PubMed Health⌕ Search

Biomedical subjects

A Weltermann

Publications and source records attributed to A Weltermann.

29 records · Page 2Linked to original sources
PubMed1998

[Disseminated intravascular coagulation (DIG) with massive hyperfibrinolysis in metastatic uterine cancer. Observations on the effects on the coagulopathy of various treatments (a case report)].

We report on a 64-year-old patient with a recurrent endometrial carcinoma which was associated with disseminated intravascular coagulation (DIC) and excessive hyperfibrinolysis. The patient presented with severe bleeding due to hypofibrinogenemia. Fibrin degradation products were excessively elevated and there were also increased levels of activation markers of coagulation. Free plasmin was demonstrated in the circulation and alpha 2-antiplasmin was almost completely depleted. No increase in t-PA or u-PA level was demonstrated. Antifibrinolytic treatment led to a decrease of fibrin degradation products, but to an increase of activation markers of coagulation and was not associated with an increase of fibrinogen. Combination chemotherapy led to a rapid decrease of activation markers of coagulation and a sustained increase of fibrinogen. The beneficial effects on DIC/hyperfibrinolysis occurred despite the absence of any measurable effect of chemotherapy on the tumour. The patient finally died due to progression of the tumour, but without recurrence of the DIC/hyperfibrinolysis.

Adenocarcinoma↗
PubMed1998

Hypofibrinogenemia in non-M3 acute myeloid leukemia. Incidence, clinical and laboratory characteristics and prognosis.

Among 379 patients with AML with FAB type M1, 2 and M4-7 diagnosed between 1978 and 1997 in our institution, 19 (5%) had hypofibrinogenemia (HF), ie a fibrinogen level <180 mg/dl. Compared to patients with normal fibrinogen (n = 360) patients with HF had significantly elevated markers of activation of coagulation (TAT, F1.2, FPA) and fibrinolysis (D-dimer, FDP) indicating that disseminated intravascular coagulation/hyperfibrinolysis was the cause of hypofibrinogenemia. Patients with HF had significantly longer prothrombin times, thrombin clotting and reptilase times. Factor X and VIII were significantly lower than in patients without HF. With the exception of M7, HF occurred in all FAB subtypes, but was most common in M5 (12.1%). Patients with HF did not differ from those with normal fibrinogen with regard to age, sex, leukocyte count and other hematological parameters. During induction chemotherapy fibrinogen normalized rapidly (median 5 days) and there was no increased incidence of early hemorrhagic death. The overall and disease-free survival was similar to that of patients without HF.

Adult↗
PubMed1998

A novel immunoassay for the quantification of human tissue factor binding to activated factor VII.

The binding of tissue factor to factors VII and VIIa (VII/VIIa) is the primary step for coagulation activation. Variants of human tissue factor leading to alterations in the binding to factor VII/VIIa have not been reported. We hypothesize that increased or decreased binding of tissue factor to factor VIIa might result in thrombosis and bleeding, respectively. The aim of this study was to establish an enzyme-linked immunosorbent assay to detect abnormalities in the binding of human tissue factor to recombinant factor VIIa (rVIIa). Tissue factor obtained from human monocytes was bound to rVIIa on microtiter wells in the presence of calcium. A murine antibody against human tissue factor and a biotinylated goat anti-mouse immunoglobuline were added. After incubation with streptavidin-horseradish peroxidase, colour development was measured using a chromogenic indicator system. Optimal assay conditions were obtained at tissue factor concentrations of 50-1500 pg/ml and rVIIa concentrations of 2.5 microg/ml. The binding of tissue factor to rVIIa was calcium-dependent and was inhibited by a monoclonal tissue factor antibody directed against the binding sites of tissue factor to rVIIa. The assay was evaluated in 23 healthy volunteers. Intra- and interassay variabilities were 3.9% and 10.2%, respectively. Among 22 subjects with unexplained bleeding and 47 patients with unexplained thrombosis, an individual with a decreased or increased binding of tissue factor to rVIIa could not yet be identified. In conclusion, this novel enzyme-linked immunosorbent assay can be used to detect and quantify an increased or a decreased binding of human tissue factor to rVIIa. Studies in patients indicate that, if such a defect exists, it is not a common cause of thrombosis or bleeding.

Adult↗
PubMed1998

Clinical studies and thrombin generation in patients homozygous or heterozygous for the G20210A mutation in the prothrombin gene.

A genetic variation in the prothrombin gene, the G-->A transition at nucleotide 20210, is a risk factor for venous thrombosis in heterozygotes and is associated with increased prothrombin activity. The homozygous phenotype and the extent of thrombin generation in heterozygous and homozygous subjects are unknown. We investigated a family that included 2 homozygous and 5 heterozygous carriers of the 20210 A allele. The homozygous propositus and his presumably heterozygous father suffered from deep-vein thrombosis. His presumably heterozygous mother and his homozygous sister had recurrent phlebitis at a young age. The remaining 5 affected family members are still asymptomatic. We studied thrombin generation in the family and in 22 unrelated carriers of the 20210 A allele by measuring (1) prothrombin fragment F1+2 (F1+2) as an index of ongoing thrombin generation and (2) the endogenous thrombin potential (ETP) as an index of the possible thrombin-forming capacity. Their F1+2 levels were not different from those of age-matched controls, and thus, ongoing hemostatic system activation was not detectable. A significantly increased ETP was found in the heterozygous carriers of the 20210A allele compared with the controls (527.8+/-114.9 versus 387+/-50.1 nmol/L x min, P<0.0001). In the 2 homozygotes, the ETP was almost twice (639 and 751 nmol/L x min, respectively) as high as in the controls. We conclude that homozygosity for the G20210A mutation in the prothrombin gene is associated with a severe, albeit more benign, thrombotic diathesis compared with homozygosity for deficiencies of antithrombin, protein C, or protein S. In carriers of the 20210 A allele, the pathomechanisms leading to thrombosis should be sought in the higher amounts of thrombin that may be formed once thrombin generation is triggered, rather than in ongoing thrombin generation in vivo.

Adult↗
PubMed1997

Inhibition rather than enhancement of hemostatic system activation during initiation of oral anticoagulant treatment.

Coumarin-induced skin necrosis is believed to be due to a transient hypercoagulable state resulting from a more rapid decline of the protein C activity relative to that of coagulation factors (F) II, IX and X during initiation of oral anticoagulant therapy. We studied hemostatic system activation during early oral anticoagulant treatment with a technique that investigates coagulation activation in the microcirculation. We determined in 10 healthy volunteers the concentrations of prothrombin fragment F1 + 2 (f1.2) and thrombin-antithrombin complex (TAT) in blood emerging from an injury of the microvasculature (bleeding time incision) before and after initiation of both high-intensity and low-intensity coumarin therapy. In addition, f1.2, TAT, activated F VII (F VIIa) and the activities of F II, F VII, F X and protein C were measured in venous blood. A rapid decline of F VII and protein C was observed in venous blood with activities at 24 h of 7 +/- 1% and 43 +/- 2%, respectively, during the high-intensity regimen. A 20 to 30% reduction of f1.2 and TAT was seen in venous blood at 72 h with no major difference between the high- and the low-intensity regimen. F VIIa levels were substantially affected by anticoagulation with a > 90% reduction at 48 h during the high-intensity regimen. Following high-intensity coumarin, a > 50% decrease in the f1.2 and TAT levels was found in shed blood at 48 h suggesting substantial inhibition of thrombin generation during early oral anticoagulation. An increase in the f1.2 and TAT levels was seen neither in shed blood nor in venous blood. Our data do not support the concept of a transient imbalance between generation and inhibition of thrombin as the underlying pathomechanism of coumarin-induced skin nekrosis.

Administration, Oral↗
PubMed1997

Prothrombin fragment F1+2 is not predictive for recurrent venous thromboembolism.

It would be important to estimate in advance the risk of recurrent thrombosis. Deficiencies of antithrombin, protein C or protein S, or resistance to activated protein C are associated with a biochemically detectable prethrombotic state. It is thus far unknown whether in patients with a history of thromboembolism but without a defined clotting abnormality a heightened coagulation activation is detectable. We investigated the value of prothrombin fragment F1+2 (F1+2) as a predictor of recurrent venous thromboembolism. Furthermore, we compared the F1+2 levels of thrombosis patients without a defined clotting defect to those of Factor V Leiden patients with a history of venous thrombosis and to those of healthy controls. 180 patients without a defined clotting abnormality and 73 patients with Factor V Leiden were prospectively followed after discontinuation of oral anticoagulants for venous thrombosis and F1+2 was measured at regular intervals. Recurrent venous thromboembolism occurred in 23 (9%) of the 253 patients. Before or at several time points after oral anticoagulants, no significant difference in F1+2 levels was found in patients with and without recurrent thrombosis. F1+2 levels at 3 weeks and prior to recurrence were not significantly different in both patient groups. Over a one-year observation period, F1+2 levels of both patients with and without Factor V Leiden were higher than those of the controls. No difference in F1+2 was seen between patients with and without Factor V Leiden. We conclude that monitoring of F1+2 is not suitable for identification of individuals at risk of recurrent venous thrombosis. Permanent hemostatic system activation is detectable both in patients with a defined abnormality of the clotting system and in patients in whom a particular defect has not (yet) been identified.

Adult↗
PubMed1997

Comparison of the effects of different low molecular weight heparins on the hemostatic system activation in vivo in man.

In a double-blind, randomized, cross-over study the effects of single subcutaneous doses of 120 anti-Xa units/kg body wt. of three different low molecular weight heparin (LMWH) preparations were investigated in 15 healthy subjects by determination of thrombin-antithrombin III complex (TAT), prothrombin fragment 1.2 (f1.2), and beta-thromboglobin (beta-TG) in shed blood and in venous blood. Certoparin, dalteparin, and enoxaparin significantly inhibited coagulation activation marker formation in shed blood. The substantial inhibition of TAT and f1.2 formation was slightly more pronounced in response to certoparin. beta-TG was decreased following certoparin and enoxaparin, but not following dalteparin. However, no difference between groups was detectable. A small but consistent decrease of f1.2 formation in venous blood was noted for all LMWHs and dalteparin and enoxaparin, but not certoparin, inhibited TAT formation. Only a minor impact of the three LMWH preparations was noted on beta-TG plasma concentrations. Our data indicate that the studied LMWH preparations have a major impact on blood clotting in the activated state and inhibit in vivo the hemostatic system to a comparable extent.

Adult↗
PubMed1997

Levels of prothrombin fragment F1+2 in patients with hyperhomocysteinemia and a history of venous thromboembolism.

Increased thrombin generation occurs in many individuals with inherited defects in the antithrombin or protein C anticoagulant pathways and is also seen in patients with thrombosis without a defined clotting abnormality. Hyperhomocysteinemia (H-HC) is an important risk factor of venous thromboembolism (VTE). We prospectively followed 48 patients with H-HC (median age 62 years, range 26-83; 18 males) and 183 patients (median age 50 years, range 18-85; 83 males) without H-HC for a period of up to one year. Prothrombin fragment F1+2 (F1+2) was determined in the patient's plasma as a measure of thrombin generation during and at several time points after discontinuation of secondary thromboprophylaxis with oral anticoagulants. While on anticoagulants, patients with H-HC had significantly higher F1+2 levels than patients without H-HC (mean 0.52 +/- 0.49 nmol/l, median 0.4, range 0.2-2.8, versus 0.36 +/- 0.2 nmol/l, median 0.3, range 0.1-2.1; p = 0.02). Three weeks and 3, 6, 9 and 12 months after discontinuation of oral anticoagulants, up to 20% of the patients with H-HC and 5 to 6% without H-HC had higher F1+2 levels than a corresponding age- and sex-matched control group. 16% of the patients with H-HC and 4% of the patients without H-HC had either F1+2 levels above the upper limit of normal controls at least at 2 occasions or (an) elevated F1+2 level(s) followed by recurrent VTE. No statistical significant difference in the F1+2 levels was seen between patients with and without H-HC. We conclude that a permanent hemostatic system activation is detectable in a proportion of patients with H-HC after discontinuation of oral anticoagulant therapy following VTE. Furthermore, secondary thromboprophylaxis with conventional doses of oral anticoagulants may not be sufficient to suppress hemostatic system activation in patients with H-HC.

Administration, Oral↗
PubMed1995

Studies on the neutralizing effects of protamine on unfractionated and low molecular weight heparin (Fragmin) at the site of activation of the coagulation system in man.

In a double-blind, randomized, cross-over study the neutralizing action of protamine towards unfractionated heparin (UFH, 150 U/kg i.v.) and a low molecular weight heparin (LMWH, Fragmin, 100 anti-Xa U/kg i.v.) was investigated in 15 healthy subjects in vitro by measuring activated partial thromboplastin time (APTT), thrombin time (TT) and anti factor Xa activity (anti-Xa) in venous blood and in vivo by determination of prothrombin fragment 1.2 (f1.2) and thrombin-antithrombin III complexes (TAT) in venous blood and in shed blood. UFH and LMWH caused a prolongation of APTT and TT, an increase in anti-Xa and significantly inhibited f1.2 and TAT formation in shed blood, whereas only a minimal effect on TAT and f1.2 formation in venous blood was noted. Administration of 1 mg protamine/100 U UFH resulted in a near complete reversal of APTT, TT and anti-Xa, whereas lower doses (0.25 and 0.5 mg) were less effective. The effects of UFH on f1.2 and TAT generation in shed blood were partially (60-70%) neutralized only by the high dose (1.0 mg). Application of 1 mg protamine/100 anti-Xa U LMWH caused a near complete reversal of both APTT and TT but had only a weak effect on anti-Xa. In shed blood, the effect of LMWH on TAT and f1.2 formation was reversed by protamine only by 14% and 23% respectively. Our data do not support the concept that to reduce the incidence of protamine's potential clinical side effects, the administration of a lower dose of protamine than 1 mg protamine/100 U UFH is justified.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Association of CD38 antigen expression with other prognostic parameters in early stages of chronic lymphocytic leukemia.

The expression of the surface molecule CD38 on B cell chronic lymphocytic leukemia (B-CLL) cells has recently been described as a prognostic marker for patient survival. We have analyzed CD19/CD38 expression in 81 patients with predominantly early stages of B-CLL (69 Binet A, seven Binet B, five Binet C). Sixty-two patients (77%) had less than 30% CD38+/CD19+ cells, while 19 (23%) had > or = 30%. There was a significant association between Binet stages (A vs. B+C, p < 0.0001), Rai stages (0-II vs. III+IV, p < 0.001) and CD38 expression, confirming the published cut-off level of 30%. A particularly strong association between CD38 expression was found with soluble CD23 (sCD23) levels of > or = 2000 U/ml (p < 0.0001) and beta2-microglobulin (beta2 MG) serum levels of > or = 3 mg/l (p < 0.0001) indicating that CD38 is a marker of tumor mass as well as disease progression. A borderline association was found with lymphocyte doubling time (LDT) < 12 months (p = 0.05) due to low patient numbers, while there was no association with age, sex or immunoglobulin deficiency. Discordant results were obtained in a number of patients: 10 of 69 patients (14%) with Binet A had a CD38 > or = 30% while three of seven patients with Binet B had a CD38 < 30%. In these two subgroups CD38 and other prognostic factors gave discrepant results. Due to the early stage and short median observation time (12 months. range 1-24 months), calculations concerning patient survival were not performed. However, our data show a strong association between CD38 and other known prognostic factors. The results also suggest that this factor is not always reliable in Binet A patients.

ADP-ribosyl Cyclase↗