1N5315 Advanced Pathophysiology
Hematologic System
Core Concepts and Objectives with Advanced Organizers
Hemostasis
1. Analyze the process of hemostasis:
a. Analyze the platelet structure and the 4 phases of platelet plug formation:
Platelet Structure Function
peripheral zone Outermost layer. Made of phospholipids. Contains many receptors responsible for
platelet adhesion and aggregation
sol-gel zone Middle layer of the platelet. Provides structural support.
Organelle Zone Innermost layer. Contains calcium, dense granule and alpha granules,
Four Phases of Platelet Plug Function
Formation
Activation First step of platelet plug formation. Injury to endothelium exposes collagen, vWf, fibronectin,
thrombospondin. Collagen is potent platelet activator. Platelets become aware of injury
Adherence Process by which Platelets adhere to endothelium. vWf is attracted to collagen, and platelets
attach to vWf via GP1B. This results in activation of GP2B3A receptors. Collective binding
anchors platelets in place.
Aggregation Process by which platelets bind together. Multiple GP2B3A receptors allow platelets to bind to
one another
Secretion Platelet granules release their contents
● ADP
o Enhances adhesion, activates and recruits platelets
, ● Serotonin
o Recruits platelets
● Fibronectin and thrombospondin
o Proteins which stabilize platelets that are adhered to site of injury
● Thromboxane A2
o Product of the arachidonic acid pathway but is stored inside of the platelet too.
Causes vasoconstriction and enhances platelet aggregation
● Growth factors
o Promote tissue repair but also have a role in the development of atherosclerosis
b. Differentiate between the functions of the extrinsic and intrinsic arms of the coagulation cascade:
· Extrinsic Pathway – It’s considered the primary pathway of coagulation, the extrinsic pathway needs tissue factor (therefore
needs tissue damage) in order to occur and to produce clotting; the extrinsic pathway has to have tissue factor in order to
activate the other clotting factors;
· Intrinsic Pathway – the intrinsic pathway can occur without damage. It will occur when you take blood and put it in a glass
vial (anionic surface). This will immediately cause the blood to clot (It is a parallel pathway for thrombin activation by factor
XII) the intrinsic pathway just always has the factors it needs present in the blood
· Contributions from both the extrinsic and intrinsic pathways are necessary for maximal induction of factor Xa and effective
clotting
Note: coagulation starts with the extrinsic arm. As soon as you make a little Xa, the extrinsic arm is turned off. The
small amount of thrombin that has been generated during the action of the extrinsic system goes up and turns on the
intrinsic arm, which finishes out the job of making the rest of the fibrin.
c. Analyze the coagulation cascade, the key coagulation factors and their function:
Coagulation Cascade Key Function
, Plasma Proteins
Tissue Factor Initiator of extrinsic pathway.
VII Forms complex with tissue factor (III) and activates factors IX and X
X Activates Prothrombin through activated Xa form
Prothrombinase Complex (prothrombin and activated factors X and V) that activates
prothrombin into thrombin
Prothrombin Factor II, source of thrombin that activates fibrinogen
Thrombin cleaves the extracellular domain
of G-protein–coupled protease-activated receptors (PARs),
thereby initiating transmembrane signaling.
Fibrinogen moves between the beta and gamma regions but is removed
during the formation of serum; precursor of fibrin clot
Fibrin Used to stabilize clot
XIII Fibrin – stabilizing factor – cross links fibrin through XIIIa to strengthen clot
XII Hageman Factor. Initiator of intrinsic pathway
VIII VIIIa is a component of tenase complex
IX IXa is a component of tenase complex, activates factor X
Antithrombin it inhibits thrombin and several activated clotting factors (e.g., VIIa, IXa, Xa, XIa,
XIIa).
Protein C in the circulation binds to thrombomodulin in a thrombin-dependent manner and is
Hematologic System
Core Concepts and Objectives with Advanced Organizers
Hemostasis
1. Analyze the process of hemostasis:
a. Analyze the platelet structure and the 4 phases of platelet plug formation:
Platelet Structure Function
peripheral zone Outermost layer. Made of phospholipids. Contains many receptors responsible for
platelet adhesion and aggregation
sol-gel zone Middle layer of the platelet. Provides structural support.
Organelle Zone Innermost layer. Contains calcium, dense granule and alpha granules,
Four Phases of Platelet Plug Function
Formation
Activation First step of platelet plug formation. Injury to endothelium exposes collagen, vWf, fibronectin,
thrombospondin. Collagen is potent platelet activator. Platelets become aware of injury
Adherence Process by which Platelets adhere to endothelium. vWf is attracted to collagen, and platelets
attach to vWf via GP1B. This results in activation of GP2B3A receptors. Collective binding
anchors platelets in place.
Aggregation Process by which platelets bind together. Multiple GP2B3A receptors allow platelets to bind to
one another
Secretion Platelet granules release their contents
● ADP
o Enhances adhesion, activates and recruits platelets
, ● Serotonin
o Recruits platelets
● Fibronectin and thrombospondin
o Proteins which stabilize platelets that are adhered to site of injury
● Thromboxane A2
o Product of the arachidonic acid pathway but is stored inside of the platelet too.
Causes vasoconstriction and enhances platelet aggregation
● Growth factors
o Promote tissue repair but also have a role in the development of atherosclerosis
b. Differentiate between the functions of the extrinsic and intrinsic arms of the coagulation cascade:
· Extrinsic Pathway – It’s considered the primary pathway of coagulation, the extrinsic pathway needs tissue factor (therefore
needs tissue damage) in order to occur and to produce clotting; the extrinsic pathway has to have tissue factor in order to
activate the other clotting factors;
· Intrinsic Pathway – the intrinsic pathway can occur without damage. It will occur when you take blood and put it in a glass
vial (anionic surface). This will immediately cause the blood to clot (It is a parallel pathway for thrombin activation by factor
XII) the intrinsic pathway just always has the factors it needs present in the blood
· Contributions from both the extrinsic and intrinsic pathways are necessary for maximal induction of factor Xa and effective
clotting
Note: coagulation starts with the extrinsic arm. As soon as you make a little Xa, the extrinsic arm is turned off. The
small amount of thrombin that has been generated during the action of the extrinsic system goes up and turns on the
intrinsic arm, which finishes out the job of making the rest of the fibrin.
c. Analyze the coagulation cascade, the key coagulation factors and their function:
Coagulation Cascade Key Function
, Plasma Proteins
Tissue Factor Initiator of extrinsic pathway.
VII Forms complex with tissue factor (III) and activates factors IX and X
X Activates Prothrombin through activated Xa form
Prothrombinase Complex (prothrombin and activated factors X and V) that activates
prothrombin into thrombin
Prothrombin Factor II, source of thrombin that activates fibrinogen
Thrombin cleaves the extracellular domain
of G-protein–coupled protease-activated receptors (PARs),
thereby initiating transmembrane signaling.
Fibrinogen moves between the beta and gamma regions but is removed
during the formation of serum; precursor of fibrin clot
Fibrin Used to stabilize clot
XIII Fibrin – stabilizing factor – cross links fibrin through XIIIa to strengthen clot
XII Hageman Factor. Initiator of intrinsic pathway
VIII VIIIa is a component of tenase complex
IX IXa is a component of tenase complex, activates factor X
Antithrombin it inhibits thrombin and several activated clotting factors (e.g., VIIa, IXa, Xa, XIa,
XIIa).
Protein C in the circulation binds to thrombomodulin in a thrombin-dependent manner and is
