Coagulation Lecture 1 Flashcards
What is Hemostasis
- process where body stops bleeding (cessation) and maintains blood in the fluid state
- one of most important natural defense mechanisms
- Result of the activation of hemostatic mechanism is a thrombus (platelet) plug
What is the Hemostatic mechanism
- the hemostatic mechanism involves a complex interaction between the blood vessels, platelets and coagulation factors
- assures the clots in the body are only formed where they should be
What are 2 types of hemostasis?
Primary and Secondary hemostasis
What is Primary hemostasis?
Primary hemostasis is platelet adhesion to exposed collagen within the endothelium of the vessel wall
What is Secondary Hemostasis?
Secondary hemostasis is the enzymatic activation of coagulation proteins to produce fibrin from fibrinogen
What is Vasoconstriction?
Damaged blood vessel contracts to decrease blood flow; blood flow is diverted around damaged vasculature
What are normal blood vessels lined with?
Endothelial cells that are normally both non-thrombogenic and inhibit platelet aggregation
For platelet adhesion to occur what two things must be true
- Adequate # of platelets
2. Platelets functioning normal
Name for Factor I
Fibrinogen
Name for factor II
Prothrombin
Name for factor III
Tissue thromboplastin
Name for factor IV
Calcium
Name for factor V
Proaccelerin (Labile Factor)
Name for Factor VII
Proconvertin, serum prothrombin conversion accelerator (SPCA)
Name for Factor VIII
Anti-hemolytic factor A
Name for Factor IX
Plasma thromboplastin component, Christmas factor, anti-hemolytic factor B
Name for Factor X
Stuart-Prower Factor
Name for Factor XI
Plasma thromboplastin anticedent
Name for Factor XII
Hageman Factor
Name for Factor XIII
Fibrin stabilizing factor
Describe: Factor I - Fibrinogen
- precursor of fibrin
* synthesize in the liver does not require vitamin K for production
Describe: Factor II - prothrombin
- precursor of thrombin
- synthesize in the liver through the action of vitamin K
- most abundant of the vitamin K dependent clotting proteins
- longest half-life of the vitamin K dependent clotting proteins
Describe: Factor III - tissue thromboplastin
- Converts prothrombin to thrombin
* found in all body tissues
Describe: Factor IV- ionized calcium
- Helps to activate thromboplastin (Factor III) and convert prothrombin to thrombin
- serves as a bridge between platelets and clotting factors
Describe: Factor V - Proaccelerin or labile factor
- necessary to convert prothrombin to thrombin
- synthesized in the liver
- it’s activity deteriorates within a few hours
- heat labile
Describe: Factor VII- Proconvertin or stable factor
- not destroyed or consumed in the clotting process
* essential only for the extrinsic coagulation pathway
Describe: Factor VIII- anti-hemophilic factor
• deficiency of this coagulation factor causes hemophilia
Describe Hemophilia A
(Factor VIII:C)
(3 key points)
- A sex linked recessive coagulation disorder
- causes bleeding into joints and intramuscular hemorrhage
- Bleeding time is normal
Describe Von Willebrands Disease
(Factor VIII:vWF)
3 key points
- Autosomal inheritance
- Platelets cannot adhere properly to subendothelial surface causing severe hemorrhaging
- Consistently abnormal bleeding time
Describe: Factor IX - plasma thromboplastin component
- absence of factor causes hemophilia B
* synthesized in the liver and requires vitamin K for production
Describe hemophilia B
- sex linked recessive coagulation disorder
- absence of factor IX causes hemophilia B
- Symptoms are similar to hemophilia
- Prolonged PT and APTT and normal bleeding time
Describe: Factor X - Stuart-Prower Factor
- essential to intrinsic pathway
* synthesized by liver and vitamin K dependent
Describe: Factor XI -plasma thromboplastin antecedent
- synthesize in the liver
* essential for intrinsic pathway
Describe: Factor XII- Hageman Factor
- Found in serum and plasma
- not consumed during the clotting process
- synthesized in the liver
- NOT vitamin K dependent
- known as contact factor because it becomes active when it comes in contact with glass, a negatively charged surface
Describe: Factor XIII - fibrin stabilizing factor
- Stabilizes fibrin clot
* important in tissue growth and repair
Fletcher Factor (Prekallikrein)
• activates plasminogen
- synthesized in the liver
- combine with factor XII, this factor helps convert XI to XIa
Fitzgerald Factor - High Molecular Weight kininogen (HMWK)
- synthesized in the liver
- Combines with factor XII and the Fletcher factor to convert XI to XIa
•Combines with Factor XIa to convert IX to IXa
What are the groups that hemostatic mechanism can be divided into
- Extravascular effects
- Vascular effects
- Intravascular effects
Describe the Extravascular effects of the hemostatic mechanism
- physical effects of the surrounding tissues which close and seal the tear in the vessel that is injured
- Biochemical effects of certain substances that are released from the tissues
Vascular Effects of the hemostatic mechanism
- platelets release serotonin during vasoconstriction which continues to narrow blood vessels on a more long-term basis
- blood vessel structure:
- endothelial membranes of the blood vessels contain collagen
- when circulating platelets come in contact with collagen platelet aggregation occurs and a clot forms
Intravascular effects of the hemostatic mechanism
- Platelet : formation of platelet plug
* plasma coagulation factors: activation of the intrinsic system of coagulation to form a fibrin network
What are the function of platelets in depth
- release substances for vasoconstriction, platelet aggregation, coagulation and vascular repair
- provide a negatively charged phospholipid surface for factor X in prothrombin activation
- provide surface membrane glycoproteins for attachment to other platelets via fibrinogen
- platelets aggregate or stick together to assist coagulation
Plasma coagulation factors
- coagulation proteins (plasma and tissue factors) and Calcium and work together on the surface of platelets to form a fibrin clot
- coagulation factors are protein in nature with the exception of calcium which is a mineral
Three categories of plasma coagulation factors
- Fibrinogen group
- Prothrombin group
- Contact group
Fibrinogen group consists of what
- consist of factors I, V, VIII and XIII
- DO NOT require vitamin K for synthesis
- Factors V and VIII are labile
- factors increase in pregnancy, inflammation, and with oral contraception use
Prothrombin group consists of what?
- includes factors II, VII, IX and X
- REQUIRE vitamin K for synthesis and or decrease in acquired vitamin K deficiencies
- prothrombin group factors are stable
Vitamin K dependent factors
II, VII, IX and X
What does the contact group consist of
- Factors XI, XII, Prekallikrein and HMWK
- DO NOT depend on Vitamin K for synthesis
- Prekallikrein and HMWK aid in the activation of the clot lysing enzyme plasminogen
How are activated factors written
With an “a” behind The Roman numeral
What are the three stages of the coagulation cascade
- Generation of thromboplastic activity
- Generation of thrombin
- Conversion of fibrinogen to fibrin
What does the generation of thromboplastic activity do
Prepares for the conversion of prothrombin to thrombin
What does the generation of thrombin do
Thromboplastin converts prothrombin to thrombin
What does conversion of the fibrinogen to fibrin mean
Fibrin clot formed
Extrinsic pathway
Tissue injury > Factor III (in presence of Calcium (Factor IV)> activates Factor VII to VIIa> which activates Factor X to Xa ……. then goes to common pathway
III (+ Ca) —> VII –> VIIa -»> common pathway (X to Xa)
Fibrinolysis
What enzyme is responsible for digestion of fibrin?
What removes the waste products of fibrinolysis?
• plasmin is the active enzyme (proteolytic enzyme) responsible for digesting fibrin
- not found in circulating blood
- plasminogen (non active) circulates in blood
• The waste products of fibrinolysis are removed from the body by the reticuloendothelial system (RES)
Intrinsic pathway
Factor XII (contact factor) -> XI (+CA IV) –> VIII-» X then common pathway
Fibrinolysis
- Result of converting fibrinogen to fibrin a.k.a. fibrin clot a.k.a thrombus
- as soon as clotting begins fibrinolysis begins to break down the clot
- The fibrinolysis system maintains equilibrium in our body
- directly proportional relationship, if coagulation is increase then fibrinolysis is increased
The common pathway
X to Xa -> V (+Ca IV and PF3) –> II -> I (+thrombin) -> fibrin in prescience of XIII
