Aetiology of sickle cell ischemic priapism: the pathophysiologic triad of hyperhaemolysis, hyperviscosity and hypercoagulability, and their therapeutic implications

Abstract

Context: Majority of literature regarding pathophysiology of sickle cell ischaemic priapism (SCIP) is focused on penile veno-occlusion due to hyperhaemolysis-induced vasculopathy with little reference to SCD-associated hyperviscosity and hypercoagulability, each of which can also potentially cause penile veno-occlusion and SCIP.

Objective: This review has triple objectives to: (1)-reappraise role of hyperhaemolysis in aetiopathogenesis of SCIP; (2)-highlight roles of hyperviscosity and hypercoagulability in aetiopathogenesis of SCIP; and (3)-underscore aetiologically-determined therapeutic implications in managing SCIP due to hyperhaemolysis, hyperviscosity, and hypercoagulability.

Methodology: Online literature search was conducted using terms relevant to SCD and priapism. Only articles that reported aetiopathogenesis and/or management of SCD-associated priapism vis-à-vis hyperhaemolysis, hyperviscosity, and/or hypercoagulability were selected.

Results: SCIP has three aetiopathogenetic categories: (1)-hyperhaemolysis vis-à-vis penile venous vasculopathy; (2)-hyperviscosity vis-à-vis penile venous sludging; and (3)-hypercoagulability vis-à-vis corporal cavernosal thrombosis. Irrespective of aetiopathogenesis, short-term management of SCIP is prompt decompression to avert erectile dysfunction. However, long-term management differs with respect to aetiology. Aetiologically rational long-term management (ARLTM) for hyperhaemolysis-induced SCIP should be based on up-regulators of nitric oxide and PDE-5 (e.g., hydroxyurea or PDE-5 inhibitors). However, ARLTM for hyperviscosity-induced SCIP should aim at reducing microvascular endothelial-adhesion, sludging, and viscosity by using p-selectin inhibitors (crizanlizumab), while ARLTM for hypercoagulability-induced thrombotic SCIP should obviously be anticoagulation.

Conclusion: Hyperhaemolysis is the prototype and predominant aetiology of SCIP. However, veno-occlusive SCIP may occur due to any one of SCD-associated pathophysiologic triad of hyperhaemolysis, hyperviscosity, and hypercoagulability. While penile decompression remains universal short-term management of SCIP, long-term management should be rationally determined by aetiopathogenesis.