refludan and Pulmonary-Embolism

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

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 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: 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