Factor V Leiden and prothrombin gene G20210A mutation in children with venous thromboembolism

To determine whether factor V Leiden (FVL) and/or prothrombin gene G20210A mutation (PT20210A) are risk factors for venous thromboembolism (VTE) in Argentinean children. One hundred and thirty consecutive children with VTE were prospectively assisted at a single centre. Blood samples were available from 110 of them for detailed haematological analysis. The prevalence of both mutations was compared with a control group. The odds ratio for VTE was significantly increased in patients with FVL (OR 3.64; 95% CI: 1.14-11.6, p < 0.029) whereas odds ratio for VTE was not significantly increased in patients with PT20210A (OR 1.06; 95% CI: 0.24-4.73, p = 0.938). Combined disorders were found in 5 of the 10 children with the aforementioned mutations. In 21 children (19%) without these mutations other inherited and acquired disorders were detected. Our data show that FVL is a risk factor for VTE whereas PT20210A does not seem to be a risk factor in our paediatric population.     

Prothrombin G20210A and factor V Leiden polymorphisms in stroke

The molecular epidemiology of stroke is critically lacking in the developing world. We explored the relationships between genetics polymorphism and risk for ischemic stroke among the residents of Casablanca, Morocco. Ninety-one stroke patients matched 1:2 for their age, gender, and ethnic background to 182 healthy controls who were genotyped for the prothrombin G20210A mutation and factor V (FV) Leiden and were assessed for conventional risk factors for stroke. No significant association was found between prothrombin gene mutation with stroke (p = .054). Regarding stroke subtypes, significant relationships between patients with a large artery disease subtype of stroke and this mutation was found compared to controls (p = .046). As a genetic risk factor to develop this event, a strong association was observed when adjusted for conventional vascular risk factors (adjusted OR, 4.3; p = .029). No FV Leiden was found. We suggest that prothrombin mutation but not FV Leiden should be considered as a modest genetic risk factor for large artery disease stroke subtype in the Moroccan population.     

Factor V Leiden and prothrombin G20210A mutations in young adults with cryptogenic ischemic stroke

The association between factor V Leiden (FVL) and prothrombin G20210A (PT 20210) mutations and ischemic stroke remains controversial, particularly in young adults with cryptogenic stroke. Prevalence of FVL (4.1%) and PT 20210 (8.2%) mutations was assessed in 49 patients under 50 years with cryptogenic stroke and compared with controls. Odd ratio (OR) for cryptogenic stroke was 2.62 (95% CI, 0.49-13.95) for FVL and 3.75 (95% CI, 1.05-13.34) for PT 20210 and 3.28 (95% CI, 1,17-9.20) for some recognized genetic thrombophilic defect. Moreover, the OR for cryptogenic stroke in young women using oral contraceptives (OC) was 3.59 (95% CI, 1.28-10.5).When some genetic thrombophilic defect was associated with OC, the OR was much higher (OR: 14.27; 95% CI, 0.66-309.99). Our results suggest that in the Mediterranean populations the PT 20210 mutation, but not FV Leiden, is a risk factor for cryptogenic stroke in young adults. OC use is also a significant risk factor for cryptogenic stroke, which is increased in women with some genetic thrombotic risk factor.     

Obstetric complications and pregnancy-related venous thromboembolism: the effect of low-molecular-weight heparin on their prevention in carriers of factor V Leiden or prothrombin G20210A mutation

Whether the administration of low-molecular-weight heparin (LMWH) during pregnancy is effective in preventing obstetric complications and pregnancy-related venous thromboembolism (VTE) in women who are carriers of factor V Leiden (FVL) and/or prothrombin variant G20210A (PTm) is controversial. This observational study investigated the possible efficacy of pharmacological treatment with LMWH ± aspirin (ASA) in pregnancy outcomes in 1,011 pregnancies of 416 women with thrombophilia (FVL and/or PTm). Most patients were chosen on the basis of previous obstetrical complications (36%), or because of familial or personal history of venous/arterial thromboembolism (28% and 18%, respectively); 74 patients (18%) were incidentally identified. The outcome was evaluated according to the type of treatment and of the period of pregnancy when the treatment was started. After adjustment for observation before and after diagnosis of thrombophilia, previous miscarriages and VTE, parity, age and centre, we observed that LMWH had a protective effect on miscarriages (odds ratio [OR] 0.52, 95% confidence interval [CI] 0.29-0.94) and VTE (OR 0.05, 95% CI 0.01-0.21). ASA appeared to have no effect on the prevention of obstetric complications and VTE. A nested analysis performed in 116 women with two or more obstetric complications confirmed that the highest number of live births was recorded in the group under LMWH prophylaxis (OR 0.19, 95% CI 0.05-0.75). These results suggest that LMWH prophylaxis reduces the risk of obstetric complications in carriers of FVL and/or PTm, particularly in those with previous obstetric events. Furthermore, LMWH prophylaxis reduces the risk of pregnancy-related VTE.     

Clinical characteristics of patients with factor V Leiden or prothrombin G20210A and a first episode of venous thromboembolism. Findings from the RIETE Registry

Background

The clinical characteristics of patients with factor V Leiden or prothrombin G20210A presenting with a first episode of venous thromboembolism (VTE) have not been thoroughly studied.

Methods

RIETE is an ongoing registry of consecutive patients with acute VTE. We compared the clinical characteristics of patients with factor V Leiden, prothrombin G20210A, or no thrombophilia, at presentation with a first episode of VTE.

Results

As of May 2009, 22428 patients had been enrolled with a first episode of VTE. Of these, 345 had factor V Leiden, 261 had prothrombin G20210A, and 2399 tested negative. Sixty-two percent of the VTE episodes in women with factor V Leiden or prothrombin G20210A (40% in men) were associated with an acquired risk factor. Among women, pregnancy or contraceptive use accounted for 63% and 67% of such risk factors. Patients with factor V Leiden presented with pulmonary embolism (PE) less likely than those with prothrombin G20210A (31% vs. 51%; p < 0.001) or with negative testing (31% vs. 45%, p < 0.001). In addition, PE patients with Factor V Leiden presented with hypoxaemia (Sat O₂ levels < 90%) less likely than those with prothrombin G20210A (4.5% vs. 17%; p < 0.001) or with no thrombophilia (4.5% vs. 20%; p < 0.001).

Conclusions

Most VTE episodes in women (not men) with factor V Leiden or prothrombin G20210A were associated with an acquired risk factor (mostly pregnancy or contraceptive use). Only 4.5% of patients with factor V Leiden presenting with acute PE had hypoxaemia.     

Hyperhomocysteinemia and other newly recognized inherited coagulation disorders (factor V Leiden and prothrombin gene mutation) in patients with idiopathic cerebral vein thrombosis

BACKGROUND: Idiopathic cerebral vein thrombosis (iCVT) represents approximately 30% of the cases of cerebral vein thrombosis (CVT). New, inherited - factor V Leiden (FVL) and prothrombin gene mutation (PTHRA20210) - and inherited/acquired - hyperhomocysteinemia (HHcy) - prothrombotic conditions have been detected recently. METHODS: We assessed fasting plasma homocysteine (Hcy) levels and main Hcy determinants, FVL and PTHRA(20210) in 30 patients with documented iCVT and 40 age- and sex-matched healthy subjects. RESULTS: A strong and significant association of PTHRA(20210) [30% (9/30) vs. 2.5% (1/40) iCVT vs. controls, respectively, p = 0.001; OR = 16.174, p = 0.002] and HHcy [13/30 (43.3%) vs. 4/40 (10%) iCVT vs. controls, respectively; p = 0.002, OR = 6.88, p = 0.002] with iCVT was found. CONCLUSIONS: PTHRA(20210) and HHcy should be considered when screening for thrombophilia and should be assessed in patients with a family or personal history of CVT.     

Cerebral vein thrombosis and prothrombin gene (G20210A) mutation

Recently, prothrombin gene mutation G20210A has been associated with elevated thrombosis risk and rarely with cerebral vein thrombosis (CVT). Three patients are described who had this genetic predisposition and who developed CVT in an unusual constellation with other factors. In the first patient, the intake of valproic acid (VPA) may have played an aggravating role in the development of CVT; in the second patient diagnosis of coagulation disorder was made during pregnancy consultation 6 years after CVT; in the third patient the CVT occurred at the age of 78 years. In patients with CVT, coagulation-examinations should include tests for the prothrombin gene (G20210A) mutation.