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Hematology > Fibrinolysis > Flashcards

Fibrinolysis Flashcards

1
Q

Fibrinolysis definition

A

Removing unwanted fibrin deposits

Fibrin is cleaved enzymatically to soluble fragments

RES system removes fragments

Re-establisheds blood flow previously occluded by thrombus

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2
Q

fibrinogen

A

soluble
coagulation cascade

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3
Q

fibrin

A

insoluble
fibrinolysis

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4
Q

FDPs

A

soluble

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5
Q

plasmin

A

Acts on fibrin to produce lysis of clot.

Generated from plasminogen

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6
Q

Plasmin is activated by

A

Tissue plasminogen activator (tPA) - other possibilities: XIIa, Kallikrein and HMWK

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7
Q

inhibitors of plasmin function to keep fibrinolysis in check

A

a2 antiplasmin
a2 macroglubolin
many more

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8
Q

tPA is produced by

A

vascular endothelial cells

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9
Q

tPA selectively binds and…

A

activates fibrin bound plasminogen
- does not activate circulating plasminogen

idea therapeutic fibrinolytic agent

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10
Q

Plasmin action:

A

destroys fibrinogen and fibrin non-selectively

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11
Q

Plasmin produces

A

FDPs - fibrin(ogen) degradation products

increases vascular perm.
interfere with thrombin induced fibrin formation

produces D dimer - degradation product from fibrin polymer

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12
Q

Plasmin destroys these factors

A

V
VIII
IX
XI

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13
Q

plasmin indirectly enhances

A

conversion of XII –> XIIa

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14
Q

Plasmin enhances conversion of PK to

A

Kallikrein

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15
Q

Plasmin cleaves

A

C3 into fragments (complement system)

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16
Q

Plasmin is an _ able to break down _ and _

A

endopeptidase
fibrinogen
fibrin

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17
Q

fibrinogen is in the bridges,

A

connecting platelets and fibrin is in the polymer form creating the fibrin clot

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18
Q

Plasmin action on fibrinogen

A

splitting off pieces of a, b, y polypeptides. These pieces are not present in the fibrin polymer

What is left: X monomer

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19
Q

X monomer

A

2 D parts, and 1 central E part

(still thrombin clottable)

From this point, fibrin and fibrinogen degradation is similar

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20
Q

Continued fibrinogen and fibrin (plasmin acting)

A

Plasmin then cleaves off one D fragment

This leaves a D fragment and a Y monomer.

Y consists of 1D part and 1 E part
- NOT thrombin clottable

Last,

Plasmin cleaves Y monomer which leaves the product: D fragment, E fragment, D fragment

21
Q

Plasmin acting on fibrin and fibrinogen product

A

D fragment, E fragment, D fragment

22
Q

Early FDP

X monomer vs Y monomer

A

X: D-E-D

Y: E-D or D-E

23
Q

Late FDP

A

D fragment (2 separate)
E fragment

24
Q

Fibrin polymers are connected by

A

the outside D parts

25
Q

When plasmin cleaves the E part

A

This leaves 2 D parts connected together (polymer)

D Dimer (End product)

26
Q

lab test - D dimer

A

Quantitative test

D dimer is product of a dissolved clot. - evidence there was a fibrin polymer

27
Q

elevated D dimer test seen in

A

thrombotic conditions

DIC
Deep vein Thrombosis
Pulmonary Embolism

28
Q

Kinin System

A

Important in inflammation, vascular permeability and chemotaxis

29
Q

Activated kinin system

A

Coagulation (Factor XII)
Fibrinolytic (plasmin) system

30
Q

Kinin system enhances

A

Coagulation system
Fibrinolytic system

31
Q

kinin end product

A

Bradykinin

32
Q

Bradykinin functions

A

increase vascular permeability

contracts smooth muscle

dilates small blood vessels

induces inflammation and pain

Stimulates release of

prostaglandins from tissues

33
Q

Coagulation inhibitory systems

A

Serine protease inhibitory System
Tissue factor pathway inhibitor
Antithrombin

34
Q

Plasmin, kvllikrein and serine protease enzymes continue to

A

circulate after they are needed

35
Q

Coag factors are eliminated by

A

Liver hepatocytes

Mononuclear Phagocytic system

Serine protease inhibitors in plasma - serine protease inhibitors bind and inactive them.

36
Q

Serine protease inhibitor

A

Protein C

37
Q

Protein C consists of

A

Thrombin (enzyme)
Thrombomodulin ( cofactor)
Protein S (cofactor)

38
Q

Protein C end product

A

cleaves Va and VIIIa

39
Q

TPFI

A

associated with a lipoprotein that inhibits plasma coagulation

40
Q

TPFI binds the

A

activated form of factor IXa or Xa

41
Q

Complex of TPFI-Xa or TPFI-IXa binds

A

cofactor VIIa on membrane and further restricts activation of the common pathway

42
Q

Heparin cofactor I

A

AT (antithrombin)

43
Q

AT funciton

A

inactivator of thrombin and Xa (common pathway)

> 90% of antithrombin activity is derived from AT

Action is increased by heparin

44
Q

Lab test - Anti-Factor Xa Assay

A

inhibition of Xa will occur in proportion to amount of heparin present.

Any uninhibited activated Xa will cleave a substrate, producing a color change. Chromogenic assay.

Degree of color is inversely proportional to heparin in sample

45
Q

Lupus anticoagulant - falsely though inhibitor

A

Antibodies against phospholipid - binding proteins.

First discovered in SLE patients

46
Q

Lupus anticoagulant in vivo

A

agonist, leading to increased thrombosis and non-needing clotting

47
Q

Lupus anticoagulant in vitro

A

inhibitor leading to delay in clotting assays including PT and APTT

48
Q

APTT/PT are useful in

A

identifying factor deficiencies and coag inhibitors

Hematology (36 decks)

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