refludan and Postoperative-Complications

Heparin induced thrombocytopenia (HIT) in addition to bleeding complications are the most serious and dangerous side effects of heparin treatment. HIT remains the most common antibody-mediated, drug-induced thrombocytopenic disorder and a leading cause of morbidity and mortality. Two types of HIT are described: Type I is a transitory, slight and asymptomatic reduction of platelet count occurring during 1-2 days of therapy. HIT type II, which has an immunologic origin, is characterized by a thrombocytopenia that generally onset after the fifth day of therapy. Despite thrombocytopenia, haemorrhagic complications are very rare and HIT type II is characterized by thromboembolic complications consisting in venous and arterial thrombosis. The aim of this paper is to review new aspects of epidemiology, pathophysiology, clinical features, diagnosis and therapy of HIT type II. There is increasing evidence that platelet factor 4 (PF4) displaced from endothelial cells, heparan sulphate or directly from the platelets, binds to heparin molecule to form an immunogenic complex. The anti-heparin/PF4 IgG immune-complexes activates platelets through binding with the Fcgamma RIIa (CD32) receptor inducing endothelial lesions with thrombocytopenia and thrombosis. Cytokines are generated during this process and inflammation could play an additional role in the pathogenesis of thromboembolic manifestations. The onset of HIT type II is independent from dosage, schedule, and route of administration of heparin. A platelet count must be carried out prior to heparin therapy. Starting from the fourth day, platelet count must be carried out daily or every two days for at least 20 days of any heparin therapy regardless of the route of the drug administration. Patients undergoing orthopaedic or cardiac surgery are at higher risk for HIT type II. The diagnosis of HIT type II should be formulated on basis of clinical criteria and confirmed by in vitro demonstration of heparin-dependent antibodies detected by functional and antigen methods. However, the introduction of sensitive ELISA tests to measure anti-heparin/PF4 antibodies has showed the immuno-conversion in an higher number of patients treated with heparin such as the incidence of anti-heparin/PF4 exceeds the incidence of the disease. If HIT type II is likely, heparin must be immediately discontinued, even in absence of certain diagnosis of HIT type II, and an alternative anticoagulant therapy must be started followed by oral dicuma

Topics: Animals; Anticoagulants; Arginine; Chondroitin Sulfates; Dermatan Sulfate; Heparin; Heparitin Sulfate; Hirudins; Humans; Peptide Fragments; Pipecolic Acids; Postoperative Complications; Recombinant Proteins; Sulfonamides; Thrombocytopenia

Heparin-induced thrombocytopenia (HIT) is an antibody-mediated syndrome associated with heparin exposure, a falling platelet count and a high risk of thrombosis. Cardiovascular patients are at increased risk of HIT due to wide use of heparin in this population. Should HIT be suspected, heparin must be avoided in most situations, and anticoagulation with an alternative anticoagulant should be instituted. Preferred agents include the direct thrombin inhibitors argatroban and lepirudin, whilst bivalirudin or desirudin (other direct thrombin inhibitors) can be used in some situations. The indirect thrombin inhibitors, danaparoid and fondaparinux, can also be considered at times. These agents and their use in cardiac patients, including patients with acute coronary syndrome, percutaneous coronary interventions, acute ST elevation myocardial infarction or cardiac surgery, will be reviewed.

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Arginine; Cardiovascular Diseases; Chondroitin Sulfates; Dermatan Sulfate; Drug Administration Schedule; Factor Xa Inhibitors; Fondaparinux; Heparin; Heparitin Sulfate; Hirudins; Humans; Pipecolic Acids; Polysaccharides; Postoperative Complications; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Recombinant Proteins; Sulfonamides; Thrombin; Thrombocytopenia

Repeated exposure to unfractionated heparin is the rule in many congenital heart disease patients. Heparin-induced thrombocytopenia occurs in 1% to 3% of adult cardiac surgeries, and carries high thrombotic morbidity (38% to 81%) and mortality (approximately 28%). Although heparin-induced thrombocytopenia appears to be infrequent in pediatric patients, particularly neonates, our evolving experience suggests postcardiopulmonary bypass congenital heart disease patients may be at increased risk. Diagnostic and therapeutic challenges include frequency of thrombocytopenia after cardiopulmonary bypass, imperfect laboratory testing, lack of established dosing of alternative anticoagulants (such as argatroban and lepirudin), and increased anticoagulant-related bleeding in young children.

Topics: Adolescent; Anticoagulants; Arginine; Autoantibodies; Cardiopulmonary Bypass; Child; Child, Preschool; Clinical Trials as Topic; Fatal Outcome; Female; Heart Defects, Congenital; Heparin; Hirudins; Hospitals, University; Humans; Hypoplastic Left Heart Syndrome; Infant; Infant, Newborn; Male; Multicenter Studies as Topic; Pipecolic Acids; Platelet Factor 4; Postoperative Complications; Postoperative Hemorrhage; Recombinant Proteins; Retrospective Studies; Sulfonamides; Thrombocytopenia; Thromboembolism; Treatment Outcome

Lepirudin (Refludan), Berlex Laboratories, USA and Canada; Pharmion, all other countries), a recombinant derivative of the naturally occurring leech anticoagulant hirudin, was the first direct thrombin inhibitor to be approved by the European Agency for the Evaluation of Medicinal Products and the US Food and Drug Administration for the treatment of heparin-induced thrombocytopenia. Since its introduction into Europe and the USA, it has been studied in over 7000 patients requiring anticoagulation in conditions including acute coronary syndromes, percutaneous coronary intervention, cardiopulmonary bypass and heparin-induced thrombocytopenia. Three European clinical trials, designated Heparin-Associated Thrombocytopenia (HAT)-1, -2 and -3, demonstrated the efficacy and safety of lepirudin in the prevention and treatment of thrombosis in patients with antibody-confirmed heparin-induced thrombocytopenia. A postmarketing, observational study, termed the Drug-Monitoring Program, evaluated lepirudin in over 1000 patients with heparin-induced thrombocytopenia in the setting of routine clinical practice. In the Drug-Monitoring Program, adverse events were substantially reduced compared with clinical trials, while clinical efficacy was maintained; suggesting that insight gained through clinical experience was translated into improved safety. Here, pharmacotherapy using lepirudin is reviewed, with particular reference to clinical studies in heparin-induced thrombocytopenia, and some recommendations based on this extensive clinical experience with lepirudin are provided. Although only approved for the treatment of heparin-induced thrombocytopenia, the use of lepirudin in acute coronary syndromes, percutaneous coronary intervention, vascular surgery and coronary artery bypass grafting is also discussed. The review concludes with a discussion of pharmacokinetic and clinical data supporting the potential for subcutaneous administration of lepirudin.

Topics: Anticoagulants; Cardiovascular Surgical Procedures; Coronary Disease; Dose-Response Relationship, Drug; Heparin; Hirudins; Humans; Myocardial Infarction; Postoperative Complications; Recombinant Proteins; Thrombin; Thrombocytopenia; Venous Thrombosis

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

Unfractionated heparin given during cardiopulmonary bypass is remarkably immunogenic, as 25% to 50% of postcardiac surgery patients develop heparin-dependent antibodies during the next 5 to 10 days. Sometimes, these antibodies strongly activate platelets and coagulation, thereby causing the prothrombotic disorder, heparin-induced thrombocytopenia. The risk of heparin-induced thrombocytopenia is 1% to 3% if unfractionated heparin is continued beyond the first postoperative week. When cardiac surgery is urgently needed for a patient with acute or subacute heparin-induced thrombocytopenia, options include an alternative anticoagulant (bivalirudin, lepirudin, or danaparoid) or combining unfractionated heparin with a platelet antagonist (epoprostenol or tirofiban). As heparin-induced thrombocytopenia antibodies are transient, unfractionated heparin alone is appropriate in a patient with previous heparin-induced thrombocytopenia whose antibodies have disappeared.

Topics: Anticoagulants; Cardiac Surgical Procedures; Diagnosis, Differential; Female; Heparin; Hirudin Therapy; Hirudins; Humans; Male; Peptide Fragments; Postoperative Complications; Recombinant Proteins; Thrombocytopenia; Thrombosis

Patients with central nervous system (CNS) malignancies have a substantial risk for developing both thrombotic and bleeding disorders. The risk of venous thromboembolism (VTE) is substantially higher in these patients, both in the perioperative period and throughout their disease course. Patients with CNS malignancy harbor a latent hypercoagulability, which predisposes to VTE, as do postoperative immobility, hemiparesis, and other factors. The management of VTE in these patients is complex, given the significant morbidity and mortality associated with intratumoral hemorrhage. In the past, the perceived risk of intracranial hemorrhage limited the use of anticoagulation for the management of VTE with many favoring nonpharmacologic methods for prophylaxis and treatment. Inferior vena cava (IVC) filters have since lost favor at many centers given significant complications, which appear to be more frequent in patients with CNS malignancy. Recent studies have demonstrated safe and efficacious use of anticoagulation in these patients with a low incidence of intracranial hemorrhage. Treatment of established VTE is now recommended in this population with many centers favoring low-molecular-weight heparin (LMWH) versus oral warfarin for short- or long-term treatment. We advocate a multimodality approach utilizing compression stockings, intermittent compression devices, and heparin in the perioperative setting as the best proven method to reduce the risk of VTE. In the absence of a strict contraindication to systemic anticoagulation, such as previous intracranial hemorrhage or profound thrombocytopenia, we recommend LMWH in patients with newly diagnosed VTE and a CNS malignancy.

Topics: Antibodies, Monoclonal, Humanized; Anticoagulants; Arginine; Bevacizumab; Central Nervous System Neoplasms; Fondaparinux; Glioblastoma; Glioma; Hemorrhage; Heparin, Low-Molecular-Weight; Hirudins; Humans; Pipecolic Acids; Polysaccharides; Postoperative Complications; Pulmonary Embolism; Recombinant Proteins; Sulfonamides; Thrombocytopenia; Vena Cava Filters; Venous Thromboembolism; Venous Thrombosis; Warfarin

A treatment strategy of a difficult and unusual problem is presented. We are reporting a case of a patient who had a documented allergy to heparin and required Cardiac surgery for an ASD closure. The anticoagulation regime used during cardiopulmonary bypass was lepirudin based. This report indicates that r-hirudin provides effective anticoagulation, however unless ECT is monitoring, post operative hemorrhage is encountered. Therefore this case is unique not only because of its rarity but also by the fact that it presents the caveats encountered when ECT is not available.

Topics: Adult; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Female; Fibrinolytic Agents; Follow-Up Studies; Heart Septal Defects, Atrial; Heparin; Hirudins; Humans; Postoperative Complications; Recombinant Proteins; Thrombosis

Up to 3% of patients receiving unfractioned heparin develop heparin-induced thrombocytopenia (HIT). We report on a polytrauma patient who developed severe HIT with bilateral pulmonary embolism. Lepirudin treatment resulted initially in rapid improvement. Ten days after discharge the patient complained of abdominal pain. A large subcapsular hepatic hematoma was diagnosed, requiring repeat surgery and ending in secondary sclerosing cholangitis. This process can potentially be avoided by regular tests of lepirudin concentration and coagulation.

Topics: Anticoagulants; Aortic Rupture; Blood Coagulation Tests; Cholangiopancreatography, Endoscopic Retrograde; Cholangitis, Sclerosing; Female; Heparin; Hernia, Diaphragmatic, Traumatic; Hirudins; Humans; Liver; Liver Diseases; Middle Aged; Multiple Trauma; Patient Readmission; Platelet Count; Postoperative Complications; Postoperative Hemorrhage; Recombinant Proteins; Reoperation; Thrombocytopenia; Tomography, X-Ray Computed

Lepirudin is a potent, direct thrombin inhibitor used for anticoagulation in patients with heparin-induced thrombocytopenia type II (HIT). The half-life of lepirudin is prolonged in patients with renal insufficiency. Preliminary studies suggest that it is safe to use lepirudin in patients being treated with intermittent hemodialysis but information regarding its use with continuous renal replacement therapy (CRRT) is scarce. CRRT is used in acute care settings to remove fluid and uremic toxins in patients with renal failure with hemodynamic instability. Patients with HIT, renal failure, and hemodynamic instability pose a complex situation for clinical management. These patients require anticoagulation with nonheparin agents with simultaneous CRRT. There are no guidelines in the literature regarding the management of this patient group. We report our experience with lepirudin at managing four such patients with HIT, being treated with CRRT.

Topics: Aged; Aged, 80 and over; Anticoagulants; Drug Evaluation; Female; Half-Life; Heparin; Hirudins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Multiple Organ Failure; Postoperative Complications; Purpura, Thrombocytopenic, Idiopathic; Recombinant Proteins; Renal Dialysis; Retrospective Studies; Systemic Inflammatory Response Syndrome

Heparin-induced thrombocytopenia (HIT) represents a serious side effect caused by an atypical immune response to platelet factor 4 leading to platelet activation and thrombin formation. These patients are at high risk of thromboembolism, with a rapid drop in platelet count between days 5 and 14 after the initiation of heparin treatment. In single cases, especially after major surgery, platelet count reduction might be absent or hidden by preceding thrombocytosis. Different clinical manifestations of HIT include unspecific skin reactions with potential necrosis at the site of heparin injection, mostly after the application of unfractionated heparin but also with low molecular weight heparin. In heparin-induced skin necrosis, administration of unfractionated or low molecular weight heparin is contraindicated and heparin therapy should be stopped immediately. Instead, an alternative anticoagulant in the form of a direct thrombin inhibitor such as argatroban, and respectively lepirudin, or danaparoid sodium must be administered. Due to frequent misinterpretations of heparin-induced unspecific skin reactions, especially in the absence of thrombocytopenia, we present two case reports which should increase the awareness of HIT's various clinical pictures.

Topics: Adult; Anticoagulants; Arginine; Chondroitin Sulfates; Dermatan Sulfate; Drug Eruptions; Female; Heparin; Heparin, Low-Molecular-Weight; Heparitin Sulfate; Hirudins; Humans; Male; Pipecolic Acids; Platelet Count; Platelet Factor 4; Postoperative Complications; Recombinant Proteins; Sulfonamides; Thrombocytopenia; Thrombosis; Time Factors

A 21-month-old boy received anticoagulation with lepirudin for heparin-induced thrombocytopenia (HIT) after undergoing cardiac surgery and receiving extracorporeal membrane oxygenation (ECMO). This report illustrates the significance of HIT in pediatric patients after cardiac surgery and the successful administration of lepirudin in this setting. To our knowledge, this is the first published report of lepirudin administered to treat HIT in a child after cardiac surgery and ECMO. Although guidelines exist that suggest the potential administration of lepirudin as treatment for children with HIT, further studies are needed to determine the safest yet most effective dosage for this population.

Topics: Anticoagulants; Cardiac Surgical Procedures; Child, Preschool; Echocardiography; Extracorporeal Membrane Oxygenation; Fontan Procedure; Heparin; Hirudins; Humans; Hypoplastic Left Heart Syndrome; Male; Platelet Count; Postoperative Complications; Recombinant Proteins; Thrombocytopenia

We report the case of 64-year-old female patient with pulmonary embolism and bilateral femoropopliteal deep vein thrombosis caused by heparin-induced thrombocytopenia type II (HIT II) resistant to danaparoid sodium and subsequently administered lepirudin in whom a single late plasmapheresis performed on day 6 of the initiation of treatment of HIT reversed the course of the disease, preventing its highly potential fatal outcome. Primarily administered lepirudin was not only ineffective but even led to further aggravation of the patient's clinical state and platelet count drop in the first stage of the HIT treatment. The improvement of the patient's clinical state was not achieved before therapeutic plasma exchange (TPE) had removed the greatest part of pathogenetic circulating substrate. Only after TPE, lepirudin, introduced again, led to the platelet count recovery. In the subsequent course of the treatment, lepirudin was combined with an overlapping oral anticoagulant. Previously positive heparin aggregation test and fast particle gel heparin-platelet factor 4 immunoassay were normalized as well as the patient's clinical status. Early plasmapheresis, administered within 4 days of the onset of thrombocytopenia in HIT, as a beneficial therapeutic measure in certain individual cases, is indisputable. However, our results do not concur with previously reported findings of the so far most comprehensive study on plasmapheresis performed in the management of HIT with thrombosis, discrediting late plasmapheresis administered 4 days after the onset of the disease not only as ineffective, but even as an aggravating factor. Our results suggest the possible beneficial impact of late plasmapheresis as a method that may reverse a prothrombotic process and lead to a fast improvement in the patient's platelet count, especially in cases initially resistant to thrombin inhibitors.

Topics: Arthroplasty, Replacement, Hip; Autoantibodies; Chondroitin Sulfates; Dermatan Sulfate; Drug Resistance; Female; Fibrinolytic Agents; Heparin; Heparitin Sulfate; Hip Fractures; Hirudins; Humans; Middle Aged; Partial Thromboplastin Time; Plasma; Plasmapheresis; Postoperative Complications; Pulmonary Embolism; Purpura, Thrombocytopenic, Idiopathic; Recombinant Proteins; Salvage Therapy; Thrombophilia; Time Factors

Patients with heparin-induced thrombocytopenia urgently requiring surgery with cardiopulmonary bypass (CPB) present a unique management challenge that must be addressed by the use of alternative anticoagulants. Although clinical success with the direct thrombin inhibitor hirudin has been reported, there is sparse information in the literature supporting the efficacy of this drug as an anti-thrombotic to prevent fibrin formation during CPB. In this report, we describe the efficacy of this drug to prevent thrombin-mediated fibrin formation during CPB.

Topics: Adult; Anticoagulants; Cardiopulmonary Bypass; Chondroitin Sulfates; Contraindications; Dermatan Sulfate; Endarterectomy; Fibrinolytic Agents; Fibrinopeptide A; Heparin; Heparitin Sulfate; Hirudins; Humans; Hypertension, Pulmonary; Hypothermia, Induced; Male; Peptide Fragments; Postoperative Complications; Prothrombin; Pulmonary Embolism; Purpura, Thrombocytopenic, Idiopathic; Recombinant Proteins; Thrombectomy; Thrombin; Thrombosis

We identified the incidence of heparin-induced thrombocytopenia and the antiheparin-platelet factor 4 (PF4) antibody in pediatric patients undergoing cardiac surgery and documented the differences in the anticoagulation management for the extracorporeal circulation.. Between January 2001 and September 2003, 559 cardiac procedures with extracorporeal circulation in 415 patients with congenital heart defects were performed in our institution. Because the development of heparin-induced thrombocytopenia requires previous exposition to heparin, only the 144 patients undergoing a scheduled second procedure on extracorporeal circulation were screened preoperatively. Of these 144 patients, 41 underwent also a third procedure and were screened before each procedure for presence of antiheparin-PF4 antibodies and for clinical signs of heparin-induced thrombocytopenia.. The incidence of antiheparin-PF4 antibodies during the study period was 1.4% (2 of 144 patients). Patients with clinically significant heparin-induced thrombocytopenia could not be identified. Outside the study protocol, 2 more patients with antiheparin-PF4 antibodies were found. In these 4 patients, surgery was performed using lepirudin (Schering, Berlin, Germany) instead of the usual heparin management for extracorporeal circulation. Three of these 4 patients had an uneventful procedure and postoperative course. In 1 patient after total cavopulmonary connection, a reoperation was necessary on the seventh postoperative day owing to partial thrombosis of the lateral tunnel.. The incidence of heparin-induced thrombocytopenia and of antiheparin-PF4 antibodies in patients undergoing repeated cardiac surgery is low. In antiheparin-PF4 antibody positive patients, the complete avoidance of heparin can be achieved and may account for an uneventful perioperative course.

Topics: Anticoagulants; Cardiac Surgical Procedures; Contraindications; Extracorporeal Circulation; Heart Defects, Congenital; Heparin; Hirudins; Humans; Incidence; Infant; Kidney Failure, Chronic; Platelet Factor 4; Postoperative Complications; Preoperative Care; Recombinant Proteins; Reoperation; Retrospective Studies; Thrombocytopenia

Heparin-induced thrombocytopenia with thrombosis (HITT) is a rare complication of cardiac surgery with cardiopulmonary bypass. We report two cases of HITT treated with the direct thrombin inhibitor Lepirudin. Immediate diagnosis was essential to prompt heparin discontinuation and successful early Lepirudin administration in the first case. In the second, the presence of an intra-aortic balloon pump delayed HITT recognition, and Lepirudin infusion could not prevent limb amputation. In both cases HITT occurred earlier (< 5 days after heparin exposure) than its usual presentation.

Topics: Adult; Aged; Amputation, Surgical; Anticoagulants; Aorta; Aortic Aneurysm; Aortic Dissection; Aortic Valve; Blood Vessel Prosthesis Implantation; Combined Modality Therapy; Coronary Artery Bypass; Early Diagnosis; Fibrinolytic Agents; Heart Valve Prosthesis Implantation; Heparin; Hirudins; Humans; Intra-Aortic Balloon Pumping; Ischemia; Leg; Male; Marfan Syndrome; Mitral Valve; Postoperative Complications; Recombinant Proteins; Thrombocytopenia; Thrombophlebitis

Cardiopulmonary bypass and surgical stress are accompanied by a systemic inflammatory response and activation of coagulation. Thrombin forms fibrin and activates platelets and neutrophils. Consequently, disseminated microthrombosis might increase capillary vascular resistance and thus impair reperfusion. We hypothesized that recombinant hirudin, a direct inhibitor of thrombin, could attenuate coagulation and enhance microvascular flow during reperfusion.. Twenty pigs undergoing 60 minutes of aortic clamping and 75 minutes of normothermic perfusion were randomized in a blinded setting to receive an intravenous bolus of recombinant hirudin (10 mg, 0.4 mg/kg; n = 10) or placebo (n = 10) 15 minutes before aortic declamping and then continued with an intravenous 135-minute infusion of recombinant hirudin (3.75 mg/h, 0.15 mg/kg) or placebo. Thrombin-antithrombin complexes, activated clotting times, and several hemodynamic parameters were measured before cardiopulmonary bypass, after weaning from cardiopulmonary bypass, and at 30, 60, 90, and 120 minutes after aortic declamping. Intramucosal pH and Pco(2) were measured from the luminal surface of ileum simultaneously with arterial gas analysis at 30-minute intervals.. Recombinant hirudin inhibited thrombin formation after aortic declamping; at 120 minutes, thrombin-antithrombin complexes levels (microg/L, mean +/- SD) were 75 +/- 21 and 29 +/- 44 (P <.001) for placebo and pigs receiving recombinant hirudin, respectively. When compared with the placebo group, pigs receiving recombinant hirudin showed significantly higher stroke volume, cardiac output, and lower systemic vascular resistance at 60 and 90 minutes after aortic declamping (P <.05). Based on arteriomucosal Pco(2) and pH differences, progressive worsening of intestinal microcirculatory perfusion occurred in the placebo group but not in the recombinant hirudin group.. Infusion of thrombin inhibitor recombinant hirudin during reperfusion was associated with attenuated postischemia left ventricular dysfunction and decreased vascular resistance. Consequently microvascular flow was improved during ischemia-reperfusion injury. Control of thrombin formation during reperfusion may be a feasible approach to improve oxygen delivery to reperfused vascular beds.

Topics: Animals; Anticoagulants; Blood Gas Analysis; Cardiopulmonary Bypass; Disease Models, Animal; Female; Hemodynamics; Hirudins; Intestines; Male; Manometry; Postoperative Complications; Random Allocation; Recombinant Proteins; Swine; Vascular Resistance

We report herein a patient with coronary artery disease that developed heparin-induced thrombocytopenia after coronary artery bypass graft with resulting thrombosis of multiple saphenous vein grafts and myocardial infarction after heparin exposure. The patient required lepirudin and a cardiac catheterization with placement of stents.

Topics: Angina Pectoris; Angioplasty, Balloon; Anticoagulants; Autoantibodies; Autoantigens; Autoimmune Diseases; Cardiac Catheterization; Coronary Artery Bypass; Coronary Restenosis; Drug Therapy, Combination; Eptifibatide; Heparin, Low-Molecular-Weight; Hirudins; Humans; Internal Mammary-Coronary Artery Anastomosis; Male; Middle Aged; Myocardial Infarction; Peptides; Platelet Factor 4; Postoperative Complications; Recombinant Proteins; Recurrence; Saphenous Vein; Stents; Thrombocytopenia; Thrombosis

Thrombosis prophylaxis using heparins is mandatory in most trauma patients. However, heparins can induce heparin-induced thrombocytopenia (HIT), the most common and clinically important immune-mediated drug-dependent thrombocytopenia. Affected patients are at risk of developing new thromboembolic complications. HIT has to be considered if platelet counts decrease >50% between day 5-10 of heparin therapy that cannot be explained alternatively or if new thromboses occur in a sufficiently heparinised patient. Immediately changing the anticoagulant to danaparoid or lepirudin is most important. Proof of anti-platelet-factor-4/heparin antibodies secures the diagnosis, usually retrospectively. Diagnosis and therapy are demonstrated in a typical HIT patient. HIT usually occurs in the second week of heparin administration. Heparin-reexposure within 100 days can lead to HIT before day 5. For early recognition of HIT, platelet counts should be monitored regularly. Because of earlier discharge of patients to rehabilitation or outpatient care, the problem of HIT-diagnosis and therapy gains increasing relevance in these sectors.

Topics: Adult; Anticoagulants; Autoantibodies; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Fractures, Bone; Heparin; Heparitin Sulfate; Hirudins; Humans; Male; Multiple Trauma; Platelet Count; Platelet Factor 4; Postoperative Complications; Recombinant Proteins; Thrombocytopenia; Thromboembolism

Outpatient treatment of deep venous thrombosis has gained widespread acceptance and is facilitated by the use of subcutaneous low molecular weight heparins (LMWH). We report two patients in whom subcutaneous lepirudin was used for long term anticoagulation after heart transplant or surgical pulmonary embolectomy because treatment with LMWH or warfarin was contraindicated, unsuccessful, or impractical. Neither bleeding complications nor recurrent thromboses developed. Subcutaneous lepirudin may be safely and effectively employed for the outpatient treatment of venous thrombosis in selected cases including patients with heparin-induced thrombocytopenia and in those who fail LMWH.

Topics: Adult; Ambulatory Care; Anticoagulants; Embolectomy; Heart Transplantation; Hirudins; Humans; Injections, Subcutaneous; Male; Postoperative Complications; Pulmonary Embolism; Recombinant Proteins; Thromboembolism; Treatment Outcome; Venous Thrombosis

The pathogenesis of allergic reactions to heparin is poorly understood. Clinically, this phenomenon is relevant because of its increasing incidence and the resulting therapeutic challenges due to various cross-reactions between unfractionated and low-molecular weight heparins as well as between heparins and heparinoids. A 44-year-old female patient had developed a delayed-type hypersensitivity to certoparin-sodium. Diagnostic allergy testing revealed various cross-reactions between different heparins as well as an intolerance to heparinoids. After subcutaneous challenge with the recombinant hirudin lepirudin (Refludan) the patient developed a local Arthus reaction at the injection site. In general, recombinant hirudins do not cross-react with high- or low-molecular weight heparins and heparinoids because of a different molecular structure and are therefore an alternative in case of adverse reactions to heparins and heparinoids. Whereas a local Arthus reaction has already been described twice for low-molecular weight heparins, this is to the best of our knowledge the first observation of a superficial leukocytoclastic vasculitis due to s.c. applied lepirudin. Intravenous administration of heparins and heparinoids in case of hypersensitivity to these drugs following topical application risks a generalized eczematous reaction in patients with delayed-type allergy to both groups of substances. In our patient with delayed-type hypersensitivity to heparins and heparinoids and superficial vasculitis due to lepirudin, the intravenous challenge with heparin and a heparinoid was justified as an ultima ratio measure and proved to be the useful therapeutical alternative.

Topics: Adult; Anticoagulants; Arthus Reaction; Female; Heparin; Heparinoids; Hirudins; Humans; Hypersensitivity, Delayed; Infusions, Intravenous; Postoperative Complications; Recombinant Proteins; Thromboembolism

Heparin induced thrombocytopenia with thrombosis (HITT) is a rare but dangerous complication related to the application of unfractionated heparin or low molecular weight heparin. Due to an antibody dependent in vivo platelet activation, severe thromboembolic episodes may occur. We present the case of a patient with HITT following implantation of an aortobifemoral graft secondary to bilateral common iliac artery stenoses. An arterial clot developed and led to a partial occlusion of the graft to the right external iliac artery. Heparin was replaced by Lepirudin, a recombinant hirudin. A bolus of 0.4 mg/kg body weight was given, thereafter 0.15 mg/kg body weight per hour was administered continuously i.v. to maintain the aPTT 2- to 2.5-fold above the baseline value. The platelet count (minimum 47 G/l) normalised within two days. During thrombectomy of the right common femoral artery we used Lepirudin intraoperatively (bolus injection of 0.2 mg/kg body weight) to prevent any further platelet and coagulation activation during the clamping phase. Six months later the patient underwent two further bypass operations due to severe stenoses of both superficial femoral arteries. Due to the high risk of thromboembolism if HITT recurred, a bolus of 0.2 mg/kg body weight of Lepirudin was given during each intervention. No bleeding complications occurred. In addition Lepirudin appeared to decrease platelet consumption in the absence of active thrombosis. Direct thrombin inhibitors such as Lepirudin possess no heparin-like immunological properties and seem to have become the therapeutic "gold-standard" in patients with HITT. Our experience suggests that the repetitive intraoperative use of Lepirudin is safe and effective.

Topics: Anticoagulants; Heparin; Hirudin Therapy; Hirudins; Humans; Male; Middle Aged; Platelet Count; Postoperative Complications; Recombinant Proteins; Thrombocytopenia; Thromboembolism

Topics: Anticoagulants; Cardiopulmonary Bypass; Fatal Outcome; Heart Valve Prosthesis Implantation; Heparin; Hirudin Therapy; Hirudins; Humans; Intraoperative Period; Male; Middle Aged; Mitral Valve; Multiple Organ Failure; Partial Thromboplastin Time; Postoperative Complications; Recombinant Proteins; Thrombocytopenia; Thrombosis

Heparin-induced thrombocytopenia type II (HIT type II) is the most serious complication of heparin treatment apart from bleeding, which is the most common side effect. Eleven days after coronary bypass grafting, a 71 year old patient showed a posterolateral myocardial infarction and a thrombocytopenia of 80,000/microliter. This was considered a postoperative thrombocytopenia. Coronary angiography revealed closed venous bypass grafts. The right coronary artery (RCA) was revascularized by percutaneous transluminal coronary angioplasty (PTCA) and stent placement. During both coronary angiography and PTCA, heparin was administered to the patient. The platelet number did not change. Four days later the patient showed an inferior myocardial infarction and an AV-block III degrees and a syncope. The following coronary angiography revealed RCA stent occlusion. HIT type II was presumed and recanalization was carried out using Lepirudin (Refludan) as the anticoagulant. After placing the guide wire, thrombi could be seen in the proximal RCA. Abciximab (Reo pro), a monoclonal antibody against the glycoprotein IIb/IIIa receptor was additionally administered. Coronary angiography on the next day revealed only a small remaining thrombus. The AV-block disappeared immediately after revascularization. The diagnosis of HIT type II was confirmed through heparin-induced-platelet-activation-test (Hipa-test) and immunoassay (PF 4/heparin-ELISA). This case report illustrates the complicated diagnosis of HIT type II and the successful simultaneous use of Lepirudin (Refludan) and Abciximab (Reo pro). The number of platelets should be checked daily during heparin treatment. In the case of a thrombocytopenia, the treatment should be stopped immediately, and Hipa-test and PF 4/heparin-ELISA should be carried out.

Topics: Abciximab; Aged; Angioplasty, Balloon, Coronary; Antibodies, Monoclonal; Coronary Artery Bypass; Heparin; Hirudin Therapy; Hirudins; Humans; Immunoglobulin Fab Fragments; Male; Myocardial Infarction; Postoperative Complications; Recombinant Proteins; Stents; Thrombocytopenia; Thrombosis