Homozygous factor V Leiden and double heterozygosity for factor V Leiden and prothrombin mutation

Abstract

The most common forms of familial thrombophilia are factor V Leiden (FVL) and prothrombin mutation (PTM). Homozygous FVL and PTM have long been feared conditions thought to cause high rates of morbidity and mortality. To analyse clinical features in patients with homozygous FVL and PTM, as well as patients with double heterozygosity for FVL and PTM. All patients with homozygous FVL, PTM or double heterozygosity in the MATS database of 1465 consecutive unselected patients were analysed regarding age at inclusion venous thromboembolism (VTE), age at first thrombosis, recurrence, clinical course and acquired risk factors. We found 36 patients homozygous for FVL. Patients homozygous for FVL were younger than controls at group level (56 ± 18 vs. 63 ± 17, p < 0.02). Homozygous women were younger than female controls (50 ± 19 vs. 63 ± 18, p < 0.002). No difference was observed when comparing male subjects. Women were younger than men at inclusion thrombosis (50 ± 19 vs. 65 ± 14, p < 0.02) and at first thrombosis (47 ± 19 vs. 64 ± 14, p < 0.01). Deep venous thrombosis (DVT) was seen in 33 patients (92 %), 6 (17 %) had pulmonary embolism (PE) and 3 (8 %) had combined DVT and PE. PE was less frequent in homozygous FVL women compared to female controls (p < 0.03). VTE recurred in 3 subjects during the duration of the study. Odds ratio for VTE in homozygous FVL patients compared to controls was 13.9 (95 % CI 9.9-19.7). We found no subjects with homozygous PTM. Double heterozygosity for FVL and PTM was seen in 12 subjects. There was no difference in age at inclusion VTE between double heterozygotes and controls (59 ± 16 vs. 63 ± 17, ns.). DVT was seen in 92 % at inclusion, 8 % had PE. Mean age at first VTE was 52 ± 17 (27-82). Consecutive homozygous FVL patients had a higher age at first thrombosis than previously described. Homozygous females are affected at an earlier age than homozygous men and female controls. It seems that thrombi in homozygous FVL have a different pattern compared to controls i.e. more prone for thrombosis in the lower extremity. The odds ratio for thrombosis among homozygous FVL seems to be lower than previously described.

Transforming growth factor (TGF)-β levels and unprovoked recurrent venous thromboembolism

“…DNA mutations for factors II and V were analyzed by TaqMan allele discrimination using gene-specific assays for these two factors (Applied Biosystems, Life Technologies Corporation, Carlsbad, CA, USA) [18].…”

Thrombophilic risk of individuals with rare compound factor V Leiden and prothrombin G20210A polymorphisms: an international case series of 100 individuals

“…This is in contrast with the study by Saemundsson et al . where the mean age at first VTE was 64 yrs for men and 47 yrs for women with either homozygous FVL or double heterozygous FVL and PTM, possibly suggesting a higher thrombogenicity of the rare compound thrombophilias that we studied. However, this discrepancy may well be due to enrollment bias, leading to a younger study population in our study compared to the enrollment of consecutive, unselected VTE patients in the Saemundsson et al .…”

“…However, this discrepancy may well be due to enrollment bias, leading to a younger study population in our study compared to the enrollment of consecutive, unselected VTE patients in the Saemundsson et al . study.…”

“…and Friedline et al . found that around 46–48% of patients with heterozygous FVL, homozygous FVL or double heterozygous FVL and PTM polymorphisms had no known acquired risk factor at the time of first VTE.…”

Fingertips Ischemia, Nephroangiosclerosis, and Focal Segmental Glomerulosclerosis: Is Genetic Thrombophilia the Unique Explanation?

“…Prothrombin (PT) (G20210A) [2], methylenetetrahydrofolate reductase (MTHFR) (C677T) [1], and Factor V Leiden (G1691A) [3] are well-recognized genetic risk factors for venous thrombosis, while their role in patients with arterial thrombosis remains to be clarified. Factor V Leiden, PT G20210A, and MTHFR C677T polymorphisms increase the risk for myocardial infarction, ischemic stroke, and peripheral vascular disease, particularly among younger patients and women [4].…”