Hereditary spherocytosis and elliptocytosis associated with prosthetic heart valve replacement: rheological study of erythrocyte modifications.

The implantation of a prosthetic heart valve (HVP) in patients with hereditary spherocytosis (HS) and hereditary elliptocytosis (HE) is rare, and the changes in the structure and deformability of erythrocytes that follow implantation in these patients have been poorly described. In the present study, the erythrocytes in HS and HE patients with mechanical HVP were compared to the erythrocytes in patients with only congenital membrane defects, in terms of biochemical modifications and rheological behaviour. Integral and cytoskeletal erythrocyte membrane proteins were studied, and blood viscosity (shear rate/shear stress ratio), aggregation ratio [eta(1 s(-1))/eta(200 s(-1))], and red cell visco-elasticity were determined. Valve replacement with a mechanical prosthesis worsened anaemia and resulted in a change in haemolysis, from sub-clinical to evident. The rheological investigation of erythrocytes from HS patients confirmed the characteristic increased viscosity and aggregation ratio and the decreased deformability. The rheological behaviour of erythrocytes from patients with HVP showed a decrease in viscosity and an increase in elastic modulus. In these patients, the prosthesis seems to have induced traumatic damage to the erythrocyte membrane, leading to fragmentation and lysis, which in turn modified rheological parameters. The biochemical and rheological investigation allowed us to understand the clinical and haematological pictures of the patients and to describe the role played by different factors in haemolytic anaemia.

Sickle cell anaemia: haemorheological aspects.

The maintenance of erythrocyte shape and membrane integrity is bound to the modification of deformability and/or permeability. Usually, this features are not investigated with normal laboratory tests. The membrane stiffness, the cell geometry, and the viscoelasticity components are influencing factors on survival and functionality of the erythrocytes. Only few studies have analyzed the viscoelastic characteristics of red blood cells, even less are the studies on patients affected by sickle cell disease (SCD), a pathology characterized by acute and chronic impairment of cell flexibility due to the formation of intracellular sickle haemoglobin (Hb S) polymers. A critical point of SCD is represented by the rheologic alterations of sickle cells determined by the transition from sol to gel of haemoglobin producing a dramatic change in cell viscosity and viscoelastic properties. We have investigated the behaviour of the blood in SCD, from an original rheological point of view, by evaluating the viscoelastic properties of sickle cells in oscillating harmonic sinusoidal mode. A comparison between patients with different severity of the disease, with transfusion dependence (TD) or without transfusion dependence (NTD), has been carried out. This study has confirmed the rheologic impairment of SC blood. The TD patients showed a minor heterogeneneity of rheologic behaviour in comparison with NTD patients, because of the normalizing effect of transfusion. The analysis of viscoelastic properties might be an additional useful tool for monitoring transfusional and pharmacological treatments.

Neuroacanthocytosis associated with a defect of the 4.1R membrane protein.

BACKGROUND: Neuroacanthocytosis (NA) denotes a heterogeneous group of diseases that are characterized by nervous system abnormalities in association with acanthocytosis in the patients' blood. The 4.1R protein of the erythrocyte membrane is critical for the membrane-associated cytoskeleton structure and in central neurons it regulates the stabilization of AMPA receptors on the neuronal surface at the postsynaptic density. We report clinical, biochemical, and genetic features in four patients from four unrelated families with NA in order to explain the cause of morphological abnormalities and the relationship with neurodegenerative processes. CASE PRESENTATION: All patients were characterised by atypical NA with a novel alteration of the erythrocyte membrane: a 4.1R protein deficiency. The 4.1R protein content was significantly lower in patients (3.40 +/- 0.42) than in controls (4.41 +/- 0.40, P < 0.0001), reflecting weakened interactions of the cytoskeleton with the membrane. In patients IV:1 (RM23), IV:3 (RM15), and IV:6 (RM16) the 4.1 deficiency seemed to affect the horizontal interactions of spectrin and an impairment of the dimer self-association into tetramers was detected. In patient IV:1 (RM16) the 4.1 deficiency seemed to affect the skeletal attachment to membrane and the protein band 3 was partially reduced. CONCLUSION: A decreased expression pattern of the 4.1R protein was observed in the erythrocytes from patients with atypical NA, which might reflect the expression pattern in the central nervous system, especially basal ganglia, and might lead to dysfunction of AMPA-mediated glutamate transmission.

Prosthetic heart valves' mechanical loading of red blood cells in patients with hereditary membrane defects.

Implantable cardiovascular devices such as prosthetic heart valves (PHVs) are widely applied clinical tools. Upon implantation, the patient can suffer from anemia as a result of red cell destruction and hemolysis can be more relevant whenever the patient is also affected by red cell disorders in which erythrocytes are more susceptible to mechanical stress such as hereditary spherocytosis (HS) and hereditary elliptocytosis (HE). Considering the typical morphological alterations observed in HS and HE, a study of the influence of cell geometry on the distribution of the shear stress on red cells in biological fluids was carried out. A numerical simulation of the loading caused by Reynolds shear stresses on a prolate spheroid was performed, with the ellipticity of the particle as the independent parameter. The average shear stress on a particle in the blood stream was found to depend on the particle's geometry, besides the stress field produced by the prosthetic device. The relevance of an increasing particle ellipticity on the global load is discussed. The model was applied to erythrocytes from implanted patients with HE or HS, enabling to explain the occurrence of moderate or severe anemia, respectively. The clinical data support the relevance of the proposed global parameter as erythrocyte trauma predictor with regard to the fluid dynamics of artificial organs.