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G F von Tempelhoff

Publications and source records attributed to G F von Tempelhoff.

At least 19 recordsLinked to original sources
PubMed2002

A whole blood flow cytometric determination of platelet activation by unfractionated and low molecular weight heparin in vitro.

The influence of unfractionated (Heparin-Natrium) and low-molecular heparin (Fragmin(R)) on platelet activation in whole blood was investigated by FACS analysis in vitro using antibodies against glycoprotein (gp) IIb/IIIa (CD 41), GMP 140 (CD 62P), gp 53 (CD 63) and fibrinogen. Samples were also labeled with anti-gp Ib (CD 42b). Neither unfractionated heparin (UFH) nor low molecular weight heparin (LMWH) led to significant (i.e., p<0.05) changes in fluorescence intensities of platelets labeled with anti-gp IIb/IIIa or anti-gp 53. Significant platelet activation due to unfractionated heparin could be observed by labeling with anti-GMP 140 (UFH: p=0.009; LMWH: p=0.16). The proportion of platelets with surface-bound fibrinogen was significantly increased (UFH: p=0.00006; LMWH: p=0.008). After incubation with heparins, activation ability of platelets by adenosine diphosphate (ADP) was significantly increased. The potentiating action of unfractionated heparin was larger. Therefore, flow cytometric results of platelet activation in patients receiving heparin should be interpreted carefully.

Adenosine Diphosphate↗
PubMed2001

Soluble urokinase plasminogen activator receptor in preoperatively obtained plasma from patients with gynecological cancer or benign gynecological diseases.

OBJECTIVE: The present study was planned to measure preoperative levels of soluble urokinase plasminogen activator receptor (suPAR) in plasma from patients with gynecological diseases, and to test for a relationship to clinical and biochemical patient characteristics. METHODS: Using a specific and sensitive kinetic ELISA, suPAR levels were determined in preoperative citrate plasma samples from 53 ovarian, 34 endometrial, and 30 cervical cancer patients, 17 patients with benign ovarian tumors, and 28 patients with benign endometrial diseases. In addition, suPAR was measured in citrate samples from 31 female blood donors. RESULTS: suPAR was measurable in all samples. No significant difference was found between plasma suPAR in the blood donors and the patients with benign diseases (P = 0.58). The groups of cancer patients had suPAR levels that were significantly higher than those found in the blood donors (P < 0.0001, P < 0.0001, and P = 0.001 for patients with ovarian, endometrial, and cervical cancer, respectively). In all groups of cancer patients a trend toward increasing suPAR levels with increasing FIGO stage was noted (P = 0.0003, P = 0.02, and P = 0.01 for patients with ovarian, endometrial, and cervical cancer, respectively). Using the median suPAR level to dichotomize the ovarian cancer patients, FIGO stages I-III, a significantly increased risk of progression/relapse was found for patients with high suPAR levels (Hazard ratio (HR) = 3.1, 95% CI: 1.1-8.8, P = 0.03). A multivariate analysis was performed, including suPAR, FIGO stage, and CA-125. Only FIGO stage III compared with FIGO stage I was significant (HR = 15, 95% CI: 1.8-129, P = 0.01). Survival analyses were not performed in the endometrial or cervical cancer patients due to few progressions/relapses during the follow-up period. CONCLUSION: This study concludes that patients with gynecological cancers have elevated plasma suPAR levels as compared with healthy female blood donors and patients with benign gynecological diseases. In addition, high preoperative plasma levels of suPAR are significantly associated with poor outcome of ovarian cancer patients. However, additional studies are needed to further validate the clinical usefulness of plasma suPAR measurements in the management of ovarian cancer patients.

Adult↗
PubMed2001

The influence of antiphospholipid antibodies on the pregnancy outcome of patients with recurrent spontaneous abortion.

Several therapeutic regimens have been proposed for women with recurrent spontaneous abortion (RSA) and antiphospholipid antibodies (APA). Conflicting results have been reported about women with history of RSA, positive APA, and failure of standard therapy. To evaluate the use of intravenous immunoglobulin in RSA patients with APA and history of treatment failure, we initiated a study with standard therapy (aspirin and low-molecular-weight heparin) and intravenous immunoglobulin. We used an enzyme-linked immunosorbent assay (ELISA) test to screen IgG and IgM anticardiolipin antibodies, and a diluted Russel viper venom time assay for the lupus anticoagulant activity. Altogether, 66 pregnant women with positive APAs at the first visit could be included. Patients with hereditable thrombophilic factors were excluded. After confirmation of the pregnancy, women received a basis immunization of 0.3 g/kg immunoglobulin in a 4-week cycle until the 28th to 32nd week of gestation. All patients received 100 mg/d aspirin and 3,000 anti-Xa U/d certoparin. Among the 66 pregnant women, 17 were persistently autoantibody positive (25.8%), of whom 11 (16.7%) were ACA positive alone, 2 (3%) were lupus anticoagulant positive, and 4 (6.4%) had both antibody types. A total of 49 patients had positive APAs at the initial test, but were negative for ACA and lupus anticoagulant at the second test administered approximately 5 weeks after the start of therapy. We described this group in our following observation as "antibody negative." Sixteen of the 17 autoantibody-positive patients (94.1%) were delivered of live infants compared with 40 patients (81.6%) in the antibody-negative group (odds ratio [OR]: 1.2; 95% CI: 0.98 to 1.4). The overall miscarriage rate was 12.1% and the fetal loss rate was 15.2%. Four patients (25%) in the antibody-positive group developed symptoms of preeclampsia and fetal growth retardation compared with four patients (9.8%) in the antibody-negative group. In conclusion, we see a reduction of the fetal loss rate in patients with RSA and positive APA (5.8%) compared with APA-negative (18.4%) women with the same therapy (OR: 0.3; 95% CI: 0.04 to 2.3).

Abortion, Habitual↗
PubMed2001

The role of intravenous volume expansion in moderate pre-eclampsia.

We examined the hemodynamic and hemorheological effects of intravenous volume expansion in women with pre-eclampsia. 20 untreated women with moderate pre-eclampsia were randomized to receive a 500 ml infusion over 4 h of either hydroxyethylstarch (HAES steril 10%, HES) or NaCl 0.9% solution. After completion of the infusion trial all patients received oral antihypertensive drugs, bed rest and free sodium and water intake. The hemodynamic responses were measured by impedance cardiography. Hemorheological parameters and blood pressure were measured before and after (24 h later) infusion. The HES infusion but not NaCl leads to a significant reduction of hematocrit and erythrocyte aggregation. In addition to that there was a nonsignificant increase of the cardiac index in the HES-group but no changes in the heart rate. Intravenous volume expansion in women with pre-eclampsia with a long acting colloid like hydroxyethylstarch is associated with a significant influence on the flow properties (hematocrit and erythrocyte aggregation) of blood.

Adolescent↗
PubMed2000

Antithrombotic therapy in high-risk pregnancy.

Venous thromboembolism remains a major cause of morbidity and mortality associated with pregnancy and puerperium. Specific risk factors for this disorder can be identified before or during pregnancy and delivery. The heritable defects believed to be associated with venous thrombosis are factor V Leiden mutation; elevated antiphospholipid antibodies; and deficiencies of antithrombin, protein C, and protein S. Women with a history of thromboembolism and thrombophilia should receive antenatal and postpartum thrombosis prophylaxis.

Adult↗
PubMed2000

Antithrombotic therapy in gynecologic surgery and gynecologic oncology.

The European Consensus Conference has assessed the risk for thrombotic complications for most women undergoing gynecologic surgery and found it to be moderate. Nonetheless, it is important to analyze a patient's individual risk before surgery so that appropriate thrombosis prophylaxis can be given if increased risk is determined. Malignancy accounts for most thrombotic complications among gynecologic patients. Patients with known malignancies should receive prophylaxis during surgery, and some patients with breast cancer should receive prophylaxis during chemotherapy. Heparin, and low-molecular-weight heparin in particular, may favorably influence the outcome of cancer in some patients and treatment with these agents is currently under investigation in a number of trials as a new approach to anticancer therapy.

Antineoplastic Agents↗
PubMed2000

Effect of low molecular weight heparin (Certoparin) versus unfractionated heparin on cancer survival following breast and pelvic cancer surgery: A prospective randomized double-blind trial.

Recent studies suggest that low molecular weight heparin (LMW heparin) therapy in malignancy may improve cancer survival following surgical resection. We studied prospectively whether cancer mortality during follow-up in women with previously untreated breast, and pelvic cancer is reduced in those who randomly received LMW heparin (Certoparin) compared to patients given unfractionated heparin (UF heparin) for thrombosis prophylaxis during primary surgery. In a prospective, randomized, double-blind clinical trial, 160 patients received Certoparin and 164 UF heparin until post-operatively day 7. Survival estimations are based on the outcome data from a subset of 140 LMW heparin - and 147 UF heparin recipients. Long-term survival in the Certoparin group compared to the UF heparin group was significantly improved after 650 days (P=0. 0066) but not thereafter when analysis was performed on all cancer cell types combined. In the probability estimates survival benefit within this time was restricted to patients with pelvic cancer but was not observed in breast cancer. However, in breast cancer patients who received LMW heparin the impact of classical tumor prognostic markers was statistically significant after 1,050 days but not after 650 days. Thus, breast cancer patients with unfavorable prognosis seem to benefit in terms of survival advantage from LMW heparin within the 650 days after surgery. These results suggest that improvement in cancer survival can be achieved after even a short course of treatment with LMWH (compared to UFH) given for DVT prophylaxis in the post-operative period. An effect of UFH on disease outcome is not excluded. Further definitive trials of LMWH vs. placebo for cancer outcome (rather then DVT) using doses and schedules that may be more optimal are indicated.

Adult↗
PubMed2000

Association between blood rheology, thrombosis and cancer survival in patients with gynecologic malignancy.

In cancer patients impaired blood rheology in the presence of coagulation activation may reduce blood flow in the vascular microcirculation that favors thrombosis but may also support tumor progression and metastasis. In 451 patients with gynecological cancer and 177 patients with corresponding benign tumor disease preoperatively, during adjuvant treatment, when venous thrombosis (VT) or cancer progression was diagnosed hematocrit (micro centrifuge), hemoglobin, leukocytes, platelets (Coulter Counter); red blood cell (RBC) aggregation (aggr.) during stasis and low shear conditions (MA 1, Myrenne), plasma viscosity (viscosimeter KSPV 1 Fresenius), and fibrinogen (Multifibren Behring Dade) were investigated. One hundred and twelve healthy women served as controls. Preoperatively, mean plasma viscosity (pv) was significantly higher in cancer patients as compared to patients with the corresponding benign tumor disease (breast cancer: n = 261; pv = 1.32 vs. 1.27 mPa s; p = 0.023; ovarian cancer: n = 68; pv = 1.39 vs. 1.31 mPa s; p < 0.001; endometrial cancer: n = 70; pv = 1.37 vs. 1.25 mPa s; p < 0.001; cervical cancer: n = 52; pv = 1.33 vs. 1.26 mPa s; p = 0.004). RBC aggr. was significantly lower in controls compared to the preoperative values in cancer patients but mean (median) values (RBC aggr. stasis < 21) were within the normal range in all. Preoperatively, plasma viscosity was a significant risk factor for the overall survival in ovarian cancer patients (p = 0.02) and for subsequent thrombosis in ovarian (p = 0.02) and cervical cancer patients (p = 0.007). In the multivariate analysis plasma viscosity was an independent prognostic marker for the overall survival of breast cancer patients (r = 99.45; 95% CI: 7.32-980.2; p < 0.0001). An optimized preoperative cut-off value above 1.40 mPa s (Log-Rank-test) was significantly associated with poor outcome in the Kaplan-Mayer survival estimates, even in node-negative breast cancer. In gynecologic cancer patients the combination of an increase in RBC aggregation and plasma viscosity impairs blood-flow-properties and may induce hypoxia in the microcirculation that favors thrombosis, settlement of tumor-cells and thus metastasis. Improvement of blood fluidity and thus oxygen transfer in the tumor-vascular-microcirculation may increase susceptibility of systemic anti-cancer therapy.

Adult↗
PubMed1999

Chemotherapy and thrombosis in gynecologic malignancy.

Thromboembolism is a severe and frequent problem in gynecologic malignancy. The average DVT incidence during chemotherapy of 5% might represent the lower range of incidence because < 55% of thrombotic complication manifest clinical signs. However, it seems likely that in addition to chemotherapy other risk factors such as menopausal status, BMI of patients, or type of preceding surgery must coincide before thrombosis manifests. While monitoring of patients using sophisticated coagulation tests did not identify patients' risk for DVT during chemotherapy, an evaluation of the coagulation status before initiating chemotherapy is recommended. Patients with a venous access device (e.g., indwelling central venous catheter or with port cart) are at a particularly high risk for DVT. This has to be considered when cytoreductive therapy is given. Thrombosis prophylaxis, orally or subcutaneously, should only be considered in a subpopulation of patients who offer a combination of the aforementioned risk factors. Thrombosis prevention trials during chemotherapy found a significant reduction of DVT in patients treated with anticoagulants.

Antineoplastic Agents↗
PubMed1998

Blood rheology during chemotherapy in patients with ovarian cancer.

The use of platinum based chemotherapy in ovarian malignancy and other cancer types is known to be associated with deep vein thrombosis. In a prospective study of 47 patients with ovarian cancer of International Federation of Gynecology and Obstetrics stage Ib-IV, serial rheological parameters were determined (plasma viscosity, red blood cell aggregation under conditions of stasis and low shear) in addition to hemoglobin, hematocrit, leukocytes, platelets, and fibrinogen. At the same time the incidence of deep vein thrombosis was recorded before, during six cycles of first line cisplatinum/epirubicin/cyclophosphamide chemotherapy, and 2 months thereafter (two-months check-up). Only six patients with previous deep vein thrombosis concomitantly received thrombosis prophylaxis once with 3000 anti Xa Units/day subcutaneously low molecular weight heparin (Certoparin, NOVARTIS) throughout chemotherapy. Before each cycle of chemotherapy impedance plethysmography was used for deep vein thrombosis screening and when this was suspected on the basis of physical examination or a pathological result of impedance plethysmography, ascending venography of both legs was performed. During chemotherapy, the venographically proven deep vein thrombosis incidence was 10.6%; (95% CI: 3.5-23.1) with no differences in occurrence between FIGO stages. Before operation mean plasma viscosity was higher in patients who developed deep vein thrombosis postoperatively (n = 5; 1.46 +/- 0.2 mPas) and during chemotherapy (n = 5; 1.49 +/- 0.1 mPas) as compared to those without deep vein thrombosis (1.38 +/- 0.2 mPas; p = 0.04). Postoperatively (before chemotherapy) none of the rheological variables were significantly different in patients with versus those without deep vein thrombosis during chemotherapy. Leukocyte and platelet counts decreased significantly during chemotherapy until the two-months check-up after chemotherapy while red blood cell aggregation (stasis & low shear), hemoglobin, and hematocrit showed a continuous but nonsignificant increase. The mean plasma viscosity, instead, declined into the normal range after the 4th cycle of chemotherapy (1.33 +/- 0.1 mPas) in patients without thrombosis. In contrast, mean plasma viscosity was increased to 1.48 +/- 0.1 mPas at the time of deep vein thrombosis diagnosis during chemotherapy. In the ovarian cancer patients of this study, the development of deep vein thrombosis postoperatively and during chemotherapy was associated with a hematocrit-independent increase in blood viscosity characterized by a high plasma viscosity and normal or low hematocrit, which was present before primary surgery as well as at the time of deep vein thrombosis diagnosis.

Adult↗
PubMed1998

Hyperviscosity syndrome in patients with ovarian carcinoma.

BACKGROUND: In patients with ovarian carcinoma, an hematocrit-independent hyperviscosity syndrome is often present. The syndrome is characterized by normal or low hematocrit and hemoglobin concentration, an elevated platelet count, and an increase in clotting factor turnover. Because deep vein thrombosis (DVT) often complicates the course of ovarian carcinoma, the aim of this study was to investigate the possible association of hyperviscosity syndrome with the development of DVT. METHODS: Rheologic estimations of the blood included red blood cell (RBC) aggregation (stasis and low shear), plasma viscosity (pv), blood cell count, and fibrinogen, which were performed before primary surgery and the beginning of perioperative heparin thrombosis prophylaxis on 63 of 65 patients with Stage I-IV ovarian malignancy (according to the staging criteria of the International Federation of Gynecology and Obstetrics). Two patients who had had DVT 5-6 weeks in advance of the study were excluded from rheologic calculations. Thrombosis screening by impedance plethysmography was performed the day before primary major surgery; postoperatively on Days 1, 3, 5, 7, and 10; before each of 6 cycles of chemotherapy (once every 3 weeks); and thereafter once every 3 months during follow-up. All blood tests were also performed on 72 healthy women and 29 patients with benign ovarian tumor the day prior to surgery. RESULTS: All ovarian carcinoma patients, including 7 patients with tumors of low malignant potential, were eligible for surgery, and all except those with Stage IV disease (n = 12) were macroscopically tumor free after surgery. Before surgery, RBC aggregation, pv, and platelet and fibrinogen concentrations were significantly higher (P < 0.05) in cancer patients than in either of the control groups, whereas hemoglobin (hb) and hematocrit (hct) were significantly lower in cancer patients than in healthy women (P < 0.001). Platelet, leukocyte, and fibrinogen concentrations were significantly correlated to disease stage, whereas pv, RBC aggregation, hb, and hct were not. The preoperative pv was significantly higher in patients who later developed DVT (n = 17; 1.46+/-0.13 mPas; P = 0.01) than in those who did not (1.34+/-0.14 mPas). Of all estimated preoperative variables, only pv was a significant risk factor for postoperative and subsequent DVT (RR: 29.84; 95% CI: 1.076-827.16; P = 0.04). CONCLUSIONS: Our results confirm the presence of a hematocrit- and stage-independent hyperviscosity syndrome in untreated ovarian carcinoma patients. In addition, a high preoperative plasma viscosity was a significant risk factor for the development of DVT in the postoperative period and even thereafter.

Adult↗
PubMed1997

Maternal and cord blood hemostasis at delivery.

Today we known that the coagulation system of the neonate differs in many ways from that of the adult system. We see a general reduction of the coagulation factors II-XIII (except VIII), the fibrinogen and of the coagulation inhibitors ATIII, protein C and heparin cofactor II at the same time. In addition the newborns show different levels of the coagulation factors for premature and full-term infants. This situation necessitates the generation of not one, but several, reference ranges for the various components of the hemostatic system. While the above-mentioned factors of the coagulation and fibrinolytic system of the newborn are well studied, our knowledge of others is still lagging behind that of the adult. That applies to the vWF and PAI and even more to D-Dimer. Our aim was to collect some data for vWF, PAI and D-Dimer to complete the understanding of the physiology of the hemostatic system in the newborn. Therefore we used the blood samples from 59 newborns and their mothers to obtain a number of different components of the coagulation and fibrinolytic system. Besides some rheological parameters (erythrocyte aggregation, plasma viscosity) we measured the aPTT, PT and the plasma levels of ATIII, fibrinogen and protein C (PC). But we paid special attention to the plasma levels of von Willebrand factor (vWF), plasma activator inhibitor (PAI) and D-Dimer. The blood samples were collected from the umbilical cord and the cubital vein of the mother immediately after delivery, anti-coagulated, centrifuged and stored until measurement at -70 degrees C. ATIII, aPTT, PT and fibrinogen were measured by the clotting technique test on the Chromotimer (Behring, Marburg, Germany). D-Dimer, vWF and protein C were determined with a commercially available ELISA obtained from Boehringer Mannheim (Mannheim, Germany). PAI activity was measured by a two-stage amiolytic method (Behring, Marburg). Besides the known differences of the neonatal hemostatic components to their mothers, such as a prolonged aPTT (52.19 s +/- 13.4 newborn, 35.26 s +/- 4.2 mother), reduced PT (64.34 s +/- 20.15 vs. 91.03 s +/- 1.25), ATIII (83.36% +/- 24.42 vs. 92.58% +/- 11.43) and fibrinogen (156.05 mg/dl +/- 91.68 vs. 344 mg/dl +/- 55.25), we found some peculiarities. The newborns show a clear reduction in the vWF (97.79 ng/ml +/- 36.33 vs. 183.43 ng/ml +/- 16.03) as well as the PAI (0.846 U/ml +/- 1.44 vs. 7.652 U/ml +/- 0.764). D-Dimer levels in the umbilical cord samples (1514.02 ng/ml +/- 953.56) are clearly prolonged in contrast to the maternal levels (740.2 ng/ml +/- 139.68). We were also able to find a difference of these factors related to gestational age. Premature infants showed a clearly higher level of PAI (2.2 U/ml +/- 2.86 vs. 0.69 +/- 1.13; p = 0.0136) compared with full-term infants, as well as significantly lower levels of ATIII (48.8% +/- 23.19 vs. 86.62 +/- 22.04; p = 0.0006) and protein C (25.33% +/- 9.37 vs. 35.73 +/- 7.53; p = 0.0027). D-Dimer, vWF, fibrinogen and the rheological parameters are similar. This seems to show an increased tendency for bleeding with the premature infant. Newborns show a balance of the coagulation system solely on a lower level. This is due to the general reduction of the coagulation factors with a reduction of the coagulation inhibitors at the same time. The physiologically low level of the vitamin K dependent and other coagulation factors and ATIII leads to a prolonged aPTT and reduced PT of the newborn. As well as these differences, known from literature, we found the following specialities: lower vWF and PAI and higher D-Dimer levels of the newborn compared with their mothers.

Antithrombin III↗
PubMed1997

Blood coagulation and thrombosis in patients with ovarian malignancy.

Ovarian cancer cells appear to be capable of both thrombin formation and induction of fibrin degradation which may be essential prerequisites for the development of deep vein thrombosis (DVT) as well as the spread of malignancy. To study further this coagulation-cancer interaction in 60 patients with untreated ovarian cancer of FIGO stage I-IV the incidence of DVT was recorded pre-operatively, post-operatively on day 1, 3, 5, 7, 10, before each of six cycles of Cisplatinum/ Epirubicin/Cyclophosphamide chemotherapy, during follow-up and in the post-operative period of second look surgery. In addition, blood coagulation tests results were determined prospectively. Two patients were excluded from these calculations due to previous DVT 5 to 6 weeks before the diagnosis of ovarian cancer but all patients were eligible for surgery and randomized to receive either daily low molecular weight heparin (LMWH) (n = 28) or unfractionated heparin (UFH) (n = 32) for perioperative thrombosis prophylaxis until the 7th post-operative day. According to the FIGO stage, patients were equally distributed in the 2 heparin treatment groups. The predictive value of pre-operative coagulation test results, clinical parameters, and type of heparin used were tested in univariate and multivariate analysis for development of post-operative DVT and overall patients survival. Impedance plethysmography for DVT screening was used. The presence of DVT was then confirmed by phlebography. Only D-dimer and fibrinogen levels were correlated significantly with the FIGO stage while antithrombin, protein C, and plasminogen activator inhibitor activity were not. The incidence of DVT was 6.7% (4/60) up to the 7th and 8.3% (5/60) between the 8th and 29th post-operative day. DVT occurred in 10.6% (5/47) during chemotherapy. Pre-operative coagulation test results, the type of heparin used, and clinical parameters were not significant risk factors for post-operative DVT development in univariate analysis. The D-dimer and fibrinogen levels were significant risk factors for reduced overall survival in univariate analysis but only the FIGO stage was an independent predictor (in multivariate analysis). After a median follow up of 26.5 months (min. 8 months, max. 41 months), 21.4% of LMWH treated and 37.5% of UFH-treated patients died of cancer (p = 0.26). Pre-operative test results were neither predictive for DVT nor the outcome of cancer but patients showed an improved though not statistically significant overall survival after LMWH treatment.

Aged↗