No abstract

SummaryThe risk of spontaneous or risk-period related venous thromboembolism in family members of symptomatic carriers of antithrombin (AT), protein C (PC) or protein S (PS) defects, as well as of the Factor V Leiden mutation is still undefined. We performed a retrospective cohort study in family members (n = 793) of unselected patients with a documented venous thromboembolism and one of these deficiencies to make an estimate of this risk. The annual incidences of total and spontaneous venous thromboembolic events in carriers of AT, PC or PS defects (n = 181) were 1.01% and 0.40%, respectively, as compared to 0.10% and 0.04% in non-carriers, respectively (relative risks both 10.6). In carriers of Factor V Leiden (n = 224), the annual incidences of total and spontaneous venous thromboembolism were 0.28% and 0.11%, respectively, as compared to 0.09% and 0.04% in non-carriers, respectively (relative risks 2.8 and 2.5). Additional risk factors (immobilisation, surgery and trauma; oral contraceptive use; and pregnancy/ post-partum) increased the risk of thrombosis in carriers of AT, PC and PS defects as compared to non-carriers (relative risks 8.3, 6.4 and 8.2, respectively). Oral contraceptive use and pregnancy/ post-partum period increased the risk of thrombosis in carriers of Factor V Leiden to 3.3-fold and 4.2-fold, respectively, whereas other risk factors had only a minor effect.These data lend some support to the practice of screening family members of symptomatic carriers of a AT, PC and PS deficiency. For family members of symptomatic carriers of Factor V Leiden, screening does not seem to be justified except for women in fertile age.

Although heparin-induced thrombocytopenia (HIT) is a known complication of intravenous unfractionated heparin (UFH), its incidence in medical patients treated with subcutaneous UFH is less well defined. To determine the incidence of HIT in this category of patients, the platelet count was performed at baseline and then every 3 ؎ 1 days in 598 consecutive patients admitted to 2 medical wards and treated with subcutaneous UFH for prophylactic (n ‫؍‬ 360) or therapeutic (n ‫؍‬ 238) indications. The diagnosis of HIT was accepted in the case of a platelet drop of 50% or more and either the demonstration of heparin-dependent antibodies or (when this search could not be performed) the combination of the following features: (1) the absence of any other obvious clinical explanation for thrombocytopenia, (2) the occurrence of thrombocytopenia at least 5 days after heparin start, and (3) either the normalization of the platelet count within 10 days after heparin discontinuation or the earlier patient's death due to an unexpected thromboembolic complication. HIT developed in 5 patients (0.8%; 95% CI, 0.1%-1.6%); all of them belonged to the subgroup of patients who received heparin for prophylactic indications. The prevalence of thromboembolic complications in patients with HIT (60%) was remarkably higher than that observed in the remaining 593 patients (3.5%), leading to an odds ratio of 40.8 (95% CI, 5.2-162.8). Although the frequency of HIT in hospitalized medical patients treated with subcutaneous heparin is lower than that observed in other clinical settings, this complication is associated with a similarly high rate of thromboembolic events.

In contrast with extensive documentation in patients treated with unfractionated heparin (UFH), the incidence of heparininduced thrombocytopenia (HIT) in medical patients receiving low-molecularweight heparin (LMWH) is less well defined. In a prospective cohort study, the platelet count was monitored in 1754 consecutive patients referred to 17 medical centers and treated with LMWH for prophylaxis or treatment of thromboembolic disorders. The diagnosis of HIT was accepted in case of a platelet drop of at least 50%, the absence of obvious explanations for thrombocytopenia, and the demonstration of heparin-dependent IgG antibodies. HIT developed in 14 patients (0.80%; 95% CI, 0.43%-1.34%), in all of them within the first 2 weeks, and was more frequent in patients who had (1.7%) than in those who had not (0.3%) been exposed to UFH or LMWH (OR ‫؍‬ 4.9; 95% CI, 1.5-15.7). The prevalence of thromboembolic complications in HIT patients (4 of 14; 28.6%) was remarkably higher than that (

Physical training increased pain-free and total walking distance in level 2 studies. Only level 3 studies support the usefulness of smoking cessation. In level 1 studies, pentoxifylline and nafronyl increased pain-free and total walking distance, but the average effects were relatively small.