hirudin and Purpura--Thrombocytopenic--Idiopathic

Heparin-induced thrombocytopenia (HIT) is a prothrombotic disorder characterized by heparin-dependent antibodies that activate platelets (PLTs) via PLT FcγIIa receptors. "Autoimmune" HIT (aHIT) indicates a HIT subset where thrombocytopenia progresses or persists despite stopping heparin; aHIT sera activate PLTs strongly even in the absence of heparin (heparin-independent PLT-activating properties). Affected patients are at risk of severe complications, including dual macro- and microvascular thrombosis leading to venous limb gangrene. High-dose intravenous immunoglobulin (IVIG) offers an approach to interrupt heparin-independent PLT-activating effects of aHIT antibodies.. A 78-year-old male who underwent cardiopulmonary bypass for aortic dissection developed aHIT, disseminated intravascular coagulation, and deep vein thrombosis; progression to venous limb gangrene occurred during partial thromboplastin time (PTT)-adjusted bivalirudin infusion (underdosing from "PTT confounding"). Thrombocytopenia recovered with high-dose IVIG, although the PLT count increase began only after the third dose of a 5-day IVIG regimen (0.4 g/kg/day × 5 days). We reviewed case reports and case series of IVIG for treating HIT, focusing on various IVIG dosing regimens used.. Patient serum-induced PLT activation was inhibited in vitro by IVIG in a dose-dependent fashion; inhibition of PLT activation by IVIG was much more marked in the absence of heparin versus the presence of heparin (0.2 U/mL). Our literature review indicated 1 g/kg × 2 IVIG dosing as most common for treating HIT, usually associated with rapid PLT count recovery.. Our clinical and laboratory observations support dose-dependent efficacy of IVIG for decreasing PLT activation and thus correcting thrombocytopenia in aHIT. Our case experience and literature review suggests dosing of 1 g/kg IVIG × 2 for patients with severe aHIT.

Topics: Aged; Aortic Aneurysm; Aortic Dissection; Cardiopulmonary Bypass; Cells, Cultured; Disease Progression; Gangrene; Heparin; Hirudins; Humans; Immunoglobulins, Intravenous; Male; Partial Thromboplastin Time; Peptide Fragments; Purpura, Thrombocytopenic, Idiopathic; Recombinant Proteins; Venous Thrombosis

The use of extracorporeal membrane oxygenation (ECMO) support for cardiac and respiratory failure has increased in recent years. Improvements in ECMO oxygenator and pump technologies have aided this increase in utilization. Additionally, reports of successful outcomes in supporting patients with respiratory failure during the 2009 H1N1 pandemic and reports of ECMO during cardiopulmonary resuscitation have led to increased uptake of ECMO. Patients requiring ECMO are a heterogenous group of critically ill patients with cardiac and respiratory failure. Bleeding and thrombotic complications remain a leading cause of morbidity and mortality in patients on ECMO. In this review, we describe the mechanisms and management of hemostatic, thrombotic and hemolytic complications during ECMO support.

Topics: Anticoagulants; Blood Coagulation; Blood Coagulation Tests; Cardiac Output, Low; Cardiac Tamponade; Extracorporeal Membrane Oxygenation; Hemolysis; Hemorheology; Hemorrhage; Heparin; Hirudins; Humans; Peptide Fragments; Purpura, Thrombocytopenic, Idiopathic; Recombinant Proteins; Respiratory Insufficiency; Thrombosis; von Willebrand Diseases

Type-2 heparin-induced thrombocytopenia (HIT) is a not infrequent complication of treatment with heparins which can lead to fatal outcomes if not recognized and timely treated. Over the last years new epidemiological knowledge, new diagnostic approaches and new therapeutic options have become available. In the present review such novelties will be briefly discussed in the frame of Italian Health System. In Italy only one drug is approved for use in HIT patients differently from other countries. Alternative possible therapeutic options will be discussed based on the scarce available evidence.

Topics: Fondaparinux; Heparin; Hirudins; Humans; Italy; Platelet Activation; Platelet Factor 4; Polysaccharides; Purpura, Thrombocytopenic, Idiopathic; Recombinant Proteins; Thromboembolism

Heparin-induced thrombocytopenia/thrombosis is an immunologic reaction to unfractionated heparin characterized by thrombocytopenia, platelet activation and thrombosis. A high index of suspicion is required for timely diagnosis and treatment. Treatment is complex and outcome maybe less then satisfactory.

Topics: Ancrod; Antibodies; Anticoagulants; Arginine; Cardiovascular Diseases; Chondroitin Sulfates; Dermatan Sulfate; Fibrinolytic Agents; Heparin; Heparin, Low-Molecular-Weight; Heparitin Sulfate; Hirudin Therapy; Hirudins; Humans; Peptide Fragments; Pipecolic Acids; Practice Guidelines as Topic; Purpura, Thrombocytopenic, Idiopathic; Recombinant Proteins; Sulfonamides; Thrombin

Heparin-induced thrombocytopenia (HIT) is a serious and common complication of heparin therapy that can lead to significant losses of life and limb. It is often under-recognized and, therefore, goes untreated until thrombosis develops. This article is meant to provide specific recommendations for treating patients with immune-mediated HIT, whether or not it is associated with thrombosis. These recommendations are based on our clinical experience treating patients with HIT and our evaluation of the published data on the efficacy and safety of lepirudin and argatroban, the 2 drugs approved by the Food and Drug Administration for treating HIT. Based on these criteria, we consider lepirudin the treatment of choice in all patients with HIT except those with severe or deteriorating renal function.

Topics: Algorithms; Anticoagulants; Antigen-Antibody Complex; Arginine; Clinical Trials as Topic; Diagnosis, Differential; Disease Management; Follow-Up Studies; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Hirudins; Humans; Immunoglobulin G; Pipecolic Acids; Platelet Activation; Platelet Count; Platelet Factor 4; Prognosis; Purpura, Thrombocytopenic, Idiopathic; Recombinant Proteins; Sulfonamides; Thrombocytopenia; Thrombophilia; Time Factors

Patients with a previous history of heparin-induced thrombocytopenia are at a higher risk for thromboembolic events, and heparin administration is formally contraindicated. Bivalirudin has been reported as an alternative therapy whenever an intervention that requires systemic anticoagulation and cardiopulmonary by-pass pump is needed. We present the case of a patient diagnosed with heparin-induced thrombocytopenia and heparin-PF4 (+) antibodies requiring a triple cardiac valve replacement who developed fulminant coagulopathy after bivalirudin administration. A discussion on the serious difficulties that the management of these types of patients involves, as well as a review of prevention strategies are presented.

Topics: Acute Kidney Injury; Aged; Anticoagulants; Antithrombins; Blood Loss, Surgical; Coronary Artery Bypass; Disseminated Intravascular Coagulation; Drug Substitution; Fatal Outcome; Heart Failure; Heart Valve Diseases; Heart Valve Prosthesis Implantation; Heparin; Hirudins; Humans; Immunoglobulin G; Intraoperative Complications; Male; Multiple Organ Failure; Peptide Fragments; Platelet Factor 4; Purpura, Thrombocytopenic, Idiopathic; Recombinant Proteins; Thrombophilia

Danaparoid is a safe and effective drug for the treatment of heparin-induced thrombocytopenia (HIT). We describe an uncommon complication: danaparoid cross-reactivity with HIT antibodies.. A retrospective observational multicenter study on HIT was conducted in France. In this study concerning HIT patients treated with lepirudin, 12 patients were treated with lepirudin because danaparoid cross-reacted with the heparin-dependent antibodies.. Three groups of situations can be separated. In a first group, four patients received a short course of danaparoid until their initial functional HIT assay showed a cross-reactivity between danaparoid and HIT antibodies. One patient presented a fatal thrombotic complication but the relationship between this thrombotic complication and danaparoid cross-reactivity cannot be certain. In a second group, four patients received for 4 days at least a danaparoid treatment while the initial functional test did not show any danaparoid cross-reactivity. During danaparoid treatment, no significant increase of platelet count was observed and two patients presented a fatal thrombotic complication. In a third group, cross-reactivity between danaparoid and HIT antibodies was not checked before danaparoid therapy. During danaparoid treatment, no significant increase of platelet count was observed and the four patients developed a venous thromboembolic complication.. Absence of any increase in platelet count after 3 to 5 days of danaparoid therapy and/or the occurrence of a new thrombotic event should lead to danaparoid cross-reactivity suspicion. However, before attributing thrombotic complications to danaparoid cross-reactivity, it is crucial to verify that the patients received the recommended danaparoid dosage regimen.

Topics: Aged; Anticoagulants; Chondroitin Sulfates; Cross Reactions; Dermatan Sulfate; Female; Hemostasis; Heparin; Heparitin Sulfate; Hirudins; Humans; Intensive Care Units; Male; Middle Aged; Purpura, Thrombocytopenic, Idiopathic; Recombinant Proteins; Retrospective Studies

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

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