losartan-potassium and Venous-Thrombosis

The objective of this study is to assess the effectiveness of erythropoietin (EPO) on mortality, neurological outcomes, and adverse event in the treatment of traumatic brain injury (TBI).. We searched databases including PubMed, OVID, and the Cochrane Library from inception until October 18, 2019 for randomized controlled trials (RCTs) to compare EPO treatment group and placebo in patients with TBI. Two authors independently processed the data and evaluated the quality of inclusion studies. Statistical analysis was performed with heterogeneity test with. Seven RCTs accounting for 1180 patients were included after meeting the inclusion criteria. Compared with placebo, the overall mortality of EPO-treated patients was significantly reduced (RR 0.68 [95% CI 0.50-0.93];. The results showed that the administration of EPO may reduce the risk of mortality without enhancing the occurrence of DVT in TBI patients. However, the effect of EPO on neurological outcome remains indistinct. Through subgroup analysis, we demonstrated that the dose of EPO may be a potential factor affecting the heterogeneity in neurological function and that the follow-up duration may influence the stability of the result.

Topics: Adult; Brain Injuries, Traumatic; Erythropoietin; Female; Humans; Incidence; Male; Middle Aged; Prognosis; Publication Bias; Risk; Treatment Outcome; Venous Thrombosis; Young Adult

To determine the value of erythropoietin in reducing allogeneic transfusions, it is important to assess the effects, safety and costs for individual indications. Previous studies neither compared the effects of erythropoietin between total hip and total knee arthroplasty, nor evaluated the safety or costs. We performed a meta-analysis to assess the effects of erythropoietin in total hip and knee arthroplasty separately. Safety and costs were evaluated as secondary outcomes.. A systematic literature search was performed to identify randomized controlled trials evaluating the effect of erythropoietin in total hip and knee arthroplasty until April 2014. Study data were extracted using standardized forms and pooled using a random-effects model. Strength of the evidence was evaluated using Cochrane's Collaboration's tool for risk of bias assessment.. Seven studies were included (2439 patients). Erythropoietin significantly reduced exposure to allogeneic transfusion in both hip (RR 0·45; 95%CI 0·33-0·61) and knee (RR 0·38; 95%CI 0·27-0·53) arthroplasty, without differences between indications (P = 0·44). Mean number of transfused red blood cell units was significantly decreased in erythropoietin-treated patients (mean difference -0·57; 95%CI -0·86 to -0·29)(unable to split). No differences in thromboembolic or adverse events were found. Only one study evaluated costs, so that no pooled cost-effectiveness estimates could be given.. Erythropoietin is effective in both hip and knee arthroplasty and can be considered as safe. However, the decision to use erythropoietin on a routine base should be balanced against its costs, which may be relatively high.

Topics: Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Clinical Trials as Topic; Erythrocyte Transfusion; Erythrocytes; Erythropoietin; Humans; Transplantation, Homologous; Venous Thrombosis

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

Preoperative autologous blood donation (PABD) with no risk of blood-borne infection transmission has been considered the supreme blood transfusion therapy, and it has been reported to decrease incidence of postoperative deep-vein thrombosis. However, the need for PABD has decreased in the USA, because 1) risk of blood-borne infection transmission through allogeneic blood transfusion (ABT) has decreased after introduction of nucleic acid amplification test (NAT), and 2) blood collection-induced anemia has been found in many cases due to inapplicability of erythropoietin (rEPO). ABT risks are decreasing in Japan as in the USA, however, ABT has several issues proper to Japan, such as, outpacing of blood demand over supply in the near future and increase of HIV positive donors. Also, as rEPO can be used in Japan, PABD-induced anemia risks are low. Accordingly, necessity of PABD should increase in Japan. However, as those who usually perform PABD in Japan are surgeons, big issues arise such as bacterial contamination during blood collection and ABO incompatibility during transfusion. Underutilization of PABD in gastrointestinal cancer surgery should also be addressed. Appropriate technique and methodology must be established to increase the safety of PABD and to spread PABD in cancer surgery.

Topics: Anemia; Blood Donors; Blood Group Incompatibility; Blood Transfusion, Autologous; Cost-Benefit Analysis; Erythropoietin; HIV Infections; Humans; Japan; Medical Errors; Postoperative Complications; Preoperative Care; Recombinant Proteins; Safety; Venous Thrombosis

One of the primary goals in the perioperative care of orthopaedic patients undergoing surgery is the avoidance of allogeneic transfusion. There are a number of ways to lessen blood loss during surgical intervention including regional hypotensive anesthesia, careful and atraumatic surgical technique, and coagulation of bleeding surfaces. Achieving coagulation is difficult in spinal and arthroplasty procedures because of the large cancellous surfaces that are vascular and are not amenable to ligature or thermal coagulation. All measures of autologous blood salvage should be used including preoperative deposit of autologous blood, hemodilution techniques, intraoperative salvage (when appropriate), and postoperative retrieval and reinfusion. The use of perioperative recombinant erythropoietin is also a useful adjunct to promote stimulation of the bone marrow and increased red cell production. Although many infectious diseases that are transmitted through allogeneic blood transfusions have been lessened by better screening techniques, there is still potential life threatening reactions and viral transmissions that may be avoided by comprehensive blood management in joint arthroplasty.

Topics: Arthroplasty, Replacement; Blood Loss, Surgical; Blood Transfusion, Autologous; Erythropoietin; Hemostasis, Surgical; Humans; Perioperative Care; Postoperative Hemorrhage; Practice Guidelines as Topic; Recombinant Proteins; Venous Thrombosis

Erythropoietin might have neurocytoprotective effects. In this trial, we studied its effect on neurological recovery, mortality, and venous thrombotic events in patients with traumatic brain injury.. Erythropoietin in Traumatic Brain Injury (EPO-TBI) was a double-blind, placebo-controlled trial undertaken in 29 centres (all university-affiliated teaching hospitals) in seven countries (Australia, New Zealand, France, Germany, Finland, Ireland, and Saudi Arabia). Within 24 h of brain injury, 606 patients were randomly assigned by a concealed web-based computer-generated randomisation schedule to erythropoietin (40,000 units subcutaneously) or placebo (0·9% sodium chloride subcutaneously) once per week for a maximum of three doses. Randomisation was stratified by severity of traumatic brain injury (moderate vs severe) and participating site. With the exception of designated site pharmacists, the site dosing nurses at all sites, and the pharmacists at the central pharmacy in France, all study personnel, patients, and patients' relatives were masked to treatment assignment. The primary outcome, assessed at 6 months by modified intention-to-treat analysis, was improvement in the patients' neurological status, summarised as a reduction in the proportion of patients with an Extended Glasgow Outcome Scale (GOS-E) of 1-4 (death, vegetative state, and severe disability). Two equally spaced preplanned interim analyses were done (after 202 and 404 participants were enrolled). This study is registered with ClinicalTrials.gov, number NCT00987454.. Between May 3, 2010, and Nov 1, 2014, 606 patients were enrolled and randomly assigned to erythropoietin (n=308) or placebo (n=298). Ten of these patients (six in the erythropoietin group and four in the placebo group) were lost to follow up at 6 months; therefore, data for the primary outcome analysis was available for 596 patients (302 in the erythropoietin group and 294 in the placebo group). Compared with placebo, erythropoietin did not reduce the proportion of patients with a GOS-E level of 1-4 (134 [44%] of 302 patients in the erythropoietin group vs 132 [45%] of 294 in the placebo group; relative risk [RR] 0·99 [95% CI 0·83-1·18], p=0·90). In terms of safety, erythropoietin did not significantly affect 6-month mortality versus placebo (32 [11%] of 305 patients had died at 6 months in the erythropoietin group vs 46 [16%] of 297 [16%] in the placebo group; RR 0·68 [95% CI 0·44-1·03], p=0·07) or increase the occurrence of deep venous thrombosis of the lower limbs (48 [16%] of 305 vs 54 [18%] of 298; RR 0·87 [95% CI 0·61-1·24], p=0·44).. Following moderate or severe traumatic brain injury, erythropoietin did not reduce the number of patients with severe neurological dysfunction (GOS-E level 1-4) or increase the incidence of deep venous thrombosis of the lower limbs. The effect of erythropoietin on mortality remains uncertain.. The National Health and Medical Research Council and the Transport Accident Commission.

Topics: Adult; Australia; Brain Injuries; Double-Blind Method; Erythropoietin; Europe; Female; Glasgow Outcome Scale; Humans; Incidence; Male; Middle Aged; New Zealand; Saudi Arabia; Treatment Outcome; Venous Thrombosis; Young Adult

Animal data suggest the use of beta-human chorionic gonadotropin followed by erythropoietin to promote brain repair after stroke. The current study directly translated these results by evaluating safety of this sequential growth factor therapy through a 3-center, single-dose, open-label, noncontrolled, Phase IIa trial.. Patients with ischemic stroke 24 to 48 hours old and National Institutes of Health Stroke Scale score of 6 to 24 started a 9-day course of beta-human chorionic gonadotropin (once daily on Days 1, 3, and 5 of study participation) followed by erythropoietin (once daily on Days 7, 8, and 9 of study participation). This study also evaluated performance of serially measured domain-specific end points.. A total of 15 patients were enrolled. Two deaths occurred, neither related to study medications. No safety concerns were noted among clinical or laboratory measures, including screening for deep vein thrombosis and serial measures of serum hemoglobin. In several instances, domain-specific end points provided greater insight into impairments as compared with global outcome measures.. Results support the safety of this sequential, 2-growth factor therapy initiated 24 to 48 hours after stroke onset.

Topics: Adult; Aged; Aged, 80 and over; Brain Ischemia; Chorionic Gonadotropin, beta Subunit, Human; Drug Therapy, Combination; Erythropoietin; Female; Hemoglobins; Humans; Male; Middle Aged; Stroke; Venous Thrombosis; Young Adult

Prospective, open-label, randomized, parallel-group study at 80 centers.. To demonstrate there is no clinically important additional risk for deep vein thrombosis with perioperative use of epoetin alfa versus standard of care in spine surgery without prophylactic anticoagulation.. Trials of epoetin alfa in orthopedic surgery that demonstrated no additional risk of thrombovascular events included perioperative pharmacologic anticoagulation.. Subjects received epoetin alfa 600 U/kg subcutaneously once weekly starting 3 weeks before spinal surgery plus standard of care for blood conservation, or standard of care alone. Perioperative anticoagulation therapy was not permitted; mechanical deep vein thrombosis prophylaxis was allowed. Doppler imaging for deep vein thrombosis was done on postoperative day 4 (or day of discharge), or for suspected deep vein thrombosis. Deep vein thrombosis was diagnosed by Doppler result or adverse event report. The criterion for no additional risk of deep vein thrombosis was a 1-sided 97.5% upper confidence limit < or =4% between groups.. Of the 680 subjects analyzed (340 in each treatment group), 16 (4.7%) in the epoetin alfa group and 7 (2.1%) in the standard of care group had a diagnosis of deep vein thrombosis either by Doppler or by adverse event report with normal Doppler. The between-group difference was 2.6% (97.5% upper confidence limit, 5.4%). Deep vein thrombosis confirmed by Doppler (4.1% vs. 2.1%), other clinically relevant thrombovascular events (1.5% vs. 0.9%), and all adverse events combined (76.5% vs. 73.2%) occurred with similar frequency in the 2 treatment groups.. This study documented a higher incidence of deep vein thrombosis and similar rates of other clinically relevant thrombovascular events with epoetin alfa versus standard of care for blood conservation in subjects who did not receive prophylactic anticoagulation before spinal surgery. Antithrombotic prophylaxis should be considered when erythropoietin is used in the surgical setting.

Topics: Aged; Anticoagulants; Elective Surgical Procedures; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Intention to Treat Analysis; Male; Middle Aged; Patient Selection; Perioperative Care; Prospective Studies; Recombinant Proteins; Spine; Ultrasonography, Doppler, Color; Venous Thrombosis

This randomized, controlled trial evaluated the effect of darbepoetin alfa on hospitalization days, transfusion requirements, hemoglobin levels, and fatigue in patients with anemia of cancer (AOC). Eligible patients were anemic (hemoglobin or=18 years old, and had not received chemotherapy or radiotherapy within 4 weeks of study screening. Patients were randomized 4:1 to receive darbepoetin alfa, 3.0 microg/kg every 2 weeks (Q2W) (n = 226), or observation only for 12 weeks (n = 59), followed by an optional 9 weeks of darbepoetin alfa, 3.0 microg/kg Q2W. Endpoints were compared between the two treatment arms at week 13. A planned interim analysis indicated that assumptions regarding hospitalization in the study design were incorrect, so the study was terminated early. Therefore, results for the primary endpoint should be interpreted cautiously. The hospitalization rate was similar (0.5 days) for both the darbepoetin alfa and observation groups (p = .73). Transfusion incidence (weeks 5-12) was significantly lower for darbepoetin alfa patients (8%) than for observation patients (22%) (p = .0092). By week 13, hemoglobin increased by 2.1 g/dl in patients receiving darbepoetin alfa, compared with 0.1 g/dl in the observation group p < .0001. Hemoglobin improvements were paralleled by an increase in Functional Assessment of Cancer Therapy-Fatigue score (mean change in score at week 13: darbepoetin alfa, 6.0; observation, 2.2; p < .05). Darbepoetin alfa Q2W can significantly improve hemoglobin levels and reduce transfusion requirements in patients with AOC, resulting in significant improvements in health-related quality of life.

Topics: Aged; Aged, 80 and over; Anemia; Darbepoetin alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Pulmonary Embolism; Treatment Outcome; Venous Thrombosis

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

The optimum regimen of epoetin alfa for prevention of allogeneic blood transfusion is unknown.. To determine whether a modified regimen of epoetin alfa reduces allogeneic blood transfusion in patients undergoing hip arthroplasty.. Randomized, double-blind, multicenter trial comparing two modified dose regimens of epoetin alfa with placebo.. 13 teaching hospitals and 4 community hospitals in Canada.. 201 patients undergoing primary hip arthroplasty who had a hemoglobin concentration of 98 to 137 g/L and did not predonate blood.. Patients were assigned in a 3:5:5 ratio to receive four weekly doses of epoetin alfa, 40 000 U (high-dose; n = 44) or 20 000 U (low-dose; n = 79), or placebo (n = 78), starting 4 weeks before surgery. All patients received oral iron supplementation, 450 mg/d, for 42 or more days before surgery.. The primary end point was allogeneic transfusion. Secondary end points were thromboembolic events and change in reticulocyte count and hemoglobin concentration.. Both modified epoetin alfa regimens significantly reduced the need for allogeneic transfusion: Five (11.4%) patients in the high-dose group (P = 0.001) and 18 (22. 8%) patients in the low-dose group (P = 0.003) had transfusion, compared with 35 (44.9%) patients in the placebo group. The hematologic response was substantial in patients who received epoetin alfa. In the high-dose group, low-dose group, and placebo group, the preoperative increase in reticulocyte count was 58.8, 37. 0 and 1.8 x 10(9) cells/L (P < 0.001), respectively, and the increase in hemoglobin concentration was 19.5, 17.2, and 1.2 g/L (P < 0.001). The incidence of thromboembolic events did not differ among groups.. Both modified epoetin alfa regimens were effective compared with placebo in reducing allogeneic transfusion in patients undergoing hip arthroplasty. Patients who received high-dose epoetin alfa had the lowest transfusion rate.

Topics: Aged; Blood Transfusion; Dietary Supplements; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Follow-Up Studies; Hematinics; Hemoglobinometry; Humans; Iron; Male; Middle Aged; Patient Compliance; Polysaccharides; Pulmonary Embolism; Recombinant Proteins; Reticulocyte Count; Transfusion Reaction; Treatment Outcome; Venous Thrombosis

Myeloproliferative neoplasms (MPNs) such as polycythemia Vera (PV) and Essential Thrombocythemia (ET) can be associated with a high risk of both venous and arterial thrombosis. However, the co-existence between these two complications is very rare and has never been described before, especially in young adults with no known history of MPNs.. We report the case of a 39 year-old Caucasian Moroccan male patient without cardiovascular risk factors (CVRF), who presented with acute chest pain. He also suffered from a severe headache since 2 weeks. Electrocardiogram (ECG) showed ST segment elevation myocardial infarction in the posterolateral leads. Cerebral Computed Tomography (CT) scan revealed subarachnoid hemorrhage (SAH), and cerebral Magnetic Resonance Angiography (MRA) found a Superior Sagittal Sinus Thrombosis (SSST). Routine blood tests showed raised hemoglobin and hematocrit in addition to leukocytosis and thrombocythemia. His coronary angiography revealed a thrombus in the ostial left circumflex artery (LCX). Further testing revealed positive Janus kinase 2 (JAK2) V617F mutation and low erythropoietin level, confirming the diagnosis of PV according to the 2008 World Health Organization (WHO) criteria. Antithrombotic and anti-ischemic treatments, in addition to myelosuppressive therapy with hydroxyurea, were initiated with a good clinical and biological evolution.. This case shows that MPNs are an important cause of thrombosis, especially in young patients with no other risk factors. Early diagnosis and appropriate management are fundamental before the occurrence of life-threatening complications that can sometimes present in unusual forms associating arterial and venous thrombotic events.

Topics: Adult; Chest Pain; Coronary Vessels; Erythropoietin; Headache; Humans; Janus Kinase 2; Male; Mutation; Polycythemia Vera; Superior Sagittal Sinus; Venous Thrombosis

The authors evaluated the patterns of use and the risk of thromboembolic events (TEE) associated with erythropoietin-stimulating agents (ESAs) in older patients with metastatic breast cancer who were receiving chemotherapy.. The study was retrospective and used the SEER-Medicare linked database. Stage IV breast cancer patients diagnosed from 1995-2005, treated with chemotherapy, ≥66 years old, with full coverage of Medicare A and B were included. The World Health Organization's International Classification of Diseases (ICD-9) and the Healthcare Common Procedure Coding System (HCPCS) were used to identify the use of ESAs, chemotherapy, and complications of therapy. Analyses included descriptive statistics and logistic regression.. Of 2266 women, 980 (43.3%) received ESAs, and 1286 (56.7%) did not. Patients diagnosed after 1999 or who received treatment with taxanes, anthracyclines, or vinorelbine were more likely to receive ESAs. Patients receiving ESAs had higher rates of stroke (18.5% vs 15.1%, P = .031); deep-vein thrombosis (DVT; 21.3% vs 14.4%, P<.001), other/unspecified thromboembolic event (TEE; 19.8% vs 14.7%, P = .001), and any clot (31.3% vs 23.4%, P<.0001). In multivariate analysis, patients receiving ESAs had increased risk for DVT (odds ratio [OR], 1.36; 95% confidence interval [CI], 1.05-1.75), and any clot (OR, 1.26; 95% CI, 1.02-1.57). A dose-dependent effect was evident for stroke, DVT, other TEE, and any clot.. In this cohort of patients, the use of ESAs increased the risk of TEEs, with a dose-dependent effect for stroke, DVT, other TEE, and any clot. The data show that among patients treated with chemotherapy and ESAs for metastatic breast cancer, TEEs are a common event. Therefore, caution is recommended when using these agents.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Erythropoietin; Female; Humans; Medicare; Neoplasm Metastasis; Retrospective Studies; SEER Program; Stroke; Thrombosis; United States; Venous Thrombosis

Topics: Drug Administration Schedule; Erythropoietin; Humans; Preoperative Care; Recombinant Proteins; Spine; Venous Thrombosis

Whereas administration of erythropoietin (EPO) acutely after myocardial infarction (MI) reduces infarct size and chronic EPO therapy attenuates post-MI remodeling, the safety of chronic EPO therapy following MI is unknown. Therefore, we examined the thrombogenic effects of a chronic EPO therapy after MI.. Rats underwent coronary occlusion followed by reperfusion. They were assigned to one of the following groups: EPO-A, single injection of EPO 5,000 U/kg at the time of reperfusion; EPO-C, injection of EPO 5,000 U/kg at the time of reperfusion followed by 300 U/kg/week; PBS-C, injection of vehicle only. After eight weeks of treatment they were exposed to a validated prethrombotic test based on partial stenosis of the inferior vena cava.. As compared to the rats receiving vehicle only, the rats treated with EPO exhibited a significant reduction in MI size (28.7 +/- 2.1% and 25.8 +/- 1.9 vs. 39.8 +/- 3.0% in EPO-A, EPO-C and PBS-C, respectively; p < 0.05). Whereas the hematocrit was significantly increased in EPO-C (59.7 +/- 2.0% vs. 44.7 +/- 0.9% in EPO-A, p < 0.001), the proportion of rats in which a thrombus occurred was similar in all groups (p = 0.52).. Chronic EPO therapy added to the single high dose of EPO injected acutely did not induce venous pro-thrombotic effect in rats.

Topics: Animals; Disease Models, Animal; Erythropoietin; Hematocrit; Male; Myocardial Infarction; Myocardium; Rats; Rats, Sprague-Dawley; Venous Thrombosis; Ventricular Remodeling

We report a rare case of deep vein thrombosis (DVT) secondary to erythropoietin (EPO) in an 89-year-old patient with myelodysplastic syndrome (MDS). The incidence of EPO-induced thrombotic episode increases with an absolute increase of hemoglobin (Hb) beyond >12 gm/dL or rate of increase of Hb level >1 gm/dL every 2 weeks.

Topics: Aged, 80 and over; Erythropoietin; Humans; Male; Myelodysplastic Syndromes; Venous Thrombosis

Haematological toxicities and thromboembolic (TE) events are common complications of myeloma therapy. TE risk may be elevated with combination regimens, notably thalidomide/lenalidomide plus high-dose dexamethasone; concomitant erythropoietin appears to further increase the risk with lenalidomide-dexamethasone. We characterised thrombocytopenia and neutropenia in the phase 3 APEX (Assessment of Proteasome Inhibition for Extending Remissions) study of bortezomib versus high-dose dexamethasone in relapsed myeloma, and calculated the incidences of deep-vein thrombosis (DVT)/pulmonary embolism (PE) with: bortezomib or dexamethasone +/- erythropoietin in APEX; bortezomib +/- dexamethasone +/- erythropoietin in two phase 2 studies of relapsed/refractory myeloma. Bortezomib-associated thrombocytopenia and neutropenia were transient, predictable and manageable; mean platelet and neutrophil counts followed a cyclical pattern, and improved over the treatment course. Grade 3/4 thrombocytopenia incidence was higher with bortezomib versus dexamethasone (26%/4% vs. 5%/1%), but significant bleeding events were comparable (4% vs. 5%). DVT/PE incidence was low (< or =3.1%) in all analyses; addition of dexamethasone/erythropoietin did not affect TE risk. In APEX, TE risk appeared lower with bortezomib versus dexamethasone. Bortezomib caused transient and cyclical thrombocytopenia and was not associated with elevated TE risk, alone or with dexamethasone +/- erythropoietin. Preliminary data suggest bortezomib may reduce the thrombogenic potential of combination regimens via inhibition of platelet function or other mechanism-specific effects on coagulation.

Topics: Boronic Acids; Bortezomib; Clinical Trials as Topic; Dexamethasone; Drug Therapy, Combination; Erythropoietin; Female; Humans; Immunosuppressive Agents; Logistic Models; Male; Middle Aged; Multiple Myeloma; Protease Inhibitors; Pulmonary Embolism; Pyrazines; Recombinant Proteins; Recurrence; Risk; Treatment Outcome; Venous Thrombosis

Recombinant epoetin alfa and darbepoetin alfa (r-HuEPO) have been shown to be safe and effective treatments for anemia, but recent reports have suggested an increased risk of thromboembolic events when these agents are used to treat chemotherapy-induced anemia among patients with breast or ovarian cancer. We examined the possible risk of such events among patients with ovarian or primary peritoneal carcinomas and chemotherapy-induced anemia.. We retrospectively analyzed data over 10 years from women at one hospital with ovarian or primary peritoneal carcinoma and chemotherapy-induced anemia. The incidence and odds ratio for development of deep venous thrombosis, unadjusted and adjusted for baseline differences and risk factors, was assessed between patients who had received r-HuEPO versus no treatment for anemia.. Of the 364 women, 90 had received r-HuEPO and 253 had not. The incidence of deep venous thrombosis was 6.7% in the group that had received r-HuEPO and 5.1% in the group that had not (unadjusted odds ratio, 1.31; 95% confidence interval [CI], 0.48-3.55). After adjustment for differences in age, body-mass index, prior thromboembolic disease or cancer, and tobacco use, the odds ratio for developing deep venous thrombosis with the use of r-HuEPO was 1.35 (95% CI, 0.49-3.75).. The use of r-HuEPO was not associated with an increased risk of deep venous thrombosis in this population. A randomized trial is needed to further explore this issue and to detail the safety and efficacy of these agents in patients with various other cancers.

Topics: Aged; Anemia; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Middle Aged; Ovarian Neoplasms; Peritoneal Neoplasms; Recombinant Proteins; Venous Thrombosis

Topics: Aged; Erythropoietin; Hematinics; Humans; Immunosuppressive Agents; Male; Middle Aged; Multiple Myeloma; Risk Factors; Thalidomide; Treatment Outcome; Venous Thrombosis

Topics: Anti-Inflammatory Agents; Dexamethasone; Drug Therapy, Combination; Erythropoietin; Humans; Lenalidomide; Multiple Myeloma; Multivariate Analysis; Thalidomide; Venous Thrombosis

Myeloproliferative disorders (MPD) are reported in 25-65% of patients with splanchnic vein thrombosis (SVT). Diagnostic criteria for MPD have not been fully established in this context. Using clusters of abnormal megakaryocytes in bone marrow (BM) biopsy as a reference standard for Philadelphia negative MPD, we assessed the relevance of other criteria currently recommended for the diagnosis of MPD in SVT (128 consecutive SVT patients). First, usual criteria were compared with BM results: endogenous erythroid colony formation (EEC) was strongly correlated with BM results; splenomegaly, blood cell count, total red cell volume, erythropoietin level and cytogenetic were much less accurate. Then, patients were assigned to three groups according to the combination of BM and EEC findings (group I: both present; group II: both absent; group III: other patients); clinical presentation and outcome were compared in each group. At a mean follow-up of 6.09 +/- 6.6 years, progression to a severe form of MPD occurred in 7 of 31 group I patients (23%), in 1 of 34 group III patients (3%) and 0 of 63 group II patients. The combination of marked splenomegaly and platelet count >200 x 10(9)/l was restricted to groups I and III. In conclusion, in patients with SVT, BM findings and EEC allowed the diagnosis of MPD at risk of aggravation. Marked splenomegaly in association with platelet counts >200 x 10(9)/l constitute a simple index with high specificity but low sensitivity.

Topics: Bone Marrow Cells; Cytogenetic Analysis; Erythrocyte Volume; Erythroid Precursor Cells; Erythropoietin; Follow-Up Studies; Humans; Megakaryocytes; Myeloproliferative Disorders; Phenotype; Platelet Count; Sensitivity and Specificity; Splanchnic Circulation; Splenomegaly; Statistics, Nonparametric; Venous Thrombosis

Topics: Cerebral Veins; Epoetin Alfa; Erythropoietin; Estrogen Antagonists; Hematinics; Humans; Recombinant Proteins; Tamoxifen; Venous Thrombosis

Among 199 patients treated with thalidomide for multiple myeloma, four thromboses occurred in 49 cases during erythropoietin therapy (prevalence 8.1%; annual rate 7.25%), and another 14 events occurred in patients not on erythropoietin (9.3%; 7.56%). Thus, erythropoietin would seem not to increase the risk of thrombosis of myeloma patients receiving thalidomide.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Antineoplastic Agents; Drug Synergism; Erythropoietin; Female; Humans; Male; Middle Aged; Multiple Myeloma; Recombinant Proteins; Risk; Thalidomide; Thrombosis; Venous Thrombosis; Warfarin

Because studies have suggested that anemia has an adverse effect on outcome for patients with cervical carcinoma who are treated with radiation, recombinant human erythropoietin (rHuEpo) has been used increasingly to maintain hemoglobin levels in these patients. Erythropoietin may increase the risk of thrombosis. The authors performed a retrospective analysis to determine whether there was an increased rate of symptomatic venous thrombosis associated with the use of rHuEpo in patients with carcinoma of the uterine cervix and vagina.. A retrospective, case-control study was performed on consecutive patients with localized carcinoma of the uterine cervix or vagina who were treated with chemotherapy and radiation (chemoradiotherapy). The primary outcome was symptomatic venous thrombosis.. One hundred forty-seven patients were reviewed. When they were divided into women who received rHuEpo (n = 75 patients) and women who did not receive rHuEpo (n = 72 patients), there were no significant differences in age, height, weight, disease stage, or body mass index. Fewer patients in the rHuEpo group required transfusions. In the rHuEpo group, 17 of 75 patients had either an upper extremity thrombosis (n = 12 patients) or a lower extremity thrombosis (n = 7 patients): 2 patients had both, and 2 patients had more than 1 event. Two of 72 patients who did not receive rHuEpo had symptomatic thrombosis. Patients who received rHuEpo had an odds ratio (OR) of developing thrombosis of 10.3 (95% confidence interval [95% CI], 2.3-46.2). Multiple logistic regression revealed that only the use of rHuEpo was associated with an increased risk of thrombosis (OR, 15.3; 95% CI, 3.1-76.7).. Patients with cervical carcinoma who received chemoradiotherapy and rHuEpo had an increased risk of symptomatic venous thrombosis.

Topics: Adult; Age Distribution; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Case-Control Studies; Combined Modality Therapy; Confidence Intervals; Erythropoietin; Female; Follow-Up Studies; Humans; Incidence; Logistic Models; Middle Aged; Multivariate Analysis; Radiotherapy; Recombinant Proteins; Retrospective Studies; Risk Factors; Severity of Illness Index; Survival Rate; Uterine Cervical Neoplasms; Venous Thrombosis

Topics: Arthroplasty, Replacement, Hip; Blood Transfusion; Christianity; Erythropoietin; Female; Humans; Male; Middle Aged; Recombinant Proteins; Religion and Medicine; Venous Thrombosis