Biomedical subjects
Publications and source records attributed to J Emmerich.
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We analyzed the clinical features of 36 patients homozygous for the Arg 506 to Gln factor V mutation and found a circumstantial event at risk for thrombosis in 29 of the 31 patients with thrombosis. The most frequent predisposing factors were the post-partum period and the use of oral contraceptives in women, and surgery in both sexes. Venous thrombosis recurred in 48% of the patients. One patient had a myocardial infarction at age 33 years, and also had an antiphospholipid syndrome. Homozygous Gln 506 mutation leads to far less severe thrombotic complications than homozygous protein C and protein S deficiencies and does not seem to predispose patients to arterial thrombosis.
There is no consensus about the investigations which should be performed to detect occult malignancy after an episode of venous thromboembolism. The authors studied 204 patients (167 in-patients and 37 day hospital patients) with deep venous thrombosis or pulmonary embolism to determine the incidence of cancers detected during or after the thrombosis and the diagnostic value of abdomino-pelvic ultrasonography. Of the 167 in-patients, 18 (10.7%) had a known malignancy. After the initial investigations, 7 tumours were detected (4.6%). In all cases, clinical history and examination or chest X-ray were suggestive of neoplasia. Abdomino-pelvic ultrasonography did not detect any cases of occult malignancy. Of the 37 patients seen in the day hospital, only one had known malignant disease and no other cases were detected. After exclusion of the 26 patients with known malignancies or tumours discovered after the initial investigations, the remaining 178 patients were followed up for an average of 27 months. Four cancers (2.5%) were detected in this period. The authors conclude that the occurrence of deep venous thrombosis should lead to investigation for malignant disease: clinical examination, chest X-ray and laboratory tests are sufficient to orientate this investigation. Systematic abdominopelvic ultrasonography does not seem to be worthwhile in this indication.
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Seven healthy physically active nonsmoking men, aged 22.4 +/- (SD) 1.8 years performed two 6 min bouts of cycling at 40% VO2max (sub-lactate threshold/low power output exercise) and 87% VO2max (supra-lactate threshold/high power output exercise) at 70 rev.min-1, separated by 20 minutes rest, on two occasions: once as a control experiment (test C) and on a different day at approximately 1.5 h after ingestion of 250 mg (3 mmol).(kg body weight)-1 of NaHCO3 (test A). At the onset of low and high power output exercise performed after ingestion of NaHCO3, antecubital venous blood pH and HCO3- were significantly elevated (p < 0.05). Moreover, blood pH and HCO3-, tested at every minute of low and high power output exercise, was significantly higher (p < 0.05) in test A than in test C. No difference was found in plasma lactate concentration [La]pl during low power output exercise between A and C tests. In the terminal phase of the high power output exercise (87% VO2max) the level of [La]pl rose more rapidly in test A than in test C, reaching in the sixth minute of cycling 8.27 +/- 1.11 and 6.76 +/- 0.68 mmol.l-1 (p < 0.01) in test A and C, respectively. No significant differences were found in the rate of VO2 measured breath-by-breath between A and C tests, both during low and high power output exercise. The slow component of VO2 kinetics (expressed by difference between VO2 measured at the 6th minute of exercise minus the VO2 reached at the 3rd minute), occurring only during exercise corresponding to 87% VO2, was not significantly different in C and A tests (0.373 +/- 0.050 and 0.339 +/- 0.078 1 O2, respectively). The total VO2 consumed throughout the six minute cycling at power output of 40 and 87% VO2max performed in control conditions and after ingestion of NaHCO3 was not significantly different. We have demonstrated that significantly reduced exercise acidemia accompanied by a significantly elevated level of [La]pl accumulation, did not affect the slow component of the VO2 kinetics and the magnitude of oxygen uptake during exercise corresponding to 40 and 87% of VO2max.
The protein C (PC) pathway, with its cofactor protein S (PS), is an important natural antithrombotic mechanism. Both PC and PS deficiencies have been implicated in thrombophilia. The molecular basis for hereditary PC and PS deficiencies is highly heterogeneous, with a large spectrum of mutations that have various effects on the expression of the relevant allele. A small subset of patients who are homozygous or compound heterozygous for a PC gene mutation have severe thrombotic complications at birth, whereas onset occurs later in the other cases. Patients heterozygous for a PC or PS gene abnormality may develop recurrent thrombosis during adulthood, with a probability of remaining free of thrombosis of about 50% at age 45. A PC or PS gene defect is associated with the factor V Arg 506 to Gln mutation in 10% to 30% of symptomatic patients, suggesting that clinical expression is controlled by several genes in heterozygous patients.
The GPIIb/IIIa receptor complex may contribute to acute coronary syndromes by mediating platelet aggregation. The Leu33/Pro polymorphism (PlA1/PlA2) of the GPIIIa has recently been shown to be associated with CHD in a small case-control study. We have investigated this polymorphism in a large multicenter study of patients with myocardial infarction and controls and found no difference in the distribution of allele and genotype frequencies between cases and controls.
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Venous thrombi are composed predominantly of fibrin and red cells with a variable platelet and leukocyte component. They usually form in regions of slow or disturbed flow as in valve cusps, or in venous segments exposed to trauma. Occlusion of the vessel by the thrombus induces venous stasis and extension of the thrombus both proximally and distally. The pathogenic factors that predispose to the occurrence of thrombosis have been described by Virchow: stasis, vascular lesion, and hypercoagulability. Immobilization, cancers, and deficiency of coagulation inhibitors and activated protein C resistance are the most important risk factors of thromboembolic disease.
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Activated protein C resistance is the most prevalent cause of thrombophilia: it is found in 20 to 30% of patients with a deep venous thrombosis history. Activated protein C resistance is due to an arginine 506 to glutamine mutation in factor V. This mutation prevents normal inactivation of activated factor V by activated protein C. The estimated increase in relative risk of venous thrombosis is 5- to 10-fold in heterozygotes, and 50- to 100-fold in homozygotes. Activated protein C resistance does not seem to play a role in arterial thrombosis and in the occurrence of myocardial infarction.
We describe a novel mutation identified in the antithrombin III (AT-III) propeptide responsible for AT-III deficiency. This mutation, a C to A transversion in exon 2, converts the cysteine at position -4 into a stop codon (TGC-->TGA). In this family with severe thrombophilia, the mutation co-segregates with the clinical phenotype.
Patients with homozygous heparin-binding-site (HBS) qualitative antithrombin deficiencies are at significant risk of venous and arterial thrombosis. We report on the eighth case of homozygous HBS deficiency, and the fourth case concerning the Arg 47-Cys mutation. The proposita is a 25 year old, without known thrombotic antecedent, despite an oral contraceptive therapy for 7 years. After 25 weeks of a first pregnancy, she presented an intrauterine fetal demise complicated with deep vein thrombosis and pulmonary embolism. Heparin therapy was inefficient (no clinical nor angiographic improvement, no biological hypocoagulability). Heparin cofactor activity was < 10%, antigen concentration was normal. The crossed immunoelectrophoresis of patient's plasma, with and without heparin, showed a typical profile of qualitative HBS antithrombin deficiency. The molecular analysis revealed an homozygous Arg 4-Cys mutation. Antithrombotic therapy was achieved with continuous infusion of antithrombin concentrates (80 IU/kg/day) and unfractionated heparin (500 IU/kg/day) during 12 days, leading to clinical improvement, and followed by treatment with vitamin K antagonists. This observation emphasizes the risk of intrauterine fetal demise and the inefficiency of heparin therapy without antithrombin infusion in type II HBS homozygous deficiency. The management of a future pregnancy will probably require repeated infusions of antithrombin.
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Activated protein C resistance is the most prevalent cause of thrombophilia: it is found in 20% to 30% of patients with a history of deep venous thrombosis history. Activated protein C resistance is due to an arginine 506 to glutamine mutation in factor V. This mutation prevents normal inactivation of activated factor V by activated protein C. The estimated increase in relative risk of venous thrombosis is 5 to 10 fold in heterozygotes, and 50- to 100- fold in homozygotes. Activated protein C resistance does not seem to play a role in arterial thrombosis or in the occurrence of myocardial infarction.
The purpose of this paper is to describe, based on our experience, the respective place of percutaneous thrombo-aspiration and in situ thrombolysis in acute inferior limb ischemia. Between july 1991 and April 1995, 46 patients presenting with acute arterial occlusion were treated by percutaneous thrombo-aspiration related to arterial emboly (n = 24) or acute in situ thrombosis (n = 22). Most of the occlusions lied in the popliteal and distal leg arteries. Complementary balloon angioplasty of the underlying stenosis was performed in 26 cases (53%). Immediat angiographical success was obtained in 96% of the embolic occlusion and 59% of the in situ thrombosis. Based on this experience, we believe that thrombo-aspiration can be performed to treat a recent acute arterial occlusion (10-20 days) of the terminal part of the superficial femoral artery, with extension distaly to the origin of the leg arteries. This technique is easy to perform and can be proposed as a alternative to the Fogarty catheter in acute short emboli occlusion (length than 15 cm long) on normal or pathologic arteries. Extension of this indication for critical ischemia in patients with no possibility of surgical revascularization, can be proposed using combination of in situ fibrinolysis and thrombo-aspiration with percutaneous angioplasty, at the site or on run off.