hirudin and Anemia

Previously, indirect thrombin inhibitors such as unfractionated heparin or low-molecular-weight heparin were used as a standard anticoagulation during percutaneous coronary intervention to prevent procedural thrombotic complications but at a risk of hemorrhagic complications. More recently, bivalirudin, a member of the direct thrombin inhibitor class, has been shown to have 1) predictable pharmacokinetics, 2) ability to inhibit free- and clot-bound thrombin, 3) no properties of platelet activation, 4) avoidance of heparin-induced thrombocytopenia, and 5) a significant reduction of bleeding without a reduction in thrombotic or ischemic endpoints compared to heparin and glycoprotein IIbIIIa inhibitors when used in patients presenting with acute coronary syndrome who are planned for an invasive treatment strategy.

Topics: Acute Coronary Syndrome; Anemia; Angina, Unstable; Angioplasty, Balloon, Coronary; Anticoagulants; Antithrombins; Blood Coagulation; Comorbidity; Coronary Thrombosis; Heparin; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Recombinant Proteins; Thrombocytopenia

The aim of this study was to assess the impact of baseline anemia on the outcomes of patients with ST elevation myocardial infarctions who underwent primary percutaneous coronary intervention in relation to contemporary adjunctive antithrombotic therapy and gender. In the Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial, patients were randomized to bivalirudin alone or to unfractionated heparin plus a glycoprotein IIb/IIIa inhibitor before primary percutaneous coronary intervention. Outcomes were assessed at 30 days and 1 year according to anemia and gender. Baseline anemia was present in 331 of 3,153 patients (10.5%). Patients with versus without baseline anemia had a more than twofold increase in major bleeding at 30 days (13.5% vs 6.7%, p <0.0001) and at 1 year (14.8% vs 7.2%, p <0.0001), an association that on multivariate analysis was independent of gender. Mortality was significantly higher in men with versus without baseline anemia (4.6% vs 1.8% at 30 days, p = 0.003; 8.9% vs 3.0% at 1 year, p <0.0001) but not in women (5.3% vs 3.6% at 30 days, p = 0.42; 7.5% vs 5.9% at 1 year, p = 0.54). On multivariate analysis, anemia independently predicted 1-year all-cause mortality in men but not in women. Bivalirudin compared with unfractionated heparin plus a glycoprotein IIb/IIIa inhibitor resulted in twofold lower rates of all-cause and cardiac mortality and major bleeding in patients without but not in those with baseline anemia. In conclusion, baseline anemia was associated with increased major bleeding and death in patients with ST elevation myocardial infarctions who underwent primary PCI but was a stronger predictor of early and late mortality in men than in women. Paradoxically, in this post hoc analysis, the reductions in major bleeding and mortality in ST elevation myocardial infarction afforded by bivalirudin occurred primarily in patients without baseline anemia.

Topics: Aged; Anemia; Angioplasty, Balloon, Coronary; Combined Modality Therapy; Drug Therapy, Combination; Electrocardiography; Female; Fibrinolytic Agents; Follow-Up Studies; Heparin; Hirudins; Hospital Mortality; Humans; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Neoadjuvant Therapy; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Probability; Proportional Hazards Models; Recombinant Proteins; Risk Assessment; Sex Factors; Survival Analysis; Thrombolytic Therapy; Treatment Outcome

The relation across anemia, hemorrhagic complications, and mortality associated with percutaneous coronary intervention (PCI) is unclear. We reviewed the Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events (REPLACE)-2 Trial, which compared bivalirudin plus provisional glycoprotein IIb/IIIa blockade with heparin plus planned glycoprotein IIb/IIIa blockade in patients undergoing urgent or elective PCI. Of the 6,010 patients randomized in REPLACE-2, 1,371 (23%) were anemic. Major bleeding was more common in anemic than in nonanemic patients (4.9% vs 2.8%, p = 0.0001). In anemic patients, treatment with bivalirudin (n = 678) resulted in a lower risk of major bleeding versus heparin plus glycoprotein IIb/IIIa blockade (n = 693, 3.5% vs 6.2%, p = 0.0221). Mortality was higher in anemic patients than in nonanemic patients at 30 days (0.9% vs 0.2%, p <0.0001), 6 months (2.6% vs 0.7%, p <0.0001), and 1 year (4.3% vs 1.5%, p <0.0001). There were no differences between anemic and nonanemic patients with regard to ischemic complications at 30 days. Although anemic patients had higher mortality rates, proportions of cardiovascular and noncardiovascular mortalities were equal in anemic and nonanemic patients. In conclusion, anemic patients undergoing PCI have an increased risk of mortality and major bleeding, but not of ischemic events, and the use of bivalirudin with provisional glycoprotein IIb/IIIa blockade decreases the risk of hemorrhagic complications compared with heparin plus planned glycoprotein IIb/IIIa blockade.

Topics: Aged; Anemia; Angina, Unstable; Angioplasty, Balloon, Coronary; Anticoagulants; Cause of Death; Double-Blind Method; Female; Heparin; Hirudins; Humans; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Postoperative Hemorrhage; Predictive Value of Tests; Proportional Hazards Models; Recombinant Proteins; Research Design; Risk Factors; Treatment Outcome

Bleeding risk stratification is an unresolved issue in older adults. Anemia may reflect subclinical blood losses that can be exacerbated after percutaneous coronary intervention . We sought to prospectively determine the contribution of anemia to the risk of bleeding in 448 consecutive patients aged 75 or more years, treated by percutaneous coronary interventions without concomitant indication for oral anticoagulation. We evaluated the effect of WHO-defined anemia on the incidence of 1-year nonaccess site-related major bleeding. The prevalence of anemia was 39%, and 13.1% of anemic and 5.2% of nonanemic patients suffered a bleeding event (hazard ratio 2.75, 95% confidence interval 1.37 to 5.54, p = 0.004). Neither PRECISE-DAPT nor CRUSADE scores were superior to hemoglobin for the prediction of bleeding. In conclusion, anemia is a powerful predictor of bleeding with potential utility for simplifying tailoring therapies.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Anemia; Angina, Unstable; Anticoagulants; Antithrombins; Aspirin; Cause of Death; Clopidogrel; Comorbidity; Coronary Artery Disease; Drug-Eluting Stents; Female; Gastrointestinal Hemorrhage; Hemorrhage; Heparin; Hirudins; Humans; Intracranial Hemorrhages; Kaplan-Meier Estimate; Male; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Postoperative Care; Postoperative Hemorrhage; Prasugrel Hydrochloride; Proportional Hazards Models; Prospective Studies; Recombinant Proteins; Risk Assessment; Stents; Ticagrelor; Urologic Diseases

A case of 68 years old women suffering from chronic anemia, myelodysplastic syndrome and treated with progestogen due to endometrial hypertrophy is presented. Initially she was admitted to a regional hospital because of progressive weakness and exertional dyspnea. Three months earlier she reported an episode of acute dyspnea and chest pain. On the basis of clinical symptoms and perfusion lung scintigraphy pulmonary embolism (PE) was diagnosed. Patient received i.v. heparin which was changed to s.c. nadroparine subcutaneously. Platelet count dropped to 55,000'/ml on fifth day of treatment from initial level of about 200,000'/ml. Heparin induced thrombocytopenia was diagnosed, heparin was stopped and ticlopidine was recommended. After 3 weeks symptoms suggesting recurrent PE were observed. The patient was transferred to National Tuberculosis and Lung Diseases Research Institute. Recombinant hirudine (Refludan) was administrated (bolus 0.4 mg/kg and initial dose of infusion 0.1 mg/kg/h) overlapping with acenocoumarol from second day. Dose of r-hirudine was adjusted to achieve APTT prolongation 1.5 to 2.5 times of mid-normal range. During treatment with r-hirudine no bleeding and new thromboembolic complications occurred. Platelets count remained within normal range. After 14 days clinical improvement was observed, though symptoms of right ventricular overload and hypoxemia were still present after 6 months of treatment with oral anticoagulants suggesting chronic thromboembolic pulmonary hypertension.

Topics: Aged; Anemia; Anticoagulants; Dyspnea; Female; Heparin; Hirudin Therapy; Hirudins; Humans; Injections, Intravenous; Myelodysplastic Syndromes; Pulmonary Embolism; Recombinant Proteins; Recurrence; Thrombocytopenia