Term
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Definition
-means cessation or prevention of bleeding from a damaged vessel.
-it involves: clotting in damaged vessels, prevention of clotting in normal vessels and uncontrolled clotting and the coordination of repair and clot dissolution.
- 2 phases:
1.primary hemostasis- a "quick-fix" by forming a small platelet plug in the defect
2.Secondary hemostasis- the plus is stabilized and strengthened to form a more resistant clot. |
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Term
| Hemostasis: Primary Hemostasis |
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Definition
-within seconds of damage axonal reflex triggers vasoconstriction to reduce blood flow to the wound therefore reduces blood loss.
-exposure of subendothelial collagen causes platelets to stick to it = PLATELET ADHESION.
*Adhesion is mediated by Von Willebrand's factor (vWF) which acts as the glue between the platelet and collagen
-once adhered, the platelets become activated and change shape resulting in the release of many mediators as well as exposing the binding sites on the surface of the platelets.
-These changes result in:
1.platelet aggregation = platelet plug growth
2.release of agonists such as ADP and thromboxane = promotes further adhesion
3.exposure of binding sites for clotting factors
4.activation of finbrinolysis
5.activation of inflammation and repair
6.activation of secondary hemostasis |
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Term
| Hemostasis- Secondary hemostasis (coagulation/clotting cascade) |
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Definition
-aim: to produce a meshwork of insoluable fibrin which can bind platelets together to strengthen the plug.
-liver produces fibrinogen -->fibrin at the site of the platelet plug via verious co-factors and enzymes = clotting factors.
-there are 2 pathways:
1.the intrinsic pathway: triggered by exposure of plasma proteins to negatively charges surfaces (such as collagen)
2.the extrinsic pathway: triggered by activation of tissue factor (activated by tissue damage).
-important concepts to note:
1.Ca2+ is a co-factor which activates clotting factors that are required for clotting. (EDTA, a chelator used to bind Ca2+ in unclotted blood collection tubes)
2.platelet factor 3 (PF3) a phospholipid found in the membrane of platelets which is needed to confine fibrin formation to the platelet surface
3.the process is self-sustaining
4.generation of thrombin also activates fibrinolysis = clot formation and then degradation at the same time. safety mechanism. |
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Term
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Definition
-when the clot is dissolved
-works in tandem with clot formation
-Damaged endothelial cells release TISSUE PLASMINOGEN ACTIVATOR which can activate PLASMINOGEN = a plasma protein -->PLASMIN which degrades fibrinogen and fibrin
-excessive fibrinolysis is prevented by circulating plasma proteins (anti-plasmins) that can bind to and inactivate free plasmin. |
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Term
| Hemostasis- Natural anti-coagulants |
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Definition
-compounds which prevent out of control coagulation:
1.anti-thrombins: (ex. AT-III) which binds to and inactivates thrombin. It is always present in circulation and its activity is enhanced when bound to heparin-like molecules on the surface of endothelial cells.
2.Proteins C and S: two Vit. K dependent proteins which inactivate factors Va and VIIa. They are activated when thrombin binds to thrombomodulin receptors on endothelial cells.
3.Tissue Factor Pathway Inhibitor (TFPI): a protein produced by endothelial cells whichs binds to and inactivates tissue factor and factor Xa. |
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Term
| Hemostasis- Prevention of clotting in intact blood vessels |
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Definition
-intact endothelium prevents clotting via:
1.production of TFPI
2.thrombomodulin on membranes activates proteins C and S whenever thrombin binds to it
3.production of prostacyclin (PGI2) which inhibits platelet aggregation and causes vasodilation
4.production of tissue plasminogen activator |
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Term
| Disorders of Hemostasis- General |
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Definition
-2 categories:
1.Excessive bleeding
a.disorders of primary hemostasis
b.disorders of secondary hemostasis
c.Disseminated intravascular coagulation (DIC)
2.Excessive clotting
*involves either the microvascualture (DIC) or large vessels. Large vessel thrombosis is predisposed to by vascular stasis (shock, inactivity, varicosities), vascular endothelial damaged (atherosclerosis) or abnormal concentrations of procoagulant substances in the blood (types of drugs). |
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Term
| Disorders of Hemostasis- Excessive Bleeding: Primary hemostasis |
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Definition
-disorder results from defective formation of the platelet plug
-manifests as prolonged bleeding after surgery or trauma or spontaneous bleeding from the capillary beds:
1.petechiae
2.Hematochezia, malaena (digested blood from the stomach)
3.epistaxis (bleeding from the nose)
4.hematuria
-primary hemostasis function depends on:
1.platelets- requires sufficient numbers with normal function.
a.thrombocytopenia: decreased numbers in the blood.
*most common cause seen in Vet.
-occurs due to:
1.decreased platelet production, due to bone marrow suppression or bone marrow replacement by tumors.
2.increased platelet destruction = immune mediated thrombocytopenia
3.increased platelet consumption (consumptive coagulopathy) = DIC and hemorrhage.
b.Impaired platelet function (thrombocytopathy): platelet aggregation, adhesion or the release reaction are imparied. Can be congenital but more likely aquired:
1.NSAIDS: reduce PG's such as thromboxane whichis needed for coagulation
2.uremic toxins induce platelet dysfunction.
2.von Willebrands factor: disease occurs when there is a decrease in vWF production or it is defective =unstable primary plug.
3.vessel walls:
a.Scurvy and copper deficiency
b.vasculitis |
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Term
| Disorders of Hemostasis- Excessive Bleeding: Secondary hemostasis |
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Definition
-results from: decreased production or impaired function of clotting factors results in the inability for fibrin. The primary plug is established but it cannot be further stabilized and strengthened.
-hemorrhage will occur if the primary plug is insufficient.
-pattern if bleeding seen:
1.ecchymoses or hematomas
2.bleeding into the body cavities and joints
3.delayed or prolonged bleeding after surgery
-3 categories:
1.Inherited clotting factor defects (hemophilia): Most common = hemophilia A which is a deficiency in clotting factor VIII. Inherited as an x-linked trait therefore females carry and males are affected.
*hemophilia B is a defect in factor IX and is also x-linked inherited.
2.Acquired clotting factor defects (acquired coagulopathies):
a.Severe liver disease: loss of more then 80% hepatic function results in deficient clotting factor production.
b.Vitamin K deficiency: Vit. K is a co-factor for hepatic carboxylase, an enzyme that activates clotting factors 2, 7, 9 and 10 as well as proteins C and S.
**disease is dependent on ingestion of compounds that interfere with Vit. K recycling such as:
a.Coumarin: found in certain plants
b.warfarin: baits
-prevention of Vit. K recycling leads to usage of all the circulating active Vit. K -->depletion. |
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Term
| Disorders of Hemostasis- Disseminated Intravascular Coagulation (DIC) |
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Definition
-involves disruption in both primary and secondary hemostasis
-characterized by widespread, generalized activation of blood clotting. (recall- whenever there is clotting there is also fibrinolysis)
-fibrin degradation products can act as anti-coagulants.
-widespread microvascular clotting, occurring at the same time as FDP production results in a depletion of platelets and clotting factors. Depletion = consumptive coagulopathy.
-Consumptive coagulopathy + FDP build up =capillary bed hemorrhage.
-DIC can be either acute and severe or chronic and smouldering. |
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Term
| Clinical Assessment of Bleeding Disorders: primary hemostasis |
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Definition
-first test done = platelet count
*if above 25 x 10^9/L then it is not thrombocytopenia.
-the buccal mucosal bleeding time (BMBT): gives an indication of primary platelet plug formation time.
*prolonged BMBT can be due to:
a.thrombocytopenia
b.abnormal platelet function
c.von Willebrand's disease (only if vWF is below 20%
-due a vWF assay to determine if it is actually VWD. |
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Term
| Clinical Assessment of Bleeding Disorders: secondary hemostasis |
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Definition
-perform a coagulation panel:
1.activated partial thromboplastin time (APTT):measure time it take for a blood clot to form when Ca2+, phospholipids and Factor XII activators are added to the non-clotted blood in the tube.
*prolonged APTT time indicates a problem in the intrinsic pathway
2.Prothrombin time (PT): the same chemials are added as above to citrate blood and time is measured.
*prolonged PT indicates a defect in the extrinsic pathway
-Thrombin time (TT):Ca2+ and thrombin are added to citrated plasma and time is measured.
*prolonged TT indicates either low levels of fibrinogen (liver failure or DIC) or increased levels of interfering compounds such as FDP's.
-can also perform an activated clotting time (ACT): is not standard, but can be done in clinic and asses the intrinsic pathway. |
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