Veränderungen des fibrinolytischen Systems bei Patienten mit peripheren arteriellen Durchblutungsstörungen

VASA ◽  
1999 ◽  
Vol 28 (2) ◽  
pp. 106-111 ◽  
Author(s):  
Poredos ◽  
Stegnar ◽  
Gacnik

Background: The fibrinolytic system may play an important role in the development and progression of peripheral arterial occlusive disease. Patients and methods: The fibrinolytic system of the whole blood and a diseased leg was investigated in twenty men with chronic peripheral atherosclerotic occlusive arterial disease (PAOD, clinical stage II according to Fontaine), aged from 46 to 66 years (mean age = 55.3 years). The diagnosis of PAOD was established by clinical examination and segmental systolic blood pressure measurements using a Doppler ultrasound detector. Twenty age-matched (mean age = 53.4 years) male volunteers with normal arterial circulation of the lower limbs and without risk factors of atherosclerosis, served as controls. In both groups fibrinolytic system was investigated in basal conditions and during provocation. Release of tissue-type plasminogen activator (t-PA) was provoked by 20 min venous occlusion of the arm and the leg and by infusion of DDAVP (1-desamino-8-D-arginine-vasopressin, 0.4 ug/kg of body weight). Blood samples were obtained from the arm and the leg before and after each stimulus. The fibrinolytic parameters: euglobulin clot lysis time, t-PA activity (amidolytic assay) and antigen (ELISA) and t-PA inhibitor (PAI) activity (amidolytic assay) were determined. Results: With the exception of a boderline increase in PAI activity in patients, no other differences between the two groups were observed in basal conditions. The most prominent deterioration of the fibrinolytic system detected in male PAOD patients was a significantly higher residual PAI activity registered during venous occlusion of the arm and two minutes after combined stimulation. Two minutes after combined stimulation (DDAVP and venous occlusion of the arm) significantly lower t-PA activity was observed in patients. In patients t-PA antigen response to venous occlusion and DDAVP was not significantly different from the response observed in healthy volunteers. The fibrinolytic response of the leg to venous occlusion was poor and after DDAVP application it was comparable to the arm. The fibrinolytic response of the diseased leg in men was not significantly different from the healthy leg. Conclusion: The results of our study indicate that alteration of the fibrinolytic system in atherosclerotic disease is predominantly a generalised phenomenon and is not directly related to a local atherosclerotic process.

1987 ◽  
Author(s):  
H Ostermann ◽  
S Koenig ◽  
H Pollmann ◽  
U Schmitz-Huebner

We identified two families in whom one member each suffered from deep venous thrombosis and subsequent pulmonary emboli at the age of 15 and 17. We were able to investigate several members of both families with regard to their fibrinolytic system. Blood sampling was done before and after ten minutes of venous occlusion. Parameters measured were euglobulin clot lysis time (ECLT), tissue-type plasminogen activator (t-PA) activity, t-PA concentration and plasminogen activator inhibitor (PAI) activity, besides several other constituents of the coagulation and fibrinolytic system commonly associated with thrombophilia.In the first family six persons could be evaluated. A prolonged ECLT was found in four probands. Three of them had no measurable t-PA activity after stasis, t-PA concentration after stasis was below the normal range in two and borderline in one of them.In the second family 13 members could be invest-gated. Three adults were found to have a prolonged ECLT. Two of these had very low t-PA activity after stasis, with normal increase in t-PA antigen. Their PAI was increased above the normal range. Six children showed no measurable PAI and increased levels of t-PA activity before stasis. After stasis four children had a prolonged ECLT. Two of them had low t-PA antigen levels, while all of them showed normal t-PA activity increases.These findings suggest, that there may be hereditary defects related to activators and inhibitors of the fibrinolytic system in the investigated families. These could possibly be responsible for the occurence of venous thrombosis early in life. However, results in the second family show that not all of the prolonged ECLT values can be explained by changes of t-PA and PAI.


1990 ◽  
Vol 63 (01) ◽  
pp. 076-081 ◽  
Author(s):  
Pascale Gaussem ◽  
Sophie Gandrille ◽  
Pascale Molho-Sabatier ◽  
Loïc Capron ◽  
Jean-Noël Fiessinger ◽  
...  

SummaryUsing a monoclonal antibody-based assay, we measured the fibrin degradation product release in the supernatant of plasma clots obtained before and after venous occlusion (VO) in 30 patients with definite or suspected vascular thrombosis (19 definite and 2 suspected deep vein thrombosis, 6 recurrent superficial thrombophlebitis, 3 arterial occlusions of lower limbs). tPA and PAI-1 concentrations were determined using ELISA assays; the post-occlusion values were corrected for haemoconcentration. The increase in tPA during VO was correlated with haemoconcentration (r = 0.74), but 3 patients had ineffective VO (<2% increase in proteins). The fibrinolytic response to VO was evaluated using the shortening of the time necessary for the release of 200 μg of fibrin degradation products per mg of fibrinogen (Δ T 200). Two among the 27 patients with effective VO were bad responders with a Δ T 200 <3 h (whereas all the others had Δ T 200 >10 h). These patients had respectively a deficient tPA release (Δ tPA = 1 ng/ml) and an elevated PAI-1 level at rest (33 ng/ml). Several other patients were bad responders in terms of tPA release or of shortening of the euglobulin clot lysis time but they had a normal Δ T 200. This plasma clot test reflects the ability of free tPA to bind to fibrin (the amount of which depends on the level of tPA and PAI-1), and may be useful in the diagnosis of a hypofibrinolytic state.


1999 ◽  
Vol 81 (04) ◽  
pp. 601-604 ◽  
Author(s):  
Hiroyuki Matsuno ◽  
Osamu Kozawa ◽  
Masayuki Niwa ◽  
Shigeru Ueshima ◽  
Osamu Matsuo ◽  
...  

SummaryThe role of fibrinolytic system components in thrombus formation and removal in vivo was investigated in groups of six mice deficient in urokinase-type plasminogen activator (u-PA), tissue-type plasminogen activator (t-PA), or plasminogen activator inhibitor-1 (PAI-1) (u-PA-/-, t-PA-/- or PAI-1-/-, respectively) or of their wild type controls (u-PA+/+, t-PA+/+ or PAI-1+/+). Thrombus was induced in the murine carotid artery by endothelial injury using the photochemical reaction between rose bengal and green light (540 nm). Blood flow was continuously monitored for 90 min on day 0 and for 20 min on days 1, 2 and 3. The times to occlusion after the initiation of endothelial injury in u-PA+/+, t-PA+/+ or PAI-1+/+ mice were 9.4 ± 1.3, 9.8 ± 1.1 or 9.7 ± 1.6 min, respectively. u-PA-/- and t-PA-/- mice were indistinguishable from controls, whereas that of PAI-1-/- mice were significantly prolonged (18.4 ± 3.7 min). Occlusion persisted for the initial 90 min observation period in 10 of 18 wild type mice and was followed by cyclic reflow and reocclusion in the remaining 8 mice. At day 1, persistent occlusion was observed in 1 wild type mouse, 8 mice had cyclic reflow and reocclusion and 9 mice had persistent reflow. At day 2, all injured arteries had persistent reflow. Persistent occlusion for 90 min on day 0 was observed in 3 u-PA-/-, in all t-PA-/- mice at day 1 and in 2 of the t-PA-/-mice at day 2 (p <0.01 versus wild type mice). Persistent patency was observed in all PAI-1-/- mice at day 1 and in 5 of the 6 u-PA-/- mice at day 2 (both p <0.05 versus wild type mice). In conclusion, t-PA increases the rate of clot lysis after endothelial injury, PAI-1 reduces the time to occlusion and delays clot lysis, whereas u-PA has little effect on thrombus formation and spontaneous lysis.


1986 ◽  
Vol 56 (01) ◽  
pp. 035-039 ◽  
Author(s):  
D Collen ◽  
F De Cock ◽  
E Demarsin ◽  
H R Lijnen ◽  
D C Stump

SummaryA potential synergic effect of tissue-type plasminogen activator (t-PA), single-chain urokinase-type plasminogen activator (scuPA) or urokinase on clot lysis was investigated in a whole human plasma system in vitro. The system consisted of a human plasma clot labeled with 125I-fibrinogen, immersed in titrated whole human plasma, to which the thrombolytic agents were added. Clot lysis was quantitated by measurement of released 125I, and activation of the fibrinolytic system in the surrounding plasma by measurements of fibrinogen and α2-antiplasmin.t-PA, scu-PA and urokinase induced a dose-dependent and time-dependent clot lysis; 50 percent lysis after 2 h was obtained with 5 nM t-PA, 20 nM scu-PA and 12 nM urokinase. At these concentrations no significant activation of the fibrinolytic system in the plasma was observed with t-PA and scu-PA, whereas urokinase caused significant α2-antiplasmin consumption and concomitant fibrinogen degradation. The shape of the dose-response curves was different; t-PA and urokinase showed a log linear dose-response whereas that of scu-PA was sigmoidal.


2021 ◽  
Vol 10 (7) ◽  
pp. 1413
Author(s):  
Judith Catella ◽  
Anne Long ◽  
Lucia Mazzolai

Some patients still require major amputation for lower extremity peripheral arterial disease treatment. The purpose of pre-operative amputation level selection is to determine the most distal amputation site with the highest healing probability without re-amputation. Transcutaneous oximetry (TcPO2) can detect viable tissue with the highest probability of healing. Several factors affect the accuracy of TcPO2; nevertheless, surgeons rely on TcPO2 values to determine the optimal amputation level. Background about the development of TcPO2, methods of measurement, consequences of lower limb amputation level, and the place of TcPO2 in the choice of the amputation level are reviewed herein. Most of the retrospective studies indicated that calf TcPO2 values greater than 40 mmHg were associated with a high percentage of successful wound healing after below-knee-amputation, whereas values lower than 20 mmHg indicated an increased risk of unsuccessful healing. However, a consensus on the precise cut-off value of TcPO2 necessary to assure healing is missing. Ways of improvement for TcPO2 performance applied to the optimization of the amputation-level are reported herein. Further prospective data are needed to better approach a TcPO2 value that will promise an acceptable risk of re-amputation. Standardized TcPO2 measurement is crucial to ensure quality of data.


Author(s):  
Patrick Veit-Haibach ◽  
Martin W. Huellner ◽  
Martin Banyai ◽  
Sebastian Mafeld ◽  
Johannes Heverhagen ◽  
...  

Abstract Objectives The purpose of this study was the assessment of volumetric CT perfusion (CTP) of the lower leg musculature in patients with symptomatic peripheral arterial disease (PAD) before and after interventional revascularisation. Methods Twenty-nine consecutive patients with symptomatic PAD of the lower extremities requiring interventional revascularisation were assessed prospectively. All patients underwent a CTP scan of the lower leg, and hemodynamic and angiographic assessment, before and after intervention. Ankle-brachial pressure index (ABI) was determined. CTP parameters were calculated with a perfusion software, acting on a no outflow assumption. A sequential two-compartment model was used. Differences in CTP parameters were assessed with non-parametric tests. Results The cohort consisted of 24 subjects with an occlusion, and five with a high-grade stenosis. The mean blood flow before/after (BFpre and BFpost, respectively) was 7.42 ± 2.66 and 10.95 ± 6.64 ml/100 ml*min−1. The mean blood volume before/after (BVpre and BVpost, respectively) was 0.71 ± 0.35 and 1.25 ± 1.07 ml/100 ml. BFpost and BVpost were significantly higher than BFpre and BVpre in the treated limb (p = 0.003 and 0.02, respectively), but not in the untreated limb (p = 0.641 and 0.719, respectively). Conclusions CTP seems feasible for assessing hemodynamic differences in calf muscles before and after revascularisation in patients with symptomatic PAD. We could show that CTP parameters BF and BV are significantly increased after revascularisation of the symptomatic limb. In the future, this quantitative method might serve as a non-invasive method for surveillance and therapy control of patients with peripheral arterial disease. Key Points • CTP imaging of the lower limb in patients with symptomatic PAD seems feasible for assessing hemodynamic differences before and after revascularisation in PAD patients. • This quantitative method might serve as a non-invasive method, for surveillance and therapy control of patients with PAD.


2015 ◽  
Vol 67 ◽  
pp. 16
Author(s):  
Natasza Balcer-Dymel ◽  
Katarzyna Korzeniowska ◽  
Artur Cieślewicz ◽  
Anna Jabłecka

VASA ◽  
2008 ◽  
Vol 37 (3) ◽  
pp. 285-288 ◽  
Author(s):  
Keo ◽  
Do ◽  
Husmann ◽  
Baumgartner

No data are currently available on the role of oral sirolimus in the prevention of recurrent stenosis in the periphery. We report the effects of oral sirolimus in the prevention of recurrent infrainguinal obstructions in patients with complex peripheral arterial disease. Three patients with ischemic rest pain of the lower limbs and repeated short-term need for surgical and/or endovascular revascularization: 9 times within 12 months, 7 times within 15 months, 11 times within 26 months, respectively. Oral sirolimus on a case by case basis, resulted in less frequent restenosis and longer intervention-free intervals: three re-interventions within 37 months in the first patient, one balloon angioplasty within 17 months in the second, and three re-interventions within 21 months in the third patient, respectively. Side effects, in particular dyspepsia and diarrhoea, were mild and tolerable. To our knowledge, this is the first report to show that oral sirolimus was successfully administered in patients with recurrent excessive neointimal proliferation after revascularization of peripheral arterial lesions lowering the necessity of re-intervention and hence prolonging intervention-free intervals.


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