Efficiency of systematic thrombophilia screening in idiopathic venous thrombosis: a prospective study in internal medicine.

In case of unprovoked venous thromboembolism (VTE), the screening of thrombophilia is recommended whatever the age of the patient and the type of risk factors (RF). This prospective study was conducted in patients with unprovoked VTE to detect some predictive factors to have a higher risk of thrombophilia, focusing on age, history of venous thromboembolism, and the existence of a triggering event. From July 2000 to July 2002, in an Internal Medicine Department, unrelated patients with unprovoked VTE were included. Those unprovoked thromboembolic events were defined by the absence of association between permanent and transient RF. The primary outcome measure was the positivity of the thrombophilia screening for any type of abnormality detected (deficit of protein C, S, antithrombin, presence of a lupus anticoagulant, research of V and II mutations). Seventy-four patients were included. Eight died during the follow-up. A higher risk of thrombophilia was found in patients younger than 40 (p=0.03), or with a family but not personal history of VTE (p=0.01) or with transient RF (p=0.02). The most frequent abnormality of coagulation found in patients younger than 40 was the presence of a lupus anticoagulant. As a new strategy for the screening of thrombophilia, one could propose the following attitude: only patients with transient RF or family history of VTE could undergo a complete screening; for all the remaining patients who are younger than 40, a research of a lupus anticoagulant would be only performed. This strategy should now be balanced against the currently recommended systematic attitude in further studies.

Efficacy of pentasaccharide on a prethrombosis model based on a calibrated stasis by the increase in up-stream venous pressure.

On a previous model using Wessler's principle in the rat, we have demonstrated that a partial ligature of the inferior vena cava leading to a 40% increase in up-stream venous pressure was thrombogenic only in association with the infusion of low dose of thromboplastin (90 microg/kg). In these thrombogenic conditions, the infusion of pentasaccharide (Arixtra, fondaparinux) should lead to a strong inhibition of thrombus formation. Therefore, we performed on five groups of 10 rats: stasis alone (group S) with a 40% increase in up-stream venous pressure; stasis and thromboplastin (group ST90); and stasis, thromboplastin and pentasaccharide (groups SPT50, SPT100 and SPT250) at three different dosages (50, 100 and 250 microg/kg). The efficacy of pentasaccharide was measured according to the variations in up-stream venous pressure, thrombus weight and thrombin-antithrombin complexes levels. Only 250 microl/kg pentasaccharide significantly reduced the thrombus weight in comparison with group ST90 (5 mg versus 23.8 mg, P = 0.01) but it was not sufficient to induce a return to the basic state (5 mg versus 0.2 mg in group S, P = 0.049). Thrombin-antithrombin complex levels measured at the end of the experiment were significantly reduced in comparison with group ST90 (16.7 versus 57.8 mg, P = 0.01) and were not statistically different from group S (16.1 versus 16.6 mg, P = 0.65). In conclusion, in a very borderline model toward thrombogenesis, pentasaccharide was able to reduce thrombus weight and abolished biological hypercoagulability.

[Rationalization of risk factors for venous thromboembolism in medical inpatients. A prospective study]. / Rationalisation des facteurs de risque de la maladie thrombo-embolique veineuse en milieu médical polyvalent hospitalier: une étude prospective.

BACKGROUND: In terms of preventive management of venous thromboembolism in medical inpatients, very large differences may be observed. Rationalization of behaviour requires the evaluation of simple and logical parameters, which takes into account both patient safety and economic considerations. AIM: The aim of this study was to evaluate a preventive scheme including the rationalization of the indications and the use of low molecular weight heparin. EXPERIMENTAL DESIGN: Epidemiologic investigation. SETTING AND PATIENTS: Patients hospitalized in five medical departments in the Hospital Center of Nantes, France. INTERVENTION: The risk of venous thromboembolism was rated as high, intermediate and low. Patients with high or intermediate risk were eligible for prevention therapy (table I). MEASURES: The main criterion was the occurrence during hospital stay of deep or superficial venous thrombosis of the lower limbs, pulmonary embolism, or unexplained sudden death. The screening was based on clinical features double-checked by venous doppler ultrasonography of the lower limbs and/or ventilation-perfusion lung scanning. RESULTS: 24,497 patients were eligible (table II), 15% were considered at risk and treated with Nadroparin, 6% had the same risk profile but were not treated and 14. 7% had low risk and no prevention. No bleeding event was reported. The incidence of venous thromboembolism was 0.75%, 1.7% and 0.14% respectively (p <0.01) (table III). This efficacy does not appear to depend on body weight or the existence of multiple risk factors observed (table IV and V). CONCLUSIONS: This analysis of risk factors separates two populations with rates of incidence dramatically and significantly different. The prevention of venous thromboembolism by fixed dose of low molecular weight heparin remains justified since it reduces the risk of venous thromboembolism by a factor of 2.5.

Coagulation activation in patients with an inflammatory syndrome: is there a link with acquired protein S deficiency?

The pathogenic mechanisms of thrombosis during inflammatory syndromes are unknown. The aim of our study was to evaluate coagulation activation and fibrinolysis and to study an acquired protein S deficiency in 58 patients with an inflammatory syndrome of neoplastic (16), infectious (24) or systemic (18) origin and in 54 control subjects. The results indicated that coagulation activation, demonstrated by an increase in the prothrombin fragment 1+2, was present in patients with an inflammatory syndrome regardless of its origin. Free protein S, the only functionally active protein, was not reduced even though C4b-binding protein was increased in inflammatory syndromes. Thus, a prothrombotic state was found in inflammatory syndromes but is not explained by an acquired protein S deficiency. All except five patients had normal plasminogen activator inhibitor-1 levels.

Screening for von Willebrand disease with a new analyzer using high shear stress: a study of 60 cases.

We have evaluated the performance of a new analyzer using high shear stress, the PFA-100 (Platelet Function Analyzer, Dade International, Massy, France), for screening of patients with von Willebrand disease (vWD). Whole citrated blood is aspirated through a capillary to the central aperture of a membrane coated with collagen and with a platelet agonist (either epinephrine or adenosine diphosphate [ADP]). The time required to obtain occlusion of the aperture by a platelet plug is defined as the closure time (CT). We studied 60 patients with different types of vWD and 96 normal subjects. Fourteen subjects with hemophilia and 15 patients with a platelet disorder were also analyzed. When omitting results from two patients with type 2N, the 58 other patients with type 1, type 2A, type 2B, type 3, or acquired vWD all exhibited an abnormal occlusion with collagen-ADP (sensitivity, 100%) and 56 of 58 had an abnormal CT with collagen-epinephrine (sensitivity, 96.5%). Only two patients with mild type 1 were not detected with collagen-epinephrine. In comparison, the bleeding time (BT) was normal in 20 patients: 17 with type 1, two with type 2A, and one with acquired vWD (sensitivity, 65.5%). The specificity of the PFA-100 was over 95% with both types of cartridges. Thus, the analyzer is well adapted to routine testing, as it has the advantages of simplicity and ease of execution, and demonstrates a high sensitivity, clearly superior to that of BT, for the screening of patients with vWD.