Date of Award


Document Type

Master Thesis

Degree Name

Masters of Science (Research)


Department of Biological Sciences

First Advisor

Dr. Seamus Fanning


Venous thrombosis occurs in about 1 per 1,000 individuals per year. It is a serious disorder and accounts for a significant number of hospital admissions and deaths annually. Thrombophilia describes the familial or acquired disorders of the haemostatic mechanism that predispose to thrombosis. Inherited thrombophilia can be defined as a genetically determined tendency to venous thromboembolism Mutations in genes that code for proteins involved directly (or indirectly) In blood coagulation have been associated with prothrombotic status. Laboratory investigations for thrombophilia include screening for deficiencies of antithrombin, protein C or protein S and testing for activated protein C resistance. Together these account for only 5-10% of individuals with thrombosis. The factor V Ledien allele and the prothrombin G20210A allele have been shown to be prevalent in 45% and 18% of patients respectively with a history of venous thrombosis. More recently the methylenetetrahydrofolate Reductase gene (MTHFR C677T) have been implicated as risk factors for thrombosis.

A test group comprised of Sixty nine individuals with deep vein thrombosis (DVT) and a Control group of 60 individuals with no history of thrombosis in the South East region of Ireland were assessed in this study. Polymerase chain reaction (PCR), site-directed mutagenesis (SDM) -PCR, and Restriction Fragment Length Polymorphism (RFLP) analysis were used to determine factor V Leiden, prothrombin G20210A and MTHFR C677T genotypes. Functional assays were used to measure antithrombin III levels and measure activated protein C resistance (APCR).


■ Screen a group of patients for mutations in genes that code for proteins involved directly or indirectly with blood coagulation that are reported to be associated with an Increase risk of thrombosis.

■ Develop and optimise laboratory protocols for the molecular diagnostic techniques including Polymerase Chain Reaction (PCR), Site Directed Mutagenesis and Restriction Fragment Length Polymorphism (RFLP) analysis.

■ Assess a suitable thrombophilia screen for the Department of Haematology at Waterford Regional Hospital on the basis of the data obtained in this study.

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