Inhibitors

Question 1

Inhibitors

Answer 1

Abs against coagulation factors or other molecules

• Phospholipid-protein complex: Lupus anticoagulant & Anticardiolipin abs
• Coagulation factor inhibitors: F8 inhibitor

Question 2

Antiphospholipid Abs (APA)

Answer 2

1. LA
   - Pt with Lupus
   - Acquired auto-abs target proteins on phospholipids: prothrombin, b2GPI, protein C, protein S, annexin V
2. Anticardiolipin abs
   - Target complex of cardiolipin bound to b2GPI

Question 3

Annexin V

Answer 3

Prevent formation of coagulation –> When annexin V is interrupted by LA, more coagulation –> Thrombosis

Question 4

Clinical characteristic of LA

Answer 4

1-5% healthy people
Not all LA and APA have thrombosis
Can be assoc. with inflammation and infection
Requires 1 clinical + 1 lab criteria for Dx

Question 5

Testing for APA

Answer 5

1. Screen test: PTT, dRVVT, dPT
   Prolongation of PL-dependent clotting
2. Mixing test:
   Demonstrating an inhibitor effect
3. Confirmation :
   Add more PL to shorten the clotting time
4. R/O inhibitors of F8, 9, 11
   Evaluate if there’re other specific factor inhibitors & anticoagulant drugs

Question 6

Testing for LA

Answer 6

1. Hexagonal-phase PL: to bind all LA
2. Compare time:
   > 8s = LA present
   <8s = Factor deficiency or F8, 9, 11 inhibitor

Question 7

Testing for Anticardiolipin

Answer 7

ELISA: anticardiolipin; anti-B2GP1, anti-prothrombin

Question 8

F8 inhibitor

Answer 8

• Alloantibody target F8 (F8 is time and temp dependent)
• Most common
• Tendency to bleed
• Clinical: hemophilia, postpartum, immunologic disorder, idiopathic in elderly.

Question 9

Lab results in hemophilia A (inhibitor)

Answer 9

• Prolonged PTT
• Mixing test result: correct with the immediate test, incorrect with 1hr incubation 37C test
• If the titer is high, the immediate test may not correct

Question 10

Bethesda test

Answer 10

• Make dilutions of pt’s plasma
• Make a standard curve (normal pool plasma + buffer)
• Mix 1:1 with normal pool plasma, incubate 37C for 2 hrs
• Measure residual F8
• Reciprocal of dilution at 50% residue = Bethesda unit

Question 11

Hemophilia A treatment

Answer 11

< 5 Bethesda unit: F8 concentration, cryoprecipitate

5-30 Bethesda unit: Large infusion F8, Immunosuppressive, Recombinant F7, Recombinant F8

Question 12

APA treatment

Answer 12

No treatment
Oral anticoagulant
Aspirin
IV immunoglobulin

Question 13

Hemophilia B treatment

Answer 13

(F9 inhibitor)
Immunosuppressive therapy
Prothrombin - complex concentrates

Question 14

DRVVT test

Answer 14

Venom activate F10 (common pathway)
Dilute to make minimal PL
LA in pt's plasma will bind to PL and prolonged the clotting time
Not affected by F8
Prolonged can be seen:
- LA
- Deficiency of X, V, II, I
- Inhibitors of X, V, II, I