Physiology Ch. 11 (Blood Clotting)

Aspirin

(A) Anti-clotting/Anticoagulant Inhibits Cox-1 (cyclooxygenase 1) Without Cox-1, thromboxane will not form. Without thromboxane, platelets lose their stickiness. If platelets cannot stick to surfaces (such as plaque), blood clot will not form, reducing chance of stroke.

Intrinsic Pathway

(A) Begins with Factor XII (Hageman Factor) Activated by collagen fibers from damaged tissue. Inside of vessel or blood in a collection tube. Leads to common pathway (Factor X)

Extrinsic Pathway

(B) Begins with Factor III (Tissue Factor - thromboplastin) Released by damaged tissue. Outside of vessel. Leads to common pathway (Factor X)

Heparin

(B) Anti-clotting/Anticoagulant Inhibits the activation of prothrombin (II) by binding to it.

Coumadin (Warfarin)

(C) Anti-clotting/Anticoagulant Prevents the action of vitamin K by binding to it. Without vitamin K, factors II, VII, IX, and X cannot be formed in the liver. Used in post surgery recover. Immobility (poor blood circulation) can cause clotting.

Common Pathway

(C) Begins with Factor X Activated by both intrinsic and extrinsic pathways to form a clot.

Sodium Citrate

(D) Anti-clotting/Anticoagulant Binds to calcium ions, preventing them from being a part of the clotting process. (same as EDTA)

EDTA (Ethylenediaminetetraacetic Acid)

(E) Anti-clotting/Anticoagulant Binds to calcium ions, preventing them from being part of the clotting process. (same as Sodium Citrate)

Fibrin

A protein produced by the liver that helps blood clots form.

Platelet Plug Formation

ADP & thromboxane A2 cause other platelets to become sticky & attach and undergo platelet release reaction. This continues until platelet plug is formed. Fibrin strands are interwoven in platelet plug, making plug become clot.

Platelet Thromboplastin Factor (PTF)

Activates the clotting process (triggers clotting cascade). Released by platelets as they begin to stick together. Release when platelets on the bottom burst from the pressure. Activates Factor 12 (Hageman/Glass Factor) - initiates clotting. (protein)

Anticlotting Agents (Anticoagulants)

Agents that interfere with the clotting process by hindering the action of various blood-clotting factors (bind to factors). NOT BLOOD THINNERS (blood thinners change consistency of blood) Aspirin (A) Heparin (B) Coumadin (C) Sodium Citrate (D) EDTA (E)

Factor VIII

Antihemophilic Factor (AHF)/(Antihemophilic Factor A) Cofactor Intrinsic Pathway More genetically common. Can be given before surgery to aid in clotting (keep from bleeding out). Harvested from people and animals.

Hemostasis

Blood/Statiic (not moving) Control of blood flow. Clotting.

Factor IV

Calcium Ions Cofactor Intrinsic, Extrinsic, Common pathway

ADP

Cause platelets to be activated. Converted to AMP (won't activate platelets) by CD39.

Stroke

Caused by small blood clot formation in the cerebral vessels. Prevented by use of aspirin. Aspirin keeps platelets from sticking to the jagged edges of the plaque that builds up with age. Excess aspirin can reduce clotting to dangerous levels.

Plasmin

Chemical produced by the body to dissolve clots.

Thromboxane

Chemical released by platelets, attracts more platelets. Cause platelets to stick. Helps create platelet plug. Initiates a series of chemical reactions involving blood-clotting factors. Vasoconstrictor, prostaglandin. (lipid)

Factor IX

Christmas Factor/Plasma Thromboplastin Component (PTC)/(Antihemophilic Factor B) Enzyme Intrinsic pathway

Platelets (damaged endothelium)

Damage to endothelium activates platelets and allows them to bind to exposed collagen & VWF. Platelets release ADP, serotonin & thromboxane A2. ADP Causes platelets to be activated. Serotonin & thromboxane A2 stimulate vasoconstriction, reducing blood flow to wound.

Cox-1 (Cyclooxygenase 1)

Enhances release of thromboxane. Produced by the liver. Acts as enzyme - helps with release of prostaglandin (thromboxane).

Streptokinase

Enzyme produced by bacteria in the body that dissolves clots. Can be injected into the circulatory system.

Hageman Factor/Glass Factor

Factor XII Jagged edges - platelets stick and rip open. Negatively charged surface. Activated by PTF (platelet thromboplastin factor) Can be activated by the rough surface of glass (ex. test tube)

Blood Clot

Fibrin polymer. Fibrin strands are interwoven with the platelets and RBCs. RBCs give the clot it's color.

XIII

Fibrin-Stabilizing Factor (FSF) Enzyme Common pathway At end of stabilizing process. Fibrin holds clot in place/keeps it firm.

Factor I

Fibrinogen Activated form is fibrin (clot). Common pathway

Blood Clot (positive feedback)

Floating platelets will stick to jagged edge of a cut and collagen beneath the epithelial cells. Platelet granules release chemicals causing area to be sticky...more platelets stick and release chemicals...etc. PTF (platelet thromboplastin factor) triggers clotting cascade.

Factor XII

Hageman Factor/Glass Factor Enzyme Intrinsic pathway Jagged edges - platelets stick and rip open. Negatively charged surface. Activated by PTF (platelet thromboplastin factor) Can be activated by the rough surface of glass (ex. test tube)

Blood-Clotting Factors

I. Fibrinogen II. Prothrombin III. Tissue Thromboplastin IV. Calcium Ions V. Proaccelerin VI. (No longer considered) VII. Proconvertin VIII. Antihemophiliac Factor (AHF)/(Antihemophiliac factor A) IX. Plasma Thromboplastin Component (PTC)/(Antihemophiliac factor B) X. Stuart-Prower Factor (autothrombin)/(thrombokinase) XI. Plasma Thromboplastin antecedent (PTA)/(Antihemophiliac factor C) XII. Hageman Factor/(Glass Factor) XIII. Fibrin-Stabilizing Factor (FSF)

von Willebrand Factor

Increases bond by binding to both collagen & platelets. Involved in platelet activation. Cause platelets to stick to it. Found in 3 places: Sub-endothelial tissue. Plasma Platelet granules (secreted by platelets)

Aspirin (and prostaglandins)

Inhibits cox-1, which inhibits the formation of prostaglandins.

Coagulation (clotting) Pathways

Intrinsic Extrinsic Common

PGI 2

Keeps platelets from sticking to intact epithelium.

CD39

Membrane protein. converts ADP to AMP

Clotting Factors (info)

Most are inactive proteins - waiting to be activated. Domino effect - activate one, the next one follows. Each factor was discovered when someone was having trouble clotting (many named after families) Problem with clotting is genetic.

Factor VI

No longer considered part of clotting. Activated form of Proaccelerin (Factor V).

Embolism

Obstruction in a blood vessel due to a blood clot (or other foreign matter) that gets stuck while traveling through the bloodstream. Traveling clot - detaches and moves through vessel - gets to brain - causes stroke. Prostacyclin inhibits platelets sticking together - keeps clotting process from getting out of hand.

Clotting Process

Once platelets have released PTF (platelet thromboplastin factor), a series of chemical reactions will occur until a clot is formed. Positive feedback.

Factor XI

Plasma Thromboplastin Antecedent (PTA)/(Antihemophilic Factor C Enzyme Intrinsic pathway

Platelets (intact endothelium)

Platelets are inactive and don't stick to intact endothelium.

Factor V

Proaccelerin Cofactor Activated form is aFV or FVa (previously Factor VI). Common pathway

Factor VII

Proconvertin Enzyme Extrinsic pathway

Prostacycline

Prostaglandin Inhibits platelet activation. Vasodilator. Helps prevent embolisms

Factor II

Prothrombin Activated form is thrombin (enzyme). Common pathway

Factor X

Stuart-Prower Factor (Autothrombin)/(Thrombokinase) Enzyme Common pathway

Factor III

Tissue Thromboplastin (tissue factor) Cofactor Extrinsic pathway. Released from damaged tissue.

Vitamin K

Used by the liver to produce Factor II, VII, IX and X. Coumadin binds to this to inhibit the production of these factors. Comes from bacteria in intestine. Antibiotics can kill the bacteria, inhibiting production of this. Can replace bacteria by eating green leafy vegetables, yogurt, probiotics.

Serotonin

Vasoconstrictor. Released by platelets during clotting.

NO

Vasodilator. Keep platelets from being activated.

How do you treat overdose of Coumadin?

Vitamin K

AMP

Won't activate platelets. converted from ADP by CD39.