Search

Heparin-induced thrombocytopenia (HIT) is a life-threatening complication of heparin therapy. Heparin is generally avoided in patients with a history of HIT; however, it remains the anticoagulant of choice for cardiac surgery requiring cardiopulmonary bypass (CPB) because of limited experience with alternative anticoagulants such as direct thrombin inhibitors (DTIs) during CPB. We report outcomes of surgery requiring CPB (30-day mortality, rate of thrombosis, and hemorrhage) in patients with prior HIT who received either heparin or a DTI intraoperatively. Seventy-two patients with a prior diagnosis of HIT confirmed by a positive serotonin release assay underwent CBP with a positive HIT antibody at the time of surgery. Thirty-day mortality was 0 and 8.5% in the DTI and heparin cohorts ( p  = 0.277). Thrombotic events occurred in 1 (7.7%) of the patients treated with DTI and 15 (25.4%) receiving heparin ( p  = 0.164). In the DTI cohort, 7 (53.8%) had minimal bleeding, 5 (38.5%) had mild bleeding, 1 (7.8%) had moderate bleeding, and none had severe bleeding. In the heparin group, 16 (27.1%) had minimal bleeding, 14 (23.7%) had mild bleeding, 25 (42.4%) had moderate bleeding, and 4 (6.8%) had severe bleeding ( p  = 0.053). DTI was associated with a lower rate of moderate to severe hemorrhage than heparin (odds ratio 0.097 [95% confidence interval 0.011-0.824], p  = 0.033) in a logistic regression model adjusted for thrombocytopenia and length on bypass. DTI appears to be safe in selected patients undergoing CPB after a diagnosis of HIT, and was not associated with higher rates of 30-day mortality, thrombosis, or hemorrhage., Competing Interests: None declared., (Georg Thieme Verlag KG Stuttgart · New York.)

Background: Heparin-induced thrombocytopenia (HIT) is an adverse immune-mediated response to unfractionated heparin and, less commonly, low molecular weight heparin. It is associated with a high thrombotic risk and the potential for limb and life-threatening complications. Argatroban is the only approved and currently available anticoagulant for HIT treatment in the USA., Objectives: To report safety and efficacy outcomes with bivalirudin for HIT treatment., Methods: We retrospectively examined records from our registry of patients with a suspected, confirmed or previous history of HIT and who had received bivalirudin for anticoagulation in a single tertiary-care center over a 9-year period., Results: We identified 461 patients who received bivalirudin: 220 (47.7%) were surgical patients, and 241 (52.3%) were medical patients. Of this population, 107 (23.2%) were critically ill, and 109 (23.6%) were dialysis-dependent. Suspected, confirmed and previous history of HIT were reported in 262, 124 and 75 patients, respectively. Of 386 patients with suspected or confirmed HIT, 223 patients (57.8%) had thrombosis at HIT diagnosis. New thrombosis was identified in 21 patients (4.6%) while they were on treatment with therapeutic doses of bivalirudin. No patient required HIT-related amputation. Major bleeding occurred in 35 patients (7.6%). We found a significant increase in major bleeding risk in the critically ill population (13.1%; odds ratio 2.4, 95% confidence interval 1.2-4.9, P = 0.014). The 30-day all-cause mortality rate was 14.5% (67 patients), and eight of 67 (1.7%) deaths were HIT-related., Conclusion: Bivalirudin may be an effective and safe alternative option for the treatment of both suspected and confirmed HIT, and appears to reduce the rate of HIT-related amputation., (© 2014 International Society on Thrombosis and Haemostasis.)

Because of an extreme risk for thromboemboli, patients with suspected heparin-induced thrombocytopenia (HIT) require immediate initiation of an alternative anticoagulant. The only therapies approved by the Food and Drug Administration require intravenous infusion of expensive direct thrombin inhibitors. This prospective, randomized, open-label, exploratory study compared the clinical and economic utility of subcutaneous desirudin vs argatroban, the most frequently used agent for suspected or immunologically confirmed HIT, with or without thrombosis. Sixteen patients were randomized to treatment with fixed-dose desirudin (15 or 30 mg) every 12 hours or activated partial thromboplastin time-adjusted argatroban by intravenous infusion. Arm A included 8 patients naive to direct thrombin inhibitor therapy, whereas Arm B included 8 patients on argatroban for at least 24 hours before randomization. The primary efficacy measure was the composite of new or worsening thrombosis (objectively documented), amputation, or death. Other end points included major and minor bleeding while on drug therapy, time to platelet count recovery, and pharmacoeconomics. No amputations or deaths occurred. One patient randomized to argatroban had worsening of an existing thrombosis. Major bleeding occurred in 2 patients on argatroban and in none during desirudin treatment. There was 1 minor bleed in each treatment group. The average medication cost per course of treatment was $1688 for desirudin and $8250 for argatroban. Desirudin warrants further study as a potentially cost-effective alternative to argatroban in patients with suspected HIT.

Background: Desirudin, a bivalent direct thrombin inhibitor (DTI), is approved by the US Food and Drug Administration for the prevention of deep vein thrombosis, which may lead to pulmonary embolism, in patients undergoing elective hip replacement surgery. It became available in the United States in March 2010., Objective: The goal of the present article was to provide an overview of the rationale and design of the PREVENT-HIT study, a randomized, prospective, open-label, active drug-controlled, exploratory trial comparing the clinical and economic utility of desirudin versus argatroban in patients with suspected heparin-induced thrombocytopenia (HIT), with or without thrombosis., Summary: The PREVENT-HIT study was designed to enroll approximately 120 patients from 20 to 25 US centers. All eligible patients were required to be aged >or=18 years. Patients with suspected HIT with or without thrombosis were divided into 2 treatment arms and randomized to receive treatment with desirudin or argatroban in a 1:1 ratio using a block randomization method. Arm A comprised patients who were naive to DTI therapy; arm B included patients whose condition was previously stabilized with intravenous argatroban. Desirudin was administered as a fixed-dose injection (15 or 30 mg SC q12h in patients without or with thrombosis, respectively). Argatroban was administered by continuous intravenous infusion in accordance with approved prescribing information or institutional prescribing guidelines at each study site. The primary efficacy outcome measure included the occurrence of any of the following up to 30 days after study drug discontinuation: new-onset or worsening thrombosis requiring discontinuation of study drug; amputation; or all-cause mortality. Other outcomes that were assessed included platelet recovery, bleeding, and pharmacoeconomic parameters. In addition, adverse events and other safety parameters were evaluated. Study enrollment began in November 2008 and ended in December 2009 due to slow enrollment (N = 16). The study results will be published separately., Conclusion: The results from the PREVENT-HIT study should enhance understanding of the comparative clinical and economic utility of desirudin and argatroban in patients with HIT with or without thrombosis. ClinicalTrials.gov identifier: NCT00787332.

Heparin-induced thrombocytopenia is an immune-mediated syndrome that results from unfractionated heparin or low molecular weight heparin exposure. It often remains unrecognized and undertreated and can cause limb and/or life-threatening thrombosis. The authors present 2 cases of thrombosis: one arterial and the other venous that occurred following endovascular abdominal aortic aneurysm repair. To the authors' knowledge, this is only the second report of arterial thrombosis and the first of deep vein thrombosis as a result of heparin-induced thrombocytopenia developing following endovascular abdominal aortic aneurysm repair. This underscores the importance of considering heparin-induced thrombocytopenia as a potential cause for postendovascular thrombotic complications in the patient who develops thrombocytopenia following this procedure.

We retrospectively evaluated argatroban dosing patterns, clinical outcomes, and the effects of heart failure and multiple organ system failure on dosing requirements in 65 adult, intensive care patients administered argatroban anticoagulation for clinically suspected heparin-induced thrombocytopenia (n=56) or history of heparin-induced thrombocytopenia (n=9). Argatroban was initiated then titrated to achieve target activated partial thromboplastin times 1.5 to 3 times normal control (ie, 42-84 seconds). Overall, argatroban was initiated at 1.14+/-0.62 microg/kg/min (mean+/-SD) and administered for 11.4+/-9.5 days, with comparable dosing patterns between patients with suspected, versus previous, heparin-induced thrombocytopenia. Sixty-four (98.5%) patients achieved target activated partial thromboplastin times, typically following no or one dose adjustment. Therapeutic doses were lower in patients with, versus without, heart failure (0.58+/-0.28 vs 0.97+/-0.6 microg/kg/min, P= .042) and decreased as the number of failed organ systems increased from 1 to 2 to =3 (1.10+/-0.67 vs 0.87+/-0.47 vs 0.58+/-0.47 microg/kg/min, P= .008). From argatroban initiation until patient discharge or death, 11 (16.9%) patients (3 off argatroban) developed thromboembolic complications; 14 (21.5%) died (11 off argatroban, 7 from multiple organ system failure); and 1 (1.5%) required amputation. Nine patients (13.8%) experienced bleeding, none fatal. This experience suggests that argatroban administered at approximately 1 micro/kg/min provides adequate levels of anticoagulation in many intensive care unit patients with suspected or previous heparin-induced thrombocytopenia. Reduced doses are needed when heart failure or multiple organ system failure is present.

Background: Argatroban, a direct thrombin inhibitor that has reduced clearance in elderly versus younger volunteers, is used for thromboprophylaxis or treatment in heparin-induced thrombocytopenia (HIT)., Objective: To evaluate the effect of aging on argatroban therapy, including dosage, anticoagulant responses, clinical outcomes and factors influencing those responses, in elderly patients with HIT or a history of HIT., Methods: This was a retrospective multicentre database analysis of 118 inpatients treated with argatroban at six medical centres between August 2001 and January 2005. Sixty-two adults aged >/=65 years were administered argatroban for clinically diagnosed HIT (n = 54) or a history of HIT (n = 8). Argatroban infusion was adjusted to achieve activated partial thromboplastin times (aPTTs) 1.5-3 times baseline. All study measures and analyses were prospectively defined. Argatroban dosage patterns, aPTTs and platelet count responses, and 37-day outcomes (death, amputation, new thrombosis, major bleeding) were summarised for patients stratified by age (65-74 years [n = 31]; 75-84 years [n = 26]; >/=85 years [n = 5]) to identify possible age-related trends. Regression analyses explored relationships between dose and patient age, liver function and renal function. Cox proportional hazards models evaluated the effect of age, dose, gender, aPTT and platelet count on the risk of new thrombosis., Results: In each age group, the median argatroban dosage was initially 1.0 microg/kg/min and was generally maintained at or near that dose during therapy (median, 5-7 days). Therapeutic aPTTs occurred within 11.5 hours; the median aPTT during therapy was 54.7 seconds, without obvious trend by age. By regression analysis, the initial and mean argatroban dosages decreased 0.08-0.09 microg/kg/min with each 0.2 mg/dL increase in serum creatinine, but no association was detected between dose and patient age, serum total bilirubin, calculated creatinine clearance or blood urea nitrogen. Platelet counts recovered within 6-7 days of initiating therapy, without apparent trend by age. No patient experienced amputation or major bleeding, and no patient in the oldest group died or had new thrombosis. Overall, 13 (21%) patients died (9 in the 65-74 years group; 1 receiving argatroban) and 5 (8%) had new thrombosis (4 in the 65-74 years group; 2 receiving argatroban), comparing favourably with previously reported rates, irrespective of patient age. By univariate (but not multivariate) analysis, the risk of new thrombosis decreased with increasing argatroban dose (hazard ratio 0.020; 95% CI 0.001, 0.757; p = 0.035). No effect of age or the other covariates considered on thrombotic risk was detected., Conclusion: Argatroban at a median initial dosage of 1.0 microg/kg/min, adjusted to achieve median aPTTs of 54.7 seconds during therapy, generally provided safe, adequate anticoagulation across a wide age range in elderly patients with HIT or a history of HIT. In these elderly patients, age was not a significant determinant of argatroban dosage or thrombotic risk. Prospective evaluation of this initial dose of argatroban in the elderly is warranted.

Heparin-induced thrombocytopenia (HIT) is an important adverse reaction of heparin therapy that can have catastrophic consequences if overlooked or misdiagnosed. Treatment with either unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) can trigger this complication. Orthopedic, cardiac, and vascular surgery patients exposed to prophylactic or therapeutic doses of heparin are at particular risk. Awareness of the clinical features and different presentations of HIT are essential for preventing severe morbidity and mortality associated with this disease.

Background: Heparin-induced thrombocytopenia (HIT) can lead to catastrophic thromboembolic complications and requires treatment with an alternative, rapidly active anticoagulant, such as a direct thrombin inhibitor (DTI), either to prevent or treat these complications. Switching to oral warfarin after initial treatment with a DTI is necessary in most patients. Most references related to warfarin suggest that an increased risk for bleeding will occur with elevated international normalized ratios (INRs) > 4.6. In patients receiving argatroban, it is not uncommon to achieve an INR > 4 during this transition. Because the clinical outcomes in patients achieving an INR > 4 during combined argatroban/warfarin therapies for HIT are not well described, we evaluated the clinical outcomes of 111 patients with this phenomenon., Methods: We identified patients from the prospective studies of argatroban anticoagulation, Argatroban-911 and Argatroban-915. Data collected from these studies included death from all causes, amputation, new thrombosis, major bleeding, INR values, argatroban doses, aPTT values, platelet counts, and duration of therapy., Results: Patients were on argatroban monotherapy for a median of 2.8 (0.1-8.1) days, and on cotherapy for a median of 3.7 (0.9-12.8) days. The median platelet count was 70.9 (18-325) x 10(9)/L at the time of HIT diagnosis and increased to 94 (30-324) x 10(9)/L by the time warfarin was initiated. At a median argatroban dose of 1.4 (0.2-2.0) mcg/kg/min, the maximum INR ranged from 4.1 to 21.2 (median 6.4, n = 111) and the corresponding aPTT ranged from 48.1 to 105 (median 71, n = 93) seconds. After argatroban cessation, the first recorded INR within 4 to 24 hours ranged from 1.5 to 12.5 (median 2.9, n = 58). Adverse clinical outcomes occurred in 9 (8.1%) patients during cotherapy and in 12 (10.8%) patients after argatroban anticoagulation was discontinued. Adverse clinical outcomes included 7 cases of new thrombosis, 3 amputations, 12 deaths and 1 major bleed. Eleven of 12 (91.7%) patients died due to causes other than thrombosis, and most deaths (83%) occurred following cotherapy. Five (4.5%) patients developed new thrombosis during argatroban/warfarin cotherapy despite an INR > 4. In contrast only 1 (0.9%) patient experienced major bleeding., Conclusion: In patients receiving argatroban/warfarin cotherapy and with an elevated INR > 4, the risk for thrombosis exceeds the risk of bleeding. Traditional paradigms concerning elevated INRs and warfarin may need to be redesigned for the patient population on cotherapy with direct thrombin inhibitors.Abbreviated Abstract. The clinical outcomes of 111 patients with INRs > 4 while on combined argatroban (dose < or = 2 mcg/kg/min) and warfarin were evaluated. Adverse clinical outcomes (7 new thrombosis, 3 amputations, 12 deaths and 1 major bleed) occurred in 21 patients. Eleven deaths were due to causes other than thrombosis. Five patients developed new thrombosis while only 1 had major bleeding. The risk for thrombosis exceeds the risk of bleeding in patients with HIT despite an INR > 4.

Heparin-induced thrombocytopenia (HIT) is a potentially devastating complication of therapy with either unfractionated or low-molecular-weight heparin. Thrombocytopenia is no longer essential for the diagnosis of HIT, since a 50% drop in the platelet count may be a more specific indicator. Once HIT is clinically suspected, heparin should be stopped immediately and direct thrombin inhibitor therapy started; waiting for laboratory confirmation may be catastrophic.

Recommendations for transitioning from therapy with heparin or a low-molecular-weight heparin preparation to therapy with an oral anticoagulant in patients with acute venous or arterial thromboembolism have undergone several changes during the last two decades. Physicians are now comfortable with beginning treatment with an oral anticoagulant once the diagnosis is confirmed, and loading doses are no longer considered to be necessary. Exceptions to early transition may be necessary in patients with an extensive iliofemoral or axillary-subclavian vein thrombosis or pulmonary embolism where thrombolytic agents may be indicated, or in individuals who require surgery or other invasive procedures, or if there are concerns about bleeding. The avoidance of early transition to oral anticoagulants in patients with acute heparin-induced thrombocytopenia also has been advised because of the potential for further thrombotic complications, including venous limb gangrene and warfarin-induced skin necrosis.

Background: Heparin-induced thrombocytopenia (HIT) is a common, often catastrophic, syndrome that produces the most hypercoagulable of states. Emerging therapeutic strategies use alternative anticoagulants; warfarin's place is being reexamined. Early in the course of warfarin therapy, there may be net procoagulant effects because of the inhibition of protein C. With HIT, it has been suggested that unopposed warfarin can precipitate venous limb gangrene. There are also reports of warfarin-induced skin necrosis. We seek to confirm and increase awareness of the risks of warfarin with HIT., Methods: We describe 6 patients with HIT seen at 3 medical centers in whom frank or impending venous limb gangrene, central skin necrosis, or both were temporally related to warfarin initiation., Results: At warfarin initiation, 5 patients had recognized HIT and 1 had it recognized later. Complications emerged after 2 to 7 days, and consisted of warfarin-induced skin necrosis (n = 5) and venous limb gangrene (n = 2); 1 patient had both. This emerged with unopposed warfarin in 4 patients and as a direct thrombin inhibitor was being withdrawn in 2. All had supratherapeutic international normalized ratios. One patient required leg and breast amputations, and another one died., Conclusions: Because of the early effects on protein C, warfarin can precipitate venous limb gangrene and/or skin necrosis in the extreme hypercoagulable milieu of HIT. With HIT, unopposed warfarin should be avoided and caution is needed during transition from a direct thrombin inhibitor. Warfarin should be initiated at modest doses in patients with HIT after platelet recovery. Implications extend to warfarin initiation with other thrombotic diatheses.

Lepirudin is indicated for anticoagulation in patients with heparin-induced thrombocytopenia (HIT). We describe 2 cases of HIT and thrombosis in children with heart disease, including one that required extracorporeal membrane oxygenation. Lepirudin, dosed in the recommended adult weight--based fashion, was an effective antithrombotic agent in pediatric patients with HIT.

Autoimmune thrombocytopenia purpura frequently is first noted during pregnancy. The severity of the disorder varies, but when the patient presents with active bleeding from any site, therapy is mandatory. Treatment generally consists of corticosteroids and/or splenectomy. A woman developed severe autoimmune thrombocytopenia purpura during pregnancy that proved refractory to corticosteroids and splenectomy. Six days after delivery her platelet count returned to normal. The etiology of autoimmune thrombocytopenia purpura remains unknown, but this experience suggests that in this patient the thrombocytopenia was related to her pregnancy.

Patients with thrombocytopenia have an increased risk of bleeding. We have used 18 courses of aminocaproic acid in 17 patients with either immune or nonimmune thrombocytopenia to successfully control hemorrhage associated with reduced platelet counts. The types of hemorrhage controlled included the following: vaginal, gastrointestinal, intracerebral, cutaneous, mucous membrane, subconjunctival, and renal, as well as that associated with dental extractions, tracheostomy, and sites of Penrose drains. The number of platelet and red blood cell transfusions administered decreased substantially following institution of aminocaproic acid therapy. We conclude that therapy with aminocaproic acid is safe and useful in the management of bleeding in patients with both immune and nonimmune thrombocytopenia.