hirudin and Pulmonary-Embolism

Anticoagulant drugs belong to the group of antithrombotic agents and are successfully used in the prophylaxis and treatment of thromboembolic disorders. The use of anticoagulants in the prevention of deep venous thrombosis has significantly lowered the risk of venous thrombosis and fatal pulmonary embolisms even in high-risk situations such as orthopedic surgery. Anticoagulants play a central role in the treatment of acute venous thrombosis and in the prevention of recurrent events. Long-term anticoagulation therapy with orally active anticoagulants significantly reduces the risk of thromboembolic complications in patients showing cardiac arrhythmias. Whereas a few years ago heparins and vitamin K antagonists were the dominant anticoagulants, today a wide range of anticoagulants with improved pharmacological profiles are available. It remains an open question whether these new anticoagulants will improve the efficacy, safety, and acceptance of anticoagulant treatment approaches.

Topics: Administration, Oral; Anticoagulants; Antithrombins; Arginine; Arrhythmias, Cardiac; Blood Coagulation Tests; Factor Xa Inhibitors; Hemorrhage; Heparin; Heparinoids; Hirudins; Humans; Infusions, Intravenous; Orthopedic Procedures; Peptide Fragments; Pipecolic Acids; Postoperative Complications; Pulmonary Embolism; Recombinant Proteins; Risk Factors; Secondary Prevention; Sulfonamides; Thromboembolism; Treatment Outcome; Venous Thrombosis; Vitamin K

In the absence of prophylaxis, elective orthopedic surgery is associated with a high risk of venous thromboembolic events that are responsible for substantial morbidity and mortality. Despite the publication of articles questioning the significance of fatal pulmonary embolism (PE) following elective hip replacement, recent reports support the need for effective thromboprophylaxis in this indication. These reports also provide evidence of a significant reduction in fatal PE and overall mortality provided by treatment with low-molecular-weight heparin (LMWH), compared with unfractionated heparin. Even with the most effective prophylaxis currently available, however, deep vein thrombosis still develops in a minority of high-risk patients, indicating a need for improved therapies. Desirudin, a novel recombinant hirudin and direct thrombin inhibitor, has been shown to provide more effective prophylaxis than the most widely used LMWH, enoxaparin, in orthopedic surgery patients with multiple thromboembolic risk factors. This benefit was not associated with any increase in bleeding. Regional anesthesia and use of graduated compression stockings may provide additional independent reductions in thromboembolic risk in elective orthopedic surgery.

Topics: Anesthesia, Conduction; Anticoagulants; Bandages; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Heparin, Low-Molecular-Weight; Heparitin Sulfate; Hirudin Therapy; Hirudins; Humans; Logistic Models; Postoperative Complications; Pulmonary Embolism; Recombinant Proteins; Risk Factors; Venous Thrombosis

Specific inhibition of thrombin is a new method for the prevention of postoperative deep-vein thrombosis. The objective of this multicenter, randomized, double-blind study was to compare the efficacy and safety of desirudin (Revasc, CGP 39393; fifteen milligrams two times a day) with that of unfractionated heparin (5000 international units three times a day) in patients having a primary elective total hip replacement. The medications were administered subcutaneously, starting preoperatively and continuing for eight to eleven days. The primary end point was a confirmed thromboembolic event during the treatment period. The presence of deep-vein thrombosis was evaluated with bilateral venograms, which were centrally assessed by two independent radiologists. A total of 445 eligible patients were randomized: 220, to management with heparin, and 225, to management with desirudin. A per-protocol analysis of efficacy was performed for the 351 patients (79 per cent) for whom an adequate bilateral venogram had been made within eight to eleven days after the operation or who had had a proved thromboembolic event. The prevalence of confirmed deep-vein thrombosis was thirteen (7 per cent) of 174 patients who had received desirudin and forty-one (23 per cent) of 177 patients who had received heparin, a significant difference (p < 0.0001). The prevalence of proximal deep-vein thrombosis was also significantly reduced (p < 0.0001), by 79 per cent, in the group that had received desirudin (six [3 per cent] of 174 patients) compared with in the group that had received heparin (twenty-nine [16 per cent] of 177). There were no confirmed pulmonary embolisms or deaths during the period of prophylaxis. During a six-week follow-up period, pulmonary embolism was confirmed in four patients, all of whom had received heparin. There was no significant difference between the treatment groups with respect to bleeding variables or bleeding complications. These data demonstrate that a fixed dose of fifteen milligrams of desirudin, started preoperatively and administered subcutaneously twice daily for at least eight days, provided effective, safe prevention of thromboembolic complications, with no specific requirements for laboratory monitoring, in patients who had a total hip replacement.

Topics: Aged; Anticoagulants; Double-Blind Method; Female; Heparin; Hip Prosthesis; Hirudin Therapy; Hirudins; Humans; Injections, Subcutaneous; Male; Postoperative Complications; Pulmonary Embolism; Recombinant Proteins; Thromboembolism; Thrombophlebitis

Saddle pulmonary embolism (PE) remains a challenge to diagnose and manage in pediatric patients. Current literature encourages early consideration of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) in high-risk PE patients with impending right ventricular failure. We present a 17-year-old patient who was admitted to a pediatric cardiac intensive care unit with saddle PE requiring emergent VA-ECMO support because of cardiovascular collapse. Despite anticoagulation with bivalirudin and receiving systemic thrombolysis with alteplase, the clot burden was persistent with minimal improvement in right ventricular function. We proceeded to catheter thrombolysis while on VA-ECMO. This ultimately led to a successful resolution of the PE and allowed for weaning off VA-ECMO. PE is rare in children compared with adults, and pediatricians may be unaware of therapies becoming increasingly used in adults such as the use of VA-ECMO, with systemic and local thrombolysis. The concurrent use of a direct thrombin inhibitor for ECMO anticoagulation alongside the thrombolysis is a novel combination in this condition and age-group.

Topics: Adolescent; Adult; Child; Extracorporeal Membrane Oxygenation; Hirudins; Humans; Peptide Fragments; Pulmonary Embolism; Recombinant Proteins; Tissue Plasminogen Activator

In patients with submassive pulmonary embolism, the use of catheter-directed thrombolysis (CDT), using low-dose alteplase is associated with improvement in overall hemodynamics. The data for use of CDT in patients with heparin-induced thrombocytopenia are limited. We report a case of CDT in a patient with HIT using bivalirudin anticoagulation. Data of the use of bivalirudin and argatroban for systemic anticoagulation with CDT are limited.

Topics: Anticoagulants; Antithrombins; Blood Coagulation; Drug Administration Schedule; Drug Substitution; Fatal Outcome; Fibrinolytic Agents; Heparin; Hirudins; Humans; Infusions, Intravenous; Male; Middle Aged; Peptide Fragments; Pulmonary Embolism; Recombinant Proteins; Thrombocytopenia; Thrombolytic Therapy; Tissue Plasminogen Activator; Tomography, X-Ray Computed; Treatment Outcome

The authors present the case of a nulliparous 34-year-old patient. At the tenth week of gestation, she developed phlebothrombosis of veins of the right leg and massive pulmonary embolism. After thrombolytic and heparin therapy she developed rethrombosis and heparin-induced thrombocytopenia type II. Lepirudin was introduced in therapy and in the 12th week of gestation acenocumarol was added. After the 34th week, she received danaparoid sodium. After a week, by cesarean section, a healthy and mature female was delivered.

Topics: Acenocoumarol; Adult; Anticoagulants; Cesarean Section; Chondroitin Sulfates; Dermatan Sulfate; Female; Fibrinolytic Agents; Gestational Age; Heparin; Heparitin Sulfate; Hirudins; Humans; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Pulmonary Embolism; Recombinant Proteins; Thrombocytopenia; Venous 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

Type II heparin-induced thrombocytopenia (HIT) is a potentially severe adverse effect of heparin treatment triggered by an immune response. Although most cases occur in patients receiving unfractioned heparin, HIT can also arise after low-molecular-weight heparin (LMWH). We report a case of HIT in a postoperative orthopedic 75-year-old woman in treatment with LMWH (nadroparin) complicated by pulmonary embolism and treated successfully with recombinant hirudin. Early recognition and proper treatment are fundamental for the management of this life-threatening disorder.

Topics: Aged; Antibodies; Female; Fibrinolytic Agents; Fractures, Bone; Hirudins; Humans; Nadroparin; Orthopedic Procedures; Platelet Count; Pulmonary Embolism; Recombinant Proteins; Thrombocytopenia; Tomography, X-Ray Computed; Treatment Outcome

Heparin-induced thrombocytopenia (HIT) type II (HIT II), is an immune-mediated complication of heparin therapy, associated with arterial and venous thrombosis. Herein we have reported a case of a 23-year-old woman who developed HIT following a living related donor, preemptive, renal transplantation. The patient was preoperatively exposed to both unfractionated and low-molecular-weight heparin as she underwent five hemodialysis sessions. HIT caused right common and external iliac vein and renal graft artery thrombosis, resulting in graft loss. Heparin-free hemodialysis was continued, and the patient was successfully treated with anticoagulation by the direct thrombin inhibitor lepirudin for both the thromboses and for hemodialysis. Finally, she was accepted for the continuous ambulatory peritoneal dialysis program. This report highlighted the importance of clinical awareness as far as previous heparin exposure is concerned for establishing an early diagnosis and delivering treatment of this life-threatening prothrombotic complication of heparin administration.

Topics: Adult; Anticoagulants; Female; Hematocrit; Heparin, Low-Molecular-Weight; Hirudins; Humans; Kidney Transplantation; Living Donors; Platelet Count; Pulmonary Embolism; Recombinant Proteins; Renal Dialysis; Thrombocytopenia; Treatment Outcome

Type II heparin-induced thrombocytopenia (HIT) is a rare but well-recognised and potentially life-threatening complication of unfractionated heparin therapy, and has been reported in association with heparin locks for central venous lines. We report a case of type II HIT complicated by iliofemoral deep venous thrombosis and pulmonary embolism in a 43-year-old woman in the course of plasma exchange for myasthenia gravis. A Gamcath central venous line had been inserted femorally due to poor peripheral venous access, and this was locked with heparin 5000 U/ml between procedures. Twelve days after initial heparin exposure, she presented with new-onset thrombocytopenia, a painfully swollen right leg, and pleuritic pain. Deep venous thrombosis and pulmonary embolism were confirmed radiologically, and serology for heparin/PF4 antibodies was unequivocally positive. The line was removed, and she was successfully managed with intravenous lepirudin, switching to warfarin on platelet recovery. This case demonstrates that Type II HIT can occur in association with heparin line locks in the course of plasmapheresis, despite previous reports of successful use of plasma exchange to treat Type II HIT.

Topics: Adult; Catheterization, Central Venous; Female; Heparin; Hirudins; Humans; Myasthenia Gravis; Plasma Exchange; Pulmonary Embolism; Recombinant Proteins; Thrombocytopenia; Venous Thrombosis; Warfarin

Heparin induced thrombocytopenia (HIT) is a life-threatening complication that can be seen in the course of heparin treatment. The syndrome is much likely to be seen during treatment with standard heparin but it can also be seen due to low molecular weight heparins. In this article, we presented a case of HIT who was given low molecular weight heparin for prophylaxis that developed massive pulmonary thromboembolism. The patient was successfully treated with lepirudin infusion and no complications due to treatment was seen.

Topics: Anticoagulants; Diagnosis, Differential; Female; Heparin, Low-Molecular-Weight; Hirudins; Humans; Infusions, Intravenous; Middle Aged; Pulmonary Embolism; Radiography; 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

Patients with heparin-induced thrombocytopenia requiring urgent cardiac surgery present a unique challenge that must be addressed by the use of nonheparin alternatives for anticoagulation during cardiopulmonary bypass. Although isolated cases have been presented involving the use of antithrombin III independent thrombin inhibitor hirudin in this situation, its ability to completely inhibit thrombin activity has not been demonstrated. In this report we describe the efficacy of this drug in inhibiting thrombin during a case requiring prolonged cardiopulmonary bypass.

Topics: Aged; Anticoagulants; Blood Coagulation; Cardiopulmonary Bypass; Chondroitin Sulfates; Contraindications; Dermatan Sulfate; Endarterectomy; Female; Heparin; Heparitin Sulfate; Hirudins; Humans; Hypertension, Pulmonary; Plasma; Platelet Transfusion; Pulmonary Embolism; Recombinant Proteins; Thrombectomy; Thrombin; Thrombocytopenia; Time Factors; Warfarin

Heparin-induced thrombocytopenia (HIT) type II is typically characterized by a decrease in platelet count to values between 20 and 120 x 10 (9)/L or a platelet count fall of greater than 50%. We report on a patient who developed a HIT syndrome, thrombosis of the vena cava, and fulminant pulmonary embolism during heparin treatment after cesarean section, without a significant decrease in platelet count. Lepirudin anticoagulation and ecarin clotting time (ECT) monitoring were used successfully during cardiopulmonary bypass.

Topics: Adult; Anticoagulants; Cardiopulmonary Bypass; Cesarean Section; Combined Modality Therapy; Female; Follow-Up Studies; Hirudins; Humans; Platelet Count; Pregnancy; Pulmonary Embolism; Recombinant Proteins; Reference Values; Risk Assessment; Thrombocytopenia; Treatment Outcome

Topics: Adenocarcinoma; Adult; Anticoagulants; Arterial Occlusive Diseases; Autoimmune Diseases; Drug Resistance; Female; Heparin; Heparin, Low-Molecular-Weight; Hepatitis C, Chronic; Hirudins; Humans; Inflammatory Bowel Diseases; Male; Middle Aged; Neoplasms, Unknown Primary; Platelet Aggregation Inhibitors; Portal Vein; Pulmonary Embolism; Recombinant Proteins; Recurrence; Thrombocytopenia; Vena Cava, Inferior; Venous Thrombosis; Warfarin

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

Apart from bleeding complications, heparin-induced thrombocytopenia (HIT) type II is the most severe side effect of heparin therapy. It is widely agreed that its most important clinical symptom is thrombocytopenia, with or without thromboembolism.Assuming, unlike other authors, that thrombosis is the leading clinical symptom of HIT type II, we investigated the frequency of an immunological reaction indicative of HIT type II in patients suffering from thrombosis. From January 1999 to December 2000, 77% ( n=6713) of our in-patients received heparin for more than 5 days as thrombosis prophylaxis. When thrombosis was suspected on the grounds of clinical appearances, the patient concerned underwent phlebography, and two different serological tests for anti-heparin antibodies were also carried out. In such cases, patients were immediately switched to hirudin instead of heparin. In 29 out of 101 patients, the clinical suspicion of thrombosis was confirmed. Three patients developed pulmonary embolism. In 4 patients both serological tests revealed the presence of anti-heparin antibodies. Three of the remaining 72 patients with negative phlebography results were found to have antibodies on serological testing. In none of the 7 patients with a confirmed diagnosis of HIT type II was the classical sign of thrombocytopenia was present. Even with thorough clinical and phlebographic examinations, the incidence of HIT type II is only 0.13% in our institution. One of the 7 patients with thrombosis was not thrombocytopenic but did show the typical immunological reaction. Since the incidence of HIT type II is low and thrombocytopenia is not a reliable indicator for HIT II, the need for frequent thrombocyte counts (twice weekly) should be reconsidered.However,patients developing thrombosis while receiving heparin need to be treated for clinically suspected HIT type II until the final diagnosis is made.

Topics: Adult; Aged; Aged, 80 and over; Algorithms; Antibodies; Anticoagulants; Drug Hypersensitivity; Enzyme-Linked Immunosorbent Assay; Female; Fibrinolytic Agents; Heparin; Hirudin Therapy; Hirudins; Humans; Male; Middle Aged; Phlebography; Platelet Count; Platelet Factor 4; Pulmonary Embolism; Thrombocytopenia; Thrombophlebitis; Thrombosis

We report the case of a 71 old woman presenting a bilateral massive pulmonary embolism with intraventricular right thrombus complicating heparin induced thrombocytopenia (HIT) persistent after one month of conventional anticoagulant processing. We underline the effectiveness of lepirudin (Refludan) in the curative processing of pulmonary embolism allowing here to avoid a complex surgical thromboembolectomy. We evoke the place of this molecule in the curative therapeutic strategy of HIT with thrombotic phenomena.

Topics: Aged; Female; Fibrinolytic Agents; Heparin; Hirudins; Humans; Pulmonary Embolism; Recombinant Proteins; Thrombocytopenia; Treatment Outcome

A patient with chronic thromboembolic pulmonary hypertension and heparin-induced thrombocytopenia successfully underwent pulmonary thromboendarterectomy with circulatory arrest, using recombinant hirudin as an alternative anticoagulant to heparin. Techniques for administration as well as monitoring of this drug's effects are discussed.

Topics: Cardiopulmonary Bypass; Endarterectomy; Female; Fibrinolytic Agents; Hirudins; Humans; Middle Aged; Pulmonary Embolism; Recombinant Proteins

A case of 68 years old women suffering from chronic anemia, myelodysplastic syndrome and treated with progestogen due to endometrial hypertrophy is presented. Initially she was admitted to a regional hospital because of progressive weakness and exertional dyspnea. Three months earlier she reported an episode of acute dyspnea and chest pain. On the basis of clinical symptoms and perfusion lung scintigraphy pulmonary embolism (PE) was diagnosed. Patient received i.v. heparin which was changed to s.c. nadroparine subcutaneously. Platelet count dropped to 55,000'/ml on fifth day of treatment from initial level of about 200,000'/ml. Heparin induced thrombocytopenia was diagnosed, heparin was stopped and ticlopidine was recommended. After 3 weeks symptoms suggesting recurrent PE were observed. The patient was transferred to National Tuberculosis and Lung Diseases Research Institute. Recombinant hirudine (Refludan) was administrated (bolus 0.4 mg/kg and initial dose of infusion 0.1 mg/kg/h) overlapping with acenocoumarol from second day. Dose of r-hirudine was adjusted to achieve APTT prolongation 1.5 to 2.5 times of mid-normal range. During treatment with r-hirudine no bleeding and new thromboembolic complications occurred. Platelets count remained within normal range. After 14 days clinical improvement was observed, though symptoms of right ventricular overload and hypoxemia were still present after 6 months of treatment with oral anticoagulants suggesting chronic thromboembolic pulmonary hypertension.

Topics: Aged; Anemia; Anticoagulants; Dyspnea; Female; Heparin; Hirudin Therapy; Hirudins; Humans; Injections, Intravenous; Myelodysplastic Syndromes; Pulmonary Embolism; Recombinant Proteins; Recurrence; Thrombocytopenia

Topics: Fibrinolytic Agents; Hematoma; Hemorrhage; Hirudin Therapy; Hirudins; Humans; Pulmonary Embolism; Recombinant Proteins; Venous Thrombosis

Topics: Anticoagulants; Coumarins; Female; Fibrinolytic Agents; Heparin; Hirudin Therapy; Hirudins; Humans; Middle Aged; Phenprocoumon; Pulmonary Embolism; Recombinant Proteins; Thrombocytopenia; Thrombophlebitis; Time Factors

A serious retroperitoneal bleeding occurred in a 56-year-old male patient receiving unfractionated heparin due to multiple pulmonary embolism. After reducing the heparin dose, the patient developed a new pulmonary embolism and a large thrombus in the right atrium. Concomitantly, the platelet count dropped to a value of 29 g/l. Heparin-induced thrombocytopenia (HIT) was confirmed by a functional assay, the heparin-induced platelet activation (HIPA) assay, whereas the results of a platelet factor 4/heparin complex ELISA were repeatedly negative. This indicated that the patient's HIT antibodies were directed towards an antigen other than platelet factor 4/heparin complexes. For treatment of the atrial thrombus, an ultra-low-dose lysis with rt-PA (2 mg/h, intravenously) was administered for a period of 52 h, overlapping with systemic treatment with recombinant hirudin (Lepirudin, Refludan, 0.06-0.14 mg/kg/h intravenously). The aim was to enhance lysis of the thrombus without increasing the haematoma, and at the same time keep the risk of fulminant pulmonary embolism due to thrombus fragmentation as low as possible. The cardiac thrombus disappeared within 48 h, without new signs of pulmonary embolism. Platelet counts normalized within nine days.

Topics: Anticoagulants; Arrhythmias, Cardiac; Autoimmune Diseases; Heart Atria; Heart Diseases; Hemorrhage; Heparin; Hirudin Therapy; Hirudins; Humans; Male; Middle Aged; Phenprocoumon; Plasminogen Activators; Pulmonary Embolism; Recombinant Proteins; Retroperitoneal Space; Thrombocytopenia; Thrombolytic Therapy; Thrombosis; Tissue Plasminogen Activator; Vena Cava Filters

The anticoagulant agents commonly used in prevention and treatment of pulmonary embolism are unfractionated heparin, and more recently, low molecular weight heparins, and oral anticoagulants. Unfractionated heparin is the drug of choice for prophylaxis and short-term treatment of pulmonary embolism. Oral anticoagulants are used for prophylaxis in high risk patients and in long-term treatment of pulmonary embolism. Independent overview analysis of clinical trials in elective surgery showed a 60 to 70% reduction in the incidence of fatal pulmonary embolism in heparin-treated patients when they were compared with placebo-treated patients. Low dose heparin has also been shown to be effective in reducing venous thromboembolism after myocardial infarction and other serious medical disorders. In high risk patients prophylaxis with low molecular weight heparins or adjusted doses of unfractionated heparin is recommended. The objectives of treating patients with pulmonary embolism are to prevent death, to reduce morbidity from the acute event, and to prevent thromboembolic pulmonary hypertension. These objectives are achieved by the administration of heparin followed by oral anticoagulants. Heparin is generally administered for 7 to 10 days and is followed by oral anticoagulants. Although widely used and effective in the prevention and treatment of pulmonary embolism, unfractionated heparin has some pharmacological limitations. Heparin presents an aspecific "nonfunctional" binding to plasma proteins such as fibrinogen, factor VIII, vitronectin, and fibronectin. This aspecific binding limits the anticoagulant effect of unfractionated heparin and, is responsible for the heparin resistance observed in some patients with pulmonary embolism as well as of the high intersubject variability of the heparin-induced anticoagulant effect. Antithrombotic agents, such as low molecular weight heparins and pure thrombin inhibitors (hirudin and its analogues), do not specifically bind to plasma protein and they will probably improve the efficacy and practicality of the treatment of pulmonary embolism.

Topics: Anticoagulants; Clinical Trials as Topic; Heparin; Heparin, Low-Molecular-Weight; Hirudin Therapy; Hirudins; Humans; Pulmonary Embolism; Thromboembolism

Pulmonary emboli are detectable by filling defects in the pulmonary vasculature upon pulmonary angiography. Emboli derived from venous thrombi are rich in fibrin to which thrombin remains bound. Hirudin, a specific thrombin inhibitor, binds to thrombin to yield a 1:1 stoichiometric complex. We examined whether 131I-recombinant hirudin (r-hirudin) could be used to detect pulmonary emboli in rabbits. Clots were formed by re-calcifying rabbit plasma in vitro, and then injected (0.034 ml) into a femoral vein to lodge in the lungs. 131I-r-hirudin (29 +/- 4 microCi/kg) was injected intravenously but emboli could not be detected by gamma camera in real time. Post-mortem analysis of lung tissue showed that 131I-r-hirudin did not associate with emboli prepared with 125I-fibrin. Because of these findings, we used different techniques to look at the binding of hirudin to plasma clots. Clots formed in vitro were incubated with 131I-r-hirudin in the presence of equimolar amounts of 125I-albumin; specific binding of 131I-r-hirudin was not observed. Experiments with immobilized fibrin(ogen) showed that 125I-r-hirudin did not bind to and remain with fibrin-bound 131I-thrombin but did lead to the inactivation and displacement of up to 70% of bound thrombin as r-hirudin-thrombin complex; residual thrombin bound to fibrin remained active. Thus, released r-hirudin-thrombin complex is probably cleared rapidly from the region of the embolus in vivo; radioiodinated r-hirudin may not, therefore, be useful as a marker for detecting emboli.

Topics: Animals; Chromatography, Affinity; Femoral Vein; Fibrin; Hirudins; Iodine Radioisotopes; Lung; Male; Protein Binding; Pulmonary Embolism; Rabbits; Radionuclide Imaging; Recombinant Proteins; Thrombin

Topics: Fibrinogen; Fibrinopeptide A; Hirudins; Humans; In Vitro Techniques; Pulmonary Embolism; Thrombin