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

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.

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

Clinical medicine Blood disorders ◽

10.4137/cmbd.s5118 ◽

2011 ◽

Vol 4 ◽

pp. CMBD.S5118 ◽

Cited By ~ 1

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.

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

Hematology ◽

10.1182/asheducation-2009.1.225 ◽

2009 ◽

Vol 2009 (1) ◽

pp. 225-232 ◽

Cited By ~ 14

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.

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Diagnosis and treatment of heparin-induced thrombocytopenia

Perfusion ◽

10.1191/0267659103pf637oa ◽

2003 ◽

Vol 18 (1) ◽

pp. 47-53 ◽

Cited By ~ 6

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.

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Retrospective Analysis of the Effect of Argatroban and Coumadin on INR Values in Heparin Induced Thrombocytopenia.

Blood ◽

10.1182/blood.v108.11.4118.4118 ◽

2006 ◽

Vol 108 (11) ◽

pp. 4118-4118

Author(s):

Maxine Lau ◽

Jin-Hyeun Huh

Keyword(s):

Combined Therapy ◽

Anticoagulation Therapy ◽

Retrospective Chart Review ◽

Thrombin Inhibitor ◽

Minor Bleeding ◽

Concomitant Therapy ◽

Heparin Induced Thrombocytopenia ◽

Primary Endpoints ◽

Increased Risk ◽

Secondary Endpoints

Abstract Background: Patients who develop Heparin-induced thrombocytopenia(HIT) are at an increased risk for thrombosis. They may require long term anticoagulant therapy and are often stepped down from either argatroba, lepirudinn or danaparoid to oral warfarin therapy. Step down of anticoagulation therapy is complicated by falsely elevated PT/INR which can cause difficultly in assessing the appropriate time to discontinue Argatroban therapy. Patients may be increased risk of bleeding due to receiving combined therapy. Previous studies analyzing this effect of combined therapy were observed in healthy individuals. The experience at this institution is complicated utilization of abnormally low rates of argatroban to achieve therapeutic aPTT levels. Method: This is a retrospective chart review study analyzing the trends of INRs with argatroban and warfarin concomitant therapy. All patients during the period of January 2002 to December 2005 receiving argatroban were identified from pharmacy records. Only patients with argatroban and warfarin stepdown therapy were considered for this analysis. The only exclusion criteria was documented end stage liver failure. ANOVA analysis was deemed appropriate and SPSS program was utilized. Direct thrombin Inhibitor (DTI) levels was utilized for argatroban monitoring starting in 2005. The primary endpoint was to determine the effect Argatroban has on INR by analyzing the INR with concomitant argatroban and coumadin therapy, argatroban alone and evaluating the true INR with coumadin alone. The secondary endpoint was to observe any adverse effects and complications from concomitant therapy mainly bleeding and mortality. Results: The primary endpoints are displayed in table 1. Ninety-three percent of patients required a maintenance argartroban rate of less than 1.0 mcg/kg/min with 68 % requiring less than 0.5 mcg/kg/min. There was a stronger correlation when argatroban rates were less than 0.25 mcg/kg/min and the associated twofold increase previously noted in other trials with combined therapy was not observed. The secondary endpoints are shown in table 2. Less than 50% of the patients in both major and minor bleeding episodes and 33% of mortality had documented INRs > 4.0. Conclusions: The argatroban rates documented in this study are 50–75% less than 2–4 mcg/kg/min usually reported in literature. In addition, the conversion from aPTT to DTI monitoring resulted in a greater than 60% reduction in argatroban rates. However the correlation was also stronger at these lower rates. Although there was not a high percentage of bleeds with INR’s greater than 4.0, the relationship between DTI and INR suggest that a lower combined INR could be targeted for therapeutic efficacy. A warfarin dosing nomogram based on these finding will be developed and tested. Information regarding ISI was not available at the time of this abstract. Primary Endpoints Argatroban Rate(mcg/kg/min) N INR on warfarin alone INR on warfarin and argatroban ANOVA < 0.05 13 3.17 ± 1.37 4.01 ± 2.90 0.734 0.06–0.25 32 3.68 ± 1.06 4.19 ± 1.17 0.704 0.26–0.5 14 2.71 ± 1.12 3.38 ± 1.69 0.22 0.5–1.0 13 3.10 ±0.79 5.00 ± 0.54 0.54 >1.0 6 2.74 ± 1.47 5.13 ± 3.69 0.162 Secondary Endpoints -Complications n (%) outcomes with INR > 4.0 on both agents * all INRs >5.5 Total Bleeding 11 (13%) 5 (45%) Major 7 (8%) 3 (43%) Minor 4 (5%) 2 (50%) High requiring PRBC with no bleeding* 5 (6%) 5 (100%) Mortality 15 (17%) 5 (33%)

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Fondaparinux in the Treatment of Heparin-Induced Thrombocytopenia.

Blood ◽

10.1182/blood.v104.11.1775.1775 ◽

2004 ◽

Vol 104 (11) ◽

pp. 1775-1775 ◽

Cited By ~ 14

Author(s):

James Bradner ◽

Robert K. Hallisey ◽

David J. Kuter

Keyword(s):

Massachusetts General Hospital ◽

Prospective Trial ◽

Cross Reactivity ◽

High Risk Group ◽

Thrombin Inhibitor ◽

Type Ii ◽

Platelet Factor ◽

Platelet Recovery ◽

Heparin Induced Thrombocytopenia

Abstract The development of new non-heparin anticoagulant therapies has increased interest in the treatment of type II heparin-induced thrombocytopenia (HIT). Standard therapy involves administration of an intravenous direct thrombin inhibitor (DTI), either argatroban or lepirudin. Due to a lack of cross-reactivity to HIT antibodies in vitro, the synthetic pentasaccharide fondaparinux sodium is an appealing alternative, but its use in this disorder has not been comprehensively examined. Here, we report our experience with fondaparinux in HIT and an analysis of safety and efficacy in this setting. We reviewed all in-patient cases of HIT at the Massachusetts General Hospital that were confirmed by the heparin-platelet factor 4 antibody test and were treated with fondaparinux. Twenty patients satisfied diagnostic criteria for HIT. Each patient studied lacked another competing, compelling etiology for thrombocytopenia and was treated with fondaparinux for more than five days within one month of diagnosis. The average duration of therapy was 17 days and 16 patients (80%) were treated within two weeks of diagnosis. Patients were grouped according to whether they received fondaparinux after initial therapy with a DTI (n=10) or as initial treatment following the diagnosis of HIT (n=10). The initial dose of fondaparinux administered was 2.5 mg in 18 patients. Neither absolute nor relative thrombocytopenia was identified in either group following treatment. Patients with HIT treated with fondaparinux while thrombocytopenic experienced platelet recovery on average in 3.7 days, as represented in Figure 1. In addition, there were no observed thrombotic complications among patients treated with fondaparinux. In this analysis of a high-risk group of inpatients with type-II HIT, fondaparinux was tolerated without the continuation or recurrence of thrombocytopenia. This suggests that cross-reactivity between the heparin-PF4 antibody and fondaparinux is not likely to be clinically significant. Additionally, the absence of thrombotic sequelae among fondaparinux-treated patients argues that fondaparinux may be a well-tolerated, effective treatment for this morbid, prothrombotic disorder. A prospective trial of fondaparinux in the treatment of type-II HIT is planned. Figure Figure

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Low Level Platelet-Activating Antibodies in Patients Suspected of Having Heparin-Induced Thrombocytopenia but Testing Negative in the ”Gold Standard” Functional Test

Blood ◽

10.1182/blood.v124.21.2757.2757 ◽

2014 ◽

Vol 124 (21) ◽

pp. 2757-2757

Author(s):

Ishac Nazi ◽

Donald M Arnold ◽

James W Smith ◽

Theodore E. Warkentin ◽

Jane C Moore ◽

...

Keyword(s):

Platelet Activation ◽

Research Funding ◽

Heparin Therapy ◽

Serotonin Release ◽

Patient Specific ◽

Platelet Factor ◽

Heparin Induced Thrombocytopenia ◽

Increased Risk ◽

Increased Sensitivity ◽

Clinical Conditions

Abstract Background: Heparin-induced thrombocytopenia (HIT) is a common drug reaction that causes arterial or venous thrombosis as a result of heparin therapy. Platelet-activating antibodies, against complexes of platelet factor 4 (PF4) and heparin, cause intense platelet activation, ultimately leading to an increased risk of thrombosis, limb-loss and even death. Most patients exposed to heparin will produce non-pathogenic anti-PF4/heparin antibodies while only a small number will produce platelet-activating and HIT-causing antibodies (pathogenic HIT antibodies). Among HIT tests, the functional assays, such as the serotonin release assay (SRA), correlate best with the disease because they can specifically identify the pathogenic HIT antibodies whereas the enzyme immunoassays (EIAs) cannot. We have previously shown that anti-PF4/heparin antibody production precedes thrombocytopenia in HIT patients (Warkentin et al., Blood 2009 113: 4963-4969) possibly indicating the need for a threshold plasma level of pathogenic HIT antibody, among other factors, to cause the disease. The objective of this study was to investigate the presence of low levels of pathogenic HIT antibodies in samples from patients suspected of HIT who had detectable anti-PF4/heparin antibodies in the EIA (EIA-positive), but who did not have platelet-activating antibodies in the standard SRA (SRA-negative). Methods: We used an in-house IgG-specific EIA to detect the presence of anti-PF4/heparin antibodies (EIA-positive: OD405nm> 0.45) and the standard SRA to detect the presence of heparin-dependent platelet-activating antibodies (SRA-positive: release >20% with 0.1-0.3 IU/mL of unfractionated heparin). We developed an enhanced SRA (eSRA) by adding increasing concentrations of exogenous PF4 (0-100 μg/mL) to detect sub-threshold levels of platelet activating antibodies undetectable in the standard SRA (eSRA-positive: release >20%). Samples tested were referred for HIT testing by the McMaster Platelet Immunology Laboratory (Hamilton, Canada). Results: Sera from healthy individuals (n=10) and from suspected HIT patients with a negative anti-PF4/heparin EIA (n=15) did not demonstrate platelet activation in the eSRA at any dose of exogenous PF4 added. SRA-positive sera (n = 7), diluted sufficiently that they were non-reactive in the standard SRA, demonstrated PF4 dose-dependent platelet activation in the eSRA. This confirmed the increased sensitivity of the eSRA in detecting low-titre platelet-activating antibodies. Reactivity in the eSRA was inhibited by high heparin (100 U/mL) and by blocking the platelet FcgRIIa receptor with the monoclonal antibody IV.3. We then tested samples (n=24) referred for HIT testing that were positive in the anti-PF4/heparin EIA (optical densities OD405nm 0.7 to 2.4) but negative in the standard SRA. Heparin-dependent platelet activation (20-99% release) was demonstrated in 11 of 24 (46%) in the eSRA. This reactivity directly correlated with the amount of PF4 added to the platelets (optimal concentration of PF4 12.5 - 100 μg/mL) but not with the strength (OD405nm) of the anti-PF4/heparin EIA. In further investigations, we concentrated (4-fold) 7 of the 11 eSRA-positive samples in an attempt to increase the concentration of the antibodies. Of those 7 samples, 5 (71%) became positive in the standard SRA upon testing of the concentrated sample. Conclusions: These data indicate that low-titre platelet-activating antibodies may be found in some patients suspected of having HIT that test negative in the standard SRA irrespective of the strength (OD405nm) of the anti-PF4/heparin EIA. The immune response during heparin therapy can produce both families of pathogenic and non-pathogenic anti-PF4/heparin antibodies but it is the titre of the pathogenic antibody that may be necessary for platelet activation. Perhaps under permissive clinical conditions and with patient-specific factors, the titre of the pathogenic HIT antibodies may increase and lead to HIT. Disclosures Warkentin: Pfizer Canada: Honoraria; Instrumentation Laboratory: Honoraria; GlaxoSmithKline: Consultancy, Research Funding; W.L. Gore: Consultancy, Research Funding.

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Heparin-induced thrombocytopenia complicating extracorporeal membrane oxygenation support in pediatric patients: review of the literature and alternative anticoagulants

Perfusion ◽

10.1177/0267659118766723 ◽

2018 ◽

Vol 33 (1_suppl) ◽

pp. 7-17 ◽

Cited By ~ 9

Author(s):

Uri Pollak

Keyword(s):

Extracorporeal Membrane Oxygenation ◽

Current Knowledge ◽

Heparin Therapy ◽

Circulatory Support ◽

Platelet Factor ◽

Heparin Induced Thrombocytopenia ◽

Membrane Oxygenation ◽

Increased Risk ◽

Alternative Anticoagulation ◽

Thrombotic Complications

Heparin-induced thrombocytopenia (HIT) is a prothrombotic, immune-mediated complication of unfractionated heparin (UFH) and low molecular weight heparin therapy. HIT is characterized by moderate thrombocytopenia 5-10 days after initial heparin exposure, detection of platelet-activating anti-platelet factor 4/heparin antibodies and an increased risk of venous and arterial thrombosis. Extracorporeal membrane oxygenation (ECMO) is a form of mechanical circulatory support used in critically ill patients with respiratory or cardiac failure. Systemic anticoagulation is used to alleviate the thrombotic complications that may occur when blood is exposed to artificial surfaces within the ECMO circuit. Therefore, when HIT complicates patients on ECMO support, it is associated with a high thrombotic morbidity and mortality. The following article reviews the current knowledge in pediatric HIT, especially in ECMO patients, and the alternative anticoagulation options in the presence of HIT.

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Defining a second epitope for heparin-induced thrombocytopenia/thrombosis antibodies using KKO, a murine HIT-like monoclonal antibody

Blood ◽

10.1182/blood.v99.4.1230 ◽

2002 ◽

Vol 99 (4) ◽

pp. 1230-1236 ◽

Cited By ~ 87

Author(s):

Zhong Q. Li ◽

Weiyi Liu ◽

Kwang S. Park ◽

Brue S. Sachais ◽

Gowthani M. Arepally ◽

...

Keyword(s):

Monoclonal Antibody ◽

Binding Site ◽

Binding Sites ◽

Heparin Therapy ◽

Common Complication ◽

Platelet Factor ◽

Heparin Induced Thrombocytopenia ◽

The Third ◽

N Terminus ◽

A Site

Heparin-induced thrombocytopenia/thrombosis (HIT/T) is a common complication of heparin therapy that is caused by antibodies to platelet factor 4 (PF4) complexed with heparin. The immune response is polyclonal and polyspecific, ie, more than one neoepitope on PF4 is recognized by HIT/T antibodies. One such epitope has been previously identified; it involves the domain between the third and fourth cysteine residues in PF4 (site 1). However, the binding sites for other HIT/T antibodies remain to be defined. To explore this issue, the binding site of KKO, an HIT/T-like murine monoclonal antibody, was defined. KKO shares a binding site with many HIT/T antibodies on PF4/heparin, but does not bind to site 1 or recognize mouse PF4/heparin. Therefore, the binding of KKO to a series of mouse/human PF4 chimeras complexed with heparin was examined. KKO recognizes a site that requires both the N terminus of PF4 and Pro34, which immediately precedes the third cysteine. Both regions lie on the surface of the PF4 tetramer in sufficient proximity (within 0.74 nm) to form a contiguous antigenic determinant. The 10 of 14 HIT/T sera that require the N terminus of PF4 for antigen recognition also require Pro34 to bind. This epitope, termed site 2, lies adjacent to site 1 in the crystal structure of the PF4 tetramer. Yet sites 1 and 2 can be recognized by distinct populations of antibodies. These studies further help to define a portion of the PF4 tetramer to which self-reactive antibodies develop in patients exposed to heparin.

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Comparison of Clinical Outcomes in Patients with Heparin-Induced Thrombocytopenia Treated with Direct Thrombin Inhibitors.

Blood ◽

10.1182/blood.v104.11.3942.3942 ◽

2004 ◽

Vol 104 (11) ◽

pp. 3942-3942 ◽

Cited By ~ 2

Author(s):

John L. Francis ◽

Ranjeev Sandhu ◽

Alane Drexler ◽

John Dougherty

Keyword(s):

Length Of Stay ◽

Clinical Outcomes ◽

Clinical Syndrome ◽

Thrombin Inhibitors ◽

Direct Thrombin Inhibitors ◽

Efficacy And Safety ◽

Platelet Factor ◽

Platelet Recovery ◽

Heparin Induced Thrombocytopenia ◽

All Cause Mortality

Abstract Heparin-induced thrombocytopenia (HIT) is a clinical syndrome that has been reported to occur in 3–5% of patients treated with unfractionated heparin. If untreated, 36–50% of patients diagnosed with HIT develop life or limb-threatening thromboses. The occurrence of thrombosis, the most common serious complication of HIT, results in rates of amputation and death of 10–20% and 20–30% respectively. Thus, the desired clinical outcomes in patients with HIT are the prevention of thromboembolic complications, limb amputation, and death. The three direct thrombin inhibitors available in the U.S. are lepirudin, argatroban and bivalirudin. Lepirudin and argatroban have both been shown in clinical trials to significantly decrease the incidence of these complications in patients with HIT. Our institution also has experience with bivalirudin as treatment for HIT. We therefore sought to confirm whether all-cause mortality, length of stay, bleeding rate, time to platelet recovery, absolute change in platelet count following therapy, and percentage of therapeutic APTTs differed among patients treated with these agents at our institution. Data were collected by retrospective chart reviews, and from the Florida Hospital pharmacy computer system. Length of stay was calculated as the time to hospital discharge following the finding of a positive heparin-platelet factor 4 antibody test. For the purposes of comparison, the therapeutic range for APTT was taken as 50–90 seconds. As shown in the table, there were no statistically significant differences in any of the endpoints, when the efficacy and safety of the three direct thrombin inhibitors were compared. It therefore appears that within our institution, each of the direct thrombin inhibitors are equally efficacious and safe in treating the clinical syndrome of HIT, with similar outcomes with respect to length of stay, recovery of platelet counts, incidence of bleeding, and overall mortality. We conclude that selection of a direct thrombin inhibitor can be guided by the patient’s clinical status and organ function instead of efficacy and safety considerations. Drug n All-cause mortality (%) Length of stay (days) Bleeding (%) Time to platelet recovery (days) Therapeutic APTT (%) Lepirudin 7 28.5 11.0 28.5 5.3 70 Argatroban 20 30.0 15.1 20.0 5.2 65 Bivalirudin 24 25.0 18.7 25.0 5.4 74 P-value NS NS NS NS NS

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Heparin-Induced Thrombocytopenia (HIT): A Rural Community Based Experience.

Blood ◽

10.1182/blood.v110.11.3925.3925 ◽

2007 ◽

Vol 110 (11) ◽

pp. 3925-3925

Author(s):

N. Mullai ◽

Amanda Brock ◽

Shona Harper

Keyword(s):

Rural Community ◽

Rapid Test ◽

Heparin Therapy ◽

Serotonin Release ◽

Rural Setting ◽

Thrombin Inhibitor ◽

Test Results ◽

Community Based ◽

Heparin Induced Thrombocytopenia ◽

Release Assay

Abstract Background: Heparin-induced thrombocytopenia (HIT) is a known complication of heparin therapy. This study was planned to assess the experience of a community based medical practice with HIT in a rural setting. Method: A retrospective study was done from medical records of patients suspected clinically of HIT from January 2006 to January 2007. The data were analyzed with regard to test results of patients, especially those who were positive for the HIT antibody and correlated with national statistics. Result: Fifty-two (52) patients were suspected clinically of having HIT during the study period. All 52 patients received heparin and most of them had cardiac surgery before the onset of thrombocytopenia. Six out of fifty-two (6/52) patients were found to have positive HIT antibody. Two out of six (2/6) also had positive serotonin release assay. Two out of six (2/6) developed heparin-induced thrombocytopenia with thrombosis (HITT). One of the two patients with HITT died of complications. The range of time to obtain test results was 5–7 days. Four out of fifty-two (4/52) patients received thrombin inhibitor lepirudin (Refludan) as alternate anticoagulation. Conclusion: The overall incidences, time of onset, relation to heparin treatment were similar to that of national averages. The time to obtain diagnostic test results ranged 5–7 days and heparin was withheld in all of them, and more expensive anticoagulation was used for some of them while waiting for the test results. This dilemma in diagnosis and treatment could be avoided if a rapid test that can help to assess the risk early in about 12–24 hrs, is possible. Such a test would be very beneficial especially in small, rural community settings where the availability of expensive testing and medications for HIT are limited.

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