Activation of coagulation and hyperfibrinolysis in patients with aortic arch atheromatosis (Aortic AA) as a risk factor for cerebral ischemia.

In patients with cerebral ischemia, a frequent finding is atheromatous plaques in the ascending aorta and the aortic arch. Since we were able to demonstrate that patients with atrial fibrillation have an increased coagulatory activity, we wanted to evaluate a potential systemic activation of the coagulatory system in patients with aortic arch atheromatosis (Aortic AA). In 134 consecutive patients, we determined several parameters of the coagulatory and fibrinolytic systems as well as several thrombophilia risk factors and compared the results with 134 age- and sex-matched healthy controls. In 90 of the 134 patients, transesophageal echocardiography showed Aortic AA, and in the remaining 44 patients, there were no aortic findings. The Aortic AA group showed higher concentrations of thrombin-antithrombin (TAT) and plasmin-antiplasmin complexes (PAP). Further division into 4 subgroups of different severity (grade I: no plaques; grade II: plaques 2-5 mm, grade III: plaques > 5 mm, grade IV: mobile plaques), revealed increasing concentrations of fibrinogen, D-dimers and tissue-type plasminogen activator. The grade IV-group displayed the highest values in comparison to all other groups. In conclusion, Aortic AA as such is a risk factor for cerebral ischemia. It causes a systemically detectable activation of coagulation which substantially exceeds the values for controls. This observation is in accordance with our findings in patients with atrial fibrillation.

Comparison of general and spinal anesthesia and their influence on hemostatic markers in patients undergoing total hip arthroplasty.

STUDY OBJECTIVE: To evaluate the profile of molecular hemostatic markers in patients receiving either spinal or balanced general anesthesia for total hip arthroplasty. DESIGN: Open, randomized, observational study. SETTING: Orthopedic unit and central laboratory of a university hospital. PATIENTS: 26 consenting ASA physical status II and III inpatients undergoing total hip arthroplasty with general balanced anesthesia (n = 10) or spinal (regional) anesthesia (n = 16). INTERVENTIONS: The time course of seven procoagulatory and fibrinolytic parameters was examined during and after surgery in both groups of patients (general and regional). Blood samples were drawn on the day before surgery, directly before induction of general anesthesia or regional anesthesia, respectively, intraoperatively (before bone manipulation), at the end of surgery, and on the mornings of postoperative days 1 and 5. MEASUREMENTS AND MAIN RESULTS: The coagulation samples were centrifuged within 1 hour of collection at 2,300 g for 15 minutes at 4 degrees C. Hemoglobin, hematocrit, platelets, fibrinogen, prothrombin time, thrombin time, activated partial thromboplastin time, antithrombin, and protein C were measured immediately on arrival at the laboratory. Specimens were then aliquoted and stored at -70 degrees C. Within 2 weeks, samples were thawed and prepared for the following assays: thrombin-antithrombin complexes (TAT complexes), D-dimers, plasminogen activator inhibitor type 1 (PAI-1), and plasminogen and plasmin inhibitor. Maximum activation of coagulation was not reached until 2 hours postoperatively and then slowly decreased until normal values were reached around the fifth postoperative day. Parameters displaying the greatest changes were antithrombin and D-dimers. No statistically significant differences were found between the two groups at the individual time points. CONCLUSION: Our initial hypothesis that the lesser risk of postoperative DVT in patients undergoing total hip arthroplasty in regional anesthesia is reflected in the course of the plasmatic molecular markers of hemostasis could not be verified. There were no significant differences in the timely course of the markers at any given time point.

Fixed-dose, body weight-independent subcutaneous low molecular weight heparin Certoparin compared with adjusted-dose intravenous unfractionated heparin in patients with proximal deep venous thrombosis.

Subcutaneous body weight-adjusted low molecular weight heparin (LMWH) has been proven as effective and safe as intravenous aPTT-adjusted unfractionated heparin (UFH) for the treatment of patients with acute deep venous thrombosis (DVT). In this study we evaluate the efficacy of the initial treatment of proximal DVT with a fixed-dose, body weight-independent application of the LMWH Certoparin with a six month follow-up. In a prospective, multicentre, randomized, active-controlled study 1220 patients with objectively diagnosed proximal DVT were randomly assigned to subcutaneous 8000 U anti-factor Xa of Certoparin twice daily for 10 to 14 days or intravenous aPTT-adjusted UFH for 5 to 8 days. Both regimen were followed by oral anticoagulation for 6 months. The primary end point was the rate of symptomatic and objectively confirmed thromboembolic events within 6 months. The aim of the study was to demonstrate the non-inferiority of the Certoparin regimen as compared to UFH. The per-protocol analysis revealed 22 (3.8%) thromboembolic events in the Certoparin group and 24 (4.3%) in patients assigned to UFH within 6 months, thereby proving the non-inferiority (p<0.01), confirmed by intent-to-treat analysis (p<0.001). Major bleeding occurred in 6 and 7 patients started on Certoparin or UFH during the treatment period. Thromboembolic events were equally distributed in body weight categories with < 50, 50-80 and >80 kg as followed: 0, 3.6% and 4.1% of patients for the Certoparin group and 0, 4.6% and 4.2% of patients for the UFH group. The same was true for major bleeding complications with 0, 2.9% and 1.5% for Certoparin and 0, 3.5% and 4.2% for UFH. Overall mortality was 1.9% in the Certoparin group and 2.7% in the UFH group. Fixed-dose body weight-independent subcutaneous LMWH Certoparin is at least as efficacious and safe as intravenous aPTT-adjusted UFH for the initial treatment of acute proximal DVT. This effect is maintained during a 6-months follow-up of treatment with oral anticoagulation.

Hemostasis and coagulation at a hematocrit level of 0.85: functional consequences of erythrocytosis.

We have generated a transgenic mouse line that reaches a hematocrit concentration of 0.85 due to constitutive overexpression of human erythropoietin in an oxygen-independent manner. Unexpectedly, this excessive erythrocytosis did not lead to thrombembolic complications in all investigated organs at any age. Thus, we investigated the mechanisms preventing thrombembolism in this mouse model. Blood analysis revealed an age-dependent elevation of reticulocyte numbers and a marked thrombocytopenia that matched the reduced megakaryocyte numbers in the bone marrow. However, platelet counts were not different from wild-type controls, when calculations were based on the distribution (eg, plasma) volume, thereby explaining why thrombopoietin levels did not increase in transgenic mice. Nevertheless, bleeding time was significantly increased in transgenic animals. A longitudinal investigation using computerized thromboelastography revealed that thrombus formation was reduced with increasing age from 1 to 8 months in transgenic animals. We observed that increasing erythrocyte concentrations inhibited profoundly and reversibly thrombus formation and prolonged the time of clot development, most likely due to mechanical interference of red blood cells with clot-forming platelets. Transgenic animals showed increased nitric oxide levels in the blood that could inhibit vasoconstriction and platelet activation. Finally, we observed that plasmatic coagulation activity in transgenic animals was significantly decreased. Taken together, our findings suggest that prevention of thrombembolic disease in these erythrocytotic transgenic mice was due to functional consequences inherent to increased erythrocyte concentrations and a reduction of plasmatic coagulation activity, the cause of which remains to be elucidated.