hirudin and Blood-Loss--Surgical

Topics: Anticoagulants; Blood Loss, Surgical; Heparin; Hirudins; Humans; Peptide Fragments; Percutaneous Coronary Intervention; Randomized Controlled Trials as Topic; Recombinant Proteins; Treatment Outcome

Radial access for percutaneous coronary intervention (PCI) has been shown to be associated with better outcomes compared with femoral access. However, it is unknown whether bivalirudin would offer any further benefit when compared with unfractionated heparin for PCI with radial access.. A systematic search of electronic databases was conducted for randomized trials comparing bivalirudin with unfractionated heparin in patients undergoing PCI with a radial access. The primary safety outcome was major bleeding, while the primary efficacy outcome was major adverse cardiac events (MACE). Random effects overall risk ratios (RR) were calculated using DerSimonian and Laird model.. A total of 8044 patients from 5 trials were included in the final analysis. The incidence of major bleeding was 1.8% in the bivalirudin group versus 2.2% in the unfractionated heparin group (RR 0.72, 95% CI 0.44-1.17, p=0.18). Meta-regression analysis demonstrated that the risk of major bleeding was lower with bivalirudin when higher doses of unfractionated heparin were used in the control arm (p=0.02). The incidence of MACE was 8.5% in the bivalirudin group versus 7.5% in the unfractionated heparin group (RR 1.15, 95% CI 0.81-1.64, p=0.44). There were no significant differences in the incidence of all-cause mortality, and net adverse clinical events between both groups (RR 0.98, 95% CI 0.70-1.36, p=0.89; and RR 0.79, 95% C I0.60-1.03, p=0.08, respectively).. Bivalirudin might not be associated with better outcomes, when compared with unfractionated heparin in patients undergoing PCI with radial access.

Topics: Blood Loss, Surgical; Heparin; Hirudins; Humans; Incidence; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Radius; Randomized Controlled Trials as Topic; Recombinant Proteins; Regression Analysis; Treatment Outcome

Topics: Animals; Blood Coagulation Tests; Blood Loss, Surgical; Factor VIIa; Fibrinolytic Agents; Hemorrhage; Heparin; Hirudin Therapy; Hirudins; Humans; Platelet Aggregation; Rabbits; Recombinant Fusion Proteins

Recombinant hirudin (r-hirudin) is currently under development as an anticoagulant for use in surgery, therapeutic anticoagulation, disseminated intravascular coagulation and other pathologic states involving the generation of thrombin. Circulating levels of r-hirudin as an antithrombotic agent range from 2 to 20 micrograms/ml (0.1-1.0 mg/kg) as determined in an animal model of stasis thrombosis. In order to establish a relationship between the r-hirudin circulating level and bleeding, we utilized a rabbit ear blood loss model. r-Hirudin did not produce any loss of blood at dosages up to 20 micrograms/ml i.v. (1.0 mg/kg). When the circulating levels were maintained at 20 micrograms/ml for periods of up to 3 h, no increase in blood loss was observed. At 50 and 100 micrograms/ml initial circulating levels (2.5 and 5.0 mg/kg) a dose-dependent increase in the blood loss was observed which was equivalent to that observed with 1.25 and 2.5 mg/kg i.v. heparin. Such levels of r-hirudin are not expected in clinical usage. In contrast to heparin, the anticoagulant actions of r-hirudin were not neutralized by protamine sulfate, platelet factor 4, other polycationic agents and heparinase. In our studies, the blood loss induced by greater than 2.0 mg/kg i.v. dosages of r-hirudin in an animal model was neutralized by the administration of an activated prothrombin complex concentrate at 25 U/kg. In a similar experimental setting, r-factor VIIa was also partially effective. These studies suggest that r-hirudin anticoagulation may not require neutralization, since bleeding effects are not observed at effective antithrombotic dosages in individuals with normal hemostatic status.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Antifibrinolytic Agents; Blood Loss, Surgical; Ear Diseases; Ear, External; Factor VIIa; Fibrinolytic Agents; Hemorrhage; Heparin; Heparin Antagonists; Heparin Lyase; Hirudins; Humans; Platelet Aggregation; Platelet Factor 4; Polysaccharide-Lyases; Protamines; Rabbits; Recombinant Proteins; Wounds, Stab

The safety and efficacy of bivalirudin during percutaneous coronary intervention (PCI) in high bleeding risk patients with chronic total occlusion lesions (CTO) has not been studied till date. The use of bivalirudin may increase the thrombotic events during CTO-PCI.Between May 2013 and April 2014, a total of 117 high bleeding risk patients with CTOs underwent PCI. Bivalirudin was used in 89 cases with different strategies, including standard usage, combination of heparin, and additional bolus of bivalirudin on the basis of standard usage. The clinical characteristics, procedural details and antithrombotic strategies were assessed, and the bleeding and ischemic events were evaluated. The first 7 of 9 patients with standard application of bivalirudin exhibited acute thrombogenesis in the procedure. Heparin was then added in decreasing amounts in the next 8 patients wherein no thrombosis occurred; however, 2 patients had bleeding complications. The subsequent 72 patients were randomly assigned to the heparin bolus or additional bivalirudin bolus groups before the percutaneous transluminal coronary angioplasty (PTCA) was performed. The baseline clinical characteristics and procedure information were identical in both the groups. There were no ischemic and bleeding events in both the groups during the 6-month follow-up.Monotherapy with bivalirudin in CTO-PCI should be treated with caution, as the potential risk of thrombogenesis may be due to the long procedure time, the frequent change of equipment and temporary blood flow convection. Combination of heparin or an additional bolus of bivalirudin before PTCA was observed to be likely to decrease the incidence of thrombogenesis.

Topics: Aged; Antithrombins; Blood Loss, Surgical; Coronary Occlusion; Female; Heparin; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Percutaneous Coronary Intervention; Postoperative Hemorrhage; Recombinant Proteins

In ISAR-REACT-4 (abciximab and heparin vs. bivalirudin for non-ST-elevation myocardial infarction [NSTEMI]), bivalirudin reduced the risk of bleeding after percutaneous coronary intervention (PCI) compared with unfractionated heparin plus abciximab (UFH + abciximab). Vascular closure devices (VCDs) may also prevent bleeding complications, and thus attenuate the benefit of bivalirudin. This analysis examined whether there exists an interaction on bleeding between VCDs and bivalirudin versus UFH + abciximab after PCI.. Patients with NSTEMI were randomly assigned to either receive UFH + abciximab or bivalirudin for PCI. The use of a VCD after femoral access was left to the operator's discretion. The effect of randomized treatment in patients who received a VCD was compared to that in patients with manual compression of the femoral access site. The primary end-point of this analysis was the 30-day incidence of ISAR-REACT-4 major bleeding.. A total of 1,711 patients were enrolled in this analysis. Among the 365 (21.3%) patients receiving a VCD, 188 (51.5%) were treated with UFH + abciximab and 177 (48.5%) with bivalirudin. ISAR- REACT-4 major bleeding was higher with UFH + abciximab than with bivalirudin, independent of whether a VCD was used (4.8% vs. 2.3% with VCD and 4.6% vs. 2.7% without VCD, Pint = 0.76). There were also no interactions between randomized treatment and VCDs with respect to any of the ischemic end-points or net clinical outcome (Pint > 0.56).. In patients undergoing PCI for NSTEMI, the reduction of major bleeding by bivalirudin compared with UFH + abciximab was not affected whether a VCD was used.

Topics: Abciximab; Antibodies, Monoclonal; Antithrombins; Blood Loss, Surgical; Collagen; Female; Heparin; Hirudins; Humans; Immunoglobulin Fab Fragments; Male; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Recombinant Proteins; Risk Factors; Vascular Closure Devices

Heparin-based anticoagulation for patients undergoing extracorporeal membrane oxygenation has many limitations, including a high risk of heparin-induced thrombocytopenia. However, little experience with other anticoagulants in these patients has been described. The aim of this study was to compare bivalirudin-based anticoagulation with heparin-based protocols in a population of patients treated with venovenous or venoarterial extracorporeal membrane oxygenation.. In this case-control study, 10 patients received bivalirudin (cases) and 10 heparin (controls). The target activated partial thromboplastin time (aPTT) was 45 to 60 seconds.. None.. aPTT variations >20% of the previous value were much more frequent in patients treated with heparin than in patients receiving bivalirudin (52 v 24, p < 0.001). The number of corrections of the anticoagulant dose was higher in the heparin group compared with the bivalirudin group (58 v 51), although it did not reach statistical significance. Bleeding, thromboembolic complications, extracorporeal membrane oxygenation (ECMO) support duration, mortality, and the number of episodes of aPTT >80 seconds were not different between the 2 groups. A further analysis was performed in the bivalirudin group according to the presence of acute renal failure requiring continuous venovenous hemofiltration. The median bivalirudin dose in patients with or without hemofiltration was 0.041 (0.028-0.05) mg/kg/h and 0.028 (0-0.041) mg/kg/h, respectively (p = 0.2).. Bivalirudin-based anticoagulation may represent a new method of anticoagulation for reducing thromboembolic and bleeding complications, which still jeopardize the application of extracorporeal membrane oxygenation. Moreover, bivalirudin is free from the risk of heparin-induced thrombocytopenia. Higher doses of bivalirudin may be needed in patients undergoing hemofiltration.

Topics: Adult; Aged; Anticoagulants; Antithrombins; Blood Loss, Surgical; Case-Control Studies; Cohort Studies; Extracorporeal Membrane Oxygenation; Female; Heparin; Hirudins; Humans; Male; Middle Aged; Partial Thromboplastin Time; Peptide Fragments; Recombinant Proteins; Retrospective Studies

Replacing heparin with bivalirudin has been beneficial in patients undergoing coronary intervention and coronary artery bypass. The use of this alternative anticoagulant during peripheral bypass operations has not been studied. Concerns over distal thrombosis using this direct thrombin inhibitor (DTI) prompted a single-arm, open-label, pilot prospective trial of bivalirudin in patients undergoing lower extremity bypass to assess perioperative safety and efficacy.. Between 2006 and 2007, 18 patients met criteria for enrollment and underwent primary lower extremity bypass using bivalirudin. All patients had severe symptomatic atherosclerotic disease requiring lower extremity bypass. Bivalirudin at a bolus dose of 0.75 mg/kg and continuous infusion of 1.75 mg/kg/hr was used as the sole anticoagulant.. Patients (mean age, 67 years) underwent femoral-popliteal (n = 14) or femoral-tibial (n = 4) bypass preferentially using saphenous vein (83%). Mean operative time was 261 minutes, with bivalirudin infusion time of 95 +/- 26 minutes (mean +/- standard deviation). Reliable anticoagulation was achieved with weight-based dosing with activated clotting time values at baseline (systemic) of 131 +/- 92 seconds, during infusion (systemic) of 347 +/- 36 seconds, and from the distal vasculature (limb) of 345 +/- 66 seconds. Distal limb bivalirudin levels were stable at 9755 +/- 3860 ng/mL during clamp occlusion. Mean estimated blood loss was 332 +/- 191 mL with four patients (22%) requiring blood products. One patient required revision of the proximal anastomosis during the initial hospitalization. At 30 days, all bypass operations were patent with improvement of mean ankle-brachial index from 0.57 to 0.81. There were no deaths, myocardial infarctions, or amputations in the 30-day postoperative period. Based on the Thrombolysis in Myocardial Infarction classification for bleeding, one patient had major bleeding (>2 units of packed red blood cells), and three patients had minor bleeding within the first 30 days.. Bivalirudin is a safe and effective anticoagulant for lower extremity bypass operations. Thrombosis beyond the distal clamp was not seen. A comparative trial to standard anticoagulation is warranted.

Topics: Aged; Ankle Brachial Index; Anticoagulants; Arterial Occlusive Diseases; Blood Loss, Surgical; Hemorrhage; Hirudins; Humans; Infusions, Intravenous; Lower Extremity; Ohio; Peptide Fragments; Pilot Projects; Prospective Studies; Recombinant Proteins; Reoperation; Saphenous Vein; Thrombin; Thrombosis; Time Factors; Treatment Outcome; Vascular Patency; Vascular Surgical Procedures

General recommendations indicate that, during a carotid artery stenting (CAS), sufficient unfractionated heparin (UFH) has to be given to maintain the activated clotting time between 250 to 300 seconds. Bivalirudin use is able to reduce postprocedural bleedings in percutaneous interventions when compared with UFH. The study purpose was to evaluate, in a randomized study, the safety and efficacy of bivalirudin versus heparin during CAS, using proximal endovascular occlusion (PEO) as a distal protection device.. From January 2006 to December 2009, 220 patients undergoing CAS using PEO have been randomly assigned to one of the study arms (control arm: 100 UI/kg UFH or bivalirudin arm: 0.75 mg/kg intravenous bolus and intraprocedural infusion at 1.75 mg/kg/h).. Procedural success was achieved in all the patients. No episodes of intraprocedural thrombosis occurred. One major stroke occurred in the bivalirudin arm, and two minor strokes occurred, one in each group. A significant difference in the incidence of postprocedural bleedings was observed between the study groups; bivalirudin use was associated with reduced number of bleedings according to Thrombolysis In Myocardial Infarction criteria.. The use of bivalirudin should be considered a safe and effective anticoagulation regimen during CAS, using PEO as a distal protection device. Bivalirudin use is associated with a reduced incidence of bleedings.

Topics: Aged; Anticoagulants; Balloon Occlusion; Blood Loss, Surgical; Carotid Artery, Internal; Carotid Stenosis; Endovascular Procedures; Female; Heparin; Hirudins; Humans; Male; Peptide Fragments; Recombinant Proteins; Stents; Stroke; Thrombosis; Whole Blood Coagulation Time

Topics: Aged; Anticoagulants; Aprotinin; Blood Loss, Surgical; Coronary Artery Bypass; Coronary Disease; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Follow-Up Studies; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Probability; Prospective Studies; Recombinant Proteins; Reference Values; Risk Assessment; Single-Blind Method; Survival Analysis; Treatment Outcome

The coronary artery bypass grafting (CABG) heparin-induced thrombocytopenia thrombosis syndrome (HITTS) on- and off-pump safety and efficacy (CHOOSE-ON) trial was designed as a safety and efficacy trial of bivalirudin for use in anticoagulation during cardiopulmonary bypass (CPB) in patients with confirmed or suspected HIT and (or) antiplatelet factor 4/heparin (anti-PF4/H) antibodies.. In an open-label, multicenter trial, 50 patients were enrolled prospectively. The primary study endpoint was in-hospital acute procedural success, defined as the absence of death, Q-wave myocardial infarction (MI), repeat operation for coronary revascularization, and stroke at day seven after surgery or hospital discharge, whichever occurred first. The secondary study endpoints were procedural success, defined as the absence of death, Q-wave MI, repeat operation for coronary revascularization, and stroke, at 30 days and 12 weeks after surgery. Perioperative blood loss, transfusions, and the incidence of major bleeding events were also captured.. There were 49 patients treated with bivalirudin of which 43 had acute HIT and thrombosis syndrome (HITTS) with antibodies at time of surgery. Procedural success in-hospital or at 7 days was achieved in 46 (94%) patients. At day 30 procedural success was achieved in 42 (86%) patients, and after 12 weeks in 40 (82%) patients. Mean intraoperative blood loss was 575 +/- 524 mL, and mean 24-hour postoperative blood loss was 998 +/- 595 mL. Forty-one (84%) patients received transfusions before day 7 or discharge with a mean of 5.6 +/- 3.8 units of red blood cells, 8.6 +/- 7.2 units of platelets, and 6.0 +/- 4.7 units of fresh frozen plasma. No differences in outcome among bivalirudin-treated patients were observed between those in the overall group and those with moderately impaired renal function (n = 10).. The current investigation expands the experience of safe and effective anticoagulation with bivalirudin during CPB to patients with confirmed or suspected HIT and anti-PF4/H antibodies, including in the setting of impaired renal function.

Topics: Acute Disease; Aged; Aged, 80 and over; Antibodies; Anticoagulants; Blood Loss, Surgical; Cardiopulmonary Bypass; Erythrocyte Transfusion; Female; Heparin; Hirudins; Humans; Intraoperative Care; Male; Middle Aged; Peptide Fragments; Recombinant Proteins; Syndrome; Thrombocytopenia; Thrombosis; Time Factors; Treatment Outcome

Lepirudin, a recombinant hirudin, is a direct acting thrombin inhibitor that has been used as a heparin alternative in patients with heparin-induced thrombocytopenia requiring on-pump cardiac surgery. To evaluate the efficacy, safety, and clinical utility of lepirudin as a cardiopulmonary bypass (CPB) anticoagulant, we compared lepirudin with heparin in a routine CPB setting.. Twenty patients were randomly assigned to receive lepirudin (0.25 mg/kg b. w. bolus and 0.2 mg/kg b. w. added to the CPB priming) or heparin (400 U/kg b. w. bolus) with protamine reversal. Lepirudin and heparin anticoagulation during CPB was monitored using the ecarin clotting time or ACT, respectively and additional lepirudin (5 mg) or heparin (5000 U) boluses were administered.. The CPB circuit was performed in both groups without thromboembolic complications. Median blood loss during the first 36 hours was statistically higher ( P = 0.007) in the lepirudin group (1.226 +/- 316 ml) compared to the heparin group (869 +/- 189 ml). One patient of the lepirudin group developed pulmonary embolism 24 hours after surgery. This patient was tested homozygous for the FV-Leiden mutation.. Lepirudin provides effective CPB anticoagulation but induces a higher postoperative blood loss than heparin. Lepirudin should be restricted to patients undergoing CPB who cannot be exposed to heparin.

Topics: Anticoagulants; Blood Loss, Surgical; Cardiopulmonary Bypass; Coronary Artery Bypass; Coronary Artery Disease; Heparin; Hirudin Therapy; Hirudins; Humans; Intraoperative Period; Middle Aged; Postoperative Hemorrhage; Recombinant Proteins

Bivalirudin is a short-acting direct thrombin inhibitor, with advantages over unfractionated heparin for anticoagulation in cardiac surgery. We hypothesized that bivalirudin is not associated with a clinically important increase in blood loss compared with heparin with protamine reversal in patients undergoing off pump coronary artery bypass (OPCAB) surgery. We also assessed flow with angiography at 3 months using a modified Thombolysis in Myocardial Infarction (TIMI) grade in the grafted coronary arteries.. One hundred patients were randomly assigned to receive bivalirudin (0.75 mg/kg bolus, 1.75 mg/kg/h infusion) or heparin (150 to 300 U/kg bolus) with protamine reversal.. A median of 3 (range, 1 to 5) grafts were inserted per patient. Blood loss for the 12 hours after study drug initiation in the bivalirudin group (median, 793 mL; interquartile range, 532 to 1,214 mL; range, 320 to 4,909 mL; n = 50) was not significantly greater than in the heparin group (median, 805 mL; interquartile range, 517 to 1,117 mL; range, 201 to 2,567 mL; n = 50; p = 0.165). Median graft flow was 3.0 in the bivalirudin group (n = 40) and 2.67 in the heparin group (n = 39; p = 0.047). The bivalirudin group had more patients with grade 3 (ie, full) flow in at least 1 graft (100% versus 90%; p = 0.04), a trend toward more patients with grade 3 flow in all grafts (60% versus 38%; p = 0.06), and more grafts with grade 3 flow (82% versus 67%; p = 0.03).. Anticoagulation for OPCAB surgery with bivalirudin was feasible without a clinically important increase in perioperative blood loss. Graft flow was better in the bivalirudin patients; the impact of this on clinical outcomes requires a larger study.

Topics: Aged; Anticoagulants; Antithrombins; Blood Loss, Surgical; Coronary Artery Bypass; Drug Therapy, Combination; Female; Heparin; Heparin Antagonists; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Protamines; Recombinant Proteins; Treatment Outcome

Hirudin is an anticoagulant originally extracted from the leech Hirudo medicinalis. Using recombinant DNA technology a new compound, recombinant desulphato hirudin CGP 39393 has now been produced. The aim of this study was to determine the maximum tolerated dose in patients undergoing elective hip replacement. This open safety trial represents, to our knowledge, the first experience of recombinant hirudin in orthopedic patients. In this study 48 patients undergoing primary total hip replacement were included and the safety of subcutaneous injections of 10, 15, 20 and 40 mg CGP 39393 twice daily, was evaluated. Prophylaxis was started immediately pre-operatively and continued for 8-10 days. A mandatory bilateral phlebography was performed at the end of the prophylactic treatment period and a clinical follow-up was done 6 weeks after surgery. A major bleeding event occurred in the first 3 patients receiving 40 mg CGP 39393 b.i.d. and the prophylaxis regimen at this dosage level was therefore discontinued. Median values of total blood loss and requirements of blood transfusion in the patients receiving 10-20 mg CGP 39393 were similar to those reported in previous studies on total hip replacement performed at the same centre, using other prophylactic drugs. Deep vein thrombosis (DVT) was confirmed by phlebography in 5 out of 12 patients in the 10 mg group (41.7%, 95% confidence limits [CL]: 15.2-72.3%), 1 out of 11 patients in the 15 mg group (9.1%, CL: 0.23-41.3%) and 2 out of 20 patients in the 20 mg group (10.0%, CL: 1.2-31.7%) during the prophylaxis period. CGP 39393 was safe and well tolerated, when administered as subcutaneous injections of 10-20 mg twice daily. The dose level of 40 mg CGP 39393 twice daily resulted in serious disturbance of the hemostasis in patients after hip prosthesis surgery.

Topics: Adult; Aged; Aged, 80 and over; Blood Loss, Surgical; Dose-Response Relationship, Drug; Female; Fibrinolytic Agents; Hemorrhage; Hip Prosthesis; Hirudin Therapy; Hirudins; Humans; Injections, Subcutaneous; Male; Middle Aged; Partial Thromboplastin Time; Postoperative Complications; Recombinant Proteins; Risk Factors; Safety; Thrombin; Thromboembolism

Practice patterns in anticoagulant strategies used during percutaneous coronary intervention (PCI) in the United States for patients with non-ST-segment-elevation myocardial infarction and the comparative outcomes between bivalirudin and unfractionated heparin (UFH) have not been well described.. Trends in anticoagulant use were examined among 553 562 PCIs performed by 9254 operators at 1538 hospitals for non-ST-segment-elevation myocardial infarction from 2009 to 2014 within the CathPCI Registry. To compare bivalirudin with UFH, propensity score matching and instrumental variable (IV) methods with operator preference for bivalirudin as the instrument were used. To determine whether differences in outcomes were because of differences in glycoprotein IIb/IIIa inhibitor (GPI) use, a test of mediation was performed using the IV. Outcomes were in-hospital bleeding and mortality. Bivalirudin use increased from 2009 to 2013 but declined during 2014. GPI use was 50.5% during UFH PCIs and 12.0% during bivalirudin PCIs. Before GPI adjustment, bleeding reductions with bivalirudin ranged from 2.04% (IV: 95% confidence interval [CI]: 1.81%, 2.27%) to 2.29% (propensity score: 95% CI: 2.14%, 2.44%) and mortality reductions ranged from 0.16% (IV: 95% CI: 0.03%, 0.28%) to 0.25% (propensity score: 95% CI: 0.17%, 0.33%). After GPI adjustment in the IV, more than half the bleeding reduction with bivalirudin was because of the lower use of GPIs (risk difference, -0.84%; 95% CI: -1.11%, -0.57%), and no survival benefit was apparent (risk difference, -0.10%; 95% CI: -0.24%, 0.05%). Bleeding reductions with bivalirudin were largest for transfemoral PCI (GPI-adjusted risk difference, -1.11%; 95% CI: -1.43%, -0.80%) and negligible for transradial PCI (GPI-adjusted risk difference, 0.09%; 95% CI: -0.32%, 0.50%).. In the largest comparative analysis of bivalirudin versus UFH for non-ST-segment-elevation myocardial infarction to date, bivalirudin was associated with lower in-hospital bleeding and mortality given current practices with respect to GPI use and access site. Bleeding differences were, in part, explained by the greater use of GPIs with UFH. Reductions in bleeding were largest among those undergoing transfemoral PCI, whereas no bleeding benefit was observed for those treated with transradial PCI.

Topics: Aged; Antithrombins; Blood Loss, Surgical; Female; Hirudins; Hospital Mortality; Humans; Incidence; Inpatients; Male; Middle Aged; Non-ST Elevated Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Postoperative Hemorrhage; Practice Patterns, Physicians'; Recombinant Proteins; Registries; Retrospective Studies; Risk Factors; Treatment Outcome; United States

Outcomes with bivalirudin compare favorably with heparin ± GPIIb/IIIa receptor inhibition (heparin ± GPI) during percutaneous coronary intervention (PCI). Patients with congestive heart failure (CHF) have increased risk for complications. The objective was to investigate clinical and economic outcomes for bivalirudin ± GPI vs. heparin ± GPI among PCI patients with CHF.. Using the Premier Hospital Database, PCI patients with CHF were stratified by anticoagulant: bivalirudin, bivalirudin ± GPI, heparin and heparin ± GPI. The probability of receiving bivalirudin ± GPI was estimated using individual and hospital variables. Using propensity scores, each bivalirudin ± GPI patient was matched to a heparin ± GPI patient. The primary outcome was in-hospital death. Bleeding rates, transfusion, length of stay and in-hospital cost were ascertained.. Overall, 116,313 patients at 315 hospitals received bivalirudin (n = 45,559) bivalirudin + GPI (n = 8,115), heparin (n = 27,972) or heparin + GPI (n = 34,667). Patients had STEMI (21.2%), NSTEMI (29.1%), unstable angina (16.6%), stable angina (5.7%) or other ischemic heart disease (24.2%). Of these, 79.1% of bivalirudin patients matched, resulting in 84,948 analyzed patients. Compared with heparin ± GPI patients, bivalirudin ± GPI patients had fewer deaths (3.3% vs. 3.9%; p < 0.0001), less clinically apparent bleeding (10.2% vs. 11.4%; p < 0.0001), clinically apparent bleeding with transfusion (2.7% vs. 3.2%, p <0.0001), and transfusion (8.5% vs. 9.8%, p < 0.0001). Patients receiving bivalirudin had shorter length of stay (6.3 vs. 6.8 days; p < 0.0001) and lower in-hospital cost (mean $26,706 vs. $27,166 [median $19,414 vs. $19,798]; p < 0.0001). In conclusion, this is the largest retrospective analysis of PCI patients with CHF and demonstrates bivalirudin ± GPI compared with heparin ± GPI is associated with lower inpatient rates of death, bleeding, and cost.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Blood Loss, Surgical; Blood Transfusion; Cost-Benefit Analysis; Databases, Factual; Drug Costs; Female; Heart Failure; Heparin; Hirudins; Hospital Costs; Hospital Mortality; Humans; Length of Stay; Male; Middle Aged; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Recombinant Proteins; Retrospective Studies; Time Factors; Treatment Outcome; United States; Young Adult

Patients with a previous history of heparin-induced thrombocytopenia are at a higher risk for thromboembolic events, and heparin administration is formally contraindicated. Bivalirudin has been reported as an alternative therapy whenever an intervention that requires systemic anticoagulation and cardiopulmonary by-pass pump is needed. We present the case of a patient diagnosed with heparin-induced thrombocytopenia and heparin-PF4 (+) antibodies requiring a triple cardiac valve replacement who developed fulminant coagulopathy after bivalirudin administration. A discussion on the serious difficulties that the management of these types of patients involves, as well as a review of prevention strategies are presented.

Topics: Acute Kidney Injury; Aged; Anticoagulants; Antithrombins; Blood Loss, Surgical; Coronary Artery Bypass; Disseminated Intravascular Coagulation; Drug Substitution; Fatal Outcome; Heart Failure; Heart Valve Diseases; Heart Valve Prosthesis Implantation; Heparin; Hirudins; Humans; Immunoglobulin G; Intraoperative Complications; Male; Multiple Organ Failure; Peptide Fragments; Platelet Factor 4; Purpura, Thrombocytopenic, Idiopathic; Recombinant Proteins; Thrombophilia

This study sought to compared the use and effectiveness of bleeding avoidance strategies (BAS) by sex.. Women have higher rates of bleeding following percutaneous coronary intervention (PCI).. Among 570,777 men (67.5%) and women (32.5%) who underwent PCI in the National Cardiovascular Data Registry's CathPCI Registry between July 1, 2009 and March 31, 2011, in-hospital bleeding rates and the use of BAS (vascular closure devices, bivalirudin, radial approach, and their combinations) were assessed. The relative risk of bleeding for each BAS compared with no BAS was determined in women and men using multivariable logistic regressions adjusted for clinical characteristics and the propensity for receiving BAS. Finally, the absolute risk differences in bleeding associated with BAS were compared.. Overall, the use of any BAS differed slightly between women and men (75.4% vs. 75.7%, p = 0.01). When BAS was not used, women had significantly higher rates of bleeding than men (12.5% vs. 6.2%, p < 0.01). Both sexes had similar adjusted risk reductions of bleeding when any BAS was used (women, odds ratio: 0.60, 95% confidence interval [CI]: 0.57 to 0.63; men, odds ratio: 0.62, 95% CI: 0.59 to 0.65). Women and men had lower absolute bleeding risks with BAS; however, these absolute risk differences were greater in women (6.3% vs. 3.2%, p < 0.01).. Women continue to have almost twice the rate of bleeding following PCI. The use of any BAS was associated with a similarly lower risk of bleeding for men and women; however, the absolute risk differences were substantially higher in women. These data underscore the importance of applying effective strategies to limit post-PCI bleeding, especially in women.

Topics: Aged; Antithrombins; Blood Loss, Surgical; Female; Hemostasis, Surgical; Hirudins; Humans; Male; Middle Aged; Myocardial Ischemia; Patient Selection; Peptide Fragments; Percutaneous Coronary Intervention; Postoperative Hemorrhage; Practice Patterns, Physicians'; Recombinant Proteins; Registries; Retrospective Studies; Risk Assessment; Sex Factors; Treatment Outcome; United States

Topics: Abciximab; Antibodies, Monoclonal; Antithrombins; Blood Loss, Surgical; Cardiac Catheterization; Collagen; Female; Heparin; Hirudins; Humans; Immunoglobulin Fab Fragments; Male; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Recombinant Proteins; Vascular Closure Devices

Patients that receive coronary bare-metal or drug-eluting stents have to be maintained on dual antiplatelet therapy (DAPT) for at least 4 weeks or 12 months, respectively. The prolonged time period required for drug-eluting stents is the result of delayed vascular healing that is associated with the drug and the polymeric coating. Premature cessation of DAPT may precipitate life-threatening stent thrombosis. However, some urgent, unplanned surgical procedures cannot be carried out under DAPT as a result of an unacceptable bleeding risk. Therefore, in these particular patients, DAPT therapy needs to be bridged for urgent surgery to avoid stent thrombosis, yet no clinical recommendation about a specific pharmacologic protocol is currently available for this specific purpose. We report about the initial experience with a novel institutional bridging protocol using bivalirudin that has been developed and applied successfully in a limited number of patients.

Topics: Antithrombins; Aspirin; Blood Loss, Surgical; Clopidogrel; Coronary Thrombosis; Drug-Eluting Stents; Hirudins; Humans; Peptide Fragments; Platelet Aggregation Inhibitors; Postoperative Hemorrhage; Recombinant Proteins; Stents; Surgical Procedures, Operative; Ticlopidine; Time Factors

In this case series, we describe our successful use of a reduced hirudin dosage as an anticoagulant during cardiac surgery using minimized extracorporeal circulation in patients with heparin-induced thrombocytopenia.

Topics: Aged; Anticoagulants; Blood Loss, Surgical; Blood Transfusion, Autologous; Coronary Artery Bypass; Erythrocyte Transfusion; Extracorporeal Circulation; Female; Fibrinolytic Agents; Heparin; Hirudins; Humans; Male; Middle Aged; Monitoring, Intraoperative; Partial Thromboplastin Time; Plasma; Postoperative Care; Recombinant Proteins; Thrombocytopenia; Whole Blood Coagulation Time

To retrospectively evaluate the safety and effectiveness of the use of bivalirudin, a direct thrombin antagonist, compared with unfractionated heparin in endovascular aneurysm repair (EVAR).. Between March 1994 and September 2007, 740 consecutive patients (mean age, 75.7 y +/- 7.7; 69 women) underwent elective EVAR for infrarenal abdominal aortic aneurysm. Bivalirudin was used in 98 of these 740 (13.2%) and unfractioned heparin was used in the other 642 (86.8%). Complications were classified according to the Society of Vascular Surgery/International Society for Cardiovascular Surgery criteria. Major bleeding was defined as clinically overt blood loss resulting in a decrease of hemoglobin of more than 3 g/dL, any decrease in hemoglobin of more than 4 g/dL, transfusion of 2 U or more of red blood cells, or intracranial or retroperitoneal hemorrhage.. Grade 1 major complications were observed in 161 of 642 patients (25.2%) in the heparin group and 12 of 98 patients (12.2%) in the bivalirudin group (P = .0046), whereas the incidences of grade 3 major complications were not significantly different between groups (P = .57). The rate of total complications was higher in the heparin group than in the bivalirudin group (247 of 642 [38.5%] vs 21 of 98 [21.4%]; P = .001). Major bleeding occurred in 10 of 98 patients (10.2%) receiving bivalirudin and in 91 of 642 patients (14.2%) receiving heparin (P = .34). One of 21 major complications (4.76%) in the bivalirudin group and 12 of 247 major complications (4.86%) in the heparin group were attributable to thrombosis (P = 1.0).. Bivalirudin is a safe and feasible alternative to unfractionated heparin in patients undergoing EVAR.

Topics: Aged; Aged, 80 and over; Anticoagulants; Aortic Aneurysm, Abdominal; Blood Loss, Surgical; Blood Transfusion; Blood Vessel Prosthesis Implantation; Feasibility Studies; Female; Hemoglobins; Hemorrhage; Heparin; Hirudins; Humans; Male; Peptide Fragments; Postoperative Hemorrhage; Recombinant Proteins; Retrospective Studies; Thrombin; Treatment Outcome

Topics: Aged; Aged, 80 and over; Anticoagulants; Blood Loss, Surgical; Coronary Artery Bypass; Endarterectomy, Carotid; Erythrocyte Transfusion; Female; Heparin; Hirudin Therapy; Hirudins; Humans; Male; Middle Aged; Monitoring, Intraoperative; Postoperative Hemorrhage; Thrombocytopenia

Heparin-induced thrombocytopenia (HIT) is a severe complication following the application of heparin; antibodies against complexes of heparin and PDF4 initiate activation of platelets. This may lead to massive thrombembolism, which is associated with a slight and transient drop of platelets in HIT I or a drop below 50% after approximately 5 days in HIT II. Further administration of heparin has to be strictly avoided in these patients. Immunologic evidence for HIT can easily be obtained by the heparin-induced platelet aggregation assay. If anticoagulation is necessary, different, alternative drugs are available. Recombinant hirudin (r-hirudin) is a well-established drug for safe anticoagulation. Monitoring is possible by estimating the plasma level of r-hirudin from the ecarin-clotting time. We report a case of a patient with prosthetic aortic valve endocarditis and HIT II who suffered from massive postoperative bleeding requiring massive substitution of blood components and coagulants caused by free circulating r-hirudin due to the use of a hemofilter.

Topics: Anticoagulants; Blood Loss, Surgical; Endocarditis; Equipment Design; Extracorporeal Circulation; Heart Valve Prosthesis; Hemofiltration; Hirudins; Humans; Male; Middle Aged; Recombinant Proteins; Thrombocytopenia

Aprotinin has recently been approved for clinical use in cardiopulmonary bypass. Although unfractionated heparin has been the only anticoagulant widely used for cardiopulmonary bypass, disadvantages involving heparin have led to ongoing investigations of alternative anticoagulant agents.. The objective of this study was to evaluate the efficacy of aprotinin in combination with other anticoagulant agents, specifically low molecular weight heparin and recombinant hirudin, using a dog model of cardiopulmonary bypass.. The blood conservation resulting from the use of aprotinin was observed only with unfractionated heparin. Efficacy of anticoagulation as measured by protein deposits in the bypass circuit filter revealed an unexpected reduction in the quantity of deposits when aprotinin was used in combination with low molecular weight heparin.. As alternative anticoagulant agents are sought, the potential benefits of aprotinin in the reduction of operative blood loss must be evaluated independently for each anticoagulant agent.

Topics: Animals; Anticoagulants; Antithrombins; Aprotinin; Blood Coagulation; Blood Loss, Surgical; Cardiopulmonary Bypass; Disease Models, Animal; Dogs; Drug Combinations; Filtration; Hemostatics; Heparin; Heparin, Low-Molecular-Weight; Hirudin Therapy; Hirudins; Male; Partial Thromboplastin Time; Recombinant Proteins

We determined changes in platelet aggregability following cardiopulmonary bypass, using optical aggregometry to assess macroaggregation in platelet-rich plasma (PRP), and platelet counting to assess microaggregation both in whole blood and PRP. Hirudin was used as the anticoagulant to maintain normocalcaemia. Microaggregation (%, median and interquartile range) in blood stirred with collagen (0.6 micrograms/ml) was only marginally impaired following bypass (91 [88, 93] at 10 min postbypass v 95 (92, 96] prebypass; n = 22), whereas macroaggregation (amplitude of response; cm) in PRP stirred with collagen (1.0 micrograms/ml) was markedly impaired (9.5 [8.0, 10.8], n = 41 v 13.4 [12.7, 14.3], n = 10; p < 0.0001). However, in PRP, despite impairment of macroaggregation (9.1 [8.5, 10.1], n = 12), microaggregation was near-maximal (93 [91, 94]), as in whole blood stirred with collagen. In contrast, in aspirin-treated patients (n = 14), both collagen-induced microaggregation in whole blood (49 [47, 52]) and macroaggregation in PRP (5.1 [3.8, 6.6]) were more markedly impaired, compared with control (both p < 0.001). Similarly, in PRP, macroaggregation with ristocetin (1.5 mg/ml) was also impaired following bypass (9.4 [7.2, 10.7], n = 38 v 12.4 [10.0, 13.4]; p < 0.0002, n = 20), but as found with collagen, despite impairment of macroaggregation (7.2 [3.5, 10.9], n = 12), microaggregation was again near-maximal (96 [93, 97]). The response to ristocetin was more markedly impared after bypass in succinylated gelatin (Gelofusine) treated patients (5.6 [2.8, 8.6], n = 17; p < 0.005 v control), whereas the response to collagen was little different (9.3 v 9.5).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aprotinin; Aspirin; Blood; Blood Loss, Surgical; Cardiopulmonary Bypass; Collagen; Hirudins; Humans; Nephelometry and Turbidimetry; Plasma; Platelet Activation; Platelet Aggregation; Platelet Count; Platelet Function Tests; Recombinant Proteins; Ristocetin

Recombinant desulphatohirudin HV1 (CGP 39393), a specific and potent peptidic inhibitor of thrombin, was evaluated as the sole anticoagulant in a dog model of cardiopulmonary bypass. CGP 39393 was administered as a bolus plus infusion for a 1-hour pump period at doses of 1.0 mg/kg + 0.75 mg.kg-1.h-1, 1.0 mg/kg + 1.50 mg.kg-1.h-1, 1.0 mg/kg + 2.25 mg.kg-1.h-1, or 1.0 mg/kg + 3.0 mg.kg-1.h-1 (n = 5 per group). The lowest dose was ineffective, as a high degree of clot formation (314 +/- 160 mg) occurred as determined by quantitation of protein deposits in the pump line filter. The three higher doses inhibited clot formation (35 to 44 mg) but did not reveal a dose-dependent effect (p = 0.308 between groups). All four doses produced the same amount of postoperative blood loss (6.5 to 10 g/kg over 2 hours; p = 0.215 between groups) and no oozing of blood from cut tissues (sternum, muscle, skin) during or after operation. No adverse hemodynamic or hematologic effects were observed. Animals were physiologically stable coming off pump, requiring minimal fluid replacement or other cardiovascular supportive measures. The chromogenic anti-IIa assay could be used to monitor CGP 39393. Some activated partial thromboplastin time and all activated clotting time values were off scale on pump, but they fell immediately after cardiopulmonary bypass, typically reaching near-normal levels within 30 to 60 minutes. No reversal of CGP 39393 was used, as blood levels declined rapidly after cessation of the infusion. This study in a dog model shows that CGP 39393 administered as a bolus plus infusion (minimum dose, 1.0 mg/kg + 1.50 mg.kg-1.h-1) can be used safely and effectively during cardiopulmonary bypass for cardiac operation.

Topics: Animals; Anticoagulants; Blood Loss, Surgical; Cardiopulmonary Bypass; Dogs; Dose-Response Relationship, Drug; Fibrinolytic Agents; Hirudin Therapy; Hirudins; Male; Partial Thromboplastin Time; Recombinant Proteins

A technique for assessing platelet reactivity to shear stress from nonanticoagulated blood samples was employed to compare the relative effects of an unfractionated heparin, a low-molecular-weight heparin, and hirudin. The in vitro platelet effect of unfractionated heparin (5 U/mL) was measured in 290, the effect of a low-molecular-weight heparin (1 anti-Xa unit/mL) in 74, and the effect of hirudin (8 micrograms/mL) in 50 cardiac surgical patients. The relative proportions of patients exhibiting an enhanced platelet reactivity, a mild to moderate inhibition, and a severe inhibition were, respectively: 8.6%, 58.6%, and 32.8% for unfractionated heparin; 22%, 66%, and 12% for the low-molecular-weight heparin; and 6%, 66%, and 28% for hirudin. At the concentrations examined, a significantly greater proportion (p < 0.01) of the patients exhibited enhanced platelet reactivity and a significantly smaller proportion (p < 0.01) showed severely inhibited platelet reactivity associated with the low-molecular-weight heparin versus the unfractionated heparin, whereas there was no significant difference between the patients treated with hirudin and unfractionated heparin. Although the relevance of this study is limited because the clinically appropriate concentration of the alternative anticoagulants and comparative doses are unknown, it can be inferred that low-molecular-weight heparin may reduce the blood loss associated with cardiopulmonary bypass.

Topics: Anticoagulants; Blood Loss, Surgical; Blood Platelets; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Female; Heparin; Heparin, Low-Molecular-Weight; Hirudins; Humans; Male; Middle Aged; Platelet Activation; Platelet Function Tests

Topics: Animals; Anticoagulants; Blood Loss, Surgical; Cattle; Dogs; Hirudins; Humans; Recombinant Proteins; Renal Dialysis; Sensitivity and Specificity

Recombinant (r) hirudin is a potent thrombin-specific inhibitor originally derived from the natural hirudin of the leech (Hirudo medicinalis). We have studied the efficacy of r-hirudin compared to heparin in a dog model of cardiopulmonary bypass (CPB) surgery. Two administration regimens were used for r-hirudin: Group I received 1.0 mg/kg intracardiac (i.c.) bolus then intravenous (i.v.) bolus at 30 min (n = 10); Group II received 1.0 mg/kg (i.c.) bolus with 1.25 +/- 0.04 mg/kg/h (i.v.) infusion (n = 8). Group III was given heparin 1.66 mg/kg (i.c.) bolus (n = 9). Aspiration of blood from the chest cavity revealed no significant difference between the three groups. Measurement of fibrin deposits in the pump line filter revealed higher amounts in the r-hirudin groups (P = 0.02). Decreases in platelets, fibrinogen and haematocrit due primarily to haemodilution were the same in each group. The bleeding time was less prolonged for r-hirudin than for heparin (p less than 0.001). No antagonist for r-hirudin was used; however, due to its short half-life, all coagulation parameters returned to baseline within 30 min after CPB. Since r-hirudin has no effect on platelets, is a poor immunogen, does not require a plasma cofactor, and may not require an antagonist, it may provide an alternative anticoagulant to heparin in CPB. Additional studies are, however, needed to optimize the dose and to evaluate other clinical aspects of r-hirudin.

Topics: Animals; Bleeding Time; Blood Loss, Surgical; Cardiopulmonary Bypass; Dogs; Extracorporeal Circulation; Fibrin; Hematocrit; Heparin; Hirudin Therapy; Hirudins; Infusions, Intravenous; Injections; Male; Recombinant Proteins; Thrombin Time; Thrombosis

After genetically engineered recombinant DNA desulfatohirudin (r-hirudin) had been investigated as to its pharmacokinetic behavior and blood level course in nephrectomized dogs, the compound was studied for its capability to prevent thrombus formation in the extracorporeal circulation. Beagle dogs underwent bilateral functional nephrectomy followed by experimental hemodialysis. r-Hirudin content in blood, fibrinogen level as well as platelet count were determined before and during the dialysis. Furthermore, the blood loss during the experiment was measured as well as the mean arterial pressure and the pressure in the blood line system. Intravenous administration of the thrombin inhibitor resulted in initial distribution in the extracellular space (distribution phase 90 min) followed by retarded decrease of the r-hirudin blood level (t1/2 beta approximately 6-8 h) which is due to the missing renal excretion of the inhibitor. This caused a long-lasting, dose-dependent anticoagulant effect, which is not only characterized by the prevention of increasing pressure before the capillary dialyzer but also by the reduced drop in fibrinogen and platelets during hemodialysis. The required dose of r-hirudin (0.5 mg/kg) is within a range where bleeding complications will not occur yet.

Topics: Animals; Anticoagulants; Blood Loss, Surgical; Blood Pressure; Dogs; Dose-Response Relationship, Drug; Female; Fibrinogen; Hirudin Therapy; Hirudins; Male; Nephrectomy; Platelet Count; Recombinant Proteins; Renal Dialysis; Thrombosis