Factor V Leiden: a genetic risk factor for thrombotic microangiopathy in patients with normal von Willebrand factor-cleaving protease activity. Blood 2002 Jan 15;99(2):437-42
Date
01/10/2002Pubmed ID
11781222DOI
10.1182/blood.v99.2.437Scopus ID
2-s2.0-0037079739 (requires institutional sign-in at Scopus site) 48 CitationsAbstract
Thrombotic microangiopathy (TM) is associated with abnormalities of von Willebrand factor-cleaving protease (VWCP) and other hemostatic factors. This study hypothesized that TM patients might have genetically determined thrombotic risk factors that predispose them to aberrant microvascular thrombosis. DNA samples from 30 white and 12 African American adult TM patients were analyzed for genetic alleles associated with vascular thrombosis, and plasma samples were analyzed for levels of VWCP activity. DNA was analyzed by using allele-specific polymerase chain reaction for factor V 1691A (Leiden), factor II 20 210A, methylenetetrahydrofolate reductase 667T, type 1 plasminogen activator inhibitor 4G/5G, and platelet GPIa 807T. Patients were segregated by race (white or African American) and plasma level of VWCP activity (normal or deficient). The prevalence of factor V Leiden was significantly increased among the white TM patients that had normal VWCP activity: 4 (36%) of 11 patients compared with 6 (3%) of 186 white control subjects possessed the factor V Leiden allele (P <.001; odds ratio, 17.1; 95% confidence interval, 5.4-54.0). No factor V Leiden alleles were detected in 19 white TM patients with intermediate or deficient levels of VWCP activity or in any of 12 African American patients. The prevalence of other thrombosis-associated alleles did not differ between TM patients and control subjects. These findings suggest that factor V Leiden may be a pathogenic risk factor in TM patients that have normal VWCP activity.
Author List
Raife TJ, Lentz SR, Atkinson BS, Vesely SK, Hessner MJAuthor
Martin J. Hessner PhD Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
3' Untranslated RegionsADAM Proteins
ADAMTS13 Protein
Activated Protein C Resistance
Alleles
Factor V
Gene Frequency
Genotype
Humans
Metalloendopeptidases
Methylenetetrahydrofolate Reductase (NADPH2)
Microcirculation
Oxidoreductases Acting on CH-NH Group Donors
Peripheral Vascular Diseases
Plasma Exchange
Polymerase Chain Reaction
Prevalence
Prothrombin
Recurrence
Risk Factors
Thrombophilia