Exam 4 - Coags Flashcards
Normal hemostasis is a balance between ?
Clot generation, thrombus formation, and regulatory mechanisms that inhibit uncontrolled thrombogenesis
3 goals of hemostasis are
limit blood loss
maintain blood flow
promote revascularization after thrombosis
2 stages of hemostasis
Primary: immediate platelet deposition at endovascular injury site with initial platelet plug formation (only adequate for minor injury)
Secondary: clotting factors activated
Vascular endothelial cells have
antiplatelet, anticoagulant, and fibrolytic effects to inhibit clot formation
Anti-clotting mechanisms of the endothelial cells:
-negatively charged to repel platelets
-platelet inhibitors such as prostacyclin and nitric oxide
-ADP degradation, protein C, TFPI, t-PA
Platelets are derived from
bone-marrow megakaryocytes
Inactive platelets circulate as
disc-shaped anuclear cells with a lifespan of 8-12 days
Normally, approx ___% of platelets are consumed to support vascular integrity with ____ billion new platelets formed daily
10%; 120-150
Damage to endothelium exposes the _________, which contains collagen, von Willebrands factor, and other glycoproteins
underlying extracellular matrix (ECM)
Upon exposure to contents in the ECM, platelets undergo 3 phases of alteration
-adhesion: occurs upon exposure
-activation: stimulated when platelet interacts w collagen and TF, releases granular contents
-aggregation: the granular contents being released activates additional platelets.
Each stage of the clotting cascade requires assembly of
membrane-bound activated tenase-complexes
Each tenase-complex is composed of 4 things
1) a substrate (inactive precursor)
2) an enzyme (activated coagulation factor)
3) a cofactor (accelerator or catalyst)
4) calcium
The Extrinsic pathway is the initiation phase of ___________.
plasma-mediated hemostasis
Steps of the extrinsic pathway (long card…)
Endothelial injury –> Exposing TF to plasma –> TF forms an active complex with VIIa –> TF/VIIa complex binds to and activates factor X, converting it to Xa –> TF/VIIa complex also activates IX into IXa in the intrinsic pathway (IXa and calcium convert factor X to Xa in intrinsic pathway) ==> Factor Xa begins the final common pathway
For the intrinsic pathway, it was initially thought to occur only in response to ?
Endovascular contact with negatively charged substances such as glass and dextran
The current understanding of the intrinsic pathway is that it plays a minor role in the
initiation of hemostasis, and is more of an amplification system to propagate thrombin generation initiate by extrinsic pathway
Intrinsic pathway hemostasis initiation steps (another long one..)
Upon contact with neg charged surface, factor XII becomes activated –> Factor XIIa converts XI to XIa –> (XIa + VIIIa +plt-membrane phospholipid + Ca++) converts factor X to Xa –> Xa initiates the final common pathway
Intrinsic pathway propagation
Activated Thrombin (IIa) activates factors V, VII, VIII, XI to amplify thrombin generation.
This process activates the platelets, leading to propagation of the FCP.
Steps of the common pathway
-Factor X becomes Xa and binds with Va to form “prothrombinase complex”
-Prothrombinase complex rapidly converts prothrombin (II) into thrombin (IIa)
-Thrombin attaches to the platelets and converts fibrinogen (I) to fibrin (Ia)
-Fibrin molecules crosslink to form a mesh that stabilizes the clot
Thrombin cleaves _________ from fibrinogen to generate ____, which polymerizes into strands to form ________.
fibrinopeptides; fibrin; basic clot
Finally, factor _____ crosslinks the fibrin strands to stabilize and make an insoluble clot, resistant to ________.
XIIIa; fibrinolytic degradation
___________ is the key-step in regulating hemostasis.
Thrombin generation
Both ___________ facilitate the formation of prothrombinase complexes
intrinsic and extrinsic tenase-complexes
Prothrombinase Complex converts PT (II) into ______.
thrombin (IIa)
