Re-evaluation of hematocrit as a determinant of thrombotic risk in erythrocytosis

Abstract

H ere we critically evaluate the role of elevated hematocrit as the principal determinant of thrombotic risk in polycythemia and erythrocytosis, defined by an expansion of red cell mass. Since red cell volume determination is no longer readily available, in clinical practice, polycythemia and erythrocytosis are defined by elevated hemoglobin and hematocrit. Thrombosis is common in Chuvash erythrocytosis and polycythemia vera. Although the increased thrombotic risk is assumed to be due to the elevated hematocrit and an associated increase in blood viscosity, thrombosis does not accompany most types of erythrocytosis. We review studies indicating that the occurrence of thrombosis in Chuvash erythrocytosis is independent of hematocrit, that the thrombotic risk is paradoxically increased by phlebotomy in Chuvash erythrocytosis, and that, when compared to chemotherapy, phlebotomy is associated with increased thrombotic risk in polycythemia vera. Inherited and environmental causes that lead to polycythemia and erythrocytosis are accompanied by diverse cellular changes that could directly affect thrombotic risk, irrespective of the elevated hematocrit. The pressing issue in these disorders is to define factors other than elevated hematocrit that determine thrombotic risk. Defining these predisposing factors in polycythemia and erythrocytosis should then lead to rational therapies and facilitate development of targeted interventions.

Time for revival of the red blood cell count and red cell mass in the differential diagnosis between essential thrombocythemia and polycythemia vera?

“…Such studies are even more urgent taking into consideration a most recent review challenging and critically discussing the role of the hematocrit as a determinant risk factor for thrombosis in erythrocytosis. 61 It is to be hoped that such studies may promote a consensus amongst MPN experts that the RCM is essential for a correct classification of JAK2V617F positive ET patients, mPV and PV patients. This will ensure timely treatment with phlebotomies in those patients who otherwise will be classified as ET and who would then carry an increased risk of potentially life-threatening or life-invalidating thrombotic complications.…”

The red blood cell count and the erythrocyte sedimentation rate in the diagnosis of polycythaemia vera

“…In this context, it is noteworthy to remember and revive the an- critically evaluated. 30 It is underscored that other factors than the HCT, including diverse cellular changes consequent to inherited and environmental factors might affect thrombotic risk, irrespective of the elevated HCT. Supporting this viewpoint are studies indicating that the thrombotic risk is paradoxically increased by phlebotomy in Chuvash erythrocytosis and that phlebotomy is associated with increased thrombotic risk in PV, when compared to chemotherapy.…”

“…Therefore, the authors conclude that there is a pressing need to define factors other than the elevated HCT that determine thrombotic risk. 30 Thus, the issue on the association between thrombosis risk and elevated HCT remains controversial with conflicting results, being substantiated by a most recent Danish study, in which 108 521 individuals from the Copenhagen General Population were prospectively followed for a median of 8 years. 31 In this study, the hypothesis was tested if individuals from the general population with high HCT or high platelet count have high risk of arterial and venous thrombosis.…”

<p>Nocturnal Mean Oxygen Saturation Is Associated with Secondary Polycythemia in Young Adults with Obstructive Sleep Apnea, Especially in Men</p>

“…Almost one billion people worldwide have OSA, with China having the highest number of affected persons, followed by the United States, Brazil, and India 1. Polycythemia is defined as an absolute increase in hemoglobin (HGB) or hematocrit (HCT) 2,3. It is classified as primary (e.g., polycythemia vera) or secondary [such as chronic continuous hypoxia (CCH) and renal lesions].…”