How to manage patients with hereditary haemorrhagic telangiectasia.

Hereditary haemorrhagic telangiectasia is a rare systemic autosomal dominantly inherited disorder of the fibrovascular tissue with a wide variety of clinical manifestations. Diagnosis is based on the clinical Curaçao criteria or molecular genetic testing. Dilated vessels can develop into telangiectases or larger vascular malformations in various organs, calling for an interdisciplinary approach.

Treatment of epistaxis in hereditary hemorrhagic telangiectasia with tranexamic acid - a double-blind placebo-controlled cross-over phase IIIB study.

Introduction: Epistaxis is the most frequent manifestation in hereditary hemorrhagic telangiectasia, in which no optimal treatment exists. It can lead to severe anemia and reduced quality of life. Positive effects of tranexamic acid, an antifibrinolytic drug, have been reported on epistaxis related to this disorder.

[Haemostatic testing prior to elective surgery? Yes!].

Haemorrhagic disorders must be excluded prior to any operation or other invasive procedure that has the potential to involve serious bleeding. When assessing the individual risk of bleeding, screening tests of hemostasis must be combined with the patient's clinical history and symptoms, and any history of bleeding must be explored under direct medical supervision using a standardized questionnaire. However, this bleeding history is neither very specific, nor is it particularly sensitive.

Effects of desmopressin on platelet membrane glycoproteins and platelet aggregation in volunteers on clopidogrel.

Purpose: The use of clopidogrel is standard in interventional cardiology. Haemorrhage occurs in some patients, which implies a need for a non-transfusional therapy. Desmopressin showed its efficacy as an antidote of acetylsalicylic acid.

The impact of a medium molecular weight, low molar substitution hydroxyethyl starch dissolved in a physiologically balanced electrolyte solution on blood coagulation and platelet function in vitro.

Background And Objectives: Hydroxyethyl starches (HES) may have the potential to impact negatively on haemostasis. Recent findings suggest that side-effects on haemostasis stem not only from the physicochemical differences between HES, but also from the composition of the solvent. We compared the effects of a newly developed medium molecular weight (MW) and low molar substitution (MS) HES dissolved in a physiologically balanced electrolyte solution (MW 130, MS 0.

Preservation of in vitro function of platelets stored in the presence of a synthetic dual inhibitor of factor Xa and thrombin.

Background: The use of citrate anticoagulant limits the clinical significance of platelet function tests. Thrombin inhibitors cannot prevent thrombin-induced platelet activation completely. We examined the influence of benzylsulfonyl-d-Arg-Pro-4-amidinobenzylamide (BAPA), a dual inhibitor of Factor Xa (FXa) and thrombin, on platelet responsiveness to agonists when measured between 2 and 24 h after venipuncture.

Variables influencing Multiplate(TM) whole blood impedance platelet aggregometry and turbidimetric platelet aggregation in healthy individuals.

We investigated the relationship between impedance platelet aggregometry (IPA) as measured by the Multiplate system and turbidimetric platelet aggregation (TPA) induced by ADP, arachidonic acid (AA), and collagen; blood cell counts; platelet function analyzer (PFA-100) closure times (CT), and von Willebrand factor (VWF) in 120 well-characterized healthy individuals. Pre-analytical and analytical conditions were standardized comprehensively. Analytical reliability of IPA and TPA and the influence of pre-analytical variables on assay results were also examined.

Variables influencing Platelet Function Analyzer-100 closure times in healthy individuals.

We investigated the relationship between platelet function analyzer (PFA-100) closure times (CT) and bleeding time (BT), platelet aggregation (PA) induced by ADP, arachidonic acid, and collagen, blood cell counts, and von Willebrand factor (VWF) in 120 well-characterised healthy individuals. Pre-analytical and analytical conditions were standardised comprehensively. In a substantial number of cases the differences between duplicate measurements exceeded 15%.

Haemocompatibility of polymer-coated stainless steel stents as compared to uncoated stents.

Acute and subacute stent thrombosis still represent an unsolved problem in connection with endovascular stents. For this reason coatings are tested now with the intention to reduce thrombogenicity of stainless steel surfaces. This comparative study examined whether a polymeric stent coating affected the haemocompatibility of a stainless steel stent.

Influence of the direct NO-donor SIN-1 on the interaction between platelets and stainless steel stents under dynamic conditions.

It was investigated whether the NO-donor SIN-1, the active metabolite of molsidomine, influenced the activation of platelets, the formation of circulating platelet aggregates, the spontaneous aggregation of platelets and the activation of the clotting system triggered by a body foreign surface in an in vitro closed-loop perfusion model. With human platelet-rich plasma at micromolar concentrations SIN-1 exerted pronounced effects on the interaction between platelets and an exogenous surface. In the absence of SIN-1, the number of circulating single platelets decreased significantly, which could be due either to the formation of circulating platelet aggregates or to the adhesion of platelets to the stent.

New molecular defects in the gamma subdomain of fibrinogen D-domain in four cases of (hypo)dysfibrinogenemia: fibrinogen variants Hannover VI, Homburg VII, Stuttgart and Suhl.

Four new molecular abnormalities in the gamma subdomain of the D domain elucidated in three unrelated thrombophilic patients and in one asymptomatic case of hypofibrinogenemia are reported: fibrinogen Suhl, gamma 326, Cys-->Tyr, fibrinogen Hannover VI, gamma 336 Met-->Ile, fibrinogen Stuttgart, gamma 345, Asn-->Asp and fibrinogen Homburg VII, gamma 354,Tyr-->Cys. In all cases, fibrin polymerization in plasma is impaired. In the case of fibrinogen Suhl, there was a normalization of fibrin polymerization in plasma at higher Ca(2+) concentration.

On the prophylactic and therapeutic use of danaparoid sodium (Orgaran) in patients with heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is a rare but dangerous complication of heparin prophylaxis or treatment. The present laboratory tests to measure heparin-associated antibodies are not specific. The diagnosis of HIT mainly depends on the decrease in platelet count and on clinical symptoms.

[Haemostatic disorders in ENT patients. Part 2: Pathophysiology, diagnostics, clinical feature and therapy].

In the first part of the medical education article on haemostatic disorders in ENT patients the basic physiology of haemostasis and main diagnostic tools were presented and discussed. The second part presents disorders of the coagulation system,thrombocyte function and blood vessels with special emphasis on clinical practice in ENT surgery. In this context, haemophilia A and B, von Willebrand disease and different forms of thrombocytopenia are of main clinical importance.

[Haemostatic disorders in ENT patients.Part 2: Pathophysiology, diagnostics, clinical feature and therapy].

In the first part of the medical education article on haemostatic disorders in ENT patients the basic physiology of haemostasis and main diagnostic tools were presented and discussed.The second part presents disorders of the coagulation system,thrombocyte function and blood vessels with special emphasis on clinical practice in ENT surgery. In this context, haemophilia A and B, von Willebrand disease and different forms of thrombocytopenia are of main clinical importance.

Impact of alloantigens and storage-associated factors on stimulated cytokine response in an in vitro model of blood transfusion.

Background: Transfusion of blood may contribute to immunosuppression in major surgery. The authors assessed the impact of alloantigens and storage on function of peripheral blood mononuclear cells cultured in their physiologic environment.

Methods: Blood units (whole blood, packed erythrocytes) were prepared with or without prestorage leukodepletion and stored for 24-26 days.

[Perioperative therapy of von Willebrand disease. Demonstration of pathophysiology, clinical problems and therapy options using two case reports].

Von Willebrand disease (vWD) is the most widespread inherited bleeding disorder caused by quantitative or qualitative abnormalities of von Willebrand factor (vWF), an adhesive glycoprotein found in blood plasma and platelets and participating in primary and secondary/endothelium haemostasis as well. Although bleeding symptoms are often mild or moderate, patients with vWD represent a very heterogenous group with different phenotypes and a wide variability of the clinical pattern. In accordance with different defects of vWF, vWD is classified into various types and subtypes.

Effect of high power ultrasound on endothelial cells--an in vitro study of the endothelium--hemostasis interaction.

Objective: The goal of this study was to develop an in vitro model system in which the hemostatic effects of high power ultrasound applied to the outer surface of blood vessels during tumor dissection can be simulated and measured.

Methods: Monolayers of endothelial cells (HUVEC, ATCC) in cell culture plates were sonicated with an ultrasound dissector (SONOCA II, Soering) at a frequency of 23.5 kHz.

Evaluation of the haemocompatibility of titanium based biomaterials.

The increased use of metallic biomaterials in contact with blood e.g. for the application as coronary stents leads to the development of new biomaterials.

In vitro hemocompatibility testing of biomaterials according to the ISO 10993-4.

The development of synthetic materials, textured polymers and metals and their increasing use in medicine make research of biomaterials' hemocompatibility very relevant. Problems arise from the polymorphism and diversity of the different materials, the static and dynamic test models and the patients' individual biologic factors. First, methods, models, tests as well as preanalytical factors have to be standardized according to the current knowledge in medicine laid down in the ISO 10993 part 4.

Activation of plasma coagulation by retransfusion of unwashed drainage blood after hip joint arthroplasty: a prospective study.

Twelve patients undergoing cementless hip joint arthroplasty were retransfused with unwashed drainage blood collected postoperatively. Global coagulation parameters, coagulation factors (factor V:C, factor VIII:C, activated factor XII, and factor XIII) and markers of thrombin generation (F1+2 Fibrin split products, thrombin-antithrombin complexes), fibrin generation (fibrinogen and fibrin degradation products), and fibrinolysis (D-dimers, thrombin degradation products, plasminogen) were determined. High levels of factor XIIa, thrombin and fibrin generation markers, and markers of fibrinolysis were present in the shed blood.

Haemocompatibility of endovascular coronary stents: Wiktor GX.

The stent to be examined (Wiktor-Stent, Medtronic ESTC, Kerkrade, NL) was mounted into a closed-loop tubular-system and perfused with platelet-rich plasma (PRP). As controls the tubular-system without stent (as non-thrombogenic control) and secondly the tube filled with glassbeads (as thrombogenic control) were evaluated. A decrease in the number of singularly circulating thrombocytes correlated well with an increases in circulating platelet aggregates.