Hemorheologic Considerations in the Pathogenesis of Vascular Occlusive Events in Polycythemia Vera

Abstract

Polycythemia vera (PV) commonly presents with vascular occlusion. Untreated patients have a poor prognosis due to the occurrence of thromboses. Treatment outcomes in PV and thrombotic events in other forms of polycythemia and in primary thrombocythemia lead to the conclusion that both raised packed cell volume (PCV) values and quantitative/qualitative platelet changes play a role in the pathogenesis of these vascular occlusive events. In vitro blood viscosity values are predominantly affected by the PCV, particularly at low shear rates and are thus high in untreated PV. Generally, under physiologic conditions blood flow is not governed by blood viscosity due to a number of factors, such as prevailing high shear rates, red cell axial migration, and adaptive vessel diameter changes. Peripheral blood flow is low in untreated PV. Whereas some untreated patients maintain adequate oxygen transport to the tissues, this may not apply in those with cardiac or local vessel disease. There is evidence that low flow rates predispose to occlusive events. Under pathologic low blood flow or static conditions, the rheologic blood changes of untreated PV, demonstrated in vitro, play a role in producing a more deleterious outcome of an occlusive event. Under blood flow conditions, red cell axial migration occurs. This leaves a plasmatic zone at the vessel wall into which platelets are dispersed and where shearing forces are maximal. These forces lead to platelet activation. Increased PCV values reduce the width of the plasmatic zone and lead to an increased possibility of platelet activation, platelet-platelet contact and platelet-vessel wall interaction, particularly when the platelet count is raised as well. These effects increase the likelihood of the initiation of thrombus formation in PV.

The revised World Health Organization diagnostic criteria for polycythemia vera, essential thrombocytosis, and primary myelofibrosis: an alternative proposal

“…46,47 However, the emphasis should really be on the behavior of blood flow in arterioles, capillaries, and venules. In these small vessels, the ratio of vessel surface area to its volume is greatest and the exposure of the blood to the frictional drag of the vessel wall is maximal.…”

Molecular basis of the diagnosis and treatment of polycythemia vera and essential thrombocythemia

“…In addition to increased blood viscosity, the axial migration of red cells under normal in vivo flow conditions tends to displace circulating platelets toward the intimal surface of the vessel wall; erythrocytosis enhances platelet-vascular interactions, especially at the high shear rates found in arterioles and capillaries. 65 The increased mass of red cells in PV may also contribute to heightened platelet activation. 66 However, the hemorrheologic effects of erythrocytosis cannot be the only explanation for the thrombotic tendency in PV; comparable or even greater degrees of secondary erythrocytosis are not associated with thrombosis, and even normalization of the hematocrit in PV does not fully protect against the risk of thrombosis.…”

Platelets and Thrombosis in Myeloproliferative Diseases

“…27 For example, reduced cerebral blood flow is documented in some patients with increased HCT as consequent increased arterial oxygen content adjusts cerebral flow rate accordingly. 27 The HCT also effects platelet activation and the opportunity for platelets to interact with leukocytes and the vessel wall as the axial flow of red cells displaces platelets and plasma to the vessel wall (further affected by the presence of vessel wall disease), thence subjecting them to maximal shear forces. Increasing HCT will naturally result in a narrowed width of the plasma/platelet zone, this has the potential to exaggerate these prothrombotic effects still further.…”

“…27 Cerebral blood flow improves by 73% when the hematocrit is less than 0.45; 27 thus, phlebotomy to achieve a target HCT < 0.45 is a mainstay of PV treatment. A target HCT < 0.42 has been suggested for females, but evidence is lacking.…”