Resistance to activated protein C (APC) is the most prevalent inherited cause of venous thrombosis. The APC resistance phenotype is associated with a single point mutation in the factor V gene, changing Arg' in the APC cleavage site to a Gln. We have investigated 50 Swedish families with inherited APC resistance for this mutation and found it to be present in 47 of them. Perfect cosegregation between a low APC ratio and the presence of mutation was seen in 40 families. In seven families, the co-segregation was not perfect as 12 out of 57 APC-resistant family members were found to lack the mutation. Moreover, in three families with APC resistance, the factor V gene mutation was not found, suggesting another still unidentified cause of inherited APC resistance. Of 308 investigated families members, 146 were normal, 144 heterozygotes, and 18 homozygotes for the factor V gene mutation and there were significant differences in thrombosis-free survival curves between these groups. By age 33 yr, 8% of normals, 20% of heterozygotes, and 40% of homozygotes had had manifestation of venous thrombosis. (J. Clin. Invest. 1994. 94:2521-2524.) Key words: blood coagulation * thrombophilia -protein C * protein S * factor V recently discovered in a single family (2) and is already recognized as a major cause of venous thrombosis (3-6). Intact factor V was found to correct APC resistance (7) which together with close linkage between APC resistance and the factor V gene (8, 9), suggested the molecular defect to be located in the factor V gene. A single point mutation (G to A at position 1691) has been found in many APC-resistant individuals (8)(9)(10)(11). This mutation predicts replacement of Arg5 in the APC cleavage site of factor Va with a Gln, which results in APCresistant factor Va (8,12). The prevalence in the European population of APC resistance is between 3 and 7% (3, 5).Recently, our laboratory found intact factor V to function in synergy with protein S as cofactor to APC in a purified factor VIIIa degradation system ( 13 ). This suggests the possibility of thrombophilia being the result of other factor V gene mutations causing defects in the anticoagulant function of factor V, but as yet there are no such cases described.We have previously described a large number of families with inherited APC resistance (2-3, 9). To elucidate whether the Arg5 to Gln mutation was present in all of them, or if other genetic defects may also cause or contribute to the APC resistance, 308 individuals from 50 families with inherited resistance to activated protein C were investigated. The APC resistance was found to be associated with the same factor V gene mutation in 47 of the 50 families.
The constant challenge to restore sensory feedback in prosthetic hands has provided several research solutions, but virtually none has reached clinical fruition. A prosthetic hand with sensory feedback that closely imitates an intact hand and provides a natural feeling may induce the prosthetic hand to be included in the body image and also reinforces the control of the prosthesis. Areas covered: This review presents non-invasive sensory feedback systems such as mechanotactile, vibrotactile, electrotactile and combinational systems which combine the modalities; multi-haptic feedback. Invasive sensory feedback has been tried less, because of the inherent risk, but it has successfully shown to restore some afferent channels. In this review, invasive methods are also discussed, both extraneural and intraneural electrodes, such as cuff electrodes and transverse intrafascicular multichannel electrodes. The focus of the review is on non-invasive methods of providing sensory feedback to upper-limb amputees. Expert commentary: Invoking embodiment has shown to be of importance for the control of prosthesis and acceptance by the prosthetic wearers. It is a challenge to provide conscious feedback to cover the lost sensibility of a hand, not be overwhelming and confusing for the user, and to integrate technology within the constraint of a wearable prosthesis.
aortitis may contribute to the spectrum of aortic diseases, perhaps linking patients with Takayasu disease and the various subgroups of degenerative and genetically related TAAs. Epidemiology, Risk and Prognostic Factors in Mesenteric VenousThrombosis Acosta S, Alhadad A, Svensson P, et al. Br J Surg 2008;95:1245-1251 Conclusion: Mesenteric venous thrombosis (MVT) can be accurately diagnosed with portal venous-phase computed tomography (CT) scanning, and activated protein C resistance is associated with MVT.Summary: The authors used an inpatient and autopsy registry to identify patients at their hospital with MVT from 2000 to 2006. MVT was diagnosed in 51 patients. The diagnosis was made at autopsy in six patients. Patients aged 70 to 79 years had the highest incidence of MVT (11.3 per 100,000 person-years). Testing for activated protein C resistance was done in 29 patients, and 13 were positive. D-dimer levels were assessed in five patients, and all had elevated D-dimer. Multidetector row CT scans were done in the portal venous phase in 20 patients. The examination was positive in all 20 patients. There were 12 patients with surgery, with a median length of bowel resection of 0.6 m (range, 0.1-2.2 m). The 30-day mortality for the entire group was 20%. Increased mortality was associated with intestinal infarction (P ϭ .046), treatment on a nonsurgical ward (P ϭ .001), and lack of performance of CT scan (P ϭ .022). Long-term mortality was associated with presence of cancer, with a hazard ratio of 4.03 (95% CI, 1.03-15.85; P ϭ .046).Comment: MVT, at least symptomatic MVT, occurs infrequently. The diagnosis is difficult because symptoms are generally nonspecific. Mortality rates can be high. The authors' data are consistent with what one would suspect. CT scanning with a venous phase works well for diagnosis, and many of these patients will have a hypercoagulable state with, at least in this study, factor V Leiden mutation identified as the most prevalent abnormality. The study highlights the current standard of care for patients with possible MVT: a CT scan for diagnosis, anticoagulation for most patients, bowel resection for those with peritonitis, and an aggressive evaluation for hypercoagulable state with likely long-term anticoagulation. Long-term prognosis is largely related to the presence of malignancy.
SummaryResistance to activated protein C (APC) caused by the R506Q mutation in factor V is the most common inherited risk factor for venous thrombosis. To elucidate whether APC-resistance is a risk factor for venous thrombosis after elective total hip replacement, the association between APC-resistance (presence of FV:Q506 allele) and postoperative thrombosis was investigated in patients (n = 198) randomised to received short (during hospitalisation, n = 100) or prolonged prophylaxis (three weeks after hospitalisation, n = 98) with low molecular weight heparin (LMWH). Among APC-resistant individuals receiving short prophylaxis, 7/10 developed thrombosis as compared to 2/12 receiving long prophylaxis (p <0.0179). Odds ratio for association between APC-resistance and thrombosis in the short prophylaxis group was 4.2 (CI 95% 1.02-17.5) (p <0.0465). Among those receiving prolonged, prophylaxis, there was no increased incidence of thrombosis associated with APC-resistance. Two unexpected observations were made. One was that APC-resistance was much more common in women (19/109) than in men (3/89) (p <0.001). The other was that even women without APC-resistance were much more thrombosis-prone than men. Thus, 24/48 of women with normal FV genotype and short prophylaxis developed thrombosis vs 8/42 among men, p = 0.002. The increased risk of thrombosis associated with female gender and APC-resistance was neutralised by the prolonged treatment. In conclusion, among patients receiving short prophylaxis, female gender was found to be a strong risk factor for venous thrombosis. Even though APC-resistance appeared to be a risk factor for postoperative thrombosis, the uneven distribution of APC-resistance between men and women, taken together with the increased risk of thrombosis among women, precluded valid conclusions to be drawn about the association between APC-resistance and an increased risk of thrombosis. Our results suggest that prolonged prophylaxis with LMWH after hip surgery is more important for women than for men.
Abstract. Själander A, Jansson J-H, Bergqvist D, Eriksson H, Carlberg B, Svensson P (Sundsvall Hospital, Sundsvall; Skellefteå Hospital, Skellefteå; Uppsala University Hospital, Uppsala; Sahlgrenska University Hospital, Ö stra, Göteborg; Umeå University Hospital, Umeå; and Malmö University Hospital, Malmö; Sweden). Efficacy and safety of anticoagulant prophylaxis to prevent venous thromboembolism in acutely ill medical inpatients: a meta-analysis. J Intern Med 2008; 263: 52-60.Objectives. Venous thromboembolism (VTE) is a potentially serious complication of hospitalization and immobilization. The use of anticoagulant prophylaxis in acutely ill medical inpatients is still under debate. New data including a recent meta-analysis have recently been published. We aim at studying the efficacy and safety of anticoagulant prophylaxis in acutely ill medical inpatients, and demonstrate differences between meta-analyses due to different data extraction from the heterogeneous studies included.Subjects. The Cochrane Library, MEDLINE and EM-BASE were searched from 1980 to present. Manual searches were performed regarding abstracts from major meetings. Seven blinded randomized controlled clinical trials assessing the prophylactic effect of heparin in acutely ill medical patients were identified and included in the meta-analysis.Results. Low-molecular weight heparin (LMWH) prophylaxis prevented 48% of symptomatic pulmonary embolism (PE), 48% of symptomatic deep vein thrombosis (DVT) (not significant) and 51% of asymptomatic DVT. A nonsignificant trend towards higher bleeding risk during LMWH prophylaxis was found. Death was not significantly affected. We compared our data with a recent meta-analysis with different study selection and data extraction and found similar results.Conclusions. As DVT and PE are manifestations of the same illness, VTE, one can argue that anticoagulant prophylaxis prevents approximately half of the expected events. Most medical inpatients have short hospital stays, and a low risk of VTE. The important task for the clinician is to identify patients with a sufficiently high risk of symptomatic VTE to warrant LMWH prophylaxis. Despite differences in study selection and data extraction, our study shows results similar to a recent meta-analysis.
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