Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Children with cyanotic congenital heart disease who undergo operation with cardiopulmonary bypass are at increased risk of thromboembolic or hemorrhagic complications, or both. Regulation of thrombin, a key enzyme in coagulation, is essential in preventing these complications. We therefore examined the in vitro capacity of plasma from 15 children with cyanotic congenital heart disease to generate thrombin and to inhibit 125I-thrombin before and after cardiopulmonary bypass. We also assessed whether thrombin had been generated in vivo by assaying levels of fibrinogen, thrombin-antithrombin III complexes, and D-dimer. Plasma levels of the thrombin inhibitors, antithrombin III, alpha-2-macroglobulin, and heparin cofactor II were also measured. Thrombin regulation was normal before operation. After cardiopulmonary bypass, the in vitro capacity to generate thrombin decreased by 50%, and this was primarily a result of hemodilution (31%). Similar postoperative decreases were noted in the levels of antithrombin III, heparin cofactor II, and alpha-2-macroglobulin (26% to 45%). However, the total in vitro plasma thrombin inhibitory capacity decreased by only 13%. Levels of thrombin-antithrombin III and D-dimer increased after operation, indicating that thrombin had been generated and inhibited in vivo. Clinically, there were no thromboembolic complications although six patients required replacement therapy for excessive small-vessel bleeding. In conclusion, thrombin regulation is significantly altered after cardiopulmonary bypass. Although thrombin is generated in vivo, the total residual capacity to do so is impaired because of hemodilution. Despite a concomitant decrease in thrombin inhibitor levels, the total residual in vitro capacity of plasma to inhibit thrombin is relatively spared. This suggests that after cardiopulmonary bypass the risk of hemorrhagic complications after an additional hemostatic challenge is relatively greater than the risk of thrombotic complications. This might be reflected in the predominance of hemorrhagic complications in our patients.
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PMID:Thrombin regulation in congenital heart disease after cardiopulmonary bypass operations. 830 75

Unfractionated heparin (UFH) is immunogenic, and heparin-dependent antibodies can be demonstrated 5 to 10 days postoperatively in 25% to 50% of adult postcardiac surgery patients. In a minority of these cases (1% to 3% if UFH is continued longer than 1 week) these antibodies strongly activate platelets, causing thrombocytopenia and massive thrombin generation (HIT syndrome). HIT is an intensely procoagulant disorder, and in adult cardiac surgery patients carries both significant thrombotic morbidity (38% to 81%) and mortality (28%). Despite the ubiquitous use of UFH in pediatric intensive care units, and the repeated and sustained exposures to UFH in neonates and young children with congenital heart disease, HIT has been infrequently recognized and reported in this patient population. However, emerging experience at our institution and elsewhere suggests that HIT is significantly under-recognized in pediatric congenital heart disease patients, and may in fact have an incidence and associated thrombotic morbidity and mortality in this patient group comparable to that seen in adult cardiac surgery patients. This article will review HIT in pediatric patients with congenital heart disease and emphasize the special challenges posed in clinical recognition, laboratory diagnosis, and treatment of HIT in this patient group. We will also outline our experience with the off-label use of the direct thrombin inhibitor, argatroban, in pediatric patients with HIT.
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PMID:Heparin-induced thrombocytopenia (HIT) in pediatric cardiac surgery: an emerging cause of morbidity and mortality. 1528 65

Warfarin is the primary treatment for those with atrial fibrillation at increased risk for stroke. The Randomized Evaluation of Long-Term Anticoagulation Therapy (RELY) trial demonstrated that dabigatran, a direct thrombin inhibitor, was associated with lower rates of systemic embolism compared to warfarin.1 Although individuals with a creatinine clearance of less than 30 mL/min were excluded from the trial, the FDA approved the use of dabigatran for those with creatinine clearances as low as 15 mL/min, with a lower dose of dabigatran recommended for individuals with creatinine clearances below 30 mL/min. This study calculated Glomerular Filtration Rates (GFR) via three existing formulas with varying levels of accuracy (ie, the Cockcroft-Gault, Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]) to evaluate how patient eligibility for the RELY trial may have varied depending upon the formula used. A retrospective study was performed based on a chart review conducted at a private cardiologist's office in Honolulu, Hawai'i using patients with non-valvular atrial fibrillation. Patients included were those with a BUN/Creatinine assessment within 12 months of the chart review and a CHADS2 (Congestive Heart Disease, hypertension, age greater than 75, diabetes mellitus, and stroke or transient ischemic attack) score of 1 or greater. Of 376 subjects assessed, 64 subjects who failed to meet criteria for the RELY trial when using the Cockcroft-Gault formula (ie, GFR estimates were lower than 30 mL/min) met eligibility criteria when the MDRD formula was used (ie, GFR estimates exceeded 30 mL/min). Subgroup analysis of the 64 subjects revealed that subjects were 89-years-old on average, predominantly female (76.5%), and mostly Japanese (62.5%). Nearly one in five individuals (17%) in the studied population would have received a lower dose of dabigatran if the Cockcroft-Gaunt formula was used for estimating GFRs. The authors recommend caution while dosing dabigatran in the Asian population, as the estimates of kidney functioning vary substantially depending on the formula used to estimate GFR, which may in turn lead in some cases of inadequate dosing of dabigatran.
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PMID:A comparison of methods for estimating glomerular filtration rate for a population in Hawai'i with non-valvular atrial fibrillation. 2405 15

Bivalirudin is a direct thrombin inhibitor that is used as a procedural anticoagulant during percutaneous coronary interventions and cardiac surgery for patients with heparin-resistant thrombosis or heparin-induced thrombocytopenia. There is a robust literature describing its safety and efficacy in adults; however, its use in the pediatric population is relatively rare, with dosing extrapolated from adult data. In this case report, we describe a 4-year-old with complex congenital heart disease and history of heparin-induced thrombocytopenia who required bivalirudin dose uptitration during cardiac catheterization.
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PMID:Titration of Bivalirudin Infusion in the Pediatric Cardiac Catheterization Laboratory: A Case Report. 3090 52

Interventional cardiology procedures require full anticoagulation to prevent thrombus formation on catheters and devices with potential development of embolic complications. Bivalirudin, a short half-life direct thrombin inhibitor, has been largely used during percutaneous coronary interventions and represents the preferred alternative to heparin in patients with heparin-induced thrombocytopenia (HIT). However, few data are available about intraprocedural use of bivalirudin during transcatheter structural heart disease interventions. Activated clotting time (ACT) monitoring during bivalirudin infusion presents some limitations and it is not mandatory. We report a case of bivalirudin use in a patient with type-2 HIT during percutaneous mitral valve repair with the Mitraclip system (Abbott, Abbott Park, Illinois, United States). Despite use of standard bivalirudin dose (0.75 mg/kg bolus and 1.4 mg/kg/min infusion-reduced infusion rate was motivated by a glomerular filtration rate of 37 mL/min), the patient developed a large thrombus on the second clip during its orientation toward the mitral orifice. ACT was measured at that time and was suboptimal (240 seconds). The case was successfully managed with clip and thrombus retrieval, adjunctive 0.3 mg/kg bivalirudin bolus and increased infusion rate, and clip repositioning with ACT monitoring. This report makes the case for mandatory ACT checking and drug titration during high-risk catheter-based structural heart disease interventions, even when thromboprophylaxis is performed with bivalirudin. Additional coagulation tests may be useful to monitor bivalirudin response in similar cases.
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PMID:Antithrombotic Management during Percutaneous Mitral Valve Repair with the Mitraclip System in a Patient with Heparin-Induced Thrombocytopenia. 3124 65