Section 10: Inhibitors Flashcards
inhibitor definition
antibody directed against single or multiple coag factors
effect of inhibitors
mostly bleeding
sometimes thrombosis
true autoantibody
- alter function or promote rapid clearance of factor(s)
- autoimmune disease, malignancy, pregnancy, advanced age
factor VIII:C inhibitor
- antibodies that prevent VIII replacement therapy from controlling bleeding in hemophilia A pt
- hemophilia pt-complication of treatment
- non-hemophilia pt get acquired hemophilia
acquired hemophilia
- 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)
factor VIII:C inhibitor lab diagnosis
- PT normal
- APTT prolonged
- 50:50 mix (APTT) remains prolonged bc Ab bind FVIII in normal plasma too
T/F FVIII inhibitors are time and temp dependent so incubate 50:50 mix at 37°C for max performance
True
T/F
only some factor specific inhibitors are possible
False
can make factor specific inhibitor to any coag factor
which anti-phospholipid antibody groups exist?
- anticardiolipin
- lupus anticoag
- anti-beta2 glycoprotein-1
- other antibodies
anti-phospholipid antibodies (APL)
- rare and asymptomatic
- most arise as response to infection or treatment with certain drugs most disappear within 12 weeks
- recurrent thrombotic disease have APL
list autoimmune-associated APL Ab
SLE
RA
Sjogrens syndrome
anti-phospholipid syndrome (APS) clinical symptoms
- thrombosis
- pregnancy complications
- unexplained cutaneous circulatory disturbances (blood flow issues)
- thrombocytopenia
- hemolytic anemia
- nonbacterial thrombotic endocarditis
lupus inhibitor specificity
not specific for any coag factor
lupus inhibitor pathophysiology
does not react w endogenous platelet phospholipid but does react with phospholipid in test systems
lupus inhibitor clinical manifestations
- 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
prostacyclin and nitric oxide
released from ECs to prevent plt from sticking to healthy ECs
lupus inhibitor lab diagnosis
- 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
list all 6 confirmatory tests for lupus inhibitor
- APTT w low phospholipid reagent (silica clotting time)
- dilute russell viper venom time (DRVVT)
- kaolin clotting time
- dilute thromboplastin time (thromboplastin inhibition test**
- platelet neutralization procedure (confirm DRVVT and KCT)
- anti-cardiolipin
silica clotting time (APTT w low phospholipid reagent)
- silica replaces kaolin or activator reagent in APTT
- if LI present, clotting time increased more than normal plasma
dilute russell viper venom time (DRVVT)
- more dilute venom reagent than used in RVVT
- sensitive to lupus inhibitors
- if LI present, clotting time will be increased more than normal plasma
kaolin clotting time
- kaolin initiates contact factors (XI, XII, PK, HMWK)
- LI inhibits initiation of contact factors
- if LI present then KCT increased (prolonged)
dilute thromboplastin inhibition assay
- LI inhibits highly diluted thromboplastin
- diluting PT reagent prolongs the PT (if LI present then PT prolonged muuuch more than normal plasma)
platelet neutralization procedure
- 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
anti-cardiolipin antibody
- 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
what is anti-beta-glycoprotein I
- polypeptide synthesized by hepatocytes, endothelial cells, and trophoblast cells
- thrombosis
- lupus inhibitor-like
- anti-phospholipid
pathologic levels of anti-beta-GP1 Ab found in
- pt with APS
- SLE
- other systemic rheumatic diseases
anti-beta-GP1 antibody detection
immunoassays and functional coag assays
anti-phospholipid syndrome
- 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
