Can automated haematology analysers discriminate thalassaemia from iron deficiency?

The use of automated analysers in population screening for beta-thalassaemia has been a matter of controversy. The new fully automated haematology analyser Sysmex E-5000 (Toa Medical Electronics Co. Ltd) facilitates the discrimination of heterozygous thalassaemia from iron deficiency anaemia. In addition to haemoglobin, mean corpuscular haemoglobin and mean corpuscular volume, the red cell size-distribution width is measured. In patients with hypochromic microcytic red cells, the Sysmex data have been evaluated and compared with the indices described by England and Fraser [Lancet i, pp. 449-452, 1973], Mentzer [Lancet i, p. 882, 1973] and by Shine and Lal [Lancet i, pp. 692-694, 1977]. For the detection of beta-thalassaemia trait, the size-distribution width is superior to the previously described indices. The sensitivity is 79%, the specificity 95% and the predictive value for a positive test 94%.

[Kala-azar imported from Yugoslavia]. / Kala-Azar aus Jugoslawien.

Two months after a vacation in Bosnia and at the Dalmatian coast, a 52-year-old Jugoslav male resident in Switzerland developed slowly progressive fever with arthralgia. Two months later his temperature became septic and his general condition deteriorated. After many wrong diagnostic tracks, six months after onset of the illness kala-azar was finally diagnosed. Treatment with Pentostam cured the disease completely.

[Benefits of routine automatic blood picture differentiation]. / Nutzen der routinemässigen automatischen Blutbilddifferenzierung.

The benefits of automated blood smear differential cell counting as a supplementary laboratory examination have been studied. The investigations focussed on patients of whom hematology requisitions were limited to total leukocyte count and hemoglobin determination. The specimens were derived from patients of departments of surgery and obstetrics and gynecology. For specimen collection the vacutainer system was used. The blood smears were prepared in a Coulter Electronics slide spinner, stained with a Hematek II slide stainer and analyzed in the Coulter Electronics Diff 3-50 cell classifier. A total of 1700 blood smears were examined. Following processing of each sample, the classification of each cell was inspected. Corrections were performed, if necessary, and the number of classification changes performed for each smear was registered. Using the in-house normal ranges, 34.5% were pathological smears. Since this group included a large number of borderline cases, new discrimination limits for clinically relevant pathological findings were set empirically. According to these wider ranges, the fraction of pathological slides amounted to 15.2%. Among these, immature granulocytes, eosinophilia and lymphopenia were the most frequent pathological findings. Microscopic control proved in 57.6% of the total number of smears. This complemental procedure was not found to be time-consuming.

Erythrocyte pyruvate kinase deficiency: characterization of a new variant (PK "Aarau").

A new PK variant with moderate hemolytic anemia is described. The enzymes of the nonanemic parents show sigmoidal reaction kinetics, with normal kinetic parameters, but differ with respect to nucleotide specificity, thermostability, and the concentrations of the glycolytic intermediates in the erythrocytes. The most characteristic features of the patient's (daughter) enzyme are a 30% activity, hyperbolic reaction kinetics and only two bands in the SDS-gel electrophoresis instead of three bands observed with the parental enzymes. Moreover, the pH-optimum is shifted to the acidic range, the affinity for PEP and ADP is decreased, ATP inhibition is negligible and FDP-activation is roughly ten times smaller than with controls. The concentrations of 2,3-DPG, 2-PG and PEP in the erythrocyte are increased, but ATP decreased. As there is no consanguinity in the parents and their enzymes are different this PK mutant can be considered to be compound-heterozygous for two different mutant PK alleles.

Oxygen affinity of erythrocytes and pulmonary gas exchange in patients on continuous ambulatory peritoneal dialysis.

In 11 patients on continuous ambulatory peritoneal dialysis 2,3-diphosphoglycerate, oxygen (O2) affinity of red cells (P50), blood gases, ventilation, and O2 consumption were studied. Contrary to patients on maintenance hemodialysis, 2,3-diphosphoglycerate and P50 were normal in patients on continuous ambulatory peritoneal dialysis; they were correlated with each other. Arterial O2 pressure was normal; under the conditions of dialysis with 35 mmol lactate per liter dialysis fluid a slight metabolic acidosis persisted; it was combined with a moderate respiratory alkalosis. Position had no influence upon pulmonary gas exchange with the exception of the alveolo-arterial gradient which was elevated when the abdominal cavity was filled with dialysis fluid and the patients assumed the supine position. Ventilation was in the normal range, whereas O2 consumption was low, possibly due to a reduction in muscle mass in some of the patients. It is concluded that pulmonary gas exchange and erythrocyte O2 transport were normal and that O2 requirements tended to be low in this group of patients on continuous ambulatory peritoneal dialysis.

Serum ferritin and bone marrow iron in patients undergoing continuous ambulatory peritoneal dialysis.

In 20 patients undergoing continuous ambulatory peritoneal dialysis (CAPD), serum ferritin concentration (radioimmunoassay) was compared with bone marrow iron stores (graded semiquantitatively). A close correlation between the two parameters was found. Patients with decreased iron stores (8/20) had serum ferritin concentrations below 70 ng/mL; those with normal or increased iron stores had concentrations above 96 ng/mL. It is concluded that serum ferritin concentrations adequately reflect bone marrow iron stores and are useful as a guide to iron-replacement therapy in patients undergoing CAPD.

[Plasmapheresis treatment in multiple myeloma with kidney insufficiency]. / Plasmapheresebehandlung bei multiplem Myelom mit Niereninsuffizienz.

Two patients with multiple myeloma and renal insufficiency are described. In both cases free lambda-chains were demonstrated in blood and urine. Plasmapheresis induced a marked reduction of lambda-chains in both patients. In one patient, a 63 year old man, oliguria ceased but renal function remained impaired and required treatment with longterm hemodialysis. The patient died after 6 1/2 months from sudden circulatory failure. In the second patient, a 68 year old woman, renal function was recovered sufficiently to enable hemodialysis to be stopped. Plasmapheresis may efficiently lower the paraprotein concentration in plasma and bring about improvement of renal function, at least in certain cases. However, treatment should be started before the terminal oliguric stage of renal insufficiency has been reached.

[Probe test for the detection of hemoglobinopathies and enzyme defect anemias]. / Suchteste zur Erfassung von Hämoglobinopathien und Enzymdefektanämien.

The simplest methods for the diagnosis of thalassaemias are the morphology of erythrocytes, the Hb-F-elution test and the Hb H Heinz bodies test. In order to prove the sickle cell anomaly sickle cell preparation and Hb-S-precipitation test can be performed in every laboratory. By means of the isopropanol precipitation test or the Heinz bodies test can be searched for instable haemoglobins without any laboratory expenditure. On the other hand, haemoglobins with increased oxygen affinity demand a measurement of the oxygen affinity of the erythrocytes. However, simple fluorescence or dye-stuff methods are out our disposal for the most important erythrocytic enzymopenias.

[Clinical demonstrations of hereditary disorders of metabolism]. / Klinische Demonstrationen von hereditären Stoffwechselstörungen.

Case reports are presented on 4 outpatients with hereditary disorders of metabolism. 1. In a 46-year-old male of Sicilian origin with haemolytic anaemia and leg ulcers, the blood contained numerous target cells, the sickling test was positive, and more than 80% of the haemoglobin was found to be HbS. Investigation of the family revealed double heterozygosity for HbS and beta-thalassaemia. 2. In a family with hereditary nonspherocytic haemolytic anaemic, the biochemical characterization of an abnormal pyruvate kinase is reported: the kinetic data were found to be normal, the electrophoretic migration rate of the abnormal enzyme was increased, and its thermostability was marked decreased. 3. Malignant hyperthermia was observed in an 18-year-old male. The limited value of all methods for identifying affected family members is discussed. 4. In 2 sisters who suffered life-threatening attacks of acute myoglobinuria, differential diagnosis comprised hereditary deficiency of phosphofructokinase, muscle phosphorylase and carnitine palmityl transferase. The activity of the former two enzymes was found to be normal. The circumstances of the myolytic crisis in the two patients provide strong evidence for the presence of a muscle carnitine palmityl transferase deficiency.

[Hemotherapy in malignant hematologic diseases]. / Hämotherapie bei malignen Blutkrankheiten

For the majority of patients with malignant blood diseases the ideal transfusion products are blood components instead of whole blood. The therapeutic use of packed red cells, platelets, leukocytes and albumin is briefly discussed.