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Phlebotomy to reduce iron overload in patients cured of thalassemia by bone marrow transplantation. Italian Cooperative Group for Phlebotomy Treatment of Transplanted Thalassemia Patients.

In thalassemia after successful bone marrow transplantation (BMT), iron overload remains an important cause of morbidity. After BMT, patients have normal erythropoiesis capable of producing a hyperplastic response to phlebotomy so that this procedure can be contemplated as a method of mobilizing iron from overloaded tissues. A phlebotomy program (6 mL/kg blood withdrawal at 14-day intervals) was proposed to 48 patients with prolonged follow-up (range, 2 to 7 years) after BMT. Seven patients were not submitted to the program (five because of refusal and two because of reversible side effects). The remaining 41 patients (mean age, 16 +/- 2.9 years) were treated for a mean period of 35 +/- 18 months. All were evaluated before and after 3 +/- 0.6 years of follow-up. Values are expressed as mean +/- standard deviation (SD) or as median with a range (25 to 75 percentile). Serum ferritin decreased from 2,587 (2,129 to 4,817) to 417 (210 to 982) microg/L (P < .0001), total transferrin increased from 2.34 +/- 0.37 to 2.7 +/- 0.58 g/L (P = .0001), transferrin saturation decreased from 90% +/- 14% to 50% +/- 29% (P < .0001). Liver iron concentration evaluated on liver biopsy specimens decreased from 20.8 (15.5 to 28.1) to 4.2 (1.6 to 14.6) mg/g dry weight (P < .0001). Aspartate transaminase decreased from 2.7 +/- 2 to 1.1 +/- 0.6 (P < .0001) and alanine transaminase from 5.2 +/- 3.4 to 1.7 +/- 1.2 (P < .0001) times the upper level of normality. The Knodell score for liver histological activity decreased from 6.9 +/- 3 to 4.9 +/- 2.8 (P < .0001). These data indicate that phlebotomy is safe, efficient, and widely applicable to ex-thalassemics after BMT.

Adolescent

Inpatient phlebotomy practices. A College of American Pathologists Q-Probes quality improvement study of 2,351,643 phlebotomy requests.

We report outcomes of requests for inpatient phlebotomy procedures from 683 institutions participating in the College of American Pathologists Q-Probes programs. Of the 2,351,643 phlebotomy requests analyzed, 93.2% of venipunctures were successful, 1.6% were unsuccessful, 0.4% were partially successful, and 4.9% were not attempted by the assigned phlebotomist. Administrative inefficiencies prevented the assigned phlebotomist from attempting these venipunctures of which the most frequent reasons were patient unavailability (1.4%), patient transferred or discharged (0.9%), followed by the specimen already collected by someone else (0.7%). These results suggest that performance improvement of phlebotomy services, in general, would achieve the greatest gains by focusing attention to specific processes associated with administrative inefficiencies identified, rather than phlebotomists' technical skills.

Appointments and Schedules

Effects of phlebotomy and autologous blood transfusion on oxygen transport in the racehorse.

Because the haemoglobin concentration Hb[ during exercise may be at the upper limit of blood viscosity for effective oxygen delivery, we hypothesised that administration of blood would not further enhance oxygen delivery or exercise capacity. Six Thoroughbred geldings were used in 5 incremental treadmill exercise tests over a period of 4 weeks. The first test was performed 6 days prior to phlebotomy, which involved the removal of 20 ml/kg bwt of venous blood. Exercise tests were performed at 1, 8 and 15 days after blood removal. Six days after the 15 day post phlebotomy exercise test, blood from each horse was reinfused and the final test performed 24 h after blood reinfusion. During the 3 weeks following blood collection, the blood, collected into acid citrate dextrose, was stored at 3 degrees C. Each exercise test involved measurements of arterial and mixed venous blood gases, plasma lactate concentrations, heart rate and VO2 using an open flow system. Cardiac output was measured by direct Fick. The removal and reinfusion of blood had significant effects on packed cell volume (PCV) with the lowest PCV value during exercise of 0.57 +/- 0.04 l/l being recorded in the second post phlebotomy test and the highest value of 0.67 +/- 0.04 l/l found after blood reinfusion. There were no significant effects of phlebotomy or blood reinfusion on arterial blood gas values. However, arteriovenous oxygen content difference was significantly altered by phlebotomy and reinfusion. The maximal values during the 3 tests following phlebotomy were significantly lower (P < 0.05) by about 7% than those before phlebotomy and after blood reinfusion, mirroring the alterations in Hb[. There was no significant effect of phlebotomy or blood reinfusion on heart rate but stroke volume was significantly higher (P < 0.01) during the 3 post phlebotomy tests than for the control or blood reinfusion tests. There was no significant effect of phlebotomy or blood reinfusion on either the submaximal or maximal values for VO2. No significant effect of blood removal or reinfusion was found on the treadmill run time to fatigue. We concluded that haemodynamic adjustments following phlebotomy or blood reinfusion maintained oxygen delivery during exercise. No detrimental effects on exercise capacity were found from phlebotomy nor beneficial effects from autologous blood transfusion. However, it should be noted that the extent of change induced in Hb[ was relatively small and with the number of horses in the study, the experimental power was not great.

Animals

A survey of phlebotomy among persons with hemochromatosis.

BACKGROUND: One in 10 whites in the United States is a carrier for hemochromatosis and an estimated 1 in 200 is clinically affected. Early treatment with therapeutic phlebotomy to remove excess iron can prevent associated chronic diseases. However, little information is available on the amount of blood withdrawn or the rates of withdrawal from hemochromatosis patients. The patterns of therapeutic phlebotomy and the magnitude of charges in persons with hemochromatosis were surveyed. STUDY DESIGN AND METHODS: Surveys were mailed to persons with hemochromatosis identified by health care providers, blood centers, patient advocacy groups, and the Internet. There were 2362 respondents to the survey from the United States. RESULTS: Thirty-seven percent of respondents reported being voluntary blood donors prior to diagnosis. The mean rate of therapeutic phlebotomy for iron depletion was 2.6 units per month (mean duration, 13 months). The mean rate of maintenance phlebotomy was 0.5 units per month. Therapeutic phlebotomy rates varied by sex, age, reason for diagnosis, and severity of symptoms. Seventy-six percent of respondents reported full or partial insurance coverage of therapeutic phlebotomy charges. Seventy-six percent received therapeutic phlebotomy services in a hospital or physician's office and 30 percent in a blood center. Charges for therapeutic phlebotomy varied by site, with a mean cost of $90 in hospitals and $52 in blood centers. Fifty-four percent of respondents attempted to donate blood after their diagnosis but were excluded. CONCLUSION: The amount of blood withdrawn from persons with hemochromatosis is substantial. The location where patients received phlebotomy services appears to be influenced by charges and time since diagnosis.

Adult

The influence of single or repeated phlebotomy on the physiological condition of normal and diseased rats.

The present experiment was performed to see the influence of phlebotomy on hematology, serum chemistry, and pathology data in rats. When normal rats received a single phlebotomy of 2 or 3 ml blood, erythrocyte count and hematocrit were slightly reduced along with a persistent depression of the blood pressure. In repeated phlebotomy studies, 0.25 to 2 ml each of blood was removed from each rat every other day for 10 days. Normal rats from which 0.5 ml and more of blood was withdrawn showed decreases in erythrocyte count and serum iron level concomitant with an increase in reticulocyte count. Similar findings were obtained in rats with CCl4 liver damage or gentamicin nephrotoxicity, except that those rats hardly exhibited anemia because of a simultaneous occurrence of hemoconcentration. Histopathological findings of the liver and kidney were not different between animals with and without phlebotomy. In phenylhydrazine-treated rats receiving repeated phlebotomy, one rat in the 1-ml phlebotomy and two rats in the 2-ml phlebotomy died from severe anemia. Surviving rats receiving 2-ml phlebotomy showed higher serum GOT and GPT activities together with fatty deposition and/or focal necrosis of hepatocytes. It is concluded that every-other-day phlebotomy of up to 0.25 ml each does not significantly influence the physiological condition of normal or diseased rats.

Anemia

Evaluation of safety devices for preventing percutaneous injuries among health-care workers during phlebotomy procedures--Minneapolis-St. Paul, New York City, and San Francisco, 1993-1995.

Health-care workers (HCWs) are at risk for infections with bloodborne pathogens resulting from occupational exposures to blood through percutaneous injuries (PIs). Phlebotomy, one of the most commonly performed medical procedures, has been associated with 13% - 62% of injuries reported to hospital occupational health services and 20 (39%) of the 51 documented episodes of occupationally acquired human immunodeficiency virus (HIV) infection reported in the United States (CDC, unpublished data, 1996). Although safety devices designed to prevent PIs associated with phlebotomy have been available for use in the United States, clinical evaluation of these devices has been difficult because 1) ascertainment of PIs is difficult (many injuries are unreported, and observation of all procedures is impractical because phlebotomy is performed throughout the hospital by different groups of HCWs at all hours), 2) data to calculate PI rates (i.e., the number of phlebotomies performed and devices used) are not routinely available, 3) a large number of phlebotomies must be evaluated because of the low rates of phlebotomy-related PI and 4) rates of safety-feature activation are difficult to assess. This report summarizes a collaborative study by CDC and six hospitals to evaluate safety devices for phlebotomy. The findings indicate that use of safety devices significantly reduced phlebotomy-related PI rates while having minimal clinically apparent adverse effects on patient care.

Accidents, Occupational

Therapeutic efficiency of phlebotomy in posttransplant hypertension associated with erythrocytosis.

Hypertension is a major complication in kidney transplantation and contributes to the high cardiovascular mortality of renal transplanted recipients. The aim of the present study was to evaluate the therapeutic effect of phlebotomy on blood pressure in posttransplant hypertension associated with erythrocytosis. In 12 renal transplanted patients (7 male, 5 female, aged 29-52 years) with erythrocytosis (defined by hematocrit > 52% or hemoglobin > 170 g/l), a 24-hour-monitoring of blood-pressure and heart rate (SpaceLabs SL90207) was performed before, 2 and 6 weeks after phlebotomy. Patients with iron-deficiency and/or transplant rejection were excluded from the study. Ten of 12 patients were on antihypertensive treatment before phlebotomy. Phlebotomy (500 ml) was repeated three times on average within the first two weeks, until hematocrit decreased below 45%. The phlebotomy therapy lowered the hematocrit after two weeks from 54.8 +/- 2.8% to 44.3 +/- 4.2% and 43.0 +/- 5.6% after six weeks. Before phlebotomy, the blood pressure was systolic 153.2 +/- 15.1 mmHg and diastolic 95.2 +/- 9.5 mmHg. After repeated phlebotomy, there was a significant decrease of blood pressure to systolic 139.0 +/- 14.1 and diastolic 85.3 +/- 8.2 mmHg (p < 0.01). Without change of hematocrit and hemoglobin, there was no further change of blood pressure after six weeks (systolic 140.1 +/- 9.9 mmHg, diastolic 86.3 +/- 9.5 mmHg). The heart rate did not change significantly during the therapy. The antihypertensive treatment could be reduced in most of the patients. The present study demonstrates the therapeutic effect of phlebotomy in posttransplant hypertension associated with erythrocytosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

[Prevention of sickle cell crises with multiple phlebotomies].

OBJECTIVES: Sickle cell disease patients suffering from frequent painful crises were submitted to phlebotomies in order to reduce hospitalization days due to pain, through hemoglobin (Hb) level reduction and iron deficiency in patients with an hemoglobin level equal to or above 9.5 g/dL. PATIENTS: Seven sickle cell disease patients (four SC, three SS), aged four to 24 years, were submitted to sequential phlebotomies during periods from 18 months to four years. METHODS: The number of hospitalization days for crises was considered. The volumes and frequencies of phlebotomies were adjusted according to the patients ages, the hemoglobin concentrations and the serum ferritin levels. RESULTS: One hundred and forty-four hospitalization days were recorded in the seven patients in the year preceding the treatment. During the study period, the annual numbers of hospitalization days were respectively 20, five, six and one. Mean hemoglobin concentration was 10.7 g/dL before phlebotomies and 8.8 to 9.2 g/dL during the four years of treatment. Mean corpuscular volume, mean corpuscular hemoglobin concentration and serum ferritin were also reduced. The volume of phlebotomies was 116 to 39 mL/kg/year according to the patients. COMMENTS AND CONCLUSION: The striking decrease of the number of hospitalization days for all the patients suggests a closed relationship between therapy and clinical improvement. The mechanism of this effect is probably multifactorial: a) the concentration of Hb level is known to influence the blood viscosity and its decrease always improved rheology in sickle cell disease patients; b) the mean corpuscular hemoglobin concentration is a critical factor concerning the HbS molecule polymerization in sickle cell disease, and its slight reduction may have an important biological effect. We observed these two biological modifications in our patients and suggest that they mediate the clinical effects. The iron deficiency induced by phlebotomies has no evident deleterious consequence either on height and weight in the children or on intellectual performance in any patients.

Adolescent

Effect of enalapril on exaggerated erythropoietin response to phlebotomy in erythrocytosic renal transplant patients.

BACKGROUND: Exaggerated erythropoietin (EPO) response to phlebotomy regardless of the baseline EPO levels have been shown in patients with post-transplant erythrocytosis (PTE) and administration of angiotensin-converting enzyme inhibitors (ACE-1) seems to be effective in controlling PTE. However, the mechanism of this ACE-1 induced reduction in haematocrit (Hct) is not well known. Although some authors have suggested that ACE-1 may reduce EPO secretion, this is still controversial. The aim of the present study was to assess the effect of a single dose ACE-1 on exaggerated EPO response to phlebotomy. METHODS: In this study, we compared serum EPO and renin (PRA) levels of 10 PTE patients, 10 non-PTE patients and 10 healthy blood donors before and after phlebotomy. The effects of a single dose of ACE-1 (enalapril, 5 mg p.o.) in PTE patients were also evaluated in the second phlebotomy. RESULTS: While the mean basal serum EPO level was significantly higher in the PTE group than the other two groups (P<0.01), the mean basal PRA levels did not differ significantly between these groups. Serum EPO and PRA levels increased significantly after the phlebotomy (P<0.001) and exaggerated EPO response to phlebotomy was suppressed by single dose enalapril (P<0.001) in the PTE patients. CONCLUSION: The present study has shown that the renin angiotensin system plays an important role in EPO formation and the Hct lowering effect of the ACE-1 is through reduction of EPO in PTE patients.

Adult

Hepatic iron concentration in hereditary hemochromatosis does not saturate or accurately predict phlebotomy requirements.

OBJECTIVE: Biochemical measurement of the hepatic iron concentration (HIC) is essential for the diagnosis of hereditary hemochromatosis (HH). The aim of this study was to determine whether the HIC at the time of diagnosis could predict the subsequent phlebotomy requirements and to determine whether saturation of HIC occurred in HH. METHODS: Fifty-four patients (32 male, 22 female) with homozygous HH were evaluated, and HIC was measured in liver biopsies. Patients were subjected to weekly phlebotomy (500 ml) until the transferrin saturation was <50% and/or the serum ferritin concentration was <50 microg/L. The relationship between HIC and total body iron stores (as measured by phlebotomy requirements) was determined using both linear and nonlinear (sigmoidal model) least squares regression. RESULTS: The HIC ranged from 3,742 to 41,040 microg/g dry wt. A linear relationship between HIC and total body iron stores (iron removed, IR, g) best described the data both in male (HIC = 1986 IR - 3494; r = 0.83; p < 0.001) and female HH patients (HIC = 1251 IR + 2690; r = 0.75; p < 0.001). Men required eight more phlebotomies (2 g iron) on average, compared with women, to reach normal iron stores. There was no evidence of saturation of hepatic iron levels at higher total body iron stores. However, accurate prediction of individual phlebotomy requirements based on the HIC or serum ferritin concentration at the time of diagnosis was not possible. CONCLUSION: The phlebotomy requirement for treatment of HH cannot be accurately predicted from the initial HIC or serum ferritin level. Within the range examined, hepatic iron deposition did not saturate in HH.

Adult

Physiological response to phlebotomies for autologous transfusion at elective hip-joint surgery.

In order to study the physiological response to phlebotomies for autotransfusion, an autotransfusion program was designed for 10 patients undergoing hip-joint replacement surgery for arthrosis. 4 phlebotomies of 450 ml each were performed within 12 days. Blood samples were taken immediately before phlebotomy for blood hemoglobin (Hb), serum erythropoietin (Epo), reticulocyte count (ret) and erythrocyte 2,3-diphosphoglycerate (DPG). All 4 phlebotomies could be performed in 9/10 patients, and only 1 patient had significant symptoms (fatigue). The operation was performed 2 weeks after the last phlebotomy. None of the patients had recovered the initial Hb level at operation (24.8 +/- 9 per liter lower than initially), and they were all even more anemic after the operation (36.8 +/- 16.9 g/l lower than initially). Serum Epo increased from 13.6 +/- 7.2 IU to 30.6 +/- 12.2 (SD) IU per liter, and reticulocyte counts increased to a maximum of 3.68 +/- 1.69%. DPG increased in all patients except the one who had significant fatigue. It is concluded that the patients tolerated the phlebotomy program well but that a significant anemia developed. The compensatory increase in erythropoietin and reticulocyte count, adequate for this degree of anemia, was small compared to the increase seen at more severe anemia, indicating that there may be a role for pharmacological stimulation of erythropoiesis in blood predeposit programs.

Adult

Evaluation of phlebotomy-induced erythropoietin production in the dog.

Erythropoietin (EPO) production in dogs was studied by reducing red blood cells with phlebotomy. In this study, the hemoglobin reduction rate (delta %Hb) was newly taken into account as the regulating factor for EPO production, and its usefulness to estimate the stimulating intensity to EPO production was examined. As the result, plasma EPO was highly correlated with delta %Hb showing the importance related to regulation of EPO production, in the increasing plasma EPO by different degrees of phlebotomy, in the change of plasma EPO through the anemia progress and recovery period after severe phlebotomy, and in the initial variation of plasma EPO induced by chronic mild phlebotomy. On the other hand, increasing EPO production appeared at least within 6 hr after acute severe phlebotomy, which revealed significantly higher plasma level compared with the mild chronic phlebotomy, suggesting the effect of time leading to red blood cell reduction on EPO production response. Simultaneously, considering an in vivo EPO half life of 8.4 hr calculated from plasma EPO disappearance after bilateral nephrectomy, endogenous plasma EPO accumulation should be taken into consideration in rapidly increasing of delta %Hb.

Anemia

The effect of phlebotomy on serum erythropoietin levels in normal healthy subjects.

We evaluated endogenous serum erythropoietin (Epo) levels in 14 normal subjects (eight males and six females) after a single 400-ml phlebotomy. The subjects were followed up for 56 days. The hemoglobin (Hb) values of both males and females decreased to a nadir on days 3 to 7 post-phlebotomy. Hb values gradually increased, but did not completely recover to pre-phlebotomy levels by day 56. Serum Epo levels increased after 6 h post-phlebotomy, to 20.1 +/- 5.4 (mU/ml) in males and 20.7 +/- 7.0 in females, from the pre-phlebotomy levels of 14.6 +/- 4.0 in males and 13.4 +/- 4.1 in females, respectively. Epo levels continued to increase to peak levels of 25.5 +/- 6.3 in males and 28.7 +/- 11.5 in females on days 7 to 14 and thereafter decreased until day 56. Thus, the Epo response to a 400-ml phlebotomy was relatively small in magnitude and was not sufficient to initiate a significant increase in erythropoiesis. This finding suggests that the administration of recombinant human erythropoietin (rHu-Epo) may be effective for the prompt correction of anemia induced by autologous blood donation and for increasing the volume of predonated autologous blood.

Adult

Prospective crossover study of the effect of phlebotomy and intravenous crystalloid on hematocrit.

OBJECTIVE: To compare the changes in hematocrit (Hct) between phlebotomized and nonphlebotomized individuals given IV crystalloid. METHODS: A prospective, crossover volunteer study was performed comparing Hct changes immediately and 30 minutes after IV crystalloid bolus in 20 healthy adults with and without prebolus phlebotomy. In the control portion, volunteers were given a 15-mL/kg bolus of normal saline over 30 minutes with Hct determination before (H1), immediately after (H2), and 30 minutes after (H3) crystalloid infusion. At least 7 days later, the same subjects were phlebotomized 1 unit of blood and then administered a 15-mL/kg IV bolus of normal saline 30 minutes later. Hcts were obtained before (H4) and 30 minutes after (H5) phlebotomy (immediately prior to crystalloid infusion). Hcts were also obtained immediately after (H6) and 30 minutes after (H7) crystalloid infusion. A post-hoc test performance analysis was then performed to determine the Hct drop thresholds that would yield the maximal sensitivity and specificity for 500 mL of blood loss (via phlebotomy) in this population. RESULTS: The Hct (%) drops in the nonphlebotomized individuals receiving IV fluids averaged 4.5 +/- 1.3 immediately and 3.2 +/- 1.3 30 minutes after infusion. These drops were different (p < 0.05) from the Hct drop in individuals receiving IV fluids after phlebotomy, which averaged 6.6 +/- 1.5 and 5.7 +/- 1.1, respectively. Post-hoc analysis revealed that Hct drops of 5.4 immediately, or 4.3 at 30 minutes after infusion, had a sensitivity of > 90% and a specificity of 75% for identification of patients in the phlebotomy group. CONCLUSIONS: The practice of measuring serial Hcts may be helpful to identify trauma patients with occult blood loss. A prospective clinical trial is needed to validate these Hct drop thresholds (immediate and 30 minutes postinfusion) in crystalloid-resuscitated trauma patients.

Adult

Phlebotomy for pulmonary edema in dialysis patients.

STUDY OBJECTIVE: To assess the efficacy of phlebotomy in the treatment of pulmonary edema in hemodialysis patients. PROCEDURE: Maintenance hemodialysis patients presenting to the emergency room in respiratory distress from apparent pulmonary edema were assessed with regard to clinical response, change in blood pressure, change in hematocrit, and interval until the next hemodialysis treatment, RESULTS: Twenty-one patients underwent phlebotomy and seventeen improved markedly and did not require intubation or emergent dialysis. Hemodialysis was initiated 15.6 +/- 13.6 SD hours later. Four were able to have their treatment 24 or more hours later. Thirteen of 21 (62%) were hypertensive at the time of treatment and blood pressure tended to normalize in this subset. Four of 21 (19%) developed transient hypotension without permanent sequelae. Pre-mean hematocrit = 25.0 + 6.0 and post phlebotomy = 22.6 + 4.6 SD. All patients receiving phlebotomy survived to hospital discharge. CONCLUSION: Phlebotomy can often obviate the need for intubation or emergent dialysis in ESRD patients presenting with pulmonary edema.

Blood Pressure