Congenital prekallikrein deficiency
- 1 December 2010
- journal article
- review article
- Published by Taylor & Francis Ltd in Expert Review of Hematology
- Vol. 3 (6), 685-695
- https://doi.org/10.1586/ehm.10.69
Abstract
The congenital deficiency of prekallikrein (PK) is a rare condition in which there is a peculiar discrepancy between a severe in vitro defect and absence of bleeding. The gene controlling PK synthesis is located on chromosome 4 and consists of 14 exons and 15 introns. Only approximately 80 cases of PK deficiency have been described in the literature. Owing to the lack of bleeding, most cases go undetected or, if detected, go unreported. Occasional bleeding or thrombosis have been reported in a few patients but this was only due to the presence of associated risk factors. It is certain that the defect does not protect from thrombosis. Diagnosis is based on the presence of a great prolongation of partial thromboplastin time and normal prothrombin time and thrombin time. The long partial thromboplastin time is fully corrected by the addition of normal plasma or normal serum and presents the unusual feature of shortening on long incubation times. Platelet and vascular tests are normal. Immunological studies allow differentiation into two types, namely cases of true deficiency, which are approximately 70% of the total, and cases with abnormal forms. PK is a glycoprotein synthesized in the liver as a single-chain peptide of 88000 Da. It mostly circulates (∼75%) as a complex with high-molecular-weight kininogen. It is cleaved by FXIIa into a heavy chain and a light chain (catalytic domain), held together by disulfide bonds. Molecular biology techniques have so far only been applied to eleven families, and these studies do not yet allow definite phenotype/genotype conclusions. The exons involved are 5, 8, 11, 14 and 15. The noncoagulative effects of PK, mainly based on the effect of kallikrein, have been studied less, since they appear to be the result of the involvement of other components of the contact phase. Kallikrein can mainly affect the formation of bradykinin from high-molecular-weight kininogen and the activation of pro-urokinase to urokinase. Bradykinin causes inflammation, vasodilatation and an increase in vessel permeability. The activation of pro-urokinase results in enhanced fibrinolysis. However, fibrinolysis has been reported to be normal or defective in these patients.This publication has 68 references indexed in Scilit:
- Fletcher Factor Deficiency: Report of a New FamilyScandinavian Journal of Haematology, 2009
- Fletcher factor deficiency in a woman requiring emergency caesarean sectionJournal of Obstetrics and Gynaecology, 2009
- A Comparison of Activated Coagulation Time–Based Techniques for Anticoagulation During Cardiac Surgery With Cardiopulmonary BypassJournal of Cardiothoracic and Vascular Anesthesia, 2008
- A renaissance for the contact system in blood coagulation?Thrombosis and Haemostasis, 2008
- Severe prekallikrein (Fletcher factor) deficiency due to a compound heterozygosis (383Trp stop codon and Cys529Tyr)Thrombosis and Haemostasis, 2003
- Identification and Characterization of Prolylcarboxypeptidase as an Endothelial Cell Prekallikrein ActivatorPublished by Elsevier BV ,2002
- Genomic Structure of the Human Plasma Prekallikrein Gene, Identification of Allelic Variants, and Analysis in End-Stage Renal DiseaseGenomics, 2000
- Human plasma prekallikrein, a zymogen to a serine protease that contains four tandem repeatsBiochemistry, 1986
- Multiple cerebral thrombosis in fletcher factor (prekallikrein) deficiency: A case reportAmerican Journal of Hematology, 1985
- Heterogeneity of Human Prekallikrein Deficiency (Fletcher Trait)The New England Journal of Medicine, 1981