23 - Thrombophilia Flashcards Preview

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Flashcards in 23 - Thrombophilia Deck (25):
1

composition of venous thrombi vs arterial thrombi

venous - RBCs
arterial - platelets

2

virchow's triad

endothelial injury
abnl blood flow
hypercoagulability

3

activated protein C affect on PTT

prolong - degrades factor Va and VIIIa

4

APC resistance gene mutation

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

5

clinical consequences / management of Factor V Leiden

relatively common, risk for venous (not arterial) thrombosis
overall significance not known, prophylactic anticoag NOT recommended

6

prothrombin gene mutation

inc synth of prothrombin > 3 fold inc thrombotic risk
common in caucasians

7

protein C

vit K dependent anticoagulant
made in liver

8

what activates protein C

thrombin/thrombomodulin complex

9

how does APC reduce coagulation?

inactivates factor Va and VIIIa w/ protein S as cofactor

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

10

congenital protein C deficiency inheritance pattern

AD inheritance, variable penetrance

11

clinical presentation/effects of heterozygous and homozygous protein C deficiency

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

homozygotes - infants w/ DIC or purpura fulminans

12

protein S

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

13

causes of acquired protein C and S deficiency

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

14

antithrombin

binds w/ heparin-like molecs > conf change

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

15

causes of antithrombin defi

congenital - AD
acquired - similar to prot C/S

16

causes of impaired fibrinolysis

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

17

lipoprotein (a)

inc levels > inc risk of venous thromboembolsim
facilitates tissue repair by inhibiting fibrinolysis in damaged area

18

hyperhomocysteinemia - clinical consequences

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

19

mechanism of homocysteine effect

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

20

MTHFR 677 C>T mutation

homozygous state > mild to mod hyperhomocysteinemia
~10% in caucasians, ~20% asians are hetero

21

acquired risk factors for venous thrombosis

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

22

antiphospholipid ab syndrome (APS)

clinical: thromboses, recurrent miscarriages, pregnancy morbidity

labs: lupus anticoag, anticardiolipin ab (IgG or IgM), anti-beta-2 glycoprotein-1 ab

23

clinical presentation of venous thromboembolism

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

24

2 methods for diagnosis of venous thromboembolism

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

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

25

dx of pulm embolism

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