Thrombophilia

Question 1

Thrombosis

Answer 1

inappropriate formation of plt or fibrin clots that obstruct blood vessels

Question 2

embolism

Answer 2

piece of thrombotic material that breaks off from the thrombus & travels through circulatory system to be lodged at a distant site

Question 3

types of thrombus formations (2)

Answer 3

arterial & venous

Question 4

Arterial Thrombi

Answer 4

formed in arteries, composed primarily of plts & fibrin

80% of AMI are due to arterial thrombosis

Question 5

Venous thrombi

Answer 5

strong relation w/ pulmonary embolism & venous thrombosis in lower limbs

Question 6

Hereditary Thrombophillia

Answer 6

antithrombin deficiency
Protein C deficiency
Protein S deficiency

Question 7

Antithrombin deficiency

Answer 7

without this heparin will not work!
autosomal dominant
2 types - quantitative vs qualitative
decreased inhibition of Factor Xa & thrombin

Question 8

Heterozygous Antithrombin

Answer 8

reduced AT activity of 30-60%

thrombotic issues increase w/ age

Question 9

Homozygous type 1 antithrombin deficiency

Answer 9

incompatible with fetal survival

Question 10

Homozygous type 2 antithrombin deficiency

Answer 10

associated w/ life threatening thrombotic problems

Question 11

Specific tests for antithrombin deficiency

Answer 11

assays: progressive AT & Heparin cofactor*****

Question 12

Protein C Deficiency

Answer 12

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

Question 13

Protein C deficiency type 1

Answer 13

more common

decrease of functional activity to 40-60% & decrease of PC antigen levels

Question 14

Protein C deficiency type 2

Answer 14

decrease in functional activity levels but normal PC antigen levels

Question 15

Protein C deficiency specific lab tests:

Answer 15

PC levels in plasma
Antigen assay
functional activity assay

Question 16

Protein S Deficiency

Answer 16

vit K dependent protein
inactivates factor Va & VIIIa (!!)
autosomal dominant

Question 17

Protein S deficiency specific lab tests

Answer 17

PS concentration in plasma
total PS assay
Free PS assay

Question 18

Activated Protein C Resistance

Answer 18

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

Question 19

Activated Protein C Resistance Specific lab test

Answer 19

screening-clot based tests

confirmatory -PCR*****

Question 20

Prothrombin gene mutation 20210

Answer 20

point mutation in the prothrombin gene
associated w/ a mild elevation of prothrombin levels
autosomal dominant
PCR -confirmatory

Question 21

Heparin Cofactor II deficiency

Answer 21

autosomal dominant

many individuals asymptomatic

Question 22

Tissue Factor Pathway Inhibitor Variant

Answer 22

natural inhibitor of coag that directly neurtalizes FXa & neutralizes the tissue factor-VIIa complex
gene mutation reports increase risk of venous thrombi embolisms

Question 23

ABO blood groups B & A1

Answer 23

have higher levels of vWF & FVIII than O type

Question 24

Hyperhomocysteinemia

Answer 24

severe inborn error of metabolism
associate w/ premature atherosclerosis & venous & arterial thrombosis
less sever elevations have been implicated in VTE

Question 25

Dysfibrinogenemia

Answer 25

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

Question 26

Elevated factor VIII & vWF

Answer 26

increase risk of thrombotic disease | specific polymorphism of FVIII & vWF genes

Question 27

Factor XII & Thromboembolic disease

Answer 27

FXII deficiency, prolonged APTT | no bleeding

Question 28

Acquired fibrinolytic defects

Answer 28

have impaired fibrinolytic function | increased plasma PAI-1 most common

Question 29

Antiphospholipid antibody syndrome (APLS)

Answer 29

most common cause of acquired thrombophilia****** includes lupus anticoagulant prolong in vitro coag studies**

Question 30

Heparin treatment

Answer 30

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

Question 31

What test monitors Heparin

Answer 31

APTT

Question 32

LMWH

Answer 32

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.

Question 33

Heparin complications

Answer 33

bleeding & association with HIT

Question 34

Coumadin/ Warfarin

Answer 34

oral anticoagulant! vitamin K antagonist does not leat to 'instantaneous' anticoagulation must be administered 4-5 days before therapeutic anticoag achieved

Question 35

Test to monitor Coumadin/Warfarin

Answer 35

PT