Bleeding & Thrombosis

Harrison’s Principles of Internal Medicine 19th Ed

Human homeostatic system provides a natural balance
between procoagulant and anticoagulant forces. Under
normal circumstances, hemostasis is regulated to promote
blood flow as well as preparing the body to clot blood
rapidly to prevent excessive blood loss.

Three major components of the hemostatic system are:

1. Platelets and other formed elements of blood (monocytes, RBC, etc.)
100

2. Plasma proteins (coagulation and fibrinolytic factors and inhibitors)

75

50
3. Vessel Wall 25

April May June July

Normal Homeostasis
Normal Homeostasis. Step by step.

1 2
Platelet Plug Fibrin Clot
Formation Formation

Antithrombotic
Fibrinolytic System
Mechanism
3 4
Platelet Plug Formation
On vascular injury, platelets adhere to the site of injury,
usually covering the vascular intimal surface.

Platelet Adhesion is mediated primalrily by

Von Willebrand Factor

Von WIllebrand Factor serves as the primary ‘molecular glue’,

providing sufficient strenght to withstand the shear stress.

Beside VWF, platelet adhesion is also facilitated by direct binding

to subendothelial collagen.
Fibrin Clot Formation
Coagulation is normally initiated through Tissue Factor (TF) exposure and
activation through the classic extrinsic pathway but with critically
important amplification through elements of the classic intrinsic pathway.

How does it start?

Immediate trigger for coagulation is vascular damage that

exposes blood to Tissue Factor (TF) that is expressed on the
surfaces of subendothelial cellular components of the vessel wall,
such as smooth muscle cells and fibroblasts.
Initiation of Coagulation

100

75

50

25

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Fibrin. Formation and Dissolution.

100

75

50

25

April May June July

Antithrombotic mechanism. Four major sites.

100

75

50

25

April May June July

Fibrinolytic System

100

75

50

25

April May June July

Bleeding & Thrombosis
Approach to the patient
CLINICAL HISTORY OF PROHEMORRHAGIC EFFECTS

1 PRESENTATION 2 BLEEDING 3 ON MEDICATION AND DIETARY

SUPPLEMENTS

Inherited? Acquired?
Determine: NSAID » precipitate GI bleeding
Easy bruising? Menorrhagia?
- the bleeding or thrombosis
Epistaxis? (Not specific)
site Effect of other NSAIDs is shorter，
Post partum haemorrhage?
- is it enhanced by medical as the inhibitor effect is reversed
Prolonged bleeding in/post surgery?
condition/medication/dietary when the drug is removed
supplement?

UNDERLYING SYSTEMIC
HISTORY OF
4 5
DISEASES THAT CAUSE OR
EXACERBATE A BLEEDING

TENDENCY THROMBOSIS

Bruising or mucosal bleeding may Influenced by both genetic and

be the presenting complaint in liver
disease， severe renal impairment，
hypothyroidism paraproteinemias or
amyloidosis， and conditions
causing bone marrow failure.
environmental influences.
Idiopathic (meaning there was no
clear precipitating factor) or was a
precipitated event.
Dietary Supplements
Herbal supplements associated with increased bleeding
Risk Factors
What can worsen the thrombosis?
Laboratory Evaluation
The use of laboratory tests of coagulation complement,
but cannot substitute for, clinical assessment.

• Screening assays
• Mixing studies
• Specific factor assays
• Testing for Antiphospholipid antibodies
• Other coagulation test
• Laboratory testing for thrombophilia
• Measures of platelet function
Hemostatic Abnormalities
And what to expect?
Thank you