losartan-potassium and Thromboembolism

Erythropoietic-stimulating agents such as erythropoietin have been used as part of patient blood management programs to reduce or even avoid the use of allogeneic blood transfusions. We review the literature to evaluate the effect of preoperative erythropoietin use on the risk of exposure to perioperative allogeneic blood transfusions.. The study involved a systematic review and meta-analysis of randomized controlled trials evaluating the use of preoperative erythropoietin. The primary outcome was the reported incidence of allogeneic red blood cell transfusions during inpatient hospitalizations. Secondary outcomes included phase-specific allogeneic red blood cell transfusions (ie, intraoperative, postoperative), intraoperative estimated blood loss, perioperative hemoglobin levels, length of stay, and thromboembolic events.. A total of 32 randomized controlled trials (n = 4750 patients) were included, comparing preoperative erythropoietin (n = 2482 patients) to placebo (n = 2268 patients). Preoperative erythropoietin is associated with a significant decrease in incidence of allogeneic blood transfusions among all patients (n = 28 studies; risk ratio, 0.59; 95% CI, 0.47-0.73; P < .001) as well as patients undergoing cardiac (n = 9 studies; risk ratio, 0.55; 95% CI, 0.37-0.81; P = .003) and elective orthopedic (n = 5 studies; risk ratio, 0.36; 95% CI, 0.28-0.46; P < .001) surgery compared to placebo, respectively. Preoperative erythropoietin was also associated with fewer phase-specific red blood cell transfusions. There was no difference between groups in incidence of thromboembolic events (n = 28 studies; risk ratio, 1.02; 95% CI, 0.78-1.33; P = .68).. Preoperative erythropoietin is associated with a significant reduction in perioperative allogeneic blood transfusions. This finding is also confirmed among the subset of patients undergoing cardiac and orthopedic surgery. Furthermore, our study demonstrates no significant increase in risk of thromboembolic complications with preoperative erythropoietin administration.

Topics: Blood Loss, Surgical; Blood Transfusion; Erythrocyte Transfusion; Erythropoietin; Hematinics; Hematopoietic Stem Cell Transplantation; Hemoglobins; Hospitalization; Humans; Inpatients; Preoperative Period; Risk; Sensitivity and Specificity; Thromboembolism; Transplantation, Homologous; Treatment Outcome

The use of erythropoietin (EPO) and intravenous (IV) iron as bloodless therapeutic modalities is being explored in the current era of restrictive transfusion strategies and perioperative blood management. It is unclear, however, whether the evidence in the literature supports their safety and efficacy in reducing perioperative red cell transfusions. Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, we conducted a systematic review to evaluate their use in a variety of perioperative settings. We performed a literature search of English articles published between July 1997 and July 2012 in MEDLINE via PubMed, The Cochrane Library, and CINAHL. Only studies with a comparator group were eligible for inclusion. Twenty-four randomized controlled trials (RCTs) and 15 nonrandomized studies were included in the final review. Using the Cochrane risk of bias tool, 8 RCTs were assessed to be at low risk for methodological bias. Of these, however, only 4 RCTs were adequately powered to detect a reduction in transfusion rates. Patients with preoperative iron deficiency anemia may have an earlier and more robust hemoglobin recovery with preoperative IV iron therapy than with oral iron supplementation. A short preoperative regimen of EPO, or a single dose of EPO plus IV iron in the preoperative or intraoperative period, may significantly reduce transfusion rates (number needed to treat to avoid any transfusion ranged from 3 to 6). With regard to the safety of erythropoietin-stimulating agent therapy, IV iron appears to be as well tolerated as oral iron; however, the incidence of severe anaphylactic-type reactions attributable to IV iron is difficult to estimate in prospective trials because of its relatively infrequent occurrence. Furthermore, EPO may increase the risk of thromboembolism in spinal surgery patients who receive mechanical antithrombotic prophylaxis in the perioperative period so pharmacological thromboprophylaxis is advised. Future low risk of bias, adequately powered prospective efficacy, and safety trials in various surgical settings that traditionally require red cell transfusions would be required to make evidenced-based conclusions about the clinical significance of erythropoietin-stimulating agent as a transfusion avoidance strategy in perioperative blood management.

Topics: Clinical Trials as Topic; Erythrocyte Transfusion; Erythropoietin; Humans; Infusions, Intravenous; Iron; Multicenter Studies as Topic; Patient Safety; Perioperative Period; Randomized Controlled Trials as Topic; Risk; Surgical Procedures, Operative; Thromboembolism; Treatment Outcome

For years, the treatment of chemotherapy-induced anemia (CIA) consisted of red blood cell transfusions. Major disadvantages of transfusions are their temporary effect and limitation to treatment of severe anemia. In an extensive clinical trial program in patients with CIA, darbepoetin alfa (DA) - a long-acting recombinant human erythropoietin - was proven to be very effective in reducing transfusion needs in patients developing CIA. The administration is suitable with most chemotherapy schemes. Caution is needed in patients with a history of thrombo-embolic events, as a slightly higher incidence of these events is noted in patients treated with darbepoetin alfa or erythropoietin substitution agents (ESAs) in general. In recent years, concerns have been raised about a potential negative influence of these agents on survival. In this respect, it is important to make the distinction between studies on the treatment of existing CIA versus treatment with ESAs outside this indication. On the other hand, it has always been assumed that transfusions were a completely safe treatment, but concerns about a potential negative effect on survival have been raised for transfusions as well. The safety concerns with DA and ESAs in general led to a pharmacovigilance program and an adaptation of the guidelines for treatment of CIA, focusing on treatment of moderate CIA but no longer on mild CIA. Now that the most recent safety data of the pharmacovigilance program of ESAs is almost completed, the clinical impact of the shift to the treatment of only moderate anemia is discussed in this review, which provides a critical view on the indications of DA and the benefit-risk assessment, in order to provide good supportive care without harm to the patient.

Topics: Anemia; Antineoplastic Agents; Darbepoetin alfa; Erythrocyte Transfusion; Erythropoietin; Hematinics; Humans; Neoplasms; Practice Guidelines as Topic; Thromboembolism

Anaemia associated with cancer and cancer therapy is an important clinical factor in the treatment of malignant diseases. Therapeutic alternatives are recombinant human erythropoiesis stimulating agents (ESAs) and red blood cell transfusions.. To assess the effects of ESAs to either prevent or treat anaemia in cancer patients.. This is an update of a Cochrane review first published in 2004. We searched the Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE and other databases. Searches were done for the periods 01/1985 to 12/2001 for the first review, 1/2002 to 04/2005 for the first update and to November 2011 for the current update. We also contacted experts in the field and pharmaceutical companies.. Randomised controlled trials on managing anaemia in cancer patients receiving or not receiving anti-cancer therapy that compared the use of ESAs (plus transfusion if needed).. Several review authors assessed trial quality and extracted data. One review author assessed quality assessment and extracted data, a second review author checked for correctness.. This update of the systematic review includes a total of 91 trials with 20,102 participants. Use of ESAs significantly reduced the relative risk of red blood cell transfusions (risk ratio (RR) 0.65; 95% confidence interval (CI) 0.62 to 0.68, 70 trials, N = 16,093). On average, participants in the ESAs group received one unit of blood less than the control group (mean difference (MD) -0.98; 95% CI -1.17 to -0.78, 19 trials, N = 4,715). Haematological response was observed more often in participants receiving ESAs (RR 3.93; 95% CI 3.10 to 3.71, 31 trials, N = 6,413). There was suggestive evidence that ESAs may improve Quality of Life (QoL). There was strong evidence that ESAs increase mortality during active study period (hazard ratio (HR) 1.17; 95% CI 1.06 to 1.29, 70 trials, N = 15,935) and some evidence that ESAs decrease overall survival (HR 1.05; 95% CI 1.00 to 1.11, 78 trials, N = 19,003). The risk ratio for thromboembolic complications was increased in patients receiving ESAs compared to controls (RR 1.52, 95% CI 1.34 to 1.74; 57 trials, N = 15,498). ESAs may also increase the risk for hypertension (fixed-effect model: RR 1.30; 95% CI 1.08 to 1.56; random-effects model: RR 1.12; 95% CI 0.94 to 1.33, 31 trials, N = 7,228) and thrombocytopenia/haemorrhage (RR 1.21; 95% CI 1.04 to 1.42; 21 trials, N = 4,507). There was insufficient evidence to support an effect of ESA on tumour response (fixed-effect RR 1.02; 95% CI 0.98 to 1.06, 15 trials, N = 5,012).. ESAs reduce the need for red blood cell transfusions but increase the risk for thromboembolic events and deaths. There is suggestive evidence that ESAs may improve QoL. Whether and how ESAs affects tumour control remains uncertain. The increased risk of death and thromboembolic events should be balanced against the potential benefits of ESA treatment taking into account each patient's clinical circumstances and preferences. More data are needed for the effect of these drugs on quality of life and tumour progression. Further research is needed to clarify cellular and molecular mechanisms and pathways of the effects of ESAs on thrombogenesis and their potential effects on tumour growth.

Topics: Anemia; Cause of Death; Darbepoetin alfa; Erythrocyte Transfusion; Erythropoietin; Humans; Hypertension; Neoplasms; Quality of Life; Randomized Controlled Trials as Topic; Recombinant Proteins; Thromboembolism

Thromboembolic complications are the second leading cause of death in cancer patients. In contrast to the large body of literature on venous thromboembolism (VTE), relatively few reports have focused on the pathogenesis, incidence, management and outcomes of arterial thromboembolic events in patients with malignancy. The purpose of this article is to review the current literature on the etiology, mechanisms, and prognosis of arterial thromboembolic events in cancer patients and outline appropriate screening and management guidelines that may help lower the rates of morbidity and mortality related to these events.

Topics: Algorithms; Amyloidosis; Antineoplastic Agents; Antiphospholipid Syndrome; Erythropoietin; Female; Humans; Ischemia; Male; Myeloproliferative Disorders; Neoplasms; Neurofibromatosis 1; Peripheral Arterial Disease; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prognosis; Radiation Injuries; Recombinant Proteins; Risk Factors; Thromboembolism; Thrombophilia; Transfusion Reaction

Disorders of coagulation are common adverse drug events encountered in critically ill patients and present a serious concern for intensive care unit (ICU) clinicians. Dosing strategies for medications used in the ICU are typically developed for use in noncritically ill patients and, therefore, do not account for the altered pharmacokinetic and pharmacodynamic properties encountered in the critically ill as well as the increased potential for drug-drug interactions, given the far greater number of medications ordered. This substantially increases the risk for coagulation-related adverse reactions, such as a bleeding or prothrombotic events. Although many medications used in the ICU have the potential to cause coagulation disorders, the exact incidence will vary based on the specific medication, dose, concomitant drug therapy, ICU setting, and patient-specific comorbidities. Clinicians must strongly consider these factors when evaluating the risk/benefit ratio for a particular therapy. This review surveys recent literature documenting the risk for adverse drug reactions specific to bleeding and/or clotting with commonly used medications in the ICU.

Topics: Anti-Infective Agents; Anticoagulants; Antifibrinolytic Agents; Blood Coagulation Disorders; Blood Coagulation Factors; Colloids; Critical Care; Deamino Arginine Vasopressin; Drug-Related Side Effects and Adverse Reactions; Erythropoietin; Estrogens, Conjugated (USP); Factor VIIa; Fibrinolytic Agents; Fondaparinux; Hemostatics; Humans; Polysaccharides; Protein C; Recombinant Proteins; Thrombin; Thromboembolism; Vitamin K

Epoetin-beta is used to treat patients with cancer undergoing chemotherapy to alleviate the symptoms of anaemia, reduce the risk of blood transfusions and improve quality of life (QoL).. This meta-analysis of all 12 randomised, controlled studies of epoetin-beta evaluated the impact of therapy at different Hb-initiation levels and to different target Hb levels on overall survival, tumour progression and thromboembolic events (TEE). An analysis of risk factors pre-disposing patients to TEEs under epoetin-beta therapy was also performed. A total of 2297 patients are included in the analysis.. Analyses based on various Hb-initiation levels indicate no detrimental impact on survival (HR 0.99; 95% CI 0.70, 1.40) and a favourable impact on disease progression (HR 0.73; 95% CI 0.57, 0.94) when epoetin-beta was used within its licensed indication (Hb initiation < or = 10 g dl(-1)) or the EORTC recommended level of 11 g dl(-1). An increased risk of TEEs is seen for all Hb-initiation level strata and a detrimental impact on survival is seen when initiating epoetin-beta therapy at Hb levels >11 g dl(-1). We observe no association between high target Hb levels (> or = 13 g dl(-1)) and an increased risk of mortality, disease progression or TEEs with epoetin-beta compared with control.. The results of this analysis indicate that epoetin-beta therapy has no detrimental impact on survival or tumour progression when initiated at Hb levels up to 11 g dl(-1). Furthermore, there is no evidence to suggest that high Hb values achieved during epoetin-beta therapy are associated with an increased mortality, disease progression or TEE rate.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Agents; Disease Progression; Erythropoietin; Female; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Randomized Controlled Trials as Topic; Recombinant Proteins; Risk Factors; Thromboembolism

Epoetin-beta is used to treat patients with metastatic cancer undergoing chemotherapy to alleviate the symptoms of anaemia, reduce the risk of blood transfusions and improve quality of life. This meta-analysis of 12 randomised, controlled studies evaluated the impact of epoetin-beta on overall survival, tumour progression and thromboembolic events (TEEs). A total of 2297 patients were included in the analysis (epoetin-beta, n=1244; control, n=1053; 65% solid and 35% nonmyeloid haematological malignancies). A prespecified subgroup analysis assessed the effects in patients with a baseline Hb

Topics: Adult; Aged; Aged, 80 and over; Anemia; Disease Progression; Erythropoietin; Female; Hematinics; Humans; Male; Middle Aged; Neoplasms; Randomized Controlled Trials as Topic; Recombinant Proteins; Survival Analysis; Thromboembolism

Evidence regarding the cost-effective use of and benefits associated with epoetin alfa in treating anemia of critically ill patients is assessed.. Anemia of critical illness is a leading cause of inadequate oxygen delivery that affects almost all patients in the intensive care unit setting after day 3. Red blood cell transfusions are commonly used to correct anemia of critical illness, but they are also associated with risks including hemolytic reactions and viral transmission. The latest evidence suggests that when a strict transfusion protocol is implemented, epoetin alfa does not decrease the transfusion requirements of critically ill patients. In the absence of a strict transfusion protocol, an average of 5.1 doses of epoetin, at a cost of $2154, is required to avoid one transfusion. Evidence is accumulating that epoetin may reduce mortality rates in trauma patients. However, important questions remain regarding the magnitude and mechanism of the potential benefit and if the benefit outweighs the risk of thromboembolism. Therefore, the reduction in transfusion-related adverse events is the only clinical outcome benefit that is well-supported by current evidence. However, the known risk of transfusion-related adverse events is low; approximately 29,000 patients would need to be treated to avoid a serious transfusion-related event. Treating these patients would cost over $25 million, and it would take over 100 years to prevent one serious event in a unit admitting 20 epoetin-eligible patients per month.. Published data suggest a prohibitive cost associated with epoetin alfa use in critically ill patients given that the only well-supported clinical benefit of this treatment is the avoidance of transfusion-related adverse events. Continued research is necessary to clarify if there is a net clinical benefit of epoetin use (especially in trauma patients) and to develop optimal blood management strategies.

Topics: Anemia; Cost-Benefit Analysis; Critical Care; Critical Illness; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Hematinics; Humans; Intensive Care Units; Oxygen; Randomized Controlled Trials as Topic; Recombinant Proteins; Thromboembolism

Venous thromboembolic events (VTEs) are frequent in cancer patients because of the effects of malignant disease, its treatment, and comorbidities. The higher risk for VTEs associated with the use of erythropoiesis-stimulating agents (ESAs) appears to be a class effect but may be particularly pronounced when these agents are used in patients who are not anemic at baseline and/or to achieve hemoglobin targets higher than those recommended in current labeling. Particular attention should be taken to assess the balance of risks and benefits in patients with a history of thromboembolism. If the goal of treatment of patients with chemotherapy-associated anemia is aimed to raise the hemoglobin level to 12 g/dl, and is confined to that, ESA-induced VTEs should rarely be a problem.

Topics: Anemia; Antineoplastic Agents; Drug Labeling; Erythropoietin; Hematinics; Hemoglobins; Humans; Neoplasms; Recombinant Proteins; Thromboembolism

Anaemia is frequently diagnosed in patients with cancer, and may have a detrimental effect on quality of life (QoL). We previously conducted a systematic literature review (1996-2003) to produce evidence-based guidelines on the use of erythropoietic proteins in anaemic patients with cancer.[Bokemeyer C, Aapro MS, Courdi A, et al. EORTC guidelines for the use of erythropoietic proteins in anaemic patients with cancer. Eur J Cancer 2004;40:2201-2216.] We report here an update to these guidelines, including literature published through to November 2005. The results of this updated systematic literature review have enabled us to refine our guidelines based on the full body of data currently available. Level I evidence exists for a positive impact of erythropoietic proteins on haemoglobin (Hb) levels when administered to patients with chemotherapy-induced anaemia or anaemia of chronic disease, when used to prevent cancer anaemia, and in patients undergoing cancer surgery. The addition of further Level I studies confirms our recommendation that in cancer patients receiving chemotherapy and/or radiotherapy, treatment with erythropoietic proteins should be initiated at a Hb level of 9-11 g/dL based on anaemia-related symptoms rather than a fixed Hb concentration. Early intervention with erythropoietic proteins may be considered in asymptomatic anaemic patients with Hb levels 11.9 g/dL provided that individual factors like intensity and expected duration of chemotherapy are considered. Patients whose Hb level is below 9 g/dL should primarily be evaluated for need of transfusions potentially followed by the application of erythropoietic proteins. We do not recommend the prophylactic use of erythropoietic proteins to prevent anaemia in patients undergoing chemotherapy or radiotherapy who have normal Hb levels at the start of treatment, as the literature has not shown a benefit with this approach. The addition of further supporting studies confirms our recommendation that the target Hb concentration following treatment with erythropoietic proteins should be 12-13 g/dL. Once this level is achieved, maintenance doses should be titrated individually. There is Level I evidence that dosing of erythropoietic proteins less frequently than three times per week is efficacious when used to treat chemotherapy-induced anaemia or prevent cancer anaemia, with studies supporting the use of epoetin alfa and epoetin beta weekly and darbepoetin alfa given every week or every 3 weeks.

Topics: Anemia; Antineoplastic Agents; Bone Marrow Transplantation; Chronic Disease; Erythropoietin; Hematopoietic Stem Cell Transplantation; Humans; Hypertension; Iron; Neoplasms; Practice Guidelines as Topic; Radiotherapy; Thromboembolism

Patients with cancer-related anaemia generally have a poor prognosis. Evidence suggests that an effective erythropoietic protein (epoetin)-mediated haemoglobin (Hb) response provides marked improvement in quality of life (QoL). An early Hb response to erythropoietic protein therapy in these patients would appear ideal but few studies have compared the speed of response to different erythropoietic proteins, or the potential benefits associated with an early Hb response.. The pharmacokinetic/pharmacodynamic profiles of commercially available erythropoietic proteins are reviewed along with available clinical data to examine Hb response and associated clinical outcomes for each of these agents. Randomised, head-to-head trials comparing epoetin alfa and darbepoetin alfa suggest that patients administered with epoetin alfa achieve a satisfactory Hb response significantly earlier than those given darbepoetin alfa, and with consistently lower monthly transfusion rates. Non-comparative studies support this, suggesting also that epoetin beta may provide a relatively faster Hb response in a greater number of patients than either epoetin alfa or darbepoetin alfa, irrespective of malignancy or chemotherapy type. Moreover, studies suggest consistently that a 'front-loading' dosing regimen with epoetin alfa does not convey improved speed of Hb response over epoetin beta administered according to current clinical practice guidelines.. Given the poor prognosis of anaemic patients with cancer, the use of an agent which provides clinical benefits quickly but with minimal thromboembolic risk, should be considered an essential component of anaemia management in these patients. However, more head-to-head studies are required to confirm the relative efficacy of currently available erythropoietic proteins.

Topics: Anemia; Antineoplastic Agents; Darbepoetin alfa; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Hemoglobins; Humans; Neoplasms; Quality-Adjusted Life Years; Recombinant Proteins; Retrospective Studies; Thromboembolism; Treatment Outcome

Anemia is a frequent problem in cancer patients, especially in those treated with chemotherapy, and has an important negative impact on quality of life. Red blood cell transfusions provide clear but rather temporary comfort. The development of erythropoietic stimulating agents (ESAs) led to a more durable anemia treatment. Darbepoetin alpha is a unique ESA with a long plasma half life, thereby suitable for administration with different dosing intervals. Apart from administration every week, darbepoetin alpha also proved to be efficient in reducing red blood cell transfusion rates and in improving health-related quality of life when administered at a dose of 500 microg once every 3 weeks. This is a convenient therapy schedule because it can be synchronized with the chemotherapy cycle in many patients. Recently, concerns have been raised about the long-term safety of ESAs, more specifically about their effect on survival. Available data must be interpreted with caution, but at present there is no clear evidence to support a negative effect on outcome with darbepoetin alpha therapy when used according to the guidelines for treatment of chemotherapy-induced anemia. Further studies focusing on survival as the primary end point are ongoing.

Topics: Anemia; Antineoplastic Agents; Blood Transfusion; Clinical Trials as Topic; Combined Modality Therapy; Darbepoetin alfa; Drug Administration Schedule; Drug Approval; Erythropoietin; Humans; Injections, Intravenous; Injections, Subcutaneous; Iron-Dextran Complex; Neoplasms; Quality of Life; Randomized Controlled Trials as Topic; Thromboembolism

This is an updated systematic review of 57 trials and 9353 cancer patients from articles, abstracts, and reports published between January 1, 1985, and April 30, 2005, on the effects of epoetin alfa and beta (i.e., epoetin) and darbepoetin alfa (i.e., darbepoetin). We included randomized controlled trials comparing epoetin or darbepoetin plus red blood cell transfusion with red blood cell transfusion alone for prophylaxis or treatment of anemia in cancer patients with or without concurrent antineoplastic therapy. The Cochrane Library, MEDLINE, EMBASE, and conference proceedings were searched. Effect estimates and 95% confidence intervals (CIs) were calculated with fixed-effects models. Treatment with epoetin or darbepoetin statistically significantly reduced the risk for red blood cell transfusions (relative risk [RR] = 0.64, 95% CI = 0.60 to 0.68; 42 trials and 6510 patients) and improved hematologic response (RR = 3.43, 95% CI = 3.07 to 3.84; 22 trials and 4307 patients). Treatment with epoetin or darbepoetin increased the risk of thrombo-embolic events (RR = 1.67, 95% CI = 1.35 to 2.06; 35 trials and 6769 patients). Uncertainties remain as to whether and how epoetin or darbepoetin affects overall survival (hazard ratio = 1.08, 95% CI = 0.99 to 1.18; 42 trials and 8167 patients). Caution is advised when using epoetin or darbepoetin in combination with thrombogenic chemotherapeutic agents or for cancer patients who are at high risk for thrombo-embolic events.

Topics: Anemia, Hypochromic; Antineoplastic Agents; Darbepoetin alfa; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Hematinics; Humans; Incidence; Neoplasms; Randomized Controlled Trials as Topic; Recombinant Proteins; Research Design; Risk Assessment; Thromboembolism; Treatment Outcome

The risk of severe cardiovascular toxicity, specifically thromboembolic events (TE), in patients with cervical cancer receiving concurrent irradiation and cisplatin chemotherapy is reported to be less than 1% in several large prospective trials. However, the anecdotal risk appears to be far higher.. A review of several prospective trials demonstrates no treatment related grade 4 cardiovascular toxicities and only two grade 5 toxicities in 1424 (0.1%) collective patients. A recent publication and our own unpublished experience finds 6 of 128 (4.7%) patients developed grade 4 to 5 cardiovascular (thrombosis/embolism) toxicity. The difference in incidence of severe or life threatening cardiovascular toxicity of 0.1 versus 4.7% is highly statistically significant (p < 0.00001.). This dramatic difference in incidence of cardiovascular toxicity raises the possibility that cardiovascular toxicities were inadequately reported on the listed prospective trials. For those patients enrolled in prospective trials, we suggest that thromboses should be diligently documented and reported. Only after the true incidence of thromboses is established can we implement appropriate levels of early screening and intervention that may prevent life threatening complications.

Topics: Antineoplastic Agents; Cisplatin; Clinical Trials as Topic; Cohort Studies; Combined Modality Therapy; Erythropoietin; Female; Humans; Incidence; Prospective Studies; Research Design; Retrospective Studies; Thromboembolism; Treatment Outcome; Uterine Cervical Neoplasms

Erythropoiesis-stimulating proteins (ESPs) are indicated for the treatment of chemotherapy-induced anemia (CIA). Evidence-based guidelines and systematic reviews of the management of CIA do not yet include all currently approved ESPs or all of the clinically relevant benefits and risks of ESPs.. The aims of this work were to provide up-to-date assessments of the clinical efficacy and effectiveness (ie, transfusions and quality-of-life [QoL] benefits) and safety (ie, risk of venous thromboembolism [VTE] and all-cause or treatment-associated death) of epoetin-alfa, epoetin-beta, and darbepoetin-alfa for the treatment of CIA in cancer patients with hemoglobin<11 g/dL. We also considered the impact of differences in study design, patients, and treatments on the results.. A systematic review of the literature was performed to identify and analyze English-language studies (controlled trials and prospective uncontrolled studies with >or=300 patients) published between 1980 and July 2005. The databases searched were MEDLINE and the Cochrane Library. Relevant abstracts from the last 2 annual meetings of the American Society of Clinical Oncology, American Society of Hematology, and European Society for Medical Oncology were also included. Studies were selected, using predefined eligibility criteria. Two reviewers had to agree on all included and excluded studies, and on all data extracted from each accepted study before they were entered into a relational database. Meta-analyses were performed to quantify benefit and risk outcomes.. In total, 40 studies including 21,378 patients were eligible for analysis. Each ESP was found to have efficacy relative to standard care or placebo. The odds ratio (OR) for transfusions in studies of epoetin versus controls was 0.44 (95% CI, 0.35-0.55) and of darbepoetin versus controls was 0.41 (95% CI, 0.31-0.55). Patients receiving ESPs experienced a significant improvement in QoL; the mean difference in Functional Assessment of Cancer Therapy-Fatigue score for ESPs versus controls was 0.23 (95% CI, 0.10-0.36; P=0.001). The frequency of VTE and death was not significantly different between ESPs and control (VTE OR, 1.41 [95% CI, 0.81-2.47]; all-cause mortality OR, 1.00 [95% CI, 0.69-1.44]).. This analysis of key clinical benefits and risks of epoetin and darbepoetin in the treatment of CIA found no clinically relevant differences between these drugs.

Topics: Adult; Anemia; Antineoplastic Agents; Blood Transfusion; Child; Clinical Trials as Topic; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Quality of Life; Recombinant Proteins; Thromboembolism; Venous Thrombosis

Anemia is extremely common in patients with cancer. Low hemoglobin levels are associated with diminished quality of life and possibly decreased overall survival. Successful treatment of anemia has undeniable benefits for patients, often yielding dramatic symptomatic improvement that can be very satisfying for clinicians to observe. This review focuses on evolving issues in the management of anemia in patients suffering from cancer. Topics addressed include new evidence-based guidelines concerning the use of epoetin alfa, the evolving role of darbepoetin alfa in cancer-associated anemia, the potential for concomitant iron supplementation to maximize response to erythropoietic agents, the unresolved question of whether erythropoietin use affects survival in cancer patients, new concerns about the risk of thromboembolism in cancer patients with higher hemoglobin levels who are receiving epoetin, and possible immunosuppressive effects of blood product transfusions that may have relevance to neoplasia progression.

Topics: Anemia; Chemotherapy, Adjuvant; Darbepoetin alfa; Drug Therapy, Combination; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Evidence-Based Medicine; Hematinics; Humans; Iron; Neoplasms; Practice Guidelines as Topic; Quality of Life; Radiotherapy, Adjuvant; Recombinant Proteins; Thromboembolism; Treatment Outcome

Anaemia is frequently diagnosed in patients with cancer, yet it is difficult to identify a single cause due to its multifactorial aetiology. We conducted a systematic literature review (1996-2003) to produce evidence-based guidelines on the use of erythropoietic proteins in anaemic patients with cancer (see ). Level I evidence exists for a positive impact of erythropoietic proteins on haemoglobin (Hb) levels when administered to patients with chemotherapy-induced anaemia or anaemia of chronic disease, when used to prevent cancer anaemia, in patients undergoing cancer surgery and following allogeneic bone marrow transplantation. The Hb level at which erythropoietic protein therapy should be initiated is difficult to determine as it varied between studies; a large number of Level I studies in patients with chemotherapy-induced anaemia or anaemia of chronic disease enrolled patients with a Hb concentration

Topics: Anemia; Bone Marrow Transplantation; Chronic Disease; Dose-Response Relationship, Drug; Erythropoietin; Hematopoietic Stem Cell Transplantation; Humans; Hypertension; Neoplasms; Quality of Life; Survival Analysis; Thromboembolism

Haematological disorders of pregnancy are common reasons for referral. It is reasonable then to devote a review to recent publications on these issues.. Several narrative reviews on the management of venous thromboembolic disease in pregnancy provide exceptional guidance. They highlight, however, that most of what is done is still based on opinions from highly qualified people, extrapolated from the non-pregnant literature but not involving randomized trials on pregnant patients. It is apparent that a consensus is nearing on the management of both pregnancy-related thrombocytopenia and idiopathic (immune) thrombocytopenic purpura. Several randomized controlled trials are reported on the treatment of non-deficiency anaemia, using oral iron, intravenous iron and erythropoietin, which contribute to the debate on the appropriate and best intervention for this common problematic issue.. This review demonstrates the need for appropriately sized randomized trials on haematological issues in pregnancy. With heparin becoming the most common medication being administered prophylactically and therapeutically in pregnancy, it is important that quality trials are performed to guide its sensible utilization.

Topics: Anemia; Erythropoietin; Female; Heparin; Humans; Iron, Dietary; Pregnancy; Pregnancy Complications, Hematologic; Prenatal Care; Prenatal Diagnosis; Randomized Controlled Trials as Topic; Thrombocytopenia; Thromboembolism

Erythropoietin has been shown to be effective both in the reversal of anaemia in patients with end-stage renal failure and to increase the volume of autologous red blood cells donated preoperatively as well as to decrease the units of homologous blood transfused. This review analyzes the side effects of erythropoietin reported in the literature for long-term administration (mainly in patients with end-stage renal failure) as well as for acute/short-term administration (in patients participating in an autologous predeposit programme). The most important adverse events reported for long-term administration are as follows: (a) arterial hypertension; (b) cerebral convulsion/hypertensive encephalopathy; (c) thrombo-embolism; (d) iron deficiency; (e) influenza-like syndrome. The numbers given for these side effects are mainly taken from the first and dose-finding studies in patients with renal failure. These figures differ very much from the data given in controlled studies analyzing adverse events as well. Summarizing the results from controlled, multi-center trials in patients with end-stage renal failure or in AIDS patients, no significant differences have been observed between the control group and the patients treated with erythropoietin. The overall-incidence of side effects occurring in either group of these two studies was of approximately 83% and 95%, respectively. In contrast to these results the data published for the dose finding/treatment studies is approximately 30% for development of arterial hypertension, approximately 5% for occurrence of cerebral convulsion/hypertensive encephalopathy, approximately 10% for thrombo-embolic complications/clotting of vascular access, approximately 50% for development of iron deficiency, and approximately 10% for symptoms summarized as influenza-like syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Blood Transfusion, Autologous; Cardiovascular Diseases; Erythropoietin; Humans; Seizures; Thromboembolism; Time Factors

Traumatic brain injury is a leading cause of death and disability worldwide. Laboratory and clinical studies demonstrate a possible beneficial effect of erythropoietin in improving outcomes in the traumatic brain injury cohort. However, there are concerns regarding the association of erythropoietin and thrombosis in the critically ill. A large-scale, multi-centre, blinded, parallel-group, placebo-controlled, randomised trial is currently underway to address this hypothesis.. The erythropoietin in traumatic brain injury trial is a stratified prospective, multi-centre, randomised, blinded, parallel-group, placebo-controlled phase III trial. It aims to determine whether the administration of erythropoietin compared to placebo improves neurological outcome in patients with moderate or severe traumatic brain injury at six months after injury. The trial is designed to recruit 606 patients between 15 and 65 years of age with severe (Glasgow Coma Score: 3 to 8) or moderate (Glasgow Coma Score: 9 to 12) traumatic brain injury in Australia, New Zealand, Kingdom of Saudi Arabia, France, Finland, Germany and Ireland. Trial patients will receive either subcutaneous erythropoietin or placebo within 24 hours of injury, and weekly thereafter for up to three doses during the intensive care unit admission. The primary outcome will be the combined proportion of unfavourable neurological outcomes at six months: severe disability or death. Secondary outcomes will include the rate of proximal deep venous thrombosis detected by compression Doppler ultrasound, six-month mortality, the proportion of patients with composite vascular events (deep venous thrombosis, pulmonary embolism, myocardial infarction, cardiac arrest and cerebrovascular events) at six months and quality of life with health economic evaluations.. When completed, the trial aims to provide evidence on the efficacy and safety of erythropoietin in traumatic brain injury patients, and to provide clear guidance for clinicians in their management of this devastating condition.. Australian New Zealand Clinical Trials registry: ACTRN12609000827235 (registered on 22 September 2009). Clinicaltrials.gov: NCT00987454 (registered on 29 September 2009). European Drug Regulatory Authorities Clinical Trials: 2011-005235-22 (registered on 18 January 2012).

Topics: Adolescent; Adult; Aged; Brain Injuries; Clinical Protocols; Data Interpretation, Statistical; Erythropoietin; Humans; Middle Aged; Outcome Assessment, Health Care; Sample Size; Thromboembolism; Ultrasonography, Doppler

There is limited information about the effect of erythropoietin or a high hemoglobin transfusion threshold after a traumatic brain injury.. To compare the effects of erythropoietin and 2 hemoglobin transfusion thresholds (7 and 10 g/dL) on neurological recovery after traumatic brain injury.. Randomized clinical trial of 200 patients (erythropoietin, n = 102; placebo, n = 98) with closed head injury who were unable to follow commands and were enrolled within 6 hours of injury at neurosurgical intensive care units in 2 US level I trauma centers between May 2006 and August 2012. The study used a factorial design to test whether erythropoietin would fail to improve favorable outcomes by 20% and whether a hemoglobin transfusion threshold of greater than 10 g/dL would increase favorable outcomes without increasing complications. Erythropoietin or placebo was initially dosed daily for 3 days and then weekly for 2 more weeks (n = 74) and then the 24- and 48-hour doses were stopped for the remainder of the patients (n = 126). There were 99 patients assigned to a hemoglobin transfusion threshold of 7 g/dL and 101 patients assigned to 10 g/dL.. Intravenous erythropoietin (500 IU/kg per dose) or saline. Transfusion threshold maintained with packed red blood cells.. Glasgow Outcome Scale score dichotomized as favorable (good recovery and moderate disability) or unfavorable (severe disability, vegetative, or dead) at 6 months postinjury.. There was no interaction between erythropoietin and hemoglobin transfusion threshold. Compared with placebo (favorable outcome rate: 34/89 [38.2%; 95% CI, 28.1% to 49.1%]), both erythropoietin groups were futile (first dosing regimen: 17/35 [48.6%; 95% CI, 31.4% to 66.0%], P = .13; second dosing regimen: 17/57 [29.8%; 95% CI, 18.4% to 43.4%], P < .001). Favorable outcome rates were 37/87 (42.5%) for the hemoglobin transfusion threshold of 7 g/dL and 31/94 (33.0%) for 10 g/dL (95% CI for the difference, -0.06 to 0.25, P = .28). There was a higher incidence of thromboembolic events for the transfusion threshold of 10 g/dL (22/101 [21.8%] vs 8/99 [8.1%] for the threshold of 7 g/dL, odds ratio, 0.32 [95% CI, 0.12 to 0.79], P = .009).. In patients with closed head injury, neither the administration of erythropoietin nor maintaining hemoglobin concentration of greater than 10 g/dL resulted in improved neurological outcome at 6 months. The transfusion threshold of 10 g/dL was associated with a higher incidence of adverse events. These findings do not support either approach in this setting.. clinicaltrials.gov Identifier: NCT00313716.

Topics: Adult; Anemia; Brain Injuries; Erythrocyte Transfusion; Erythropoietin; Female; Glasgow Outcome Scale; Hemoglobins; Humans; Male; Middle Aged; Neurologic Examination; Persistent Vegetative State; Reference Values; Severity of Illness Index; Thromboembolism; Treatment Outcome; Young Adult

Patients with systolic heart failure and anemia have worse symptoms, functional capacity, and outcomes than those without anemia. We evaluated the effects of darbepoetin alfa on clinical outcomes in patients with systolic heart failure and anemia.. In this randomized, double-blind trial, we assigned 2278 patients with systolic heart failure and mild-to-moderate anemia (hemoglobin level, 9.0 to 12.0 g per deciliter) to receive either darbepoetin alfa (to achieve a hemoglobin target of 13 g per deciliter) or placebo. The primary outcome was a composite of death from any cause or hospitalization for worsening heart failure.. The primary outcome occurred in 576 of 1136 patients (50.7%) in the darbepoetin alfa group and 565 of 1142 patients (49.5%) in the placebo group (hazard ratio in the darbepoetin alfa group, 1.01; 95% confidence interval, 0.90 to 1.13; P=0.87). There was no significant between-group difference in any of the secondary outcomes. The neutral effect of darbepoetin alfa was consistent across all prespecified subgroups. Fatal or nonfatal stroke occurred in 42 patients (3.7%) in the darbepoetin alfa group and 31 patients (2.7%) in the placebo group (P=0.23). Thromboembolic adverse events were reported in 153 patients (13.5%) in the darbepoetin alfa group and 114 patients (10.0%) in the placebo group (P=0.01). Cancer-related adverse events were similar in the two study groups.. Treatment with darbepoetin alfa did not improve clinical outcomes in patients with systolic heart failure and mild-to-moderate anemia. Our findings do not support the use of darbepoetin alfa in these patients. (Funded by Amgen; RED-HF ClinicalTrials.gov number, NCT00358215.).

Topics: Aged; Anemia; Darbepoetin alfa; Double-Blind Method; Erythropoietin; Female; Heart Failure, Systolic; Hematinics; Hemoglobins; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Proportional Hazards Models; Shock, Septic; Stroke; Thromboembolism; Treatment Failure

The HEBE III trial showed that epoetin alfa administration in patients with a first ST-elevation myocardial infarction (STEMI) did not improve left ventricular function at 6 weeks after primary percutaneous coronary intervention (PCI). The long term effects of erythropoiesis- stimulating agents on cardiovascular morbidity and mortality are unknown, therefore we evaluated clinical events at 1 year after PCI.. A total of 529 patients with a first STEMI and successful primary PCI were randomized to standard optimal medical treatment (N = 266) or an additional bolus of 60,000 IU epoetin alfa administered intravenously (N = 263) within 3 h after PCI. Analyses were performed by intention to treat.. At 1 year after STEMI, 485 patients had complete follow-up. The rate of the composite end point of all-cause mortality, re-infarction, target vessel revascularization, stroke and/or heart failure was 6.4 % (N = 15) in the epoetin alfa group and 9.6 % (N = 24) in the control group (p = 0.18). Thromboembolic events were present in 1.3 % (N = 3) of patients in the epoetin alfa group and 2.4 % (N = 6) in the control group. There was no evidence of benefit from epoetin alfa administration in subgroups of patients.. Administration of a single bolus of epoetin alfa in patients with STEMI does not result in a reduction of cardiovascular events at 1 year after primary PCI. There was a comparable incidence of thromboembolic complications in both treatment groups, suggesting that epoetin alfa administration is safe at long term.

Topics: Aged; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Recombinant Proteins; Thromboembolism

Increased viscosity may increase the risk of thrombosis or thromboembolic events. Recombinant human erythropoietin (rHuEPO) is the key stone treatment in anemic ESRD patients with the thrombotic limiting side effect. We evaluated the influence of clinical and laboratory findings on plasma viscosity in MHD patients in the present study.. After applying exclusion criteria 84 eligible MHD patients were included (30 female, age: 54.7 ± 13.7 years).. Patients with high viscosity had longer MHD history, calcium × phosphorus product, and higher rHuEPO requirement (356.4 versus 204.2 U/kg/week, P: 0.006). rHuEPO hyporesponsiveness was also more common in hyperviscosity group. According to HD duration, no rHuEPO group had the longest and the low rHuEPO dosage group had the shortest duration. Despite similar Hb levels, 68% of patients in high rHuEPO dosage group; and 38.7% of patients in low rHuEPO dosage group had higher plasma viscosity (P: 0.001). Patients with hyperviscosity had higher rHuEPO/Hb levels (P: 0.021). Binary logistic regression analyses revealed that rHuEPO hyporesponsiveness was the major determinant of hyperviscosity.. We suggest that the hyperviscous state of the hemodialysis patients may arise from the inflammatory situation of long term HD, the calcium-phosphorus mineral abnormalities, rHuEPO hyporesponsiveness, and related high dosage requirements.

Topics: Adult; Aged; Anemia; Arteriovenous Shunt, Surgical; Blood Viscosity; Calcium; Drug Resistance; Erythropoietin; Female; Hemoglobins; Humans; Iron; Kidney Failure, Chronic; Male; Middle Aged; Myocardial Infarction; Phosphorus; Prospective Studies; Recombinant Proteins; Renal Dialysis; Thromboembolism

Extended-interval dosing of epoetin alfa (EPO) is commonly used to treat anemia in patients with chronic kidney disease (CKD). This study aimed to demonstrate that EPO dosed every 2 weeks (Q2W) and every 4 weeks (Q4W) was noninferior to once-weekly (QW) dosing.. 430 anemic subjects with stage 3 to 4 CKD receiving a stable QW dose of EPO were randomized 1:1:2 to QW, Q2W, and Q4W dosing for 36 weeks. Hemoglobin (Hb) was measured weekly, and the dose of EPO was adjusted to maintain an Hb level of 11.0 to 11.9 g/dl. The primary endpoint was change in Hb from baseline to the average of the last 12 weeks of treatment.. Both the Q2W and Q4W dosing groups were noninferior to the QW group. The estimated difference of the mean change in Hb between Q2W and QW was -0.03 g/dl; and between Q4W and QW was -0.09 g/dl. From weeks 13 to 37, the mean percentage of weeks per subject with Hb 10.0 to 11.9 g/dl, inclusive, was 81% for QW, 81% for Q2W, and 75% for Q4W. Death occurred, respectively, in 4%, 3%, and 4%; thromboembolic vascular events occurred in 3%, 5%, and 3%; and serious adverse events occurred in 22%, 26%, and 26% of subjects.. Q2W and Q4W EPO dosing maintained Hb levels in subjects with stage 3 to 4 CKD. Deaths, thromboembolic vascular events, and serious adverse events were comparable across the dosing groups.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Drug Administration Schedule; Drug Monitoring; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Iron Compounds; Kidney Diseases; Male; Middle Aged; Recombinant Proteins; Risk Assessment; Severity of Illness Index; Thromboembolism; Time Factors; Treatment Outcome; United States; Young Adult

In clinical practice, physicians often use once-weekly (QW) and biweekly (Q2W) dosing of epoetin alfa to treat anemia in patients with chronic kidney disease (CKD). Although the literature supports this practice, previous studies were limited by short treatment duration, lack of randomization, or absence of the approved three times per week (TIW) dosing arm. This randomized trial evaluated extended dosing regimens of epoetin alfa, comparing QW and Q2W to TIW dosing in anemic CKD subjects. The primary objective was to show that treatment with epoetin alfa at QW and Q2W intervals was not inferior to TIW dosing.. 375 subjects with stage 3 to 4 CKD were randomized equally to the three groups and treated for 44 wk; to explore the impact of changing from TIW to QW administration on hemoglobin (Hb) control and adverse events, subjects on TIW switched to QW after 22 wk. The Hb was measured weekly, and the dose of epoetin alfa was adjusted to achieve and maintain an Hb level of 11.0 to 11.9 g/dl.. Both the QW and Q2W regimens met the primary efficacy endpoint. More subjects in the TIW group than in the QW and Q2W groups exceeded the Hb ceiling. Adverse events were similar across treatment groups and consistent with the morbidities of CKD patients.. Administration of epoetin alfa at QW and Q2W intervals are potential alternatives to TIW dosing for the treatment of anemia in stage 3 to 4 CKD subjects.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Dose-Response Relationship, Drug; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Hypertension, Renal; Incidence; Iron; Kidney Failure, Chronic; Male; Middle Aged; Morbidity; Recombinant Proteins; Renal Dialysis; Thromboembolism; Treatment Outcome

To determine whether maintaining HGB levels > or = 12.0 g/dL with recombinant human erythropoietin (R-HUEPO) compared to "standard" treatment (transfusion for HGB < or = 10.0 g/dL) improves progression-free survival (PFS), overall survival (OS) and local control (LC) in women receiving concurrent weekly cisplatin and radiation (CT/RT) for carcinoma of the cervix. In addition, to determine whether platinum-DNA adducts were associated with clinical characteristics or outcome.. Patients with stage IIB-IVA cervical cancer and HGB < 14.0 g/dL were randomly assigned to CT/RT+/-R-HUEPO (40,000 units s.c. weekly). R-HUEPO was stopped if HGB > 14.0 g/dL. Endpoints were PFS, OS and LC. Platinum-DNA adducts were quantified using immunocytochemistry assay in buccal cells.. Between 08/01 and 09/03, 109 of 114 patients accrued were eligible. Fifty-two received CT/RT and 57 CT/RT+R-HUEPO. The study closed prematurely, with less than 25% of the planned accrual, due to potential concerns for thromboembolic event (TE) with R-HUEPO. Median follow-up was 37 months (range 9.8-50.4 months). PFS and OS at 3 years should be 65% and 75% for CT/RT and 58% and 61% for CT/RT+R-HUEPO, respectively. TE occurred in 4/52 receiving CT/RT and 11/57 with CT/RT+R-HUEPO, not all considered treatment related. No deaths occurred from TE. High-platinum adducts were associated with inferior PFS and LC.. TE is common in cervical cancer patients receiving CT/RT. Difference in TE rate between the two treatments was not statistically significant. The impact of maintaining HGB level > 12.0 g/dL on PFS, OS and LC remains undetermined.

Topics: Adult; Aged; Anemia; Antineoplastic Agents; Cisplatin; Combined Modality Therapy; DNA Adducts; Erythropoietin; Female; Hemoglobins; Humans; Middle Aged; Neoplasm Staging; Recombinant Proteins; Thromboembolism; Uterine Cervical Neoplasms

Partial correction of renal anaemia with erythropoietin improves quality of life (QoL). We aimed to examine if normalization of haemoglobin with epoetin alfa in pre-dialysis and dialysis patients further improves QoL and is safe.. 416 Scandinavian patients with renal anaemia [pre-dialysis, haemodialysis (HD) and peritoneal dialysis patients] were randomized to reach a normal haemoglobin of 135-160 g/l (n=216) or a subnormal haemoglobin of 90-120 g/l (n=200) with or without epoetin alfa. Study duration was 48-76 weeks. QoL was measured using Kidney Disease Questionnaires in 253 Swedish dialysis patients. Safety was examined in all patients.. QoL improved, measured as a decrease in physical symptoms (P=0.02), fatigue (P=0.05), depression (P=0.01) and frustration (P=0.05) in the Swedish dialysis patients when haemoglobin was normalized. In pre-dialysis patients, diastolic blood pressure was higher in the normal compared with the subnormal haemoglobin group after 48 weeks. However, the progression rate of chronic renal failure was comparable. In the normal haemoglobin group (N-Hb), 51% had at least one serious adverse event compared with 49% in the subnormal haemoglobin group (S-Hb) (P=0.32). The incidence of thrombovascular events and vascular access thrombosis in HD patients did not differ. The mortality rate was 13.4% in the N-Hb group and 13.5% in the S-Hb group (P=0.98). Mortality decreased with increasing mean haemoglobin in both groups.. Normalization of haemoglobin improved QoL in the subgroup of dialysis patients, appears to be safe and can be considered in many patients with end-stage renal disease.

Topics: Aged; Anemia; Antihypertensive Agents; Blood Pressure; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Hospitalization; Humans; Kidney; Male; Middle Aged; Peritoneal Dialysis; Quality of Life; Recombinant Proteins; Renal Dialysis; Safety; Sick Leave; Thromboembolism

A phase II trial was conducted to explore the efficacy and tolerability of combining thalidomide (100 mg/d p.o.) with an erythropoietic growth factor (darbepoietin-alpha 2.25 micro g/kg/d s.c.) in patients with low-to-intermediate-risk myelodysplastic syndromes (MDS). However, the trial had to be discontinued early because of an unexpectedly high incidence of thromboembolic events. Of the first seven patients enrolled, two developed deep-vein thrombosis and one died of massive pulmonary embolism. We concluded that thalidomide might significantly increase the thromboembolic risk of erythropoietic proteins in MDS patients. Careful clinical surveillance and thrombosis prophylaxis (heparin or oral anticoagulation) should be considered for MDS patients undergoing combined treatment with thalidomide and erythropoietic growth factors.

Topics: Aged; Anticoagulants; Darbepoetin alfa; Drug Therapy, Combination; Erythropoietin; Heparin, Low-Molecular-Weight; Humans; Immunosuppressive Agents; Middle Aged; Myelodysplastic Syndromes; Pulmonary Embolism; Thalidomide; Thromboembolism; Venous Thrombosis

In a double-blind, randomized, placebo-controlled trial we evaluated the effects of the administration of recombinant human erythropoietin (5 x 500 U epoetin beta/kg body weight intravenously over a 14-day period before surgery) in patients undergoing cardiac surgery and in whom autologous blood donation was contraindicated on platelet count, platelet distribution width, mean platelet volume (MPV), and certain hemostaseologic parameters. All patients received 3 x 70 IU heparin/kg per day s.c. from 2 days before operation. No thromboembolic events were associated with epoetin beta therapy during the study period. The thrombocytic parameters showed no significant changes in the placebo group before surgery, and the preoperative hematocrit increase in the epoetin beta group was accompanied with an MPV drop (in contrast to the known MPV rise in recombinant human erythropoietin-treated patients with uremia) by a mean of 0.85 fl and a platelet distribution width rise by 3.3% without a significant change in platelet count. In the epoetin beta group the coagulation time (K) of thromboelastogram (TEG) showed an increase from 4.8 to 5.4 minutes by the seventh study day and after the initiation of heparin therapy a further increase to 7.5 minutes. The higher preoperative K increase in the epoetin beta group may partly be a result of the MPV reduction, because smaller platelets are less reactive, a fact underlined by the negative correlation between the preoperative changes of MPV and reaction time of TEG (r = -0.58, p = 0.0148). In contrast, in the placebo group the K of TEG increased only after the start of heparin therapy (from 5.1 to 6.4 minutes). The significant drop in MPV in the epoetin beta group and the higher increase in K of TEG and the other investigated hemostatic parameters do not suggest any increased thromboembolic risk during the preoperative epoetin beta therapy. Therefore this treatment seems to be a safe way for increasing mean hematocrit by approximately 0.06 within the normal range and reducing the homologous blood requirement in patients undergoing elective cardiac surgery.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Blood Transfusion; Cardiac Surgical Procedures; Double-Blind Method; Erythropoietin; Female; Hematocrit; Hemostasis, Surgical; Humans; Intraoperative Period; Male; Middle Aged; Placebos; Platelet Activation; Platelet Count; Premedication; Recombinant Proteins; Risk Factors; Thromboembolism

Erythropoietin corrects anemia and improves hemostasis, but on the other hand bears a risk of thrombotic complications. Therefore in the present study an attempt has been made to evaluate bleeding time, platelet functions and some hemostatic and fibrinolytic parameters in relation to blood and platelet serotonin before and after 1, 2, 4, 8 and 12 weeks of treatment. 22 chronically hemodialyzed patients were administered with human recombinant erythropoietin (rHuEPO) in a dose of 2000 IU s.c. 3 times a week. Bleeding time was shortened significantly as early as after 1 week of the therapy, whereas hematocrit and hemoglobin increased after 2 weeks. These changes lasted throughout the study. Only a transient rise in platelet count, collagen-induced platelet aggregation, beta-thromboglobulin and VIII:C activity were observed during therapy relative to baseline values. ADP- and arachidonic acid-induced platelet aggregation seemed to be unaffected by rHuEPO treatment, whereas a gradual and progressive enhancement in platelet aggregation in response to ristocetin was found, starting from the 2nd week of the therapy. It lasted throughout the study and correlated inversely with the bleeding time and positively with a rise in both blood and platelet serotonin. rHuEPO did not alter plasminogen, fibrinogen, platelet factor 4, alpha 2 macroglobulin levels, protein C activity and euglobulin clot lysis time. A decline in protein C and S concentrations and antithrombin III activity observed during the therapy were counterbalanced by a fall in the activity of alpha 2 antiplasmin, C1 esterase inhibitor and plasminogen activator inhibitor. It is concluded that rHuEPO may improve platelet/vessel wall interactions possibly by means of serotonergic mechanisms. A lowered activity of inhibitors of fibrinolysis may be regarded as a protection against a general tendency to thrombosis during rHuEPO therapy.

Topics: Adenosine Diphosphate; Adult; Anemia; Arachidonic Acid; Biomarkers; Bleeding Time; Blood Platelets; Blood Proteins; Erythropoietin; Female; Fibrinolysis; Hematocrit; Hemoglobins; Hemostasis; Humans; Kidney Failure, Chronic; Male; Middle Aged; Platelet Aggregation; Recombinant Proteins; Renal Dialysis; Ristocetin; Serotonin; Thromboembolism; Time Factors

Topics: Aged; Algorithms; Alleles; Bone Marrow Examination; Diagnosis, Differential; Erythropoietin; Female; Hemoglobinometry; Humans; Hydroxyurea; Janus Kinase 2; Male; Middle Aged; Phlebotomy; Point Mutation; Polycythemia; Polycythemia Vera; Prognosis; Thromboembolism

With the emerging new warnings surrounding the use of erythropoiesis-stimulating agents (ESAs), the pharmacist's role as health educator and risk communicator expands further to include patient scrutiny to check for eligibility and patient monitoring to check for response or toxicity. This review explores the benefits and risks linked to ESAs use, and the proposed role.. ESAs have been increasingly used for the treatment of chemotherapy-induced anemia because of its documented effect on decreasing transfusion dependency. However, their use has been associated with thromboembolic complications, tumor progression, and decreased overall survival. This review covers current recommendations and guidelines that surround ESAs use in the supportive care of cancer patients.. To minimize or prevent the complications associated with ESAs use, cancer patients should be adequately monitored and counseled. This highlights the importance of the pharmacist's involvement to optimize patient care.

Topics: Anemia; Contraindications; Disease Progression; Drug Monitoring; Erythropoiesis; Erythropoietin; Hematinics; Humans; Neoplasms; Patient Education as Topic; Pharmacists; Practice Guidelines as Topic; Professional Role; Quality of Life; Risk Factors; Thromboembolism

To increase the survival rate of patients with acute superior mesenteric artery thromboembolism (ASMAT) treated by catheter thrombolysis, we examined the effects of delivering edaravone and asialoerythropoietin, agents with tissue-protective activities, using a rabbit autologous fibrin clot ASMAT model. Japanese white rabbits (n=32) were randomly separated into four equal groups. 45 min after introducing autologous fibrin clot, Group U received urokinase and heparin; Group E received urokinase and heparin plus edaravone; Group A received urokinase and heparin plus asialoerythropoietin; and Group EA received urokinase, heparin and edaravone plus asialoerythropoietin via a catheter. The intestines were removed 6 h later and intestinal mucosal damage was scored using the Park's injury score. Survival time was assessed. Average mucosal injury was 5.78+/-1.52 (Group U), 2.88+/-0.72 (Group E), 1.90+/-1.23 (Group A) and 1.18+/-1.25 (Group EA). The degree of mucosal injury was significantly lower in Group EA than in Groups U and E (p<0.05). Conversely, there was no significant difference between Group A and Group EA, or between Group A and Group E. The survival times were 31.50+/-13.30 h (Group U), 51.00+/-24.74 h (Group E), 48.00+/-16.97 h (Group A) and 82+/-51.07 h (Group EA); the difference among the four groups was not significant. In conclusion, the concomitant administration of asialoerythropoietin and edaravone reduced mucosal membrane injury significantly compared with edaravone alone. However, to improve the survival of ASMAT rabbit models, the delivery of an appropriate dose of asialoerythropoietin is required, together with the development of methods to assess peripheral recanalisation.

Topics: Animals; Antipyrine; Asialoglycoproteins; Catheterization; Disease Models, Animal; Drug Combinations; Edaravone; Erythropoietin; Fibrin; Fibrinolytic Agents; Free Radical Scavengers; Heparin; Injections, Intra-Arterial; Intestinal Mucosa; Mesenteric Artery, Superior; Mesenteric Vascular Occlusion; Rabbits; Random Allocation; Reperfusion Injury; Survival Rate; Thromboembolism; Urokinase-Type Plasminogen Activator

To investigate whether the incidence of thromboembolic events (venous and arterial) increases when bevacizumab-based chemotherapy and erythropoietin stimulating agents (ESAs) are used in combination versus alone.. A retrospective, pilot study of 79 colorectal cancer patients treated with chemotherapy were divided into 3 groups: bevacizumab (n = 28), ESA (n = 21), and bevacizumab plus ESA (n = 28). The primary end point was the incidence of thromboembolic events. Secondary endpoints included median time-to-event; effect of anticoagulation; and association with concurrent chemotherapy, baseline risk factors, hemoglobin, and performance status.. The incidence of thromboembolic events was 11% in the bevacizumab group, 23.8% in the ESA group, and 30% in the combination group (P = 0.194). The median time-to-event was 7.5, 3.5, and 2.5 months, respectively (P = 0.060). The 5 month difference in time-to-event between the bevacizumab group and combination group was significant (P = 0.045). When combining all patients, ESA treatment, prior venous thromboembolic event (VTE), obesity, cardiac disease, and use of exogenous hormones were strong predictors for thromboembolic events. Prior VTE was a strong predictor in those patients in the combination group.. The incidence of thromboembolic events was increased with the combination of bevacizumab plus ESA compared with either agent alone with chemotherapy. Median time-to-event in the combination group was significantly shorter compared with the bevacizumab group. Prior VTE, cardiac disease, obesity, and exogenous hormone use should be taken in consideration when using the combination of bevacizumab and ESAs.

Topics: Adult; Aged; Aged, 80 and over; Angiogenesis Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Bevacizumab; Colorectal Neoplasms; Drug Therapy, Combination; Erythropoietin; Female; Hemoglobins; Humans; Male; Middle Aged; Neoplasm Staging; Pilot Projects; Prognosis; Recombinant Proteins; Retrospective Studies; Survival Rate; Thromboembolism; Vascular Endothelial Growth Factor A

To critically examine the cardiovascular and thromboembolic risks associated with erythropoietin stimulating proteins (ESPs) in men with normal hemoglobin levels undergoing open radical retropubic prostatectomy.. Between October 1, 2000, through December 31, 2006, a total of 1308 men underwent open radial retropubic prostatectomy by a single surgeon. Of these men, 1095 received preoperative ESPs. Hematocrit levels measured at baseline, immediately before anesthesia induction and at hospital discharge, were prospectively entered into a database. Thromboembolic and cardiovascular complications were prospectively captured during the hospitalization and after surgery.. The mean Delta preoperative hematocrit level was 5.9 g/dL. The pre-anesthesia induction hematocrit level was 49.2%. Hospital discharge hematocrit level was 33.6 g/dL. The overall risk of cardiovascular and thromboembolic complications in men receiving ESP were 0.55% and 0.45%, respectively. The risk of cardiovascular and thromboembolic complications were independent of the Delta in preoperative hematocrit or the absolute level of the pre-anesthesia induction hematocrit.. ESPs represent a safe and effective preoperative blood management strategy for men undergoing open radical retropubic prostatectomy.

Topics: Aged; Analysis of Variance; Cardiovascular Diseases; Cohort Studies; Erythropoietin; Follow-Up Studies; Hematocrit; Hemoglobins; Humans; Male; Middle Aged; Postoperative Complications; Preoperative Care; Prospective Studies; Prostatectomy; Prostatic Neoplasms; Recombinant Proteins; Risk Assessment; Survival Rate; Thromboembolism; Treatment Outcome

Topics: Anemia; Cardiovascular Diseases; Erythropoietin; Humans; Male; Postoperative Complications; Preoperative Care; Prognosis; Prostatectomy; Prostatic Neoplasms; Recombinant Proteins; Risk Assessment; Survival Analysis; Thromboembolism

Topics: Anemia; Antineoplastic Agents; Darbepoetin alfa; Double-Blind Method; Epoetin Alfa; Erythropoiesis; Erythropoietin; Female; Hematinics; Humans; Incidence; Male; Neoplasms; Prognosis; Randomized Controlled Trials as Topic; Recombinant Proteins; Risk Assessment; Survival Analysis; Thromboembolism; Treatment Outcome

Topics: Anemia; Antineoplastic Agents; Disease Progression; Erythropoietin; Hemoglobins; Humans; Neoplasms; Recombinant Proteins; Thromboembolism

For reasons of religious belief, Jehova's Witnesses do not accept blood transfusions or the infusion of blood products. In situations in which severe, life-threatening anemia develops, patient refusal to receive a transfusion can create serious ethical and legal problems. The principle of patient autonomy, which implies the freedom to accept or reject treatment, comes into conflict with the physician's obligation to safeguard the patient's life using all means possible. We report 2 cases of severe anemia in Jehova's Witnesses. One was due to menorrhagia and the other to postpartum bleeding. The physician should be aware of alternatives to infusion of blood products and know how to cope with an unexpected critical event in these patients. The measures we took were effective in our patients. In the case of menorrhagia, hormone treatment is effective when the woman wishes to preserve the ability to conceive and avoid surgery (endometrial ablation and hysterectomy). In postpartum bleeding refractory to conservative treatment, selective embolization of bleeding vessels may make it unnecessary to resort to more aggressive treatment, such as obstetric hysterectomy.

Topics: Adult; Anemia; Anti-Anxiety Agents; Anticoagulants; Cervix Uteri; Combined Modality Therapy; Contraceptives, Oral, Hormonal; Dalteparin; Embolization, Therapeutic; Erythropoietin; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Humans; Immobilization; Jehovah's Witnesses; Menorrhagia; Oxygen Inhalation Therapy; Parenteral Nutrition; Postpartum Hemorrhage; Pregnancy; Recombinant Proteins; Thromboembolism; Treatment Refusal; Young Adult

Topics: Adult; Anemia; Antiviral Agents; Carcinoma, Hepatocellular; Cohort Studies; Drug Therapy, Combination; Erythropoietin; Female; Hepatitis C, Chronic; Humans; Liver Neoplasms; Male; Middle Aged; Thromboembolism

In 2007, several international studies brought useful information for the daily work of internists in hospital settings. This summary is of course subjective but reflects the interests and questions of the chief residents of the Department of internal medicine who wrote this article like an original trip in medical literature. This trip will allow you to review some aspects of important fields such as heart failure, diabetes, endocarditis, COPD, and quality of care. Besides the growing diversity of the fields covered by internal medicine, these various topics underline also the uncertainty internists have to face in a practice directed towards evidence.

Topics: Accidental Falls; Aged; Albuterol; Anemia; Anticoagulants; Antidiuretic Hormone Receptor Antagonists; Atrial Fibrillation; Attitude of Health Personnel; Benzazepines; Bronchitis, Chronic; Bronchodilator Agents; Cardiac Pacing, Artificial; Diabetes Mellitus; Endocarditis, Bacterial; Erythropoietin; Heart Failure; Heparin; Humans; Internal Medicine; Interprofessional Relations; Medical Staff, Hospital; Myocardial Infarction; Recombinant Proteins; Risk Management; Rosiglitazone; Salmeterol Xinafoate; Thiazolidinediones; Thromboembolism; Tolvaptan; Vasodilator Agents; Ventricular Dysfunction, Left; Workload

Topics: Anemia; Antineoplastic Agents; Erythropoietin; Hemoglobins; Humans; Neoplasms; Recombinant Proteins; Risk Assessment; Thromboembolism

Topics: Anemia; Cardiovascular Diseases; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Recombinant Proteins; Renal Insufficiency, Chronic; Thromboembolism

Topics: Advisory Committees; Anemia; Darbepoetin alfa; Drug and Narcotic Control; Drug Labeling; Epoetin Alfa; Erythropoiesis; Erythropoietin; Hematinics; Humans; Neoplasms; Recombinant Proteins; Risk; Stimulation, Chemical; Thromboembolism; United States; United States Food and Drug Administration

Topics: Anemia; Blood Platelets; Erythropoietin; Hematinics; Hemoglobins; Humans; Neoplasms; Neovascularization, Pathologic; Receptors, Erythropoietin; Thromboembolism

Topics: Anemia; Clinical Trials as Topic; Erythropoietin; Humans; Neoplasms; Risk Factors; Thromboembolism; Treatment Outcome

Topics: Clone Cells; Erythropoietin; Female; Humans; Myelopoiesis; Risk Factors; Thrombocythemia, Essential; Thromboembolism

We have generated a transgenic mouse line that reaches a hematocrit concentration of 0.85 due to constitutive overexpression of human erythropoietin in an oxygen-independent manner. Unexpectedly, this excessive erythrocytosis did not lead to thrombembolic complications in all investigated organs at any age. Thus, we investigated the mechanisms preventing thrombembolism in this mouse model. Blood analysis revealed an age-dependent elevation of reticulocyte numbers and a marked thrombocytopenia that matched the reduced megakaryocyte numbers in the bone marrow. However, platelet counts were not different from wild-type controls, when calculations were based on the distribution (eg, plasma) volume, thereby explaining why thrombopoietin levels did not increase in transgenic mice. Nevertheless, bleeding time was significantly increased in transgenic animals. A longitudinal investigation using computerized thromboelastography revealed that thrombus formation was reduced with increasing age from 1 to 8 months in transgenic animals. We observed that increasing erythrocyte concentrations inhibited profoundly and reversibly thrombus formation and prolonged the time of clot development, most likely due to mechanical interference of red blood cells with clot-forming platelets. Transgenic animals showed increased nitric oxide levels in the blood that could inhibit vasoconstriction and platelet activation. Finally, we observed that plasmatic coagulation activity in transgenic animals was significantly decreased. Taken together, our findings suggest that prevention of thrombembolic disease in these erythrocytotic transgenic mice was due to functional consequences inherent to increased erythrocyte concentrations and a reduction of plasmatic coagulation activity, the cause of which remains to be elucidated.

Topics: Age Factors; Animals; Blood Coagulation; Blood Coagulation Tests; Erythropoietin; Hematocrit; Hemostasis; Humans; Mice; Mice, Transgenic; Nitric Oxide; Polycythemia; Thromboembolism

Recombinant human erythropoietin (EPO) therapy in uremic patients raises the hematocrit (Hct) and increases physical exercise capacity (1,2) and quality of life (1). In general, partial correction of anemia to subnormal levels in uremic patients has proven to be safe with few serious adverse effects apart from hypertension (3). Ever since the advent of EPO the prospect of abuse of the hormone by sportsmen has been subject to scrutiny. Both maximal oxygen uptake and endurance capacity are increased after EPO treatment in healthy subjects (4). Moreover, EPO treatment in healthy subjects has been found to induce an accentuated blood pressure reaction after submaximal exercise (5). Previous studies have shown that extreme physical exertion can predispose to an increased intravascular coagulation (6). Moreover there is a significantly increased risk of thrombosis in patients with myeloproliferative disorders, particularly in polycythemia vera (7). An enhanced risk of cardiovascular events may therefore arise should sportsmen abuse EPO as a blood doping agent. The aim of this study was to examine the effects of an EPO-induced increase in Hct on the coagulation system in healthy subjects.

Topics: Adult; Antithrombin III; Blood Coagulation Tests; Erythropoietin; Fibrinopeptide A; Hematocrit; Humans; Male; Peptide Hydrolases; Recombinant Proteins; Reference Values; Risk; Sports Medicine; Substance-Related Disorders; Thromboembolism

A 44-year-old man developed idiopathic membranous nephropathy and true secondary polycythaemia. With advancing azotemia, polycythaemia gradually resolved and venesection was no longer required. Only 2 cases of polycythaemia associated with membranous nephropathy have been reported previously. Secondary polycythaemia is a rarely reported association of membranous nephropathy and may increase the risk of thromboembolism, which might be prevented with venesection.

Topics: Adult; Bloodletting; Erythropoietin; Glomerulonephritis, Membranous; Humans; Male; Polycythemia; Thromboembolism

After sporadic reports of renal graft artery thromboses, prophylaxis against thrombosis (PAT) was given to all of our r-HuEPO-treated patients (n = 35) during a period of 2 years. No thromboembolic events (TEE) occurred in the r-HuEPO-treated group receiving PAT. However, the PAT-protocol (500 ml dextran on days 0, 1, 3 and 5, followed by low doses of aspirin, 160-250 mg daily) resulted in a 54.3% incidence of bleeding complications, of which 22.9% were major (i.e., necessitating multiple transfusions or invasive procedures). A group of renal graft recipients (n = 83), who were not treated with r-HuEPO and were not given PAT, showed a 10.8% incidence of bleeding complications of which 2.4% major. Two cases of TEE were noted in the untreated group. The difference in bleeding complications between the two groups was statistically significant (0.025 > P > 0.01). The difference in TEE between the groups was not significant. We found no difference between the groups with regard to early and late graft function and the incidence of acute rejections. In summary, r-HuEPO treatment did not influence the prognosis in renal graft recipients. The use of PAT in the r-HuEPO-treated group resulted in a high incidence of bleeding complications. In consequence, we have abandoned the routine use of PAT in this patient group.

Topics: Adult; Erythropoietin; Humans; Kidney Transplantation; Postoperative Complications; Recombinant Proteins; Retrospective Studies; Thromboembolism; Treatment Outcome

Between 1971 and 1990, 251 kidney transplanted patients with a well functioning graft were evaluated to determine the frequency of post-transplant erythrocytosis (PTE). Thirty-one patients (13 percent) developed polycythaemia 10.6 +/- 10 months after transplantation. Thromboembolic complications occurred in 22 percent of the cases. The frequency of PTE was higher in males than in females (sex ratio: 7.2 vs 2.1; P < 0.05). Patients with renal dysplasia had a lower incidence of PTE (3 vs 22 percent; P < 0.05) as did those who had been treated with azathioprine (9.4 vs 19 percent; P < 0.05). None of the patients treated with recombinant erythropoietin before transplantation developed PTE during a mean follow-up of 15.1 +/- 4.5 months. The majority of polycythaemic patients had normal erythropoietin levels. These results show that there is an erythropoietin-independent proliferation due to an increased sensitivity of erythroid progenitors or to an erythroid stem cell stimulation by cytokines.

Topics: Adult; Azathioprine; Erythropoietin; Female; Humans; Kidney Transplantation; Male; Middle Aged; Polycythemia; Postoperative Complications; Retrospective Studies; Thromboembolism

Thromboembolism might complicate the treatment of patients with chronic renal failure with Recombinant Human Erythropoietin (ReHuEPO). In order to detect prothrombotic changes, a number of hemostatic and fibrinolytic parameters was determined during ReHuEPO treatment of fifteen chronic hemodialysis patients (mean age 47.1 years; ten females, five males). To avoid the influence of hemoconcentration and/or dilution, the patients were kept normovolemic, using the method of echography of the inferior vena cava diameter. In a first group of eight patients, we investigated platelet count and function. During ReHuEPO, a significant rise of hematocrit (19 +/- 3 to 34 +/- 5%, p < 0.001) was observed. Bleeding time shortened (7'33'' +/- 3'39'' to 3'41'' +/- 3'19''; p < 0.001) and platelet count increased (222 +/- 45 to 254 +/- 49 10 9/l; p < 0.005). The initial negative in vitro spontaneous platelet reactivity became positive in two of them, whereas the decrease in ADP threshold in the whole group (2.0 +/- 0.1 to 1.10 +/- 0.4 mumol, p < 0.02) indicated an increased induced platelet reactivity. In all patients prothrombotic changes were observed. The protein-C antigen and protein-C activity and the total and free protein-S antigen decreased significantly. The plasminogen activator inhibitor (PAI) activity in the whole group did not change significantly (6.4 +/- 4.1 to 5.4 +/- 4.8 AU/ml). However, in the patients with fistula thrombosis (n = 3), higher values in all test points were found compared to those without thrombosis.

Topics: Erythropoietin; Female; Fibrinolysis; Hematocrit; Hemostasis; Humans; Kidney Failure, Chronic; Male; Middle Aged; Protein C; Renal Dialysis; Thromboembolism

Topics: Alkylating Agents; Erythropoietin; Hematocrit; Hemorrhage; Humans; Leukemia; Polycythemia; Polycythemia Vera; Smoking; Thromboembolism