Blood Cells and Blood Clotting

Stimulus of RBC production

Decreased blood oxygen (anemia) stimulates erythropoietin production by the kidneys, a hormone that stimulates RBC production. 

Factors of RBC effectiveness

1. RBC production in the marrow. Radiation or drugs may suppress the marrow and decrease the number of RBCs. 
2. Iron in the diet to produce the hemoglobin molecule. An iron deficiency causes anemia. 
3. Vitamin B₁₂ and folic acid, important in the synthesis of DNA and the development of RBCs in the bone marrow. A deficiency of either will lead to megaloblastic anemia, where cells are large, fragile and short-lived.
4. Defects in the structure of hemoglobin may cause anemia. For example, sickle cell anemia. 
5. Defects in the red cell membrane. 
6. Defect in the metabolic pathway of RBCs. 
7. Immune reaction against RBCs, especially due to the cell defects above. 

Platelets

Platelets are small, anuclear cell fragments responsible for blood clotting. They secrete ADP and thromboxane A2 to activate other platelets to become "sticky". They also produce a fibrin-stabilizing factor that binds fibrin molecules to strengthen and form the clot, and prostaglandins that have various effects on blood flow and wound healing. They possess actin and myosin that allow them to retract and help close damaged blood vessel. The glycoprotein Von Willenbrand factor is the initial bridge that connects platelets to injured vessel wall. 

Blood clotting

1. Severed blood vessel causes local blood vessels to constrict. 
2. Extrinsic or Intrinsic pathway: 
• Extrinsic is a quick response triggered by tissue trauma releasing tissue thromboplastin. 
• Intrinsic is a slow reaction triggered by damage to RBCs, or by RBC contact with a foreign surface. 
3. Formation of prothrombin activator. 
4. Prothrombin activator catalyzes prothrombin to thrombin. 
5. Thrombin changes fibrinogen to fibrin threads that mix with RBCs, platelets and plasma to form a clot. 
6. Clot retraction and healing. 

Negative feedback mechanisms of blood clotting

• Fibrin absorbs excess thrombin, preventing the formation of more fibrin. 
• A globulin called anti-thrombin III inactivates excess thrombin. Heparin, produced by mast cells and basophils, is an anti-coagulant that works by enhancing anti-thrombin III activity. 
• Tissue plasminogen activator, released from damaged tissues, activates plasma protein plasminogen (profibrinolysin) to become plasmin (fibrinolysin). Plasmin lyses fibrin and helps remove the clot. 

Diseases of clotting

• Von Willenbrand's disease, caused by a defect in plasma adhesion and results in prolonged bleeding. 
• Hemophilia A and B are caused by missing Factor VIII and Factor IX, respectively. 
• Bleeding problems caused by vitamin K deficiency. Vitamin K is important in the formation of prothrombin and factors VII, IX and X.