Clotting Cascade Flashcards
Clotting Cascade
Extrinsic v. Intrinsic pathway
Extrinsic: starts with TF; due to vessel injury
Intrinsic pathway: starts wtih XI = due to contact
Tissue Factor
Subendothelial protein released during vascular damage
First clotting factor in extrinsic pathway
Activates Factor VII to VIIa
Factor VII
Part of extrinsic pathway
Vitamin K dependent hepatic synthesis
VIIa converts X to Xa, IX to IXa
- connects intrinsic and extrinsic pathways
VIIa as shortest half-life of all clotting factors
Factor IX
Part of intrinsic pathway
Vitamin K dependent hepatic synthesis
IXa combines with VIIIa to form “tenase complex,” which converts X to Xa
X linked inheritance –> hemophilia B
Factor VIII
Part of intrinsic pathway
Endothelial syntheesis: it releases VIII when damaged
Protected by spontaneous degradation by vWF
Thrombin converts it to VIIIa & it becomes part of tenase complex
X linked inheritance –> hemophilia A
von Willebrand Factor
Massive multimeric protein cleaved by ADAMTS13
Endothelial and megakaryocyte synthesis (platelets produce it)
Binds collagen in damaged vascular bed
Carries factor VIII
Binds activated platelets via glycoprotein Ib receptor
Factor X
Activated to Xa by ‘Tenase complex’
Vitamin K dependent hepatic synthesis
Converts prothrombin to thrombin as a part of the prothrombinase complex (Factor Xa, Va, and phospholipid
Factor II
Prothrombin is cleaved to form Thrombin (IIa)
Thrombin is Two
Key positive upregulator of coagulation
Vit K dependent hepatic synthesis
It converts fibrinogen to fibrin
Also converts V to Va, VII to VIIa, VIII to VIIIa, XIII to XIIIa, XI to XIa, Protein C to activated Protein C
Factor I
Fibrinogen
“Fibrinogen is First”
Forms protein meswork around platelet plug that strengthens clot
Cloth is further stabilized when Factor XIIIa crosslinks fibrin strands
Factor XI
Part of intrinsic pathway
Can be activated to XIa by: XIIa or thrombin
Non-vitamin K dependent hepatic synthesis
Hereditary deficiency often noted only as post-operative bleeding (Hemophilia C)
Two major ways to turn off coagulation
Protein C: thrombin turns on protein C to activated protein C, which turns of VIIIa and Va
Protein S: makes Protein C more efficient
Protein C
“Natural anticoagulant”
Vitamin K dependent hepatic synthesis
aPC inactivates Va and VIIIa
aPC activity potentialted by Protein S
Antithrombin
“natural anticoagulant”
Non-Vitamin K dependent hepatic synthesis
Incativates Factor Xa and Thrombin
Protein S
Vitamin K dependent hepatic synthesis
Potentiates Protein C
Fibrinolysis
Breaking up of the fibrin clot
Plasmin chews up the fibrin clot and breaks it into fragments (fibrin degradation products)
D-Dimer
Not a coagulation factor
Biomarker of clotting: tells you clotting is happening
By-product of fibrinolysis
Elevated when there is excessive coagulation and in renal failure
Vitamin K dependent factors
II, VII, IX, X, Protein C, Protein S
2+7=9, 10 comes after + C and S
Normal platelet count?
How low can you go for neurosurgery, most other surgeries, spontaneous bleeding, CNS bleeding?
Normal = 180,000-400,000
>100,000 = safe for neurosurgery
>50,000 = safe for most other surgeries
<20,000 = spontaneous bleeding
<10,000 = CNS bleeding
What are the 2 ways that platelets unite the pathways & do clotting?
(1) They are sticky, bind vWF, endothelium, and ahve granules (fibrinogen, factor V, etc.) = one way to get the pathway bc all the factors are packed in one
(2) Platelets produce thromboxane = potent vasoconstrictor and a second way to do clotting
(remember that aspirin inhibits thromboxane)
Which 2 tests can you use to assess pt’s coagulation systems? What are the pros/cons to this system?
Prothrombin time (PT): extrinsic pathway
Partial Thromboplastin Time (PTT): intrinsic pathway
This is what happens in tests tubes, not what happens in people; sometimes you can get tests that don’t reflect their risk for bleeding
PTT
Partial thromboplastin Time
Measures intrinsic pathway: time needed to complete coagulation starting at top of intrinsic pathway through prouduction of fibrin
Normal 23-35 seconds
Prolonged by deficiency of any involved factor; then go back and check the levels of each protein to see which protein they are deficient in
Longer times do not necessarily reflect bleeding risk
PT
Addition of tissue factor to patient plasma allows measurement of time needed to complete coagulation via the extrinsic pathway
Typically 10-13 seconds
Also expressed as international normalized ratio (INR)
Most sensitive to Factor VII deficiency
Which disorders have normal PT and PTT?
Platelet disorders (meds, uremia, inherited)
Factor XIII deficiency
Hyperfibrinolysis
Which disorders have long PT & normal PTT?
Vitamin K Deficiency
Warfarin effect
Which disorders have long PTT only?
Hemophilias (VIII, IX, XI)
von Willebrand dz
Heparin effect
Lupus anticoagulant
Contact factor deficiency
Which disorders have prolonged PT and PTT?
DIC: disseminated intravascular coagulation
Extreme warfarin effect
Rare common pathway factor deficiency
What is a mixing study? What can you learn from it?
To determine if prolonged PT and/or PTT is secondary to factor deficiency or inhibitory antibody to part of clotting cascade
Mix 50% pt and 50% pooled plasma
Recheck PT and PTT
- if normal: factor deficiency present (check which)
- if prolonged, inhibitor present (antibody is binding to the factors)
