Thrombosis

Learning objectives
At the end of the lecture student should be able to
 Describe mechanisms that lead to thrombosis
 Describe the possible outcomes of thrombus formation
 Identify and classify thrombi based on gross or microscopic
features
Virchow Triad In Thrombosis

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© 2005 Elsevier
Prothrombotic alterations
 PROCOAGULANT CHANGES
Downregulation of Thrombomodulin
Protein C
Tissue factor pathway inhibitor (TFPI)
 ANTIFIBRINOLYTIC EFFECTS
Downregulate the t-PA by secreting PAIs
(Plasminogen activator inhibitors)
Abnormal Blood Flow
 Stasis & turbulence
therefore
 Promote endothelial activation and procoagulant activity

 Disrupts laminar flow and bring platelets into contact

with endothelium

 Prevent washout and dilution of activated clotting factors

by fresh flowing blood and inflow of clotting factor
inhibitors
Conditions causing thrombosis
 Ulcerated Atherosclerotic Plaque
 Abnormal aortic or arterial dilatation
(aneurysm)- stasis
 Acute Myocardial Infarction
 Mitral Valve Stenosis
 Atrial Fibrillation
 Hyper viscosity
Polycythemia , Sickle cell anemia
HYPERCOAGULABITY
(THROMBOPHILIA)
Hypercoagulable States

Primary (Genetic)
 Common
 Mutation in factor V gene (factor V Leiden)
 Mutation in prothrombin gene
 Mutation in methyltetrahydrofolate gene
 Rare
 Antithrombin III deficiency
 Protein C deficiency
 Protein S deficiency
 Very rare
 Fibrinolysis defects
Primary (Hereditary) Thrombophilia
 Less than 50 years of age

 Family history of venous thrombosis

 History of recurrent events

 Absence of acquired risk factors except for pregnancy and

oral contraceptive use
Secondary (Acquired) Hypercoagulable States
 HIGH RISK FOR THROMBOSIS
 Prolonged bed rest or immobilization
 Myocardial infarction
 Atrial fibrillation
 Tissue damage (surgery, fracture, burns)
 Cancer
 Prosthetic cardiac valves
 Disseminated intravascular coagulation
 Heparin-induced thrombocytopenia
 Antiphospholipid antibody syndrome (lupus anticoagulant syndrome)
 LOWER RISK FOR THROMBOSIS
 Cardiomyopathy
 Nephrotic syndrome
 Hyperestrogenic states (pregnancy)
 Oral contraceptive use
 Sickle cell anemia
 Smoking
Antiphospholipid Antibody syndrome
(APS)
 Acquired autoimmune disorder that manifests clinically as
recurrent venous or arterial thrombosis and/or fetal loss.

 Persistently elevated levels of antibodies directed against

membrane anionic phospholipids or their associated plasma
proteins …..hypercoagulable state
 Autoantibodies produce hypercoagulable state by endothelial
damage, activating platelets and complement directly

 Primary and secondary

Morphology of Thrombus
 Site
 Size & shape
 Propagate towards the heart
 Line of Zahn
Types of Thrombi
 Arterial (usually occlusive)
 site of turbulence or endothelial injury
 retrograde propagation
 Mural
 heart chambers
Venous
 occur in sites of stasis
 propagate in direction of blood flow
 Vegetations
heart valves
 infective endocarditis
 non-bacterial thrombotic endocarditis
MURAL THROMBI, HEART
 Post mortem clot
 Gelatinous with dark red dependent portion
 Yellow ‘chicken fat upper portion
 Not attached to underlying vessel wall
 Often mistaken as venous thrombi
 No lines of Zahn
 Difference between
Arterial Thrombi Venous Thrombi
Endothelial injury, turbulence Stasis

Retrograde propagation Ante grade propagation

Usually occlusive
Firmly adherent
Lines of Zahn prominent
Grey, white and friable
Composed of platelet,WBC ,
RBCs and Fibrin
Invariably occlusive
Loosely adherent
Lines of Zahn less prominent
Red
More red cells and few other
enmeshed cells
 THROMBUS POSTMORTEM
CLOT
Location Intravascular Extravascular or I/V

Composition Platelets Lacks platelet

Fibrin Rich in RBCS
RBCs &WBCs
Lines of Zahn Present Absent
Shape Has shape No shape
Attachment Firmly attached Loosely/not attached
Fate of the Thrombus
Propagation
Embolization
Dissolution – Fibrinolysis
older thrombi with cross linked fibrin
are resistant to lysis
Organization and recanalization.
Potential Outcomes Of Venous Thrombosis

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© 2005 Elsevier
Disseminated Intravascular
Coagulation (DIC)
 Widespread fibrin thrombi in the micro-circulation (brain,
heart, lungs, kidneys)
 Consumption of platelets and coagulation proteins
(consumption coagulopathy)
 Production of fibrin split products with fibrinolysis
 Is a syndrome, not a disease, and occurs in sepsis, malignancy
and other conditions
16.07.21

 SUMMARY