General Principles ofHemostasis

Kristine Krafts, M.D.

Hemostasis is a balancing act!

pro-clotting anti-clotting

plugs up holes in blood vessels

keeps clotting under control

Pro-Clotting

clot

vessels platelets cascade

Pro-Clotting

Blood vessel constricts.

• Blood loss decreases• Platelets and factors meet

Pro-Clotting

Platelets form a plug.• Proteins are exposed• Platelets adhese• Granules release contents• Platelets aggregate• Phospholipids are exposed

Pro-Clotting

Fibrin seals up plug.• Tissue factor is exposed• Cascade begins• Cascade makes fibrin• Fibrin solidifies plug

Pro-Clotting

Final common pathway

clotfibrinfibrinogen

thrombinprothrombin

XaVa

TFVIIa VII

exposed TF

X

IXa

VIIIaVIII

V

IX

Intrinsic Extrinsic

XIaXIXIIaXII

thrombin

Coagulation Cascade

fibrinfibrinogen

thrombinprothrombin

XaVa

TFVIIa VII

exposed TF

X

IXa

VIIIaVIII

V

IX

Intrinsic Extrinsic

XIaXI

thrombin

clot

fibrinfibrinogen

thrombinprothrombin

XaVa

TFVIIa VII

exposed TF

X

IXa

VIIIaVIII

V

IX

Intrinsic Extrinsic

XIaXI

thrombin

clot

fibrinfibrinogen

thrombinprothrombin

XaVa

TFVIIa VII

exposed TF

X

IXa

VIIIaVIII

V

IX

Intrinsic Extrinsic

XIaXI

thrombin

clot

fibrinfibrinogen

thrombinprothrombin

XaVa

TFVIIa VII

exposed TF

X

IXa

VIIIaVIII

V

IX

Intrinsic Extrinsic

XIaXI

thrombin

clot

fibrinfibrinogen

thrombinprothrombin

XaVa

TFVIIa VII

exposed TF

X

IXa

VIIIaVIII

V

IX

Intrinsic Extrinsic

XIaXI

thrombin

clot

Where does tissue factor come from?

• �Hidden� cells exposed during injury

• Microparticles floating in blood

• Endothelial cells and monocytes (during inflammation)

fibrinfibrinogen

thrombinprothrombin

XaVa

TFVIIa VII

exposed TF

X

IXa

VIIIaVIII

V

IX

Intrinsic Extrinsic

XIaXI

thrombin

clot

fibrinfibrinogen

thrombinprothrombin

XaVa

TFVIIa VII

exposed TF

X

IXa

VIIIaVIII

V

IX

Intrinsic Extrinsic

XIaXI

thrombin

clot

fibrinfibrinogen

thrombinprothrombin

XaVa

TFVIIa VII

exposed TF

X

IXa

VIIIaVIII

V

IX

Intrinsic Extrinsic

XIaXI

thrombin

clot

fibrinfibrinogen

thrombinprothrombin

XaVa

TFVIIa VII

exposed TF

X

IXa

VIIIaVIII

V

IX

Intrinsic Extrinsic

XIaXI

thrombin

clot

TFVIIIX

VIII

fibrin

clot

thrombin

XV

Intrinsic Extrinsic

fibrin

clot

tissue factor

busydistracting

sinful

simplerivetingsexy

fibrinfibrinogen

thrombinprothrombin

XaVa

TFVIIa VII

exposed TF

X

IXa

VIIIaVIII

V

IX

Intrinsic Extrinsic

XIaXI

thrombin

clot

fibrinfibrinogen

thrombinprothrombin

XaVa

TFVIIa VII

exposed TF

X

IXa

VIIIaVIII

V

IX

Intrinsic Extrinsic

XIaXI

thrombin

busydistractingsinful

SINtrinsic

clot

clotfibrinfibrinogen

thrombinprothrombin

XaVa

TFVIIa VII

exposed TF

X

IXa

VIIIaVIII

V

IX

Intrinsic Extrinsic

XIaXI

thrombin

simplerivetingsexy

SEXtrinsic

TFVIIIX

VIII

fibrin

clot

thrombin

XV

SINtrinsic SEXtrinsic

clot

Anti-Clotting

1

cascade inhibition

clotfibrinfibrinogen

thrombinprothrombin

XaVa

TFVIIa VII

exposed TF

X

IXa

VIIIaVIII

V

IX

Intrinsic Extrinsic

XIaXI

thrombin

proteinC

ATIII

TFPI

clot

Anti-Clotting

1

cascade inhibition• TFPI• ATIII• Proteins C, S

2

clot lysis

clot

Anti-Clotting

plasminplasminogen

t-PA

Hemostasis Outline

• The big picture• Laboratory tests

Platelet Lab Tests

Count• Done by particle counter• 150 – 450 x 109/L

Morphology• Size• Granulation

Platelets

Normal Platelets

Why?• Evaluate platelet response to vascular injury• Some platelet disorders have a long bleeding time How?• Inflate blood pressure cuff• Make incision• Time how long it takes to stop bleedingCareful!• Lots of things affect the test!• Some consider the test unreliable.

Bleeding Time

• Draw blood into citrate tube

• Spin tube, decant plasma

• Add reagents to plasma

• Watch for formation of fibrin

Coagulation Lab Tests

• Plasma + thromboplastin

• Measures extrinsic pathway

Prothrombin Time

TFVIIIX

VIII

fibrin

clot

thrombin

XV

Intrinsic SEXtrinsic

TFVIIIX

VIII

fibrin

clot

thrombin

XV

Intrinsic Extrinsic

The PT is increased in:• ¯ VII, X, V, II, I• Coumadin• Heparin• DIC

• Never!

• Order an INR instead.

When should you order a PT?

What is an INR?

Just a corrected PT.

• To assess liver function

• To monitor Coumadin therapy

• To diagnose DIC*

• To assess pre-op status

When should you order an INR?

* Disseminated intravascular coagulation

• Plasma + phospholipid

• Measures intrinsic pathway

• APTT = same thing

Partial Thromboplastin Time

TFVIIIX

VIII

fibrin

clot

thrombin

XV

ExtrinsicSINtrinsic

TFVIIIX

VIII

fibrin

clot

thrombin

XV

Intrinsic Extrinsic

The PTT is increased in:• hemophilia A• hemophilia B• DIC• heparin

• To investigate a history of abnormal bleeding

• To monitor heparin therapy

• To diagnose DIC

• To assess pre-op status

When should you order a PTT?

• Measures FDPs (including D-dimers)

• VERY sensitive!

Fibrin Degradation Product Assay

clot

Anti-Clotting

fibrinogen fibrin cross-linked fibrin

Thrombin XIII

fibrinogen fibrin cross-linked fibrin

FDPs D-dimers

plasmin

clot

Anti-Clotting

FDPs are increased when there is:• A nasty thrombus• Minor clotting

• Not to rule in a clot...

• but to rule out a clot.

When should you order an FDP assay?