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Biomedical subjects

B Kemkes-Matthes

Publications and source records attributed to B Kemkes-Matthes.

At least 19 recordsLinked to original sources
PubMed2006

Elevated Lipoprotein(a) does not promote early atherosclerotic changes of the carotid arteries in young, healthy adults.

BACKGROUND: Elevated levels of Lipoprotein(a) [Lp(a)] have been linked to an increased risk of ischemic cardiovascular events. Yet the mechanism by which Lp(a) might contribute to this increased risk is not clear. METHODS: To elucidate whether high plasma levels of Lp(a) contribute to the development of early atherosclerotic vessel wall changes, the intima-media thickness of the common carotid arteries [CCA-IMT] of 151 healthy young volunteers without additional relevant cardiovascular risk factors was measured by high-resolution ultrasound. Plasma concentrations of Lp(a) were quantified and other established risk factors, such as body mass index [BMI], plasma levels of cholesterol, triglycerides and homocysteine, were determined. Furthermore, the carotid arteries were examined for the presence of plaques and stenoses. RESULTS: Univariate analysis showed a significantly negative correlation of CCA-IMT with HDL cholesterol and positive correlations with age, BMI, total and LDL cholesterol, triglycerides and even with homocysteine, but not with Lp(a). When the study population was dichotomized according to Lp(a) levels, no statistically significant differences in CCA-IMT could be detected between persons with plasma Lp(a)<300mg/l or >or=300mg/l, respectively. CONCLUSION: Our data suggest that elevated Lp(a) levels alone do not contribute to increased cardiovascular risk by promoting early atherogenesis in vivo.

Adult↗
PubMed2004

[Osteoporosis in patients under oral anticoagulant treatment].

BACKGROUND AND OBJECTIVE: Osteoporosis is thought to be one possible side-effect of oral anticoagulant therapy, especially after long-term treatment. Nevertheless, data concerning this problem only exist from earlier years. Therefore, we decided to look for the incidence of osteoporosis in patients under long-term oral anticoagulant treatment. PATIENTS AND METHODS: 30 patients (15 female, 15 male) - age between 38 and 77 years (average age 65,1+/-11,2 years) were examined. Group A: 10 patients with a capture time between 0,5 - 5 years, Group B: 10 patients with a capture time between 6 - 11 years, Group C: 10 patients with a capture time more than 11 years. The control group consisted 30 healthy persons - age between 39 and 81 years (18 female, 12 male, average age 61,5 +/- 12 years). RESULTS: In 21 out of 30 patients (9 female, 12 male) osteoporosis was found due to results of x-ray and bone-density-measurements. In 9 patients (6 female, 3 male) no osteoporosis was detected. No correlation between appearance of osteoporosis and duration of oral anticoagulant treatment was detected. Nevertheless, the number of patients presenting with osteoporosis in comparison with the control group was highly unexpected and astonishing. CONCLUSION: While treating patients with oral anticoagulants the possibility of appearing osteoporosis should be kept in view. In those circumstances the therapy should be supported by calcium and vitamin D.

Administration, Oral↗
PubMed2004

[Oral anticoagulants and coumarin classes].

A survey is given on pharmacology and indications for the treatment with vitamin K antagonists. The therapeutic handling and self control by the patient is described.

Administration, Oral↗
PubMed2003

Arthritis is linked to local and systemic activation of coagulation and fibrinolysis pathways.

BACKGROUND: Activation of coagulation and fibrinolysis play a role in the pathophysiology of experimental arthritis. OBJECTIVE: To determine the extent of activation of the coagulation and fibrinolytic pathways in different joint diseases in humans and to ascertain the factors that may influence fibrin deposition within the joint. METHODS: Plasma from normal subjects (controls, n= 21) and plasma and synovial fluid samples from patients with rheumatoid arthritis (RA; n = 64), osteoarthritis (OA; n = 29), spondyloarthropathy (SpA; n = 22) and crystal arthritis (CA; n = 25) were analyzed for the levels of TF (tissue factor) and tissue factor pathway inhibitor (TFPI) activities, thrombin-antithrombin III (TAT) complexes, and F1 + 2 (thrombin fragment), fibrin d-dimer and thrombin-activated fibrinolysis inhibitor (TAFI) antigenic levels. The measurements were analyzed by pairwise correlation with each other as well as with standard parameters of inflammation [C-reactive protein (CRP), joint leukocyte count]. Inter-group comparisons were performed to look for disease-specific differences. RESULTS: Compared with healthy controls, patients with joint diseases had higher levels of TAT, F1 + 2 and d-dimers in their plasma. In the synovial fluid, TF activity, TAT, d-dimers, and TAFI were significantly higher in inflammatory arthritides than in OA. The levels were highest in RA patients. In the plasma, TF activity was correlated with TAT and d-dimer levels with CRP, TFPI, and TAT. In the synovial fluid, TF activity correlated with plasma CRP levels, synovial fluid leukocyte count, and synovial TAT and TAFI levels. In addition, synovial d-dimers correlated with CRP, and synovial TAFI levels were correlated with synovial F1 + 2 and TAT. CONCLUSIONS: Activation of the coagulation and fibrinolytic cascades in the joint and in the circulation is evident in both inflammatory and degenerative joint diseases. Within the joint, inflammatory mechanisms leading to TF-mediated activation of the coagulation pathway and subsequent fibrin deposition is the most likely explanation for the observed findings. In the plasma, the link between inflammation (CRP increase) and TF activation is weak, and a non-TF-mediated mechanism of coagulation activation could explain these findings. RA is characterized by significantly higher levels of TAT in the synovial fluid and plasma than other arthritides. Although fibrinolytic activity is linked to inflammation, the increased amounts of TAFI in the joint, particularly in RA, may explain why fibrin formation is so prominent in this condition compared with other joint diseases.

Adult↗
PubMed2002

[Initiation of oral anticoagulant treatment: comparison between different dosage regimens of warfarin and phenprocoumon].

A high "loading dosage" is often given during initiation of oral anticoagulant treatment in order to reach sufficient anticoagulation within short time. Increased bleeding risk as well as a transient prothrombotic tendency are complications of this treatment schedule. The aim of our study was to find proper dosage regimens of phenprocoumon and warfarin allowing initiation of oral anticoagulant treatment in a short time. For 50% of the patients 7.5 mg warfarin daily resulted in stable INR values within 4 days. Patients receiving higher (10 mg) or lower (5 mg) daily dosages of warfarin or 6 or 9 mg phenprocoumon daily during the first days of therapy reached the therapeutic range significantly later. Furthermore, no significant differences of prothrombin fragment F 1+2 were observed, indicating that no enhanced thrombin formation occurred. Thus, initiation of oral anticoagulant treatment using 7.5 mg warfarin daily is a simple and safe dosage regimen.

Administration, Oral↗
PubMed2001

Comparison of GP IIB/IIIA inhibitors and their activity as measured by aggregometry, flow cytometry, single platelet counting, and the rapid platelet function analyzer.

BACKGROUND: GP IIb/IIIa inhibitors have primarily been used short-term e.g., during PTCA. They failed to show clinical benefit during long-term therapy. One reason might be the absence of a method to monitor inhibitor activity. This study compared platelet aggregometry, the rapid platelet function analyzer (RPFA) test, single platelet counting, and flow cytometric determination of receptor occupancy to measure GP IIb/IIIa-receptor inhibitor activity. METHODS: Increasing doses of abciximab, tirofiban, and eptifibatide were added to whole blood in vitro. Whole blood was used for the RPFA, for single platelet counting and flow cytometry. Platelet rich plasma was prepared for aggregometry. RESULTS: The correlation between aggregometry and RPFA results was linear for abciximab and eptifibatide. Tirofiban was a stronger inhibitor with the RPFA (IC(50) 7.7nM) than with aggregometry (IC(50) 19.6nM). The single platelet counting technique showed that even supratherapeutic concentrations of all three inhibitors could not completely suppress microaggregation. Abciximab concentrations that were equipotent to tirofiban with aggregometry were less potent with regards to the inhibition of microaggregation. This difference was more pronounced with TRAP induced microaggregation than with ADP. The flow cytometric receptor occupancy test showed that occupancy was 95% with 5 microg/ml abciximab and almost 97% with 10 microg/ml. Tirofiban reached a maximum receptor occupancy of 56%, eptifibatide 64%. CONCLUSIONS: While aggregometry is time consuming the RPFA provides results fast and with little variability. There is still a discrepancy between aggregometry and RPFA results for tirofiban. The single platelet counting technique detects the inhibition of microaggregation the relevance of which for the clinical outcome is not known. The flow cytometric receptor occupancy assay is best suited for abciximab.

Dose-Response Relationship, Drug↗
PubMed2001

[Diagnosis of thrombophilia]].

Using laboratory testing, coagulation alterations can be detected in about 50% of familial thrombophilia. Most common hereditary coagulation defects leading to enhanced thrombosis risk are aPC resistance/Factor V Leiden mutation, protein C- and S-deficiency, prothrombin 20210A polymorphism and antithrombin deficiency. Moreover, elevated plasma levels of homocysteine also are associated with enhanced thrombosis risk. Severity of thromboembolic risk depends upon type of coagulation defect, hetero- or homocygosity and occurrence of additional acquired risk factors like immobilisation. Therapy of thromboembolic diseases must always be planned considering both clinical circumstances and laboratory findings.

Activated Protein C Resistance↗
PubMed2001

Protein Z.

Protein Z is a vitamin K-dependent protein. The first cases of protein Z deficiency were described in patients suffering from a bleeding tendency from otherwise unknown origin. Today, diminutions of protein Z seem to play a role not only in bleeding patients but also in patients with factor V Leiden mutation: Patients presenting with factor V Leiden mutation and low protein Z levels show earlier onset and higher frequency of thromboembolic events than do patients presenting with factor V Leiden mutation and normal protein Z levels. Thus, protein Z is a good example for the--at first sight--paradox action of coagulation proteins.

Adult↗
PubMed2001

[Changes in the blood coagulation system in pregnancy].

Extensive alterations of the coagulation system occur during pregnancy: Increasing levels of coagulation factors and continuous decrease of coagulation inhibitor protein S contribute to the increase of prothrombotic potential. Moreover, enhanced activation of coagulation factors, platelets and fibrinolytic system can be demonstrated by determination of activation parameters like prothrombin fragment F 1 + 2, beta-thromboglobulin and D-dimer. The alterations in the coagulation system are one cause for the enhanced thromboembolic risk during pregnancy.

Blood Coagulation Factors↗
PubMed2000

Simvastatin attenuates vascular hypercoagulability in cardiac transplant recipients.

BACKGROUND: 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have been shown to reduce cardiac allograft failure and to lower the incidence of transplant coronary artery disease. These effects result from as yet unknown mechanisms not clearly attributable to lipid lowering. We here report that low-dose simvastatin treatment inhibits excessive expression of monocyte tissue factor (TF) and reduces the persistent hypercoagulability state seen in cardiac transplant recipients. METHODS: Fifteen consecutive heart transplant recipients receiving standard oral immunosuppression were newly assigned to a 10 mg daily simvastatin therapy. Levels of TF activity in both unstimulated and lipopolysaccharide-stimulated peripheral blood mononuclear cells drawn from transplant recipients before and under simvastatin therapy were evaluated by one-stage clotting assay. RESULTS: Monocyte TF activity was found to be significantly increased in cardiac transplant recipients when compared with healthy controls. Excessive monocyte procoagulant activity was reduced in cardiac transplant recipients during simvastatin treatment. This effect occurred independently of the reduction of serum low-density lipoprotein cholesterol. As demonstrated by reverse transcriptase-polymerase chain reaction, monocyte TF reduction by simvastatin, observed in 13 of the 15 transplant recipients investigated, could be ascribed to an inhibition of monocyte TF gene transcription. The reduction of monocyte TF activity during treatment with simvastatin paralleled with the normalization of elevated levels of thrombin-antithrombin complex, prothrombin fragment F1+2, and D-dimer, which are markers of thrombin and fibrin formation indicating coagulation activation after cardiac transplantation. CONCLUSION: Inhibition of monocyte TF expression and attenuation of the persistent hypercoagulable state observed in cardiac transplant recipients during treatment with simvastatin may represent an important mechanism by which HMG-CoA reductase inhibitors protect against the development of transplant coronary artery disease.

Adult↗
PubMed2000

Screening for thrombophilic risk factors among 25 German patients with cerebral venous thrombosis.

OBJECTIVES: In this study the frequency of inherited thrombophilic risk factors in a population of German CVT patients and their influence on clinical outcome were evaluated. MATERIAL AND METHODS: Twenty-five patients (age 37.1 +/- 16.3 years) with CVT were screened for inherited coagulation disorders. All participants received a full clinical follow-up (mean follow-up period 4.8 +/- 6.4 years). RESULTS: Inherited thrombophilic risk factors were identified in 9 (36%) of the 25 patients studied. Four were found positive for the heterozygous factor V Leiden mutation, 2 were heterozygous carriers of the prothrombin-G20210A-polymorphism. APC resistance proved to be a reliable screening method for factor V Leiden mutation, whereas genetic evaluation for protein S and C deficiencies failed to demonstrate any mutations despite the identification of 1 patient with a protein C and protein S deficiency each. One patient suffered from a familial plasminogen deficiency. These 9 patients had a less favorable outcome (P < 0.05). CONCLUSION: Our results demonstrate that screening for inherited thrombophilia should be an integral part in the diagnostic work up of CVT patients. Patients with inherited coagulopathies tended to have a less favorable outcome, corroborating recommendations for a longer period of oral anticoagulation.

Adult↗
PubMed2000

Effect of glycoprotein IIb/IIIa inhibitors on CD62p expression, platelet aggregates, and microparticles in vitro.

Flow cytometry can detect platelet activation (CD62p), aggregate formation, microparticle formation, and glycoprotein IIb/IIIa (GP IIb/IIIa) receptor occupancy in one sample at the level of single particles. We studied the effect of GP IIb/IIIa inhibitors on platelet activation with flow cytometry in vitro. Citrated whole blood was incubated with increasing concentrations of three different GP IIb/IIIa inhibitors (c7E3, DMP728, XJ757), then thrombin or adenosine diphosphate (ADP) was added, and after 1 minute the sample was fixed. Samples with thrombin but without c7E3 had a decrease in platelet count, from a mean of 260,000 platelets/microl to 56,000 platelets/microL, and aggregates increased. Samples with concentrations of c7E3 that resulted in 80% or more receptor blockade had no decrease in platelet count, and no aggregates were formed, but the number of CD62p-positive single platelets increased from 1200 to 7400 platelets/microL. The two other inhibitors (DMP 725, XJ757) or ADP instead of thrombin gave similar results. Microparticle formation did not change with platelet activation in the presence of a GP IIb/IIIa inhibitor. With small inhibitor doses resulting in <80% receptor blockade, the number of aggregates did not change or was even higher than that in samples without inhibitor. GP IIb/IIIa inhibitors do prevent aggregate formation but they do not prevent activation of platelets. With GP IIb/IIIa inhibition, more activated single platelets remain in the blood. One may expect an increasing number of circulating, activated platelets with the use of GP IIb/IIIa inhibitors.

Antibodies, Monoclonal↗
PubMed2000

Ocular pulse amplitude in diabetes mellitus.

BACKGROUND: The influence of diabetes mellitus on ocular pulse amplitude (OPA), an indirect measure of choroidal perfusion, is unclear. METHODS: OPA, using the Langham ocular blood flow (OBF) system, applanation intraocular pressure (IOP), systemic blood pressure (BP), heart rate, and haemoglobin (Hb) A(1c) were measured in patients with insulin dependent diabetes mellitus (IDDM) with no (DR-0, n = 22) non-proliferative (DR-1, n = 24), and proliferative (DR-2, n = 18) diabetic retinopathy. RESULTS: Neither local (OPA, IOP) nor systemic perfusion parameters (BPs, HR) nor HbA(1c) were significantly altered in DR-0, DR-1, or DR-2 IDDM patients. CONCLUSION: Choroidal circulation remains unaffected as diabetic retinopathy advances.

Adult↗
PubMed1999

Lepirudin (recombinant hirudin) for parenteral anticoagulation in patients with heparin-induced thrombocytopenia. Heparin-Associated Thrombocytopenia Study (HAT) investigators.

BACKGROUND: We prospectively investigated lepirudin for further parenteral anticoagulation in patients with heparin-induced thrombocytopenia (HIT). METHODS AND RESULTS: Patients with confirmed HIT (n=112) received lepirudin according to need for 2 to 10 days (longer if necessary): A1, treatment: 0.4 mg/kg IV bolus, followed by 0.15 mg. kg(-1). h(-1) intravenous infusion, n=65; A2, treatment in conjunction with thrombolysis: 0.2 mg/kg, followed by 0.10 mg. kg(-1). h(-1), n=4; and B, prophylaxis: 0.10 mg. kg(-1). h(-1), n=43. Outcomes from 95 eligible lepirudin-treated patients were compared with those of historical control patients (n=120). Complete laboratory response (activated partial thromboplastin time ratio >1.5 with </=2 dose increases and platelet count normalization by day 10) was achieved in 65 lepirudin-treated patients (69.1%; 95% CI, 59. 3% to 78.3%). At 2 weeks after cessation of lepirudin, 11 patients died (9.8%), 10 underwent limb amputation (8.9%), and 20 suffered a new thromboembolic complication (17.9%). The average combined event rate per patient-day decreased from 5.1% in the pretreatment period to 1.5% in the treatment period. Thirty-five days after HIT confirmation, fewer lepirudin-treated patients than historical control patients had experienced >/=1 outcome (cumulative incidence 30.9% versus 52.1%; relative risk [RR] 0.71; P=0.12, log-rank test). Bleeding events were more frequent in the lepirudin group than the historical control group (cumulative incidence at 35 days, 44.6% versus 27.2%; RR 2.57; P=0.0001, log-rank test). No difference was observed in bleeding events requiring transfusion (cumulative incidence at 35 days, 12.9% versus 9.1%; RR 1.66; P=0.23, log-rank test); no intracranial bleeding was observed in the lepirudin group. CONCLUSIONS: Lepirudin effectively prevents death, limb amputations, and new thromboembolic complications and has an acceptable safety profile in HIT patients. Treatment should be initiated as soon as possible if HIT is suspected.

Aged↗
PubMed1999

Pharmacology of warfarin and clinical implications.

The history of oral anticoagulants started in the 1920s in North Dakota and Alberta when a new type of hemorrhagic disease struck cattle in these areas. The group of Karl Paul Link finally succeeded in isolating the causative agent, dicumarol. It was not before the 1940s, that dicumarol or its derivatives were introduced to medicine. Acenocoumarol, phenprocoumon, and warfarin are the most commonly used oral anticoagulants. There is no known difference in the pharmacodynamic activity of these agents on the vitamin K metabolism. They are completely absorbed from the gastrointestinal tract and are firmly bound to plasma albumin and metabolized in the liver. The different elimination half-lives of the coumarins have several implications for patient management. Absorption, protein binding, and anticoagulant activity of oral anticoagulants are affected in many different ways. Also the different pharmacological properties of coumarins require different strategies in the clinical management of patients.

Animals↗