Clotting Cascade and Hemostasis

Question 1

Primary Hemostasis

Answer 1

Platelet plug formed at endothelial injury site

Question 2

Secondary Hemostasis

Answer 2

Initial platelet plug enlarged, stabilized by adding fibrin via coagulation cascade

Question 3

Tissue factor (thromboplastin/Factor III)

Answer 3

Released/exposed when endothelial cells damaged at injury site - initiates extrinsic pathway of cascade

Question 4

Steps in extrinsic pathway

Answer 4

Factor III - Factor VII - add Ca2+ - Common pathway (X)

Question 5

Vitamin K dependent factors

Answer 5

II, VII, IX, X

Question 6

Effects of Vitamin K deficiency

Answer 6

Coagulation impaired; clinically significant

Question 7

Steps in intrinsic pathway

Answer 7

XII (HMWK) - prekallikrein to kallikrein - XI - IX - VIII - Common pathway (X)

Question 8

Common pathway

Answer 8

X, V, Ca2+, PLs (prothrombinase) - II (prothrombin to thrombin) - I (fibrinogen to fibrin)

Question 9

Thrombin

Answer 9

1. Activates downstream cascade (fibrin, XIIIa)
2. Positive feeback to upstream (more thrombin)
3. Has paracrine activity influencing hemostasis

Question 10

Factor XIII

Answer 10

Crosslinks fibrin to form stable fibrin when activated

Question 11

Activated Partial Thromboplastin Time (aPTT)

Answer 11

Measures function of Intrinsic + Common pathway factors
Reference range: 25-35 sec
Heparin Therapy (inhibits IIa, IX, Xa)
Hemophilia (VIII or IX deficiency)

Question 12

Prothrombin Time (PT)

Answer 12

Measures function of Extrinsic + Common pathway factors
Reference range: 10-13 sec
Coumadin/warfarin therapy (inhibits Vit K pathway)
Vitamin K deficiency (II, VII, IX, X)

Question 13

What are the 4 steps of Hemostasis?

Answer 13

1. Vascular Spasm
2. Platelet Plug
3. Blood Clot
4. Damage Repair

Question 14

Thrombopoietin (TPO)

Answer 14

Continually secreted by liver, kidney; destroyed by platelets when platelet levels are high (mpl receptor)

Question 15

Thrombopoiesis

Answer 15

Increases differentiation of stem cells, maturation rate; thus: effects on ALL cell lines

Question 16

Polycythemia vera

Answer 16

Mutation on mpl receptor - TPO not destroyed

Question 17

Erythropoiesis

Answer 17

EPO released from kidney during low O2 delivery; controlled by HIF accumulation; binds to EPoR on stem cells and commits to erythroid lineages

Question 18

Vascular spasm

Answer 18

Myogenic response: vascular SM contracts
Platelet factors involved: 5HT, TXA2
Reduces blood loss by slowing/stopping flow out

Question 19

Platelet plug formation

Answer 19

Initiation: exposed collagen on damaged blood vessels binding to receptor on platelet (VWF)
Platelets swell, stick to each other = plug (TXA2, ADP)

Question 20

Blood coagulation

Answer 20

Coagulation: 1. Thrombin activator activated
2. Thrombin activated
3. Fibrin created from fibrinogen
Clot stabilization/retraction-requires platelets

Question 21

Damage repair

Answer 21

Platelets secrete platelet-derived growth factor which stimulates fibroblasts to grow into the area - close hole

Question 22

Clot removal

Answer 22

Requires plasmin to breakdown fibrin; pathway:
Thrombin + thrombomodulin = Protein C
Protein C inhibits t-PA inhibitor
t-Pa converts plasminogen to plasmin

Question 23

Prevention of clotting

Answer 23

1. SM endothelial cells; glycocalyx repels platelets
2. Endogenous anticoagulants: fibrin, heparin, prostacyclin, anti-thrombin 3
3. Protein C: inactivates factors V, VIII