Clotting factors

Question 1

Draw clotting cascade including inhibitors

Answer 1

Intrinisc:
12 -> 12a
11-> 11a
9 -> 9 a  (hemophilia B)
8 – acceleration factor inhibited by protein C and S

Extrinsic:
TF -> 7

Common path:

X-> Xa
5 – acceleration factor inhibited by protein C and S
2 -> 2a – inhibited by antithrombin (heparin promotes antithrombin)
1 – XIIIa —> fibrin mesh “clot” – covalent bonds

Question 2

Warfarin inhibition

Answer 2

10, 9, 7, 2, c and S: diSCo 1972

transient hypercoagulation at initiation
-start heparin for a few days to overcome

Question 3

S. aureus effect on clotting

Answer 3

Coagulase can convert fibrinogen -> fibrin

Question 4

Prekallikrein pathway

Answer 4

12a (of coagulation cascade) ->
prekallikrein to kallikrein

-> plasminogen to plasmin
or
high molecular weight kininogen -> bradykinin

Question 5

Plasmin

Answer 5

Breaks down fibrin mesh

Cascade started by factor 12a

Question 6

Bradykinin

Answer 6

Inflammation

Vasodilator
Increased vascular permeability
Mediates pain

Degraded by ACE

Question 7

Relationship of inflammation and coagulation

Answer 7

Inflammation promotes coagulation

Coagulation promotes inflammation

Question 8

Prothrombin time (PT)

Answer 8

Pt plasma + TF
-time clot formation
10-13 seconds normal

tests effectiveness of TF to activate tissue factor pathway (extrinsic) and final common pathway

tests VII, X, V, II

reported w/ INR
1 = normal
over 1 longer to clot

Question 9

Partial thromboplastin time (PTT)

Answer 9

Add silica to activate the contact activation pathway (intrinsic)
Masure clot formation time
25-40 seconds normal

need to add phospholipids

tests: 12, 11, 9, 8, 10, 5, 2

Question 10

Bleeding time

Answer 10

Standardized cut, blot blood away and measure how long it takes to stop
2-9 min normal

platelet function NOT coagulation cascade

Pt and PTT not affecting bleeding time

Question 11

Liver dz effect on clotting

Answer 11

Decreased coagulation factors -> increased PT and PTT

Question 12

Hemophilia A

Answer 12

Factor VIII deficiency

Intrinsic pathway
Increased PTT – no affect on PT or INR

Question 13

Hemophilia B

Answer 13

Factor 9 deficiency

Intrinsic pathway
Increased PTT – no affect on PT or INR

Question 14

Vit K deficiency

Answer 14

Cofactor for factors 10, 9, 7, 2, proteins C and S

Deficiency -> low factors

Causes:
Vit K inadequate intake
Newborns – gut bacteria not established, give vit K IM
Warfarin – functional vit k deficiency
End stage liver dz – can’t make factors and protein C and S, look clinically like vit K deficiency

Question 15

Factor V Leiden

Answer 15

40-50% heritable hypercoaguable states

Factor V mutation -> resistance to inactivation by protein C

Factor V active longe r-> more clotting

Question 16

Prothrombin G20210A mutation

Answer 16

Predisposes to thrombosis

Guanine to adenine at position 20210

Question 17

Antithrombin deficiency

Answer 17

Unable to inactivate thrombin

Resistant to heparin or bigger dose to get same effect

Question 18

Protein C/S deficiency

Answer 18

Unable to inactivate acceleration factors 5 and 8

Question 19

Coagulation disorders

Answer 19

Macrohemorrhages
Hemarthrosis
Easy bruising
Major hemorrhages w/ trauma