Ch. 23 Notes

• Hemorrhage + Clotting
• Balance between the two

• Vasculature (blood vessels)
• Thrombocytes (Platelets)
• Plasma coagulation proteins
• Fibrinolytic system (Inhibits/removes clots)

• Vasoconstriction: Blood vessels diameter decreases
• Formation of platelet plug at damaged site
• Platelet--Plasma protein--vasculature
• Fibrin clot formation
• Clot removal: fibrinolysis

• Vessels transporting oxygenated blood away from the heart.
• High BP: 100-120 mm/hg

• Vessels transporting de-oxygenated blood back to the heart
• Veins are thinner and weaker than arteries
• Low BP: 60-80 mm/Hg

• middle ground between arteries and veins
• oxygen delivered to the cells
• Very thin, only a single cell layer thick

• Innermost
• Single endothelial cell layer in contact with blood
• Underneath lies collagen

Middle layer of smooth muscle and elastic tissue

• Outer layer
• Connective tissue nerve endings, and the vas vasorm (layers of tissue on outside)

• If intact, then inert with blood components
• If traumatized then physiologically active
• First: Responder to injury (vasoconstriction)
• Synthesis and stores active chemicals
• Prostacyclins: inhibit platelet aggregation and adhesion)
• Plasminogen activators: Clot dissolution
• Von Willebrand Factor: platelet adhesion protein
• Collagen activates plasma coagulation proteins: Factor 7

• Collagen: Binds to platelet membrane GP Ib/IIa
• vWF: Binds to platelet membrane GP Ib/IIa
• PG12: Prostacyclin inhibits plt. aggregation
• Tissue factor: Liproprotein activates plasma coagulation protein
• Thrombomodulin: Protein C cofactor (inhibits fibrin formation)
• TPA: starts fibrinolysis

• Vasculature: Short term vasoconstriction closes small blood vessels and limits blood loss.
• Platelets: Aggregation and adhesion form small clumps at injured site
• Plasma proteins: proteins begin formation of an insoluble protein "glue" fibrin clot
• Fibrinolysis: proteins begin the process of limiting formation, eventual removal of clot.
• Endoreplication: Cell division without cytoplasmic division (nucleus divides, cytoplasm does not)

Fluffy outer coat, regulates shape platelet adhesion and aggregation

• Sponge like
• Porous network system that permeates the platelet
• Releases the cytoplasmic granule contents to the outside.

Structural proteins

vWF (platelet adhesion), fibronectin, thrombospondin (platelet aggregation), platelet fibrinogen, Platelet factor 4

• ADP
• Serotonin (vasoconstriction)

• Life span 8-10 days
• 1 megakarocyte produces 1-2000 platelets. Matures in 5 days
• 2/3 platelets circulate in blood
• 1/3 platelets sequestered in spleen
• Old platelets phagocytized by the RE system (mainly spleen)

• Endothelium is damaged, platelets will being to interact with exposed sub-endothelium tissues.
• Platelets are activated by exposure to the sub-endothelium, they lose their disk shapes to form pseudopods that extend and attach to exposed collagen

• adhesion
• Epithelial cells

• adhesion
• Alpha granule

• Adhesion
• Alpha granule

• Adhesion
• Alpha granules

Plasma and Platelets

Attaches to other platelets with Fibrinogen

Attaches to collagen with vWF

Platelets "stick" to the surfaces of damaged blood vessels

• Platelets sticking to each other at the damaged vessel
• Promoted by: Collagen, Thrombin, Serotonin, TXA2
• Inhibited by: Aspirin, Some prostaglandins

• Impairs the synthesis of thromboxane (TXA2), stimulates platelet granule release.
• Platelet aggregation is impaired for the entire life span of the platelet.
• Commonly prescribed to inhibit vascular occlusions (clots) in patients at risk for coronary occlusions
• Effect on platelet's take place within 5-15 minutes after ingestion.

• Inhibits platelet GP IIb/IIIa
• When people die from hemostasis disorders, they usually die from excessive clotting

• A normal platelet count does not necessarily imply normal function.
• Excessive bruising or bleeding with a normal platelet count suggests a qualitative platelet disorder.

• Synthesized in liver
• "Cascading-domino" sequence of chemical interactions between the proteins, tissue substances and calcium leads to the formation of an insoluble protein-the fibrin clot at the site of the injured blood vessel.
• The fibrin clot seals off the damaged blood vessel and limits blood loss.
• Other proteins in the fibrinolytic system limit fibrin formation and eventually its dissolution.

Thrombin

Prothrombin

• Individually (factor assays test, fibrinogen)
• Collectively (PT and PTT tests)

• Consumed during clotting (absent in serum)
• Factors 5 and 8 extremely liable
• Increased in inflammation, pregancy, and oral contraceptives

• Not consumed during clotting (except 2)
• Requires Vitamin K for synthesis

• PK=Fletcher
• HMWK=Fitzgerald
• Not consumed during clotting
• Stable storage

• Soluble plasma protein precursor to fibrin
• Fibrinogen--Fibrin clot

• Stable precursor of thrombin
• Prothrombin---Thrombin

• Active form of prothrombin
• Thrombin converts fibrinogen--fibrin
• Promotes platelet aggregation

Any tissue (non-plasma) phospholipid substance (cell membrane guts)

• Electrolyte
• Only ionized Ca is active in hemostasis

• Very liable (1/2 life=16 hours)
• Consumed during clotting

• 2 Complex components
• High Molecular Weight: vWF, VIII RCo (Platelet aggregation), VIII Ag (Antigenic site)
• Low Molecular Weight: VIII C (Procoagulant), VIII Ag (Antigenic Site)

Proconvertin

Plasma Thromboplastin Component

Stuart Factor

Plasma Thromboplastin Antecedent

Stuart Factor

Fibrin Stabilizing Factor

Goal=Fibrin clot

Activated by contact with tissue phospholipids following endothelial damage.

Activated by contact with negatively charged solid surfaces (collagen, glass)

Represents the merging of the extrinsic and intrinsic pathway

Fibrinogen--(thrombin)---Fibrin Monomers--- Fibrin

Thrombin splits fibrinogen into smaller parts

Monomers polymerize using (weak) hydrogen bonds

Factor 13 promotes stronger covalent bonding between monomers forming a strong fibrin polymer

• Plasminogen----Plasmin
• Plasminogen activators can include such substances as endothelial cell enzymes, bacterial products.
• Plasmin, enzyme that breaks fibrin and fibrinogen into small pieces.
• Pieces are fibrin degradation products (X, Y, D,E)

• Inhibit platelet aggregation, fibrin, fibrin polymerization.
• Plasminogen activators can be used to treat AMI's pulmonary emboli and other vascular occlusion.

• Special tube in kit.
• Serum specimen
• Fibrinolytic activity of plasmin--fibrinogen and fibrin into small fragments
• DIC, DVT, PE have presence of FDPs
• Latex particles coated with anti-fibrinogen.
• No agglutination in either tube: < 10 ug/ml
• Agglutination in 1:5: 10-20 ug/ml
• Test doesn't differentiate between Primary and Secondary because it uses an anti-fibrinogen antibody that reacts with FDPs and fibrinogen.

normal blood flows limits the concentration of pro-coagulants at the injury site.

• Most active natural anticoagualnt
• Inhibits thrombin (9,10,11,12)
• Synthesize by liver, platelets, endothelium

• Inhibits Factor 5,8
• Synthesized by liver (vitamin K dependent)

• Both Natural anticoagulant
• Protein C-Protein S pathway a major system involved in the regulation of blood coagulation and in the protection against thrombotic diseases.
• Congenital or acquired Protein C and Protein S deficiencies, causes recurrent thrombotic diseases, in the absence, in the absence of any obvious underlying cause.
• Factor 5 mutation: results in a prolonged survival of thrombotic activated Factor 5, following stimulation of the coag cascade, and increases the risk of thrombosis.

• PT measures
• Oral anticoagulants
• Effective for long term, self-medication
• Vitamin K antagonists
• Group 2 (2,7,9,19)
• Slow acting (8-12 hour before effects)
• Long acting

Originally utilized as rat poison after research into the unexplained deaths of cows during 1920s discovered a naturally occuring substance that caused internal bleeding

• PTT measured
• IV anti-coagulant
• Given in hospital
• Inactivates factors IIa and Xa
• Fast acting
• Short duration (1/2 life=one hour)
• Standard dose acheived when the PTT is 1.5 times the baseline