Use Of Phlebotomy Research Articles

Gender-affirming hormone therapy in the transgender patient: influence on thrombotic risk.

Research regarding the hematologic sequelae of estrogen and testosterone therapy for transgender people is an emerging area. While estrogen therapy has been widely studied in cisgender women, studies in transgender individuals are limited, revealing variable adverse effects influenced by the dose and formulation of estrogen used. Thrombotic risk factors in transgender and gender-diverse individuals are multifactorial, involving both modifiable and nonmodifiable factors. Management of venous thromboembolism (VTE) in individuals receiving gender-affirming estrogen entails standard anticoagulation therapy alongside shared decision-making regarding hormone continuation and risk factor modification. While data and guidance from cisgender women can offer a reference for managing thrombotic risk in transgender individuals on hormone therapy, fully applying these insights can be challenging. The benefits of gender-affirming hormone therapy include significantly reducing the risk of suicide and depression, highlighting the importance of a contemplative approach to the management of hormonal therapy after a VTE event. Although limited, the available data in the literature indicate a low thrombotic risk for transgender individuals undergoing gender-affirming testosterone therapy. However, polycythemia is a common adverse effect necessitating monitoring and, occasionally, adjustments to hormonal therapy. Additionally, iron deficiency may arise due to the physiological effects of testosterone or health care providers' use of phlebotomy, an aspect that remains unstudied in this population. In conclusion, while the set of clinical data is expanding, further research remains vital to refine management strategies and improve hematologic outcomes for transgender individuals undergoing gender-affirming hormone therapy.

JAK2 unmutated erythrocytosis: 2023 Update on diagnosis and management.

JAK2 unmutated or non-polycythemia vera (PV) erythrocytosis encompasses a heterogenous spectrum of hereditary and acquired entities. Foremost in the evaluation of erythrocytosis is the exclusion of PV through JAK2 (inclusive of exons 12-15) mutation screening. Initial assessment should also include gathering of previous records on hematocrit (Hct) and hemoglobin (Hgb) levels, in order to streamline the diagnostic process by first distinguishing longstanding from acquired erythrocytosis; subsequent subcategorization is facilitated by serum erythropoietin (Epo) measurement, germline mutation screening, and review of historical data, including comorbid conditions and medication list. Hereditary erythrocytosis constitutes the main culprit in the context of longstanding erythrocytosis, especially when associated with a positive family history. In this regard, a subnormal serum Epo level suggests EPO receptor mutation. Otherwise, considerations include those associated with decreased (high oxygen affinity Hgb variants, 2,3-bisphosphoglycerate deficiency, PIEZO1 mutations, methemoglobinemia) or normal oxygen tension at 50% Hgb saturation (P50). The latter include germline oxygen sensing pathway (HIF2A-PHD2-VHL) and other rare mutations. Acquired erythrocytosis commonly results from central (e.g., cardiopulmonary disease, high-altitude habitat) or peripheral (e.g., renal artery stenosis) hypoxia. Other noteworthy conditions associated with acquired erythrocytosis include Epo-producing tumors (e.g., renal cell carcinoma, cerebral hemangioblastoma) and drugs (e.g., testosterone, erythropoiesis stimulating agents, sodium-glucose cotransporter-2 inhibitors). Idiopathic erythrocytosis is an ill-defined terminology that presumes the existence of an increased Hgb/Hct level without an identifiable etiology. Such classification often lacks accounting for normal outliers and is marred by truncated diagnostic evaluation. Current consensus treatment guidelines are not supported by hard evidence and their value is further undermined by limited phenotypic characterization and unfounded concerns for thrombosis. We are of the opinion that cytoreductive therapy and indiscriminate use of phlebotomy should be avoided in the treatment of non-clonal erythrocytosis. However, it is reasonable to consider therapeutic phlebotomy if one were to demonstrate value in symptom control, with frequency determined by symptoms rather than Hct level. In addition, cardiovascular risk optimization and low dose aspirin is often advised. Advances in molecular hematology might result in better characterization of "idiopathic erythrocytosis" and expansion of the repertoire for germline mutations in hereditary erythrocytosis. Prospective controlled studies are needed to clarify potential pathology from JAK2 unmutated erythrocytosis, as well as to document the therapeutic value of phlebotomy.

Rusfertide (PTG-300), a Hepcidin Mimetic, Maintains Liver Iron Concentration in the Absence of Phlebotomies in Patients with Hereditary Hemochromatosis

▪Introduction: Patients with hereditary hemochromatosis (HH) require continued phlebotomies to limit end-organ damage. Approximately 25% of patients in maintenance felt receiving phlebotomies was “inconvenient” or “very inconvenient” (Brisott et al, 2011). Patient compliance with phlebotomies generally declines with time (Hicken et al, 2003), and therapeutic phlebotomies may not be medically suitable for some HH patients. Rusfertide, a peptide mimetic of hepcidin, is an effective regulator of iron distribution and utilization that has demonstrated control of iron in an animal model of HH.Methods: We conducted an open-label, dose-finding efficacy study that investigated subcutaneous rusfertide in HH patients on a stable phlebotomy regimen of 0.25 to 1 phlebotomy per month for at least 6 months. Patients with clinical laboratory abnormalities and those receiving iron chelation therapy or erythrocytapheresis were excluded. Subjects received individually titrated rusfertide doses once or twice a week to maintain transferrin saturation (TSAT) below 45% and were followed for 6 months. Study measures included TSAT, serum iron, transferrin and ferritin, liver iron concentration (LIC) measured by MRI, and adverse events (AEs).Results: Sixteen subjects (10 male/6 female) were enrolled. Mean age and weight were 62.5 years and 88.1 kg, respectively. LIC values were maintained at pre-study levels, with minimal use of phlebotomies during the duration of the study (Figure 1A). Average pre-study phlebotomy rate was 0.27 phlebotomies/month compared to 0.03 phlebotomies/month during the study (p<0.0001; Figure 1B). There was a dose- and concentration-dependent decrease in serum iron and TSAT (Figure 2A and 2B). Transferrin levels were relatively constant over the course of the study. There were no notable changes in hematological parameters such as hematocrit, erythrocytes, leucocytes, or platelets. Rusfertide was generally well tolerated. Adverse events reported in 2 or more subjects included diarrhea, fatigue, injection site reactions (erythema, induration, pain, pruritis), dizziness, and headache.Conclusions: Rusfertide demonstrated a pharmacodynamic effect in reducing TSAT and serum iron, with corresponding significant reduction in the number of phlebotomies, and with LIC maintained at pre-study levels with minimal use of phlebotomies. These data indicate rusfertide was well tolerated in patients with HH and controls LIC, supporting development of rusfertide as a potential treatment for HH. [Display omitted] DisclosuresKowdley: PTG: Consultancy, Research Funding. Modi: Protagonist Therapeutics: Current Employment. Valone: Protagonist Therapeutics: Current Employment, Current equity holder in publicly-traded company. Gupta: Protagonist Therapeutics: Current Employment.

Rusfertide (PTG-300) Induction Therapy Rapidly Achieves Hematocrit Control in Polycythemia Vera Patients without the Need for Therapeutic Phlebotomy

▪Background. Polycythemia (PV) patients with hematocrit above 45% are at increased risk of thrombotic complications and are treated with phlebotomy and/or cytoreductive therapy to reach a hematocrit target below 45%. Rusfertide (PTG-300) is a peptidic mimetic of hepcidin that is being developed for treatment of polycythemia vera (PV). A Phase 2 trial has indicated that rusfertide is effective at reducing the number of phlebotomies and maintaining hematocrit below 45% without phlebotomy in PV patients who are either high-risk or low-risk, patients treated with cytoreductive therapy (hydroxyurea, interferon, ruxolitinib) and patients treated with phlebotomy alone (Kremyanskaya, ASH 2020). The current trial (PTG-300-08) tested the ability of rusfertide to normalize hematocrit in PV patients with elevated hematocrit without instituting phlebotomy treatment to normalize hematocrit to below 45% in PV patients without requiring phlebotomy and/or cytoreductive treatment.Methods. Eligible study subjects were diagnosed with PV (in accordance with the WHO 2016 criteria), had baseline hematocrit above 48%, and a history of 3 or more hematocrit values above 48% in the year prior to enrollment. High-risk and low-risk subjects treated with phlebotomy alone or with concurrent cytoreductive therapy were eligible. Rusfertide was added on to each subject's current therapy. The initial rusfertide dose was 40 mg administered subcutaneously twice weekly. When each subject's hematocrit was below 45%, the dosing schedule was changed to weekly and the rusfertide dose was adjusted to maintain hematocrit below 45%.Results. Sixteen subjects (12 male and 4 females) have been enrolled. The mean age is 56.1 years; the mean time since diagnosis is 3.74 years; 10 subjects are low risk PV; 12 subjects are receiving concurrent hydroxyurea and 4 subjects were not receiving cytoreductive therapy. Baseline values (mean, min-max) HCT (51.0%, 47.4 - 59), WBC (12,338/µL, 7,000 - 24,600), RBCs (5.9x10 6/µL, 4.3 - 7.6), platelets (486,500/µL, 242,000 - 904,000). All subjects had rapid decreases in hematocrit to below 45% without the use of phlebotomy (Figure 1a). Hematocrit levels remained well controlled after falling below 45% as investigators reduced rusfertide dose to maintenance once weekly regimen. Hemoglobin (Figure 1b) fell rapidly. Erythrocyte counts (Figure 1c) also fell rapidly, indicating that decreased hematocrit is due to decreased erythrocytosis. For the 11 subjects with adequate follow-up, the mean rate of absolute hematocrit decrease was 1.76% per week (median: 1.81%/week; min - max: 0.65 - 2.69%) and the mean time to reach goal hematocrit below 45% was 4.79 weeks (median: 4.14 weeks, min - max: 3.57 - 8.14).Eight subjects reported adverse events (AEs). Injection site reactions (ISRs) occurred in 7 subjects and were mild or moderate in severity. The most common ISRs were erythema (n=7), induration (n=5) and pruritis (n=2). Adverse events other than ISRs that occurred in 2 or more subjects were hypertension (n=2), pyrexia (n=2) and thrombocytosis (n=2). There were two serious adverse events (worsening migraine and pleuritic chest pain) and both were considered unrelated to rusfertide. Overall, rusfertide was well tolerated.Conclusions. This study demonstrates that induction therapy with twice weekly rusfertide administration was effective in rapidly achieving target hematocrit below 45% without phlebotomy in all PV patients which was then successfully maintained with weekly rusfertide treatment. Moreover, the twice weekly injections of rusfertide used to rapidly lower hematocrit levels were safe and well tolerated.Key words: Hepcidin, Hematocrit, Rusfertide, PTG-300, Polycythemia Vera, PV, Therapeutic Phlebotomy [Display omitted] DisclosuresGupta: Protagonist Therapeutics: Current Employment. Valone: Protagonist Therapeutics: Consultancy, Current equity holder in publicly-traded company. Khanna: Protagonist: Current Employment, Current equity holder in publicly-traded company. Modi: Protagonist Therapeutics: Current Employment. Hoffman: Kartos Therapeutics, Inc.: Research Funding; Protagonist Therapeutics, Inc.: Consultancy; Novartis: Other: Data Safety Monitoring Board, Research Funding; AbbVie Inc.: Other: Data Safety Monitoring Board, Research Funding.

Successful Use of Phlebotomy to Treat Severe Secondary Polycythemia Due to Chronic Lung Disease

Secondary polycythemia (SP) occurs as a result of increase erythropoietin levels most commonly as a result of tissue hypoxia. Symptoms such as erythromelalgia, pruritis, and bleeding, which are frequently seen in polycythemia vera (PV), do not commonly occur in SP. Phlebotomy is considered one of the mainstays of therapy for PV but is rarely used for treatment of SP due to concern about worsening tissue hypoxia. We present the case of a patient with severe SP due to chronic hypoxic lung disease who presented with erythromelalgia, pruritis, and bleeding and was treated successfully with therapeutic phlebotomy. This case illustrates the importance of considering the use of therapeutic phlebotomy in symptomatic patients with severe SP.

Cytoreductive Treatment in ‘Real Life’ - Interim-Analysis of 434 Polycythemia Vera Patients in Germany

Treatment recommendations for cytoreductive treatment of patients with polycythemia vera (PV) are well established. However, the clinical use and limitation of phlebotomies remain a matter of current debate (Barbui et al, Leukemia, 32; Heidel et al, Leukemia, 32). While multicenter trials investigating therapeutic strategies for PV have been conducted at specialized academic centers, the majority of patients is treated in an outpatient (ambulatory) setting. The aim of this study is to evaluate the 'real live' situation especially in regard to the use of phlebotomy and cytoreductive therapy in a cohort of 1500 patients from a survey conducted at private practices and primary care centers. Eligible centers treating patients with MPN in Germany were recruited to participate in a paper-pencil based ongoing survey conducted from December 2018 and planned until December 2019. Hematologists were asked to report from patient charts. Descriptive analyses were conducted to assess for therapeutic interventions and outcomes and examined by reported prognostic risk scores, symptom scores, and clinical response criteria. For this interim analysis (data cutoff on May 31, 2019) a total of 11 centers participated in a retrospective survey and provided data on 434 patients. Gender was balanced with 211 (48.6%) male and 223 (51.4%) female patients. Most patients were of older age (mean 71.4 years; 62.7 years at diagnosis and 63,4% over the age of 60), which is a main risk factor according to published criteria (Tefferi et al, Am J Hematol, 94). 154 patients (35.5%) had a disease history of more than 10 years, 95 pts (21.9%) 6 to 10 years and 42.6% less than 6 years. Thromboembolic complications were reported in 100 patients (23.0%) at time of diagnosis and for 61 (14.1%) during treatment. Additional cardiovascular (CV) risk-factors were reported for 320 patients (73.7%), whereas 107 (24.7%) had none (and no data available in 1,6% (n=7) of cases). Hypertension was the most prevalent CV risk factor with 86.9% (n=278) affected, followed by hypercholesteremia 18.8% (n=60), diabetes mellitus 16.2% (n=52) and smoking 15.9% (n=51). Phlebotomy was the primary therapy in 301 patients (69.4%). Of those, 83 (27.6%) received 1-3 phlebotomies/year, 113 (37.5%) 4-6/year, 71 (23.6%) 7-12 times/year and 8 pts (2,6%) &gt;13 times/year. Main triggers to start pharmacologic cytoreduction included the presence of high-risk criteria (53.2%) and insufficient disease control (22.6%). Of note, asymptomatic iron deficiency (5.6%), symptomatic iron deficiency (9.3%) and intolerance to phlebotomy (5.3%) have been reported in a significant number of patients and contributed to the limitation of phlebotomy treatment. Choice of cytoreductive agents included hydroxycarbamide (n=320; 73.3%), JAK-inhibitors (n=80, 18.4%), Interferon alpha (n=15; 3,5%), IMIDEs (n=2; 0.5%) and other cytoreductive agents (n=6; 1.4%). While 11 patients (2.5%) required combination of cytoreductive agents, 137 (31.3%) patients had a persistent need for phlebotomy. In summary, the patient population investigated here was older than in published large multicenter trials. Age was the main factor accounting for the majority of patients being categorized as 'high risk'. Although the majority of patients (&gt;60%) presented as 'high risk' according to international guidelines, 69.4% of patients received phlebotomy as primary therapeutic approach, in part at high frequency (&gt;25% with more than 7 phlebotomies per year). The low number of primary cytoreductive treatment and occurrence of symptomatic iron deficiency in 9.3% and of intolerance in 5.3% of patients indicates the need to reconsider indication and limitations of phlebotomy. We conclude that phlebotomy as a prophylactic measure of risk reduction should result in mild iron-deficient erythropoiesis and hematocrit control without inducing a severe iron-deficiency syndrome as indicated by increased levels of soluble transferrin-receptor or Zn-protoporphyrin. Pharmacologic cytoreduction is necessary for high risk patients older than 60 years or with previous thromboembolic complications. For patients, who require permanent phlebotomies at high frequency for sufficient hematocrit control (&lt;45%), pharmacologic intervention should be discussed even in the low-risk situation to balance the looming risk of iron-deficiency symptoms with potential side effects of pharmacologic compounds. Disclosures Wunschel: Novartis Inc.: Employment. Hochhaus:MSD: Research Funding; Incyte: Research Funding; BMS: Research Funding; Pfizer: Research Funding; Novartis: Research Funding. Heidel:Novartis: Research Funding.

Treatment of Eye Diseases in the Hippocratic Era

For the treatment of eye diseases, Hippocrates described the application of ointments, administration of herbs, implementation of surgical interventions and the use of phlebotomy and cauterization along the “ancient vessels”.The Hippocratic use of bleeding and cauterization as a medical treatment has significant similarities to traditional Chinese medicine. The “ancient vessels” described by Hippocrates are not related to human anatomy, but are similar to the meridians of traditional Chinese medicine. The points chosen for cautery are similar to those described in ancient Chinese texts. The treatment of ophthalmic diseases with phlebotomy and cauterization during the Hippocratic period can undoubtedly be considered as alternative medicine.

Systematic review and meta-analysis to determine the impact of iron depletion in dysmetabolic iron overload syndrome and non-alcoholic fatty liver disease.

Iron reduction has been proposed as treatment for dysmetabolic iron overload syndrome (DIOS) and non-alcoholic fatty liver disease (NAFLD), but results of published trials are conflicting. We undertook a systematic review and meta-analysis to determine the impact of phlebotomy in DIOS and NAFLD. We searched multiple databases systematically for studies evaluating the impact of phlebotomy in DIOS and NAFLD. We calculated weighted summary estimates using the inverse variance method. Study quality was assessed using the Cochrane collaboration tool. We identified nine studies with 820 patients (427 had phlebotomy, 393 lifestyle changes alone). Iron depletion did not improve the Homeostasis Model Assessment (HOMA) index (mean difference [MD] -0.6; confidence interval (CI), -1.7, 0.5; P = 0.3), insulin level (MD -0.8mU/L; CI, -5.3, 3.7; P = 0.73), or aspartate aminotransferase (AST) (MD -0.7IU/L; CI, -3.2, 1.8; P = 0.6) in DIOS and/or NAFLD patients as compared to lifestyle changes alone (five studies, 626 patients). There was mild improvement in alanine aminotransferase (ALT) (MD -6.6IU/L; CI, -11, -2.1); P < 0.01), but the effect size was very small (Cohen's d, 0.15; r statistic, 0.07). Even in the subgroup of patients with NAFLD and hyperferritinemia, phlebotomy did not improve the HOMA index, insulin level, ALT, or AST. Additionally, no study showed significant improvement in liver inflammation or fibrosis with iron reduction. Phlebotomy does not bring about significant improvement in indices of insulin resistance, liver enzymes, or liver histology in patients with DIOS and/or NAFLD compared to lifestyle changes alone. Current evidence does not support the use of phlebotomy in patients with DIOS or NAFLD.

New Therapeutic Approaches in Polycythemia Vera.

Polycythemia vera (PV) is 1 of the 3 Philadelphia-negative myeloproliferative neoplasms. Clinically, PV is an indolent disease, but its course can be complicated by arterial and venous vascular incidents, evolution to myelofibrosis, or leukemic transformation. Treatment of PV is therefore aimed at preventing such acute complications. The cornerstone of therapy of low-risk patients remains strict control of cardiovascular risk factors, the use of phlebotomy, and low-dose aspirin. Higher-risk patients should also receive cytoreductive treatments. Hydroxyurea and interferon α represent standard first-line options for newly diagnosed high-risk PV patients. Recommendations for patients whose disease fails to respond to these therapies are less clearly defined. The discovery of a mutation in the Janus kinase (JAK) 2 gene (V617F) in almost all cases of PV has prompted the development of molecularly targeted agents for the treatment of these patients. In this review, we discuss key clinical aspects, the current therapeutic armamentarium, and data on the use of novel agents in patients with PV.

A Retrospective Review of the Management of Patients with Porphyria Cutanea Tarda At a Tertiary Care Centre

Abstract 5290 Porphyria Cutanea Tarda (PCT) is caused by a deficiency in uroporphyrinogen decarboxylase, an enzyme in the heme biosynthesic pathway. This leads to an excess of porphyrins, which cause blistering and skin fragility on sun exposure. The goals of treatment are iron depletion and reduction of plasma porphyrins to ameliorate skin symptoms. We reviewed the management of all PCT patients at St. Joseph's Hospital followed by the Hematology service, with the objective of describing their treatment course and its efficacy. The type of treatment received as well as the number and volume of phlebotomies were recorded. Outcomes of interest were skin symptom resolution (clinical remission) and biochemical remission, as measured by serum ferritin. Target ferritin was set at 30–50 μg/L. A total of 18 patients with PCT met our inclusion criteria; 14 males and 4 females. Three patients had the familial subtype of PCT while 15 had the sporadic form. Precipitants included alcohol, hepatitis C, hemochromatosis and estrogens. All patients received phlebotomy and three received hydroxychloroquine. Most patients were referred and initially diagnosed by dermatologists. The total volume of phlebotomies per patient ranged from 750–9500 mL for resolution of cutaneous symptoms which was achieved in 75% of patients. At the end of the study period, 15/18 (83%) patients were in clinical remission and 12/18 (67%) were in biochemical remission. Follow-up of PCT patients by a hospital hematology service allows for symptomatic control and biochemical remission in the vast majority of patients through the use of phlebotomy and occasionally hydroxychloroquine. Disclosures: No relevant conflicts of interest to declare.

Diagnostic Blood Loss From Phlebotomy and Hospital-Acquired Anemia During Acute Myocardial Infarction

Hospital-acquired anemia (HAA) during acute myocardial infarction (AMI) is associated with higher mortality and worse health status and often develops in the absence of recognized bleeding. The extent to which diagnostic phlebotomy, a modifiable process of care, contributes to HAA is unknown. We studied 17,676 patients with AMI from 57 US hospitals included in a contemporary AMI database from January 1, 2000, through December 31, 2008, who were not anemic at admission but developed moderate to severe HAA (in which the hemoglobin level declined from normal to <11 g/dL), a degree of HAA that has been shown to be prognostically important. Patients' total diagnostic blood loss was calculated by multiplying the number and types of blood tubes drawn by the standard volume for each tube type. Hierarchical modified Poisson regression was used to test the association between phlebotomy and moderate to severe HAA, after adjusting for site and potential confounders. Moderate to severe HAA developed in 3551 patients (20%). The mean (SD) phlebotomy volume was higher in patients with HAA (173.8 [139.3] mL) vs those without HAA (83.5 [52.0 mL]; P < .001). There was significant variation in the mean diagnostic blood loss across hospitals (moderate to severe HAA: range, 119.1-246.0 mL; mild HAA or no HAA: 53.0-110.1 mL). For every 50 mL of blood drawn, the risk of moderate to severe HAA increased by 18% (relative risk [RR], 1.18; 95% confidence interval [CI], 1.13-1.22), which was only modestly attenuated after multivariable adjustment (RR, 1.15; 95% CI, 1.12-1.18). Blood loss from greater use of phlebotomy is independently associated with the development of HAA. These findings suggest that HAA may be preventable by implementing strategies to limit blood loss from laboratory testing.

Imatinib mesylate therapy for polycythemia vera: final result of a phase II study initiated in 2001

Polycythemia vera (PV) is a chronic myeloproliferative neoplasm (MPN) characterized by excessive production of red blood cells. Patients with PV are at a risk of thrombosis, bleeding, and transformation to myelofibrosis or acute myeloid leukemia. Therapy for PV is based on the use of phlebotomy, aspirin, and in high-risk patients, cytoreductive agents such as hydroxyurea. Anecdotal evidence suggests that imatinib mesylate, a selective tyrosine kinase inhibitor of ABL1, ARG, PDGFR, and KIT kinases has activity in PV. We conducted an open-label phase II clinical trial of imatinib at the standard dose of 400 mg daily in 24 patients with PV. The median duration of imatinib therapy was 5.1 months (range 0.2-86.4). Overall, 4 (17%) patients responded: one had a complete and three partial hematological response. The median time to response was 17.5 months (range 6-28), and the median duration of response was 17 months (range 9-68). No significant changes in JAK2(V617F) mutation burden were noted during imatinib therapy when compared with pretreatment values (P = 0.46). Therapy with imatinib was generally well tolerated. Our data indicate that imatinib has minimal clinical activity in PV.

Erythropoietic therapy: Cost efficiency and reimbursement

The practice of blood conservation is aimed at improving patient outcomes by avoiding allogeneic transfusions via a coordinated multidisciplinary, multipronged approach. The numerous blood conservation techniques and transfusion alternatives now available are described. Ongoing concerns exist regarding the availability of the nation's and the world's blood supply. In addition, the number of measures required to ensure blood safety has led to increases in the price of blood and blood products over the past 10-15 years. Moreover, blood transfusion carries inherent risks even under the most favorable circumstances. Investigations have established that injudicious transfusion is associated with development of ventilator-associated pneumonia, nosocomial infection, and organ dysfunction. Because most single blood-conservation techniques reduce blood usage by a mere 1-2 units, a series of integrated conservation approaches are required. These include preoperative autologous donation, use of erythropoietic agents, blood conservation techniques such as acute normovolemic hemodilution, individualized assessment of anemia tolerance, implementation of conservative transfusion thresholds, meticulous surgical techniques, and judicious use of phlebotomy and pharmacologic agents for limiting blood loss. Erythropoietic agents such as epoetin alfa have been used successfully to increase hemoglobin and decrease transfusion requirements, and are appropriate when used in advance of elective surgical procedures. Acquisition costs of erythropoietic stimulating agents versus costs of blood justify economic evaluation by hospitals to make the most cost-effective choice under current economic constraints. Initiating a blood management program requires planning and support from those who are concerned about blood usage reduction and outcomes improvement. Launching a vigorous and ongoing educational program to raise awareness about the risks and hazards associated with blood transfusion is an important step in helping to reshape the medical staffs' attitudes about transfusion and the most cost-effective way to achieve clinical goals.

Objectives and limitations of bloodless medical care

To outline the rationale, limitations, and execution of bloodless medical and surgical programs, highlighting characteristics that contribute to successful outcomes. Clinical experiences with patients who refuse blood transfusions for religious reasons have provided valuable lessons and raise intriguing questions about the necessity of routine blood transfusions. Healthcare centers with bloodless medicine and surgery programs feature a novel concept of patient care aimed at improving outcomes. A one-tiered approach to minimize blood usage for all patients, regardless of religious beliefs, is being successfully adopted at an increasing number of institutions. Since most single blood-conservation techniques reduce blood usage by just 1-2 units, a series of integrated preoperative, intraoperative, and postoperative conservation approaches is required. These include preoperative autologous donation, erythropoietic support, acute normovolemic hemodilution, individualized assessment of anemia tolerance, implementation of conservative transfusion thresholds, meticulous surgical techniques, and judicious use of phlebotomy and pharmacologic agents for limiting blood loss. The objectives of bloodless medicine and surgery programs are straightforward but require staff with expertise in transfusion medicine, intensive teamwork, patient-specific customization, careful planning, and integrated use of multimodal strategies.

Therapeutic options for essential thrombocythemia and polycythemia vera.

Several options exist for treating essential thrombocythemia and polycythemia vera. One approach is to assign the patient to a risk category from which treatment recommendations follow. The principal risks of essential thrombocythemia include thrombosis, major hemorrhage, and conversion to leukemia or myelofibrosis. Risk factors for thrombosis include age and prior thrombosis. Smoking and obesity have been implicated in isolated series. High-risk patients with essential thrombocythemia can be defined as those 60 years of age or older or those who have had a thrombosis at any age. These patients should be treated with hydroxyurea. If hydroxyurea cannot be tolerated, anagrelide and interferon-alpha (IFN-alpha) are alternatives. Low-dose aspirin (40 to 325 mg) can be used for patients whose platelet counts are < 1,500 x10(9)/L. Low-risk patients are those less than 60 years old who have not had thrombosis, who have no cardiovascular risk factors, and whose platelet counts are < 1,500 x 10(9)/L. These patients can be observed or placed on low-dose aspirin. Intermediate-risk patients are those less than 60 years who have not had thromboses, but who have platelet counts > 1,500 x 10(9)/L or who have significant cardiovascular risk factors. These patients should have their risk factors treated and may be given low-dose aspirin if the platelet count is < 1,500 x 10(9)/L. They can be observed or treated with anagrelide, hydroxyurea, or IFN-alpha. The Mayo Clinic experience suggests that no specific treatment affects outcomes of pregnancies. In high-risk pregnant women who need treatment, IFN-alpha is used. The principal risks of polycythemia vera are thrombosis, postpolycythemia myeloid metaplasia, and acute leukemia. Risk factors for thrombosis include age, the use of phlebotomies, the rate of phlebotomies, and a prior history of thrombosis. Platelet counts have not been definitively linked to an increased risk of thrombosis. High-risk polycythemia vera patients are those 60 years of age or older (some groups use 70 years) or those of any age who have had thrombosis. They should be treated with phlebotomy and hydroxyurea or IFN-alpha. Selected patients may be treated with anagrelide. A typical target range for phlebotomy is a hematocrit of < 42% for women and < 45% for men. Low-dose aspirin can be used if the platelet count is < 1,500 x 10(9)/L. Low-risk patients are those less than 60 years old who have had no thrombosis, no cardiovascular risk factors, and whose platelets are < 1,500 x 10(9)/L. These patients can be managed with phlebotomy alone or phlebotomy and low-dose aspirin. Intermediate-risk patients are those who are less than 60 years old, who have not had thrombosis, but who have platelet counts > 1,500 x 10(9)/L or who have cardiovascular risk factors. The cardiovascular risk factors should be treated, along with phlebotomy alone or with IFN-alpha. Low-dose aspirin is reasonable for those with platelet counts < 1,500 x 10(9)/mL. Anagrelide can be used with phlebotomy in selected patients. Women of childbearing age who are in the low-risk or intermediate-risk group can be treated with phlebotomy alone and low-dose aspirin if the platelet count is < 1,500 x 10(9)/L. For high-risk patients or pregnant patients, IFN-alpha can be added.

Therapeutic options for essential thrombocythemia and polycythemia vera

Several options exist for treating essential thrombocythemia and polycythemia vera. One approach is to assign the patient to a risk category from which treatment recommendations follow. The principal risks of essential thrombocythemia include thrombosis, major hemorrhage, and conversion to leukemia or myelofibrosis. Risk factors for thrombosis include age and prior thrombosis. Smoking and obesity have been implicated in isolated series. High-risk patients with essential thrombocythemia can be defined as those 60 years of age or older or those who have had a thrombosis at any age. These patients should be treated with hydroxyurea. If hydroxyurea cannot be tolerated, anagrelide and interferon-alpha (IFN-α) are alternatives. Low-dose aspirin (40 to 325 mg) can be used for patients whose platelet counts are < 1,500 ×10 9/L. Low-risk patients are those less than 60 years old who have not had thrombosis, who have no cardiovascular risk factors, and whose platelet counts are < 1,500 × 10 9/L. These patients can be observed or placed on low-dose aspirin. Intermediate-risk patients are those less than 60 years who have not had thromboses, but who have platelet counts > 1,500 × 10 9/L or who have significant cardiovascular risk factors. These patients should have their risk factors treated and may be given low-dose aspirin if the platelet count is < 1,500 × 10 9/L. They can be observed or treated with anagrelide, hydroxyurea, or IFN-α. The Mayo Clinic experience suggests that no specific treatment affects outcomes of pregnancies. In high-risk pregnant women who need treatment, IFN-α is used. The principal risks of polycythemia vera are thrombosis, postpolycythemia myeloid metaplasia, and acute leukemia. Risk factors for thrombosis include age, the use of phlebotomies, the rate of phlebotomies, and a prior history of thrombosis. Platelet counts have not been definitively linked to an increased risk of thrombosis. High-risk polycythemia vera patients are those 60 years of age or older (some groups use 70 years) or those of any age who have had thrombosis. They should be treated with phlebotomy and hydroxyurea or IFN-α. Selected patients may be treated with anagrelide. A typical target range for phlebotomy is a hematocrit of < 42% for women and < 45% for men. Low-dose aspirin can be used if the platelet count is < 1,500 × 10 9/L. Low-risk patients are those less than 60 years old who have had no thrombosis, no cardiovascular risk factors, and whose platelets are < 1,500 × 10 9/L. These patients can be managed with phlebotomy alone or phlebotomy and low-dose aspirin. Intermediate-risk patients are those who are less than 60 years old, who have not had thrombosis, but who have platelet counts > 1,500 × 10 9/L or who have cardiovascular risk factors. The cardiovascular risk factors should be treated, along with phlebotomy alone or with IFN-α. Low-dose aspirin is reasonable for those with platelet counts < 1,500 × 10 9/mL. Anagrelide can be used with phlebotomy in selected patients. Women of childbearing age who are in the low-risk or intermediate-risk group can be treated with phlebotomy alone and low-dose aspirin if the platelet count is < 1,500 × 10 9/L. For high-risk patients or pregnant patients, IFN-α can be added. Semin Oncol 29 (suppl 10):10-15. Copyright 2002, Elsevier Science (USA). All rights reserved.

Cardiac transplantation in a patient with hereditary hemochromatosis: role of adjunctive phlebotomy and erythropoietin

We describe the case of a 36-year-old woman with hereditary hemochromatosis (HH) resulting in end-stage cardiomyopathy and treated successfully with orthotopic cardiac transplantation. Before and after transplantation, the patient underwent aggressive treatment with frequent phlebotomy. We used erythropoietin concomitantly to maintain adequate hematocrit to support continued phlebotomy. We believe that aggressive use of phlebotomy provided the patient hemodynamic benefit and hastened the return of endocrine function post-transplantation. We also believe that the patient’s history of high-dose vitamin C usage may have accelerated iron deposition in the heart and other vital organs.

Management of porphyria cutanea tarda in the setting of chronic renal failure: A case report and review

The treatment of porphyria cutanea tarda (PCT) in patients with chronic renal failure poses a therapeutic challenge. In the absence of renal failure, phlebotomy and oral antimalarials have been the standard of care for PCT. However, in the presence of renal failure, associated chronic anemia often precludes the use of phlebotomy, and oral antimalarials are usually ineffective. We describe a patient with severe symptomatic PCT and chronic renal failure whose disease was successfully managed with a combination of high-dose erythropoietin and small volume phlebotomy. We also review several previously reported approaches to management of PCT in the setting of renal failure, which include small repeated phlebotomy, erythropoietin, deferoxamine, chloroquine, plasma exchange, high-efficiency/high-flux hemodialysis, cholestyramine, charcoal hemoperfusion, and kidney transplantation. An algorithm for the management of these patients is proposed. (J Am Acad Dermatol 2000;42:645-52.)

Are haematological tests warranted prior to tonsillectomy?

The use of phlebotomy for a full blood count (FBC) and group and serum storage (G&S) prior to tonsillectomy with or without adenoidectomy was assessed by means of a postal questionnaire sent to consultant otolaryngologists within the South West Thames region. This was compared with 'countrywide' practice assessed by means of questions to attenders at an otolaryngology course. A postal response rate of 86 per cent was obtained with 67 per cent within the region requesting a FBC prior to tonsillectomy and 50 per cent to adenoidectomy alone. This was much greater than for the 'countrywide' group with 24 per cent and 6 per cent respectively. Requests for pre-operative G&S were 17 per cent and 6 per cent respectively. This large difference in practice suggests that in the clinically healthy patient with no specific indications, pre-operative haematological investigations may be non-contributory, which has important financial implications. The maintenance of post-operative intravenous access is considered to be much safer, less traumatic and cheaper.