A thrombus is a blood clot that is formed inside

a blood vessel, sometimes blocking blood flow

Thrombosis
Thrombotic Disorders
Thrombosis = closure of a vessel

Arterial Venous

Myocardial infarction Deep venous thrombosis(DVT)

Stroke Pulmonary Embolism (PE)
Peripheral art. Dis.

Thrombus
mainly platelets mainly red cells
(white thrombus) (red thrombus)
Virchows Triad
Pathophysiology of thrombosis involves

Changes in the vessel wall

Changes in blood flow
Changes in the coagulability of blood
( deficiencies of the natural anticoagulants)
 Thrombophilia
Inherited or acquired disorders of
hemostasis that predispose to thrombosis

Thrombophilia = Hypercoagulable state

Thrombophilia = Hypercoagulable state

• Condition(s) that predisposes to

thrombosis
such as : deficiencies of one of the natural
anticoagulants = Protein C, S,
antithrombins, …etc. Or acquired
inhibitors of coagulation (lupus
anticoagulant LA)
Deep Venous Thrombosis((DVT

= closure of veins

occurs mostly in leg & thigh veins

Venous Thrombo-embolism (VTE)
(other sites)
 Hereditary or Acquired
Thrombophilic Defects
• Antithrombin • Factor V Leiden (APC
Deficiency resistance)
• Prothrombin Gene • Elevated Factor VIII
Mutation • Sticky Platelet
• Protein C and S Syndrome
Deficiency • Plasminogen Activator
• Elevated Factor XI Inhibitor
• Dysfibrinogenemia • Homocystinemia
• Tissue Plasminogen • Antiphospholipid
Activator Defects Antibodies
 Provoking Risk Factors
• Prolonged • Estrogens
Immobilization • Nephrotic Syndrome
• Chronic Inflammatory • Pregnancy
Disease • Trauma
• Oral Contraceptives • General Surgery
• Cardiovascular
Disease
Antithrombin Deficiency

Incidence
In healthy blood donors: type 1: 1:4200
type 2: 1:600

In patients with thrombotic disease: 4-6 %

Acquired deficiency in pregnancy

Antithrombin Deficiency – Classification
Type 1
Reduction in functional and immunological antithrombin
level to < 50 % of normal

Type 2
Presence of a dysfunctional protein which may be present
in normal or reduced amounts
Protein C deficiency
In healthy blood donors 1: 200 – 300

In patients with thrombotic diseases 4 – 12 %

Heterozygotes:
may be asymptomatic
may not present until middle age
Homozygotes:
may present with neonatal disease
Protein S
Circulates in plasma in 2 forms
free 40% active
bound 60% inactive
Type 1 Protein S deficiency:
Reduced total and free PS levels
Type 2 reduced functional protein
Activated protein C resistance (APC – R)
2 Dahlback
APTT based assay, patient’s plasma shows resistance to
adding APC
1993-1994 30-60% of patients with thrombotic diseases
showed APC-R
In normal people, it is seen in ~ 5%
Activated protein C resistance (APC – R)

Later APC-R was linked to an abnormality in F V

FV Leiden = Arginine 506 – Glutamine in factor V

Mutant FV is resistant to cleavage by APC
30% of patients with thrombosis have FV mutation
 Acquired Thrombophilia
Lupus Anticoagulant (LA)
Antibodies against phospholipid
Inhibit phospholipid-dependent pathways (prolonged
APTT that is not corrected by normal plasma)
Causes arterial & venous thrombosis
Mechanism of thrombosis unknown
Clinical associations: SLE, thrombocytopenia, fetal
loss, miscarriages
 Lupus Anticoagulant (LA)
Inhibits the APTT by preventing the
intrinsic pathway factors, IXa and VIII, from
successfully attaching to phospholipid
surfaces and activating factor X

Prolonged APTT, yet liability for thrombosis

rather than bleeding
Tumor invasion of vessels, chemotherapy
Reduced AT, PC
Whom to Test ?
 Anticoagulants
Heparin
An anticoagulant
A mucopolysaccharide
It activates antithrombin (AT) which
inactivates thrombin, prothrombin, Xa, IXa
It also impairs platelet function
Not absorbed orally (given I.V or S.C)
 - Heparin

Used for treatment of thrombosis (mainly

venous)

Monitoring of heparin therapy

By APTT
Oral Anticoagulants – Coumadin (Warfarin)

Mode of action:

It inhibits the function of vitamin K

thus vit. K dependent factors II, VII, IX, X
become non-functioning
- Coumadin / Warfarin

Taken orally (by mouth)

Starts to act in 2 – 3 days

Monitoring of Warfarin therapy:

by PT & INR
Side effects of anticoagulants bleeding
 Patients with
DVT

elevate legs When you sit, put

your feet up