[Platelet retention test Homburg (RTH) and drug monitoring of platelet adhesive properties of von Willebrand factor]. / Plättchen-Retentionstest Homburg: Drugmonitoring der Plättchenadhäsivität des von-Willebrand-Faktors.

Platelet plug formation is initiated by the process of platelet adhesion, mainly mediated by the von Wille-brand factor (VWF). Therefore, apart from established criteria the platelet adhesion property is a further criterion to determine VWF e. g. in diagnosis and treatment of von Willebrand disease (VWD). The new platelet retention test Homburg (RTH) is designed to close this gap. It is characterized by its non-thrombogenic filter with interconnecting pores, which retains platelets from blood when pressed through this filter due to the resulting shear stress. The RTH, in particular, proved to be highly sensitive in detecting the platelet adhesive property of VWF after its release from endogenous storage sites by desmopressin or infusion in VWD patients or its supplementation in vitro.

A novel 5'-upstream mutation in the factor XII gene is associated with a TaqI restriction site in an Alu repeat in factor XII-deficient patients.

The factor XII gene from factor XII-deficient patients was screened for mutations at the genomic level. In patients negative for cross-reacting material, a T to C transition 224 bp upstream of exon 3 was identified (exon 3-224 (T --> C)) that creates an additional TaqI restriction site in intron B. This mutation is located within a putative hormone responsive element and within a B box promoter of an Alu repeat of the Sb0 family. The TaqI site is associated with a G to C transversion upstream of the transcription initiation site (exon 1-8 (G --> C)). We discuss the possible roles of these elements in factor XII gene regulation.

Factor XII (Hageman) deficiency in women with habitual abortion: new subpopulation of recurrent aborters?

OBJECTIVE: To examine the possible association between factor XII (FXII) deficiency and an elevated number of abortions. DESIGN: Factor XII activity, FXII antigen concentration, other blood clotting parameters, and phospholipid antibodies were examined in venous blood from 43 women with repeated (3 to 7) abortions before the 28th week of gestation but without gynecological and chromosomal abnormalities. The data were compared with those obtained from 49 age-matched women without fetal loss. RESULTS: Eight cases with moderately reduced FXII activity (35% to 68% of normal) could be identified in the abortion group, whereas among controls no abnormalities in FXII activity and antigen concentration were found. The relative occurrence of reduced FXII level was higher among patients with more than three abortions as compared with those with three abortions. CONCLUSION: Repeated abortions may be associated with reduced level of FXII activity of unknown origin.

[Antithrombin III control in patients with long-term anticoagulant therapy]. / Antithrombin-III-Kontrolle bei zahnärztlich-kieferchirurgischen Patienten mit Langzeitantikoagulationstherapie.

Antithrombin III and protein C are the major inhibitors of the plasma clotting system. Since adequate thromboembolism protection requires a cofactor AT III for heparin to provide full antithrombotic coverage, the preoperative AT III and protein C levels in the plasma of 105 patients treated with marcumar are measured. The understanding of the physiological role of these inhibitors of the plasma clotting system and of the causes for their decrease should directly lead to the indications for laboratory analysis.

[Diagnosis of disseminated intravascular coagulation: the value of soluble fibrin, D-dimers and fibrin(ogen) split products]. / Diagnostik der disseminierten intravasalen Gerinnung: Aussagekraft von löslichem Fibrin, D-Dimeren und Fibrin(ogen)-Spaltprodukten.

The validity of the fibrin(ogen) derivatives 'soluble fibrin, D-dimers and fibrin(ogen) degradation products' was compared with other parameters in early and sensitive diagnosing of disseminated intravascular coagulation (DIC). In a clinical study 900 patients' samples from separate, defined groups were examined, including course observations of intensive care patients (n = 38) and patients with acute pancreatitis. The fibrin(ogen) derivatives correlated very well with the degree of blood coagulation disturbances: in particular, D-dimers and soluble fibrin proved to be more sensitive in early diagnosis of DIC than other parameters. The SF-PS-turbidimetry demonstrated a good validity and practicality in the quantitative determination of soluble fibrin, but a suitable analyzer is essential. Determination of D-dimers is preferable to that of fibrin(ogen) degradation products (both in the latex-agglutination test) because of the better sensitivity and practicality; even more sensitive results were provided by the D-dimer-ELISA, which is, however, not practical in acute diagnostics. The decrease in protein C was at least equally sensitive as the antithrombin III-levels in indicating the consumption of the hemostatic potential. The decrease of thrombocyte counts and fibrinogen levels could first be detected in a later stage of DIC. In conclusion, D-dimers and soluble fibrin can improve the DIC diagnostics, making them more reliable; additionally, antithrombin III and possibly protein C deserve further consideration, although the fibrin(ogen) derivatives are apparently of greater importance.

Enhanced procoagulatory activity (PCA) of human monocytes/macrophages after in vitro stimulation with chemically modified LDL.

In cultured human monocytes/macrophages, surface expression of procoagulatory activity (PCA) was induced by chemically modified LDL (acetyl-LDL and MDA-LDL) in a dose- and time-dependent manner. Maximum PCA (30-fold increase) was detected after 24 h of culture with modified LDL at doses of 25-750 micrograms protein/ml. Using factor VII deficient human plasma and phospholipase C this PCA was identified as tissue thromboplastin activity (factor III). These results suggest a further atherogenic potential for modified LDL through stimulation of the conversion of fibrinogen to fibrin in the atheromatous lesion.

[Homologous collagen implants in oral surgery in hemorrhagic patients]. / Homologe Kollagenvlies-Implantation in der zahnärztlichen Chirurgie bei blutungsgefährdeten Patienten.

In 154 hospitalized hemorrhagic patients 883 oro-surgical procedures were done under continuous anticoagulation. Human collagen material combined with fibrin adhesive offered a safe hemostatic effect. A total of 12, mostly minor, postoperative bleedings occurred, which did not lead to delayed wound healing. Good tissue tolerance towards both homologous partners and healing by primary intention should be emphasized. These observations are to be corroborated by further clinical trials. Human collagen can make surgical treatment in hemorrhagic patients safer yet.

Determination of soluble fibrin by turbidimetry of its protamine sulphate-induced paracoagulation.

Protamine sulphate-induced aggregation of soluble fibrin causes an increase of turbidity in the plasma sample, which can be measured by means of kinetic turbidimetry. A method was developed which is sufficiently sensitive for the determination of soluble fibrin in plasma without interfering with the sensitivity for fibrinogen. The performance of the assay was studied by analysing plasma samples with high concentrations of fibrinogen and soluble fibrin at different pH values, at different concentrations of plasma and protamine sulphate, and using different wavelengths and analysis times. Measurement of thrombin-induced fibrinogen-fibrin-transformation by the developed turbidimetric method, gave results that correlated well with the release of fibrinopeptide A. The new protamine sulphate method for turbidimetric determination of soluble fibrin is characterized by its practicability, rapid availability of reproducible, quantitative results, and its economy of reagents and time in single and serial analysis. Therefore it seems well-suited for the routine diagnosis of hypercoagulability with increased fibrinogen turnover.

Comparison of low molecular weight heparin to standard heparin in hemodialysis/hemofiltration.

Low molecular weight (LMW) heparin has been compared to standard unfractionated (UF) heparin in hemodialysis/hemofiltration in a 12 month, randomized study. Seventy patients with end-stage chronic renal failure starting dialysis treatment were randomly assigned to one of two groups treated with either LMW or UF heparin. The LMW and UF heparin doses used produced similar plasma anti-FXa levels, and comparable antithrombotic effectiveness was observed in the two groups as reflected in similar incidences of thrombus formation in the extracorporeal circulation: 1.59% and 1.33% for LMW and UF heparin, respectively. No bleeding complications were seen with either heparin, but significantly (P less than 0.05) fewer erythrocyte concentrates were needed in the LMW heparin patients. Mean factor VIII activities had risen significantly (P less than 0.001) after 12 months in the UF heparin group, whereas they were unchanged in the LMW heparin group. A significant (P less than 0.05) increase in plasma triglycerides was observed in the UF heparin group which was attributable to six (18.8%) of the patients in this group. Triglyceride concentrations remained relatively constant in the LMW heparin group. Post-heparin lipolytic activity, and in particular hepatic lipase activity, was not stimulated to the same extent in the LMW heparin-treated patients as compared to the UF heparin group. We conclude that LMW heparin is a suitable alternative to standard UF heparin for anticoagulation in hemodialysis/hemofiltration therapy. It may offer potential advantages with regard to a lower requirement for erythrocyte concentrates and less derangement of certain metabolic parameters, such as factor VIII, triglycerides and plasma lipase activity.

Continuous intravenous infusion of elastase in normal and agranulocytic minipigs--effects on the lungs and the blood coagulation system.

In order to investigate the acute effects on lung morphology, lung function, hemodynamic and blood coagulation system, elastase (330 units (U) kg-1 h-1) was continuously infused into 16 anesthetized and mechanically ventilated minipigs. Elastase infusion induced a disturbance of blood coagulation leading to hypocoagulability, a pulmonary leukostasis, interstitial edema, a progressive respiratory failure with prompt increase in pulmonary vascular resistance, decrease in systemic vascular resistance, increased venous admixture, and increased dead space ventilation. Agranulocytosis prevented interstitial edema but not disturbances in pulmonary or hemodynamic function or hypocoagulability. The results clearly indicate that elastase may be involved in the pathophysiology of acute lung failure and defects in the blood coagulation system.

Fibrinolytic activity in renal venous blood in man.

In 50 patients without renal insufficiency, fibrinolytic activity, as reflected by euglobulin lysis time, was determined in blood obtained from the renal veins, the renal artery and a peripheral vein. Fibrinolytic activity was found to be significantly higher in the renal veins than in the renal artery and the peripheral vein. Other coagulation and fibrinolysis parameters did not show such differences. In addition, a patient with acute oligoanuric renal failure was investigated. This patient demonstrated reduced overall fibrinolytic activity, but there were no differences between the activity in the blood of the renal veins and that of the renal artery or peripheral vein. It seems, therefore, that the kidneys release plasminogen activators into the systemic circulation. This may be decreased in renal failure, probably contributing to the well-known diminished fibrinolysis in some kidney diseases.

[Significance of antithrombin III in kidney diseases]. / Bedeutung von Antithrombin III bei Nierenerkrankungen.

This article deals with the clinical importance of antithrombin III (AT III) in renal disease. Patients with nephrotic syndrome demonstrates a high risk of thromboembolism. A renal AT III loss is an important pathogenetic factor in these events. Patients with serumalbumin below 2.0 g/dl are mostly endangered. In patients with acute oligoanuric renal failure low AT III-levels due to consumption were often found that lead to diminished protection against intravascular coagulation processes and can therefore contribute to progression of illness. An AT III-substitution may be of some benefit in these patients. Additionally AT III was given in patients with dialysis-dependent renal failure and low levels of AT III leading to a reduced incidence of thrombosis of the extracorporeal system. Unnecessary high doses were also avoided and a minimal heparinization could be performed more efficiently in bleeding risk patients. Furthermore, AT III-levels during renal transplantation and during organ rejection are reported.

Comparison of unfractionated heparin and low molecular weight heparin during long-term use in chronic haemodialysis and haemofiltration patients.

Antithrombotic activity, necessary doses and effects on coagulation and lipid variables of the low molecular weight heparin derivative Fragmin were compared to unfractionated (UF) heparin in long-term multicentre trials. Results of more than 10,000 dialyses are reported. On the basis of preliminary studies, UF heparin and Fragmin doses were used that lead to anti-Xa activities of more than 0.5 U/ml. With this dose, sufficient antithrombotic activity was achieved with both heparins. Bleeding complications were not noticed. Partial thromboplastin time (PTT) and thrombin time were only marginally increased by Fragmin (5-8 s) in contrast to UF heparin (PTT 90-120 s, thrombin time 230-260 s). Surprisingly, the elevated levels of factor VIII strongly decreased during the 6-month treatment period with Fragmin and increased again during the following 6-month treatment period with UF heparin. Creatinine, urea, haemoglobin and transaminases did not change in both heparin groups: this excluded reduced dialysis efficiency or occult blood loss. Additionally, 15 patients with acute renal failure and high bleeding risk were dialysed with low doses of Fragmin (anti-FXa: 0.2-0.3 U/ml). No severe bleeding occurred. A continuous ambulant peritoneal dialysis patient with deep vein thrombosis was treated effectively with intraperitoneal application of Fragmin for 6 months without any problems.

[Effect of Expafusion (HES 40/0.5) on the corpuscular elements of blood and inhibitors of blood coagulation]. / Einfluss von Expafusin (HAS 40/0.5) auf die korpuskulären Anteile des Blutes und die Inhibitoren der Blutgerinnung.

The present study reports on an investigation of 32 normal subjects who were given intravenously 500 ml of hydroxyethyl starch (HES) over 30 min. In 16 normal subjects, 500 ml of blood had been previously withdrawn over 20 min. Tolerance proved to be good. Side effects such as hyperergic reactions, influence on circulatory or cardiac function were not observed. Changes in corpuscular elements of blood did not exceed the dilution effect and mostly returned to the initial value 60 min after termination of HES infusion. The change in thrombocyte function, immunoglobulins and the inhibitors alpha 1-antitrypsin, alpha 2-macroglobulin, as well as C1-inactivator and C3-activator only slightly, but not more pronounced than it could have been expected by the dilution effect. A favorable effect could be recorded in erythrocyte filtration according to Schmidt-Schoenbein. Here, we found an improved flow property which exceeded the hemodilution effect and lasted over the 4-hour test period. In addition, thrombocyte aggregation during ADP administration in the Born chamber did not show any change which suggests that a clinically relevant effect on thrombocyte function and thus the danger of hemorrhage during HES administration can be excluded.

Low molecular weight heparin in hemodialysis and hemofiltration patients.

Low molecular weight (LMW)-heparin was used as the sole anticoagulant during hemodialysis and hemofiltration in a pilot study on 32 patients. A LMW-heparin dose corresponding to 50% of the patients usual unfractionated, standard (UF)-heparin dose was found to produce comparable plasma heparin levels (anti-FXa-activity). No thrombosis of the extracorporal system and no bleeding complications occurred at this LMW-heparin dose. In contrast to UF-heparin, LMW-heparin produced only slight increases in PTT and thrombin time in all patients. Lipoprotein lipase was stimulated only marginally by LMW-heparin, with a correspondingly reduced release of free fatty acids. Both heparin species caused similar elevations in factor VIII and fibrin monomers, thus excluding a difference in coagulation activation. On the basis of these results, long-term studies have been started at four nephrology centers. To date, 26 patients have been treated with LMW-heparin for 6 months. A LMW-heparin dose was used that produced plasma anti-FXa-activity of 0.5 to 0.9 U/ml (initial dose: 30 to 40; dose/hr: 8 to 15 anti-FXa-units/kg body wt). PTT and thrombin time were only increased by 5 sec on average. Surprisingly, the elevated pre-dialysis levels of factor VIII and fibrin monomers decreased during this 6-month period. Bleeding complications did not occur and thrombotic complications were not observed when the anti-FXa levels were above 0.5 U/ml. LMW-heparin, therefore, appears to be a good alternative to UF-heparin for dialysis patients and may present less risk of bleeding because of its reduced effect on PTT, thrombin time, and thrombocytes.

Efficacy of large-volume plasma exchange in patients with chemotherapy-resistant metastatic colorectal cancer.

23 patients with advanced metastatic colorectal adenocarcinoma and measurable metastases were treated with chemotherapy until resistance to chemotherapy was evident. Chemotherapy was then not discontinued but administered for at least a further cycle combined with large-volume plasma exchange (PE). 15 of 23 patients responded again for 4-45 weeks, an average of 13. This effect was thought to be due to dilution or elimination of serum-blocking factors, which could be measured by mixed lymphocyte culture (MLC) assay. 16 of 20 patients showed a positive correlation between the clinical course and MLC activity, if the basic MLC reactivity was compared with the MLC levels at the start of each subsequent PE in each patient. It is postulated that in some tumors there is a resistance to chemotherapy mediated by plasma-blocking factors.

[The behavior of blood clotting and its inhibitors under long term treatment with 5,6-benzo-alpha-pyrone (coumarin). Double blind study]. / Das Verhalten der Blutgerinnung und deren Inhibitoren unter Langzeitbehandlung mit 5,6-Benzo-alpha-pyron (Cumarin). Doppelblindstudie.

The analyses on hemostaseological variables are recorded in connection with blood tests in the course of a double-blind study in 41 patients suffering from chronic venous insufficiency of higher degrees of severity. They were treated in addition to compression measures with two active ingredients, a coumarin (5,6-benzo-alpha-pyrone)/troxerutin combination (Venalot Depot) (n = 20) or benzarone (n = 21) receiving 3 X 2 dragees daily for 6 weeks. Good clinical efficacy and the improvement of symptoms were observed together with almost no side-effects. The coagulation analysis showed no influence of the active principles on the global coagulation or the clotting factors and the inhibitors and factors of the fibrinolysis. In particular there was no phenprocoumon-like effect on the blood clotting system.

[Use of low molecular-weight heparin in hemodialysis patients]. / Anwendung von niedermolekularem Heparin bei Hämodialysepatienten.

Low-molecular-weight (LMW) heparin has been compared to standard unfractionated (UF) heparin in a total of 49 patients on hemodialysis and hemofiltration in order to determine the necessary therapeutic dose and its effect on the coagulation system. A LMW heparin dose corresponding to 50% of the normal UF heparin dose was found to produce similar plasma heparin levels (anti-FXa-U/ml) in particular on minimal heparinization. At higher doses, UF heparin produced a more marked increase in plasma-heparin than did LMW heparin. Highly significant differences were found between UF and LMW heparin in their effects on PTT and thrombin time. Partial thromboplastin time (PTT) increased under UF heparin by an average of 120 s whereas LMW heparin only produced an increase of 5-7 s. Thrombin time was increased by 250-280 s under UF heparin and by 5-8 s under LMW heparin. With this LMW heparin dose of 50% of the UF heparin dose, no thrombosis of the extracorporal system occurred and no macroscopic detectable thrombotic material was found in the dialyzers or filters. No significant differences were observed between the effects of UF and LMW heparin on Factor VIII activity and fibrin monomers, so that a difference in coagulation activation between the two heparins can be excluded. Furthermore, there were no changes in thromboplastin time according to Quick, fibrinogen, antithrombin III, plasminogen, and a2-antiplasmin.(ABSTRACT TRUNCATED AT 250 WORDS)