Haptoglobin metabolism in polycythemia vera.

P LASMA HAPTOGLOBIN ( Hp ) is a well-characterized a2-glycoprotein which possesses the ability to bind hemoglobin ( Hb ), forming the haptoglobin-hemoglobin ( Hp-Hb ) complex.1 Under physiologic conditions, it is estimated that 20-40 per cent of the HP catabolized daily is degraded via complex formation with hemoglobin released during normal intravascular hemolysis.2’3 The hemoglobin thus made available for Hp binding constitutes about 10 per cent of the total Hb catabolized daily as a result of normal red cell senescence.4 Once formed, the Hp-fib complex is cleared rapidly from the circulation with a half-life of 9-30 minutes2’5 so that little Hp-Hb complex can be detected in the plasma at any time ( -0.3 mg./100 ml.). That portion of plasma Hp not removed as the Hp-Hb complex is catabolized by another, slower route, similar, perhaps, to that by which other plasma proteins are catabolized. Thus, the normal disappearance curve of radioiodinated Hp ( T3 of 2.8-4 days ) 68 is the resultant of both catabolic processes.68 When the degree of intravascular hemolysis increases above normal levels, as in hemolytic states, plasma Hp is low or absent, since the increased formation and clearance of Hp-Hb is unaccompanied by any acceleration of Hp production.2’3 In a variety of diverse pathologic states ( infection, neoplasia, trauma ) characterized by connective tissue injury and repair, Hp levels increase as a result of increased hepatic synthesis of the glycoprotein in response to an unkown, possibly humoral, mediator, while the degradation rate remains essentially unchanged. Where inflammation and hemolysis coexist, the Hp levels may be low, normal, or elevated, depending upon which of the opposing influences predominates at the time of observation. In polycythemia vera, the occurrence of diminished Hp levels is not uncommon, in the absence of overt signs of hemolysis at a time when the red cell mass may be either elevated or normal as a result of prior treatment. In an effort to define the mechanism of this hypohaptoglobinemia, and clarify the role of Hp in Hb catabolism in this condition, the turnover of ‘25I-labeled human Hp was studied in patients with polycythemia vera.