Repository of Research and Investigative Information

Repository of Research and Investigative Information

Baqiyatallah University of Medical Sciences

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

(2020) Severe plasma prekallikrein deficiency: Clinical characteristics, novel KLKB1 mutations, and estimated prevalence. Journal of Thrombosis and Haemostasis. pp. 1598-1617. ISSN 1538-7933

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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 of mutations and relevant genetic variants. Results We assembled a cohort of 111 cases from 89 families and performed new genetic analyses in eight families (three unpublished). We identified new KLKB1 mutations, excluded the pathogenicity of some of the previously described ones, and estimated a prevalence of severe PK deficiency of 1/155 668 overall and 1/4725 among Africans. One individual reported with PK deficiency had, in fact, congenital kininogen deficiency associated with decreased PK activity. One quarter of individuals had factor XII clotting activity below the reference range. Four major bleeding events were described in 96 individuals, of which 3 were provoked, for a prevalence of 4 and an annualized rate of 0.1. The prevalence of cardiovascular events was 15 (6 65 years) for an annualized rate of 0.4. Conclusions We characterized the genetic background of severe PK deficiency, critically appraised mutations, and provided prevalence estimates. Our data on laboratory characteristics and clinical course of severe PK deficiency may have clinical implications.

Item Type: Article
Keywords: bleeding intrinsic pathway KLKB1 mutations prekallikrein deficiency thrombosis fletcher factor deficiency partial thromboplastin time molecular-weight kininogen factor-xii hereditary angioedema variant prekallikrein asymptomatic patient fitzgerald trait prolonged aptt pk deficiency Hematology Cardiovascular System & Cardiology
Page Range: pp. 1598-1617
Journal or Publication Title: Journal of Thrombosis and Haemostasis
Journal Index: ISI
Volume: 18
Number: 7
Identification Number:
ISSN: 1538-7933
Depositing User: مهندس مهدی شریفی

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