Ics-Heme-Thrombotic D/o (Pathogenesis & Genetics)

Front 1

arterial thrombosis most frequently caused by

Back 1

vascular dz (atherosclerosis)

Front 2

Lupus Anticoagulants (LA)

Back 2

paradoxically prolong IN VITRO coagulation tests while producting a risk for thrombophilia IN VIVO

Front 3

mech of DIC

Back 3

secondary mechanism of dz that results in intravascular generation of thrombin and plasmin that exceed their natural inhibitors

Front 4

acquired/genetic risk factors assoc w/arterial atherosclerosis

Back 4

1. hyperhomocysteinemia
2. HIT
3. lupus anticoagulants

Front 5

pathogenesis of arterial thrombosis

Back 5

1. arterial atheosclerosis (like vessel wall abnormality)
2. platelet activation
(like hypercoagulability)
3. rheology of blood flow (shear stress)
(like venous stasis)

Front 6

what is the final event in MI

Back 6

thrombosis

Front 7

what genes cause VTE?

Back 7

VTE is multicausal and multigenetic

Front 8

Virchow's Triad

Back 8

1. endothelial/vessel wall abnormality
2. venous stasis
3. intrinsic hypercoagulability of blood

Front 9

what are examples of intrinsic hypercoagulability

Back 9

-pregnancy
-anti-phospholipid Ab (lupus anticoagulant or anticardiolipin Ab)
-estrogen (oral contraceptives, hormone replacement therapy)

Front 10

antiphospholipid AB syndrome

Back 10

prsence of antiphospholipid antibodies (LAC or ACA)in assoc w/
a. arterial/venous thrombosis
b. recurrent fetal wastage
c. thrombocytopenia

Front 11

what are examples of antiphospholipid antibodies?

Back 11

lupus anticoagulants

Front 12

lupus anticoagulants

Back 12

-prolong the aPTT in an inhibitor pattern (mixing studies do not correct)
-neutralized by xs lipid (phospholipid) or platelets

Front 13

Acquired risk factors for VTE

Back 13

1. lupus anticoagulants/antiphospholipid Ab
2. HIT
3. DIC
4. TTP/HUS
5. Myeloproliferative/bone marrow D/O
6. nephrotic syndrome (hypercoagulability results from loss of natural anticoagulant proteins such as AT; assoc w/renal vein thrombosis)

Front 14

ex of myeloproliferative/bone marrow D/O

Back 14

1.polycythemia vera
2.essential thrombocytopenia
3.Paroxysmal nocturnal hemoglobinuria

Front 15

paroxysmal nocturnal hemoglobinuria

Back 15

stem cell D/O w/complement-dependent destruction of RBC's assoc w/increased risk of DVT

Front 16

inherited risk factors for VTE

Back 16

1. AT deficiency
2. Protein C deficiency
3. Protein S deficiency
4. Factor V Leiden
5. Prothrombin 20210A

Front 17

Factor V Leiden

Back 17

MC inherited risk factor for VTE;
point mutation (arg 506) eliminates protein C cleavage site in Factor 5A-->resistnace to Activated protein C-->Protein C can't terminate coag

Front 18

Risk factors for VTE that can be genetic or acquired

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1. Hyperhomocysteinemia (homozygous cystathionine synthetase deficiency)
2. elevated Factor 8 levels (assoc w/inflammatory states)
3. dysfibrinogenemias

Front 19

complications of VTE

Back 19

1. post-phlebitic syndrome
2. pulmonary insufficiency/embolus

Front 20

anticoagulants

Back 20

Hirudin
Argatroban

Front 21

mechanism of HIT

Back 21

heparin generates Ab that recognizes platelet factor 4PF4-heparin complex-->Fc dependent platelet activation and destruction

Front 22

Tx for HIT

Back 22

-stop heparin Tx and instead use hirudin and argotroban

Front 23

pathogenesis of TTP/HUS

Back 23

endothelial injury triggers the diffuse deposition of platetlet and fibrin
-->fragmentation of RBC's

Front 24

Myeloproliferative/BM

Back 24

1.polycythemia
2.essential thrombocytopenia
3.paroxysmal nocturnal hemoglobinuria

Front 25

what constitutes severe HIT?

Back 25

severe is greater than 50% reduction in platelet counts, usually "late" (5-14 days)