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Phlebotomy: a treatment of ischaemic necrosis of the femoral head? Analysis of a hypothesis.

The treatment of non-traumatic ischaemic osteonecrosis of the femoral head (ONFH) remains problematical and there is evidently scope to seek for a medical treatment of this disease which often leads to a surgical procedure for hip prosthesis. If we exclude the context of hemoglobin disorders, necrosis appears mainly in adults, when their limb bones contain a fatty marrow. Investigations such as intramedullary pressure measurement and transosseous phlebography suggest a disorder of the intraosseous blood circulation. Various studies in animals and man have provided arguments indicating that a kind of intraosseous 'obesity' due to hyperplasia and/or hypertrophy of the fatty tissue of the femoral marrow play a role in the development of necrosis. In this respect, the blood flow of the yellow marrow is close to ischemia, whereas red marrow flow can be very high. In various conditions, mainly hemolytic anemias, the femoral yellow marrow can convert to red marrow, which has also been described in anemias induced by blood loss. If it is not thought unreasonable to consider ONFH an 'ischemic' disease, these observations are an encouragement to attempt treatment by repeated phlebotomies. This procedure may locally restore red marrow, and then an adequate blood flow which could stabilize or even reverse the lesions if they are diagnosed early.

Femur Head Necrosis↗

[Successful treatment using iron depletion phlebotomy combined with recombinant erythropoietin after allogeneic bone marrow transplantation for myelodysplastic syndrome complicated by secondary hemochromatosis].

A 33 year-old female patient presented with apparent skin pigmentation, sustained liver dysfunction and impaired glucose tolerance. She had received blood transfusions totalling more than 40,000 ml for myelodysplastic syndrome and an allogeneic bone marrow transplant from her HLA-matched sister at the age of 31. Ferrokinetic data showed a significant iron overload. Magnetic resonance imaging suggested excessive iron deposition in the liver. The patient was diagnosed as having secondary hemochromatosis. She was given subcutaneous injections of 6,000 units of recombinant human erythropoietin initially twice a week and then weekly, and phlebotomies were performed to maintain her hemoglobin level above 10 g/dl. Three years later, the total volume of phlebotomized blood reached 24,000 ml, and her ferrokinetic data, serum transaminase levels, glucose tolerance and skin color were significantly improved.

Adult↗

Normalization of elevated hepatic 8-hydroxy-2'-deoxyguanosine levels in chronic hepatitis C patients by phlebotomy and low iron diet.

Accumulation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in DNA, which may result from the continuous reactive oxygen species (ROS) generation associated with chronic inflammation, has been reported in various human preneoplastic lesions and in cancerous tissues. However, no direct causative relationship between the 8-OHdG formation and carcinogenesis has been thus far demonstrated in humans. Directly proving the causality requires showing that depletion of 8-OHdG levels in tissue by interfering with ROS generation results in a reduction in cancer. Chronic hepatitis C virus (HCV) infection is associated with a high risk of hepatocellular carcinoma (HCC). Several studies on patients with chronic HCV have shown that hepatic iron overload is attributable to liver injury and that iron depletion improved serum aminotransferase levels. Excess iron is known to generate ROS within cells, which causes mutagenic lesions, such as 8-OHdG. In this study, therefore, we have evaluated whether therapeutic iron reduction (phlebotomy and low iron diet) with a long-term follow-up (6 years) would decrease the hepatic 8-OHdG levels and the risk of HCC development in patients with chronic HCV. Patients (34) enrolled were those who had undergone standard IFN therapy but had no sustained response. Quantitative immunohistochemistry using the KS-400 image analyzing system and electrochemical detection was used for 8-OHdG detection. With this treatment, elevated hepatic 8-OHdG levels in patients with chronic hepatitis C (8.3 +/- 4.6/10(5) dG) significantly decreased to almost normal levels (2.2 +/- 0.9/10(5) dG; P < 0.001) with concomitant improvement of hepatitis severity, including fibrosis, whereas HCV titers were unaffected. None of these patients developed HCC. Thus, long-term iron reduction therapy in patients with chronic hepatitis C may potentially lower the risk of progression to HCC.

8-Hydroxy-2'-Deoxyguanosine↗

Blood sample collection from a peripheral catheter system compared with phlebotomy.

Hospital experiences often are punctuated with pain related to common procedures, such as venipuncture. An alternative to venipuncture involves obtaining samples from an existing peripheral vascular saline lock device. To validate such a collection, this study compared the accuracy of serum chemistry tests performed on samples taken concurrently from the saline locks and by phlebotomy. No clinical differences were noted within the 17 sets of ion assays, and both potassium and chloride determinations demonstrated no significant statistical differences between the sample groups. Documented rates of sample hemolysis (21%) and difficulties experienced in collection suggest that blood sampling from an existing peripheral saline lock device is best suited to inpatients undergoing multiple blood sampling necessitated by short-term investigative procedures or crisis management.

Blood Chemical Analysis↗

Porphyria cutanea tarda symptomatica (PCT-S). A study of the effect of phlebotomy therapy.

The effect of phlebotomy therapy on porphyrin metabolism was evaluated in five patients with porphyria cutanea tarda symptomatica (PCT-S). The removal of 2,500 to 4,500 cc over a three to four and one-half month period resulted in a marked reduction in urine and fecal uroporphyrin excretion in three of the subjects. Clinical improvement accompanied the chemical response in each case. In one patient, the induced chemical and clinical remission has persisted for six months without further treatment.

Adult↗

Combined false hyperkalemia and hypocalcemia due to specimen contamination during routine phlebotomy.

Combined pseudohyperkalemia and pseudohypocalcemia have not been previously reported in the clinical setting. We report 2 cases in which specimen contamination during routine phlebotomy with ethylenediaminetetraacetic acid (EDTA) caused alteration in serum levels of potassium and calcium. This alteration could be misleading when making clinical decisions and could produce adverse patient outcomes.

Adolescent↗

ACQUIRED PORPHYRIA CUTANEA TARDA: REPORT OF A CASE SUCCESSFULLY TREATED BY PHLEBOTOMY.

CURRENTLY, THE PORPHYRIAS ARE CLASSIFIED IN FOUR MAIN GROUPS: congenital porphyria, acute intermittent porphyria, porphyria cutanea tarda hereditaria, and porphyria cutanea tarda symptomatica. The acquired form of porphyria (porphyria cutanea tarda symptomatica) occurs in older males and is nearly always associated with chronic alcoholism and hepatic cirrhosis. The main clinical changes are dermatological, with excessive skin fragility and photosensitivity resulting in erosions and bullae. Biochemically, high levels of uroporphyrin are found in the urine and stools. Treatment to date has been symptomatic and usually unsuccessful.A case of porphyria cutanea tarda symptomatica is presented showing dramatic improvement of both the skin lesions and porphyrin levels in urine and blood following repeated phlebotomy.Possible mechanisms of action of phlebotomy on porphyria cutanea tarda symptomatica are discussed.

Alcoholism↗

Effects of vitamin E administration on the hemorheological status and redox homeostasis of patients with porphyria cutanea tarda treated with phlebotomy.

BACKGROUND: Conflicting results were reported about the efficacy of vitamin E (E) treatment in porphyria cutanea tarda (PCT). We conducted a study in PCT patients to investigate whether E treatment has any additional beneficial effects compared with phlebotomy (P) treatment alone on rheological and oxidative stress parameters. METHODS: Twenty three patients with sporadic PCT in clinical remission and 10 healthy control patients were studied. All patients were treated with P prior to the study until clinical remission was achieved. Baseline routine laboratory [blood glucose, serum lipids, C-reactive protein (CRP), iron metabolism indices, liver function tests], oxidative stress [serum thiobarbituric acid reactive substances (TBARS), plasma H-donor activity, plasma free SH-groups, erythrocyte glutathion peroxidase activity] and rheological parameters (whole blood and plasma viscosity, cell transit time, clogging rate) were measured in both groups. Then all PCT patients received E (tocopherol acetate) 200 mg/day for 8 weeks and at the end of treatment measurements identical to those performed at baseline were repeated. RESULTS: Increased urine uroporphyrin, serum CRP, TBARS concentrations, whole blood and plasma viscosity and decreased plasma H-donor activity, free SH-group level, erythrocyte glutathione peroxidase activity were detected in PCT patients treated with P alone compared with control group consistent with residual oxidative stress in PCT patients. E treatment decreased urine uroporphyrin and serum TBARS concentrations; increased plasma H-donor activity and did not influence whole blood and plasma viscosity compared with P treatment alone. CONCLUSIONS: E treatment reduced the residual oxidative stress and did not influence increased plasma and whole blood viscosity present in PCT patients receiving P treatment prior to clinical remission.

Adult↗

Arthritis of hemochromatosis. Clinical spectrum, relation to histocompatibility antigens, and effectiveness of early phlebotomy.

Five patients who presented with arthritis as the sole manifestation of hereditary hemochromatosis and 51 family members were studied. Studies included clinical evaluation for the presence of arthritis and hemochromatosis, roentgenography of hands, knees, and pelvis, serum iron and serum ferritin measurements, complete HLA typing for 50 of the A and B loci, and, when indicated, liver biopsy. Arthritis occurred in 45 percent of persons with hemochromatosis. Although typical involvement of second and third metacarpophalangeal joints was observed in all five patients and some family members, two with typical arthritis did not have characteristic radiographic changes, two had constitutional symptoms without arthropathy, and one had unilateral hand changes. A specific HLA haplotype (A2/B17 in Family 1 and A29/B15 in Family 2) correlated with hereditary hemochromatosis but not with the arthropathy. Phlebotomy alleviated the early constitutional symptoms but did not help advanced arthritis. Anti-inflammatory drugs, intraarticular injections of glucocorticoids, and resection osteotomies of metacarpal heads were other treatment modalities.

Anti-Inflammatory Agents↗

The effect of phlebotomy as a treatment of Fabry disease.

Senescent erythrocytes are considered a major source of the ceramide trihexoside which accumulates in Fabry disease patients. We have evaluated weekly phlebotomy as a method to reduce the catabolic load imposed by the senescence of erythrocytes and thereby ceramide trihexoside in one Fabry patient; no change was observed in either plasma or urinary level of ceramide trihexoside. The implications of this observation are discussed with regard to glycolipid metabolism in man.

Bloodletting↗

Studies on ferritin in rat liver and spleen during repeated phlebotomy.

1. The ferritin content of liver and spleen in normal and iron-loaded rats decreased during repeated phlebotomy. 2. During increased iron demand, ferritin is degraded in toto. 3. With the ESI and EELS technique the iron distribution was followed in different cell types and cellular compartments. 4. We have demonstrated two methods of iron mobilisation: (a) catabolism of lysosomal ferritin in toto and (b) delivery of ferritin from parenchymal cell into the bile and degradation of ferritin in toto.

Animals↗

Childhood-onset familial porphyria cutanea tarda: effects of therapeutic phlebotomy.

Cutaneous fragility at age 2 years with blistering, scarring, milia, and hypertrichosis at age 4 years were noted in an otherwise healthy girl who had no family history of porphyria. Results of porphyrin analyses of urine, serum, and red blood cells revealed a pattern consistent with porphyria cutanea tarda. Red blood cell uroporphyrinogen decarboxylase activity was diminished to approximately 50% of normal in the child and in her mother and maternal grandmother, who were without symptoms; activity was normal in her sister, father, and maternal grandfather. Therapeutic phlebotomies were followed by a biochemical and clinical remission.

Bloodletting↗

Phlebotomy--a minimalist approach.

For each patient, laboratories usually collect more blood than is needed for specific determinations. We reviewed the amount of blood collected for laboratory measurements for an entire hospital stay of 113 patients admitted during a 1-week period to a medical ward or to a medical intensive-care unit in our tertiary-care facility. The amount of blood obtained was also compared with the minimal amount needed for analysis for 18 of the most frequently ordered laboratory tests in our facility. For routine collections, a mean of 45 times the required volume of specimen (range, 2 to 102 times) was obtained. For optimal utilization of laboratory services, both the positive and the negative consequences of testing must be thoughtfully considered. Two potential adverse effects of withdrawal of blood for laboratory determinations are iatrogenic anemia and infection. Moreover, the cost of care is increased with additional analyses. Practical strategies for decreasing the amount of blood collected include an increased awareness of ordering practices, a thorough knowledge of the volume of blood needed for each laboratory test, experienced phlebotomy personnel, storage of blood specimens for potential subsequent use, and communication of accurate minimal volumes needed for specific measurements.

Anemia↗

The use of nuclear magnetic resonance imaging in monitoring total body iron in hemodialysis patients with hemosiderosis treated with erythropoietin and phlebotomy.

Two hemodialysis patients with hemosiderosis were treated with combined erythropoietin and repeated phlebotomy. Serial nuclear magnetic resonance (NMR) imaging and serum ferritin levels were used to monitor the efficacy of treatment. This treatment modality has definite advantages over chronic deferoxamine therapy. NMR image-derived parameters offer an objective, accurate, and noninvasive indication of tissue iron stores.

Adult↗

Cerebral borderzone infarcts after phlebotomy.

We describe a 68-year-old patient with cerebral ischaemia who underwent a phlebotomy to lower an elevated haematocrit (0.61 l/l. The procedure was complicated by the development of a total hemiplegia after two hours. CT scanning showed two borderzone infarcts. We conclude that the plasma volume of patients with cerebral ischaemia and a high haematocrit may be contracted to such an extent that venesection is hazardous. The most appropriate treatment in these patients is expansion of the plasma volume.

Aged↗

Survival and biochemical characteristics of stored red cells preserved with citrate-phosphate-dextrose-adenine-one and two and prepared from whole blood maintained at 20 to 24 degrees C for eight hours following phlebotomy.

Studies were conducted to evaluate the characteristics of red cells stored for 35 days following preparation from units of whole blood anticoagulated with citrate-phosphate-dextrose-adenine-one and two (CPDA-1 and CPDA-2) and maintained at 20 to 24 degrees C for 8 hours after phlebotomy. The mean (+/- 1 SD) 24-hour survival for transfused CPDA-1 autologous red cells with hematocrit levels of 78.1 +/- 2.3 percent was 78.0 +/- 8.1 percent (n = 9). The 24-hour survival of red cells from units preserved with CPDA-2 with hematocrit levels of 79.3 +/- 4.5 percent was 74.8 +/- 8.6 percent (n = 15). This difference in survival was not significant. Red cells from control units stored for 1 day showed a 24-hour survival of 91.9 +/- 4.2 percent (n = 7). During the 8-hour holding, red cell adenosine triphosphate levels increased by 15 to 25 percent in units drawn into both CPDA-1 and CPDA-2. After the initial 8-hour period, the red cell 2,3 diphosphoglycerate levels were 54 +/- 12 percent (mean +/- 1 SD) of initial levels in units drawn into CPDA-1 and 58 +/- 8 percent of initial levels in units drawn into CPDA-2. Following 35 days of storage, units of red cells prepared from whole blood drawn into CPDA-1 and CPDA-2 had comparable plasma cation and ammonia levels and similar amounts of cell-free hemoglobin. These data indicate that red cells can be stored satisfactorily for 35 days when prepared from whole blood held at 20 to 24 degrees C for 8 hours.

2,3-Diphosphoglycerate↗

Polycythaemia vera in a dog treated by repeated phlebotomies.

Polycythaemia vera (PV) was diagnosed in a dog by demonstration of an increased red cell mass in association with normal arterial oxygen saturation and the absence of conditions known to be associated with secondary polycythaemia. The dog was treated exclusively by repeated phlebotomies and replacement of the removed volume by colloid and crystalloid solutions. It survived for one year and was generally free of signs.

Animals↗

Effects of phlebotomy on urinary porphyrin pattern and liver histology in patients with porphyria cutanea tarda.

Urinary porphyrin profiles and liver histology have been investigated in a group of adult alcoholics with porphyria cutanea tarda (PCT) before and after one year phlebotomy. Both parameters were evaluated during the same period in a group of patients who did not undergo specific therapy for PCT. All patients were advised to abstain from alcohol. At the end of the one year observation period there was a significant fall of urinary total porphyrins and in the uro/coproporphyrin ratio in treated patients compared to basal values whereas no changes were found in controls. Liver biopsy findings revealed a significant reduction of hepatic fatty degeneration and siderosis with no changes in inflammatory infiltrates and fibrosis in treated patients, so the progression of liver disease was similar to controls. These results show that clinical and biochemical remission of PCT can occur independently of the evolution of the concomitant liver disease.

Alcoholism↗