Platelet Factor 4 and longevity of patients with essential thromobocythaemia: an example of Antagonistic Pathogenic Pleiotropy (APaP).

Abstract

This paper presents the concept of Antagonistic Pathogenic Pleiotropy (APaP), in which an abnormality that causes a specific pathology can simultaneously reduce other morbidities through unrelated mechanisms, resulting in the pathology causing less morbidity or mortality than expected. The concept is illustrated by the case of Essential Thrombocythaemia (ET). ET patients have substantially elevated platelets, and are therefore expected to have increased thrombotic events leading to reduced life expectancy. However ET patients do not have reduced life expectancy. A possible explanation is that elevated platelets produce higher levels of Platelet Factor 4 (PF4), which has been found to reduce age-associated decline in immune and cognitive function in mice, and has been suggested as a treatment for age-associated illness. The benefit of elevated PF4 is hypothesised to balance the increased morbidity from hematological causes. Searches for other indications where a well-defined pathology is not associated with concomitant reduction in overall mortality may be a route to identifying factors that could protect against, prevent or treat chronic disease.