Section 10: Inhibitors

Question 1

inhibitor definition

Answer 1

antibody directed against single or multiple coag factors

Question 2

effect of inhibitors

Answer 2

mostly bleeding
sometimes thrombosis

Question 3

true autoantibody

Answer 3

• alter function or promote rapid clearance of factor(s)
• autoimmune disease, malignancy, pregnancy, advanced age

Question 4

factor VIII:C inhibitor

Answer 4

• antibodies that prevent VIII replacement therapy from controlling bleeding in hemophilia A pt
• hemophilia pt-complication of treatment
• non-hemophilia pt get acquired hemophilia

Question 5

acquired hemophilia

Answer 5

• usually bleeding not as severe, but can be fatal
• auto-Ab can form from SLE, RA, drug rxns…etc or with no underlying disease (e.g., post-partem)

Question 6

factor VIII:C inhibitor lab diagnosis

Answer 6

• PT normal
• APTT prolonged
• 50:50 mix (APTT) remains prolonged bc Ab bind FVIII in normal plasma too

Question 7

T/F FVIII inhibitors are time and temp dependent so incubate 50:50 mix at 37°C for max performance

Answer 7

True

Question 8

T/F
only some factor specific inhibitors are possible

Answer 8

False
can make factor specific inhibitor to any coag factor

Question 9

which anti-phospholipid antibody groups exist?

Answer 9

• anticardiolipin
• lupus anticoag
• anti-beta2 glycoprotein-1
• other antibodies

Question 10

anti-phospholipid antibodies (APL)

Answer 10

• rare and asymptomatic
• most arise as response to infection or treatment with certain drugs most disappear within 12 weeks
• recurrent thrombotic disease have APL

Question 11

list autoimmune-associated APL Ab

Answer 11

SLE
RA
Sjogrens syndrome

Question 12

anti-phospholipid syndrome (APS) clinical symptoms

Answer 12

• thrombosis
• pregnancy complications
• unexplained cutaneous circulatory disturbances (blood flow issues)
• thrombocytopenia
• hemolytic anemia
• nonbacterial thrombotic endocarditis

Question 13

lupus inhibitor specificity

Answer 13

not specific for any coag factor

Question 14

lupus inhibitor pathophysiology

Answer 14

does not react w endogenous platelet phospholipid but does react with phospholipid in test systems

Question 15

lupus inhibitor clinical manifestations

Answer 15

• not associated with bleeding, pt thrombose
• lupus inhibitor inhibits prostacyclin production or release from endothelial cells, leading to plt plug formation on healthy endothelium
• prostacyclin normally inhibits plt adhesion on healthy ECs

Question 16

prostacyclin and nitric oxide

Answer 16

released from ECs to prevent plt from sticking to healthy ECs

Question 17

lupus inhibitor lab diagnosis

Answer 17

• all phospholipid-dep tests affected
• APTT affected most
• APTT increased
• 50:50 mix (APTT) increased (doesn’t correct)
  - must determine that inhibitor is not heparin. Heparin may be neutralized with heparinase

Question 18

list all 6 confirmatory tests for lupus inhibitor

Answer 18

1. APTT w low phospholipid reagent (silica clotting time)
2. dilute russell viper venom time (DRVVT)
3. kaolin clotting time
4. dilute thromboplastin time (thromboplastin inhibition test**
5. platelet neutralization procedure (confirm DRVVT and KCT)
6. anti-cardiolipin

Question 19

silica clotting time (APTT w low phospholipid reagent)

Answer 19

• silica replaces kaolin or activator reagent in APTT
• if LI present, clotting time increased more than normal plasma

Question 20

dilute russell viper venom time (DRVVT)

Answer 20

• more dilute venom reagent than used in RVVT
• sensitive to lupus inhibitors
• if LI present, clotting time will be increased more than normal plasma

Question 21

kaolin clotting time

Answer 21

• kaolin initiates contact factors (XI, XII, PK, HMWK)
• LI inhibits initiation of contact factors
• if LI present then KCT increased (prolonged)

Question 22

dilute thromboplastin inhibition assay

Answer 22

• LI inhibits highly diluted thromboplastin
• diluting PT reagent prolongs the PT (if LI present then PT prolonged muuuch more than normal plasma)

Question 23

platelet neutralization procedure

Answer 23

• used to confirm prolonged DRVVT or KCT
• washed donor plts freeze and thaw (source of phospholipid)
• incubate pt plasma w platelets so that Ab can attach to plt phospholipid
• rerun DRVVT or KCT on plasma and if result is shortened by at least 10% then LI confirmed bc removed Ab in plt fraction

Question 24

anti-cardiolipin antibody

Answer 24

• anti-cardiolipin Ab and LI coexist in 60% of cases
• test by enzyme immune assay (Ag-bovine heart + pt plasma
• enzyme labeled anti-IgG and anti-IgM

Question 25

what is anti-beta-glycoprotein I

Answer 25

• polypeptide synthesized by hepatocytes, endothelial cells, and trophoblast cells
• thrombosis
• lupus inhibitor-like
• anti-phospholipid

Question 26

pathologic levels of anti-beta-GP1 Ab found in

Answer 26

• pt with APS
• SLE
• other systemic rheumatic diseases

Question 27

anti-beta-GP1 antibody detection

Answer 27

immunoassays and functional coag assays

Question 28

anti-phospholipid syndrome

Answer 28

• many cases no treatment necessary
• steroids may diminish effect
• plasmpheresis for emergency
• anti-thrombotic therapy of pt thrombosing
• may cause miscarriages
• leading cause of stroke in adults