Term
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Definition
| the process of blood clotting and then dissolution of the clot following tissue repair |
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Term
| what four major systems are involved in clinical hemostasis? |
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Definition
vascular system
platelets
coagulation cascade
fibrinolytic system |
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Term
| list the main order of hemostasis. |
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Definition
vascular injury
arteriolar vasoconstriction
primary hemostasis
secondary hemostasis |
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Term
| describe primary hemostasis. |
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Definition
| involves the formation of an occlusive platelet plug due to damage of the endothelial cell barrier and exposure of the extracellular matrix |
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Term
| describe secondary hemostasis. |
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Definition
| involves the formation of an insoluble fibrin clot due to activation of the coagulation cascade via factor VII and tissue factor released by platelets |
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Term
| release of what chemical causes vasoconstriction in the formation of a clot? |
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Definition
| endothelin released by the vascular endothelium |
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Term
| describe the steps of primary hemostasis. |
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Definition
| platelets adhere to the von Willebrand factor attached to the basement membrane, then they undergo a shape change and flatten to fill the injured site, the platelets release ADP and thromboxane which recruit more platelets, these platelets aggregate and form the primary hemostatic plug |
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Term
| describe the steps of secondary hemostasis. |
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Definition
| vascular endothelial cells release tissue factor and other coagulation factors, expression of phospholipid complex increases affinity of tissue factor for VIIa, this initiates the extrinsic pathway and thrombin activation, fibrinogen is converted to fibrin resulting in fibrin polymerization, and this forms the insoluble fibrin clot |
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Term
| what two factors mediate the formation of the platelet fibrin plug? |
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Definition
| platelet vessel interaction and the coagulation system |
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Term
| what prevents the vascular endothelial lining from interacting with platelets when there is not an injury? |
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Definition
| the smooth endothelial surface is inert to coagulation factors or platelets |
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Term
| what properties does the subendothelial basement membrane have and how does it assist in vessel protection and tissue repair? |
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Definition
| it contains adhesive proteins like collagen, elastin, and von Willebrand factor which provide binding sites for platelets and leukocytes |
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Term
| what determines whether clot formation or dissolution occurs? |
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Definition
| the balance between endothelial cell anti-thrombotic and pro-thrombotic activities |
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Term
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Definition
| the process of preventing blood clots from growing |
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Term
| what anti-thrombotic properties do endothelial cells have and what do they consist of? |
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Definition
anti-coagulant - contain heparin like molecules that accelerate inactivation of the coagulation cascade, thrombomodulin which convert thrombin to an anticoagulant form, and TFPI which inhibits tissue factor production
fibrinolytic - contains TPA which activates plasminogen to plasmin lysing fibrin clots
anti-platelet properties - contain prostacylin and NO which cause dilation and inhibit platelet aggregation, as well as ADPase which degrades ADP and inhibits aggregation |
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Term
| what are some pro-thrombotic properties of endothelial cells and what do they consist of? |
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Definition
platelet effects - vWf facilitates platelet adhesion to ECM
pro-coagulant effects - produce TF that activates the extrinsic clotting cascade
anti-fibrinolytic effects - plasminogen activator inhibitors depress fibrinolysis |
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Term
| what granules are released by platelets during clot formation and what do they contain? |
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Definition
alpha granules contain fibrinogen, vWf and fibronectin
dense bodies contain ADP/ATP |
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Term
| what are four platelet abnormalities and what do they cause? |
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Definition
thrombocytopenia - due to decreased number of platelets, causes bleeding
grey platelet syndrome - congenital deficiency of alpha granules, causes large grey platelets, bleeding, and defects in primary hemostasis
bernard soulier syndrome - Gp Ib receptor deficiency, causes platelet adhesion problems, and bleeding out of proportion to thrombocytopenia
glanzmann's thrombasthenia - Gp IIb-IIIa receptor deficiency, fibrinogen aggregation defect, causes bleeding |
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Term
| what is the order of enzymatic conversions in coagulation cascade? |
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Definition
| inactive pro enzymes, activated enzymes, thrombin, fibrinogen, fibrin |
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Term
| what are the three groups of coagulation factors, what factors are in each group and what do they do? |
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Definition
substrate - fibrinogen, form a fibrin clot
cofactors - proteins (factors III, IV, VIII and HMWK), accelerate reactions involved in coagulation
enzymes - factor XIII (transamidase), serine protease |
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Term
| what three groups can coagulation proteins be classified into and what do they do? |
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Definition
Contact proteins - are activated immediately and
involved in the initial phase of the intrinsic pathway
Prothrombin proteins - are very important in activating the coagulation cascade. They are Vitamin K dependent and can be lost after prolonged use of antibiotics
The Fibrinogen group - is activated by thrombin and plays a role in secondary hemostasis. |
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Term
| what are the two coagulation cascade pathways and what similarities do they share? |
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Definition
| the intrinsic and extrinsic pathways, they both share common coagulation factors with the common pathway (factor X), and they both require initiation and subsequent activation of coagulation factors in a domino effect, deficiency of any one factor results in coagulopathy. |
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Term
| what is the most important factor in the extrinsic pathway? |
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Definition
|
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Term
| describe the extrinsic coagulation pathway. |
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Definition
it is activated by TF, it bypasses the intrinsic pathway to produce a small amount of thrombin very
quickly which then goes back to accelerate the intrinsic pathway via factors V and VIII |
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Term
| what vitamin and mineral are important in the clotting cascade? |
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Definition
|
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Term
| what clinical test is used to measure the extrinsic pathway? |
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Definition
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Term
| describe the intrinsic coagulation pathway. |
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Definition
| begins with activation of factor XII following contact with foreign substance (collagen), factor VIII is the largest portion in cascade (made of major carrier portion - vWf, and smaller portion - procoagulant), factor VIII needs thrombin for activity, and then it joins the extrinsic pathway at factor X |
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Term
| what clinical test is used for the intrinsic coagulation pathway? |
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Definition
| the activated partial thromboplastin time (APTT) |
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Term
| describe the common coagulation pathway. |
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Definition
| it is where the intrinsic and extrinsic pathways join at factor X, activated X (Xa) converts prothrombin to thrombin, thrombin converts fibrinogen to fibrin (monomers), XIIIa cross links fibin forming strong clot |
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Term
| what interconnections exist between the intrinsic and extrinsic pathway and what is the key regulatory protein that initiates coagulation? |
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Definition
| factor VIIa of the intrinsic pathway can activate IX of the extrinsic pathway, and VII can be activated by XIIa, IXa, Xa, and thrombin, therefore VII is the key regulatory protein |
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Term
| what are three common disorders of coagulation? |
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Definition
| Von Willebrand disease, hemophilia (A, B, C), and factor VII deficiency |
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Term
| what factors prevent continued clot formation and which is the most important anticoagulant? |
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Definition
antithrombins - AT-III (most important), and thrombomodulin - convert thrombin to anticoagulant
tissue factor pathway inhibitor - inhibit TF production
protein C / protein S system - degrade factors V and VIII |
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Term
| what are two systems involved in the regulation of coagulation and what do they do? |
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Definition
fibrinolytic system - plasmin (breaks down clot)
protease inhibitors - regulate fibrinolytic process (prevent too much coagulation or anticoagulation) |
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Term
| what three major influences predispose someone to thrombosis? (Virchow's triad) |
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Definition
| injury to endothelium, alteration in normal blood flow, alteration in the blood (hypercoagulability) |
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Term
| true or false, thrombosis can be arterial or venous? |
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Definition
|
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Term
| what is the major cause of thrombosis and is the only influence that can lead to thrombosis by itself? |
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Definition
|
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Term
| what two alterations in normal blood flow can occur and how do they contribute to thrombosis? |
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Definition
they both allow for platelets to come in contact with vessel endothelium instead of traveling in the middle
turbulence - results in arterial and cardiac thrombi
stasis - contributes to venous thrombi |
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Term
| what is the difference between primary and secondary hypercoagulability? |
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Definition
primary is an inherited disorder in which someone has a specific defect in an anticoagulant or fibrinolytic mechanism
secondary is an acquired state that predisposes someone for increased risk of thrombi |
|
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Term
| list some prothrombotic risk factors. |
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Definition
hereditary deficiency - protein s and c
acquired state - auto antibodies
disease state - malignancy
physical factors - surgery, inactivity
hormonal effects - pregnancy, the pill |
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Term
| true or false, most patients with a DVT or PE only have one risk factor. |
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Definition
| false, they usually have multiple |
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Term
| what is disseminated intravascular coagulation (DIC) and why is it referred to as consumptive coagulopathy? |
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Definition
it is an acute, subacute or chronic thrombo-hemorrhagic disorder that results in the formation of micro-emboli throughout the body,
it uses up all of the platelet and clotting factors throughout the body and thus normal clotting activity cannot occur and results in bleeding |
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Term
| what are some major disorders associated with disseminated intravascular coagulation (DIC)? |
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Definition
obstetric complications
infections
sepsis
neoplasms
massive tissue injury
snake bite
shock
heat stroke
giant hemangioma |
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Term
|
Definition
it is an inherited connective tissue disorder in which the body cannot synthesize collagen, it is broken into 6 types which fall into 3 categories based on the areas affected.
classical - affects the skin,
hypermobility - affects the joints and musculoskeletal system, and
vascular - affects the blood vessels and organs |
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Term
| describe von willebrand disease. |
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Definition
| it is the most common hereditary bleeding disorder resulting from a deficiency in vWf which leads to platelet adhesion problems. |
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