Peri-procedural use of rivaroxaban in elective percutaneous coronary intervention to treat stable coronary artery disease. The X-PLORER trial.

Patients on rivaroxaban requiring percutaneous coronary intervention (PCI) represent a clinical conundrum. We aimed to investigate whether rivaroxaban, with or without an additional bolus of unfractionated heparin (UFH), effectively inhibits coagulation activation during PCI. Stable patients (n=108) undergoing elective PCI and on stable dual antiplatelet therapy were randomised (2:2:2:1) to a short treatment course of rivaroxaban 10 mg (n=30), rivaroxaban 20 mg (n=32), rivaroxaban 10 mg plus UFH (n=30) or standard peri-procedural UFH (n=16). Blood samples for markers of thrombin generation and coagulation activation were drawn prior to and at 0, 0.5, 2, 6-8 and 48 hours (h) after start of PCI. In patients treated with rivaroxaban (10 or 20 mg) and patients treated with rivaroxaban plus heparin, the levels of prothrombin fragment 1 + 2 at 2 h post-PCI were 0.16 [0.1] nmol/l (median) [interquartile range, IQR] and 0.17 [0.2] nmol/l, respectively. Thrombin-antithrombin complex values at 2 h post-PCI were 3.90 [6.8]µg/l and 3.90 [10.1] µg/l, respectively, remaining below the upper reference limit (URL) after PCI and stenting. This was comparable to the control group of UFH treatment alone. However, median values for thrombin-antithrombin complex passed above the URL with increasing tendency, starting at 2 h post-PCI in the UFH-alone arm but not in rivaroxaban-treated patients. In this exploratory trial, rivaroxaban effectively suppressed coagulation activation after elective PCI and stenting.

Rivaroxaban versus placebo in patients with acute coronary syndromes (ATLAS ACS-TIMI 46): a randomised, double-blind, phase II trial.

BACKGROUND: Rivaroxaban is an oral direct factor Xa inhibitor that has been effective in prevention of venous thromboembolism in patients undergoing elective orthopaedic surgery. However, its use after acute coronary syndromes has not been investigated. In this setting, we assessed the safety and efficacy of rivaroxaban and aimed to select the most favourable dose and dosing regimen. METHODS: In this double-blind, dose-escalation, phase II study, undertaken at 297 sites in 27 countries, 3491 patients stabilised after an acute coronary syndrome were stratified on the basis of investigator decision to use aspirin only (stratum 1, n=761) or aspirin plus a thienopyridine (stratum 2, n=2730). Participants were randomised within each strata and dose tier with a block randomisation method at 1:1:1 to receive either placebo or rivaroxaban (at doses 5-20 mg) given once daily or the same total daily dose given twice daily. The primary safety endpoint was clinically significant bleeding (TIMI major, TIMI minor, or requiring medical attention); the primary efficacy endpoint was death, myocardial infarction, stroke, or severe recurrent ischaemia requiring revascularisation during 6 months. Safety analyses included all participants who received at least one dose of study drug; efficacy analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00402597. FINDINGS: Three patients in stratum 1 and 26 in stratum 2 never received the study drug. The risk of clinically significant bleeding with rivaroxaban versus placebo increased in a dose-dependent manner (hazard ratios [HRs] 2.21 [95% CI 1.25-3.91] for 5 mg, 3.35 [2.31-4.87] for 10 mg, 3.60 [2.32-5.58] for 15 mg, and 5.06 [3.45-7.42] for 20 mg doses; p<0.0001). Rates of the primary efficacy endpoint were 5.6% (126/2331) for rivaroxaban versus 7.0% (79/1160) for placebo (HR 0.79 [0.60-1.05], p=0.10). Rivaroxaban reduced the main secondary efficacy endpoint of death, myocardial infarction, or stroke compared with placebo (87/2331 [3.9%] vs 62/1160 [5.5%]; HR 0.69, [95% CI 0.50-0.96], p=0.0270). The most common adverse event in both groups was chest pain (248/2309 [10.7%] vs 118/1153 [10.2%]). INTERPRETATION: The use of an oral factor Xa inhibitor in patients stabilised after an acute coronary syndrome increases bleeding in a dose-dependent manner and might reduce major ischaemic outcomes. On the basis of these observations, a phase III study of low-dose rivaroxaban as adjunctive therapy in these patients is underway. FUNDING: Johnson & Johnson Pharmaceutical Research & Development and Bayer Healthcare AG.

Oral rivaroxaban for the prevention of symptomatic venous thromboembolism after elective hip and knee replacement.

A once-daily dose of rivaroxaban 10 mg, an oral, direct Factor Xa inhibitor, was compared with enoxaparin 40 mg subcutaneously once daily for prevention of venous thromboembolism in three studies of patients undergoing elective hip and knee replacement (RECORD programme). A pooled analysis of data from these studies (n = 9581) showed that rivaroxaban was more effective than enoxaparin in reducing the incidence of the composite of symptomatic venous thromboembolism and all-cause mortality at two weeks (0.4% vs 0.8%, respectively, odds ratio 0.44; 95% confidence interval 0.23 to 0.79; p = 0.005), and at the end of the planned medication period (0.5% vs 1.3%, respectively; odds ratio 0.38; 95% confidence interval 0.22 to 0.62; p < 0.001). The rate of major bleeding was similar at two weeks (0.2% for both) and at the end of the planned medication period (0.3% vs 0.2%). Rivaroxaban started six to eight hours after surgery was more effective than enoxaparin started the previous evening in preventing symptomatic venous thromboembolism and all-cause mortality, without increasing major bleeding.

Differences in urinary prothrombin fragment 1 + 2 levels after total hip replacement in relation to venous thromboembolism and bleeding events.

BACKGROUND: Prothrombin fragment 1 + 2 is excreted in urine (uF1 + 2) as a result of thrombin generation and, therefore, may be a useful marker of coagulation status. OBJECTIVES: To assess uF1 + 2 levels after total hip replacement (THR) in patients with venous thromboembolism (VTE) and bleeding events. PATIENTS/METHODS: This study was conducted in parallel with a prospective, dose-finding study evaluating the efficacy and safety of different doses of rivaroxaban (Xarelto, Bayer HealthCare AG, Wuppertal, Germany) for thromboprophylaxis, relative to enoxaparin. Deep vein thrombosis was diagnosed by mandatory venography performed 5-9 days after THR, or earlier if symptomatic. Symptomatic pulmonary embolism was diagnosed by objective testing. Bleeding complications were registered and stratified into major bleeding, clinically relevant, non-major bleeding, and minor bleeding, using predefined criteria. RESULTS: Eighty-four patients had a VTE and 57 patients had a bleeding event (n = 722). Significantly higher median uF1 + 2 levels were observed in the VTE group on day 3 after THR (P = 0.03), compared with control. Median uF1 + 2 levels were lower in the bleeding group on day 3 after THR (P = 0.005) and on the day of venography (P = 0.36), compared with control. Comparisons between the VTE and bleeding groups showed significantly lower median uF1 + 2 levels in the bleeding group on day 3 after THR and on the day of venography (P < 0.0001 and P = 0.006, respectively). CONCLUSIONS: Measurement of uF1 + 2 could provide a simple clinical test to evaluate non-invasively the intensity of coagulation activation after THR. However, further studies are required to confirm these encouraging preliminary results.

Rivaroxaban. A novel, oral, direct factor Xa inhibitor in clinical development for the prevention and treatment of thromboembolic disorders.

Rivaroxaban (Xarelto) is a novel, oral, direct Factor Xa (FXa) inhibitor in late-stage development for the prevention and treatment of thromboembolic disorders. Rivaroxaban inhibits clot-associated and free FXa activity, and prothrombinase activity, and reduces thrombin generation. In animal models, rivaroxaban prevented venous and arterial thrombosis, and was effective at treating venous thrombosis. Rivaroxaban has high oral bioavailability, a rapid onset of action and predictable pharmacokinetics. In phase II studies, rivaroxaban was effective and well tolerated for the prevention of venous thromboembolism (VTE) after major orthopaedic surgery, and for the treatment of deep vein thrombosis. In a phase III study, rivaroxaban demonstrated significantly superior efficacy to enoxaparin for thromboprophylaxis after total knee arthroplasty, with similar low bleeding. Rivaroxaban is also being assessed for the treatment and secondary prevention of VTE, prevention of stroke in patients with atrial fibrillation and secondary prevention in patients with acute coronary syndrome. Rivaroxaban is a promising alternative to current pharmacological agents for thromboembolic disorders.

Ultrasound screening for asymptomatic deep vein thrombosis after major orthopaedic surgery: the VENUS study.

BACKGROUND: Venography is currently used to assess the incidence of deep vein thrombosis (DVT) in dose-finding and confirmatory trials of new antithrombotic agents. Centrally adjudicated, complete compression ultrasound (CCUS) could be a non-invasive alternative to venography. OBJECTIVES: A substudy of two, similarly designed, phase IIb trials of a novel, oral anticoagulant for the prevention of venous thromboembolism after elective hip or knee arthroplasty was undertaken to validate CCUS against venography. PATIENTS/METHODS: Patients received study drugs until mandatory, bilateral venography was performed 7 +/- 2 days after surgery. CCUS was performed within 24 h after venography by sonographers blinded to the venography result. Sonographers were trained and certified for the standardized examination and documentation procedure. Venograms and sonograms were adjudicated centrally at different sites by two independent readers; discrepancies between readers were resolved by consensus. RESULTS: A total of 1104 matching pairs of evaluable venograms and sonograms were obtained from the participants of the two trials (n = 1435): 19% of venograms and 20% of sonograms were not evaluable. The observed frequency of any DVT was 18.9% with venography and 11.5% with CCUS. Sensitivity of CCUS compared with venography was 31.1% for any DVT (95% confidence interval 23.4, 38.9), 21.0% (2.7, 39.4) for proximal DVT, and 30.8% (23.1, 38.6) for distal DVT. The figures for specificity were 93.0% (91.0, 95.1), 98.7% (98.0, 99.5), and 93.3% (91.5, 95.3), respectively. CONCLUSIONS: Based on these results, centrally adjudicated CCUS will be unable to replace venography for DVT screening early after major orthopaedic surgery in studies evaluating anticoagulant drugs.

Prevention of major venous thromboembolism following total hip or knee replacement: a randomized comparison of low-molecular-weight heparin with unfractionated heparin (ECHOS Trial).

AIM: Venous thromboembolism remains a frequent complication after total hip or knee replacement surgery despite routine prophylaxis. However, the ability of pharmacologic thromboprophylaxis to prevent major venous thromboembolism, defined as proximal deep vein thrombosis, and/or pulmonary embolism, and/or death, has not been previously validated. METHODS: In a double-blind randomized study, 2018 patients, undergoing either total hip or knee replacement surgery, were allocated to receive subcutaneous preoperative reviparin (4,200 anti Xa IU) once daily or 7,500 IU unfractionated heparin twice daily, for a minimum of 11 days. The primary efficacy outcome was major venous thromboembolism, defined as the composite of venographically confirmed proximal deep vein thrombosis, and/or symptomatic pulmonary embolism and death, recorded up to day 14. RESULTS: The primary efficacy outcome was assessed in 1,628 patients and demonstrated a significant reduction in the reviparin group (3.4% [28 of 813 patients] compared with unfractionated heparin (5.5% [45 of 815]) (odds ratio, 0.61; 95% confidence interval, 0.38 to 0.99, P=0.04) by day 11 to 14. A significant reduction in venous thromboembolism was maintained up to 6-8 weeks (3.4% [28 of 813 reviparin patients] versus 5.6% [46 of 815 unfractionated heparin patients]) (odds ratio, 0.6; 95% confidence interval, 0.37 to 0.97, P=0.03). Major bleeding events occurred in 9 reviparin-treated patients (0.9%) and in 12 unfractionated heparin-treated patients (1.2%). CONCLUSIONS: Prophylaxis with reviparin significantly reduces the risk of major venous thromboembolism compared with unfractionated heparin in patients undergoing elective hip or knee replacement without increasing the risk of bleeding.

Oral, direct Factor Xa inhibition with BAY 59-7939 for the prevention of venous thromboembolism after total hip replacement.

BACKGROUND: Joint replacement surgery is an appropriate model for dose-ranging studies investigating new anticoagulants. OBJECTIVES: To assess the efficacy and safety of a novel, oral, direct factor Xa (FXa) inhibitor--BAY 59-7939--relative to enoxaparin in patients undergoing elective total hip replacement. METHODS: In this double-blind, double-dummy, dose-ranging study, patients were randomized to oral BAY 59-7939 (2.5, 5, 10, 20, or 30 mg b.i.d.), starting 6-8 h after surgery, or s.c. enoxaparin 40 mg once daily, starting on the evening before surgery. Treatment was continued until mandatory bilateral venography was performed 5-9 days after surgery. RESULTS: Of 706 patients treated, 548 were eligible for the primary efficacy analysis. The primary efficacy endpoint was the incidence of any deep vein thrombosis, non-fatal pulmonary embolism, and all-cause mortality; rates were 15%, 14%, 12%, 18%, and 7% for BAY 59-7939 2.5, 5, 10, 20, and 30 mg b.i.d., respectively, compared with 17% for enoxaparin. The primary efficacy analysis did not demonstrate any significant trend in dose-response relationship for BAY 59-7939. The primary safety endpoint was major, postoperative bleeding; there was a significant increase in the frequency of events with increasing doses of BAY 59-7939 (P = 0.045), but no significant differences between individual BAY 59-7939 doses and enoxaparin. CONCLUSIONS: When efficacy and safety were considered together, the oral, direct FXa inhibitor BAY 59-7939, at 2.5-10 mg b.i.d., compared favorably with enoxaparin for the prevention of venous thromboembolism in patients undergoing elective total hip replacement.

BAY 59-7939: an oral, direct factor Xa inhibitor for the prevention of venous thromboembolism in patients after total knee replacement. A phase II dose-ranging study.

BACKGROUND: BAY 59-7939, a novel, oral, direct factor Xa inhibitor, is in clinical development for the prevention of venous thromboembolism (VTE), a frequent complication following orthopaedic surgery. METHODS: In a multicenter, parallel-group, double-blind, double-dummy study, 621 patients undergoing elective total knee replacement were randomly assigned to oral BAY 59-7939 (2.5, 5, 10, 20, and 30 mg b.i.d., initiated 6-8 h postsurgery), or subcutaneous enoxaparin (30 mg b.i.d., initiated 12-24 h postsurgery). Treatment was continued until mandatory bilateral venography 5-9 days after surgery. The primary efficacy endpoint was a composite of any deep vein thrombosis (proximal and/or distal), confirmed non-fatal pulmonary embolism and all-cause mortality during treatment. The primary safety endpoint was major, postoperative bleeding during treatment. RESULTS: Of the 613 patients treated, 366 (59.7%) were evaluable for the primary efficacy analysis. The primary efficacy endpoint occurred in 31.7%, 40.4%, 23.3%, 35.1%, and 25.4% of patients receiving 2.5, 5, 10, 20 and 30 mg b.i.d. doses of BAY 59-7939, respectively (test for trend, P = 0.29), compared with 44.3% in the enoxaparin group. The frequency of major, postoperative bleeding increased with increasing doses of BAY 59-7939 (test for trend, P = 0.0007), with no significant difference between any dose group compared with enoxaparin. Bleeding endpoints were lower for the 2.5-10 mg b.i.d. doses compared with higher doses of BAY 59-7939. CONCLUSIONS: Oral administration of 2.5-10 mg b.i.d. of BAY 59-7939, early in the postoperative period, showed potential efficacy and an acceptable safety profile, similar to enoxaparin, for the prevention of VTE in patients undergoing elective total knee replacement.

Prevention of venous thromboembolism after knee arthroscopy with low-molecular weight heparin (reviparin): Results of a randomized controlled trial.

PURPOSE: Deep venous thrombosis (DVT) is a common, important complication of major orthopaedic surgery, particularly knee arthroplasty. Knee arthroscopy is increasingly performed on an outpatient basis. Few reports have elucidated the incidence of venous thromboembolism (VTE) in patients undergoing arthroscopic surgery receiving no prophylaxis. The objective of the present trial was to evaluate the risk of VTE in those patients and to determine efficacy and safety of a low-molecular weight heparin (LMWH) in preventing VTE. TYPE OF STUDY: This is the first controlled randomized trial using objective diagnostic methods with blinded outcome assessment to reveal the incidence of VTE in outpatient arthroscopy and determine efficacy and safety of a LMWH (reviparin sodium) in preventing VTE in these patients. METHODS: There were 262 patients undergoing elective knee arthroscopy prospectively randomized to receive either no treatment or reviparin once daily subcutaneously for 7 to 10 days. The blindly assessed primary outcome measure was the incidence of DVT detected by compression color-coded sonography. Both groups were comparable with regard to demographics and baseline characteristics. RESULTS: 239 patients were evaluable (122 no treatment, 117 receiving LMWH). 6 DVT were detected - 5 in the control group (5/117 - 4.1%) and only one in the active treatment group (1/116 - 0.85%). This particular patient had a low level of protein C and a subnormal level of protein S. The odds ratio of 4.95 approximates a relative risk reduction of about 80%. Treatment with reviparin was safe and well tolerated. There was no major bleeding, four patients with minor bleedings. One patient had a transitory fall in platelet count below 100 giga-particles/L without any clinical symptoms. CONCLUSIONS: Patients undergoing knee arthroscopy have a moderate risk of VTE and effective prophylaxis can be achieved with LMWH (reviparin).

[Prevention of thromboembolism with low-molecular-weight heparin in ambulatory surgery and unoperated surgical and orthopedic patients]. / Thromboembolieprophylaxe mit niedermolekularem Heparin bei ambulanten operierten und nicht-operierten chirurgischen und orthopädischen Patienten.

Prophylaxis of thromboembolism is now well established in orthopaedic outpatients with plaster cast and after elective hip surgery. The present study was undertaken to evaluate the safety of out-of-hospital prevention of venous thromboembolism and to determine the incidence of thromboembolic complications in orthopaedic and surgical patients with or without surgical intervention on an out-patient basis during prophylaxis of thromboembolism with low-molecular-weight heparin and to study the feasibility of this treatment regimen. The treatment period was 1-4 weeks (mean 17 days). Main indications for prophylaxis of thromboembolism were arthroscopy and surgical or non-surgical intervention of bone fractures of the lower leg. The incidence of clinically diagnosed venous thromboembolism was 11/1604 (0.7%) in operated and 8/1017 (0.8%) in non-operated patients. Pulmonary embolism occurred twice in operated patients (0.1%) and in none of the non-operated patients. Minor bleeding complications were rare and major bleeding complications did not occur. Haematomas at the injection site occurred in only 4% of patients. Thrombocytopenia did not occur in any patient. The present study demonstrates the feasibility and safety to prophylaxis of thromboembolism with low-molecular-weight heparin in orthopaedic operated and non-operated out-patients with various orthopaedic or surgical diseases leading to immobilization. The incidence of clinically apparent thromboembolic complications is low and similar to medical bedridden inpatients.

[Prevention of thromboembolism in minimal invasive interventions and brief inpatient treatment. Results of a multicenter, prospective, randomized, controlled study with a low molecular weight heparin]. / Thromboembolieprophylaxe bei minimal-invasiven Eingriffen und kurzstationärer Behandlung. Ergebnisse einer multicentrischen, prospektiven, randomisierten, kontrollierten Studie mit einem niedermolekularen Heparin.

A prospective, randomised, controlled clinical trial was carried out in order to elucidate the incidence of venous thromboembolism in selected patients undergoing laparoscopic cholecystectomy and other types of minimally invasive surgery, as well as to show safety and efficacy of a low-molecular-weight heparin (LMWH) in the prevention of post-operative venous thromboembolism. Seven hundred and eighteen patients were randomly allocated to one of two groups: One group received physical measures for prevention of deep-vein thrombosis, i.e. graduated elastic stockings (n = 359). The second group also received graduated elastic stockings and, additionally, a LMWH (reviparin sodium, Clivarin) s.c. once daily (n = 359). For safety reasons, with respect to the untreated control group, patients with three or more risk factors for venous thromboembolism were not included into the trial. Diagnosis for DVT was systematically done by duplex scan. In this, rather artificial low-risk selection the overall incidence of thromboembolic events was surprisingly low: five cases of suspected pulmonary embolism, confirmed by scintigraphy in one case only, and one patient with phlebographically confirmed calf vein thrombosis. The use of reviparin for prevention of venous thromboembolism was safe and convenient--the rate of post-operative bleeding complications was 2.3% in the LMWH group, even lower than in the control group (3.2%). The real incidence of venous thromboembolism in patients undergoing laparoscopic cholecystectomy remains unclear. Further trials with unselected patients are needed.

The role of platelet prostanoids and dense granule compounds in initial attachment, spreading and aggregation of platelets on collagen substrates.

The role of platelet prostanoids, ADP and 5HT in initial attachment, spreading and aggregation of platelets on collagen substrates (CI, CIII, CIV, CV, CC) was studied. A positive linear correlation was found between thrombi-like aggregate formation on collagen substrates and production of platelet prostanoids. No correlation was established between platelet aggregation and 14C-5HT release. Thrombi-like aggregate formation was completely inhibited by indomethacin and TXA2/PGH2 antagonists (13-APA and BM 13.177). Both 13-APA and BM 13.177 had no effect on platelet spreading, while indomethacin inhibited this process by 25%. The ADP-scavenger system (CP/CPK) inhibited platelet aggregation and spreading by 25-30%. Initial attachment was not influenced by aspirin, indomethacin and CP/CPK. The data obtained indicate that platelet aggregation on collagen substrates is mediated by PGH2 and TXA2 production. These compounds slightly affect the platelet spreading. Both platelet spreading and aggregation on collagen substrates are only partially mediated by ADP and 5HT release. Initial attachment of platelets does not depend on the release reaction and PGH2/TXA2 synthesis.

Phorbol ester stimulates platelet spreading and thrombi-like aggregate formation on the surface of immobilized type V collagen.

We have studied the effect of the tumor-promoting phorbol ester, 4 beta-phorbol-12 beta-myristate-13 a-acetate (PMA), and of the stable prostaglandin endoperoxide analogue U46619 on the interaction of human blood platelets with surfaces coated with monomeric human type V collagen (CV) and on free calcium concentration in platelet cytoplasm. It was shown by scanning electron microscopy that native resting platelets sparingly attach to CV and fail to spread or aggregate on the collagenous substrate in the absence of PMA and U46619. Addition of 0.15-1.5 nM PMA or 1.5 microM U46619 stimulates platelet spreading and formation of multilayer (thrombi-like) platelet aggregates on the per se non-thrombogenic type V collagen substrate. It was further demonstrated using the fluorescent indicator quin2 that U46619 (0.1 microM) increases cytoplasmic free calcium concentration from basal level (100-120 nM) up to 600 nM, whereas PMA (0.75-15 nM) exerts only a minor effect, increasing free calcium level by 30-40 nM. These results indicate that the tumor-promoting phorbol ester PMA induces massive platelet spreading and aggregation on surfaces coated with non-thrombogenic type V collagen via activation of protein kinase C with little or no apparent change in free cytoplasmic calcium.

Individually controlled aspirin in the long-term treatment of patients with chronic arterial diseases.

A simple method of measuring the biological effect of acetylsalicylic acid (ASA), based on the determination of the disaggregation rate (DR) of platelet aggregation induced by adenosine diphosphate (ADP), is described. The DR was found to correlate with the inhibition of the production of malondialdehyde (MDA) by platelets (r = 0.66, P less than 0.001). Therefore, the DR was used for laboratory monitoring of the ASA effect. The study included 63 arteriosclerotic patients--patients with ischemic heart disease (IHD), peripheral arterial disease (PAD), or cerebrovascular insufficiency (CVI) -- who were analyzed before treatment and after receiving ASA in an individually controlled dosage. Before treatment the authors found an increased level of MDA and a longer euglobulin clot lysis time in patients when compared with healthy volunteers (n = 16). Extremely different doses of ASA were required to normalize initially elevated MDA levels in patients. Normalization of the MDA level corresponds to a DR of at least 50% (in comparison with 0-13% without treatment). When judging the ASA dose individually from the 50% DR, the authors demonstrated that there were no differences in the levels of cyclooxygenase- and lipoxygenase-derived eicosanoids between healthy volunteers (n = 16) and arteriosclerotic patients receiving 100-250 mg (n = 18), 500 mg (n = 17), or 750-1500 mg ASA per day (n = 6). Thus, their results support the idea of using individually controlled ASA as the most promising way of resolving the "aspirin dilemma" and provide a simple and reproducible method of measuring the biological effect of ASA.

[Influencing the fibrinolytic activity by antithrombotics in patients with atherosclerosis]. / Die Beeinflussung der Fibrinolysekapazität durch Antithrombotika bei Patienten mit Arteriosklerose.

In 106 atherosclerotic patients receiving an anticoagulant therapy and 91 patients receiving acetylsalicylic acid, fibrinogen and fibrin degradation products were determined as well as euglobulin lysis before and after venous occlusion. Platelet function data and thromboxane (TXB2) were also determined. Since "moderate" anticoagulant therapy with thromboplastin time values 26-40% results in deteriorated fibrinolysis data, anticoagulant therapy is strictly to remain within the therapeutic range of 15-20% up to 25% thromboplastin time at maximum. Treatment with acetylsalicylic acid proved useful on condition that the required dose was determined individually. This type of treatment will then be able to reduce the thromboxane level and positively influence the fibrinolytic potential.