Biomedical subjects

W Speiser

Publications and source records attributed to W Speiser.

At least 37 records · Page 2Linked to original sources

PubMed1999

The Factor V (Leiden) test: evaluation of an assay based on dilute Russell Viper Venom Time for the detection of the Factor V Leiden mutation.

In the present study a new clotting assay for the detection of an increased resistance of coagulation factor V against degradation by activated protein C (Factor V Leiden mutation, FVLM) was evaluated. The Factor V (Leiden) Test (Gradipore, North Ryde NSW, Australia) is based on the dilute Russell Viper Venom Time (DRVVT), which is prolonged when the plasma sample is preincubated with dilute whole Agkistrodon contortrix contortrix venom for activation of protein C (PC). In contrast to the DRVVT based global assay, Protein C Pathway Test (Gradipore, North Ryde NSW, Australia) this new assay is expected to be more specific for FVLM because of optimized amounts of the venom. The test result is expressed as the ratio between the DRVVT with and without addition of the venom. The following precision values were found: intraassay coefficient of variation (CV): 5.53% (n=20) in the normal range, 4.30% (n=20) in the pathological range; interassay CV: 6.90% (n=10) and 7.64% (n=10), respectively. A normal range (5th to 95th percentile) of 2.12 to 3.08 was calculated from 50 healthy controls. A ratio below 2.12 was found in all samples from patients with FVLM (n=21), in 9 of 12 patients with PC, in 0 of 6 with protein S (PS), and in 0 of 4 with antithrombin (AT) deficiency. There was, however, a good discrimination between carriers of the FVLM (highest ratio 1.44) and patients deficient in PC (lowest ratio 1.59), in particular when samples were prediluted with factor V deficient plasma FVDP (1.16 vs. 1.96, respectively). Predilution of samples with FVDP caused a clear discrimination between controls and patients deficient in PC, PS, AT, and FVLM-positive individuals and also in patients on oral anticoagulant treatment. Our data show that the Factor V (Leiden) Test discriminates well between carriers of the FVLM and healthy controls or patients deficient in PC, PS, and AT. Individuals presenting values between the lower cutoff of controls and the range in which FVLM-positive individuals are found are highly suspicious for protein C deficiency.

Antithrombins↗

PubMed1999

Evaluation of the automated coagulation analyzer SYSMEX CA 6000.

In the present study the coagulation analyzer SYSMEX CA 6000 (TOA Medical Electronics Co., Kobe, Japan), an analyzer equipped with a photooptical clot detection unit and a cap-piercing system, was evaluated with respect to its technical characteristics in the determination of standard coagulation tests (prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen, and antithrombin) and in the determination of coagulation single factor activities. In the normal and in the pathological range the intraassay coefficients of variation (CV) and interassay CV for most parameters were below 5% (exceptions: intraassay CV 5.4% for prolonged thrombin time; intraassay CV 9.26% and interassay CV 10.7% for decreased antithrombin; interassay CV 5.62% for fibrinogen in the normal range, intraassay CV 10.1% for fibrinogen greater than 7.0 g/L; intraassay CV 6.36% and interassay CV 11.7% for decreased fibrinogen; interassay CV 11.6% for prolonged activated partial thromboplastin time; interassay CV 6.12% for decreased factor VII). Interference studies with lipemic, icteric, and hemolytic samples showed just minor influences of these abnormal sample characteristics on prothrombin time, activated partial thromboplastin time, fibrinogen, and antithrombin measurements when compared to the results obtained by using mechanical clot detection (STA, Stago Diagnostica, Asnieres-Sur-Seine, France). No carryover was detected in alternating measurements of heparinized (3 U/mL unfractionated heparin) and normal plasma samples. Measurement of the activities of clotting factors V, VII, VIII, and IX showed a good correlation (r=0.993 to r=0.977) between SYSMEX CA 6000 and STA. Our results demonstrate that using SYSMEX CA 6000 analyzer basal routine coagulation testing as well as specialized tests for single factor activities can be performed with satisfactory precision; in particular, the cap-piercing system has no negative effect on the performance of the analyzer.

Adult↗

PubMed1999

The green tea extract epigallocatechin gallate is able to reduce neutrophil transmigration through monolayers of endothelial cells.

Green tea is widely used in Asia and has also become popular in Western countries. The influence of green tea extracts on leukocytes is not well understood. Leukocytes play a crucial role in the process of inflammation. They migrate from the intravascular space into the tissue to attack micro-organisms. The aim of the current study was to investigate the influence of epigallocatechin gallate on leukocyte transmigration through endothelial cell monolayers and thereby evaluate its potential role in the inflammatory process. Human umbilical vein endothelial cells were cultured on microporous membranes to achieve a monolayer. Freshly isolated neutrophils from healthy subjects were measured with a migration assay. The amount of untreated neutrophils migrating through untreated endothelial cell monolayers was used as control and set as 100%. Neutrophils and/or endothelial cell monolayers were pre-treated with epigallocatechin gallate using relevant, as well as higher and lower concentrations. The relevant plasma concentration of epigallocatechin gallate was able to significantly inhibit neutrophil migration through endothelial cell monolayers (69 +/- 6.4% SD; p < 0.05 compared to control), when both cell types (leukocytes and endothelial cell monolayer) were treated. This is similar to the situation after resorption in-vivo. Treating either neutrophils or endothelial cell monolayers alone led to significant reductions in migratory response (only neutrophils treated: 86 +/- 8.1% SD, p < 0.05; only endothelial cell monolayers: 77 +/- 6.1%, p < 0.05). In conclusion, epigallocatechin gallate was identified as a potent inhibitor of leukocyte migration through endothelial cell monolayers. The treatment of both cell types showed an additive effect. Endothelial cells seem to be more affected than neutrophils. Further clinical investigations are necessary to understand the potential clinical consequences.

Catechin↗

PubMed1999

The mast cell as site of tissue-type plasminogen activator expression and fibrinolysis.

Recent data suggest that mast cells (MC) and their products (heparin, proteases) are involved in the regulation of coagulation and fibrino(geno)lysis. The key enzyme of fibrinolysis, plasmin, derives from its inactive progenitor, plasminogen, through catalytic action of plasminogen activators (PAs). In most cell systems, however, PAs are neutralized by plasminogen activator inhibitors (PAIs). We report that human tissue MC as well as the MC line HMC-1 constitutively produce, express, and release tissue-type plasminogen activator (tPA) without producing inhibitory PAIs. As assessed by Northern blotting, highly enriched lung MC (>98% pure) as well as HMC-1 expressed tPA mRNA, but did not express mRNA for PAI-1, PAI-2, or PAI-3. The tPA protein was detectable in MC-conditioned medium by Western blotting and immunoassay, and the MC agonist stem cell factor (c-Kit ligand) was found to promote the release of tPA from MC. In addition, MC-conditioned medium induced fibrin-independent plasmin generation as well as clot lysis in vitro. These observations raise the possibility that MC play an important role in endogenous fibrinolysis.

Cell Line↗

PubMed1999

Dexamethasone inhibits leukocyte migration through endothelial cells towards smooth muscle cells.

Leukocyte interactions with endothelial cell monolayers (ECM) and smooth muscle cells (SMC) play an important role during inflammatory processes. Several studies describe an inhibitory effect of dexamethasone on polymorphonuclear leukocytes (PMNL), endothelial cell function, and interleukin-1 (IL-1) release. Aim of the current study was to investigate the influence of dexamethasone on leukocyte migration through an endothelial cell monolayer towards SMC-layers stimulated by tumor necrosis factor-alpha (TNF-alpha). Using a recently developed triple chamber migration system, SMC-layers were cultured on the bottom of a 24-well plate. On the upper surface of the first filter, ECM were cultured, the second filter was a collecting filter. The amount of leukocyte migration through ECM towards TNF-alpha-stimulated smooth muscle cell layers with and without dexamethasone-pretreatment was measured using a fluorescence technique. The pretreatment of SMC-layers with dexamethasone reduced the amount of leukocyte migration down to 92 +/- 8.8% (0.001 mM, p=n.s.), to 67 +/- 5.7% (0.01 mM, p<0.05), to 53 +/- 4.6% (0.1 mM, p<0.05), and to 41 +/- 5.0% (1 mM, p<0.05). In conclusion, dexamethasone treatment of smooth muscle cell layers inhibits leukocyte migration through ECM towards smooth muscle cell layers. The inhibition seems to be due to a decrease in IL-1 release. Treatment of all cell types, PMNL, endothelial cells, as well as smooth muscle cell layers, simulating an in-vivo situation, seems to have an additive effect.

Cell Culture Techniques↗

PubMed1999

Heparin lowers plasma levels of activated factor VII.

Based on heparin's antithrombin and anti-FXa activity and its in vitro inhibition of activated factor VII (FVIIa) activity, we hypothesized that unfractionated heparin (UFH) may decrease plasma levels of FVIIa in humans. Therefore, 10 healthy young male volunteers received an intravenous UFH infusion over 24 h. Heparin decreased FVIIa levels by 30% (95% CI 14-47%) at 12 h, which was sustained until 24 h. In contrast, neither the substrate pool (i.e. total factor VII) as measured by FVII antigen nor FVII activity were affected by UFH. These results may improve our understanding of the regulation of FVIIa levels and heparin's mode of action.

Adult↗

PubMed1999

Thromboembolism and resistance to activated protein C in patients with inflammatory bowel disease.

OBJECTIVE: Thromboembolic events are serious complications in patients with inflammatory bowel disease (IBD). Resistance of factor V to degradation by activated protein C (APC) is a major cause for venous thrombosis and is found in approximately 30% of patients with thromboembolism. The aim of the present study was to assess the prevalence of APC resistance and clinical risk factors in patients with IBD. METHODS: One-hundred-two patients with IBD (64 women and 38 men; median age, 35 yr; range, 17-77 yr; 77 with Crohn's disease, 25 with ulcerative colitis) and 102 gender- and age-matched healthy control subjects were investigated prospectively for the presence of APC resistance. None of the healthy controls but 16 patients with IBD had a history of thromboembolism. RESULTS: Patients with IBD and thromboembolism were young, with a median age of 37 yr (range, 17-61 yr). Five (31.3%) of them had APC resistance, which was more common than in patients with IBD without thromboembolism (7%) and in controls (5.9%) (p < 0.01). Three patients had two thromboembolic events, the other 13 each had one. Deep vein thrombosis of the leg and pulmonary emboli were the most common thromboembolic complications (84.2%). Active disease, fistula, or bowel stenosis were found in 10 (52.6%) of 19 thromboembolic events; in three (15.8%) cases thromboembolism happened postoperatively. CONCLUSIONS: APC resistance is not associated with IBD but, when present, increases the risk of thromboembolism. Patients with IBD and thromboembolism are mostly young and clinical risk factors can be found in one-half of cases.

Activated Protein C Resistance↗

PubMed1999

Endotoxin-induced activation of the coagulation cascade in humans: effect of acetylsalicylic acid and acetaminophen.

During Gram-negative septic shock, lipopolysaccharide (LPS, endotoxin) induces tissue factor (TF) expression. TF expression is mediated by nuclear factor kappaB and amplified by activated platelets. TF forms a highly procoagulant complex with activated coagulation factor VII (FVIIa). Hence, we hypothesized that aspirin, which inhibits LPS-induced, nuclear factor kappaB-dependent TF expression in vitro and platelet activation in vivo, may suppress LPS-induced coagulation in humans. Therefore, we studied the effects of aspirin on systemic coagulation activation in the established and controlled setting of the human LPS model. Thirty healthy volunteers were challenged with LPS (4 ng/kg IV) after intake of either placebo or aspirin (1000 mg). Acetaminophen (1000 mg) was given to a third group to control for potential effects of antipyresis. Neither aspirin nor acetaminophen inhibited LPS-induced coagulation. However, LPS increased the percentage of circulating TF(+) monocytes by 2-fold. This increase was associated with a decrease in FVIIa levels, which reached a minimum of 50% 24 hours after LPS infusion. Furthermore, LPS-induced thrombin generation increased plasma levels of circulating polymerized, but not cross-linked, fibrin (ie, thrombus precursor protein), whereas levels of soluble fibrin were unaffected. In summary, a single 1000-mg dose of aspirin did not decrease LPS-induced coagulation. However, our study showed, for the first time, that LPS increases TF(+) monocytes, substantially decreases FVIIa levels, and enhances plasma levels of thrombus precursor protein, which may be a useful marker of fibrin formation in humans.

Acetaminophen↗

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

Ibuprofen inhibits leukocyte migration through endothelial cell monolayers.

During inflammation leukocytes are playing a tremendous role in the defense against bacterial infections. Tumor necrosis factor alpha (TNF alpha) increases adhesion of leukocytes to endothelial cells. The non steroidal anti-inflammatory drug ibuprofen is able to reduce inflammatory processes in humans and is a widely used drug. The influence of ibuprofen on TNF-alpha-induced expression of adhesion molecules on endothelial cells is well investigated and has been published recently by our group. For leukocyte migration, leukocytes have to attach and finally migrate through monolayers of endothelial cells. The aim of the current study was to investigate leukocyte migration through endothelial cell monolayers (ECM) under ibuprofen using a migration assay system. Ibuprofen was identified as a potent inhibitor of the leukocyte migration through endothelial cell monolayers in a dose dependent manner. The treatment of either leukocytes (87 +/- 17.6 %; p>0.05) or endothelial cell monolayers (62.5 +/- 9.4 %; p<0.05) showed that the influence is more mediated through endothelial cells, the treatment of both cell types demonstrated an additive effect. In conclusion, the previously published changes of adhesion molecules on endothelial cells could be confirmed with this functional migration test. The inhibition of the leukocyte migration may contribute to the anti-inflammatory actions of the drug.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1998

Human endothelial cells do not exert heparin like accelerating effects on thrombin-antithrombin-complex formation.

In the present study the formation of thrombin-antithrombin-complexes (TAT) during incubation of thrombin (0.89, 4.5, 8.9 nmol/l) and antithrombin (4.6 micromol/l) on the surface of cultured human EC, derived from different parts of the circulation, and on the surface of human vessel segments was studied. In the absence of EC TAT increased over time reaching a maximum at 60 sec; 10 sec (8.9 nmol/l thrombin): 6.35+/-0.72 nmol/l, 60 sec: 10.49+/-1.04 nmol/l. In the presence of exogenous heparin (0.1 IU/ml) maximum TAT levels were already reached after 10 sec (10.75+/-0.97); cultured EC and EC on vessel segments did not show such heparin effects. Incubation of EC with heparin resulted in an EC-surface localized heparin activity only when very high doses (3.0 IU/ml) of the drug were used. When thrombin was incubated on the EC surface in the presence of AT the efficiency of the thrombomodulin(TM)-protein C(PC)-system was markedly reduced, while in the presence of exogenous heparin (0.5 IU/l) the activity of this pathway was nearly abolished. Our results demonstrate that 1) human EC do not exert heparin-like accelerating effects on TAT formation, 2) an EC localized heparin activity is only generated when EC are incubated with amounts clearly exceeding therapeutical doses, and 3) an acceleration of TAT formation at the EC surface by heparin causes a switching off of the TM-PC-system.

Anticoagulants↗

PubMed1998

Leukocyte migration: a new triple migration chamber assay allows investigation of various cell interactions simultaneously.

Examination of the interactions between various cells of the vascular wall and blood components are essential for understanding different pathophysiological processes. Such investigations require appropriate techniques. Several groups have attempted to establish different methods. In all blood vessels except capillaries, endothelial cells (EC) and smooth muscle cells (SMC) coexist and interact very closely. The current study describes a new 3-dimensional triple chamber migration assay, studying leukocyte migration through human endothelial cell monolayers (ECM) towards human SMC layers simultaneously. To test the new assay, SMC-layers were prestimulated with different concentrations of tumor necrosis factor alpha (TNF-alpha, 1 ng/ml, 10 ng/ml, 100 ng/ml) over 6 hours. Then, two microporous membranes, a collecting membrane and a third membrane with cultured ECM, were inserted. Freshly isolated peripheral blood mononuclear cells (PBMNC) were seeded on the ECM and transmigrated cells were measured after further 3 hours incubation. The migration against non stimulated SMC-layers was used as control. Prestimulated SMC-layers led to a dose dependent increase of PBMNC migration into the subendothelial cell space. Antibodies against interleukin-1 reduced the PBMNC migration. In conclusion, this assay allows to study cell migration into the subendothelial space and interactions between different vascular cells. Moreover, this assay can also be used for studies on other cell-cell interactions in man.

Cell Migration Inhibition↗

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

Anticoagulation with prostaglandin E1 and unfractionated heparin during continuous venovenous hemofiltration.

OBJECTIVE: To determine the effect of two doses of prostaglandin E1 (PGE1, alprostadil) combined with unfractionated heparin on the hemofilter life-span and the coagulation profile during continuous venovenous hemofiltration. DESIGN: Prospective, randomized, controlled trial. SETTING: Intensive care unit at a university-affiliated hospital. PATIENTS: Twenty-four critically ill, mechanically ventilated patients with postoperative acute renal failure who require continuous venovenous hemofiltration. INTERVENTIONS: The patients were anticoagulated with 5 ng/kg/min PGE1 and 6 IU/kg/hr heparin or 20 ng/kg/min PGE1 and 6 IU/kg/hr heparin, injected into the extracorporeal circuit before the hemofilter. MEASUREMENTS AND MAIN RESULTS: The life-span of 43 hemofilters was evaluated. They were used until extracorporeal line pressure exceeded 250 mm Hg, ultrafiltration rate decreased to 16 mL/min, or grossly visible extracorporeal clotting occurred. Blood was sampled from the afferent (prefilter) and efferent (postfilter) lines of the extracorporeal circuit. Platelet counts, in vitro platelet function, plasma concentrations of platelet factor 4, prothrombin fragment F1+2, thrombin-antithrombin complex, routine plasma coagulation tests, and hemodynamic profile were determined before and during hemofiltration. Hemofilter usage was significantly longer in patients anticoagulated with 20 ng/kg/min PGE1 (32 +/- 3 [SEM] hrs) than with 5 ng/kg/min PGE1 (22 +/- 3 hrs). In vitro bleeding parameters were significantly prolonged in postfilter blood in patients receiving 20 ng/kg/min PGE1. Prefilter, there was no antiplatelet activity in either group and platelet counts remained stable. No intra- or intergroup differences in plasma coagulation profile or hemodynamic parameters were detected. CONCLUSION: Extracorporeal administration of PGE1, combined with low-dose heparinization, inhibits platelet reactivity and preserves hemofilter life dose-dependently.

APACHE↗

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↗

PubMed1998

Familial lupus anticoagulant: a case report and review of the literature.

The antiphospholipid antibody (APLA) syndrome is defined by the presence of a lupus anticoagulant or markedly elevated plasma levels of anticardiolipin antibodies (ACAs), associated with venous or arterial thromboembolic events, fetal loss or thrombocytopenia. Familial clustering of raised APLA levels has been described, but the reports are heterogeneous with regard to the characterization of the APLA syndrome, coexisting autoimmune diseases and clinical complications. We describe two siblings with a lupus anticoagulant, elevated ACA-immunoglobulin G levels and systemic lupus erythematosus or related autoimmune disorders. Both patients experienced venous thrombotic complications at an early age. We provide a review of the literature, giving special consideration to the familial occurrence of lupus anticoagulants complicated by venous thrombosis, and emphasize the importance of family screening.

Adolescent↗

PubMed1998

Plasma levels of activated factor VII decrease during the menstrual cycle.

Men have an increased cardiovascular risk as compared to women, which is largely ascribed to the cardioprotective effects of female sex steroids. We hypothesised that this may be reflected by differences in the activation status of the coagulation system. Hence the aim of this study was to compare plasma levels of activated factor VII (FVIIa) in men and women, and to study the influence of the menstrual cycle on FVIIa levels. In a prospective study we investigated 20 healthy young women and 20 men. Men had significantly higher levels of activated factor VII (60 mU/ml, CI: 52 to 67) than women during all phases of the menstrual cycle. In women FVIIa was higher during the follicular phase (41 mU/ml, CI: 33 to 50) than during midcycle (34 mU/ml, CI: 24 to 45; p = 0.022 vs. follicular phase) and during the luteal phase (33 mU/ml, CI: 24 to 42; p = 0.006 vs. follicular phase). Prothrombin fragment (F1 + 2) levels decreased from 0.86 nmol/l (CI: 0.51-1.21) by -23% (-39% to -8%; p = 0.011) during midcycle and by -25% (CI: -51% to 1%; p = 0.023) during the luteal phase. These data support the contention that plasma levels of FVIIa, a key enzyme of the coagulation cascade, may be down-regulated by endogenously produced female sex hormones during the menstrual cycle. This may at least partially explain the marked gender differences found in FVIIa.

Adult↗

PubMed1997

Enhanced blood coagulation and enhanced fibrinolysis during hemodialysis with prostacyclin.

In the present study the effect of unfractionated heparin (UFH) (Liquemin, 750-1000 IU/h), low molecular weight heparin (LMWH) (Fragmin, 3000-7250 IU bolus), and prostacyclin (Flolan, 5 ng/kg body weight/min) on the activation of blood coagulation and fibrinolysis, induced by polysulfone membrane dialyzers during hemodialysis, was compared. Plasma levels of thrombin-antithrombin III complex (TAT), fibrin split product D-dimer, and plasmin-plasmin inhibitor-complex (PPI) were measured in the arterial and venous line of the dialyzer at the beginning and at 10, 60, 120, and 180 minutes of hemodialysis. Five patients on chronic hemodialysis treatment were investigated in a cross over study. Clinically all three anticoagulation regimen were sufficient for hemodialysis treatment. Using UFH or LMWH TAT, PPI, and D-dimer levels were similar in the venous and the arterial line of the dialyzer. However, during prostacyclin treatment the levels of these activation markers were significantly higher in the venous line. Based on these data the dialyzer membrane can be considered as a site of activation of blood coagulation and of fibrinolysis during anticoagulation with prostacyclin in hemodialysis.

Adult↗