wafl 5 hemostasis

What is hemostasis?

The process that stops bleeding through the interaction between blood vessels, platelets (thrombocytes), and clotting factors.

What is the goal of hemostasis?

To prevent blood loss and maintain the integrity of the vascular system.

What are procoagulants and anticoagulants?

Procoagulants promote clotting, while anticoagulants inhibit it. Normally anticoagulants dominate, but after injury, procoagulants become more active.

What are the main steps of hemostasis?

1. Vessel constriction 2. Platelet aggregation 3. Coagulation (clot formation)

What happens during vessel constriction?

The injured vessel constricts to limit blood loss, especially effective in small vessels, due to contraction of vascular smooth muscle.

What triggers vessel constriction?

Damage to the endothelium exposes collagen, which also begins the platelet aggregation phase.

What are platelets?

Fragments of megakaryocytes that circulate for 6-10 days and play a crucial role in forming the platelet plug.

What are normal platelet levels?

150,000-400,000 cells per mm³ of blood.

What happens when there is a platelet aggregation defect?

It causes mucosal bleeding such as nosebleeds, gum bleeding, gastrointestinal bleeding, and heavy menses.

What is von Willebrand factor (vWF)?

A plasma protein secreted by endothelial cells and platelets that helps platelets adhere to exposed collagen at injury sites.

What happens when platelets adhere to collagen?

They become activated and release vesicles containing TXA₂, serotonin, and ADP, which recruit more platelets and enhance vasoconstriction.

What role does fibrinogen play in platelet aggregation?

Fibrinogen bridges neighboring platelets together to strengthen the platelet plug.

What is coagulation?

The formation of a blood clot (thrombus) through a cascade of reactions involving clotting factors.

What happens when coagulation is defective?

Blood collects in tissues forming hematomas; genetic examples include hemophilia (loss of factor VIII or IX).

What are the two coagulation pathways?

Intrinsic pathway: initiated by factors in the blood. Extrinsic pathway: initiated by factors outside the vascular system.

Where do the intrinsic and extrinsic pathways converge?

On factor II (prothrombin), which is converted to thrombin (factor IIa).

What are the key functions of thrombin?

1. Converts fibrinogen into fibrin. 2. Provides positive feedback in the coagulation cascade. 3. Activates factor XIII → XIIIa to stabilize fibrin. 4. Stimulates endothelial cells to release mediators like NO, ADP, vWF, PGI₂, and TPA.

What nutrients are required for normal coagulation?

Vitamin K, bile salts, and calcium (factor IV).

What is the role of the body's anticlotting system?

To limit clot formation and prevent excessive coagulation.

What are the key anticlotting mechanisms?

1. NO and PGI₂ inhibit platelet activation. 2. TFPI inhibits clotting factor X. 3. Protein C inactivates clotting factors after activation by thrombin-thrombomodulin complex. 4. Antithrombin III inactivates thrombin and other clotting factors; enhanced by heparin.

What is the fibrinolytic system?

A system that dissolves clots after formation through plasminogen → plasmin conversion.

What is tissue plasminogen activator (t-PA)?

An enzyme released from endothelial cells that activates plasminogen into plasmin, which digests fibrin and dissolves clots.

What is the function of plasmin?

It breaks down fibrin, dissolving the blood clot.

How does aspirin (ASA) affect clotting?

It inhibits cyclooxygenase (COX), reducing prostaglandin and thromboxane production, which decreases platelet aggregation and clotting.

How does heparin work?

It enhances antithrombin III activity to inactivate thrombin and prevent clot formation; given IV or subcutaneously.

How does warfarin (Coumadin) work?

It acts as a vitamin K antagonist, reducing synthesis of clotting factors; given orally or IV.

What is the action of t-PA as a drug?

It activates plasminogen to plasmin and is used acutely to dissolve clots in ischemic stroke or myocardial infarction.

Name new anticoagulant drugs that target the coagulation cascade.

Apixaban (Eliquis), Dabigatran (Pradaxa), Edoxaban (Savaysa), and Rivaroxaban (Xarelto).

What type of bleeding occurs from platelet disorders?

Mucosal bleeding (nose, gums, GI, heavy menses).

What type of bleeding occurs from coagulation disorders?

Deep bleeding such as hematomas or hemarthrosis.

When are anticlotting mechanisms active?

After clotting begins—to restrict clot size and prevent spreading.

What are TXA₂ and PGI₂?

Eicosanoids derived from arachidonic acid metabolism; TXA₂ promotes clotting, while PGI₂ inhibits it.

Which enzyme acts on arachidonic acid to form eicosanoids?

Cyclooxygenase (COX), which is inhibited by aspirin and NSAIDs.