[New platelet inhibitors].

The antiplatelet action of acetylsalicylic acid is mostly used in vascular medicine. In the meantime two other classes of platelet inhibiting agents have been introduced. Thieopyridines (Ticlyridin, Clopidogrel) have been shown to inhibit ADP induced platelet aggregation with persistence of this effect for several days after withdrawal.

Platelet-associated tissue factor contributes to the collagen-triggered activation of blood coagulation.

The extravascular localization of tissue factor (TF), the central initiator of coagulation, is thought to ensure that thrombus formation is prevented in the intact vessel. We observed that during a 5-min stimulation of human blood with collagen (type I), TF antigen appeared on the surface of platelets adhering to leukocytes. The rapidly presented intravascular TF was competent to start the coagulation cascade.

Low preoperative antithrombin activity causes reduced response to heparin in adult but not in infant cardiac-surgical patients.

Unlabelled: We evaluated the interaction of preoperative antithrombin (AT) activity and intraoperative response to heparin in cardiac surgery. Heparin anticoagulation is essential during cardiopulmonary bypass (CPB). Heparin itself has no anticoagulant properties, however it causes a conformational change of the physiologic plasma inhibitor AT that converts this slow-acting serine protease inhibitor into a fast acting one.

Are factor V Leiden carriers who use oral contraceptives at extreme risk for venous thromboembolism?

Background: Major concern was raised by an earlier study regarding oral contraceptive use in women with the factor V Leiden mutation. A more than 30-fold increase in relative risk for venous thromboembolism was reported; for homozygotes, the relative risk was as much as 100-fold or more.

Objective: To replicate the reported risk estimates with a new population-based case-control study.

c7E3 Fab inhibits low shear flow modulated platelet adhesion to endothelium and surface-absorbed fibrinogen by blocking platelet GP IIb/IIIa as well as endothelial vitronectin receptor--results from patients with acute myocardial infarction and healthy controls.

The c7E3 Fab reduces ischemic complications in patients undergoing high-risk coronary angioplasty or atherectomy. The present study investigated how c7E3 Fab inhibition of the platelet receptor glycoprotein IIb/IIIa and the endothelial vitronectin receptor affected platelet adhesion to endothelium and surface adsorbed fibrinogen under flow conditions. Platelet adhesion was examined using a stagnation point flow device with shear stress and shear rates up to 2.

[The Bavarian Thromboembolic Risk Cohort Study (BATER). Study protocol, state of the investigation and first results].

Objective: Familiar venous thromboembolic disease (VTE) is known to be related with factor V Leiden mutation (FVL), but also with other genetic markers. It is the objective to investigate of the BATER-study in a representative Bavarian cohort, and to assess whether they could predict VTE events. This paper shortly describes the study protocol, gives an overview of planned sub-studies, and provides first results of the historic cohort analysis.

Replacement of coagulation factors in liver or multiple organ dysfunction.

Due to the complexity of alterations in hemostasis, replacement therapy in multiple organ dysfunction is a domain for nonspecific replacement therapy by means of fresh frozen plasma. Refined methods of virus inactivation as well as the consequent declaration of the major components of plasma derivatives have led to an increasing use of high-purity blood coagulation factor concentrates. Furthermore, the problem of activated factors and their inherent thrombogenic effect is meanwhile considerably attenuated.

Importance of levonorgestrel dose in oral contraceptives for effects on coagulation.

Combined oral contraceptives show clear differences in effect on the tissue factor-initiated coagulation test of activated protein C resistance, which is dependent on the presence and dosage of levonorgestrel. Multiphasic levonorgestrol oral contraceptives differ from monophasic contraceptives and resemble third-generation contraceptives.

Mechanisms underlying increased platelet reactivity in patients with peripheral arterial disease. Preliminary results.

Background: In peripheral arterial disease (PAD) atherosclerosis is disseminated and thrombosis risk is high. We have not only shown the platelets of PAD patients to by hyperreactive and aspirin resistant, but have recently verified them to be hypersensitive to heparin as well. In the present study we have begun to clarify the mechanisms underlying these regularly observed clinical findings.

[Skin necrosis in the front foot area during anticoagulation with phenprocoumon].

History And Admission Findings: A 52-year-old woman was admitted because of pain for several days in the lower left leg and increasing pretibial swelling with livid discoloration. Six months before she had undergone a bilateral adnexectomy with removal of the omentum and subsequent chemotherapy for ovarian cancer.

Investigations: Duplex sonography on the day of admission revealed thrombosis of the left popliteal vein with an unobstructed femoral vein.

Normalized activated protein C ratio itself not associated with increased risk of venous thromboembolism.

Recently, discussions focused on the question whether acquired activated (APC) resistance is a clue to the observed association between venous thromboembolism (VTE) risk and oral contraceptive (OC) use, especially with the so-called third-generation OC. The objective of our study was to check the validity of acquired APC resistance regarding VTE risk in a case-control study. Sixty-seven women with confirmed VTE diagnosis (n = 67) were consecutively ascertained in primary health care settings, interviewed and blood samples taken (at the earliest 6 months after VTE).

Resistance to activated protein C in women using oral contraceptives.

Resistance to activated protein C (APC resistance) is an important and common risk factor for deep vein thrombosis. The majority of patients with APC resistance carry a mutation on the factor V gene at nucleotide position 1691 (G/A), called factor V Leiden mutation. Besides the factor V Leiden mutation several acquired risk factors like lupus anticoagulant, elevated levels of acute phase proteins (increased plasma levels of factor VIII and fibrinogen), pregnancy, or the use of oral contraceptives are known to induce APC resistance in plasma.

Delayed treatment with desulfato-hirudin prevents fibrin formation in lipopolysaccharide-induced shock.

Previous work has shown that pre-treatment with the thrombin inhibitor recombinant desulfato-hirudin prevented fibrin formation and respiratory dysfunction in porcine lipopolysaccharide shock. We examined the effects of delayed administration of recombinant desulfato-hirudin in bacterial lipopolysaccharide shock. Miniature pigs were studied under anaesthesia and ventilation, and received a bacterial lipopolysaccharide infusion (2 microg/kg/h) for 7 h; recombinant desulfato-hirudin was started 1 h after bacterial lipopolysaccharide in 10 animals (bolus 12.

Influence of high- and low-dose aprotinin on activation of hemostasis in open heart operations.

Background: The protease inhibitor aprotinin reduces hemostatic activation and blood loss after cardiac operations. The aim of the present study was to investigate the influence of two different aprotinin doses on hemostatic activation and to identify the most effective dose to reduce the postoperative bleeding tendency.

Methods: In a prospective, randomized, double-blind clinical trial, 230 patients scheduled for routine open heart operations received either high-dose (group H) or low-dose (group L) aprotinin.

Coagulation- and fibrinolysis-related antigens in plasma and dialysate of CAPD patients.

Objective: The present study is aimed at gaining insight into coagulation and fibrinolysis in the peritoneal cavity of patients on continuous ambulatory peritoneal dialysis (CAPD). For this purpose we measured coagulation- and fibrinolysis-related antigens in plasma and dialysate, comparing patients with and without peritonitis.

Design: Markers of activated coagulation and fibrinolysis in plasma and dialysate of CAPD patients were determined at different time points (0 hr, 2 hr, 4 hr) after infusion of the dialysis solution in the peritoneal cavity.

Urticaria haemorrhagica profunda.

Substantial subcutaneous haemorrhage without preceding trauma or underlying bleeding disorder is a rare occurrence in dermatological practice, essentially restricted to early childhood (acute haemorrhagic oedema of childhood). We report an adolescent with a morphologically unique bleeding manifestation. A 16-year-old boy presented with two episodes of massive subcutaneous haemorrhage in association with urticarial vasculitis.

Autoantibodies against the protease inhibitor calpastatin: a new risk factor for venous thrombosis?

Autoantibodies reactive against human calpastatin were detected by screening a cDNA expression library with the serum of a 53 year old white female patient with a history of venous thrombosis and suspected antiphospholipid syndrome. When further sera were analyzed it could be shown that > 90% of calpastatin autoantibodies, detected by Western blotting against the partial calpastatin clone, react with the C-terminal amino acids of the protein. Therefore, an ELISA based on a synthetic peptide containing the C-terminal 27 amino acids of calpastatin was developed and 205 healthy blood donors and 138 random sera from hospital patients were analyzed.