Measurement of haemolysis in patients with prosthetic heart valves.

Haemolysis following prosthetic heart valve insertion can be precisely and sensitively measured by means of a 59Fe ferrokinetic technique. Results obtained in a small series of patients with either Starr-Edwards or Brunwald-Cutter valve replacement are presented.

Erythropoiesis and iron.

Iron and erythropoiesis are inextricably linked. Erythropoiesis is a dynamic process that requires 30-40 mg of iron per day. In normal circumstances this is met from red cell destruction but in anaemia this will not be the case. Reduced iron stores will limit iron supply to erythroblasts but normal or raised iron stores may not be able to supply iron fast enough. This is particularly true when the marrow is stimulated by erythropoietin therapy; the most common cause of failure to respond is "functional iron deficiency"'. This entity can only be effectively addressed by intravenous iron therapy. While haemoglobin and serum ferritin concentrations reflect the major iron pools, iron supply to erythroid cells can only be assessed by measuring effective haemoglobinization through the percentage of hypochromic red cells in the circulation.

An evaluation of two methods of laboratory quality control.

Two methods for quality control of automated blood counters have been compared: (1) monitoring results from patients' samples, and (2) analysis of results of a stable whole-blood control. The latter method proved better able to distinguish calibration changes from patient variation.

Quality control in routine haemoglobinometry.

An analysis of haemoglobin estimations in a routine laboratory shows that quality control methods based on mean values are unsatisfactory. The use of a cusum method together with control samples is a sensitive and convenient technique for the early discovery of minor deviations in results and it is not dependent on a stable population of patients.

The preparation of 59 Fe-labelled transferrin for ferrokinetic studies.

Serum labelled with (59)Fe for ferrokinetic studies should contain only [(59)Fe] transferrin. [(59)Fe] ferric citrate was incubated at 37 degrees C for up to 24 hours with sera having an excess latent iron-binding capacity. The results showed that unbound [(59)Fe] ferric citrate may be present for several hours. An anion exchange resin (IRA 400 Cl(-)) column removed all the [(59)Fe] ferric citrate and left only [(59)Fe] transferrin in the eluate. It is suggested that all (59)Fe-labelled preparations for ferrokinetic studies should be passed through a resin column before injection.

Automated quality control for the haematology laboratory.

Two simple methods of using sophisticated statistical techniques to analyse intralaboratory quality control data are described. One method uses a plastic grid to assess the cumulative sum (cusum) graph. An equivalent procedure, which may be carried out by a laboratory computer, gives automated on-line quality control of the Coulter S blood counter. The possible development of simple apparatus to carry out the same function is discussed.

The platelet count in pregnancy.

The platelet count was measured at approximately monthly intervals during the course of 44 normal pregnancies. There was no evidence of any fall in the platelet count during pregnancy. Any significant change in the platelet count in pregnant women is unlikely to be the result of a normal pregnancy.

Hypochromic macrocytes: are they reticulocytes?

Automated full blood counters measuring the size and haemoglobin concentration of individual red cells by high and low angle light scatter can provide estimates of the percentage of cells which are abnormal in either or both of these variables. The hypothesis that an increase in the number of large cells with a reduced haemoglobin content ("hypochromic macrocytes") was indicative of a reticulocytosis was investigated. A correlation was shown between the percentage of hypochromic macrocytes and the reticulocyte count. This correlation was too weak to allow the actual reticulocyte percentage to be predicted from the percentage of hypochromic macrocytes. An increased percentage of hypochromic macrocytes, however, often indicates an increased reticulocyte count and thus serves to chart the haematologist to this possibility.

Assessment of cellularity in bone marrow fragments.

Bone marrow cellularity was measured using the Quantimet 720 Image Analyser in 50 biopsy samples. In haematologically normal subjects the percentage cellularity of the marrow was between 40 and 63%. Subjective assessment of cellularity was an unreliable indicator of the quantitative measure.

Comparison of a modified thiazole orange technique with a fully automated analyser for reticulocyte counting.

Two independent methods for quantitating reticulocyte counts were compared. One used a modified thiazole orange technique and a flow cytometer (Becton Dickinson FACS); the other was a fully automated whole blood analyser (Sysmex R1000). Both methods gave comparable results with a coefficient of variation of less than 5%. Samples measured using the R1000 showed a negligible decrease in the reticulocyte count over five days at room temperature, although there was evidence of continuing intracellular maturation: with thiazole orange there was an apparent increase. A practical reference range of 20-70 x 10(9)/l was established from 89 normal subjects. The close correlation between the two independent estimates indicates the validity of the quantitation of the reticulocyte count and shows that automation allows significant changes within and below the normal range to be detected with a degree of reliability which was not previously possible.

Ascorbic acid status in iron-deficiency anaemia.

Leucocyte ascorbic acid concentration declines with age. Patients with iron-deficiency anaemia have higher concentrations than normal while those with iron overload have a reduced concentration. It is suggested that these phenomena may be a result of reduced ascorbate catabolism in iron-deficiency anaemia and they provide support for the suggestion that the amount of iron in the tissues may be an important factor in determining ascorbic acid utilization.

A whole blood control for the Coulter Model S.

The white cell count, red cell count, haemoglobin, and mean cell volume of a new preserved whole blood preparations used as a control material for the Coulter Model S were found to be stable for at least two months. This material provides a cheap and stable whole blood control which is now in routine use in 18 laboratories throughout Wales.

A system for data processing in haematology.

The data processing problems which arise in the provision of a modern haematology service are discussed in the light of available resources, and the basic requirements of any automated data processing system are defined. The differences between the needs of haematology and those of other pathology specialities are emphasized. A strategy for the development of a simple system which covers data capture, analysis, and retrieval is described. Separation of the short-and long-term functions of the system provides a relatively simple, inexpensive solution which can be modulated to meet the particular circumstances of each laboratory.

Role of iron in optimizing responses of anemic cancer patients to erythropoietin.

Approximately 50% of cancer patients develop anemia. In the past, the only available treatment option for these patients was transfusion. Since the late 1980s, recombinant human erythropoietin (rHuEPO, epoetin alfa [Epogen, Procrit]) has provided a treatment alternative. Controlled clinical trials have shown that rHuEPO increases hemoglobin and hematocrit levels and reduces the need for transfusions in patients with cancer-related anemia. These controlled trials have suggested (as larger, uncontrolled studies) that the improvements in hemoglobin are associated with increases in energy level, functional status, and overall quality of life. However, only about 50% of patients respond adequately to usual doses of rHuEPO. In the chronic renal failure population, functional iron deficiency is the most common cause of inadequate response to rHuEPO. It has been hypothesized that functional iron deficiency may also occur in cancer patients receiving rHuEPO and may account for the lack of response in up to half of those patients. Studies in renal failure patients have shown that administration of intravenous iron can correct functional iron deficiency more effectively than oral iron and may improve response to rHuEPO. Intravenous iron also reduces the total amount of rHuEPO needed to normalize hematocrit and hemoglobin levels, thereby reducing treatment costs. Ongoing clinical trials are evaluating whether IV iron can also improve rHuEPO responsiveness in patients with cancer-related anemia.

Ferrokinetics: methods and interpretation.

The measurement of erythroid activity is based on the study of plasma iron kinetics. The radioiron injected should be bound specifically to transferrin, and the measurement of plasma 59Fe activity should be corrected for variation in plasma iron concentration. In addition, 59Fe-transferrin activity should be measured free of 59Fe-haemoglobin contamination. Analysis of the plasma 59Fe clearance curve over 14 days can give measures of total, effective and ineffective erythropoiesis, together with the red cell lifespan. Simpler ferrokinetic studies cannot be reliably used to assess erythropoiesis.

Treating renal anaemia with recombinant human erythropoietin: practical guidelines and a clinical algorithm.

Treatment with erythropoietin is highly effective and beneficial if given with care. In view of its cost, however, it is essential to exclude and treat other causes of anaemia before considering using this hormone. After treatment is started the important points for success are regular review of iron availability state combined with a slow correction of the anaemia. Failure of response requires a thorough search for a possible cause, which should be corrected before considering an increased dose of the hormone. Regular monitoring for potential complications, particularly a rise in blood pressure, is required.