The Effects of Apohemoglobin-Haptoglobin on Heme-Induced Coagulation

Introduction:In conditions with significant hemolysis, like sickle cell and thalassemia, red blood cells break down, leading to higher levels of cell-free hemoglobin (Hb) in the bloodstream. When this cell-free Hb is oxidized into methemoglobin, it releases heme, a crucial iron-protoporphyrin complex essential for oxygen transport. However, excessive free heme can become problematic, since plasma concentrations of the body protective proteins, haptoglobin and hemopexin, to scavenge and clear hemoglobin and heme is very limited. Thus, these protective mechanisms can get overwhelmed by high levels of free Hb or heme in the blood. Additionally, heme can interact with the coagulation cascade, potentially causing harmful pro-coagulant effects in the body. To address this, we introduce a new synthetic scavenger protein called apohemoglobin-haptoglobin (apoHb+Hp). It mimics hemopexin's function and binds to free heme with even greater affinity. Moreover, it utilizes haptoglobin's clearance mechanism for efficient removal from the plasma. Our aim is for apoHb+Hp to effectively clear free heme from the plasma, thereby alleviating pro-coagulatory markers induced by heme. This novel approach may enhance the body's natural defense against heme, leading to potential therapeutic benefits.