TBPP_Haptoglobin, Hemopexin

scavenging of cell-free hemoglobin, 1. erythrocyte lysis, 2. tetrameric a2b2 Hb dissociates in ab dimers, 3. ab-dimers bound with high affinity by Hp: prevents oxidative damage, 4. binding to CD163 receptor of a cell. Free Hb = oxidate hotspot, formation of toxic free radicals = inflammation and cytotoxicity, kidney and vascular damage, vasosconstriction (Verstopfung). Hb ab-dimers complexed with Hp are protected from oxidation.

scavenges heme from circulation, physiological removal of old RBC: erythrophagocytosis by macrophages, heme degraded by HO-1, iron recycled, intravascular hemolysis (10%), massive hemolysis: free heme released, binding to albumin and transport to Hpx and then transport to liver. Hpx-heme complex binds to CD91 on hepatocytes, macrophages, neurons = endocytosis. other proteins activated by binding to receptor (for cellular defense)

1. degradation in lysosome, release of heme, 2. heme degradation by Hemoxigenase 1 to CO, Fe2+ and Biliverdin, 7. reduction of Biliverdin to Bilirubin, 5. Bilirubin transport to liver.

source of redox-active iron, produces ROS (damage, inflammation), intercalation into membranes: cell lysis and death, vascular leakage. Prevention by Hpx (no product available on the market)

both proteins are precipitated in Fraction IV-4 and V, co-purification from fraction IC-4, extraction/amonium sulfate (salting out). Hemopexin: filtration --> chr. --> diafiltration/sterile filtration --> capto Q --> BioEX --> final concentration / DF, Haptoglobin: extraction --> chr. --> concentration/pasteurization --> dilution --> concentration / DF

acute or chronic hemolysis in which free Hb causes severe clinical issues. Haptoglobin marketed in Japan (acute hemolysis: burn, trauma, blood transfusion), HELLP syndrome (pregnant women), thermal injury, malaria, AB0 mismatched transfusion, acute infection, sickle cell disease (SCD)

point mutation in Beta-Hb gene, aggregation of Beta-Hb, rigid and sickle-shaped RBC, prone to lysis, symptoms: pro-oxidative damage of free Hb and heme, vaso-occlusive crisis (pain, organ damage), major complications depend on age, heart attack or kidney fail cause to death, high heme concentration inside sickle RBC (lifespan 10-20 days), bone marrow cannot match rate of destruction: more sickle cells = chronic hemolysis, Haptoglobin and Hemopexin depleted in SCD.

Hpx protects the vascular endothelial system from oxidative damage, reduces inflammation (detoxification via liver)and iron accumulation, functional consequence: Hpx therapy normalizes blood pressure and cardiac output, measurements of stasis = vaso-occlusion after repetitive post injections: free Hb-infusion causes stasis, protection only by Hb, Hpx, and Hb+Hpx.