These results support a role for platelet turnover, factor V, and aAPCR in the thrombosis of ET as well as the association between JAK2 V617F allele burden and either decreased free PS or increased TF and soluble markers of platelet and endothelial activation.
In addition, mild and moderate hyperhomocysteinaemia and Factor V Leiden (FVL; Arg506Gln) have recently been identified as thrombotic risk factors.FVL. which renders resistance to activated Protein C, is the most common inherited genetic risk factor for thrombosis with a high allelic frequency amongst Caucasians.
The diagnosis of factor V Leiden thrombophilia is established in a proband by identification of a heterozygous or homozygous c.1691G>A variant (referred to as the factor V Leiden variant in <i>F5</i>, the gene encoding factor V) in conjunction with coagulation tests such as the APC resistance assay.
Hemostaseological function tests demonstrated a pathologic activated protein c resistance and PCR analysis a heterozygous defect of the factor V (Leiden).
This reduction in APC-R ratio was not explained by (1) the presence of the factor V Leiden, found in only one of 165 patients with SS disease including those tested for APC-R, or (2) the presence of lupus anticoagulants.
Laboratory tests revealed a pathologic activated protein C resistance and a reduced functional protein S. The underlying genetic defect was identified as a heterozygous coagulation factor V mutation.
A point mutation in coagulation factor V (factor V Leiden) results in resistance to activated protein C and probably represents the most common genetic risk factor for venous thrombosis.
The factor V Leiden (FVL) mutation, causing resistance to activated protein C, has recently been recognised as the most important genetic thrombophilia in the Western population.
Evidence against heterozygous coagulation factor V 1691 G-->A mutation with resistance to activated protein C being a risk factor for coronary artery disease and myocardial infarction.
In the 5 years that have elapsed since initial identification of these individuals, resistance to activated protein C (APC resistance), which is associated with the factor V Leiden gene mutation, has emerged as an important and highly prevalent inherited thrombophilic risk factor.
Activated protein C resistance was measured in all subjects and factor V Leiden genotype testing was performed in those individuals with phenotypic activated protein C resistance.
Congenital risk factors include deficiencies or defects in natural anticoagulants, such as antithrombin, Protein C and Protein S, and genetic polymorphisms such as prothrombin G20210A and cleavage-resistant forms of factor V (in particular factor V Leiden), that lead to a condition commonly known as activated protein C resistance.
High APC resistance was associated with breast cancer in both factor V Leiden non-carriers (OR 6.5, 95% CI 4.1-10.4) and carriers (OR 38.3, 95% CI 6.2-236.6).
In addition, a significantly increased frequency of APC resistance was found in patients who suffered from occlusion after reconstruction; 13 of 41 (32%) had the factor V Leiden gene mutation (P < .001), and 19 of 39 (49%) had an abnormal APC ratio (P < .001).
Subgroup analysis revealed significant associations between functional APCR and total early postoperative thrombotic complications and early graft failure, and between factor V (Leiden) and early cerebrovascular events and late graft thrombosis (p < 0.03).
Also, in comparison with patients with LDVT carrying GG genotype of FV gene 1691G>A polymorphism, the following activities reduced significantly: prothrombin time, activated partial thromboplastin time, fibrinogen, protein C, and protein S, while activated protein C resistance and lupus anticoagulant positive rate increased in patients carrying A allele (GA + AA).
In the thrombophilic cohort, the degree of activated protein C resistance (APCR), measured by a clotting time-based test, was associated significantly with the presence of 0 (n = 255; APCR = 2.59 +/- 0.26), 1 (n = 84; APCR = 1.61 +/- 0.13), or 2 (n = 5; APCR = 1.16 +/- 0.04) copies of the mutant factor V Leiden allele.
The level of antibodies to anionic phospholipids (PLa), a response to activated protein C (APC), and the presence for the mutation in the coagulation factor V gene causing APC resistance were studied.
Seventy women with thrombosis in pregnancy were investigated for the presence of APC resistance and the associated Arg506-Gln mutation in coagulation factor V. The mutation was found in 46% of the investigated women.