hirudin and coumarin

Inflammatory plaques at injection sites are frequent side effects of heparin treatment and a clinical symptom of delayed-type hypersensitivity (DTH) to heparin. In most cases, changing the subcutaneous therapy from unfractionated to low-molecular-weight heparin or treatment with heparinoids does not provide improvement because of extensive cross-reactivity. Because of their completely different chemical structure, hirudins are a safe alternative for anticoagulation. Despite DTH to subcutaneously injected heparins, patients tolerate heparin intravenously. Therefore, in case of therapeutic necessity and DTH to heparins, the simple shift from subcutaneous to intravenous heparin administration is justified. Skin necrosis is a rare complication of anticoagulation. Heparin-induced skin necrosis is 1 of the symptoms of immune-mediated heparin-induced thrombocytopenia and should result in the immediate cessation of heparin therapy to prevent potentially fatal thrombotic events. This is in contrast to coumarin-induced skin necrosis, where therapy may be continued or restarted at a lower dose.

Topics: Anaphylaxis; Anticoagulants; Coumarins; Drug Eruptions; Fibrinolytic Agents; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Hirudins; Humans; Hypersensitivity, Delayed; Polysaccharides; Thrombin; Thrombocytopenia; Vitamin K

Anticoagulant-induced skin reactions appear as allergic or necrotic responses to vitamin K antagonists or heparins. Cutaneous allergy has been reported with danaparoid sodium and flush reactions have been seen with hirudins. The pathogenesis of the reactions differs between drugs. Generally, they occur between days 3 to 10 after the start of treatment, but may also occur later. In patients experiencing necrosis with a vitamin K antagonist, concomitant protein C deficiency, protein S deficiency or lupus anticoagulant has been described, whereas the precise mechanism of the other reactions is unknown. In patients with allergic reactions to heparins, cutaneous tests may help to identify alternative anticoagulants. Such a test cannot be performed in patients with skin necrosis. In patients with heparin-induced skin reactions danaparoid sodium may be used after negative intracutaneous testing in some patients and a hirudin may be used without testing in all patients. Heparin-induced skin necrosis has been reported to be mediated by immunologic mechanisms and to be associated with a high frequency of heparin-induced thrombocytopenia type II. Surgical excision of the necrosis may be required. If further anticoagulation is indicated in any patient, extreme caution has to be taken when restarting oral anticoagulants. Because a large number of anticoagulants available today, safe treatment of all patients experiencing anticoagulant-induced skin reactions is feasible.

Topics: Anticoagulants; Coumarins; Fibrinolytic Agents; Heparin; Hirudins; Humans; Skin Diseases

Topics: Anticoagulants; Coumarins; Fibrinolytic Agents; Hemorrhage; Heparin; Hirudins; Humans; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Preoperative Care; Purinergic P2 Receptor Antagonists; Risk Factors; Thrombosis; Thromboxane A2

From injury through healing, thrombin has several important functions in blood clotting, subsequent clot lysis, and tissue repair. These include edema, inflammation, cell recruitment, cellular releases, transformations, mitogenesis, and angiogenesis. Thrombin also participates in disease states, such as venous thrombosis, coronary thrombosis, stroke, and pulmonary emboli, among others and is implicated in atherosclerosis, the growth and metastasis of certain cancers, Alzheimer's disease, and perhaps other conditions. Thrombin must be continually generated to sustain normal and pathogenic processes. This is because of a variety of consumptive mechanisms. Unlike other activated factors in thrombotic and fibrinolytic pathways, and because thrombin promotes its own generation (feedback and cellular activation), thrombin is a primary target for therapeutics. Besides recombinant hirudins, Argatroban (Novastan) and Bivalirudin (Hirulog) are promising thrombin-directed inhibitors for antithrombotic intervention.

Topics: Blood Coagulation; Blood Coagulation Factors; Coumarins; Enzyme Activation; Factor VIII; Fibrinolytic Agents; Heparin; Hirudins; Humans; Prothrombin; Thrombin; Thromboplastin; Vitamin K

Hirudin is a potent and specific thrombin inhibitor. Since recombinant hirudin is being considered for anticoagulant and antithrombotic therapy we developed a fast and sensitive chromogenic substrate assay for its determination in plasma. The plasma samples (20 microliters) were incubated with 1 ml reagent mixture (0.2 M Tris buffer, 0.025 M NaCl, pH 8.1, containing 0.833 M urea, 0.7 trypsin inhibitor U/ml aprotinin, 100 ng/ml Polybrene and 0.31 NIH U/ml bovine thrombin) for 1 min. Thereafter 100 microliters Chromozym TH (Tos-Gly-Pro-Arg-pNA, 1.9 mM) was added. The change in absorbance/min (delta A/min) was recorded at 405 nm. delta A/min was linear for at least 3 min. The calibration curve was linear at least up to 800 ng hirudin/ml plasma. Intra-assay and inter-assay coefficients of variation were 2.8-3.1% and 5.3-5.8% respectively. The influence of progressive thrombin inhibitors can be neglected because of the short incubation time. Plasma samples can be assayed directly if aprotinin, polybrene and urea are added to the reagent mixture.

Topics: Calibration; Chromogenic Compounds; Coumarins; Disseminated Intravascular Coagulation; Heparin; Hexadimethrine Bromide; Hirudins; Humans; Oligopeptides; Predictive Value of Tests; Recombinant Proteins; Thrombin