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MLSCI 230 > Fibrinolysis > Flashcards

Fibrinolysis Flashcards

1
Q

process of fibrinolysis mainly mediated by

A

plasmin - breaks down fibrin

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2
Q

too much fibrinolysis

A

risk of bleeding

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3
Q

too little fibrinolysis

A

risk of thrombosis

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4
Q

system designed to digest and remove fibrin clots to re-establish blood flow through an injured vessel

A
  • fibrinolytic system
  • plasmin
  • fibrinolytic proteins incorporated into fibrin clot = keeps fibrinolysis localized
  • activated a few hours after clot formation
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5
Q

fibrinolytic system components

A
  • plasminogen (acts on fibrin primarily; can also break down fibrinogen)
  • activators: endogenous, exogenous
  • substrates: fibrinogen and fibrin
  • inhibitors: alpha2-antiplasmin, plasminogen activator inhibitor, thrombin-activatable fibrinolysis inhibitor
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6
Q

where is plasminogen made?

A

liver

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7
Q

T or F. Plasmine is a serin protease

A

T

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8
Q

when free plasmin digests fibrin, factors V, VIII

A

primary fibrinolysis disorder

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9
Q

alpha 2-antiplasmin

A

inactivates plasmin

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10
Q

plasminogen activators

A
  • endogenous (inside body): intrinsic activators + extrinsic activators
  • exogenous: recombinant TPA (rTPA), urokinase, streptokinase; used for therapeutic reasons - storke, MI, etc.
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11
Q

intrinsic activators (plasminogen activators)

A
  • in plasma

- XIIa, kallikrein, XIa, HMWK

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12
Q

extrinsic activators (plasminogen activators)

A
  • not in plasma
  • tissue plasminogen activator (TPA)
  • urokinase/urokinase plasminogen activator (UPA)
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13
Q

streptokinase

A
  • exogenous (from bacteria; beta-hem streptococci)
  • not specific for fibrin; lso digests fibrinogen
  • drawback when using as clot buster = potential immune response
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14
Q

thrombin time

A
  • assessing specific portion of coag pathway
  • uses dilute thrombin reagent
  • measure time for thrombin to convert fibrinogen to fibrin clot
  • detects presence of thrombin inhibitors and low/abnormal fibrinogen
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15
Q

prolonged thrombin time

A
  • hypofibrinogenemia/dysfibrinogenemia
  • heparin
  • fibrin degradation products
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16
Q

TPA

A
  • tissue plasminogen activator
  • major activator of plasminogen
  • released by endothelial cells (thrombin and APC induce release)
  • binds to fibrin during clot formation (fibrin-bound plasminogen)
  • circulating TPA bound to inhibitors; keeps fibrinolysis local
  • can be given therapeutically as exogenous clot buster
17
Q

urokinase plasminogen activator

A
  • endogenous plasminogen activator
    > not fibrin specific
  • secreted by urinary tract epithelial cells, monocytes, and macs
  • circulates in plasma and binds to clot during formation
  • can also be given therapeutically (exogenous activator)
18
Q

plasmin

A
  • degrades fibrinogen and fibrin; destroys V, VII, XIII, GPIb
  • fibrin forms = bound plasminogen is activated to plasmin by TPA
  • free plasmin destroyed
    > alpha 2 antiplasmin
    > bound plasmin not affected
19
Q

fibrin degradation products

A
  • X, Y, D, and E fragments from fibrinogen or weakly linked fibrin
  • D-D from cross-linked fibrin = D-dimers
    > marker of thrombosis and fibrinolysis
    > found in disseminated intravascular coagulation and venous thromboembolism
20
Q

inhibitors of fibrinolysis

A
  • plasminogen activator inhibitor (PAI-1)
  • alpha 2- antiplasmin
  • thrombin-activatable fibrinolysis inhibitor (TAFI)
21
Q

PAI-1

A
  • main plasmin inhibitor
  • produced by several cells including endothelial cells; also stored in PLTs
  • inactivates tissue plasminogen activator and urokinase plasminogen activator
22
Q

alpha 2-antiplasmin

A
  • inhibits free plasmin

- competes with fibrin for plasmin

23
Q

thrombin-activatable fibrinolysis (TAFI)

A
  • activated by the thrombin-thrombomodulin complex

- inhibits fibrinolysis by cleaving fibrin’s target site for TPA/plasminogen

24
Q

D- dimer assays

A
  • detects active fibrinolysis and occurrence of thrombosis
    > D-dimers are only present after a clot
  • normal D-dimer conctn <2 ng/mL
  • increased D-diers >200 ng/mL
    > DIC
    > venous thromboembolism = deep vein thrombosis and pulmonary embolism
25
Q

qualitative D-dimer test

A
  • ‘semi-quantitative’
  • latex agglutination principle
    > latex particles coated with anti-D-dimer
    > agglutinate if D-dimers present
  • add patient plasma to latex particles; mix
  • positive = make plasma dilutions; report lowest dilution that still agglutinates
26
Q

quantitative D-dimer immunoassay

A
  • immunoassay
    > microlatex particles coated with monoclonal anti-D-dimer
    > agglutinate in presence of D-dimers
    > measure absorbance; increased turbidity correlates to amount of D-dimer
  • exclude diagnosis of DVT and Pe
    > negative result = high specificity to rule out
    > positive result does not mean above conditions present; could be due to inflammation
  • test to monitor DIC progression

MLSCI 230 (36 decks)

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