Bleeding and Blood Clotting Problems

Diseases or drugs that affect the production of platelets or plasma proteins responsible for clotting cause excessive bleeding problems. The most common are diseases of the bone marrow and chemotherapy, both of which deplete platelets by inhibiting 

Multimeric VWF is degraded by an adamalysin, ADAMTS-13, which is secreted into the blood from endothelial cells along with VWF. AD AMTS-13 resembles procollagenN-peptidase (ADAMTS-2 Fig. 8.7b) except that the C-terminal domain of ADAMTS-2 is replaced by four 

Activated platelets possess a phosphatidylserine surface that binds calcium ions (as in matrix vesicles Sect. 9.3.3). This surface attaches various proteins that circulate in the blood and possess a negatively charged Ca+2 binding domain of up to niney-carboxyglutamate (gla) residues (Fig. 11.4). Osteocalcin (Sect. 9.4.2.) also possesses this gla domain. 

A gla protein is secreted into the endoplasmic reticulum (ER) of the liver where its N-terminal domain binds to and activates an enzyme that converts glutamic acid residues in the gla domain to y-carboxyglutamic acid. The activated carboxylase enzyme then binds to a reduced form of vitamin K, a diphenol (KH2) to which it adds molecular oxygen. The 

---