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 Stroke Peripheral art. Dis.

Deep venous thrombosis(DVT) Pulmonary Embolism (PE)

Thrombus mainly platelets (white thrombus) mainly red cells (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 Deficiency • Prothrombin Gene Mutation • Protein C and S Deficiency • Elevated Factor XI • Dysfibrinogenemia • Tissue Plasminogen Activator Defects • Factor V Leiden (APC resistance) • Elevated Factor VIII • Sticky Platelet Syndrome • Plasminogen Activator Inhibitor • Homocystinemia • Antiphospholipid Antibodies

Provoking Risk Factors
• Prolonged Immobilization • Chronic Inflammatory Disease • Oral Contraceptives • • • • • • Estrogens Nephrotic Syndrome Pregnancy Trauma General Surgery Cardiovascular Disease

Antithrombin Deficiency Incidence
In healthy blood donors: type 1: type 2: 1:4200 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

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