The Hyperviscosity Syndromes

A major determinant of normal blood flow is its fluidity. The physical laws governing fluidity are complex, involving the rheologic properties of both the plasma and the cellular components. Viscosity is an important rheological characteristic of blood and gives the inherent resistance to blood flow. In addition, the vessel size and rate of flow, as well as the characteristics of the cellular components, of blood are among various factors governing blood flow. Any changes in these parameters would lead to an impaired flow and result in failure of delivering adequate oxygen and nutrients to tissues. In the early stages, this affects the microcirculation and is less apparent than when major thromboembolic events take place. Clinically, serious impediment of blood flow can occur, complicating many diseases; this is designated as the hyperviscosity syndrome. The better-known ones are in polycythemia vera, when the hematocrit becomes abnormally high, or in plasma cell dyscrasias, when the plasma proteins levels are elevated. Yet there are many other disorders with hyperviscosity that are receiving less attention. The resulting impaired blood flow is often the pathogenic basis of many diseases. A number of factors can lead to increased blood viscosity, including changes in the plasma proteins or changes in the cellular content. Abnormalities in the former may lead to changes in the latter. For example, abnormal plasma proteins can cause increased red cell aggregation. Although the ultimate complication of thrombosis in the larger vessels is widely recognized, the occlusion of the microcirculation receives much less attention. Furthermore, the in vitro methods commonly used to detect abnormal viscosity are not sophisticated enough to yield useful information on the in vivo status, nor are there uniform methods for the detection of increased red cell aggregation.

It is the objective of this issue of Seminars in Thrombosis and Hemostasis to provide the clinician and the basic scientist with updated information on the hyperviscosity syndromes. The first article by Baskurt and Meiselman will familiarize the readers with the principles of rheology of blood and plasma. It paves the way for a comprehensive understanding of the fundamentals, such as the role of shear rate, red cell deformability, and plasma proteins. They also describe how red cell aggregation affects the microcirculation and the importance of rheological factors in tissue perfusion. This is followed by a series of articles describing the clinical disorders often complicated by hyperviscosity. The first article, by Kwaan and Wang, is on the red cell abnormalities as seen in polycythemia vera and a number of conditions associated with increased red cell aggregation. Abnormalities in the leukocytes and factors leading to leukostasis in leukemia, as well as excessive rouleaux formation in rheumatoid arthritis, are then discussed by Rampling. The following article by Mehta and Singhal describes the effect of abnormal gammaglobulins as seen in multiple myeloma and Waldenström's macroglobulinemia. They describe how the pathophysiology and the clinical features are related to hyperviscosity. Another abnormal plasma protein causing hyperviscosity is cryoglobulin. This is discussed by Bombardieri et al, who relate their experience in treating patients with cryoglobulinemia. The next two articles illustrate how a rheological approach can be applied to the study of diseases. In the article by Tsai, the effect of shear stress in activation of cell adhesive molecules and on circulating von Willebrand factor is presented, with important implications to the pathogenesis of thrombotic thrombocytopenic purpura. Baronzio and colleagues discuss the rheological effects of hypoxia in the microenvironment of malignant tumors. The sequence of events following hypoxia is presented, showing a different viewpoint on tumor biology and a new therapeutic challenge. The articles that follow are from clinicians practicing in different specialties who describe the rheological problems they encounter. Tempelhoff and colleagues discuss these in cancer; Rosenkrantz looks at hyperviscosity in neonatal practice; and Kwaan et al review rheological data in patients with heart disease and discuss the echocardiographic changes caused by red cell aggregation. Finally, detailed information on the management of hyperviscosity by the use of apheresis is presented. In a symposium on a subject in which knowledge is being developed at an accelerated pace, it is unavoidable to have many areas of overlap. As long as these overlapping writings are complementary to each other, the reader will find benefit in reading the viewpoints from different experts.