Effect of lovastatin on hemorheology in type II hyperlipoproteinemia.

To assess the effect of lovastatin on blood rheology, the hemorheological determinants fibrinogen, red cell aggregation, plasma viscosity, hematocrit and platelet aggregation (spontaneous and ADP-induced) were studied in 15 patients with type II hyperlipoproteinemia in the course of treatment with lovastatin. Prior to therapy, fibrinogen (Fgen), red cell aggregation (RCA-S, RCA-L) and plasma viscosity (PV) as well as cholesterol (Chol) and triglycerides (Tg) were increased in the hyperlipemic patients compared with healthy normolipemic controls (Fgen: 319.3 +/- 65 vs. 269.8 +/- 48 mg/dl; RCA-S: 7.93 +/- 1 vs. 6.62 +/- 1, RCA-L: 9.86 +/- 1 vs. 7.8 +/- 1 arbitrary units; PV: 1.75 vs. 1.63 mPa/s; Chol: 317.0 +/- 32 vs. 176.5 +/- 21 mg/dl; Tg: 154.5 +/- 88 vs. 72.8 +/- 16 mg/dl; all P less than 0.05). Three months of treatment with lovastatin resulted in a marked decrease in red cell aggregation and plasma viscosity, parallel to a fall in cholesterol (the following pretreatment values were monitored after a standard lipid-lowering diet; RCA-S: 7.59 +/- 1 vs. 6.65 +/- 0.9, RCA-L: 9.34 +/- 1 vs. 8.15 +/- 1 arbitrary units; PV: 1.74 vs. 1.65 mPa/s; Chol: 309.8 +/- 41 vs. 217.1 +/- 30 mg/dl; all P less than 0.01); fibrinogen however, remained unchanged throughout the treatment period (346.4 +/- 73.3 vs. 330.5 +/- 70.2 mg/dl, n.s.). No differences were seen in hematocrit and platelet aggregability between hyperlipemic patients and controls and no changes occurred in these parameters during the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Laser Doppler imaging and capillary microscopy in ischemic ulcers.

The local distribution of laser Doppler flux (mainly thermoregulatory perfusion) and capillary density (nutritive circulation) within 25 ischemic leg ulcers and their adjacent skin were investigated. For this purpose the technique of laser Doppler imaging and capillary microscopy were applied. In each ulcer a non granulation tissue area (NGTA), a granulation tissue area (GTA) and in adjacent skin a skin area (SA) were defined. In these areas the average laser Doppler area flux (arbitrary units, AU) and the number of capillaries/mm2 were determined for each patient. The mean+/-S.D. of laser Doppler area fluxes were: NGTA 1.30+/-1.93, GTA 2.13+/-1.53 and SA 1.21+/-0.77 AU, respectively. The differences between GTA and NGTA or SA was statistically significant (p < 0.001, each) The mean+/-S.D. of capillary densities were as follows: NGTA: 0.56+/-2.06, GTA 6.76+/-8.39 and SA 16.80+/-7.38 capillaries/mm2, respectively. The following differences were statistically significant: NGTA versus GTA (p < 0.01) and SA versus NGTA or GTA (p < 0.001, each). In conclusion following characteristics of the three areas can be described: In NGTA low laser Doppler area flux is combined with very low capillary density (ulcer area without healing). In GTA the highest laser Doppler area flux of all three areas and an intermediate capillary density (wound healing) is found. In SA an intermediate laser Doppler area flux is associated with the highest capillary density of all three areas with the healing process nearly completed and no granulation tissue.

Elevated lipoprotein(a) and increased incidence of restenosis after femoropopliteal PTA. Rationale for the higher risk of recurrence in females?

It has been shown that the incidence of recurrent stenosis following successful percutaneous transluminal coronary angioplasty (PTCA) is correlated with serum Lipoprotein(a) [Lp(a)] levels. The aim of the present study was to examine the influence of Lp(a) on restenosis after primary successful femoropopliteal PTA. One hundred and thirty nine consecutive patients with peripheral arterial occlusive disease (PAOD) and successful femoropopliteal PTA were studied. Follow-up included clinical examination and non-invasive laboratory testing (pulse volume recordings, ankle-brachial arterial pressure measurement) in every patient before and after 1, 3, 6 and 12 months following intervention. Duplex sonography was performed 1 year after PTA. Suspicion of restenosis (> or = 50% diameter reduction) was verified by angiography. Lp(a) was determined using ELISA technique (mg/dl). Twelve months after successful PTA no restenosis was found in 82 patients (59%: group A). The one-year recurrence rate of 41% (group B) was due to significant restenosis in 35 patients (25%) and reocclusion in 22 patients (16%). The corresponding mean values +/- S.E.M. for Lp(a) were as follows: group A, 28 +/- 5.3; group B 59 +/- 11 (P < 0.01). Women showed a higher frequency of recurrences (55%) versus men (30%, P < 0.01) also corresponding with a high Lp(a) level (51.8 +/- 8 versus 32.7 +/- 5; P < 0.05). Furthermore Lp(a) aggravated the well known increased risk for recurrence in multiple stenoses or occlusions of > or = 5 cm in length. There were no significant differences between groups A and B with respect to age, diabetes, hyperlipidaemia, obesity and cigarette smoking. The results support the view that Lp(a) is an independent risk factor for recurrence after PTA in the femoropopliteal area. It might also be a causal basis for the higher incidence of recurrences in female PAOD patients.

Platelet deposition at angioplasty sites and platelet survival time after PTA in iliac and femoral arteries: investigations with indium-111-oxine labelled platelets in patients with ASA (1.0 g/day)-therapy.

In this study we have assessed the deposition of 111-In-oxine-labelled platelets--using a dual radiotracer method--at angioplasty sites of the lower extremities in 20 patients (14 male, 6 female; median age: 60 years) with ASA (1.0 g/day)-therapy. The platelet survival time (PST)--using the multiple hit model--was evaluated before and after percutaneous transluminal angioplasty, and we also measured the plasma levels of beta-thromboglobulin (beta-TG) and platelet factor 4 (PF 4) before and after PTA. Before PTA, scintigraphy was positive in only one patient, while 24 hours after PTA a positive scintigraphic result was observed in 16/20 patients. The median target/non target-ratio was 1.0 (0.66-1.3) before PTA, and this ratio increased significantly (p less than 0.0005) to 1.53 (1.0-3.3) after PTA. The median PST decreased significantly (185.0 hours before PTA----145.2 hours after PTA; p less than 0.001), while the median platelet turnover increased from 34,000/microliter/day to 47,900/microliter/day (p less than 0.01). The median plasma levels of the platelet specific proteins increased significantly immediately after PTA (p less than 0.001), but one day later they were not significantly different from the pretreatment values. The quantitative methods used in this study seem a valuable tool to evaluate the effects of different therapeutical--especially antiplatelet--interventions after PTA in humans, thus helping to find the best antithrombotic regimen for this widely used therapeutical procedure.

D-dimer in local thrombolytic therapy with low doses of recombinant human tissue-type plasminogen activator (rt-PA) in patients with peripheral arterial occlusive disease.

The generation of D-dimer was studied in the course of local thrombolytic therapy of peripheral arterial occlusions with low doses of recombinant human tissue-type plasminogen activator (rt-PA) in 7 patients. Intermittent local application of rt-PA resulted in a marked increase in D-dimer exceeding values usually seen after intravenous application of manifold higher doses used in myocardial infarction. The increase in D-dimer was related to the estimated thrombus size (length of the occlusion) and the total dose of rt-PA applied. During local rt-PA infusion of 6 of 7 patients maintained plasminogen activator inhibitor capacity (PAI-cap) between 34% and 79% of their corresponding pre-treatment levels; detectable levels of PAI-cap in circulating blood during the procedure did not interfere with the success of therapy.

An exploratory trial of two dosages of a novel synthetic thrombin inhibitor (napsagatran, Ro 46-6240) compared with unfractionated heparin for treatment of proximal deep-vein thrombosis -- results of the European multicenter ADVENT trial.

One hundred and ten patients with acute proximal deep-vein thrombosis were randomized in a sequential dose-finding design, to receive continuous intravenous infusion of napsagatran, a novel synthetic thrombin-inhibitor, at a fixed dose of 5 mg/h (n = 37) or 9 mg/h (n = 26), or APTT-adjusted unfractionated heparin (n = 47). Oral anticoagulants were started on the 2nd day and the study drug was discontinued from the 5th treatment day, as soon as the International Normalized Ratio was above 2. Control venogram (97 venogram pairs evaluable) after 5-8 days of treatment showed improvement in 3 napsagatran-treated patients (versus none in heparin-treated patients) and worsening in 4 napsagatran-treated patients (versus 2 in heparin-treated patients). The venographic Marder's score did not change among the treatment groups. New lung scan perfusion defects (99 scintigram pairs evaluable) occurred in 4 (11%), 4 (21%), and 4 (10%) patients in the napsagatran (5 mg/h) group, in the napsagatran (9 mg/h) group, and in the heparin control group, respectively. There was no statistically significant difference in any of these endpoints between the 3 groups. No major bleeding was observed and the rare minor bleedings occurred at a similar rate in the three treatment groups. In conclusion, the ADVENT trial has shown data that suggest comparable efficacy and safety of a synthetic, direct thrombin inhibitor (napsagatran) and conventional heparin therapy for treatment of proximal DVT. These results suggest that synthetic direct thrombin inhibitors are a promising class of antithrombotic agents which deserves further development in this field.

D-dimer and TAT measurement in patients with deep venous thrombosis: utility in diagnosis and judgement of anticoagulant treatment effectiveness.

The plasma levels of thrombin-antithrombin III-complexes (TAT) and the fibrin split product D-Dimer were measured in 39 patients with phlebographically proven acute DVT: 34 patients had proximal DVT, 5 had calf DVT. The sensitivity of D-Dimer and TAT measurements in the diagnosis of proximal DVT was found to be dependent on the duration of symptoms: 0 to 7 days (n = 27): elevated D-Dimer levels (greater than 120 ng/ml) = 1, D-Dimer Latex test positive (greater than 500 ng/ml) = 1, elevated TAT levels (greater than 6 ng/ml) = 0.88. Eight to 14 days (n = 7): elevated D-Dimer levels = 1, D-Dimer Latex test positive = 0.33, elevated TAT levels = 0.66; specificity: elevated D-Dimer: 0.48, D-Dimer Latex test: 1, elevated TAT: 0.76. Calf DVT patients (n = 5) had elevated D-Dimer levels, negative Latex tests and 3 of them had normal TAT values. Hemostatic and fibrinolytic parameters were also determined in 13 patients during heparin treatment of proximal DVT. Elevated D-Dimer and TAT levels rapidly decreased after initiation of anticoagulant therapy. In 2 of 13 patients a marked increase in D-Dimer and TAT levels was observed in periods of ineffective heparinization, documented by normal or only slightly prolonged thrombin clotting times. We conclude from our results that 1) D-Dimer EIA measurement, in contrast to TAT measurement, shows a very high sensitivity in the diagnosis of DVT, 2) due to low specificity this test can only be used to exclude thrombosis in patients with suspected DVT, and 3) the determination of the plasma levels of D-Dimer and TAT may be useful for judging the effect of anticoagulant treatment on thrombotic processes.

Differential inhibition of thrombin activity and thrombin generation by a synthetic direct thrombin inhibitor (napsagatran, Ro 46-6240) and unfractionated heparin in patients with deep vein thrombosis. ADVENT Investigators.

BACKGROUND: Direct thrombin inhibitors belong to a new class of antithrombotic drugs whose effects on blood coagulation in vivo in patients suffering from acute thrombotic conditions have not yet been fully explored. METHODS AND RESULTS: One hundred and five patients with acute proximal deep-vein thrombosis were randomized to receive a continuous intravenous infusion of napsagatran, a novel synthetic thrombin inhibitor, at a fixed dose of 5 mg/h (n = 36) or 9 mg/h (n = 25) for five days, or APTT-adjusted unfractionated heparin (UFH, n = 44) for the same time. In these patients, thrombin activity and thrombin generation could be assessed by measuring thrombin-antithrombin III complexes (TAT) and prothrombin fragment 1+2 (F1+2), respectively, on three occasions. At baseline, TAT and F1+2 did not differ among the three groups. On Day 2 (steady state), TAT significantly decreased in all groups, and the decrease was significantly more pronounced in the patients given higher-dose napsagatran. F1+2 decreased significantly only in UFH-treated patients. Two hours after cessation of the infusion, the TAT levels increased in the two napsagatran groups but not in the UFH group, whilst F1+2 went back to the baseline levels in the napsagatran-treated patients but remained low in the UFH-treated patients. There was no rebound effect. CONCLUSIONS: The data presented suggest that direct thrombin inhibition with napsagatran at 9 mg/h is more potent than UFH in attenuating thrombin activity, but is less potent than UFH in inhibiting thrombin generation. The real significance of these findings will have to be substantiated in further trials with clinically relevant endpoints.

Blood rheology after cardiac valve replacement with mechanical prostheses or bioprostheses.

Arterial thromboembolism is a serious complication in patients after heart valve replacement. Abnormalities in blood rheology may contribute to this complication. Therefore, the aim of this study was to compare various determinants of blood rheology in patients with substitute heart valves with those in healthy controls; furthermore, differences between patients with mechanical valves and those with bioprostheses should be investigated. The hemorrheologic determinants--fibrinogen, plasma viscosity, red cell aggregation, hematocrit and platelet aggregation--were studied in 92 patients with mechanical bileaflet valves, in 28 patients with bioprostheses and in 29 control subjects; the time since valve replacement was greater than or equal to 9 months. Fibrinogen, plasma viscosity, red cell and spontaneous platelet aggregation were found to be increased in all patients after heart valve replacement compared with normal subjects (fibrinogen: 348 +/- 87 vs 267 +/- 66 mg/dl, p less than 0.01; plasma viscosity: 1.71 +/- 0.1 vs 1.66 +/- 0.1 mPas, p less than 0.05; red cell aggregation: 9.9 +/- 2 vs 7.8 +/- 2 U, p less than 0.01; platelet aggregation: 22 +/- 15 vs 13 +/- 13%, p less than 0.01); among patients, fibrinogen, plasma viscosity and spontaneous platelet aggregation were higher in mechanical valves than in bioprostheses (fibrinogen: 359 +/- 95 vs 314 +/- 41 mg/dl, p less than 0.01; plasma viscosity: 1.72 +/- 0.1 vs 1.68 +/- 0.1 mPas, p less than 0.1; platelet aggregation: 23 +/- 15 vs 16 +/- 11%; p less than 0.05), whereas no difference could be found for red cell aggregation (9.7 +/- 2 vs 10.5 +/- 2%, p greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood rheology in patients with native heart valve disease and after valve replacement.

Patients with heart valve disease have rheologic abnormalities that are more pronounced in double valve disease than in mitral or aortic valve disease; after valve replacement surgery, the degree of rheologic abnormality is more pronounced in patients with mechanical and biological prostheses than in those with homografts and pulmonary autografts. Rheologic abnormalities seen in these patients might be related to the different incidences of thromboembolism in the presence of various valve defects and various types of prostheses.

Increased serum laminin and angiogenin concentrations in patients with peripheral arterial occlusive disease.

AIM: To measure serum laminin and angiogenin concentrations in patients with peripheral arterial occlusive disease (PAOD) Fontaine stages IIb, III, and IV. METHODS: The study population comprised 38 patients (20 men and 18 women) with stage IV PAOD, 11 patients (six men and five women) with stage III PAOD, 18 patients (10 men and eight women) with stage IIb PAOD, and 23 patients (10 men and 13 women) with deep vein thrombosis. Fifteen normal subjects (matched for risk factors) and 10 patients (five men and five women) without PAOD served as controls. Serum samples were obtained at admission and serum laminin and angiogenin concentrations were measured using an enzyme linked immunosorbent assay. RESULTS: Patients with stage IV PAOD had higher serum laminin (mean +/- SEM; 826 +/- 97 ng/ml) and angiogenin concentrations (467 +/- 26 pg/ml) than normal subjects (laminin: 379 +/- 21 ng/ml; angiogenin: 358 +/- 16 pg/ml) and patients without PAOD (laminin: 277 +/- 34 ng/ml; angiogenin: 406 +/- 25 pg/ml). A significant correlation was found between angiogenin and laminin and between serum laminin and fibrinogen concentrations in patients with stage IV disease. CONCLUSIONS: Raised laminin and angiogenin concentrations may be indicators of endothelial damage caused by reduced vascular perfusion or compensatory revascularisation, or both.

The influence of anticoagulant treatment on the probability of function in femoropopliteal vein bypass surgery: analysis of a clinical series (1970 to 1985) and interim evaluation of a controlled clinical trial.

During the years 1970 to 1985, 463 patients with obliterative atherosclerosis at the femoropopliteal level underwent elective surgery. The operation performed was an autologous saphenous vein bypass using the reversed technique. The vascular surgical treatment was documented in reasonable detail (both baseline and follow-up) in accordance with the documentation system of the Austrian Society of Vascular Surgery. On-line data entry with use of SAS data-base management software was used. The patency curves were estimated in accordance with the Kaplan-Meier method; possible differences were checked by means Breslow's and Mantel's tests. The preoperative clinical status (claudicants, n = 200; limb salvage, n = 263) influenced the postoperative results in a statistically significant manner (Breslow p less than 0.01; Mantel p less than 0.03). All the other risk factors analyzed (site of distal anastomosis above versus below the knee, n = 231, and n = 232, respectively; Breslow p less than 0.58, Mantel p less than 0.58. Presence [n = 122] or nonpresence [n = 341], of diabetes mellitus [Breslow p less than 0.77, Mantel p less than 0.68]; smoking habits [nonsmokers, n = 93, smokers n = 370, Breslow p less than 0.68, Mantel p less than 0.69;]) did not reach statistical significance. Anticoagulant treatment (n = 101) had no effect (Breslow p less than 0.93, Mantel p less than 0.72), even when the therapy was restricted to cases with disease at advanced clinical stages (stages III, IV; n = 50; Breslow p less than 0.55, Mantel p less than 0.95). On the basis of these analyses, a prospective trial was initiated in 1979. Eighty-eight patients were studied; those in group I (n = 42) received dicumarol, and those in group II (n = 46) were controls who did not receive anticoagulant treatment. At present, the median follow-up time is at 30 months. Treatment with dicumarol favorably influenced graft patency (Breslow, p less than 0.03, Mantel p less than 0.07; one-tailed tests). The patients' preoperative clinical status affected the results of surgery (Breslow p less than 0.03, Mantel p less than 0.02; one-tailed tests). In relation to the preoperative clinical status, a therapeutic effect was observed in stages III and IV (n = 45; Breslow p less than 0.03, Mantel p less than 0.07; one-tailed tests), while no effect of therapy was demonstrable in claudicants (n = 43; Breslow p less than 0.3, Mantel p less than 0.4; one-tailed tests).(ABSTRACT TRUNCATED AT 400 WORDS)

Diagnostic and therapeutic approaches to carotid body tumors. Review of 24 patients.

OBJECTIVE: To determine the clinical characteristics of carotid body tumors to define better a standardized proceeding in the management of carotid body tumors. DESIGN: Retrospective survey. Duration of postoperative follow-up was 4 months to 16 years (median, 57 months). SETTING: Institutional, tertiary care medical center. PATIENTS: Consecutive sample of 24 patients (10 men and 14 women) with 28 carotid body tumors treated in the University of Vienna (Austria) General Hospital in 35 years. INTERVENTIONS: Surgical resection, preoperative embolization. MAIN OUTCOME MEASURES: Initial signs, duration of symptoms, extension of the tumors, methods of investigations, and treatment modality, with special respect to the operative technique. RESULTS: Doppler color flow imaging and angiography provided essential mainstays for definite diagnosis. Computed tomography and magnetic resonance imaging contributed additional information about tumor extension. Nineteen patients (79%) underwent surgical resection of 22 tumors, 8 (42%) after preoperative embolization. There were no perioperative deaths. Hemiplegia occurred in 1 patient, and cranial nerve palsy occurred in 5 patients. Tumor recurrence was observed in 3 patients. Five patients refused surgery or tumors were unresectable. CONCLUSIONS: Our standard diagnostic procedure consists of establishing diagnosis by Doppler color flow sonography, angiography for detailing the vascularization of the tumor, and selective embolization to enable safer surgery with less bleeding. Early surgery is recommended to minimize major risks.

Influence of acetylsalicylic acid (1.0 g/day) on platelet survival time, beta-thromboglobulin and platelet factor 4 in patients with peripheral arterial occlusive disease.

In this study we investigated the influence of acetylsalicylic acid (ASA) 1.0 g/day on 111-In-platelet survival time (PST) and on plasma levels of beta-thromboglobulin (beta-TG) and platelet factor 4 (PF 4) in 37 patients (median age: 63.4 years) with arteriographically proven peripheral arterial occlusive disease (PAOD) in a chronic stable phase. We found a slight but significant increase of PST during therapy with ASA (weighted mean (WM): 184.3----193.2 [median] hours, p less than 0.05; multiple hit (MH): 182.4----192.8 hours, p less than 0.005) for the total group of patients. Concerning the influence of risk factors of PAOD on PST during ASA-therapy, there was a significant increase of PST only in the nondiabetics (WM: 180.3----204.6 hours, p less than 0.01; MH: 176.8----195.3 hours, p less than 0.01). There was a negative correlation between the baseline values of PST and their increase following ASA therapy (WM: r = -0.63; p less than 0.0001; MH: r = -0.61, p less than 0.0001). The pretreatment levels of beta-TG--but not PF 4--were significantly (p less than 0.001) elevated compared to healthy controls. Therapy with ASA caused a significant decrease in the plasma levels of beta-TG (median: 30.4----26.6 ng/ml, p less than 0.001) and PF 4 (2.95----2.2 ng/ml, p less than 0.01).

Reproducibility of platelet survival time measurements in patients with peripheral arterial occlusive disease.

In this study we investigated the reproducibility of 111-In-platelet survival time (PST) measurements and of plasma levels of beta-thromboglobulin (beta-TG) and platelet factor 4 (PF 4) in 30 patients (median age: 60.5 years) with arteriographically proven peripheral arterial occlusive disease (PAOD) in a chronic stable phase. PST calculated by both the weighted mean - WM - (1. investigation: 187.1 [median] hours - repeat investigation: 188.3 hours) and multiple hit - MH - model (181.4----177.4 hours) demonstrated only a small spontaneous variation. The median coefficient of variation (CV) was 3.0 (WM) and 3.2 (MH), respectively. The reproducibility of beta-TG (CV: 6.1) was also satisfactory. We conclude that the good reproducibility of PST and plasma levels of beta-TG make them well suited to judge the influence of platelet-suppressant drugs on these parameters in patients with PAOD.

Hemorheology in systemic ultrahigh-dose thrombolytic therapy with streptokinase and urokinase.

The course of fibrinogen (Fgen), red cell aggregation (RCA), plasma viscocity (PV), platelet aggregation (PA) and hematocrit (Hc) was studied in patients with ultrahigh - dose thrombolytic therapy (1.5 x 10(6) units/hour for 6 hours = 1 cycle) with streptokinase (SK) or urokinase (UK) over a period of 3 cycles. Both ultrahigh - dose SK and UK produced significant changes in the course of Fgen, RCA and PV, whereas PA (spontaneous and ADP-induced) and Hc remained unchanged. After termination of each cycle Fgen progressively increased while RCA and PV further decreased. The extent of alteration in cycle 1 - concerning the baseline values - was more pronounced with SK than with UK, but the overall effect of SK decreased through the consecutive cycles because of more rapid increase during the SK-free period. In UK-therapy hemorheological alterations were initially moderate but increased from cycle to cycle.

Lack of influence of low-dose acetylsalicylic acid (100 mg daily) on platelet survival time, beta-thromboglobulin and platelet factor 4 in patients with peripheral arterial occlusive disease.

In this study we investigated the influence of low-dose (100 mg daily) acetylsalicylic acid (ASA) on 111-In-platelet survival time (PST) and on plasma levels of beta-thromboglobulin (beta-TG) and platelet factor 4 (PF 4) in 30 patients (median age: 60 years) with arteriographically proven peripheral arterial occlusive disease in a chronic stable phase. We observed no significant changes of PST during therapy with ASA (weighted mean: 169.8----166 [median] hours; multiple hit: 168.3----170.6 hours), and also the plasma levels of beta-TG (median: 31.8----32.3 ng/ml) and of PF 4 (3.6----3.9 ng/ml) remained unchanged.

Activation of coagulation and fibrinolysis in patients with arteriosclerosis: relation to localization of vessel disease and risk factors.

Activation markers of blood coagulation and fibrinolysis and several fibrinolytic parameters were determined in arteriosclerotic patients to investigate the relation between extension and main localization of vessel disease, risk factors and disturbances within the blood coagulation and the fibrinolytic system. Indications of an increased intravascular fibrin formation and subsequent fibrinolysis were found in peripheral artery disease (PAD) patients but not in coronary artery disease (CAD) patients. Compared with healthy controls PAD patients had elevated TAT (median: 3.2 ng/ml, 1.5-70 vs. 2.1, 1.2-4.7, p less than 0.005) and D-Dimer (median: 365 ng/ml, range 85-2000 vs. 185, 79-360; p less than 0.0001) plasma levels, whereas TAT (2.4, 1.2-13) and D-Dimer (190, 58-1000) levels of CAD patients were in the normal range. No associations were detected between risk factors of arteriosclerosis (hyperlipidemia, diabetes mellitus, cigarette smoking, hypertension) and the plasma levels of the activation markers TAT and D-Dimer. Independent from risk factors PAD and CAD patients had elevated plasma plasminogen activator inhibitor capacity (PAI cap). Our results provide evidence that 1) increased plasma levels of blood coagulation and fibrinolysis activation markers are not related to risk factors of arteriosclerosis but seem to be unspecifically caused by activation processes on arteriosclerotic vessel wall defects, 2) increased plasma PAI cap found in arteriosclerotic patients is a relatively unspecific phenomenon associated with arterial vessel disease.

Changes in blood rheology caused by Crohn's disease.

BACKGROUND: Patients with Crohn's disease (CD) are at increased risk for thromboembolism, and multifocal microvascular infarction has even been suggested as a pathogenetic mechanism in CD. Abnormalities in blood rheology may contribute to the thromboembolism. OBJECTIVES: To assess blood rheology in CD patients. DESIGN: Prospective evaluation of rheological parameters. SETTING: Out-patients at the gastroenterological department of a university hospital. PATIENTS: Thirty-seven patients with inactive CD (Crohn's disease activity index (CDAI) < 150), 31 patients with active CD (CDAI > 150), and 39 control subjects with no CD were included in the study. METHODS: C-reactive protein and orosomucoid were used as serum inflammatory parameters. Fibrinogen, red cell aggregation (low shear, 3/s) and plasma viscosity were used as rheological parameters. RESULTS: Fibrinogen (active CD: median 530 mg/dl (interquartile range 410-630); inactive CD: 377 (316-499); and controls: 246 (220-280)), red cell aggregation (active CD: 9.97 arb. units (8.58-11.77); inactive CD: 9.03 (7.25-10.37); controls: 7.58 (7-8.52)); and plasma viscosity (active CD: 1.82 mPa.s (1.68-1.95); inactive CD: 1.72 (1.65-1.82), controls: 1.61 (1.58-1.64)) were all significantly higher in patients with active and inactive CD than they were in controls. Additionally, fibrinogen was significantly higher in patients with active CD than it was in patients with inactive CD. The rheological parameters correlated with serum inflammatory parameters. CONCLUSION: Changes in blood rheology seem to be associated with inflammatory activity in patients with CD. These changes may be involved in the development of thromboembolism and the pathogenesis of mucosal inflammation, especially in patients with high inflammatory activity.

Colour duplex sonography-guided local lysis of occlusions in the femoro-popliteal region.

BACKGROUND: To evaluate colour duplex sonographic guidance of local lysis of occlusions in the femoropopliteal region. METHODS: Thirteen consecutive patients (8 female, mean age 67) with peripheral artery disease with acute and subacute occlusions in the superficial femoral or popliteal artery were included in this study. The lesions were identified by colour duplex ultrasound (Acuson 128 XP/10) After anterograde puncture the guidewire was advanced through the arterial lesions under B-mode image control. The Mewissen Infusion Catheter and a Katzen infusion wire were then accurately positioned within the lesion under B-mode image control. The fibrinolytic drugs were then inserted into the occlusions, initially 2.5 mg rt-PA as a bolus followed by Urokinase (50,000 IU/h) for 24 hours. After control duplex sonography (over 24 hours) the additional angioplasty was performed either under fluoroscopic or exclusively under ultrasound guidance. RESULTS: Eleven of 13 patients with occlusions in the femoro-popliteal region were partially recanalised after ultrasound guided local lysis and after the additional angioplasties (nine under fluoroscopic and three under ultrasound guidance) the arteries were completely recanalised. CONCLUSIONS: Our data show that not only is the positioning of the catheter and the guidewire for local lysis exclusively under colour duplex guidance possible, but also the surveillance of the local lysis and the additional angioplasty. In the case of any complications, however, easy access to angiography should be possible.