Thrombophilia Flashcards
Thrombosis
inappropriate formation of plt or fibrin clots that obstruct blood vessels
embolism
piece of thrombotic material that breaks off from the thrombus & travels through circulatory system to be lodged at a distant site
types of thrombus formations (2)
arterial & venous
Arterial Thrombi
formed in arteries, composed primarily of plts & fibrin
80% of AMI are due to arterial thrombosis
Venous thrombi
strong relation w/ pulmonary embolism & venous thrombosis in lower limbs
Hereditary Thrombophillia
antithrombin deficiency
Protein C deficiency
Protein S deficiency
Antithrombin deficiency
without this heparin will not work!
autosomal dominant
2 types - quantitative vs qualitative
decreased inhibition of Factor Xa & thrombin
Heterozygous Antithrombin
reduced AT activity of 30-60%
thrombotic issues increase w/ age
Homozygous type 1 antithrombin deficiency
incompatible with fetal survival
Homozygous type 2 antithrombin deficiency
associated w/ life threatening thrombotic problems
Specific tests for antithrombin deficiency
assays: progressive AT & Heparin cofactor*****
Protein C Deficiency
vitamin K dependent inhibitor of coagulation
protein C is converted to an active form by thrombin bound to endothelial cells which degrades factor Va & VIIIa (!!!!)
autosomal dominant
2 types
Protein C deficiency type 1
more common
decrease of functional activity to 40-60% & decrease of PC antigen levels
Protein C deficiency type 2
decrease in functional activity levels but normal PC antigen levels
Protein C deficiency specific lab tests:
PC levels in plasma
Antigen assay
functional activity assay
Protein S Deficiency
vit K dependent protein
inactivates factor Va & VIIIa (!!)
autosomal dominant
Protein S deficiency specific lab tests
PS concentration in plasma
total PS assay
Free PS assay
Activated Protein C Resistance
see diminished ability of APC (activated protein C) to destroy FVa during its normal inhibitory functions
point mutation in FVgene which makes it resistant to APC inactivation
Activated Protein C Resistance Specific lab test
screening-clot based tests
confirmatory -PCR*****
Prothrombin gene mutation 20210
point mutation in the prothrombin gene
associated w/ a mild elevation of prothrombin levels
autosomal dominant
PCR -confirmatory
Heparin Cofactor II deficiency
autosomal dominant
many individuals asymptomatic
Tissue Factor Pathway Inhibitor Variant
natural inhibitor of coag that directly neurtalizes FXa & neutralizes the tissue factor-VIIa complex
gene mutation reports increase risk of venous thrombi embolisms
ABO blood groups B & A1
have higher levels of vWF & FVIII than O type
Hyperhomocysteinemia
severe inborn error of metabolism
associate w/ premature atherosclerosis & venous & arterial thrombosis
less sever elevations have been implicated in VTE
Dysfibrinogenemia
various range of symptoms
decreased fibrinolysis due to:
fibrin resistance to lysis by plasminogen
reduced plasminogen activation
mutated fibrinogen which forms high fiber density clots
Elevated factor VIII & vWF
increase risk of thrombotic disease
specific polymorphism of FVIII & vWF genes
Factor XII & Thromboembolic disease
FXII deficiency, prolonged APTT
no bleeding
Acquired fibrinolytic defects
have impaired fibrinolytic function
increased plasma PAI-1 most common
Antiphospholipid antibody syndrome (APLS)
most common cause of acquired thrombophilia****
includes lupus anticoagulant
prolong in vitro coag studies**
Heparin treatment
unfractionated heparin*
injection only (IV or subQ)
doesn’t have direct effect on blood coagulation but potentiates formation of complexes between ANTITHROMBIN & factors : thrombin, XIIa, XIa, Xa, IXa, VIIa
ergo it increases coag inhibition
What test monitors Heparin
APTT
LMWH
can be administered subcutaneously
typically does not require routine lab monitoring but can use factor Xa
effect is to catalyze the interaction between AT and F- Xa.
Heparin complications
bleeding & association with HIT
Coumadin/ Warfarin
oral anticoagulant!
vitamin K antagonist
does not leat to ‘instantaneous’ anticoagulation
must be administered 4-5 days before therapeutic anticoag achieved
Test to monitor Coumadin/Warfarin
PT
