Hemostasis

Question 1

Hemostasis

Answer 1

Arrest of bleeding. A normal physiological response to localized vascular injury

Question 2

What are the factors of hemostasis

Answer 2

-Blood vessels
-Platelets
-Coagulation
-Fibrinolytic and thrombolytic factors (Regulating factors)

Question 3

Anti-coagulant factos made by endothelium

Answer 3

-Prostacyclin
-NO
-Thrombomodulin
-Protein S

Question 4

Prostacyclin

Answer 4

Ehance relaxation and inhibits platelet adhesions and activation

Question 5

NO

Answer 5

Maintains vascular relaxation and inhibits platelet activation. Participates with Protein C and antithrombin to suppress thrombin production

Question 6

Thrombomodulin

Answer 6

Binds tothrombin and activates protein C

Question 7

Protein S

Answer 7

Cofactor in Protein C pathway and independently inhibits activation of factors VIII and X

Question 8

Endothelium in hemostasis

Answer 8

Damage to endothelium produces pro clotting properties like Tissue factor
-Exposure of underlying collagen and other components activates coagulation and platelet adhesion

Question 9

Pro clooting endothelial mediators

Answer 9

-Tissue Factor (Factor III)
-Von willebrand Factor
-Plasminogen Activator Inhibitor-1

Question 10

Platelets

Answer 10

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)

Question 11

Main regulator of platelet production

Answer 11

Thrombopoietin

Question 12

Primary Hemostasis

Answer 12

Primary vascular and platelet response.
-Best for minor injuries
-Vascular contraction and endothelial activation of pro and anticlotting activity
-Platelet plug formation

Question 13

Vascular changes in primary hemostasis

Answer 13

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

Question 14

Platelets in primary hemostasis

Answer 14

Sequential activities
-Adhesion
-Aggregation
-Secretion
-Contraction

Question 15

Platelet adhesion

Answer 15

-Coat to subendothelial collagen
-Von Willebrand factor accelerates adhesion
-GPlb binds to vWF on damaged surface

Question 16

Platelet aggregation

Answer 16

Build up of plaque allows for conformational change which induces GPIIb-IIIa binds fibrinogen forms bridges between platelets

Question 17

Platelet secretion

Answer 17

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

Question 18

Why is calcium an important co factor

Answer 18

Want a lot of calcium at the site of wound so released by platelets

Question 19

Thromboxane and platelets

Answer 19

Part of COX pathway enhances platelet aggregation and vasoconstriction. TBX synthase is in higher concentrations in platelets

Question 20

Platelet Factor 3

Answer 20

Substrates for coagulation to happen

Question 21

Contraction of platelets

Answer 21

Want to minimize size in vessel so blood can flow through
-Use actin and mysoin
-Get concurrent fibrinolysis to minimize size and initiate repair

Question 22

Contraction of platelets

Answer 22

Want to minimize size in vessel so blood can flow through
-Use actin and myosin
-Get concurrent fibrinolysis to minimize size and initiate repair

Question 23

Enzymatic coagulation

Answer 23

All are proenzymes. Once activated add an a at the end. Produced mainly by hepatocytes

Question 24

Non-enzymatic coagulation factors

Answer 24

Non enzymatic participants for enzymatic coagulation reaction. Calcium is the mediator of the binding of these factors to the phospholipids of the platelets

Question 25

Types of coagulation models

Answer 25

-Classical coagulation -Integrated model of coagulation

Question 26

Intrinsic pathway

Answer 26

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

Question 27

Intrinsic pathway role

Answer 27

Usually secondary to extrinsic and amplify thrombin when everything is formed and extrinsic gets going. Can have deficiencies here and not a huge issue

Question 28

Extrinsic pathway

Answer 28

Activated by the release of Tissue Factor (Factor III) by damaged endothelial surfaces-> get activation of Factor X -Works most invivo

Question 29

Common pathway

Answer 29

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

Question 30

Prothrombinase complex

Answer 30

Factor Xa and Va and calcium on phospholipid surface

Question 31

Integrated model

Answer 31

Many points of interaction between each of the classical pathways

Question 32

Key points of integration

Answer 32

-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

Question 33

Regulation of hemostasis

Answer 33

Need balance between pro and anti coagulation -Deplete -Clear -inactivate activated coagulation factors

Question 34

Antithrombin

Answer 34

major circulating anticoagulant -Degrades all activated coagulation factors except for Factor VIIa

Question 35

Protein C

Answer 35

Vitamin K dependent -Pro-fibrinolytic agent -Activated by thrombin -Complexes with Protein S on phospholipid surfaces and inactivates Factors Va and VIIa

Question 36

Fibrinolysis

Answer 36

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

Question 37

FDPS

Answer 37

Fibrin degradation products produce anti-thrombotic and pro hemorrhagic -Compete with fibrinogen for binding sites -Impair platelet function -Used as a landmark for coagulopathies

Question 38

Plasminogen activator inhibitor-

Answer 38

Inhibits plasminogen activators so you don't get plasmin

Question 39

Antiplasmins

Answer 39

-Prevent excessive plasmin activity -Alpha 1 and 2

Question 40

C1 inhibitor

Answer 40

Modulates complement, coagulation, kinin, and fibrinolytic pathways