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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

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

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

Primary hemochromatosis: anatomic and physiologic characteristics of the cardiac ventricles and their response to phlebotomy.

M-mode and 2-dimensional echocardiography and gated equilibrium blood pool imaging (rest and exercise) were used in 10 patients with primary hemochromatosis to characterize the spectrum of pathophysiologic abnormalities of the cardiac ventricles and to determine the response to chronic therapeutic phlebotomy. Dilated and restrictive cardiomyopathic patterns were identified in 1 patient each, but our data do not permit conclusions on when in the natural history a given pattern becomes overt. On entry into study, 3 patients had normal ventricles and 7 had ventricular abnormalities on echocardiography and blood pool angiography. In 2 of the latter patients, biventricular dysfunction and increased left ventricular (LV) mass normalized after phlebotomy; 1 patient achieved a normal LV response to exercise. Of the 4 patients with isolated abnormal LV ejection fraction responses to exercise, the EF normalized in 2 after phlebotomy. In 1 patient, isolated right ventricular enlargement and dysfunction (echocardiographic and radionuclide imaging) normalized after phlebotomy. Thus, primary hemochromatosis can effect LV and RV size and function; clinically occult cardiac involvement can be identified by echocardiography and equilibrium blood pool imaging; therapeutic phlebotomy can ameliorate or reverse the deleterious effects of excess cardiac iron deposition which appears to exert its harm, at least in part, by a mechanism other than irreversible connective tissue replacement.

Adult

Improved exercise tolerance of the polycythemic lung patient following phlebotomy.

The present study evaluated the effects of therapeutic phlebotomy on the exercise tolerance and the maximal carbon dioxide output of polycythemic patients with chronic obstructive pulmonary disease. Fifteen maximal exercise studies were performed before and after phlebotomy in patients with moderate to severe chronic obstructive pulmonary disease (mean forced expiratory volume in one second [FEV1]= 970 ml). After phlebotomy there were no significant differences in pulmonary function, blood gases, oxygen consumption, or carbon dioxide production at rest. However, after phlebotomy there was a significant increase in the exercise tolerance of the patients. The mean workload, the duration of exercise, the maximal oxygen consumption, the maximal carbon dioxide production, and the ventilation at maximal exercise all increased significantly. The improved exercise tolerance after phlebotomy appeared due to an increased cardiac output generated mainly through an increased stroke volume. We hypothesize that the increased stroke volume was due to a higher ejection fraction of the right ventricle secondary to a lower pulmonary artery pressure. This study provides further evidence that patients with chronic obstructive pulmonary disease who have polycythemia benefit by therapeutic interventions that maintain their hematocrits below 55 percent.

Aged

Influence of phlebotomy treatment on abnormal hypothalamic-pituitary function in genetic hemochromatosis.

To test the hypothesis that deficiencies in hypothalamic-pituitary function in genetic hemochromatosis result from cellular injury by iron deposits, we conducted provocative tests in 11 men with genetic hemochromatosis before and after iron depletion by serial phlebotomy and in 10 control subjects. We gave combination intravenous injections of insulin (0.15 U/kg), luteinizing hormone releasing hormone (LHRH, 100 micrograms), and thyrotropin releasing hormone (400 micrograms) and then measured plasma glucose, growth hormone, corticosteroids, follicle-stimulating hormone, luteinizing hormone, prolactin, and thyroid-stimulating hormone at 30-minute intervals for 90 minutes. Phlebotomy caused a substantial decrease in median values for serum ferritin, deferoxamine-chelatable iron, and hepatic iron concentration. Before phlebotomy, stimulation by hypoglycemia and thyrotropin releasing hormone caused significantly less secretion of growth hormone (P = 0.004) and prolactin (P = 0.03) in patients than in control subjects. No significant improvement was noted, however, in growth hormone or prolactin secretion after phlebotomy. Of the 11 patients, 7 had secondary hypogonadism, and phlebotomy did not improve the serum testosterone, follicle-stimulating hormone, luteinizing hormone, or responses to LHRH in any case. Chlorpromazine injections failed to elevate serum prolactin in all patients, and administration of levodopa caused a partial reduction in serum prolactin; thus, the hypothalamus may be an important locus of endocrine malfunction in these patients. We conclude that abnormal hypothalamic-pituitary function in genetic hemochromatosis is not substantially improved by iron-depletion therapy.

Adult