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.)

Treatment strategies for complex patients with pulmonary embolism (PE) are often debated given patient heterogeneity, multitude of available treatment modalities, and lack of consensus guidelines. Although multidisciplinary Pulmonary Embolism Response Teams (PERT) are emerging to address this lack of consensus, their impact on patient outcomes is not entirely clear. This analysis was conducted to compare outcomes of all patients with PE before and after PERT availability. We analyzed all adult patients admitted with acute PE diagnosed on computed tomography scans in the 18 months before and after the institution of PERT at a large tertiary care hospital. Among 769 consecutive inpatients with PE, PERT era patients had lower rates of major or clinically relevant nonmajor bleeding (17.0% vs 8.3%, p = 0.002), shorter time-to-therapeutic anticoagulation (16.3 hour vs 12.6 hour, p = 0.009) and decreased use of inferior vena cava filters (22.2% vs 16.4%, p = 0.004). There was an increase in the use of thrombolytics/catheter-based strategies, however, this did not achieve statistical significance (p = 0.07). There was a significant decrease in 30-day/inpatient mortality (8.5% vs 4.7%, p = 0.03). These differences in outcomes were more pronounced in intermediate and high-risk patients (mortality 10.0% vs 5.3%, p = 0.02). The availability of multidisciplinary PERT was associated with improved outcomes including 30-day mortality. Patients with higher severity of PE seemed to derive most benefit from PERT availability., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Bleeding is one of the most feared complications of flexible bronchoscopy. Although infrequent, it can be catastrophic and result in fatal outcomes. Compared to other endoscopic procedures, the risk of morbidity and mortality from the bleeding is increased, as even a small amount of blood can fill the tracheobronchial tree and lead to respiratory failure. Patients using antithrombotic agents (ATAs) have higher bleeding risk. A thorough understanding of the different ATAs is critical to manage patients during the peri-procedural period. A decision to stop an ATA before bronchoscopy should take into account a variety of factors, including indication for its use and the type of procedure. This article serves as a detailed review on the different ATAs, their pharmacokinetics and the pre- and post-bronchoscopy management of patients receiving these medications., Competing Interests: Conflict of interest: None declared., (Copyright ©ERS 2017.)

Pulmonary embolism (PE) is a common thrombotic event that is variable in its presentation. Depending on the patients' risk for mortality, guidelines provide several treatment strategies including thrombolysis, catheter-directed therapies, pulmonary embolectomy, anticoagulation, and inferior vena cava filters. However, there is considerable disagreement between guidelines regarding the optimal treatment strategy for patients, particularly for those with intermediate-risk PE. In order to provide rapid and individualized care, PE response teams (PERT) have been developed. These teams consist of members from different specialties with a particular interest in PE, varying technical skills, and clinical experience, thereby allowing for a multidisciplinary approach. PERT allows for consensus decision making, and for rapid intervention in patients whose conditions worsen. In this review, we provide an overview of treatment guidelines for PE, and of results from recent clinical trials involving patients with submassive PE. In addition, we discuss an outline of our approach and use of PERT.

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.

Some patients need higher-than-expected doses of warfarin (Coumadin) to get their international normalized ratio (INR) into the therapeutic range. The cause of warfarin resistance can be either acquired (eg, poor compliance, drug interactions, dietary interactions) or hereditary, but the genetic mechanisms of warfarin resistance are not well understood. This review offers an algorithm for the evaluation of patients with suspected warfarin resistance.

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.

Rectus sheath hematoma (RSH) is a known complication of anticoagulation therapy and a source of potential morbidity and mortality. Early diagnosis and appropriate treatment may help to prevent complications including hemodynamic instability, the abdominal compartment syndrome or multiorgan dysfunction. Although the diagnosis can be made clinically, it can be confirmed with computed tomography of the abdomen. Most patients can be managed conservatively; however, it is often necessary to suspend anticoagulation in the acute setting. Rectus sheath hematoma is not a contraindication to resuming anticoagulation once the hematoma has been adequately managed and the patient has returned to a stable clinical baseline.

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.

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.

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.