Markers of activated coagulation in patients with factor V Leiden and/or G20210A prothrombin gene mutation.

The activated protein C (APC) resistance phenotype associated with an abnormal factor V Leiden (FVL), and the G20210A prothrombin gene mutation are the most common findings in patients with venous thromboembolism (VTE). In a group of 210 patients, we compared the levels of markers of coagulation activation in carriers of FVL (71 heterozygous, 30 homozygous), G20210A prothrombin mutation (88 heterozygous) or both mutations combined (21 heterozygous), in order to assess whether these markers allow identification of a group of patients with a higher risk of thrombosis; they were also compared to normal values. A total of 143 patients had a personal history of VTE and 67 were asymptomatic. None of them had other hereditary causes of thrombophilia or an antiphospholipid syndrome. None were currently treated with either anticoagulant or hormonal treatment. Pregnant women were excluded. No significant difference between the four groups of patients could be found in the levels of F1+2, TAT and DDI. Levels were all significantly higher than the control values (p<0.05). The levels of F1+2 and TAT were similar in patients with or without a history of VTE, regardless of the type of mutation. DDI levels were significantly higher in patients with a history of VTE than in asymptomatic subjects (443+/-248 vs. 333+/-222 ng/ml, p=0.02) but with only 57% sensitivity and specificity. In conclusion, our study confirms the hypercoagulable state found in mutation carriers and points out the inability of F1+2 and TAT assays to identify a group of subjects at higher risk of thrombosis, within carriers of genetic risk factors. Although the sensitivity and specificity of DDI assay are low, high DDI concentrations tend to be associated with the risk of VTE.

[Comparison of two groups of 22 women homozygous or heterozygous for factor V Leiden mutation]. / Comparaison de deux groupes de 22 femmes homozygotes ou hétérozygotes pour la mutation du facteur V Leiden.

Clinical characteristics of thrombophilia associated with heterozygous mutation of factor V are well characterized. In contrast, they are not well documented in homozygous subjects who are rare. Moreover, estroprogestative intake and pregnancy are important precipitating factors of venous thromboembolism in women with factor V mutation. In order to determine difference in clinical expression between homo and heterozygous subjects, two groups of 22 age matched women were compared. A modified technique for the diagnosis of activated protein C resistance has been used, and its great specificity and sensitivity has been confirmed. In these two small series of patients, a greater severity of clinical profile was not clearly evident. However, recurrences and thrombosis during pregnancy were more frequent in homozygous than in heterozygous women. However, the differences did not reach significance. Molecular markers of hypercoagulable states were not regularly increased even in homozygous untreated patients, but they were more often increased in untreated than in treated patients. In contrast, to other varieties of thrombophilia, homozygous mutation of factor V may be associated with a minor clinical severity suggesting the role of environmental factors and/or still unknown molecular alterations.

[Value of plasma D-dimer assays in the diagnosis of venous thromboembolism]. / Intérêt du dosage des D-dimères plasmatiques dans le diagnostic des accidents thrombo-emboliques veineux.

The diagnostic usefulness of measuring plasma D-dimers using the ELISA method and the latex agglutination test has been prospectively evaluated in 117 patients hospitalized for suspicion of acute venous thrombo-embolism (AVTE): pulmonary embolism was suspected in 80 patients and the remaining 37 had a suspicion of deep vein thrombosis of the lower limbs. The diagnosis of AVTE was confirmed in 50% of the patients, all of whom underwent gold standard invasive investigation i.e. pulmonary angiography and/or contrast venography. The sensitivity, specificity, negative predictive value and positive predictive value of a D-dimers plasma concentration exceeding 500 ng/ml for the diagnosis of AVTE were respectively 98, 58, 97 and 70% when using the ELISA method, and 86, 71, 84 and 75% when using the latex assay. In 47 patients whose lung scans yielded abnormalities of indeterminate probability of pulmonary embolism, the sensitivity of the ELISA method was very high (94%), but that of latex assay was low (67%). Our results demonstrate that measuring the plasma D-dimers by the latex assay should not be used in the diagnosis of AVTE. On the other hand, the ELISA method might be of great interest in the diagnostic strategy of AVTE, as a normal concentration of D-dimers rules out almost definitely the diagnosis of AVTE, and hence, spares from performing invasive investigations.