Osteometabolic and osteogenetic pattern of Turkish immigrants in Germany.

INTRODUCTION: The etiology of osteoporosis comprises environmental and genetic factors. This study investigated vitamin D deficiency and specific genetic alterations of bone metabolism in a group of 183 Turkish immigrants in Germany in comparison with 46 age and sex matched healthy German controls (females in both groups were pre-menopausal). METHODS: Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry. Serum levels of osteologic parameters were determined after overnight fasting. Polymorphisms of the vitamin D receptor (VDR) and lactase genes were genotyped using genomic DNA from peripheral leukocytes. Statistical analysis comprised student's t-test, Mann-Whitney rank sum test, Chi-square analysis and Fisher's exact test. RESULTS: Severe 25-OH D3 hypovitaminosis (83.1%) and elevated parathyroid hormone (82%) were common among immigrants. Osteoporosis but not osteopenia was more prevalent in immigrants. Among immigrants with osteoporosis, TRAP5b was elevated in 26.7%, and ß-crosslaps in 13.3%. Only the FokI FF VDR-gene-polymorphism was significantly more prevalent among immigrants. In contrast, Ff-genotyped Turkish women exhibited significantly decreased BMD. Lactase polymorphisms were significantly more common among immigrants (84.2% vs. 30.4%) and the CC genotype was commonly associated with reduced BMD (41.6%) but rarely osteoporosis (8.4%). CONCLUSIONS: Vitamin D deficiency, secondary hyperparathyroidism and osteoporosis are common among Turkish immigrants in Germany. Thus, in this population osteologic parameters and BMD should be analyzed and deficiencies be treated. Specifically, the VDR gene polymorphism FokI Ff is of clinical value in identifying females at risk of osteoporosis. In contrast, LCT polymorphisms, though common, do not appear to be a risk factor.

[New anticoagulant drugs for atrial fibrillation. Feasibility and necessity of monitoring]. / Neue Antikoagulanzien bei Vorhofflimmern. Ist ein Monitoring möglich und notwendig?

Two novel oral anticoagulants, namely the direct thrombin inhibitor dabigatran and the direct factor Xa inhibitor rivaroxaban, have recently been approved for treatment of atrial fibrillation. They differ in many ways from vitamin K antagonists, including rapid onset of action, shorter half-life, fewer drug-drug interactions, lack of a need for monitoring and no need for titration or dose adjustments. Commonly available global coagulation time assessments (e.g. prothrombin time and activated partial thromboplastin time) are highly influenced by rivaroxaban and dabigatran but these assays are relatively insensitive. Ideally these anticoagulant agents would be assessable using a sensitive and standardized test with a linear dose-response curve. Optimized assays are currently under investigation and may quantify the anticoagulant effect. At present the therapeutic ranges for dose adjustment have not yet been established.

Recombinant hirudin for cardiopulmonary bypass anticoagulation: a randomized, prospective, and heparin-controlled pilot study.

BACKGROUND: Lepirudin, a recombinant hirudin, is a direct acting thrombin inhibitor that has been used as a heparin alternative in patients with heparin-induced thrombocytopenia requiring on-pump cardiac surgery. To evaluate the efficacy, safety, and clinical utility of lepirudin as a cardiopulmonary bypass (CPB) anticoagulant, we compared lepirudin with heparin in a routine CPB setting. METHODS: Twenty patients were randomly assigned to receive lepirudin (0.25 mg/kg b. w. bolus and 0.2 mg/kg b. w. added to the CPB priming) or heparin (400 U/kg b. w. bolus) with protamine reversal. Lepirudin and heparin anticoagulation during CPB was monitored using the ecarin clotting time or ACT, respectively and additional lepirudin (5 mg) or heparin (5000 U) boluses were administered. RESULTS: The CPB circuit was performed in both groups without thromboembolic complications. Median blood loss during the first 36 hours was statistically higher ( P = 0.007) in the lepirudin group (1.226 +/- 316 ml) compared to the heparin group (869 +/- 189 ml). One patient of the lepirudin group developed pulmonary embolism 24 hours after surgery. This patient was tested homozygous for the FV-Leiden mutation. CONCLUSION: Lepirudin provides effective CPB anticoagulation but induces a higher postoperative blood loss than heparin. Lepirudin should be restricted to patients undergoing CPB who cannot be exposed to heparin.

[The management of patients with heparin-induced thrombocytopenia]. / Management von Patienten mit heparininduzierter Thrombozytopenie.

Heparin-induced thrombocytopenia is a strong risk factor for the development of arterial and venous thromboembolic events. In patients clinically suspected for HIT, immediate cessation of heparin treatment and continuation of anticoagulant treatment using alternative anticoagulants is mandatory in order to minimize the risk of thrombotic events. Alternative anticoagulants that have been successfully used in HIT include the direct acting thrombin inhibitors hirudin, bivalirudin and argatroban, and the heparinoid orgaran. In addition, there is growing evidence that the synthetic pentasaccharide fondaparinux is usable for the treatment of HIT patients. This short review summarizes the strategies of alternate anticoagulant treatment in HIT patients and also describes long-term treatment of HIT patients.

Monitoring of recombinant hirudin: assessment of a plasma-based ecarin clotting time assay.

Assay conditions of a plasma-based ecarin clotting time (ECT) were evaluated and the precision of the ECT in monitoring plasma levels of r-hirudin assessed. The snake venom enzyme ecarin converts prothrombin to meizothrombin possessing only weak coagulant but strong esterase activity. In r-hirudin containing plasma samples, meizo thrombin is rapidly neutralized by r-hirudin resulting in a dose-dependent prolongation of the clotting times. Among the different assay conditions tested, addition of 50 microliters of ecarin (4 U/ml) to 100 microliters of undiluted citrate-anticoagulated plasma gave optimal results with respect to precision and reproducibility. The measuring range of the ECT performed in this way is about 0.02-5.0 micrograms/ml r-hirudin. In vitro studies performed on r-hirudin-spiked plasma samples of 50 healthy individuals demonstrate remarkably low interindividual differences in r-hirudin responsiveness as indicated by CV-values below 5% and 7% at r-hirudin concentrations between 0-3 micrograms/ml and 4-5 micrograms/ml, respectively. The specificity for r-hirudin of the ECT is further demonstrated by the strong correlation (r = 0.94) between the results of a chromogenic assay and the ECT-measured r-hirudin concentrations obtained on 67 ex vivo blood samples. Depending on the concentration of r-hirudin the ECT is sensitive to plasma levels of prothrombin. In the absence of r-hirudin the critical prothrombin concentration was found to be 20% but increasing to 60% in the presence of 2.0 micrograms/ml r-hirudin. A fibrinogen concentration of 50 mg/dl was found to be the minimal concentration independent of the r-hirudin concentration. The precision of the ECT in measuring plasma levels of r-hirudin is not influenced by treatment with heparin, aprotinin or oral anticoagulants. The data demonstrate that the ECT is a rapid and easily perfor mable clotting assay which allows accurate measurement of r-hirudin plasma levels. ECT-monitored hirudin treatment will help to establish optimal dose regimens that are more efficacious but still as safe as heparin.

Monitoring of r-hirudin anticoagulation during cardiopulmonary bypass--assessment of the whole blood ecarin clotting time.

The use of recombinant (r) hirudin as an anticoagulant in performing extracorporeal circulation systems including cardiopulmonary bypass (CPB) devices requires a specific and easy to handle monitoring system. The usefulness of the celite-induced activated clotting time (ACT) and the activated partial thromboplastin time (APTT) for r-hirudin monitoring has been tested on ex vivo blood samples obtained from eight patients treated with r-hirudin during open heart surgery. The very poor relationship between the prolongation of the ACT and APTT values and the concentration of r-hirudin as measured using a chromogenic factor IIa assay indicates that both assays are not suitable to monitor r-hirudin anticoagulation. As an alternative approach a whole blood clotting assay based on the prothrombin-activating snake venom ecarin has been tested. In vitro experiments using r-hirudin-spiked whole blood samples showed a linear relationship between the concentration of hirudin added and the prolongation of the clotting times up to a concentration of r-hirudin of 4.0 micrograms/ml. Interassay coefficients (CV) of variation between 2.1% and 5.4% demonstrate the accuracy of the ecarin clotting time (ECT) assay. Differences in the interindividual responsiveness to r-hirudin were analyzed on r-hirudin-spiked blood samples obtained from 50 healthy blood donors. CV-values between 1.8% and 6% measured at r-hirudin concentrations between 0.5 and 4 micrograms/ml indicate remarkably slight differences in r-hirudin responsiveness. ECT assay results of the ex vivo blood samples linearily correlate (r = 0.79) to the concentration of r-hirudin. Moreover, assay results were not influenced by treatment with aprotinin or heparin. These findings together with the short measuring time with less than 120 seconds warrant the whole blood ECT to be a suitable assay for monitoring of r-hirudin anticoagulation in cardiac surgery.