2.1 Thrombophilia Flashcards
What are the three components of thrombus formation?
Hypercoaguability
Abnormal blood flow
Endothelial damage
What are the genetic risk factors for vein thrombosis?
AT deficiency. PC and PS deficiency, FV Leiden, APCR, ProThrombin G20210A, MTHFR mutation, increased VIIIc
What are the acquired risk factors for vein thrombosis?
Cancer, surgery, acute illness with bed rest
Pregnancy/puerperium, hormonal preparations (OCP), obesity, autoimmune disease, elevated homocysteine
Define thrombophilia
abnormal occurrence of vein thrombosis without adequate provocation
Define thrombophilia
abnormal occurrence of vein thrombosis without adequate provocation
abnormal = young patients, unprovoked, recurrent, unusual sites, family history
What are the coagulation factors?
I: Fibrinogen II: Prothrombin III: Tissue Factor or Thromboplastin IV: Ca V: Labile factor VII: Proconvertin VIII: Antihemophilic factor IX: Christmas factor X: Stuart or Stuart-Prower factor XI: Plasma thromboplastin antecedent XII: Hageman factor, contact factor XIII: Fibrin stablizing factor
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What are the genetic risk factors for vein thrombosis?
AT deficiency Protein C and Protein S deficiency FV Leiden APCR ProThrombin G20210A, MTHFR mutation Increased VIIIc
What are the coagulation factors?
I: Fibrinogen II: Prothrombin III: Tissue Factor or Thromboplastin IV: Ca V: Labile factor VII: Proconvertin VIII: Antihemophilic factor IX: Christmas factor X: Stuart or Stuart-Prower factor XI: Plasma thromboplastin antecedent XII: Hageman factor, contact factor XIII: Fibrin stablizing factor
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What is fibrinolysis?
The breakdown of clots from plasmin (fibrin degradation products)
What factors promote the production of plasmin from plasminogen?
tPA (from endothelial cells) and Urokinase Streptokinase
What is the clinical definition of thrombophilia?
Patients who develop PE spontaneously, VTE is out of proportion to any recognised stimulus, recurrent venous thrombosis and developing venous thromboembolism at an early age
What patients have been shown to have high rates of VTE?
Cancer patients (20% new cases associated with cancer) - especially those with pancreatic and stomach cancer
What is antiphospholipid syndrome?
A non inflammatory auto immune disease in which there is presence of antibodies against anionic phospholipids. Associated with the occurrence of venous and arterial thrombosis and/or recurrent miscarriage.
What are the most common antibodies directed against in antiphospholipid syndrome?
B2 glycoprotein 1 and prothrombin
anti B2 glycoprotein 1 antibodies
What do the antiphospholipid antibodies do?
Inhibit the inhibiting factors of the coagulation cascade.
Interfere with coagulation and anticoagulation pathways and activation of platelets.
Endothelial activation in vessels
Why does deficient protein C usually occur?
resistance of factor Va to be cleaved by activated protein C leading to excessive levels of factor V stimulating clotting
Usually because of Factor V Leiden mutation
What mutation leads to elevated prothrombin?
mutation at position 20210
What is the role of antithrombin?
form a 1:1 complex with activated clotting factors (thrombin and Xa) at the active site thus preventing the protease enzymes that would normally bind from doing so.
When does antithrombin accelerate its action?
In the presence of heparin or when it is activated by cell surface heparin sulfate
What two factors does protein C inhibit?
factor Va and VIIIa
What is the role of protein S?
to act as a cofactor for protein C in the inactivation of FVa and FVIIIa
When do you usually test for thrombophilia?
1 month after commencing therapy
When do you usually test for thrombophilia?
1 month after completion therapy
Who do you normally test for thrombophilia?
Recurrent/spontaneous PE or DVT
Thrombosis at young age
Family history or thrombosis at unusual site
What tests do you use to evaluate thrombophilia
FBC, FCP (clotting) and ESR Factor V leiden (ACPR) Prothrombin mutation AT Protein C and S Lupus anticoagulant
Which two abnormalaties will cause both arterial and venous clotting?
Hyperchromocysteinemia and Lupus anticoagulant
