coagulation concepts a review of hemostasis answers are in the notes pages
TRANSCRIPT
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Coagulation ConceptsA review of hemostasis
Answers are in the notes pages.
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Hemostasis Outline
• The big picture
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Hemostasis is a balancing act!
pro-clotting anti-clotting
plugs up holes in
blood vessels
keeps clotting
under control
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PRO-CLOTTING
clot
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Platelets
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Granules: (fibrinogen, vWF) (serotonin, ADP, Ca2+)
Membrane:Phospholipids (activate coag factors)GP Ia (binds collagen)GP Ib (binds vWF) GP IIb-IIIa (binds fibrinogen)
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fibrin clotfibrinogen
thrombinprothrombin
XaVa
TFVIIa VII
TF
X
IXaIX
VIIIaVIII
V
thrombin Intrinsic Extrinsic
COAGULATION CASCADE
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Aaahhhhh!
I can’t tell a Blahnik from a
Louboutin!
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Cruel Shoes
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TFVII
IX
VIII
fibrin
clot
thrombin
XV
IX
Intrinsic SEXtrinsic
PTT PT
simple
XIaXIXIIaXII
thrombin
focusessexy
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TFVII
IX
VIII
fibrin
clot
thrombin
XV
IX
SINtrinsic Extrinsic
PTT PT
simplefocuses
sexy
busy
XIaXIXIIaXII
thrombin
distractssinful
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ANTI-CLOTTING
clot
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ANTI-CLOTTING
clot
1
cascade inhibition• TFPI• ATIII• Proteins C, S
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fibrin clotfibrinogen
thrombinprothrombin
XaVa
TFVIIa VII
TF
X
IXaIX
VIIIaVIII
V
thrombin
proteinC
ATIII
TFPI
Intrinsic Extrinsic
ANTI-CLOTTING
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ANTI-CLOTTING
clot
1
cascade inhibition• TFPI• ATIII• Proteins C, S
2
clot lysis• t-PA• plasmin
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Hemostasis Outline
• The big picture• Laboratory tests
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Lab Tests: Platelets
Count/Morphology• at what count do you start bleeding?• how often do platelets look weird?
Bleeding time• measures what?• why is it bad?
Platelet aggregation studies• for which disorders are they helpful?
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Lab Tests: Coagulation
PT/INR• which pathway?• what makes it go up?
PTT• which pathway?• what makes it go up?• what’s an aPTT?• what’s the mixing study used for?
FDP (D-dimer) assay• what would you use this for?
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TFVII
IX
VIII
fibrin
clot
thrombin
XV
FDPs
fibrinogen
PTT PT
TT
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Hemostasis Outline
• The big picture• Laboratory tests• Bleeding disorders
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Platelet bleeding• • •
Factor bleeding• • •
Bleeding Disorders: Clinical Features
What does each look like?
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• How common is it?
• How is it transmitted?
• What is von Willebrand factor?
• What is the problem?
• How bad is it?
• What labs are abnormal?
von Willebrand Disease
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Hemophilia
• How common is it?
• How is it transmitted?
• What is the problem?
• How bad is it?
• What labs are abnormal?
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Bernard-Soulier
Glanzmann
Grey platelet syndrome
δ granule deficiency
Matching
Hereditary Platelet Disorders
No IIb-IIIa
No δ granules
No Ib
No α granules
Which ones have big platelets?
Which ones have severe bleeding?
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Disseminated Intravascular Coagulation
• What causes it?
• What’s going on in the patient?
• What does the blood look like?
• Which labs are abnormal?
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Other bleeding factoids
• What are the vitamin-K dependant factors?
• What causes a decrease in these?
• Why do patients with liver failure bleed?
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Hemostasis Outline
• The big picture• Laboratory tests• Bleeding disorders• Thrombotic disorders
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Thrombosis risk factors
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Thrombosis risk factors
Endothelialdamage
Stasis Hypercoagulability
Atherosclerosis Immobilization
Varicose veins
Heart stuff
Surgery
Carcinoma
Estrogen
Thrombotic disorders
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When should you start to worry about a thrombotic disorder?
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Factor V Leiden
• How common is it?
• How is it transmitted?
• What is factor V Leiden?
• How bad is it?
• What labs are abnormal?
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• How common are these (relative to factor V Leiden)?• What’s the genetic abnormality?• How do you diagnose them?
Matching
Other hereditary thrombotic disorders
MTHFR gene
Heparin won’t work
Usually not serious
Gain-of-function mutation
Purpura fulminans/Warfarin induced skin necrosis
ATIII deficiency
Protein C deficiency
Factor II mutation
Hyperhomocysteinemia
Anti-phospholipid antibodies