Hemostasis 1 Flashcards
Components of normal hemostasis (3)
- vasculature
- platelets
- coagulation factors
What 4 things does circulation require?
- functional pump
- regulation of fluid balance and oncotic pressure
- normal plumbing and vascular tone
- blood maintained in fluid state
Alterations in factors affecting hemostasis can result in what two effects? (2)
hemorrhage (deficient coagulation/hemostasis)
thrombosis (excessive coagulation/hemostasis)
Normal hemostasis is because of what 3 properties that allow the endothelium to antagonize clot formation?
promotes vasodilation
inhibits platelet adhesion and aggregation
inhibits coagulation
Characteristics of laminar flow
- minimizes vascular trauma
- dilutes local accumulation of procoagulants
- minimizes platelet interaction with endothelium
What can cause vascular injury?
physical trauma endotoxins cytokines infectious agents immune reactions
What is primary hemostasis?
platelets and vasculature
What is secondary hemostasis?
coagulation cascade
What is endothelin?
a potent vasoconstrictor released from injured endothelial cells (results in temporary decrease on blood flow)
How does primary hemostasis occur?
- endothelial injury exposes subendothelial matrix
- platelets adhere and become activated
- platelet aggregation leads to formation of unstable platelet plug
How does secondary hemostasis occur?
- tissue factor III (a procoagulant) is released from endothelial cells
- formation of meshwork of cross-linked fibrin containing platelets, erythrocytes, leukocytes
- fibrin network stabilizes platelet plug
Characteristics of prostacyclin (PGI2) and nitric oxide (NO)
- maintain vascular relaxation (vasodilation)
- inhibit platelet adhesion and aggregation
What do membrane-associated heparin-like molecules do?
potentiate the actions of antithrombin III (AT III), a potent anticoagulant
Thrombomodulin
binds thrombin (a potent procoagulant)
Protein C and S
degrade clotting factors
Tissue plasminogen activator (t-PA)
promotes fibrinolysis (clot dissolution)
Adenosine-Diphosphatase
enzyme that degrades ADP (a stimulant of platelet aggregation)
von Willebrand factor (vWF)
needed for platelet binding to subendothelial surface
Plasminogen activator inhibitors (PAIs)
inhibit fibrinolysis (procoagulant)
Name procoagulants associated with endothelium (3)
tissue factor (factor III)
von Willebrand factor (vWF)
plasminogen activator inhibitors
Characteristics of platelets
- membrane bound
- can change shape
- contain granules with pro-coagulants, vasoactive substances, and growth factors
4 events platelets go through following vascular injury
adhesion
secretion
activation
aggregation
Adhesion of platelets to the subendothelial extracellular matrix is mediated by what?
von Willebrand factor
Secretion event following vascular injury involves what?
release of contents of alpha granules and dense bodies containing Ca2+, ADP, and other vasoactive/inflammatory mediators
Activation event following vascular injury leads to what?
expression of phospholipid complex on platelet surface (binding site for Ca2+ and coagulation factors)
What creates the primary hemostatic plug?
platelet aggregation mediated by ADP and thromboxane A2
What creates the secondary hemostatic plug?
thrombin causes platelet contraction and converts fibrinogen to fibrin, which cements platelets together
Coagulation cascade
series of enzymatic reactions that results in formation of thrombin and the conversion of fibrinogen into insoluble fibrin strands leading to clot formation
How can the extrinsic coagulation cascade activate the intrinsic coagulation cascade?
factor 7 of extrinsic can activate factor 9 of intrinsic
Intrinsic pathway of coagulation
Factors XII, XI, IX, VIII
(think of Wal-Mart: It’s not $12, it’s $11.98)
Factor XII initiates the pathway
Leads to activation of factor X and common pathway
Extrinsic pathway of coagulation
Factors III and VII
Factor III initiates the pathway
Common pathway of coagulation
Factors XIII, X, V, II, and I
Factor X activated by intrinsic and extrinsic pathways
What does Factor X do?
converts prothrombin to thrombin followed by fibrinogen to fibrin
What does Factor XIII do?
converts fibrin to cross-linked fibrin
What does thrombin do?
- promotes platelet aggregation and activation
- activates factors XI, VIII, V, and XIII
Which factors are Vitamin K dependent?
factors II, VII, IX, and X
What is plasmin?
- derived from circulating plasminogen
- breaks down fibrin (clot dissolution)
Plasmin results in formation of what?
Fibrin(ogen) degradation products (FDPs)
- have weak anticoagulant activity
Clinical signs of defect in primary hemostasis
petechiae
ecchymoses
bleeding from mucosal surfaces
Characteristics of thrombocytopenia (defect in primary hemostasis)
- decreased platelet concentration
- inadequate numbers to form primary hemostatic plug
- can be due to decreased production or consumption/destruction
Characteristics of abnormal platelet function (defect in primary hemostasis)
- known as a thrombopathy
- can be caused by von Willebrand disease (vWD), other inherited conditions, or acquired platelet dysfunction (from NSAIDs or renal failure)
Characteristics of abnormal vasculature (defect in primary hemostasis)
- can be from vasculitis
- can be from congenital or acquired abnormalities of vessel structure (rare)
Evaluation of primary hemostasis
- quantification of platelet concentration
- Buccal Mucosal Bleeding Time (BMBT)
Clinical signs of defect in secondary hemostasis
hematomas
bleeding into body cavities
bleeding into joints
Characteristics of liver failure (defect in secondary hemostasis)
- decreased production of coagulation factors
- decreased clearance of activated coagulation factors
- altered blood flow in an extremely vascular organ
Characteristics of congenital absence of clotting factors (defect in secondary hemostasis)
- ex: hemophilia
Characteristics of Vitamin K deficiency/antagonism (defect in secondary hemostasis)
- rodenticide intoxication (vit K antagonists)
- moldy sweet clover (cattle)
Evaluation of secondary hemostasis
- partial thromboplastin time (PTT)
- prothrombin time (PT)
- thrombin time (TT)/fibrinogen concentration
- activated clotting time (ACT)
- fibrin(ogen) degradation products (FDPs)
Clinical signs of mixed hemostatic disorder
- evidence of both primary and secondary hemostatic defects
- any type of bleeding
- (clinical bleeding not always present)
Characteristics of disseminated intravascular coagulation (DIC) (mixed hemostatic disorder)
- systemic activation of coagulation, widespread thrombus formation, and hemorrhage
- platelet numbers classically decreased due to consumption
- coagulation factors are consumed in widespread thrombus formation (increased clot times)
Name anticoagulants associated with endothelium (4)
thrombomodulin
proteins C and S
tissue plasminogen activator (t-PA)
ADPase
