deficiency and is common in Afri…

Severe High Molecular Weight Kininogen (HK) Deficiency: Clinical Characteristics, Deficiency-Causing KNG1 Variants in Reported and New Cases, and Estimated Prevalence

Abstract Background: Severe high molecular weight kininogen (HK) deficiency is an autosomal recessive defect of the contact system caused by mutations in KNG1. Limited scientific interest in HK deficiency due to the rarity of the seemingly asymptomatic condition may increase, as HK, the precursor of bradykinin, is now discussed as a therapeutic target e.g. in hereditary angioedema. Aims: We provide a comprehensive analysis of the diagnostic, clinical, and genetic features of HK deficiency and estimate its frequency. Methods: We identified a new case of HK deficiency, systematically review the literature, conduct new genetic studies of reported cases, and comprehensively analyze the clinical…

The Evolution of Hemophilia Care: Clinical and Laboratory Advances, Opportunities, and Challenges

AbstractHemophilia A (HA) and B (HB) are X-linked bleeding disorders caused by mutations in the F8 or F9 gene that result in the absence, or reduced activity, of the corresponding clotting factor. The severity of bleeding and related complications is proportional to the amount of residual circulating functional factor. The development of a safe and effective hemophilia treatment lasted several decades and has been mainly based on clotting factor replacement. Advances in the engineering and manufacturing of clotting concentrates have led to the widespread availability of extended half-life products that reduced the number of intravenous infusions needed to achieve adequate trough levels. The…

Severe plasma prekallikrein deficiency : clinical characteristics, novel KLKB1 mutations, and estimated prevalence

BACKGROUND Severe plasma prekallikrein (PK) deficiency is an autosomal-recessive defect characterized by isolated activated partial thromboplastin time prolongation. To date, no comprehensive methodologically firm analysis has investigated the diagnostic, clinical, and genetic characteristics of PK deficiency, and its prevalence remains unknown. PATIENTS/METHODS We described new families with PK deficiency, retrieved clinical and laboratory information of cases systematically searched in the (gray) literature, and collected blood of these cases for complementary analyses. The Genome Aggregation Database (gnomAD) and the population-based Gutenberg Health Study served to study the prevalence …

Comment on “Worldwide Distribution of PK Deficiency: the Defect Seems Mainly Concentrated in West African Countries and the United States.”

Sex-specific differences in the distal versus proximal presenting location of acute deep vein thrombosis

Abstract Background and aims Women present with pulmonary embolism (PE) more often than men, while the opposite is true for proximal deep vein thrombosis (DVT). We investigated whether sex-specific differences exist in the presenting location of acute symptomatic DVT among patients without concomitant PE. Methods We tested our hypothesis in a meta-analysis of studies selected by systematically reviewing PubMed, Embase, and the grey literature. Thereafter, we analysed data of a single-center cohort including patients with first isolated acute DVT to assess the additional impact of age and provoking risk factors on the presenting location of DVT. Results We identified 7 studies for a total of…

Detection and Differential Diagnosis of Prekallikrein Deficiency: Genetic Study of New Families and Systematic Review of the Literature

Abstract Introduction. Prekallikrein (PK) and high-molecular-weight kininogen (HK) deficiencies are ultra-rare, autosomal-recessive defects of the contact system caused by biallelic mutations in the KLKB1 and KNG1 genes, respectively. Since affected subjects do not manifest a bleeding phenotype, a correct diagnosis is essential to prevent the administration of prohemostatic agents or plasma and to avoid delay of surgery. We describe a new case of PK deficiency identified at UMC Mainz. In addition, we performed a systematic review of the literature in order to i) collect blood material for genetic studies of reported PK deficient cases lacking this information, and ii) perform a comprehensiv…