[Interferon therapy of chronic hepatitis C in hemophilia].
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Hemophilia A↗
Biomedical subjects
E Seifried
Publications and source records attributed to E Seifried.
Autologous platelet transfusion in alloimmunized patients with acute leukemia.
Seventy-eight transfusions of autologous platelets were given to eight alloimmunized patients receiving curative chemotherapy for acute leukemia. Platelets were collected at regeneration of hematopoiesis after a chemotherapy cycle, cryopreserved with 5% dimethylsulfoxide in liquid nitrogen, and retransfused during bone marrow aplasia following the next treatment cycle. The in vitro platelet recovery after freezing, thawing, and washing was 85 +/- 4%. The in vivo corrected count increment 1 h after autologous platelet transfusions was 11 +/- 5 x 10(9)/l. With the exception of moderate urticaria and slight nausea each after one transfusion, no immediate or chronic side effects occurred. The bleeding time was shortened and hemorrhage during bone marrow aplasia was prevented in all alloimmunized patients by autologous platelet transfusions.
Acute Disease↗
[Fibrinolytic agents--who benefits when?].
Thrombolytic therapy mimics and enhances physiological fibrinolysis. The following substances are presently available for clinical use: the nonphysiological thrombolytics streptokinase, the APSAC (acylated plasminogen-streptokinase activator complex), the physiological plasminogen activators urokinase and tissue plasminogen activator (t-PA). Whereas the first three systematically activate the fibrinolytic system, t-PA possesses relative fibrin selectivity. The fibrin-selective active pro-urokinase has not yet been officially approved for the treatment of thromboembolic diseases, but it is being clinically tested. Fibrinolytic therapy has an established place in the management of acute myocardial infarction and of massive pulmonary embolism. When an acute deep venous thrombosis is diagnosed with a proximal extension into the popliteal vein, thrombolytic therapy is clearly superior to heparin. The lysis has proven to be an effective form of treatment of peripheral occlusive arterial disease. Local thrombolytic therapy is an option for acute and chronic femoro-popliteal occlusions involving the trifurcation into the calf arteries and for embolic occlusions of the same segment in patients with contraindications to surgical therapy. First study results of thrombolytic therapy of stroke are promising.
Anistreplase↗
Anticoagulant-induced pseudothrombocytopenia and pseudoleucocytosis.
Pseudothrombocytopenia (PTP) is the phenomenon of falsely low platelet counts due to in vitro platelet clumping in the presence of platelet autoantibodies and anticoagulants. We assessed anticoagulant-dependence, time course of platelet counts and impact of different counter devices on the phenomenon. Blood of 10 persons with previously recognized pronounced EDTA-dependent PTP was collected into 7 different anticoagulants and counted after different intervals in parallel in a Coulter T540 and a Coulter STKS counter and by phase contrast microscopy. With the Coulter T540 model PTP was most pronounced in blood samples anticoagulated with EDTA, Na-oxalate or Na-citrate. In the STKS counter EDTA, heparin and oxalate presented as the worst anticoagulants. The time course of platelet counts was significantly different between the two counters. Our results demonstrate that PTP is not restricted to EDTA, but is also present with other anticoagulants. In contrast, pseudoleucocytosis was observed only in EDTA-anticoagulated blood in the Coulter T540 device. We investigated the expression of platelet integrins and activation antigens on platelets of persons with anticoagulant-dependent PTP and in healthy controls without PTP. In the presence of EDTA the expression of GpIIb/IIIa was significantly reduced in the PTP subjects compared to control. Activation antigens CD62, CD63 and thrombospondin-antigen were upregulated in the presence of EDTA. These alterations in the expression of platelet antigens could also be induced on platelets of normal donors by incubation with sera of PTP subjects and EDTA.(ABSTRACT TRUNCATED AT 250 WORDS)
Anticoagulants↗
[Costs of safety of blood and blood products].
The safety of blood and blood components in transfusion medicine has become a very important factor. While diagnostic and therapeutic medical procedures need an increasing amount of special blood products, increasing demands on safety result in a reduction of blood donations. Considerable costs are caused by the requirement of self-sufficiency, additional assays to detect virus infections such as HIV, HCV and others, virus inactivation of blood and plasma, storing of plasma in quarantine, increase of autologous blood donation, and a great many of further steps to improve the safety in transfusion medicine. To obtain absolute safety, efforts are required that necessarily exceed the financial capacity of our health system. Because of budget limitations increasing costs of blood products will interfere with progress of other areas of health care. In addition ethical aspects of the use of funds have to be taken into consideration.
Blood Component Transfusion↗
Quality of pooled platelet concentrates prepared from buffy coats and stored in an additive solution after filtration.
Platelet concentrates prepared from buffy coat were pooled and stored for 6 days after removal of leukocytes by filtration. The platelets were stored in plasma or in an additive solution, Plasmalyte-A. In vitro platelet function was better preserved using Plasmalyte-A than plasma with regard to osmotic reversal and aggregation. No significant differences for the release of platelet markers beta-thromboglobulin, platelet factor 4, or lactate dehydrogenase pre- and post-filtration and storage in plasma or Plasmalyte-A was observed. Expression of the surface membrane glycoproteins Ib, Ia/IIa, IIb/IIIa, and IV measured by flow cytometry after binding of monoclonal antibodies did not change during storage. The expression of activation-dependent alpha-granula glycoprotein GMP140, the thrombospondin, and the glycoprotein 53 from the lysosomal granules was not different between platelet pools stored in plasma or in Plasmalyte-A. The in vitro quality of platelets stored as pools is comparable for plasma and the additive solution Plasmalyte-A.
Acetates↗
Prospective randomized clinical study in general surgery comparing a new low molecular weight heparin with unfractionated heparin in the prevention of thrombosis.
A prospective, randomized, controlled clinical trial was performed comparing the antithrombotic efficacy of the low molecular weight heparin LMWH 21-23, (Braun) with an unfractionated heparin in elective general surgical patients over an observation period of 7 postoperative days. A total of 230 patients were admitted: 103 (group I) received low molecular weight heparin and 100 (group II) low-dose unfractionated heparin treatment given subcutaneously. In group I 41 patients (46%) were operated on for malignant disease and in group II 54 patients (54%). Due to the large amount of great abdominal procedures the intra- and perioperative application of hydroxyethyl starch was allowed for volume substitution. None of the patients died due to fatal pulmonary embolism. In group I four patients revealed positive 125I-labeled fibrinogen uptake (3.9%); two patients belonged to the hydroxyethyl starch subgroup. In group II five patients displayed a positive fibrinogen uptake (5%); two belonged to the hydroxyethyl starch subgroup. The results of the hemostaseological investigations (e.g., prothrombin time, activated partial thromboplastin time, thrombin clotting time, fibrinogen, antithrombin III, protein C, plasminogen, alpha 2-antiplasmin, tissue-type plasminogen activator, plasminogen activator inhibitor) revealed no statistically significant differences between groups I and II or their subgroups, although a tendency to prolonged clotting times was observed. The antifactor Xa activity values, however, displayed a statistically significant difference between the two groups (P < 0.05). The antifactor Xa activity measured up to 0.16 U/ml for the low molecular weight heparin (group I) and 0.05 U/ml for the unfractionated heparin (group II) in the postoperative period.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
[Blood coagulation parameters as prognostic factors in multiple trauma: can clinical values be an early diagnostic aid?].
INTRODUCTION: Polytraumatized patients develop complex changes in blood coagulation and fibrinolysis even before their arrival at the emergency room (ER). Hemostaseological parameters (i.e. antithrombine 3, alpha-2-antiplasmine, D-dimers) obtained upon admission however, permit advance differentiation of later mortality vs. survival and of possible future secondary organ failure with varying specification. OBJECTIVES: Which clinical findings enable to identify such patients early in the ER even when no specialized hemostaseological laboratory is available? MATERIAL AND METHODS: a) Prospective study of 40 polytraumatized adults upon arrival at the hospital; b) Blood sampling at the earliest possible time during takeover in the ER; c) Injury Severity Score (ISS) for descriptive purposes; d) Evaluation of the prehospital emergency physician's records in regard to respiratory therapy, fluid resuscitation, and arterial blood pressure; e) Statistics; Wilcoxon test, Spearman correlation coefficient. RESULTS: All 40 patients (m:f = 28:12; mean age: 36 (SD: 16.6) years; mean ISS: 34.7 (SD: 11.4)) displayed advanced disseminated intravascular coagulation with secondary hyperfibrinolysis upon arrival in the ER. The amount of deviation from the hemostaseological norm could not be derived from either the correlation of the typical activated parameters of coagulation of fibrinolysis with the ISS or the analysis of the separate injuries. On the other hand the subgroup of patients displaying a systolic blood pressure of less than 100 mmHg at the site of the accident or upon arrival at the ER all had significantly lower antithrombine 3, protein C, and alpha-2-antiplasmine activities as well as increased concentrations of specific reaction products resulting from activated coagulation (thrombine-antithrombine 3-complex) and of fibrinolysis (D-dimers). CONCLUSION: In our study patients with multiple injuries displaying a systolic blood pressure of less than 100 mmHg either at the scene of the accident or upon arrival in the ER showed coagulation values which by other investigators were regarded as a sign of potential secondary organ failure or death.
Adult↗
Hematologic effects of recombinant human interleukin-6 in dogs exposed to a total-body radiation dose of 2.4 Gy.
The hematologic effects of recombinant human interleukin-6 (rhIL-6) were studied in dogs exposed to a total-body irradiation (TBI) of 2.4 Gy. IL-6 was administered over a period of 14 days at a daily dose of 18 micrograms/kg by single subcutaneous injection. Treatment was started 1 day after TBI. The data obtained for the different hematologic parameters of the irradiated IL-6-treated dogs were compared with the data obtained from dogs who received TBI of 2.4 Gy and were treated with the carrier (control). No clear influence of IL-6 treatment on the pattern of recovery of lymphocytes could be detected in comparison to the irradiated control animals. The thrombocyte counts in the period from day 1 to 16 after TBI were similar for both groups of dogs, showing a sharp decrease in counts between days 6 and 12 with a stabilization thereafter at approximately 30 x 10(3)/microL. In three of the four IL-6-treated dogs, however, thrombocyte counts increased at day 18 after the beginning of treatment. This increase occurred 7 days earlier than in the controls. In two of the three dogs showing an accelerated recovery of platelet counts, however, treatment with IL-6 caused a strong decrease in the erythrocyte counts associated with a prolonged depression in reticulocyte concentration. There was no influence on the recovery of blood granulocytes. In one of the animals responding with an accelerated thrombocyte recovery, IL-6 had no adverse effect on erythropoiesis. However, IL-6 forced the recovery of blood granulocytes in the period beyond day 10 after TBI. Another animal showed no influence of IL-6 on thrombocyte recovery but a strong depressive effect on erythrocyte and reticulocyte counts. The results show that for standardized conditions of radiation-induced bone marrow damage, the pattern of response to IL-6 in different hematopoietic lineages may show considerable variations between individuals, in contrast to what has been observed in irradiated animals treated with granulocyte-macrophage or granulocyte colony-stimulating factor (GM- or G-CSF).
Animals↗
[Essential thrombocythemia. Clinical significance, diagnosis and therapy].
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Adult↗
Successful treatment of haemolytic uraemic syndrome with recombinant tissue-type plasminogen activator.
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Child, Preschool↗
Influence of acute myocardial infarction and rt-PA therapy on circulating fibrinogen.
In 12 patients treated with 100 mg rt-PA/3 h for acute myocardial infarction (AMI), serial fibrinogen levels were measured with the Clauss clotting rate assay ("functional fibrinogen") and with a new enzyme immunoassay for immunologically intact fibrinogen ("intact fibrinogen"). Levels of functional and "intact fibrinogen" were strikingly different: functional levels were higher at baseline; showed a more pronounced breakdown during rt-PA therapy; and a rebound phenomenon which was not seen for "intact fibrinogen". The ratio of functional to "intact fibrinogen" was calculated for each individual patient and each time point. The mean ratio (n = 12) was 1.6 at baseline, 1.0 at 90 min, and increased markedly between 8 and 24 h to a maximum of 2.1 (p < 0.01), indicating that functionality of circulating fibrinogen changes during AMI and subsequent thrombolytic therapy. The increased ratio of functional to "intact fibrinogen" seems to reflect a more functional fibrinogen at baseline and following rt-PA infusion. This is in keeping with data that the relative amount of fast clotting "intact HMW fibrinogen" of total fibrinogen is increased in initial phase of AMI. The data suggest that about 20% of HMW fibrinogen are converted to partly degraded fibrinogen during rt-PA infusion. The rebound phenomenon exhibited by functional fibrinogen may result from newly synthesized fibrinogen with a high proportion of HMW fibrinogen with its known higher degree of phosphorylation. Fibrinogen- and fibrin degradation products were within normal range at baseline. Upon infusion of the thrombolytic agent, maximum median levels of 5.88 micrograms/ml and 5.28 micrograms/ml, respectively, were measured at 90 min.(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
Different effects of two methods of low-density lipoprotein apheresis on the coagulation and fibrinolytic systems.
OBJECTIVE: Immunoadsorption (IMA) and dextran sulfate adsorption (DSA) are two methods for selective extracorporeal elimination of low-density lipoproteins which are known as LDL apheresis. Their influence on haemostasis until now is widely unknown. DESIGN: The effects of both LDL apheresis procedures on the coagulation and fibrinolytic systems were compared amongst five patients treated with IMA and four patients who received a DSA therapy. SUBJECTS: All patients with severe heterozygous familial hypercholesterolaemia were participants in a long-term LDL apheresis programme with treatments every 1-2 weeks. INTERVENTION: Combined anticoagulation with heparin and citrate in IMA, and also heparin exclusively in DSA were used for the extracorporeal circulation. MEASURES: Blood samples were taken immediately before and after a single LDL apheresis and five times during the weekly interval until the next therapy. RESULTS: DSA had a significantly greater effect on standard clotting tests than IMA at the end of plasma therapy despite identical dosages of heparin. DSA caused a considerable reduction of the coagulation factors V, VIII:C, vWF:Ag, XI, XII, and prekallikrein by 48-99% at the end of apheresis treatment whereas only factor VIII:C showed a marked decrease of 72% after IMA. All abnormalities of the global coagulation tests and of most clotting factors were restored 1 day after treatment in both procedures followed by a moderate rebound phenomenon of single coagulation factors during the next few days in IMA-treated patients. CONCLUSION: DSA exerts a more profound effect on the coagulation system than IMA by a substantial co-elimination of various clotting factors in addition to the desired removal of atherogenic lipoproteins.
Adsorption↗
[Effect of preparation and preservation modality on thrombocyte quality].
In patients with acute leukemia, chemotherapy leads to subsequent aplasia-associated thrombocytopenia requiring the substitution of platelets to avoid and treat bleeding complications. A multitude of tests to assess the quality of platelet concentrates is available to date. In this study, we investigated the quality of platelet concentrates prepared by two different methods, preparation from platelet-rich plasma versus preparation from buffy coat, and stored under varying conditions, namely horizontal versus vertical rotation, by measuring the binding rate of corresponding antibodies to platelet membrane glycoproteins GPIb, GPIIb-IIIa, GPIa-IIa and GPIV using flow cytometry. Expression of platelet surface antigens was well maintained during platelet preparation and storage for 7 days. Preparation and storage modalities showed no significant effect on the expression of membrane glycoproteins. These results indicate that platelet function as represented by antibody binding is well maintained during platelet preparation and storage leading to sufficient hemostasis following transfusion.
Acute Disease↗
[Laboratory monitoring of thrombolytic therapy in clinical practice and research].
Numerous attempts to predict the hazard of bleeding during therapeutic fibrinolysis by means of the analysis of parameters for coagulation or fibrinolytic systems have failed to produce reliable results. In the near future the measurement of markers of enhanced thrombin activity TAT, FPA and, to a lesser extent, F1+2 may provide an important non-invasive diagnostic tool with satisfactory reliability for the prediction of thromboembolic events or rethrombosis after successful recanalization by thrombolytic therapy. Measurement of fibrin(ogen) degradation products, such as D-dimers, FbDP and FgDP may provide important help for the diagnosis of thromboembolic events or the danger of reocclusion, though they still lack specificity and are therefore unsuitable as the solely base for diagnosis or therapeutic decisions. Efficient control of anticoagulation with heparin is practicable through the measurement of aPTT. For the prevention of artifacts correct collection and processing of blood samples is mandatory; sample tubes must contain inhibitors of fibrinolytic action such as PPACK or aprotinin.
Blood Coagulation Tests↗
[Deep venous thromboses--established treatment procedures and new trends].
Thrombolysis in deep venous thrombosis is indicated in documented thrombosis of the legs, because, in most cases, it is due to no or minimal collateral flow with bad prognosis. Thrombolysis should not be used regularly in isolated thrombosis of the veins of the lower legs and in subclavian vein thrombosis. The aims in therapy of deep venous thrombosis are reduction of possible complications such as fatal pulmonary embolism, avoidance of progression and recurrence, respectively, and avoidance of a postthrombotic syndrome. In contrast to heparinization, thrombolysis has the advantage of high recanalization rates, but the disadvantage of higher incidence of hemorrhage. With clinically proven dosage regimens of streptokinase and urokinase in our experience, complete recanalization rates are in the range of 30% of primary occluded vessels. According to pivotal and dose-finding studies, the results with tissue plasminogen activator (t-PA) are within the same range. In a different approach, the thrombolytic substances are delivered in a loco-regional type via a vein of the foot. There is some evidence from pivotal clinical trials that the same recanalization rates are obtainable as with streptokinase in ultrahigh dosage. Considering the individual importance and also the epidemiologic and economic value of deep venous thrombosis, there is a need for prospective, randomized trials. Results of clinical studies currently under way will hopefully show the benefit of such new therapeutic strategies.
Heparin↗
[What forms of thromboembolism prevention and therapy can be used in patients with chronic inflammatory bowel diseases?].
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Anticoagulants↗
[Therapy of autoimmune thrombocytopenia in adults].
Autoimmune thrombocytopenic purpura (AITP) is an immune disease characterized by the destruction of antibody-coated platelets in the reticuloendothelial system. It is a relatively common hematologic problem. The diagnosis is established by exclusion of differential diagnoses. Clinically, an acute and a chronic form of AITP can be distinguished. We discuss the different treatment modalities based upon data provided by various studies on AITP. If treatment with glucocorticoids or with immunoglobulins fails, or after unsuccessful splenectomy, then experimental treatment strategies may have to be used. Some of these treatments are described with reference to their mode of action and therapeutic benefit.
Adult↗