section 10 - inhibitors

Question 1

definition of inhibitors and function (general)

Answer 1

• antibody directed against single or multiple coagulation factors
• alter the function or promote rapid clearance of respective factor = decrease amount

Question 2

VIII:C inhibitor

Answer 2

• most common
• hemophilia patient = complication of treatment
• non hemophilia/acquired = less severe bleeding peak 50-80 yrs old

Question 3

laboratory diagnosis of factor inhibitors (they’re all the same)

Answer 3

• PT: normal
• APTT: prolonged
• 50/50 APTT: prolonged

Question 4

what can be done to confirm an inhibitor is causing the prolonged APTT

Answer 4

incubate 50/50 mix and rerun - inhibitors remain prolonged

Question 5

desribe antiphospholipid antibodies

Answer 5

group of immunoglobulins that bind protein-phospholipid complexed
- lupus anticoagulant
- Anti-cardiolipin antibodies
- anti-beta2 glycoprotein

Question 6

true or false
1-2% of pop have APL antibodies and are asymptomatic that arise post-infection and will disappear

Answer 6

true

Question 7

true or false
5-15% of individuals with recurrent thrombotic diseases have APL antibodies

Answer 7

true

Question 8

list autoimmune disease associated APL antibodies

Answer 8

• SLE
• RA
• Sjogrens

Question 9

describe antiphospholid syndrome (APS)

Answer 9

associated with variety of clinical symptoms leading to thrombosis

Question 10

pathophysiology of lupus inhibit (LI) aka lupus anticoagulant

Answer 10

• anti phospholipid Ab
• does NOT react w/ ENDOgenous platelet phospholipid
• reacts with phospholipid in test system

Question 11

clinical manifestations of lupus inhibitor (lupus anticoagulant)

Answer 11

• associated with thrombosis
• LI inhibits prostacyclin production = platelets adhere to non injured endothelial cells
• prostacyclin is normally an inhibitor of platelet adhesion

Question 12

how is LI diagnosed

Answer 12

• APTT prolonged
• 50/50 APTT prolonged -> differentiate between heparin and this
• use low reagent phospholipid test

Question 13

list most common tests to confirm LI

Answer 13

• APTT w/ low phospholipid reagent (SCT)
• dilute russell viper venom time (DRVVT)
• platelet neutralization procedure (PNP) - confirmatory

Question 14

describe the silica clotting time (SCT)

Answer 14

• APTT w/ silica replacing phospholipid -> contact activator
• if LI is present = prolonged

Question 15

describe the dilute russell viper venom time (DRVVT)

Answer 15

• sensitive to LI
• prolonged with LI

Question 16

describe the dilute thromboplastin inhibition assay

Answer 16

used for LI confirmation
- dilute PT reagent -> prolonged with LI

Question 17

describe the platelet neutralization procedure (PNP)

Answer 17

• used to confirm prolonged DRVVT or KCT
• washed and lysed platelets incubated with patient plasma
• spin down and re run supernatant DRVVT or KCT
• LI will be bound to platelets and in pellet
  –> reran DRVVT or KCT shortened by >10% confirms LI

Question 18

what result of PNP confirms LI

Answer 18

• Reran DRVVT or KCT with supernatant
• result shortened by >10%

Question 19

describe anticardiolipin Ab (ACL)

Answer 19

• anticardiolipin Ab and LI coexist in 60% of cases
• enzyme immunoassay
• looking for Ab in patient plasma

Question 20

describe anti-betaa2 glycoprotein

Answer 20

pathologic levels occur in APS patients
- anti phospholipid antibody
- increased in RA and SLE
- immunoassay detection