Plasma Hyperviscosity Research Articles

4 Rheology of paraproteinaemias and the plasma hyperviscosity syndrome

The proper understanding of the causes, pathophysiology, diagnosis and management of the plasma hyperviscosity syndrome is based on good knowledge of malignant paraproteinaemias, properties of immunoglobulins, rheology of blood in the microcirculation, and modern plasma separation techniques. This multifaceted syndrome complicates less than ten per cent of IgA and IgG myelomas, and up to one-third of Waldenström's macroglobulinaemias. A few cases of HVS have also been reported in association with polyclonal hypergammaglobulinaemias. Excessive paraproteinaemia may cause the plasma HVS, especially when paraproteins are extraordinarily large, asymmetrical or cryosensitive, or if they aggregate into hyperviscous macroaggregates. The resultant severe microcirculatory impairment is mainly due to the combined effects of plasma hyperviscosity, significant plasma volume expansion and intense red cell aggregation. The individually variable general symptoms, bleeding tendency, ocular, neurological, cardiovascular, and renal manifestations and laboratory parameters of the HVS are summarized briefly. The majority of patients present hyperviscosity manifestations when the plasma viscosity exceeds 5-6 mPa.s. Plasmapheresis or plasma exchange have established themselves as efficient and safe modes of therapy of hyperviscosity and hypervolaemia. The therapeutic guidelines for the plasma HVS are briefly discussed with regard to recent experience with developing plasma separation techniques. Diagnostic and therapeutic advances combined with increasing haemorheological knowledge have greatly improved the proper management of this potentially lethal complication of paraproteinaemias.

1 Blood rheology in vitro and in vivo

Blood rheology tests are traditionally used for detection of organic disease and for monitoring disease activity. More recently they have been used for prediction of blood flow in vivo, not only in overt hyperviscosity syndromes but also in the covert hyperviscosity of low-flow states. The traditional ESR test result increases with red cell aggregation induced by increases in large, asymmetrical plasma globulins. However, small increases in haematocrit and large increases in plasma viscosity each decrease the ESR, reducing both its diagnostic utility and its ability to predict blood flow in vivo. The ESR should be corrected to a standard haematocrit, or else replaced by the ZSR or plasma viscosity, which are more rapid, simple, sensitive and independent of haematocrit. For prediction of blood flow in vivo, these tests can be supplemented by measurement of whole-blood viscosity, which can be performed simply and cheaply in capillary viscometers at high shear rates. Whole-blood viscosity is determined by plasma viscosity, haematocrit and red cell deformability at high shear rates. Its measurement is useful in overt hyperviscosity syndromes, particularly in estimating the effect of red cell transfusion in anaemic patients with plasma hyperviscosity, hyperleukocytic leukaemias or sickling disorders. Blood viscosity should be related to the haematocrit or haemoglobin concentration in order to estimate oxygen delivery to tissues. Changes in blood viscosity can be compensated readily in the normal circulation but not in the compromised, low-flow circulation. In these circumstances, systemic increases in plasma viscosity, haematocrit, whole-blood viscosity, red cell aggregation and in the numbers of circulating rigid red or white blood cells can perpetuate low-flow states and ischaemia. Red cell deformability in narrow vessels is best measured by micropore filtration systems, in which the effect of white cells has been eliminated. Red cell deformability is reduced by change in shape, decrease in the ratio of surface area to volume, decreased membrane flexibility and increased internal viscosity (MCHC and inclusions). White cells have negligible effects on bulk-blood viscosity but have important effects on blood flow in narrow vessels, due to their high internal viscosity and their adhesiveness when activated. White cell filterability is lowest for monocytes and for activated granulocytes and these adhesive and rigid cells may have important effects on microcirculatory blood flow in low-flow states.

The role of plasma hyperviscosity in subcortical arteriosclerotic encephalopathy (Binswanger's disease).

Five haemorheological variables (haematocrit, plasma viscosity, red cell aggregation, red cell deformability and yield shear stress) and the plasma fibrinogen concentration were determined in blood samples from 21 untreated patients with subcortical arteriosclerotic encephalopathy (SAE, Binswanger's disease). The results were compared with those obtained in blood samples from 40 untreated patients with lacunar infarcts and from 275 healthy control subjects without vascular risk factors. Pathological ("solid body") flow behaviour was detected in the blood of both groups of patients (SAE and lacunar infarcts). However, highly elevated plasma viscosity was a consistent feature only of SAE. The authors present the hypothesis that the high plasma viscosity in patients with SAE may account for the progressive degeneration of cerebral white matter. It is postulated that microcirculatory abnormalities due to microrheological changes may be one of the many missing links in the pathophysiology of SAE.

Evaluation of hyperviscosity in monoclonal gammopathies

The serum or plasma hyperviscosity syndrome has been described in both monoclonal and polyclonal immunoglobulin disorders. The usefulness of initial and serial plasma viscosity measurements by an automated viscometer technique was evaluated and compared with serum protein electrophoresis data in 107 patients without monoclonal gammopathies and 153 patients with monoclonal gammopathies. In patients without monoclonal gammopathies, plasma viscosity correlated best with the concentration of gamma globulins. In patients with monoclonal gammopathies, plasma viscosity correlated best with the serum monoclonal protein concentration, but individual patient variations in the ratio of plasma viscosity to monoclonal protein concentration made accurate prediction of plasma viscosity difficult without direct measurement. Six of eight patients with plasma viscosity above 5.0 cp had classic symptoms of hyperviscosity syndrome, and four of the six had recurrent episodes. Six other patients with plasma viscosity above 4.0 cp had more subtle presentations of hyperviscosity but responded equally well to therapeutic lowering of plasma viscosity. These patients are part of a larger subset of 27 patients in whom initial plasma viscosity was above 3.0 cp. No patient with an initial plasma viscosity below 3.0 cp subsequently showed hyperviscosity symptoms. Plasma viscosity measured by this technique is a useful tool in screening patients with dysproteinemias to identify and monitor those with and at risk for the hyperviscosity syndrome.

Military cold injury during the war in the Falkland Islands 1982: an evaluation of possible risk factors.

Throughout the history of war, there have been many instances when the cold has ravaged armies more effectively than their enemies. Delineated risk factors are restricted to negro origins, previous cod injury, moderate but not heavy cigarette smoking and the possession of blood group O. No attention has been directed to the possibility that abnormal blood constituents could feasibly predispose to the development of local cold injury. This study considers this possibility and investigates the potential contribution of certain components of the circulating blood which might do so. Three groups of soldiers from two of the battalions who served during the war in the Falkland Islands in 1982 were investigated. The risk factors which were sought included the presence or absence of asymptomatic cryoglobulinaemia, abnormal total protein, albumin, individual gamma globulin or complement C3 or C4 levels, plasma hyperviscosity or evidence of chronic alcoholism manifesting as high haemoglobin, PCV, RBC, MCV or gamma glutamyl transpeptidase (GGT). No cases of cryoglobulinaemia were isolated and there was no haematological evidence to suggest that any of those men who had developed cold injury, one year before this study was performed, had abnormal circulating proteins, plasma hyperviscosity or indicators of alcohol abuse. Individual blood groups were not incriminated as a predisposing factor although the small numbers of negroes in this series fared badly. Although this investigation has excluded a range of potential risk factors which could contribute to the development of cold injury, the problem persists.(ABSTRACT TRUNCATED AT 250 WORDS)

Paraproteinemia: blood hyperviscosity and clinical manifestations.

Many of the clinical features of paraproteinemia result from impairment of blood flow through the vascular tree because of blood hyperviscosity. Studies were carried out in 65 patients with serum paraproteins (31 with IgG, 25 with IgM, and 9 with IgA) to examine the relationship between the blood viscosity and the frequency of selected clinical features. The blood and plasma viscosities were measured at low rates of shear. Blood hyperviscosity was present in 91% of the patients and plasma hyperviscosity in 75% of the patients. In each of the three immunoglobulin classes both the blood and plasma viscosities increased logarithmically with the paraprotein concentration being greatest in the case of IgM. In addition, the relationship between the hematocrit and the logarithm of blood viscosity tended to be linear at any given protein concentration. In patients with very high levels of paraprotein the blood viscosity was modified by low hematocrits; the latter was below 30 in 70% of patients in whom the concentration of paraprotein was above 4 g/100 ml. The prevalence of clinical complications involving the retinal circulation, the peripheral vascular system, and the central nervous system increased markedly with increasing blood viscosity, measured at 0.18 S-1. One or more of these regions was affected in greater than 80% of patients with blood viscosity above 60 centipoise and in less than 23% of patients with blood viscosity below 40 centipoise. These observations illustrate the complex relationship between blood viscosity, concentration of paraprotein, immunoglobulin class and hematocrit, and emphasize the importance of measuring the whole blood viscosity at low rates of shear in determining the risk of vascular complications.