Rheology, the science of the deformation and flow of matter, has become of considerable interest to haematologists, and now the measurement of blood and plasma viscosity is a familiar part of the investigation of vascular disorders and the paraproteinaemias. Developments in instrumentation have led to the measurement of plasma viscosity and the zeta sedimentation ratio as practical alternatives to the erythrocyte sedimentation rate, and a variety of methods have also been introduced for the study of red cell deformability. It is therefore an appropriate time to review these recent developments and to examine their potential application to the investigation and management of clinical disorders. Determinants of viscosityAll fluids resist, to a greater or lesser extent, attempts to alter their shape, and this resistance to flow is a measure of a fluid's viscosity. During flow, as layers of fluid move parallel to one another at different rates, a velocity gradient forms between these layers and is known as the shear rate; it is measured in reciprocal seconds (s-1). The force required to produce this velocity gradient is the shear stress and is measured in newtons per square metre (NM-2). Viscosity can now be redefined as the ratio of shear stress to shear rate, the unit of viscosity being the pascal second (Pa s; conversion factor -1 mPa s = 1 centipoise).Simple fluids, such as plasma and most oils, show a linear relationship between shear stress and shear rate (Newtonian behaviour) so that the viscosity remains constant. Whole blood, however, behaves as a non-Newtonian fluid in that viscosity increases exponentially at the low shear rates (below 50 s-1) that characterize venous flow. This increase is due to the larger molecular weight plasma proteins (fibrinogen and certain globulins) which overcome the zeta potential between erythrocytes and form rouleaux; these large cellular aggregates cause a disproportionate increase in viscosity. At shear rates below 1 s51, alterations in plasma fibrinogen around the upper limit ofthe physiological range have a pronounced

SUMMARY Platelet function was measured on 29 occasions in 16 adult patients in the asymptomatic steady state of sickle-cell anaemia. There was a significant increase in platelet number and microaggregate formation, and a lower aggregation threshold with adenosine diphosphate, compared with 23 healthy controls. Similar changes were found, however, in 12 splenectomised patients without sickle-cell disease. The platelet hyperactivity of the sickle-cell steady state therefore reflects an increased circulating population of young, metabolically active platelets resulting from previous autosplenectomy.

A study of rheological determinants (plasma viscosity, whole-blood viscosity, and erythrocyte deformability) was made in 24 matched pairs of patients with homozygous sickle cell disease, with and without homozygous alpha-thalassaemia 2. Patients with coexisting alpha-thalassaemia showed a significant increase in erythrocyte deformability measured as filtration of washed erythrocytes through 5 micron diameter pores and also as viscosity of whole blood at high shear rate (230s-1) and standard haematocrit (0.45). This rheological advantage may explain the beneficial effect of alpha-thalassaemia 2 on haematological parameters and clinical events in homozygous sickle cell disease.

A serial study of erythrocyte deformability, plasma viscosity, and whole-blood viscosity has been made during 10 sickle-cell vaso-occlusive crises. The peak serum lactate dehydrogenase level was used to confirm the duration of crisis and the rheological changes were compared with 19 estimations made on the same patients when asymptomatic. Erythrocyte deformability, measured by filtration of washed erythrocytes through polycarbonate filters of 5 microgram pore size, was significantly reduced on day 1 of crisis and, in one additional patient, this occurred 24 h before the onset of pain. There was no increase in irreversibly-sick-led-cell counts and plasma- and blood-viscosity did not increase significantly until day 5 of crisis, in parallel with the acute-phase rise in plasma fibrinogen. Measurement of erythrocyte filterability is therefore a valuable technique for investigating the pathogenesis of the early stages of sickle-cell crisis.

SUMMARY Haematological and rheological (plasma and serum viscosity, whole blood viscosity, and erythrocyte filterability) factors were studied in 31 age-sex matched pairs of patients with sickle cell haemoglobin C disease with and without proliferative sickle retinopathy (PSR). Patients with PSR had significantly higher mean cell haemoglobin and lower Hb F levels on average than the matched controls, but the viscosity and erythrocyte filtration indices did not differ between the 2 groups. There was, therefore, no evidence of rheological differences between patients with and without PSR at the time of the study, although transient rheological abnormalities at the time of development of PSR could not be excluded. Prospective longitudinal studies of rheology before, during, and after the development of PSR would be necessary to detect such changes.Proliferative sickle retinopathy (PSR) is an important complication of sickle cell disease and is a consequence of vaso-occlusion in the peripheral retina.'It occurs most commonly in sickle cell-haemoglobin C (SC) disease2which is an otherwise generally benign clinical condition. The reasons for the greater prevalence of ocular complications in SC disease are not understood. Preliminary observations which had suggested that the prevalence was related to high haemoglobin levels were not confirmed by further analysis that showed the effect to be entirely secondary to a strong age related trend in haemoglobin level.3 Significant haematological relationships that were found with PSR in SC disease included a high mean cell volume (MCV) in males and low fetal haemoglobin (HbF) in both sexes.3There remained the possibility that some determinant of blood flow or viscosity other than those observed on routine haematological examination contributed to this susceptibility to PSR in SC disease. Blood rheology is known to be abnormal in homozygous sickle cell (SS) disease, these patients showing a raised blood viscosity, provided adjustment is made for the low haematocrit,4 and a loss of erythrocyte deformability5 compared with normal controls.

An elderly woman with mild von Willebrand's disease presented with acute myocardial infarction. Percutaneous transluminal coronary angioplasty, to mechanically disrupt the thrombus without anticoagulation, was successfully undertaken. Haemostatic cover was also avoided.

Venous blood from patients with sickle-cell disease in the steady state or in crisis was progressively deoxygenated in vitro to study the effect of BW12C, a new compound designed to stabilize haemoglobin in the oxy-conformation, on the deformability (filterability) of washed erythrocytes. At a final concentration of 1.5 mM, BW12C significantly increased erythrocyte deformability, compared with no added compound, at all levels of deoxygenation below normal arterial PO2. At concentrations of 3.0 and 5.0 mM, BW12C prevented any significant reduction of erythrocyte deformability, or increase in sickled cells, with deoxygenation down to PO2 values below the normal venous level. These in vitro results demonstrate the considerable potential, as an anti-sickling agent, of this novel compound.

A 2-year-old male with acute lymphocytic leukemia died with histiocytic reticulosis 19 weeks later. A comparison with previously reported cases is made, and the relationship of ALL and HMR is discussed.