Making and Unmaking the Clot

Question 1

define the term hemostasis

Answer 1

highly balanced interaction between blood vessels, platelets, coagulation factors, and fibrinolytic factors in the formation and dissolution of blood clots to stop hemorrhage without obstructing blood flow; has 3 parts:
1. primary hemostasis: formation of primary platelet plug
2. secondary hemostasis: stabilization of the plug with cross-linked fibrin
3. fibrinolysis

Question 2

list the major mechanisms by which hemostasis is achieved in a bleeding vessel (8)

Answer 2

1. vessel is injured
2. vasoconstriction limits blood loss
3. primary hemostasis begins as platelets adhere to exposed subendothelial collagen and spread to patch the defect
4. when platelets adhere they release products (serotonin, ADP, and thromboxane A2) from their granules to attract and activate more platelets
5. platelets adhere and aggregate to form the primary hemostatic plug
6. secondary hemostasis begins with activation of the extrinsic and intrinsic pathways to promote cascade reactions that eventually activate the common pathway (factor X)
7. this leads to production of thrombin, which is essential for conversion of fibrinogen to fibrin within the primary hemostatic plug
8. fibrin forms the stable, secondary hemostatic plug to seal vessel injury and maintain bloodflow

Question 3

describe the role of platelet plugs in hemostasis

Answer 3

the primary hemostatic plug is unstable, but a quick first patch while the much more stable secondary hemostatic plug is formed from fibrin

Question 4

list and describe the common factors and mechanisms that may initiate blood coagulation (6)

Answer 4

1. complete vessel injury such as bleeding
2. injury to blood vessel endothelium (inflammation or abnormal blood vessel formation)
3. abnormal blood flow (turbulent or blood stasis)
4. diseases that cause release of large amount of tissue factor
5. conditions that cause unbalanced or excessive coagulation
6. conditions that cause a decrease in anticoagulant factors

Question 5

list the blood factors contributing to and the major steps involved in the formation of a blood clot

Answer 5

need 3 factors:
1. blood vessels: intact endothelium prevents coagulation and damaged endothelium initiates coagulation
2. platelets: form primary hemostatic plug and facilitate assembly of coagulation factors to form secondary hemostatic plug and repair vascular damage
3. coagulation factors are sequentially generated; thrombin is formed and amplifies coagulation, converts fibrinogen to fibrin, activates coagulation control pathways

see other card for major steps

Question 6

describe primary hemostasis (4) plus final result

Answer 6

1. platelet adhesion
2. platelets change their shape (pseudopodia) and become activated
3. platelets release granule contents (promote further coagulation and recruit additional platelets)
4. aggregation: via vWF and fibrinogen
   FINAL RESULT: formation of platelet mass called primary hemostatic plug (a loose seal)

Question 7

what is von Willebrand factor (vWF)?

Answer 7

platelets adhere to each other and also arrest on exposed subendothelial collagen following enodthelial injury via vWF; stored in endothelial cells; during formation of primary plug

Question 8

describe secondary hemostasis generally

Answer 8

formation of a stable clot = platelets + cross=linked fibrin + red cells

key participants are coagulation factors in the coagulation cascade

Question 9

which coagulation factors are vitamin K dependent? (4)

Answer 9

1. factor II (thrombin)
2. factor VII
3. factor IX
4. factor X

Question 10

give the order of factors of the intrinsic pathway

Answer 10

1. XII: activated by exposed collagen to XIIA, which activates
2. XI to XIa which activates
3. IX which complexes with
4. VIIIa that circulates with vWF for protection; VIII is activated to VIIIa by thrombin (factor II)
5. IXa and VIIIa activate factor X

Question 11

give the order of factors of the extrinsic pathway

Answer 11

1. TF (tissue factor III) is released from injured endothelium or tissue and activates
2. VII to VIIa which activates
3. X to Xa

Question 12

give the order of factors of the common pathway

Answer 12

1. Xa activates
2. V to Va and the Xa/Va complex activates prothrombin (II) to thrombin (IIa)
3. thrombin (IIa) converts fibrinogen (I) to fibrin (Ia)
4. XIII comes in and forms a cross-link that makes the fibrin strands stable

Question 13

list the blood factors contributing to and the major steps involved in the dissolution of a blood clot

Answer 13

1. fibrin degradation results in production of fibrin degradation products
2. fibrinolysis begins once the fibrin clot forms
3. primarily mediated by plasmin, which degrades multiple prothrombotic factors

Question 14

describe action of plasmin

Answer 14

1. acts as scissors to degrade fibrin and fibrinogen
2. degrades both stable (cross-linked) and unstable fibrin
3. cross-links remain intact during degradation, resulting in formation of D-dimers

Question 15

explain the mechanisms by which blood is prevented from clotting in the normal circulatory system

Answer 15

1. constant blood flow: dilutes local concentration of clotting factors, removes clotting factors, and maintains all the things to prevent the need for clotting in the first place (hydration, BP, HR)
2. intact blood vessel endothelium
3. phagocytic cells remove activated factors
4. anticoagulants regulate activities of coagulation factors and fibrinolytic enzymes

Question 16

list and describe 3 anticoagulants (not a learning objective but seemed important)

Answer 16

1. antithrombin (AT, antithrombin III): binds and inhibits thrombin, XIIa, XIa, IXa, and Xa, activity enhanced by heparin
2. protein C and S: activated by thrombin, converted from pro to anti coagulant state; inactivate factors Xa and XIa
3. protein Z: inactivates factors Xa and XIa