Combined Hemostasis

Question 1

Extrinsic pathway

Answer 1

tissue factor pathway

Question 2

intrinsic pathway

Answer 2

contact activation pathway

Question 3

extrinsic tenase

Answer 3

7a, TF –> 10 or 9 + anionic phospholipid + Ca

Question 4

Intrinsic tenase

Answer 4

9a, 8a –> 10 + anionic phospholipid + Ca

Question 5

Prothrombinase

Answer 5

5a, 8a –> prothrombin + anionic phospholipid + Ca

Question 6

Protein C complex

Answer 6

thrombin, thrombomodulin –> protein C + anionic phospholipid + Ca

Question 7

Initiation

Answer 7

1) Tissue injury exposes TF
2) Circulating 7 binds to TF and becomes activated
3) TF/7a complex (extrinsic 10ase) activates 10 or 9
4) 10a binds to 5a (prothrombinase) activates prothrombin

Question 8

Amplification

Answer 8

1) Thrombin activates 5, 8, 11 while 7a/TF activates 9

2) 9a binds to 8a (intrinsic 10ase) activates 10 to make more thrombin

Question 9

Propagation

Answer 9

1) Thrombin convert fibrinogen → fibrin which undergoes polymerization
2) Thrombin activates 13
3) 13a crosslinks and strengthens overlapping fibrin strands

Question 10

Antithrombin

Answer 10

SERPIN; inactivates 7a, 9a, 10a, 11a

Heparin is co-factor

Question 11

Protein C pathway

Answer 11

1) thrombomodulin induces conformational change in thrombin
2) altered thrombin not able to activate platelets or convert fibrinogen to fibrin but can activate protein C
3) activated protein C with protein S (cofactor) inactivates 5a and 8a

Question 12

TFPI

Answer 12

single chain polypeptide reversibly inhibit 10a and 7a-TF complex

Question 13

Fibrinolysis

Answer 13

1) plasminogen (proenzyme) activated by conversion to plasmin by either
a. t-PA secreted from vascular endothelial cells
b. u-PA secreted from many cells

2) Plasmin cleaves fibrin at multiple sites releasing fibrin degradation products (D-dimer) → 2 D domains from adjacent fibrin monomers

Question 14

1) PAI-1

Answer 14

inactivates t-PA and u-PA

Question 15

2) Alpha 2 antiplasmin

Answer 15

inactivates plasmin

Question 16

3) TAFI

Answer 16

acts on fibrin by cleaving terminal residues reducing binding sites for plasminogen

Question 17

Heparin and LMWK

Answer 17

activate antithrombin → inhib 10a and thrombin

Question 18

tPa and streptokinase

Answer 18

activate plasmin → break up fibrin

Question 19

Warfarin

Answer 19

vitamin K reductase inhibitor → cannot recycle vitamin K → inhib 2, 7, 9, 10, S, C

Question 20

Hemostasis

Answer 20

forms thrombus (clot) to repair vessel injury

Question 21

Primary hemostasis-

Answer 21

FORMATION OF WEAK PLATELET PLUG 
	Adhesion
	Activation
	Aggregation	
	Forms a platelet plug

Question 22

Steps in Primary hemostasis 
#1: Vessel wall injury

Answer 22

1) Vessel wall injury- exposes subendothelium + collagen

2) Transient vasoconstriction of vessels, decr blood supply

Question 23

Steps in Primary hemostasis #2: Platelet adhesion

Answer 23

3) vWF binds subendothelial collagen
4) Platelet bind vWF using Gp1b receptor
5) vWF derived from Weibel Palade bodies of endothelial cells and alpha granules

Question 24

Steps in Primary hemostasis
#3: Platelet Activation

Answer 24

6) Adhesion induces shape change in platelets

7) Degranulation releases ADP (dense grnaules to expose Gp2b/3a receptor) and TXA2 for platelet AGGREGATION

Question 25

``` Steps in Primary hemostasis #4: PLATELET Aggregation ```

Answer 25

8) Platelets aggregate at site of injury via Gp2b/3a using fibrinogen as linking molecule → forms platelet plug

Question 26

Secondary hemostasis

Answer 26

Fibrin is crosslinked yielding a stable fibrin-thrombus

Question 27

What is required to activate zymogens?

Answer 27

Requires phospholipid surface (SURFACE OF PLATELETS) and calcium

Question 28

PT

Answer 28

measures extrinsic + common pathway (LESS #s) | better for measuring effect of Warfarin

Question 29

PTT

Answer 29

measures intrinsic + common pathway (MORE #S) | better for measuring effect of Hep

Question 30

What activates factor 12

Answer 30

lupus anticoagulant: How to test for it? subendothelial collagen

Question 31

What activates factor 7

Answer 31

tissue thromboplastin

Question 32

Hemophilia A

Answer 32

Factor 8 deficiency X linked recessive; mostly affects males Incr PTT; normal PT; decr Factor 8; normal platelet count

Question 33

Hemophilia B; Christmas disease

Answer 33

Factor 9 deficiency

Question 34

Coagulation factor inhibitor

Answer 34

Acquired antibody against coag factor → so can’t be involved in coag cascade

Question 35

Explain how a 1:1 mixing study can distinguish a clotting factor deficiency from an inhibitor of coagulation.

Answer 35

• A 1:1 mixing study of normal plasma with patients plasma can indicate if disease is due to a clotting factor deficiency or from an inhibitor of coagulation. ○ If PTT is not corrected after two hours of incubation--> disease is due to inhibitor. ○ If PTT corrects, clotting factor deficiency.

Question 36

lupus anticoagulant: | How to test for it?

Answer 36

Q • Detect by: - greatly prolonged PTT, - no bleeding tendency, - can have thrombotic syndromes (DVT, PE, thrombotic strokes, or recurrent miscarriages). (more likely to clot, but slower to clot)

Question 37

vWF Disease

Answer 37

most common inherited coagulation disorder Increased bleeding time (poor platelet adhesion so can’t seal off blood vessel quickly); incr PTT (because can’t stabilize factor 8 so simil to hemophilia A); normal PT Abnormal ristocetin- Ristocetin normally causes platelets to aggregate

Question 38

treatment of vWF

Answer 38

DDAVP | Increases vWF release from Weibel-Palade bodies of endothelial cells

Question 39

Vitamin K purpose in coag cascade

Answer 39

gut → liver → activated by epoxide reductase → gamma carboxylate 2, 7, 9, 10, C, S

Question 40

Liver failure

Answer 40

Decreased production of coat factors Decreased activation of vit K by epoxide reductase Test using PT

Question 41

DIC

Answer 41

Widespread microthrombi result in ischemia and infarction Consumption of platelets and factors

Question 42

Lab tests for DIC

Answer 42

Decr platelet count Incr PT/PTT (b/c forming thrombi) Decr fibrinogen (using up linker proteins btwn platelets) Microangiopathic hemolytic anemia (RBC sheared as cross frags of platelets → forming schistocytes) Elev fibrin split products (D-dimer) Crosslinked with fibrinogen → when get cut in blood vessel → lyse crosslinked fibrin = D-dimer

Question 43

Fxn of plasmin

Answer 43

(1) cleaves cross-linked fibrin and serum fibrinogen (prevent future thrombus production) (2) destroys coag factors to shut down formation of thrombus (3) blocks platelet aggregation

Question 44

Purpose of fibrinolysis

Answer 44

Fibrinolysis = after form thrombus, must remove thrombus to heal wound site