Sickle cell trait: dual picture of blood films

The picture of the blood films of subjects with the sickle cell trait is still controversial. While some authors report the presence of sickled cells in the blood films of these subjects, others disagree. This paper submits that sickled cells could be seen in the blood films of subjects with the sickled cell trait, especially in those resident in high altitude areas (AU)

The red cell distribution width in sickle cell disease: is it of clinical value?

The red cell distribution width (RDW) has been studied during the clinical steady state in 1121 patients with homozygous sickle cell (SS) disease, 344 with sickle cell-haemoglobin C (SC) disease, 68 with sickle cell-beta+ thalassaemia, 49 with cell beta§ thalassaemia and in 130 control subjects with a normal (AA) genotype. The mean RDW was moderately increased in Sbeta+ thalassaemia and SC disease and markedly increased in Sbeta§ thalassaemia and SS disease. In SS, SC and Sbeta§ thalassaemia genotypes, lower RDW values occurred in females and with alpha thalassaemia. The RDW correlated negatively with total haemoglobin, mean cell haemoglobin concentration, mean cell volume and fetal haemoglobin (HbF) and positively with reticulocyte count in SS disease. A low RDW was associated with higher weight and less frequent dactylitis, painful crisis, acute chest syndrome, acute splenic sequestration and hospital admissions. A low RDW in SS disease is consistent with a high total haemoglobin, high HbF, low reticulocyte count, alpha thalassaemia and a more mild clinical course. (AU)

Megaloblastic change in sickle cell disease obscured by genetically determined microcytosis

Changes in mean cell volume in sickle cell disease must be judged against the patient's own steady state values. Two cases are reported in which megaloblastic erythropoiesis was overlooked because of genetically determined microcytosis. The effect of megaloblastic change was to increase the mean cell volume(MCV) but values remained in the range normal for other patients (AU)

The determinants of irreversible sickled cells in homozygous sickle cell disease

The relationship between the irreversible sickled cell (ISC) count and other haematological parameters has been investigated. Positive correlations occurred with MCH, MCHC, and with two expressions of intracellular Hb S content. Since the ISC has a high MCHC, the positive correlations with MCHC and with factors derived from the MCHC may be difficult to evaluate. Negative correlations occurred with total haemoglobin and Hb F. The MCHC was found to affect the relationship between HbF and ISC count, a low MCHC being associated with, and probably determining, lower ISC counts at any level of Hb F. It is proposed that a low MCHC may inhibit ISC formation and the practical implications of this are discussed (AU)

The fragility of normal and abnormal erythrocytes in a controlled hydrodynamic shear field

Fresh human erythrocytes (suspended in a compatible isotonic viscous saline medium containing plasma) were disrupted by the uniform shear stresses generated in the laminar flow field of a conventional cone and plate viscometer. A range of normal fragilities were established and blood samples from patients having certain well-defined haematological abnormalities were found to be partially or completely outside these limits. The present technique is sensitive enough to distinguish between young and old cell fraction isolated from the same original population and also appears to be able to resolve discrete sub-populations having different mechanical fragilities within unfractionated samples from certain patients (e.g macrocytosis). This technique provide additional information which could aid or facilitate diagnosis and might eventually form the basis of a routine screening test in clinical haematology.(AU)

Coagulation changes during the steady state in homozygous sickle-cell disease in Jamaica

Coagulation studies were carried out in 117 Jamaicans with homozygous sickle-cell disease in the steady state, and 40 local controls. The patients had significantly higher factor-VIII levels, higher platelet counts, lower factor-V and plasminogen levels, shorter thrombin times and higher serum fibrinogen degradation products(FDP) than the control group. The low factor-V and plasminogen levels, and high FDP levels, might be explained by activation of the coagulation system and continuous clot lysis even in the absence of painful crisis. The high factor-VIII levels and short thrombin times found in these patients could not be explained.(Summary)

Erythrocyte Hb-S concentration: an important factor in the low oxygen affinity of blood in sickle cell anemia

The blood in sickle cell anemia has a very low oxygen affinity and, although 2,3-diphosphoglycerate (2,3-DPG) is increased, there is doubt as to whether this is the only factor responsible. In this study of 15 patients with sickle cell anemia (Hb SS) no correlation was found between oxygen affinity (P 50 at pH 7.13) and 2,3-DPG in fresh venous blood. Whole populations of Hb SS erythrocytes were therefore separated, by an ultracentrifuge technique, into fractions of varying density. The packed red cell column was divided into three fractions; a bottom fraction rich in deformed cells or irreversibly sickled cells (ISC), with a very high mean corpuscular hemoglobin concentration (MCHC); a middle fraction containing cells but free of deformed cells. Oxygen affinity was shifted to the right in all layers (mean P 50 (pH 7.13)ñ1SD: top 46.3ñ2.9 mm Hg; middle 49.8ñ4.9 mm Hg; bottom 61.0ñ5.8mm Hg) compared with normal blood (top 32.1ñ0.7 mm Hg; bottom 30.1ñ0.5 mm Hg). 2,3-DPG was increased in the top fraction, but was low or normal in the bottom fraction (top 21.8ñ3.4 æmol/g Hb; middle 17.7ñ2.2 æmol/g Hb; bottom 13.8ñ3.1 æmol/g Hb; normal whole blood 14.3ñ1.2 æmol/g Hb). The level of 2,3-DPG in top fractions could not account for the degree of right shift of P 50, and in the middle and bottom fractions the even greater right shifts were associated with lower levels of 2,3-DPG had a higher, but still abnormally low, oxygen affinity. A strong relationship was found between oxygen affinity and MCHc. The fractions with the greatest right shift in P 50 had the highest MCHC (top 32.4ñ2.0; middle 36.2ñ3.1; bottom 44.6ñ3.2 g/100 ml, respectively) and the plot of P 50 vs. MCHC showed a positive corelation (r=0.90,P<0.001). The red cell popualtion in sickle cell anemia is not homogeneous but contains cells of widely varying HB F content, 2,3-DPG, but they also have the highest concentration of Hb S. The dense, deformed cell called the ISC is but the end stage in a process of membrane loss and consequent increase in hemoglobin concentration. The P 50 of Hb SS blood is, to a large extent, determined by the presence of these cells (r=0.85, P<0.001). Increased concentration of Hb S in the cell favors deoxygenation and crystallization even at relatively high Poý. Lowered affinity for oxygen appears to be closely associated with Hb S concentration and not with 2,3-DPG content (AU)

A comparison of erythrocyte characteristics in sickle cell syndromes in Jamaica

Red-cell characteristics were studied in the steady state in 3 sickle-cell syndromes, homozygous sickle-cell disease (SS), sickle-cell/heamoglobin-C disease (SC), and sickle-cell/á-thalassaemia (S/thal). Hb-SC disease had the highest haemoglobin levels, red cells counts, and mean corpuscular haemoglobin concentrations, all of which may contribute to the high thrombotic tendency noted in this disease. The two types of S/thal (with and without Hb A) generally had different haematological features. The non-Hb-A type of S/thal, which may resemble SS disease on electrophoretic techniques and present a diagnostic problem, was distinguishable on many red cell characteristics reported here (Summary)

Clinical features of homozygous SS disease in Jamaican children

The clinical features in the first 12 years of life of 100 patients with homozygous SS anaemia are described. The majority of patients presented before age 2 years. The earliest diagnosis was made at 3 months of age. The hand foot syndrome, painful crisis and megaloblastic change were early manifestations of disease, whereas leg ulceration did not occur until beyond the age of 6 years. No examples of haemolytic crises were seen. Growth did not appear to be retarded by Jamaican standards. Death occurred in 2 cases (AU)

Irreversibly sickled cells and splenomegaly in sickle-cell anaemia

Low levels of irreversibly sickled cells occur in patients with sickle-cell anaemia and splenomegaly. The Hb F level appears to influence both the level of ISCs and the persistence of splenomegaly. It is suggested that low levels of ISCs allow splenomegaly to persist and hence are the cause and not primarily the result of persistent splenomegaly (AU)

Irreversibly sickled erythrocytes: a consequence of the heterogeneous distribution of hemoglobin types in sickle-cell anemia

The amount of fetal hemoglobin (Hb F) in erythrocytes of patients with sickle cell anemia (Hb SS disease) was measured by two methods: (a) photometry of individual cells strained for Hb F by the Kleihauer-Betke technique; and (b) chemical assay of alkali-resistant hemoglobin in cells distributed according to specific gravity by ultracentrifugation. Irreversibly sickled cells (ISC), which could be identified directly during photometry and which were found to gather in high concentration at the bottom of ultracentrifuged cell columns, contained significantly less Hb F than non-ISC. Cell content of total Hb was constant regardless of cell size, shape, or ultracentrifugal behavior: thus absolute amounts of Hb F and S varied reciprocally from cell to cell. In experiments designed to estimate age, at formation, and rate of destruction of ISC, Hb SS blood was incubated with selenomethionine-75Se (which labels reticulocytes) of 51Cr (which labels erythrocytes at random) and reinfused. Sequential blood samples were separated by ultracentrifugation into fractions rich in reticulocytes, non-ISC, ans ISC; and chronological changes in the specific activity of each fraction were determined. Analogous information was obtained from radioautography of sequential blood samples after reinfusion of whole blood labeled with amino acids-3H: this technique permitted direct visual characterization of labeled erythrocytes as ISC of non-ISC, all of which had been reticulocytes at the time of reinfusion. The transformation of non-ISC into ISC, presumably a manifestation of membrane damage, proved to begin soon after cell release from the marrow; and ISC subsequently underwent rapid removal from the circulating blood. It is therefore apparent from these studies that, in Hb SS disease, relatively small reciprocal changes in the amounts of the two major hemoglobins carry predictive importance: (a) net synthesis of Hb F is least in erythroid cells destined to become ISC; and (b) these irreversibly deformed erythrocytes suffer preferential destruction. (AU)