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Wolfgang Korte

Publications and source records attributed to Wolfgang Korte.

13 recordsLinked to original sources

[Clinical assessment of potential fields of application of recombinant factor VIIa in internal and pediatric diseases. Recommendations of an expert group].

Recombinant factor VIIa (rFVIIa) is increasingly used outside the labeled indications for treatment of life-threatening bleeding episodes after failure of the respective standard therapy. An interdisciplinary group of experts summarizes the state of knowledge of the use of rFVIIa in gastroenterology and hepatology, thrombocytopenia and -pathia, coagulation factor deficiencies, von Willebrand's disease, periinterventional bleeding without specific bleeding diathesis, drug-induced bleeding, disseminated intravascular coagulation, and neonatology. The most commonly used dose is 90 microg/kg body weight rFVIIa as bolus, if necessary followed by additional injections at intervals of 2-3 h. In factor VII deficiency lower dosages of 15-30 microg/kg body weight of rFVIIa are given every 4-6 h, whereas higher doses of 150-200 microg/kg body weight are used in neonates.

Adult↗

Successful treatment of acute disseminated intravascular coagulation in a patient with metastatic melanoma.

BACKGROUND: Acute disseminated intravascular coagulation (DIC) in cancer is rare and often fatal, whereas chronic forms are more frequent. CASE REPORT: A 37-year-old man with a known history of melanoma excised 6 years ago, presented with abdominal pain, fatigue and epistaxis. A computed tomography scan revealed diffuse metastatic disease of the liver, and laboratory analysis was consistent with accentuated DIC. After chemotherapy with dacarbacine, vinblastine and cisplatine, the acute DIC improved rapidly. After a second cycle, the tumor marker S-100 dropped from 15 to 3.1 microg/l (< 0.15 microg/l), suggesting that the improvement of the DIC was associated with a response to chemotherapy. After 2 cycles of chemotherapy, a palliative right hemihepatectomy was performed followed by 4 additional postoperative chemotherapy cycles. The patient survived 1 more year without relapse of the DIC. CONCLUSION: The cornerstone of managing DIC in cancer consists in treatment of the underlying disease. The rapid control of DIC in our patient can be explained by early diagnosis of the coagulopathy and the fast response of the tumor to the multidrug therapy. Thus, combination chemotherapy of metastatic melanoma is justified if an effective response has to be obtained in a limited time.

Adult↗

Sensitivity and specificity of a quantitative point of care D-dimer assay using heparinized whole blood, in patients with clinically suspected deep vein thrombosis.

D-dimer assays are efficient in the exclusion diagnostics of deep vein thrombosis (DVT) in patients without severe concomitant diseases. We have determined diagnostic sensitivity and specificity of a new point-of-care rapid assay for quantitative determination of D-dimer in heparinized whole blood in outpatients with suspected DVT. In 19 participating centers, 637 patients were included in the study, of which 77 were excluded, the majority because of inadequate documentation of analytical quality control measures. DVT was diagnosed in 223 of the remaining 560 patients by duplex ultrasound examination. The POC D-dimer assay showed a high sensitivity of 96.9% for the diagnosis of DVT and a high specificity of 60.8% at a pre-specified cutoff of 0.5 microg/ml. For Tina-quant D-dimer, sensitivity was slightly lower at 94.9%, with a specificity of 64.8%. The VIDAS D-dimer assay showed a sensitivity of 98.2%, but specificity was 40.7%. The area under the curve (AUC +/- standard error, 95% confidence interval) was 0.879 +/- 0.019 (0.845-0.909) for POC D-dimer, 0.908 +/- 0.016 (0.877-0.934) for Tina-quant D-dimer, and 0.895 +/- 0.018 (0.862-0.922) forVIDAS D-dimer. Differences were not statistically significant. The new whole blood POC D-dimer assay is a reliable tool for exclusion of DVT in symptomatic outpatients, displaying a comparable diagnostic performance as VIDAS D-dimer and Tina-quant D-dimer assays.

Adolescent↗

Impact of aspirate smears and trephine biopsies in routine bone marrow diagnostics: a comparative study of 141 cases.

The diagnostic impact of bone marrow cytology in combination with flow cytometry analysis of aspirate smears and bone marrow histology together with immunohistochemical examination of trephine biopsies was compared in 141 routine cases. Diagnoses achieved by the two methods were concordant in 80.5% of cases. In discordant cases, clinical follow-up data of at least one year confirmed the correctness of cytological and histological diagnoses. For infiltration by malignant disease, both methods were concordant in 86.5% of samples and correlated well for the degree of infiltration (r = 0.64, p <0.001). Overall, regression analysis showed a good correlation for cellularity (r = 0.67) lymphopoiesis (r = 0.75), granulopoiesis (r = 0.73) and megakaryopoiesis (r = 0.65) while erythropoiesis displayed a lower degree of correlation (r = 0.43, all p <0.001). Regression analysis on all immunological data obtained by flow cytometry (FC) and immunohistochemistry (IHC) showed a good overall linear correlation (r = 0.67, p <0.001), but significant differences were found for a few phenotypic markers. Furthermore, the correlation was found to be dependent on IgG subclasses and the fluorochromes used for FC. Thus, analyses with IgG2 antibodies and phycoerythrin (PE) as fluorochrome showed significantly more expression than IHC. In conclusion, cytology and histology, both in association with the respective immunophenotyping, are of equal value in bone marrow diagnostics and should be used in combination. However, in some specific settings, one of the two procedures might be preferable.

Antibodies↗

Proposal of a morphologic bone marrow response score for imatinib mesylate treatment in chronic myelogenous leukemia.

Cytogenetic and molecular analyses are essential disease-monitoring parameters in chronic myelogenous leukemia (CML) treated with imatinib. However, a bone marrow morphologic response has not been defined. We reviewed bone marrow histology and cytology of 39 imatinib-treated patients with CML over 49 weeks and introduced a morphologic response score. A significant positive correlation with a complete cytogenetic response was shown for absence of dry tap (P = .04) and abnormal megakaryocytes (P < 0.001), normalization of cellularity (P = .001) and reduction of fibrosis (P = .01), myelopoiesis:erythropoiesis index (P = .001), blast (P = .001) and basophil count (P < 0.001). The morphologic score integrating these parameters showed an early and late correlation with cytogenetic response. In conclusion, morphologic criteria for complete cytogenetic response in patients with CML treated with imatinib can be defined. Persistent high-level morphologic abnormalities herald early on a high likelihood to fail treatment and call for more intense or alternative therapy.

Adult↗

Preoperative fibrin monomer measurement allows risk stratification for high intraoperative blood loss in elective surgery.

We recently demonstrated that patients with increased blood loss due to intraoperative coagulopathy show a persistent pre-, intra- and postoperative increase in fibrin monomer concentration. We thus tested the hypothesis that preoperative fibrin monomer concentrations can be used as a risk indicator for intraoperative blood loss in a study designed for diagnostic test evaluation in 168 patients admitted to the surgical service of our hospital. Intraoperative blood loss increased with preoperative fibrin monomer concentration (median blood loss of 50, 100, 200 and 400 ml in preoperative fibrin monomer quartile groups 1 to 4, p<0.001, ANOVA on ranks; interquartile comparisons p < 0.05 (4/6), Mann Whitney Rank Sum test). In contrast, intraoperative blood loss was unrelated to preoperative values of prothrombin time, activated partial thromboplastin time and platelet count. By multivariate (logistic regression) analysis, only fibrin monomer remained a significant predictor of intraoperative blood loss > 500 ml when age, gender, BMI, fibrin monomer and the different types of surgical procedures (tumor surgery, vascular surgery, cholecystectomy, gastric banding, varicous vein surgery and hernia repair) were included as independent variables. Most importantly, accuracy evaluation showed that preoperative fibrin monomer concentration < 3 microg/l excluded intraoperative blood loss > 500 ml with 92% sensitivity and 95% negative predictive value. These results support our hypothesis that preoperative fibrin monomer concentrations are related to intraoperative blood loss in elective surgery. Fibrin monomer should be further investigated for it's potential to serve as a routine tool for preoperative risk stratification of intraoperative bleeding.

Adult↗

Properties of proteins in cancer procoagulant preparations that are detected by anti-tissue factor antibodies.

Cancer procoagulant (CP) and tissue factor (TF; only in complex with Factor VIIa (FVIIa)) can activate FX to FXa. Controversy still exists whether or not CP is an entity different from TF, or whether CP activity is due to contamination of CP preparations with TF/FVIIa complex. We therefore looked for proteins in CP preparations that were detected by anti-TF antibodies and then sequenced these proteins. One- and two-dimensional gels of CP and TF were used to identify proteins immunoreactive to monoclonal anti-CP and anti-TF antibodies (Mabs). Those proteins in the CP preparation recognized by anti-TF antibodies were sequenced. Angiotensinogen precursor, alpha-1-antitrypsin precursor, and vitamin D-binding protein were identified along with one so far unidentified sequence; however, no TF-sequences were identified. Also, no proteins with the correct molecular weight for TF were identified using anti-TF antibodies. It seems possible that CP preparations contain proteins that have some epitopes similar to the epitopes recognized in TF by anti-TF Mab. However, these proteins do neither have the molecular weight nor the amino acid sequence of TF.

Angiotensinogen↗

Interpretation of erythropoietin levels in patients with various degrees of renal insufficiency and anemia.

BACKGROUND: Chronic renal failure leads to hyporegenerative anemia due to erythropoietin deficiency. The creatinine clearance and hemoglobin levels, at which anemia treatment with recombinant erythropoietin should be started, are unclear. Interpretation of serum erythropoietin levels in the context of renal insufficiency remains controversial and was addressed in this study. METHODS: Three hundred and ninety-five patients were randomly chosen out of over 5000 consecutive patients investigated by coronary angiography at a single center between 1997 and 2001. Laboratory values and clinical information were prospectively collected in a central registry. Serum samples were frozen before angiography and now used to measure serum erythropoietin levels and evaluate the relationship between erythropoietin and hemoglobin levels in the context of various degrees of renal insufficiency. RESULTS: The patients with the lowest renal function (creatinine clearance <20 mL/min) had significantly lower hemoglobin levels than the group with normal renal function. However, erythropoietin levels were identical indicating a lower set point for erythropoietin regulation. Above a creatinine clearance of 40 mL/min a significant inverse correlation between erythropoietin and hemoglobin levels was observed and described with the formula erythropoietin [U/L]= 2.5 x (140 - hemoglobin [g/L]) or alternatively Deltaerythropoietin (U/L) =-2.5 xDeltahemoglobin (g/L). Below 40 mL/min no significant correlation was found. CONCLUSION: A cut-off level for an altered set point of erythropoietin regulation was determined at 40 mL/min creatinine clearance. Above this cut-off hemoglobin negatively regulates erythropoietin. Below the cut-off erythropoietin levels remain stable. Pathophysiologic concepts for this finding and clinical implications in patients with moderate renal failure are discussed.

Adult↗

Decreased factor XIII availability for thrombin and early loss of clot firmness in patients with unexplained intraoperative bleeding.

To explore relevant changes in unexplained intraoperative bleeding, we evaluated elements of the final steps of the coagulation cascade in 226 consecutive patients undergoing elective surgery. Patients were stratified for the occurrence of unexplained intraoperative bleeding according to predefined criteria. Twenty patients (8.8%) developed unexplained bleeding. The median intraoperative blood loss was 1350 mL (bleeders) and 400 mL (nonbleeders) (P < 0.001). Fibrinogen and Factor XIII (F. XIII) were more rapidly consumed in bleeders (P < 0.001). Soluble fibrin formation (fibrin monomer) was increased in bleeders throughout surgery (P < or = 0.014). However, F. XIII availability per unit thrombin generated was significantly decreased in bleeders before, during, and after surgery (P < or = 0.051). Computerized thrombelastography showed a parallel, significant reduction in clot firmness. We suggest that mild preexisting coagulopathy is not rare in surgical patients and probably can result in clinically relevant intraoperative bleeding. This hemostatic disorder shows impaired clot firmness, probably secondary to decreased cross-linking (due to a loss of F. XIII, both in absolute measures and per unit thrombin generated). We suggest that the application of F. XIII might be worthwhile to test in a prospective clinical trial to increase clot firmness in patients at risk for this intraoperative coagulopathy.

Adolescent↗

Telehematology: critical determinants for successful implementation.

Despite modern technologies, such as immunophenotyping and molecular probing, cytomorphologic examination of stained peripheral blood smears by microscopy remains the mainstay of diagnosis in a large variety of diseases. This holds true especially in underdeveloped or rural areas where profound expertise and equipment are not easily available. Although communication technologies have been dramatically improved, telehematology has not become routine. To date, little information is available on which procedures are critical for successful implementation. Therefore, a study evaluating possible factors that prevented implementation of telehematology was initiated. We found that staining technique, smearing procedure, training skills, number of captured images, and prevalent disease influenced the accuracy of diagnosis by the reference laboratory. Using realtime teleconferencing allowed for overcoming these deficits. Together, when certain rules are observed, telehematology allows for rapid, accurate, standardized, and cheap expert advice. This technology should improve treatment of patients in remote areas where expertise is not available.

Hematology↗