Hemoglobinemia (or haemoglobinaemia) is a medical condition in which there is an excess of hemoglobin in the blood plasma. This is an effect of intravascular hemolysis, in which hemoglobin separates from red blood cells, a form of anemia. Hemoglobinemia can be caused by intrinsic or extrinsic factors. When hemoglobinemia is internally caused, it is a result of recessive genetic defects that cause the red blood cells to lyse, letting the hemoglobin spill out of the cell into the blood plasma. In intravascular hemolysis, hemoglobin is released and binds with haptoglobin. This causes haptoglobin levels to decrease. Once haptoglobin is saturated, free hemoglobin readily distributes to tissues where it might be exposed to oxidative conditions. In such conditions, heme can be released from ferric hemoglobin. The free heme can then accelerate tissue damage by promoting peroxidative reactions and activation of inflammatory cascades. Hemopexin (Hx) is another plasma glycoprotein able to bind heme with high affinity. Hx sequesters heme in an inert, non-toxic form and transports it to the liver for catabolism and excretion. As long as both haptoglobin and hemopexin are saturated, the remaining free hemoglobins are filtered in the kidney and some of them will be reabsorbed by way of proximal tubules. In externally caused hemoglobinemia, an outside attacker acts as an antibody against the red blood cells. This can cause the cells to be destroyed and their hemoglobin released.
The effectiveness of plasminogen was demonstrated by at least 50% improvement of their lesions in all 11 participants who had lesions at baseline, and absence of recurrent or new lesions in any of the 15 participants through the 48 weeks of treatment.The U.S. Food and Drug Administration (FDA) granted the application for plasminogen  orphan drug designation, fast track designation, priority review, and a rare pediatric disease priority review voucher. The FDA granted approval of Ryplazim to ProMetic Biotherapeutics Inc.

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This article incorporates public domain material from the United States Department of Health and Human Services. External links
"Plasminogen". Drug Information Portal. U.S. National Library of Medicine.