Hemostasis Mechanisms in Blood Loss Prevention

Hemostasis

• Hemostasis is the prevention of blood loss.
• It's achieved through several mechanisms when a vessel is cut/ruptured.
• Mechanisms include:
  • Vascular constriction
  • Platelet plug formation
  • Blood clot formation (coagulation)
  • Fibrous tissue growth into the clot to permanently close the hole in the vessel.

Vascular Constriction

• Immediately after a blood vessel is damaged, the smooth muscle in the vessel wall contracts.
• This reduces blood flow from the ruptured vessel.
• The contraction results from:
  • Local myogenic spasm
  • Local autacoid factors from traumatized tissues and blood platelets
  • Nervous reflexes initiated by pain nerve impulses or other sensory impulses from the traumatized vessel or nearby tissues.
• Increased vasoconstriction in smaller vessels is often caused by platelets releasing thromboxane A2.

Platelet Plug

• A platelet plug seals very small cuts.
• Platelets (thrombocytes) are minute discs (1-4 micrometers in diameter).
• They are formed from megakaryocytes in the bone marrow (150,000 - 300,000 per microliter).
• Platelets do not have nuclei, cannot reproduce, and have a lifespan of 8-12 days, being eliminated by the spleen's tissue macrophage system.

Platelet Cytoplasm

• Platelets contain contractile proteins (actin and myosin and thrombosthenin), which cause contraction.
• They contain residuals of the ER and Golgi apparatus that synthesize enzymes and store calcium ions.
• They also have mitochondria and enzyme systems that form ATP and ADP.
• Platelets synthesise prostaglandins (local hormones affecting blood vessels and tissues).
• They produce fibrin-stabilizing factor and a growth factor to repair damaged vascular walls.
• Platelet membranes have glycoproteins (prevent adherence to normal endothelium) that cause adherence to injured areas (especially injured endothelial cells), and exposed collagen in the vessel wall.

Mechanism of Platelet Plug

• When platelets contact damaged vessel surfaces (especially collagen), they swell, assume an irregular shape, and form numerous radiating pseudopods.
• Their contractile proteins contract strongly.
• Granules are released containing multiple active factors.
• The platelets become sticky.
• They adhere to collagen in the tissues and von Willebrand factor leaking from the plasma.
• The platelets secrete large quantities of ADP and thromboxane A2.
• This activates nearby platelets, causing them to adhere to the original activated platelets, forming a platelet plug.

Blood Coagulation

• The clot develops 15-20 seconds after severe trauma to the vessel wall, and in 1–2 minutes following minor trauma.
• Within 3-6 minutes, if the vessel opening isn't too large, the entire opening is filled with a clot.
• The clot retracts 20 minutes to one hour after formation, closing the vessel further.

Fate of Blood Clot

• Clots can become invaded by fibroblasts which form connective tissue, turning the clot into a small hole of the vessel wall over time within 1-2 weeks.
• Excess blood in a tissue can promote the clot dissolving by enzymes within the clot itself.

Mechanism of Blood Coagulation

• Procoagulants and anticoagulants normally dominate in the bloodstream to prevent blood from clotting.
• However, if a vessel is damaged, the procoagulants from the damaged tissue become activated, overpowering the anticoagulants and causing the clot to develop.

General Mechanism

• Rupture triggers a series of chemical reactions in the blood involving various clotting factors.
• The result is the formation of a complex of activated substances called prothrombin activator.
• Prothrombin activator catalyzes the conversion of prothrombin into thrombin.
• Thrombin acts as an enzyme to convert fibrinogen into fibrin fibers, which trap platelets, blood cells, and plasma to form the clot.

Conversion of Prothrombin to Thrombin

• Prothrombin activator, in the presence of ionic calcium (Ca++), converts prothrombin to thrombin.
• Thrombin causes the polymerization of fibrinogen molecules into fibrin fibers within 10–15 seconds.
• Prothrombin activator formation is usually the rate-limiting factor in blood coagulation.
• Prothrombin on the platelets first attaches to the damaged tissue.

Clot Retraction

• Within minutes of clot formation, it begins to contract, expressing most of the fluid (serum).
• Platelets adhere to fibrin fibers, tying them together.
• Platelets continue releasing fibrin-stabilizing factor, increasing cross-linking bonds.
• Thrombosthenin, actin, and myosin (contractile proteins) activate and contribute to clot retraction
• Thrombin also helps to activate and accelerate clot retraction as well as calcium ions released from calcium stores in the mitochondria, endoplasmic reticulum, and Golgi apparatus.

Initiation of Coagulation

• Prothrombin activator is formed via two pathways:
  • Extrinsic pathway—starts with trauma to the vascular wall and surrounding tissues.
  • Intrinsic pathway—starts with trauma to the blood itself or exposure to collagen from a damaged vessel wall.

Clotting Factors

• Detailed list of clotting factors and their synonyms provided.

Extrinsic Pathway

• Tissue damage releases tissue factor (a complex of several factors).
• Tissue factor complexes with Factor VII, then with Factor X.
• Calcium ions catalyze the conversion of Factor X to activated Factor X (Xa).
• Activated Factor X combines quickly with tissue phospholipids from tissue factor or platelet phospholipids to initiate the prothrombin activator complex.
• Calcium ions split prothrombin into thrombin.

Intrinsic Pathway

• Blood trauma or contact with collagen activates factor XII to form activated factor XII (XIa).
• Activated factor XII acts on factor XI to activate factor XI.
• Activated factor XI activates factor IX.
• Activated factor IX, activated factor VIII, platelet phospholipids, and platelet factor 3 activate Factor X.
• Factor X forms the prothrombin activator complex.

Role of Calcium

• Crucial for all clotting reactions except the first two steps in the intrinsic pathway.
• Calcium ion concentration rarely becomes so low as a to significantly affect clotting in a healthy body.
• Blood can be prevented from clotting by lowering the calcium ion concentration (using substances like oxalate ion).

Interaction Between Pathways

• The extrinsic pathway is relatively fast, often only taking 15 seconds.
• The intrinsic pathway is much slower, usually taking 1-6 minutes.

Bleeding Disorders

• Almost all bleeding disorders involve factors created by the liver
• Vitamin K is important for liver function and the formation of several clotting factors.
• Vitamin K deficiency occurs rarely in healthy adults as it is produced by intestinal bacteria.
• Bleeding disorders can occur due to problems with GI absorption of fats, liver disease, or obstruction of the bile ducts.
• Bleeding disorders in newborns before their gut bacteria produce Vitamin K

Hemophilia

• Hemophilia is a bleeding disorder occurring almost exclusively in men.
• Hemophilia A (classic hemophilia) is due to the deficiency of Factor VIII.
• Hemophilia B affects Factor IX.

Hemophilia (cont.)

• Females are often carriers of hemophilia genes.
• A female carrier will pass on hemophilia to half of her male offspring.
• A female will not have hemophilia if she has at least one X chromosome containing the normal gene for a clotting factor.

Thrombocytopenia

• Bleeding usually happens from small venules and capillaries in thrombocytopenia.
• Small purplish spots (thrombocytopenic purpura) often develop on the skin due to small hemorrhages.
• Bleeding does not start until the platelet count drops below 50,000/µl. 

Thrombocytopenia (cont.)

• Clot retraction test can be performed.
• Idiopathic thrombocytopenia is an autoimmune condition.
• Treatment may involve corticosteroids or splenectomy

Thrombi and Emboli

• A thrombus is an abnormal blood clot that forms inside a blood vessel.
• An embolus is a thrombus that dislodges and travels through the bloodstream.
• Emboli can block blood flow in major arteries or the pulmonary arteries.
• In the case of pulmonary emboli, this may cause massive pulmonary embolism

Thromboembolic Conditions

• Conditions that may cause blood clots include:
  • Roughened/damaged endothelial surfaces (e.g., from arteriosclerosis, infections, trauma.)
  • Slow blood flow (where small quantities of thrombin and other procoagulants are always being formed).

Use of tPA

• tPA (tissue plasminogen activator) is a genetically engineered enzyme.
• tPA is delivered directly to a thrombosed area through a catheter.
• tPA activates plasminogen into plasmin.
• Plasmin dissolves intravascular clots.
• Effective if administered within the first hour or so of a coronary artery occlusion.

Thrombosis and Embolism

• Blood clots often occur in individuals confined to bed due to limited blood flow in the lower extremities.
• Blood clots can dislodge from their initial site, traveling to other parts of the body as emboli.
• Large emboli may block major arteries.
• Pulmonary emboli can lead to massive pulmonary blockage.

Disseminated Intravascular Coagulation

• Widespread activation of clotting mechanisms occurs in widespread areas of the circulation due to the presence of large amounts of traumatized/dying tissue, releasing a large amount of tissue factor.
• Resulting small clots lead to decreased oxygen and nutrient delivery.
• Can result in circulatory shock and/or bleeding due to the consumption of clotting factors.

Anticoagulants - Heparin

• Commercial heparin is derived from animal tissues and purified.
• Heparin injection increases clotting time from a normal 6 minutes to 30 minutes or more.
• Immediate prevention or slowing of further thromboembolic conditions is possible.
• The effects of heparin last 1.5-4 hours, broken down by the enzyme known as heparinase in the blood.

Summary of Hemostasis Test Values

• Bleeding time: 1–6 minutes
• Clotting time: 6–10 minutes
• Prothrombin time: 12 seconds

Explore the vital processes involved in hemostasis, the prevention of blood loss. This quiz covers the mechanisms like vascular constriction, platelet plug formation, and blood clotting. Learn how these mechanisms interact to heal damaged blood vessels effectively.