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Biomedical subjects

G Pindur

Publications and source records attributed to G Pindur.

At least 73 records · Page 4Linked to original sources

[Quality control of prothrombin complex preparations: in vivo and in vitro findings].

Prothrombin complex concentrates (PCC) are frequently used for the treatment of acquired coagulation factor deficiencies. However, a major problem when using these preparations is their thrombogenic potential. Thus, the potency and tests for thrombogenicity were studied prospectively in 7 different PCC's. Human albumine and a factor IX concentrate served as controls. The potency of coagulation factors and inhibitors varied considerably, especially for proteins S and C. Two preparations exhibited high amidolytic activities in vitro. These activities could be quenched in part by the addition of hirudin or antithrombin III. Additionally, these two preparations caused more severe cardiopulmonary reactions in rabbits and an increase of fibrin split products. We conclude that the use of these preparations in patients, in whom an acquired protein C or S defect, or a hypercoagulable state, can be suspected, cannot be recommended.

Blood Coagulation Factors↗

[Recombinant human erythropoietin (rh-EPO) in chronic, dialysis-dependent renal failure: effects on macro- and microcirculation and hematologic parameters].

Recombinant human erythropoietin (rh-EPO) has been shown to be effective in the treatment of renal anemia. Additionally, rh-EPO improves the hemostatic defect of uremia. On the other hand, a hypertensinogen effect and an increased risk for thrombosis have been reported in hemodialysis (HD) patients with rh-EPO. 20 HD patients in Homburg were recruited for a multicenter, placebo-controlled study (MF 3981), aiming to assess the risk of rh-EPO. Initially, 10 patients received rh-EPO at a dose of 3 x 80 U/kg body weight and week which was subsequently adjusted according to the hematocrit. After 6 months, the patients receiving placebo were changed to rh-EPO therapy. Clinical and laboratory data were obtained before, as well as 1, 3, 6 and 12 months after beginning of the study. Erythrocyte counts increased significantly in the rh-EPO group. Also, an increase of platelet count, fibrinogen and plasma viscosity was observed during rh-EPO. Tissue type plasminogen activator and plasminogen activator inhibitor as well as von-Willebrand-factor remained unchanged, although a shortening of the bleeding time was observed. Blood pressure and arterial blood flow were not influenced by rh-EPO.

Blood Viscosity↗

[Pharmacologic and clinical principles for rational anti-thrombotic preventive treatment with low molecular weight heparin].

Heparin exerts its anticoagulant function by accelerating the inhibitory effect of antithrombin III. Low molecular weight heparin (LMWH), which is derived from unfractionated heparin (UFH), exhibits marked anti-Xa activity and minor thrombin inhibition. It has an elevated bioavailability and longer half-life as to the anti-Xa clearance when compared to UFH. Platelet, endothelial and fibrinolytic effects are also involved in antithrombotic action. Clinical trials have shown that LMWH compared to UFH is an equivalent and even advantageous method of antithrombotic prophylaxis in surgical patients and has also a minor risk of bleeding.

Blood Coagulation Tests↗

Effects of garlic on blood fluidity and fibrinolytic activity: a randomised, placebo-controlled, double-blind study.

In summary, it can be said that the improvement of blood fluidity and the simultaneous increase in fibrinolytic activity are an ideal complement. While the increase in fibrinolytic activity supports the physiological reparation process in the microcirculation, the improvement of blood fluidity produces an increase in capillary perfusion that has, in some way, a cleaning effect, with a 'purification' of the microcirculation.

Adult↗

[Intraspinal, extradural hemorrhage in a 7-year-old boy with hemophilia B].

A 7-year-old boy with severe hemophilia B suffered an intraspinal extradural hemorrhage without preceding trauma. Since the age of 3 years the patient is HIV-1 positive. The actual hemorrhage caused a strong pain in the thoracolumbar area without signs of spinal cord compression. It was diagnosed by CT-scan. By early high dose factor-IX substitution the hemorrhage was stopped and no neurological complications occurred. The further substitution regime is described.

Child↗

Study of a new low molecular weight heparin (LU 47311) administered to healthy volunteers.

A newly developed low molecular weight heparin (LU 47311) was given to 6 healthy volunteers (males, mean age: 30.5 years, range: 20-39 years). They obtained a single dose of 40 and 60 anti FXaU per kg body weight, respectively, by subcutaneous administration. The anti FXa elimination half-life was close to 3 hours. The APTT showed slight response following high dose. No significant influence on fibrinolysis as measured by t-PA and PAI assays was noticed. There was no clear evidence of enhancement of platelet function when detected by Born's method and platelet factor 4 and beta-thromboglobulin assays. However, a moderate but significant increase of thromboxane B2 was noticed in the group obtaining an elevated dose of LMW heparin. Serum levels of triglycerides and cholesterol remained unaltered. The aminotransferases, electrolytes, renal function parameters and cell counts of the peripheral blood were not influenced by LMW heparin.

6-Ketoprostaglandin F1 alpha↗

In vivo recovery and half-life time of a steam-treated factor IX concentrate in hemophilia B patients. The influence of reagents and standards.

Factor IX (FIX) recovery and half-life was measured in ten hemophilia B patients under standardized conditions. Each patient received a steam-treated high-purity factor IX concentrate at a dose of 19-39 U/kg body weight. FIX activity was determined using a one-stage assay, which was calibrated against the international concentrate standard (reagents from Immuno, Heidelberg). The in vivo recovery ranged from 24% to 53% (mean value 37.7%) and the half-disappearance time (HDT) from 8-30 h (mean 16.7 h). In four of the ten patients, the distribution and elimination half-lives were estimated and ranged from 0.3 h to 3.9 h (mean 1.4 h) and from 28.6 h to 39.7 h (mean 33.1 h), respectively. In six patients FIX was redetermined using a different FIX deficient plasma and a plasma standard (reagents from Merz & Dade, Munich, FRG). Recoveries and HDT based on the results obtained with this method were significantly higher (68.2% vs 39.7%; p less than 0.05), and longer (14.8 h vs 10.6 h; p less than 0.05), respectively. FIX activity was also measured by both assay systems in 100 healthy subjects (50 males, 50 females). The reagents from Immuno yielded a mean value of 0.77 U/ml, while the mean FIX activity utilizing standards and reagents from Merz & Dade was 1.11 U/ml (p less than 0.000001). The coefficient of correlation between the FIX activity measurements, as determined in 100 healthy subjects and 6 hemophilia B patients using the different test systems, was r = 0.9 (N = 159; y = 0.08 +/- 1.3* chi; p less than 0.001). Our data suggest that recovery and HDT of factor IX concentrate strongly depend on the assay and calibration conditions and that an international FIX activity plasma standard is urgently required.

Adolescent↗

Characterization of commercially available plasminogen preparations in vitro: purity and reactivity.

Three different commercially available plasminogen preparations (Immuno-, Kabi-, and Behring-plasminogens) were examined regarding purity and reactivity to different activators (high molecular weight [HMW] or low molecular weight [LMW] two-chain urokinase type plasminogen activator [tcu-PA], single chain urokinase type plasminogen activator [scu-PA], tissue type plasminogen activator [t-PA], and streptokinase [SK]). The Immuno-preparation was a Lys-plasminogen, commercially available for therapeutical use, whereas the research reagents for KabiVitrum and Behringwerke were Glu-plasminogen. Activity data provided by the manufacturers correlated well with our findings. Also a good correlation of reactivity to activators measured with a chromogenic substrate and on fibrin plates could be observed. The Immuno-plasminogen showed a minimum contamination with plasmin which has to be taken into consideration for the interpretation for its apparently higher activation by plasminogen activators compared to the plasmin-free plasminogens. Further in vitro and in vivo research has to be performed to find out criteria for a practicable scheme of administration of fibrinolytic agents for therapeutical thrombolysis.

Electrophoresis, Polyacrylamide Gel↗

HTLV III antibodies and immunological alterations in hemophilia patients.

The clinical, immunological, and serological status of 28 patients with hemophilia A and of 13 patients with hemophilia B was investigated. Thirty-four patients were treated regularly by clotting factor concentrates and 7 patients had been substituted only 1 to 4 times. Almost all patients with severe hemophilia suffered from hepatopathy. No patient had clinical evidence of the acquired immunodeficiency syndrome (AIDS). Asymptomatic hemophiliacs showed a decreased number of T-helper (OKT 4) cells and an increased number of T-suppressor (OKT 8) cells, which resulted in an inversed OKT 4/OKT 8 cell ratio. Natural killer cell activity of all patients was decreased compared to controls. After culture there was no significant difference of NK cell activity between hemophiliacs and controls. This phenomena was interpreted as a possible maturation defect of NK-cells in vivo. No relationship between immunological alterations and hepatopathy, hepatitis markers, CMV antibodies, amount and source of required factor concentrates, and the kind of hemophilia was observed. IgG immunoglobulins were higher and the OKT 4/OKT 8 ratio lower in the eight patients with lymphadenopathy than in patients without lymphadenopathy. The prevalence of antibodies to human T-lymphotropic virus (HTLVIII) was measured in 35 hemophiliacs and in 25 polytransfused patients, most of whom were suffering from acute leukemia. In 8 of 35 hemophiliacs antibodies to HTLVIII virus were detected by an enzyme linked immunosorbent assay (ELISA) and confirmatory tests. All seropositive patients were treated by blood products from the United States. Eight hemophiliacs treated by factor concentrates from German donors only were seronegative. In comparison 2 of 25 examined non-hemophilia patients receiving multiple blood products from local donors were seropositive for HTLVIII. The results show that hemophilia patients treated by imported clotting factor concentrates have a high risk of HTLVIII positivity. Hemophiliacs substituted by blood products obtained by local donor pools have only a small risk of infection. Because non-hemophiliac polytransfused patients had HTLVIII antibodies, there must be asymptomatic virus carriers in the local donor pool. The HTLVIII antibody screening of all donors and the heat treating of factor concentrates will give better therapeutic safety.

Acquired Immunodeficiency Syndrome↗

Treatment of refractory chronic idiopathic thrombocytopenic purpura with high dose intravenous immunoglobulin.

Three patients with a history of chronic idiopathic thrombocytopenic purpura stretching back over 20 years are reported. Despite splenectomy and immunosuppressive therapy satisfactory control of their disease has not been achieved. They had remained refractory to all therapeutic manoeuvres with corticosteroids and immunosuppressives for years with thrombocyte counts between 5,000 and 25,000/microliters and the concommitant risk of bleeding. This report describes the treatment of bleeding complications in these patients with high dose intravenous immunoglobulin; the peripheral blood thrombocyte count increased in all three patients from subnormal towards normal, but 2 to 4 weeks later returned to its initial low value. During the therapeutically induced raised thrombocyte count a normal bleeding time and only a moderate inhibition of thrombocyte adhesion and aggregation was observed resulting in reasonable haemostasis. High dose intravenous immunoglobulin is therefore a practical method for the control of bleeding complications in patients with refractory chronic idiopathic thrombocytopenic purpura. A clear explanation for its mode of action has not been found - the lymphocyte subpopulations remained unchanged and immunoglobulin production in vitro during the course of treatment was only minimally decreased.

Antibody Formation↗

The treatment of haemophilia A inhibitor with high dose intravenous immunoglobulin.

In patients with Haemophilia A, the development of inhibitor is a life-threatening complication of treatment. These patients are at high risk for dangerous bleeding as a result of this acquired resistance to human Factor VIII concentrate. Although treatment of bleeding complications has been improved with the introduction of an activated prothrombin complex preparation, therapy remains unsatisfactory. Two patients with Haemophilia A inhibitor were treated with high dose intravenous immunoglobulin in the expectation of an immunosuppressive effect. A rise in the antibody titre at the same time as the administration of factor VIII concentrate showed that this treatment was ineffective in patients with Haemophilia A inhibitor.

Adolescent↗

Impaired natural killer cell function in hemophiliacs with or without continuous substitution.

In the present study, 28 hemophiliacs substituted continuously and 5 hemophiliacs who had received almost no blood products were investigated. Cells of OKT 3+, OKT 4+, and OKT 8+ subsets were counted. Percoll separated fractions of peripheral blood mononuclear cells were examined by morphological criteria and were tested for NK cell activity. We found that the NK cell activity of both groups of hemophiliacs was decreased on testing Ficoll separated cells or low density Percoll separated cells. Normal NK cell activity was found in medium density cells of hemophiliacs. Two possible explanations are discussed: first, the NK cell activity may be suppressed in hemophiliacs and secondly, there may be a block in maturation of NK cell activity. It is unlikely that chronic substitution by blood products counts for these alterations. The possible role of chronic infections is discussed.

Acquired Immunodeficiency Syndrome↗

[Thrombocytopenia and disseminated intravascular coagulation in low-dose heparin prophylaxis].

During postoperative prophylaxis of thrombosis using subcutaneous low-dose heparin thrombocytopenia and consumption coagulopathy without manifest haemorrhage were observed in a female patient with gynaecologic problems on the tenth postoperative day. Using gel-electrophoresis, demonstration of cross-linked fibrin derivatives, which occur only after contact with thrombin, was proof that disseminated intravascular coagulation must have been present. Cancellation of heparin prophylaxis was sufficient for regression of the haemostatic disorder. Platelet function tests performed two months later showed as the only reproducible abnormality that the patient's plasma caused inhibition of desaggregation of normal platelets only when heparin was present. The remarkably close chronologic connection of heparin prophylaxis with thrombocytopenia and consumption coagulopathy suggests a possible causal connection. However, at present the possibly heterogeneous aetiology cannot be explained satisfactorily.

Adult↗

[Blood clotting factor XIII substitution in acute leukaemia: result of a randomized and controlled study].

A randomized and controlled study was undertaken to test whether substitution with factor XIII concentrates influences the clinical course in patients with acute leukaemia and acquired factor XIII deficiency (less than or equal to 60%). A control group of 31 patients was compared with a factor XIII-treated group of 29 patients. Partial factor XIII deficiency was successfully corrected by substitution. On the other hand, there was no statistically significant difference between the two patient groups in the frequency and severity of bleeding complications, transfusion requirements, and the number of remissions. Undesirable side-effects as a result of substitution treatment were not observed.

Acute Disease↗