hirudin and Necrosis

Recommendations for transitioning from therapy with heparin or a low-molecular-weight heparin preparation to therapy with an oral anticoagulant in patients with acute venous or arterial thromboembolism have undergone several changes during the last two decades. Physicians are now comfortable with beginning treatment with an oral anticoagulant once the diagnosis is confirmed, and loading doses are no longer considered to be necessary. Exceptions to early transition may be necessary in patients with an extensive iliofemoral or axillary-subclavian vein thrombosis or pulmonary embolism where thrombolytic agents may be indicated, or in individuals who require surgery or other invasive procedures, or if there are concerns about bleeding. The avoidance of early transition to oral anticoagulants in patients with acute heparin-induced thrombocytopenia also has been advised because of the potential for further thrombotic complications, including venous limb gangrene and warfarin-induced skin necrosis.

Topics: Administration, Oral; Anticoagulants; Arginine; Blood Coagulation; Blood Coagulation Factors; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Gangrene; Heparin; Heparitin Sulfate; Hirudins; Humans; Ischemia; Leg; Necrosis; Pipecolic Acids; Recombinant Proteins; Skin; Sulfonamides; Thrombocytopenia; Thrombosis; Warfarin

Topics: Anticoagulants; Aortic Valve Insufficiency; Arginine; Autoantibodies; Autoimmune Diseases; Female; Fingers; Heart Valve Prosthesis Implantation; Heparin; Hirudins; Humans; Ischemia; Middle Aged; Necrosis; Pipecolic Acids; Platelet Activation; Platelet Factor 4; Postoperative Complications; Raynaud Disease; Recombinant Proteins; Sulfonamides; Thrombocytopenia; Thrombosis; Toes; Warfarin

This study was performed to evaluate the efficacy of peri-interventional treatment with recombinant hirudin (r-hirudin [HBW 023]) compared with heparin in the prevention of troponin T release in patients with unstable angina.. Percutaneous transluminal coronary angioplasty in patients with unstable angina is associated with a high risk of acute thrombotic complications.. Serial troponin T measurements were performed in 61 patients with unstable angina during the 48-h observation period after coronary angioplasty of the ischemia-related lesion. Patients were randomly assigned to peri-interventional intravenous treatment with either r-hirudin (dosage group I: 0.3-mg/kg body weight bolus, 0.12 mg/kg per h for 24 h; dosage group II: 0.5-mg/kg bolus, 0.24 mg/kg per h for 24 h) or heparin (150-IU/kg bolus, 20 IU/kg per h for 24 h). All patients received acetylsalicylic acid before coronary angiography. After 24 h, patients received a constant low dose infusion of either hirudin (0.04 mg/kg per h) or heparin (7 IU/kg per h) for another 24 h. The power of the study to detect a decrease in abnormal troponin T levels from 60% (heparin group) to 20% (combined r-hirudin groups) was 88%.. Serial troponin T measurements revealed two peaks within the 48 h after coronary angioplasty in the heparin but not the hirudin groups. An elevated serum troponin T concentration (> 0.2 ng/ml) within 48 h of coronary angioplasty was found in 9 (24%) of 38 patients in the hirudin groups (5 [25%] of 20 in dosage group I; 4 [22%] of 18 in dosage group II) compared with 11 (58%) of 19 in the heparin group (p = 0.01). We observed major cardiac events (death, myocardial infarction, abrupt vessel closure) in 1 (4.8%) of 21 patients in dosage group I, 1 (5.3%) of 19 in dosage group II and 3 (14.3%) of 21 in the heparin group (p = 0.33).. In this pilot trial, hirudin appears to be superior to heparin in preventing troponin T release after coronary angioplasty.

Topics: Angina, Unstable; Angioplasty, Balloon, Coronary; Coronary Angiography; Heparin; Hirudin Therapy; Hirudins; Humans; Myocardium; Necrosis; Pilot Projects; Premedication; Recombinant Proteins; Thrombosis; Troponin; Troponin T

To investigate the effect of natural hirudin combined with hyperbaric oxygen therapy on the survival of transplanted random-pattern skin flap in rats.. A random-pattern skin flap in size of 10.0 cm×2.5 cm was elevated on the dorsum of 72 Sprague Dawley rats. Then the 72 rats were randomly divided into 4 groups (. Partial necrosis occurred in each group after operation, and the flap in combined group had the best survival. The survival rate of flap was significantly higher in hyperbaric oxygen group, natural hirudin group, and combined group than that in control group, and in combined group than in hyperbaric oxygen group and natural hirudin group (. Hyperbaric oxygen and natural hirudin therapy after random-pattern skin flap transplantation can improve the survival of flaps. Moreover, combined therapy is seen to exhibit significant synergistic effect. This effect maybe related to promotion of angiogenesis and the reduction of inflammation response.. 探讨天然水蛭素联合高压氧治疗对大鼠随意皮瓣成活的影响。.. 取 72 只 SD 大鼠，于背部制备面积为 10.0 cm×2.5 cm 的随意皮瓣移植模型后，随机分为 4 组（. 术后各组皮瓣均出现部分坏死，其中联合组皮瓣成活最佳；术后第 6 天高压氧组、水蛭素组及联合组皮瓣成活率明显高于对照组，联合组高于水蛭素组、高压氧组，比较差异有统计学意义（. 高压氧和天然水蛭素干预均能提高随意皮瓣移植后成活率，且两者联合发挥协同效应，可能与促进血管生成和减轻炎性反应有关。.

Topics: Animals; Antithrombins; Graft Survival; Hirudins; Hyperbaric Oxygenation; Inflammation; Necrosis; Rats; Rats, Sprague-Dawley; Skin; Skin Transplantation; Surgical Flaps; Transcription Factor RelA; Transplants; Tumor Necrosis Factor-alpha

Life-threatening heparin-induced thrombocytopenia (HIT) is treated with the alternative nonheparin anticoagulants argatroban, lepirudin, or danaparoid. Frequently, the pentasaccharide fondaparinux is used off-label.. The authors sought to investigate the safety and efficacy of the different anticoagulants for treating HIT.. In a national, multicenter registry study, hospitalized patients who were diagnosed with HIT, an at least intermediate clinical HIT-risk (4Ts score ≥4 points), and received treatment with ≥1 dose of the aforementioned anticoagulants were included. Main outcome measures were the incidences of HIT-specific complications (thromboembolic venous/arterial events, amputations, recurrent/persistent thrombocytopenia, skin lesions) and bleedings.. Of 195 patients, 46 (23.6%), 4 (2.1%), 61 (31.3%), and 84 (43.1%) had been treated first-line with argatroban, lepirudin, danaparoid, and fondaparinux, respectively. The composite endpoint of HIT-specific complications (thromboembolic events, amputation, skin necrosis) occurred in 11.7% of patients treated with approved alternative anticoagulation and in 0.0% of fondaparinux-treated patients. The all-cause in-hospital mortality rates were 14.4% during approved alternative anticoagulation and 0.0% during fondaparinux treatment. Bleeding complications occurred in alternatively anticoagulated patients and in fondaparinux-treated patients in 6.3% and 4.8%, respectively. Post hoc analysis of clinical and laboratory features confirmed "true" HIT in at least 74 of 195 (38.0%) patients; 35 of 74 (47.3%) were treated with fondaparinux.. Fondaparinux is effective and safe in suspected acute HIT; no HIT-specific complications occurred in the fondaparinux-treated patients, even among those with a high clinical HIT probability. Further data from randomized controlled trials are urgently needed because lepirudin was recalled from the market; danaparoid access has been limited and is not approved in the United States; and argatroban is contraindicated in patients with impaired liver function, and activated partial thromboplastin time confounding may interfere with monitoring. (Retrospective Registry of Patients With Acute Heparin-induced Thrombocytopenia Type II; NCT01304238).

Topics: Anticoagulants; Arginine; Chondroitin Sulfates; Dermatan Sulfate; Factor Xa Inhibitors; Female; Fondaparinux; Hemorrhage; Heparin; Heparitin Sulfate; Hirudins; Hospital Mortality; Hospitalization; Humans; Male; Necrosis; Off-Label Use; Partial Thromboplastin Time; Patient Safety; Pipecolic Acids; Polysaccharides; Recombinant Proteins; Registries; Retrospective Studies; Sulfonamides; Thrombocytopenia; Thromboembolism; Treatment Outcome

The effect of local administration of hirudin on random pattern skin flap survival was investigated in a porcine model.. Three random pattern skin flaps (4 × 14 cm) were created on each flank of five Chinese minipigs. The experimental group (10 flaps) received 20 antithrombin units of hirudin, injected subdermally into the distal half immediately after surgery and on days 1 and 2; a control group (10 flaps) was injected with saline and a sham group (10 flaps) was not injected. All flaps were followed for 10 days postoperatively.. Macroscopically, the congested/necrotic length in the experimental group was significantly decreased compared with the other two groups by day 3. Histopathological evaluation revealed venous congestion and inflammation in the control and sham groups from day 1, but minimal changes in the experimental group. By day 10, the mean ± SD surviving area was significantly greater in the experimental group (67.6 ± 2.1%) than in the control (45.2 ± 1.4%) or sham (48.3 ± 1.1%) groups.. Local administration of hirudin can significantly increase the surviving area in overdimensioned random pattern skin flaps, in a porcine model.

Topics: Animals; Antithrombins; Free Tissue Flaps; Graft Survival; Hirudins; Hyperemia; Inflammation; Necrosis; Plastic Surgery Procedures; Skin; Skin Transplantation; Surgical Flaps; Swine

Giant-cell myocarditis (GCM) is a rare, idiopathic disorder of young adults with high rates of morbidity and mortality. We describe a unique case of giant cell myocarditis associated with heparin-induced thrombocytopenia and thrombosis syndrome (HITTS). Our patient responded to therapy with bivalirudin, but later succumbed to complications from multiorgan failure. To our knowledge, this is the first reported case of GCM associated with HITTS, which was treated with bivalirudin (Angiomax; The Medicines Company; Parsippany, NJ).

Topics: Adult; Anticoagulants; Fatal Outcome; Giant Cells; Heparin; Hirudins; Humans; Male; Multiple Organ Failure; Myocarditis; Necrosis; Peptide Fragments; Recombinant Proteins; Thrombocytopenia; Thrombosis

Tumor/host-generated thrombin (endogenous thrombin) was investigated with tumor growth and metastasis experiments in mice by the use of hirudin, a highly potent specific inhibitor of thrombin. Pretreatment with hirudin inhibited tumor implantation in nude or syngeneic mice, following subcutaneous injection of 2 human and 2 murine tumors. Hirudin induced a considerable lag period in the appearance of tumor growth, compared with phosphate-buffered saline (PBS) treatment, but had no effect on established tumor nodule growth in vivo or on tumor growth in vitro. Hirudin treatment induced central necrosis of the tumor nodule compared with no effect with PBS treatment. Greater protection was noted with longer duration of treatment. Tumor seeding into blood was examined with green fluorescent protein (GFP)-labeled tumor cells. Hirudin inhibited seeding into the blood as well as systemic organs which varied from complete protection to 15- to 32-fold in the blood and 17- to 395-fold in the lung. Hirudin inhibited spontaneous metastases from subcutaneously implanted tumor by reducing the number of tumor nodules in the lungs. Mouse survival in animals injected subcutaneously with highly aggressive 4T1 cells revealed 5 of 5 deaths of PBS-treated animals on day 40 compared with no deaths with hirudin treatment, with prolongation of survival with hirudin treatment of 16 days to more than 31 days. Thus, endogenous thrombin contributes to tumor implantation, seeding, and spontaneous metastasis. A potent antithrombin agent should be of clinical benefit to patients with cancer.

Topics: Animals; Cell Line, Tumor; Hirudins; Humans; Lung Neoplasms; Mice; Mice, Nude; Necrosis; Neoplasm Metastasis; Neoplasm Transplantation; Neoplastic Cells, Circulating; Survival Rate; Thrombin; Transplantation, Heterologous; Transplantation, Isogeneic

We report two patients with deep-vein thrombosis complicating immune heparin-induced thrombocytopenia who developed venous limb gangrene during overlapping therapy with a direct thrombin inhibitor (lepirudin or argatroban) and warfarin. In both patients, therapy with the direct thrombin inhibitor was interrupted during persisting severe athrombocytopenia while warfarin administration continued. Both patients exhibited the typical feature of a supratherapeutic international normalized ratio (INRs, 5.9 and 7.3) that has been linked previously with warfarin-associated venous limb gangrene. These data suggest that warfarin anticoagulation be postponed in patients with acute heparin-induced thrombocytopenia until substantial recovery of the platelet count has occurred.

Topics: Aged; Aged, 80 and over; Amputation, Surgical; Anticoagulants; Arginine; Autoimmune Diseases; Catheterization, Central Venous; Contraindications; Drug Administration Schedule; Drug Therapy, Combination; Female; Gangrene; Heparin; Hirudin Therapy; Hirudins; Humans; International Normalized Ratio; Leg; Male; Middle Aged; Necrosis; Pipecolic Acids; Protein C Deficiency; Recombinant Proteins; Sulfonamides; Surgical Wound Infection; Thrombin; Thrombocytopenia; Thrombophlebitis; Warfarin

The assumption that fibrin and crosslinked fibrin impart irreversibility to arterial thrombi is explored with procedure developed for measuring changes in platelet function, morphology and fibrinogen metabolism in aging occlusive thrombi, in which the condition of stasis is imposed uniformly. Arterial thrombi containing autologous (111)In labeled platelets were generated in vivo by bilateral mechanical injury of porcine carotid arteries. Vessels containing the platelet-rich thrombi were harvested and incubated intact (37 degrees C) for intervals ranging from 30 min to 12 h. The isolated vessels were then bisected and agitated in culture medium containing tick anticoagulant and hirudin for 60 min. Disaggregated platelets were evaluated for yield (from (111)In radioactivity) viability (dense body ATP secretion) and morphology (electron microscopy). Western analysis of fibrin(ogen) in thrombus extracts was performed using anti-fibrinogen Bbeta- and gamma-chain monoclonal antibodies for thrombi at each time point. A stable recovery of nearly 50% of platelets was observed during 12 h of thrombus aging. As thrombi aged, viability of disaggregated platelets gradually decreased with platelet necrosis the predominant feature beyond 6 h. By western analysis of thrombus extracts, nearly 50% of fibrinogen was cleaved to fibrin and extensively crosslinked within 30 min of injury with no evidence of fibrinolysis. With the exception of a declining proportion of gamma-monomer, these features remain relatively constant during 12 h of thrombus maturation. It is concluded that neither fibrin nor crosslinked fibrin are dominant factors imparting cohesion within platelet thrombi. Furthermore, under conditions of complete arterial occlusion imposed by this experimental design, there is no evidence of endogenous fibrinolysis.

Topics: Adenosine Triphosphate; Animals; Arthropod Proteins; Blood Platelets; Carotid Artery Injuries; Carotid Artery Thrombosis; Cytoplasmic Granules; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinolysis; Fibrinolytic Agents; Hirudins; Intercellular Signaling Peptides and Proteins; Necrosis; Peptides; Recombinant Proteins; Swine; Time Factors