Hemostasis Flashcards
Hemostasis
Arrest of bleeding. A normal physiological response to localized vascular injury
What are the factors of hemostasis
-Blood vessels
-Platelets
-Coagulation
-Fibrinolytic and thrombolytic factors (Regulating factors)
Anti-coagulant factos made by endothelium
-Prostacyclin
-NO
-Thrombomodulin
-Protein S
Prostacyclin
Ehance relaxation and inhibits platelet adhesions and activation
NO
Maintains vascular relaxation and inhibits platelet activation. Participates with Protein C and antithrombin to suppress thrombin production
Thrombomodulin
Binds tothrombin and activates protein C
Protein S
Cofactor in Protein C pathway and independently inhibits activation of factors VIII and X
Endothelium in hemostasis
Damage to endothelium produces pro clotting properties like Tissue factor
-Exposure of underlying collagen and other components activates coagulation and platelet adhesion
Pro clooting endothelial mediators
-Tissue Factor (Factor III)
-Von willebrand Factor
-Plasminogen Activator Inhibitor-1
Platelets
Come from bone marrow
-Membrane bound cytoplasmic fragments
-Get pinched off megakaryocytes
-Bind to damaged endothelium or subendothelium to form hemostatic plug to prevent blood loss (primary hemostasis)
Main regulator of platelet production
Thrombopoietin
Primary Hemostasis
Primary vascular and platelet response.
-Best for minor injuries
-Vascular contraction and endothelial activation of pro and anticlotting activity
-Platelet plug formation
Vascular changes in primary hemostasis
Contraction of muscle layers to prevent blood loss
-Neurogenic stimuli
-Endothelial and platelet products
Endothelial activation
-Pro and anti-coagulation to get clotting but not too much
Platelets in primary hemostasis
Sequential activities
-Adhesion
-Aggregation
-Secretion
-Contraction
Platelet adhesion
-Coat to subendothelial collagen
-Von Willebrand factor accelerates adhesion
-GPlb binds to vWF on damaged surface
Platelet aggregation
Build up of plaque allows for conformational change which induces GPIIb-IIIa binds fibrinogen forms bridges between platelets
Platelet secretion
Induced by adhesion and aggregation start to release granules. Things like Factor V, fibrinogen, fibronectin, growth factors, and platelet factors to enhance coagulation and start healing. Most are preformed
Why is calcium an important co factor
Want a lot of calcium at the site of wound so released by platelets
Thromboxane and platelets
Part of COX pathway enhances platelet aggregation and vasoconstriction. TBX synthase is in higher concentrations in platelets
Platelet Factor 3
Substrates for coagulation to happen
Contraction of platelets
Want to minimize size in vessel so blood can flow through
-Use actin and mysoin
-Get concurrent fibrinolysis to minimize size and initiate repair
Contraction of platelets
Want to minimize size in vessel so blood can flow through
-Use actin and myosin
-Get concurrent fibrinolysis to minimize size and initiate repair
Enzymatic coagulation
All are proenzymes. Once activated add an a at the end. Produced mainly by hepatocytes
Non-enzymatic coagulation factors
Non enzymatic participants for enzymatic coagulation reaction. Calcium is the mediator of the binding of these factors to the phospholipids of the platelets
Types of coagulation models
-Classical coagulation
-Integrated model of coagulation
Intrinsic pathway
Activation of Factor XII->XIIa which initiates the cascade leading to factor X
-Also get contact factors (XII, HMWK, and PK) these are involved in binding to activating surfaces
Intrinsic pathway role
Usually secondary to extrinsic and amplify thrombin when everything is formed and extrinsic gets going. Can have deficiencies here and not a huge issue
Extrinsic pathway
Activated by the release of Tissue Factor (Factor III) by damaged endothelial surfaces-> get activation of Factor X
-Works most invivo
Common pathway
Starts with Factor X and gets activated-> Get conversion of prothrombin ( factor II) into thrombin (IIa) by prothrombinase complex-Thrombin cleaves fibrinogen to fibrin monomers and form polymers
-Facter XIII stabilizes with cross linking of the fibrin polymers
Prothrombinase complex
Factor Xa and Va and calcium on phospholipid surface
Integrated model
Many points of interaction between each of the classical pathways
Key points of integration
-TF-VIIa activates X and IX (intrinisic)
-Thrombin-initiated activation of factors V, VIII, and XI amplifies intrinsic and common pathways
-Activation of extrinsic Factor VII by XIIa and IXa and kallikrein
Regulation of hemostasis
Need balance between pro and anti coagulation
-Deplete
-Clear
-inactivate activated coagulation factors
Antithrombin
major circulating anticoagulant
-Degrades all activated coagulation factors except for Factor VIIa
Protein C
Vitamin K dependent
-Pro-fibrinolytic agent
-Activated by thrombin
-Complexes with Protein S on phospholipid surfaces and inactivates Factors Va and VIIa
Fibrinolysis
Dissolution of clots to maintain homeostasis
-Plasmin (from plasminogen) is important to break the fibrin monomer
-Needs to be timed not too slow or too fast
FDPS
Fibrin degradation products produce anti-thrombotic and pro hemorrhagic
-Compete with fibrinogen for binding sites
-Impair platelet function
-Used as a landmark for coagulopathies
Plasminogen activator inhibitor-
Inhibits plasminogen activators so you don’t get plasmin
Antiplasmins
-Prevent excessive plasmin activity
-Alpha 1 and 2
C1 inhibitor
Modulates complement, coagulation, kinin, and fibrinolytic pathways
