H. Niessner

Activation of coagulation and fibrinolysis in patients with arterio-sclerosis: Relation to localization of vessel disease and risk factors

Activation markers of blood coagulation and fibrinolysis and several fibrinolytic parameters were determined in arteriosclerotic patients to investigate the relation between extension and main localization of vessel disease, risk factors and disturbances within the blood coagulation and the fibrinolytic system. Indications of an increased intravascular fibrin formation and subsequent fibrinolysis were found in peripheral artery disease (PAD) patients but not in coronary artery disease (CAD) patients. Compared with healthy controls PAD patients had elevated TAT (median: 3.2 ng/ml, 1.5-70 vs. 2.1, 1.2-4.7, p less than 0.005) and D-Dimer (median: 365 ng/ml, range 85-2000 vs. 185, 79-360; p less than 0.0001) plasma levels, whereas TAT (2.4, 1.2-13) and D-Dimer (190, 58-1000) levels of CAD patients were in the normal range. No associations were detected between risk factors of arteriosclerosis (hyperlipidemia, diabetes mellitus, cigarette smoking, hypertension) and the plasma levels of the activation markers TAT and D-Dimer. Independent from risk factors PAD and CAD patients had elevated plasma plasminogen activator inhibitor capacity (PAI cap). Our results provide evidence that 1) increased plasma levels of blood coagulation and fibrinolysis activation markers are not related to risk factors of arteriosclerosis but seem to be unspecifically caused by activation processes on arteriosclerotic vessel wall defects, 2) increased plasma PAI cap found in arteriosclerotic patients is a relatively unspecific phenomenon associated with arterial vessel disease.

Plasmapheresis: Its Value in the Management of Patients with Antibodies to Factor VIII

12 plasmapheresis were carried out in 5 patients with antibodies to F VIII (3 haemaophilic antibodies; 2 spontaneous antibodies). Plasmapheresis led in all instances to a marked reduction of the antibody level there was a good correlation between the amount of plasma exchanged and the decrease of the antibody level. About 40 ml of plasma/kg body weight have to be removed to reduce the antibody level to half. In patients with low titre antibody who need treatment for serious bleeding, plasmapheresis is a more rapid and less expensive procedure than neutralisation of the inhibitor by high doses of F VIII. In one haemophiliac repeated plasmapheresis and subsequent high dose F VIII treatment eliminated the antibody within a short time. Plasmapheresis should always be considered when patients with antibodies to F VIII have to be treated because of severe bleeding.

IIB von Willebrand's disease: pathogenetic and therapeutic studies.

Summary. Infusion of 1‐deamino‐(8‐D‐arginine)‐vasopressin (DDAVP) into patients with IIB von Willebrands disease (vWD) has been reported to induce thrombocytopenia. In some families with this disorder thrombocytopenia is present even in the resting state. We have investigated the basis of this chronic thrombocytopenia in one such patient by performing platelet recovery and survival studies. Increased platelet consumption was suggested by a decrease in platelet recovery (40.5%, normal 45%) and mean platelet survival (112 h, normal range 144–224 h). In addition, we have administered test infusions of DDAVP and observed the effect on bleeding time and platelet count. DDAVP caused a decrease in the median platelet count from 86 × 109/1 (range 30–221) to 60 × 109/1 (range 5‐144), the individual decline in the nine subjects ranging from 12% to 84% compared to the pretreatment values. Formation of platelet aggregates was observed in all patients following DDAVP. The bleeding time was prolonged before DDAVP in all patients and lengthened further in two after the infusion. However, partial correction of the bleeding time was seen in three and normalization in one patient following DDAVP infusion.

Efficacy of rhesus antibodies (anti-Rh0 (D)) in autoimmune thrombocytopenia: Correlation with response to high dose IgG and the degree of haemolysis

SummaryWe have compared the efficacy of high-dose IgG with that of Rhesus antibodies (anti-Rh0 (D)) in 5 patients with autoimmune thrombocytopenic purpura (3 adults and 2 children). Although only transient, high-dose IgG (0.4 g/kg×5 days) was effective in all patients (peak values 50–200×109/l), whereas anti-Rh0(D) (11–20 μg/kg×5 days) led to comparable results in only 3 patients (165×109/l, 72×109/l, 33×109/l). This response to anti-Rh0 (D) was neither related to the degree of induced haemolysis (increase of LDH and decrease of haptoglobin) nor to the amount of IgG antibodies bound to red blood cells, as quantified by the 125-I-antiglobulin test. A decrease of platelet-associated IgG was recorded in 3 patients: 2 of them showed an improvement of platelet counts and in one of them there was no response.We conclude that the therapeutic response of high-dose IgG and anti-Rh0 (D) is independent of the degree of induced haemolysis and may not be predicted from the effectiveness of either therapy alone.

Coumarin induced acral skin necrosis associated with hereditary protein C deficiency

SummaryHemorrhagic skin necrosis of the toes was observed in a patient with heterozygous protein C deficiency (protein C:Ag 32% and protein C activity 30%) on the 4th day of coumarin treatment overlapping with effective intravenous anticoagulation with heparin. Family studies revealed protein C deficiency in two sisters of the proposita without a history of thromboembolic disease. Immunologic studies in the proposita at the time of coumarin necrosis revealed slight depression of complement factor C4 and the presence of immune complexes. The present case and review of the literature show that the pathogenetic mechanism leading to coumarin necrosis in patients with protein C deficiency seems not yet to be fully understood.

Leitlinien für die venöse Thromboembolieprophylaxe in Österreich

Venous thromboembolism occurs in a significant number of patients in typical risk situations (e.g. surgery or trauma). However, in these special high-risk situations anticoagulants, particularly low molecular weight heparin, allow for a decrease in the number of venous thromboses, pulmonary embolisms and deaths caused by pulmonary embolism. Only the wide-spread and adequate use of antithrombotics can safeguard against venous thromboembolism in these various risk situations. Guidelines constitute an integrative part of quality management and ensure the application of evidence-based medicine. The present consensus on thrombosis prophylaxis in Austria has been elaborated by 23 experts in the fields of hemostasis research, angiology, surgery, orthopedics, internal medicine, anaesthesiology and pharmacology. The recommendations for the management of thrombosis prophylaxis in the fields of general surgery, orthopaedic and trauma surgery and internal medicine have been elaborated drawing on the Guidelines issued by the American College of Chest Physicians. Included are recommendations on indications as well as the choice of antithrombotics, dose and duration of therapy for the various conditions. The Austrian Guidelines for Venous Thromboembolism Prophylaxis are meant to be a basis for standardising procedures in the above-mentioned fields, thus contributing to an improved management of risk situations by physicians and health care staff and providing more safety for patients.SummaryVenous thromboembolism occurs in a significant number of patients in typical risk situations (e.g. surgery or trauma). However, in these special highrisk situations anticoagulants, particularly low molecular weight heparin, allow for a decrease in the number of venous thromboses, pulmonary embolisms and deaths caused by pulmonary embolism. Only the wide-spread and adequate use of antithrombotics can safeguard against venous thromboembolism in these various risk situations. Guidelines constitute an integrative part of quality management and ensure the application of evidence-based medicine. The present consensus on thrombosis prophylaxis in Austria has been elaborated by 23 experts in the fields of hemostasis research, angiology, surgery, orthopedics, internal medicine, anaesthesiology and pharmacology. The recommendations for the management of thrombosis prophylaxis in the fields of general surgery, orthopaedic and trauma surgery and internal medicine have been elaborated drawing on the Guidelines issued by the American College of Chest Physicians. Included are recommendations on indications as well as the choice of antithrombotics, dose and duration of therapy for the various conditions. The Austrian Guidelines for Venous Thromboembolism Prophylaxis are meant to be a basis for standardising procedures in the above-mentioned fields, thus contributing to an improved management of risk situations by physicians and health care staff and providing more safety for patients.ZusammenfassungVenöse Thromboembolien treten bei einem bedeutenden Anteil von Patienten in typischen Risikosituationen (z.B. Operation oder Trauma) auf. Durch gerinnungshemmende Medikamente, insbesondere die niedermolekularen Heparine, ist es möglich, die Anzahl an venösen Thrombosen, Pulmonalembolien und Tod durch Pulmonalembolie in diesen speziellen Risikosituationen zu senken. Nur die breite und richtige Anwendung von Antithrombotika stellt sicher, dass die Patienten in den jeweiligen Risikosituationen effektiv vor venösen Thromboembolien geschützt werden. Leitlinien (Guidelines) sind integrativer Bestandteil des Qualitätsmanagements und stellen die Anwendung evidenzbasierter Medizin sicher. Der Konsensus zur Durchführung der Thromboseprophylaxe in Österreich wurde von 23 Experten aus dem Gebiet der Hämostaseologie, Angiologie, Chirurgie, Orthopädie, Inneren Medizin, Anästhesiologie und Pharmakologie erarbeitet. Basierend auf den Guidelines des American College of Chest Physicians wurden die Vorschläge für die Durchführung der Thromboseprophylaxe auf den Gebieten Allgemeinchirurgie, Orthopädische Chirurgie, Unfallchirurgie und Innere Medizin erarbeitet. Es werden die Indikationen, die Art der Antithrombotika, Dosis und Dauer in den verschiedenen Indikationen vorgeschlagen. Die Erstellung der Österreichischen Leitlinien für die Venöse Thromboembolieprophylaxe soll durch eine Harmonisierung des Vorgehens ein größeres Maß an Sicherheit in Organisationsstrukturen für den Arzt, den Pflegebereich und den Patienten schaffen.

IMPAIRED FIBRINOLYTIC RESPONSE TO DDAVP AND VENOUS OCCLUSION IN A SUB-GROUP OF PATIENTS WITH VON WILLEBRAND'S DISEASE

Abstract 8 healthy volunteers, 15 patients with mild haemophilia A and 14 patients with von Willebrands disease received an infusion of DDAVP (0,4 μg/kg bodyweight). Shortly after infusion, in all normals and in all haemophiliacs a marked increase of fibrinolytic activity was observed. In 6 out of 14 patients with von Willebrands disease, however, activation of fibrinolysis was absent or only slight. In these patients, venous occlusion did also not induce activation of fibrinolysis. Fibrinolytic response was normal in the remaining 8 patients with von Willebrands disease. A combined endothelial cell deficiency is discussed for a sub-group of von Willebrand patients, resulting in impaired production/release of F VIII and impaired production/release of vascular plasminogen activator.

Austrian Guidelines for Prophylaxis of Venous Thromboembolism

Venous thromboembolism occurs in a significant number of patients in typical risk situations (e.g. surgery or trauma). However, in these special high-risk situations anticoagulants, particularly low molecular weight heparin, allow for a decrease in the number of venous thromboses, pulmonary embolisms and deaths caused by pulmonary embolism. Only the wide-spread and adequate use of antithrombotics can safeguard against venous thromboembolism in these various risk situations. Guidelines constitute an integrative part of quality management and ensure the application of evidence-based medicine. The present consensus on thrombosis prophylaxis in Austria has been elaborated by 23 experts in the fields of hemostasis research, angiology, surgery, orthopedics, internal medicine, anaesthesiology and pharmacology. The recommendations for the management of thrombosis prophylaxis in the fields of general surgery, orthopaedic and trauma surgery and internal medicine have been elaborated drawing on the Guidelines issued by the American College of Chest Physicians. Included are recommendations on indications as well as the choice of antithrombotics, dose and duration of therapy for the various conditions. The Austrian Guidelines for Venous Thromboembolism Prophylaxis are meant to be a basis for standardising procedures in the above-mentioned fields, thus contributing to an improved management of risk situations by physicians and health care staff and providing more safety for patients.SummaryVenous thromboembolism occurs in a significant number of patients in typical risk situations (e.g. surgery or trauma). However, in these special highrisk situations anticoagulants, particularly low molecular weight heparin, allow for a decrease in the number of venous thromboses, pulmonary embolisms and deaths caused by pulmonary embolism. Only the wide-spread and adequate use of antithrombotics can safeguard against venous thromboembolism in these various risk situations. Guidelines constitute an integrative part of quality management and ensure the application of evidence-based medicine. The present consensus on thrombosis prophylaxis in Austria has been elaborated by 23 experts in the fields of hemostasis research, angiology, surgery, orthopedics, internal medicine, anaesthesiology and pharmacology. The recommendations for the management of thrombosis prophylaxis in the fields of general surgery, orthopaedic and trauma surgery and internal medicine have been elaborated drawing on the Guidelines issued by the American College of Chest Physicians. Included are recommendations on indications as well as the choice of antithrombotics, dose and duration of therapy for the various conditions. The Austrian Guidelines for Venous Thromboembolism Prophylaxis are meant to be a basis for standardising procedures in the above-mentioned fields, thus contributing to an improved management of risk situations by physicians and health care staff and providing more safety for patients.ZusammenfassungVenöse Thromboembolien treten bei einem bedeutenden Anteil von Patienten in typischen Risikosituationen (z.B. Operation oder Trauma) auf. Durch gerinnungshemmende Medikamente, insbesondere die niedermolekularen Heparine, ist es möglich, die Anzahl an venösen Thrombosen, Pulmonalembolien und Tod durch Pulmonalembolie in diesen speziellen Risikosituationen zu senken. Nur die breite und richtige Anwendung von Antithrombotika stellt sicher, dass die Patienten in den jeweiligen Risikosituationen effektiv vor venösen Thromboembolien geschützt werden. Leitlinien (Guidelines) sind integrativer Bestandteil des Qualitätsmanagements und stellen die Anwendung evidenzbasierter Medizin sicher. Der Konsensus zur Durchführung der Thromboseprophylaxe in Österreich wurde von 23 Experten aus dem Gebiet der Hämostaseologie, Angiologie, Chirurgie, Orthopädie, Inneren Medizin, Anästhesiologie und Pharmakologie erarbeitet. Basierend auf den Guidelines des American College of Chest Physicians wurden die Vorschläge für die Durchführung der Thromboseprophylaxe auf den Gebieten Allgemeinchirurgie, Orthopädische Chirurgie, Unfallchirurgie und Innere Medizin erarbeitet. Es werden die Indikationen, die Art der Antithrombotika, Dosis und Dauer in den verschiedenen Indikationen vorgeschlagen. Die Erstellung der Österreichischen Leitlinien für die Venöse Thromboembolieprophylaxe soll durch eine Harmonisierung des Vorgehens ein größeres Maß an Sicherheit in Organisationsstrukturen für den Arzt, den Pflegebereich und den Patienten schaffen.

Coincidence of acquired factor-X deficiency and disseminated intravascular coagulation in patients with acute nonlymphoblastic leukemia

SummarySystematic clotting studies were performed in 157 patients with de novo acute nonlymphoblastic leukemia (ANLL) prior to treatment. Sixteen patients had disseminated intravascular coagulation (DIC). Three of the patients with DIC (two with M3, one with M5 leukemia) had a marked isolated factor-X deficiency (factor X∶C 21%, 33%, and 41%, respectively). Another four patients had a mild isolated factor-X deficiency (factor X∶C 55%–68%). In these seven patients the remaining liver-synthesized clotting factors (factors II, VII, IX, V) as well as serum albumin and cholinesterase were within the normal range. Liver disease or vitamin-K deficiency could therefore be excluded. In none of the 141 patients without DIC was a marked isolated factor X deficiency observed; two patients had moderately reduced factor X∶C levels but normal liver-synthesized proteins. Induction treatment led to the control of DIC with an almost parallel increase of fibrinogen and factor X up to normal in all patients with factor-X deficiency who achieved complete remission. In one patient, recurrence of leukemia was associated with reoccurrence of DIC and marked factor-X deficiency. We conclude that there is a coincidence of isolated factor-X deficiency and DIC in some patients with ANLL. In some patients, this factor-X deficiency may be severe enough to contribute to the bleeding tendency.

Survival and Quality of Life in 23 Patients with Severe Aplastic Anemia Treated with Bone Marrow Transplantation (BMT)

SummarySurvival and quality of life are reported in 23 pretransfused patients with severe aplastic anemia (SAA) who underwent bone marrow transplantation (BMT). The projected survival is 76% with 18 of 23 patients being alive 332 to 1677 days post graft (median: 842). 5 patients died between day 4 and 416. 12 of 17 patients at risk developed chronic graft versus host disease (GVH-D). 4 of these patients have a diminished quality of life due GVH-D related disabling manifestations. Autologous haemopoietic recovery was excluded in all patients by the demonstration of haemopoietic chimerism. We recommand age-adapted rejection prophylaxis; such strategy may help to diminish disabling graft versus host disease in otherwise haematologically reconstituted survivors.