Safety and Efficacy of Argatroban in the Management of Heparin-Induced Thrombocytopenia

2011 ◽  
Vol 4 ◽  
pp. CMBD.S5118 ◽  
Author(s):  
Bernd Saugel ◽  
Roland M. Schmid ◽  
Wolfgang Huber
Keyword(s):  
Arterial Thrombosis ◽  
Pharmacokinetic Profile ◽  
The United States ◽  
Heparin Therapy ◽  
Direct Thrombin Inhibitor ◽  
Thrombin Inhibitor ◽  
Heparin Induced Thrombocytopenia ◽  
Safety And Efficacy ◽  
Increased Risk ◽  
Life Threatening

Heparin-induced thrombocytopenia (HIT) is a life-threatening adverse reaction to heparin therapy that is characterized by thrombocytopenia and an increased risk of venous and arterial thrombosis. According to guidelines, in patients with strongly suspected or confirmed HIT all sources of heparin have to be discontinued and an alternative, nonheparin anticoagulant for HIT treatment must immediately be started. For both the prophylaxis of thrombembolic events in HIT and the treatment of HIT with thrombosis the direct thrombin inhibitor argatroban is approved in the United States. The objective of this review is to describe the mechanism of action and the pharmacokinetic profile of argatroban, to characterize argatroban regarding its safety and therapeutic efficacy and to discuss its place in therapy in HIT.

Argatroban Therapy in Heparin-Induced Thrombocytopenia

2009 ◽  
Vol 20 (1) ◽  
pp. 37-43
Author(s):  
Melanie L. Sparks
Keyword(s):  
Response Rate ◽  
Direct Thrombin Inhibitor ◽  
Ease Of Use ◽  
Alternative Form ◽  
Thrombin Inhibitor ◽  
Test Results ◽  
Heparin Induced Thrombocytopenia ◽  
Safety And Efficacy ◽  
Increased Risk ◽  
Consistent Response

Patients who develop heparin-induced thrombocytopenia (HIT) are at increased risk for morbidity and mortality if the disorder is not recognized and treated early. Upon initial suspicion of HIT, providers should promptly discontinue all heparin products and initiate an alternative form of anticoagulation without waiting for diagnostic test results confirming the presence of HIT antibodies. The direct thrombin inhibitor, argatroban (Argatroban), is a reasonable alternative anticoagulant in patients with HIT, based on its proven safety and efficacy, ease of use, and consistent response rate between individuals. Further clinical trials are warranted to evaluate and expand the use of argatroban in other thrombotic states.

Diagnosis and treatment of heparin-induced thrombocytopenia

Perfusion ◽  
2003 ◽  
Vol 18 (1) ◽  
pp. 47-53 ◽  
Author(s):  
William J DeBois ◽  
Junli Liu ◽  
Leonard Y Lee ◽  
Leonard N Girardi ◽  
Charles Mack ◽  
...  
Keyword(s):  
New York ◽  
Platelet Inhibition ◽  
Heparin Therapy ◽  
Serotonin Release ◽  
Antibody Detection ◽  
Thrombin Inhibitor ◽  
Heparin Infusion ◽  
Platelet Factor ◽  
Heparin Induced Thrombocytopenia ◽  
Life Threatening

Heparin-induced thrombocytopenia (HIT) is a major side effect secondary to the administration of heparin. This syndrome is serious and potentially life threatening. This response is the result of antibodies formed against the platelet factor 4 (PF4)/heparin complex. The incidence of this immune-mediated syndrome has been estimated to be 1-3% of all patients receiving heparin therapy. The occurrence of HIT in patients requiring full anticoagulation for cardiopulmonary bypass (CPB), therefore, presents a serious challenge to the cardiac surgery team. The diagnosis of HIT should be based on both clinical and laboratory evidence. While functional assays, platelet aggregation tests, and the serotonin release assay can be used to support the diagnosis, the negative predictive value of these tests is generally less than 50%. In contrast, although non-functional antibody detection assays are more sensitive, they have a low specificity. HIT can be treated in several ways, including cessation of all heparin and giving an alternative thrombin inhibitor, platelet inhibition followed by heparin infusion, and the use of low molecular weight heparins. In this presentation, the pathology and current diagnostic tests, as well as the successful management of patients with HIT undergoing CPB at New York Presbyterian Hospital, are reviewed.

Successful Use of Bivalirudin in the Treatment of Patients Suspected, or at Risk of, Heparin-Induced Thrombocytopenia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4077-4077 ◽  
Author(s):  
John L. Francis ◽  
Alane Drexler ◽  
Gage Gwyn ◽  
Rebecca Moroose
Keyword(s):  
Severe Renal Impairment ◽  
Retrospective Chart Review ◽  
Heparin Therapy ◽  
Thrombin Inhibitor ◽  
Published Data ◽  
Minor Effect ◽  
Platelet Factor ◽  
Platelet Recovery ◽  
Heparin Induced Thrombocytopenia ◽  
Increased Risk

Abstract Heparin-induced thrombocytopenia (HIT) is a serious complication of heparin therapy. As thrombosis occurs in 50% of untreated patients, prompt treatment with a direct thrombin inhibitor (DTI) is recommended. Lepirudin and argatroban are currently approved for the treatment of HIT. However, their use is complicated by antibody formation with potential for anaphylactic shock (lepirudin), effects on the PT/INR that complicate transition to coumadin (argatroban), and significant dose adjustments in patients with renal (lepirudin) or liver (argatroban) impairment. The effectiveness of bivalirudin, another DTI, as a replacement for heparin has been well documented in percutaneous coronary intervention, but there are little published data on its use in treating HIT. We now report our experience with bivalirudin in 52 patients with clinical suspicion of HIT, or at increased risk of this complication. HIT was suspected on the basis of a falling platelet count and/or thrombosis in the setting of current or recent heparin therapy (n=49). Patients were considered at increased risk of HIT if they required ongoing intravenous anticoagulation in a setting associated with a high incidence of heparin-platelet factor 4 (HPF4) antibodies (n=3). Data were collected by retrospective chart review, and patients classified according to whether HIT was very likely (n=13), likely (n=17), unlikely (n=11) or very unlikely (n=11). Bivalirudin was given by intravenous infusion, typically at an initial dose of 0.15 - 0.20 mg/kg/h and adjusted to achieve an APTT of approximately 1.5–2.5 x baseline. Twenty-one patients had moderate or severe renal impairment. The infusion rate was significantly lower for patients with severe renal insufficiency, but was not different in those with mild renal dysfunction. ELISA-detectable HPF4 antibodies were present in 43/52 cases. Twenty-seven patients were significantly thrombocytopenic (<100,000 x 109/L) and 22 had thrombosis before therapy. Transition to warfarin was achieved in 44/52 patients with a median overlap of therapy of 4 (0.5–14) days. Bivalirudin therapy was continued for an average of 8.0 (3–47) days, and had a relatively minor impact on the PT/INR. The mean INR on monotherapy was 1.50 (1.23–2.18) with a mean change in INR due to bivalirudin therapy of 0.33 ± 0.22. Therapeutic APTTs were achieved in all patients, with approximately 92.5% of tests in the desired range. The average time to platelet recovery was 3.0 (1–10) days. There were no cases of major bleeding, no deaths attributable to HIT, and no patient required amputation. We conclude that bivalirudin provides safe and effective anticoagulation for patients with suspected HIT, as well as for those with an increased risk of HIT that require intravenous anticoagulation. Potential advantages of bivalirudin include the relatively minor effect on the PT, which facilitates transition to warfarin therapy, and its short half-life in patients at high risk of bleeding or who require invasive procedures at short notice.

Heparin-induced thrombocytopenia: when a low platelet count is a mandate for anticoagulation

Hematology ◽  
2009 ◽  
Vol 2009 (1) ◽  
pp. 225-232 ◽  
Author(s):  
Thomas L. Ortel
Keyword(s):  
Platelet Count ◽  
Heparin Therapy ◽  
Severe Thrombocytopenia ◽  
Drug Induced ◽  
Platelet Factor ◽  
Heparin Induced Thrombocytopenia ◽  
Immune Mediated ◽  
Number Of Patients ◽  
Increased Risk ◽  
Antibody Levels

Abstract Heparin-induced thrombocytopenia (HIT) is an immune-mediated disorder caused by the development of antibodies to platelet factor 4 (PF4) and heparin. The thrombocytopenia is typically moderate, with a median platelet count nadir of ~50 to 60 × 109 platelets/L. Severe thrombocytopenia has been described in patients with HIT, and in these patients antibody levels are high and severe clinical outcomes have been reported (eg, disseminated intravascular coagulation with microvascular thrombosis). The timing of the thrombocytopenia in relation to the initiation of heparin therapy is critically important, with the platelet count beginning to drop within 5 to 10 days of starting heparin. A more rapid drop in the platelet count can occur in patients who have been recently exposed to heparin (within the preceding 3 months), due to preformed anti-heparin/PF4 antibodies. A delayed form of HIT has also been described that develops within days or weeks after the heparin has been discontinued. In contrast to other drug-induced thrombocytopenias, HIT is characterized by an increased risk for thromboembolic complications, primarily venous thromboembolism. Heparin and all heparin-containing products should be discontinued and an alternative, non-heparin anticoagulant initiated. Alternative agents that have been used effectively in patients with HIT include lepirudin, argatroban, bivalirudin, and danaparoid, although the last agent is not available in North America. Fondaparinux has been used in a small number of patients with HIT and generally appears to be safe. Warfarin therapy should not be initiated until the platelet count has recovered and the patient is systemically anticoagulated, and vitamin K should be administered to patients receiving warfarin at the time of diagnosis of HIT.

Argatroban and Renal Replacement Therapy in Patients with Heparin-Induced Thrombocytopenia

2005 ◽  
Vol 39 (2) ◽  
pp. 231-236 ◽  
Author(s):  
Ignatius Y Tang ◽  
Donna S Cox ◽  
Kruti Patel ◽  
Bharathi V Reddy ◽  
Linda Nahlik ◽  
...  
Keyword(s):  
At Risk ◽  
Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Direct Thrombin Inhibitor ◽  
Thrombin Inhibitor ◽  
Systemic Clearance ◽  
Recovery Method ◽  
P Values ◽  
Heparin Induced Thrombocytopenia ◽  
Alternative Anticoagulation

BACKGROUND: Argatroban, a direct thrombin inhibitor, is an effective anticoagulant for patients who have heparin-induced thrombocytopenia (HIT). Anticoagulation is usually required for renal replacement therapy (RRT). OBJECTIVE: To prospectively evaluate the pharmacokinetics, pharmacodynamics, and safety of argatroban during RRT in hospitalized patients with or at risk for HIT. METHODS: Five patients with known or suspected HIT underwent hemodialysis (n = 4) or continuous venovenous hemofiltration (CVVH, n = 1), while receiving a continuous infusion of argatroban 0.5–2 μg/kg/min. Activated partial thromboplastin times (aPTTs), activated clotting times (ACTs), argatroban concentrations (plasma, dialysate, CVVH effluent), and safety were assessed before, during, and after a 4-hour session of RRT. Systemic and dialytic argatroban clearances were calculated. RESULTS: Among the 4 hemodialysis patients, aPTT, ACT, and plasma argatroban concentrations remained stable during RRT, with respective mean ± SD values of 74.3 ± 34.2 seconds, 198 ± 23 seconds, and 499 ± 353 ng/mL before RRT, and 70.6 ± 21.4 seconds, 181 ± 12 seconds, and 453 ± 295 ng/mL 2 hours after starting RRT (p values NS). Systemic clearance was 17.7 ± 12.8 L/h before hemodialysis and 17.0 ± 9.5 L/h during hemodialysis (n = 2). The dialyzer clearance (dialysate recovery method) was 1.5 ± 0.4 L/h (n = 4). Generally similar responses occurred in the CVVH patient: systemic argatroban clearance was 4.8 L/h before CVVH and 4 L/h during CVVH. The hemofilter argatroban clearance was 0.9 L/h. No bleeding or thrombosis occurred. CONCLUSIONS: Argatroban provides effective alternative anticoagulation in patients with or at risk for HIT during RRT. Argatroban clearance by high-flux membranes during hemodialysis and CVVH is clinically insignificant, necessitating no dose adjustment.

Heparin-Induced Thrombocytopenia during Obstetric Hospital Admissions

2018 ◽  
Vol 35 (09) ◽  
pp. 898-903 ◽  
Author(s):  
Deepika Sagaram ◽  
Zainab Siddiq ◽  
Andrew Eisenberger ◽  
Cande Ananth ◽  
Jason Wright ◽  
...  
Keyword(s):  
Heart Failure ◽  
Arterial Thrombosis ◽  
Low Molecular Weight Heparin ◽  
Hospital Admissions ◽  
The United States ◽  
Limb Amputation ◽  
Administrative Database ◽  
Low Molecular Weight ◽  
Heparin Induced Thrombocytopenia ◽  
Pharmacologic Prophylaxis

Introduction The rate of heparin-induced thrombocytopenia (HIT) on a population basis is unknown. The objective of this study was to characterize the risk for HIT during antepartum, delivery, and postpartum hospitalizations in the United States. Materials and Methods A large administrative database was used to determine the risk of HIT in hospitalized obstetric patients who received unfractionated heparin (UFH) or low molecular weight heparin (LMWH). Patients were presumed to have HIT if they were exposed to UFH or LMWH, received a diagnosis of HIT, and were administered a medication for the treatment of HIT including bivalirudin, argatroban, fondaparinux, or lepirudin. We queried severe complications of HIT including arterial thrombosis, limb amputation, heart failure, and death. Results We identified 66,468 antepartum hospitalizations, 66,741 delivery hospitalizations, and 16,325 postpartum readmissions where women received pharmacologic prophylaxis. Of these, 10 antepartum admissions, 1 delivery admission, and 14 postpartum readmissions involved a diagnosis of HIT with treatment of bivalirudin, argatroban, fondaparinux, or lepirudin. There were no deaths and no diagnoses of arterial thrombosis, limb amputation, heart failure, and death. Conclusion Risk for HIT among hospitalized obstetric patients is low. In this cohort, no cases of death or severe complications were noted in relation to the diagnosis.

scholarly journals Venous limb gangrene during overlapping therapy with warfarin and a direct thrombin inhibitor for immune heparin-induced thrombocytopenia

2002 ◽  
Vol 71 (1) ◽  
pp. 50-52 ◽  
Author(s):  
Maureen A. Smythe ◽  
Theodore E. Warkentin ◽  
Jennifer L. Stephens ◽  
Dana Zakalik ◽  
Joan C. Mattson
Keyword(s):  
Direct Thrombin Inhibitor ◽  
Thrombin Inhibitor ◽  
Heparin Induced Thrombocytopenia

scholarly journals Use of Edoxaban for the Treatment of Heparin-Induced Thrombocytopenia

2020 ◽  
Vol 2020 ◽  
pp. 1-4
Author(s):  
Ryo Kanamoto ◽  
Shinichi Hiromatsu ◽  
Tomoyuki Anegawa ◽  
Kanako Sakurai ◽  
Shohei Yoshida ◽  
...  
Keyword(s):  
Adverse Drug Reaction ◽  
Esophageal Cancer ◽  
Oral Treatment ◽  
Length Of Hospital Stay ◽  
Heparin Therapy ◽  
Vitamin K Antagonist ◽  
Bleeding Complications ◽  
Heparin Induced Thrombocytopenia ◽  
Life Threatening

Heparin-induced thrombocytopenia (HIT) is a life-threatening adverse drug reaction of heparin therapy, which increases a patient’s risk of developing venous and/or arterial thromboembolism. HIT should be treated through discontinuation of heparin and administration of nonheparin anticoagulants such as argatroban. For long-term anticoagulation, parenteral nonheparin anticoagulants are generally converted to oral treatment with a vitamin K antagonist such as warfarin. Although administration of warfarin is recommended to overlap with a nonheparin anticoagulant for a minimum of 5 days, overlapping with argatroban and warfarin presents high risks of bleeding. We describe a case of HIT treated with edoxaban. A 78-year-old man underwent surgery for esophageal cancer and was administered heparin perioperatively. After surgery, he was diagnosed with HIT and venous thromboembolism. We immediately stopped heparin and initiated parenteral argatroban. The patient was subsequently started on edoxaban without any overlap between the two drugs. The treatment was successful. The treatment of edoxaban following argatroban for HIT could reduce bleeding complications and shorten the length of hospital stay. To the best of our knowledge, this is the first report of the use of edoxaban for HIT treatment.

The Antithrombotic Efficacy of AT-1459, a Novel, Direct Thrombin Inhibitor, in Rat Models of Venous and Arterial Thrombosis

2001 ◽  
Vol 86 (12) ◽  
pp. 1512-1520 ◽  
Author(s):  
Chi-ho Yun ◽  
Hyoung-sik Seo ◽  
Takaki Koga ◽  
Takashi Dan ◽  
Hak-yeop Kim ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Arterial Thrombosis ◽  
Bleeding Time ◽  
Thrombus Formation ◽  
Direct Thrombin Inhibitor ◽  
Vehicle Group ◽  
Thrombin Inhibitor ◽  
Rat Models ◽  
Vessel Patency ◽  
Antithrombotic Efficacy

SummaryThe antithrombotic efficacy of AT-1459, a novel, direct thrombin inhibitor (Ki = 4.9 nM) was evaluated in rat models of venous thrombosis combined with a bleeding time test and arterial thrombosis.After drugs were given by i. v. bolus injection plus a continuous infusion, the ID50 (a dose that exhibits 50% inhibition of thrombus formation over each vehicle group) values of AT-1459, argatroban, and dalteparin were 0.04 mg/kg plus 0.04 mg/kg/h, 0.1 mg/kg plus 0.4 mg/ kg/h, and 13.0 IU/kg plus 26.0 IU/kg/h, respectively, in the venous thrombosis study. The BT2 (a dose that causes 2-fold prolongation of bleeding time over each vehicle group) values of AT-1459, argatroban, and dalteparin were 0.9 mg/kg plus 0.9 mg/kg/h, 1.0 mg/kg plus 0.6 mg/kg/h, and 345.5 IU/kg plus 691.0 IU/kg/h in the rat tail transection model. The ratios of BT2/ID50 of AT-1459, argatroban, and dalteparin were 22.5, 10.0, and 26.6, respectively.In a rat model of arterial thrombosis induced by topical FeCl2 application, intravenous administration of AT-1459, argatroban, and dalteparin improved the vessel patency significantly (P <0.01) at 0.6 mg/kg plus 0.6 mg/kg/h, 0.6 mg/kg plus 2.4 mg/kg/h, and 300 IU/kg plus 600 IU/kg/h, respectively.The oral antithrombotic effect of AT-1459 lasted for 6 after administering 30 mg/kg and improved the vessel patency significantly 1 h after administering the same dose in venous and arterial thrombosis models, respectively, with a rapid onset of action. Warfarin also inhibited thrombus weight and improved the vessel patency significantly after oral administration of 0.3 mg/kg for three consecutive days in the same study. The antithrombotic and hemorrhagic effects of all drugs studied were correlated with plasma concentration or clotting times.These results suggest that AT-1459 may be clinically useful as an orally available antithrombotic agent for the prevention of venous and arterial thrombosis.

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