23 - Thrombophilia

Question 1

composition of venous thrombi vs arterial thrombi

Answer 1

venous - RBCs

arterial - platelets

Question 2

virchow’s triad

Answer 2

endothelial injury
abnl blood flow
hypercoagulability

Question 3

activated protein C affect on PTT

Answer 3

prolong - degrades factor Va and VIIIa

Question 4

APC resistance gene mutation

Answer 4

factor V Leiden mutation - makes V less susceptible to cleavage by APC

Question 5

clinical consequences / management of Factor V Leiden

Answer 5

relatively common, risk for venous (not arterial) thrombosis

overall significance not known, prophylactic anticoag NOT recommended

Question 6

prothrombin gene mutation

Answer 6

inc synth of prothrombin > 3 fold inc thrombotic risk

common in caucasians

Question 7

protein C

Answer 7

vit K dependent anticoagulant

made in liver

Question 8

what activates protein C

Answer 8

thrombin/thrombomodulin complex

Question 9

how does APC reduce coagulation?

Answer 9

inactivates factor Va and VIIIa w/ protein S as cofactor

also a powerful inhibitor of PAI-1 (plasminogen activator inhibitor)

Question 10

congenital protein C deficiency inheritance pattern

Answer 10

AD inheritance, variable penetrance

Question 11

clinical presentation/effects of heterozygous and homozygous protein C deficiency

Answer 11

heterozygotes - 5-10 fold inc in venous thrombosis risk, rarely symptomatic until >20yo. assoc w/ pregnancy loss

homozygotes - infants w/ DIC or purpura fulminans

Question 12

protein S

Answer 12

vit K dependent
60% binds to C4b-BP, no anticoag fn
40% free - cofactor for APC, anticoag

Question 13

causes of acquired protein C and S deficiency

Answer 13

liver dz
DIC
acute thromboses
post surg
BC pill, hormone replacement
warfarin / vit K deficiency

L-asparginase - C only
ARDS - C only
nephrotic syndrome - S only

Question 14

antithrombin

Answer 14

binds w/ heparin-like molecs > conf change

complex inactivates thrombin and F.Xa
accelerates dissoc of F.VIIa-TF complex

Question 15

causes of antithrombin defi

Answer 15

congenital - AD

acquired - similar to prot C/S

Question 16

causes of impaired fibrinolysis

Answer 16

congenital plasminogen defi
tPA defi
high PAI-1
congenital dysfibrinogenemia
F.XII defi
high lipoprotein (a)

Question 17

lipoprotein (a)

Answer 17

inc levels > inc risk of venous thromboembolsim

facilitates tissue repair by inhibiting fibrinolysis in damaged area

Question 18

hyperhomocysteinemia - clinical consequences

Answer 18

risk factor for premature CAD, stroke, venous thrombosis, periph vasc dz

Question 19

mechanism of homocysteine effect

Answer 19

inc endothelial cell toxicity
promotes proteolyis of F.V > F.Va
blocks protein C activation
may block tPA binding to endothelial cells > dec fibrinolysis
may inc monocytes binding to endothelial cells

Question 20

MTHFR 677 C>T mutation

Answer 20

homozygous state > mild to mod hyperhomocysteinemia

~10% in caucasians, ~20% asians are hetero

Question 21

acquired risk factors for venous thrombosis

Answer 21

history of thrombosis
central venous cath / cannulation attempt
older
immobilization / venous stasis
malignancy
inflammation / severe infxn
surgery
pregnancy / estrogen therapy
obesity
smoking
antiphospholipid ab syndrome

Question 22

antiphospholipid ab syndrome (APS)

Answer 22

clinical: thromboses, recurrent miscarriages, pregnancy morbidity
labs: lupus anticoag, anticardiolipin ab (IgG or IgM), anti-beta-2 glycoprotein-1 ab

Question 23

clinical presentation of venous thromboembolism

Answer 23

unilateral thigh/calf swelling / tenderness, pitting edema, presence of collateral superficial non-varicose veins

Question 24

2 methods for diagnosis of venous thromboembolism

Answer 24

serial compression ultrasounds - most reliable/practical but cant tell btwn acute and chronic

contrast venography - most sensitive, but painful and can induce thromboembolism

Question 25

dx of pulm embolism

Answer 25

CXR often normal
ventilation-perfusion scan shows areas not perfused but ventilated
spiral CT pulm angiography
echo may pick up large saddle embolus