Coagulation ConceptsA review of hemostasis

Answers are in the notes pages.

Hemostasis Outline

• The big picture

Hemostasis is a balancing act!

pro-clotting anti-clotting

plugs up holes in

blood vessels

keeps clotting

under control

PRO-CLOTTING

clot

Platelets

Granules: (fibrinogen, vWF) (serotonin, ADP, Ca2+)

Membrane:Phospholipids (activate coag factors)GP Ia (binds collagen)GP Ib (binds vWF) GP IIb-IIIa (binds fibrinogen)

fibrin clotfibrinogen

thrombinprothrombin

XaVa

TFVIIa VII

TF

X

IXaIX

VIIIaVIII

V

thrombin Intrinsic Extrinsic

COAGULATION CASCADE

Aaahhhhh!

I can’t tell a Blahnik from a

Louboutin!

Cruel Shoes

TFVII

IX

VIII

fibrin

clot

thrombin

XV

IX

Intrinsic SEXtrinsic

PTT PT

simple

XIaXIXIIaXII

thrombin

focusessexy

TFVII

IX

VIII

fibrin

clot

thrombin

XV

IX

SINtrinsic Extrinsic

PTT PT

simplefocuses

sexy

busy

XIaXIXIIaXII

thrombin

distractssinful

ANTI-CLOTTING

clot

ANTI-CLOTTING

clot

1

cascade inhibition• TFPI• ATIII• Proteins C, S

fibrin clotfibrinogen

thrombinprothrombin

XaVa

TFVIIa VII

TF

X

IXaIX

VIIIaVIII

V

thrombin

proteinC

ATIII

TFPI

Intrinsic Extrinsic

ANTI-CLOTTING

ANTI-CLOTTING

clot

1

cascade inhibition• TFPI• ATIII• Proteins C, S

2

clot lysis• t-PA• plasmin

Hemostasis Outline

• The big picture• Laboratory tests

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?

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?

TFVII

IX

VIII

fibrin

clot

thrombin

XV

FDPs

fibrinogen

PTT PT

TT

Hemostasis Outline

• The big picture• Laboratory tests• Bleeding disorders

Platelet bleeding• • •

Factor bleeding• • •

Bleeding Disorders: Clinical Features

What does each look like?

• 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

Hemophilia

• How common is it?

• How is it transmitted?

• What is the problem?

• How bad is it?

• What labs are abnormal?

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?

Disseminated Intravascular Coagulation

• What causes it?

• What’s going on in the patient?

• What does the blood look like?

• Which labs are abnormal?

Other bleeding factoids

• What are the vitamin-K dependant factors?

• What causes a decrease in these?

• Why do patients with liver failure bleed?

Hemostasis Outline

• The big picture• Laboratory tests• Bleeding disorders• Thrombotic disorders

Thrombosis risk factors

Thrombosis risk factors

Endothelialdamage

Stasis Hypercoagulability

Atherosclerosis Immobilization

Varicose veins

Heart stuff

Surgery

Carcinoma

Estrogen

Thrombotic disorders

When should you start to worry about a thrombotic disorder?

Factor V Leiden

• How common is it?

• How is it transmitted?

• What is factor V Leiden?

• How bad is it?

• What labs are abnormal?

• 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