P3. Molecular background of acquired thrombophilia. Fibrin stabilization and the study of soluble fibrin monomers

Question 1

Characteristics of Antiphospholipid syndrome

Answer 1

-One of the most common acquired thrombophilias
-systemic autoimmune disease

Question 2

Symptoms of Antiphospholipid syndrome

Answer 2

(arterial or venous) thrombosis, pregnancy morbidities

Question 3

Antiphospholipid syndrome
-> What is the inducing epitope?

Answer 3

a phospholipid-protein complex

Question 4

What are the 2 most antiphospholipids?

Answer 4

-anti-phospholipid-prothrombin-IgG
-anti-phospholipid-β2-glycoprotein 1-IgM

Question 5

What are the -2 main routes of patomechanism:

Answer 5

-binding to anionic phospholipids (cardiolipin, PS)
-binding to protein cofactors (prothrombin, protein C, protein S)

Question 6

describe -binding to protein cofactors (prothrombin, protein C, protein S) (a route of patomechanism)

Answer 6

-binding to protein cofactors (prothrombin, protein C, protein S)
-> Inhibition of anticoagulant and fibrinolytic system -
- binding to β2-glycoprotein 1
-> Cell activation by antibody-β2-glycoprotein1 complex

Question 7

What are Physiological functions of ß2-GP1?

Answer 7

• A part of the innate immune system(„clean up protein”)
• Circulates in a cyclic form
• 2-3: scavenging bacterial lipopolysaccharides via LRP receptors
• 4: scavenging apoptotic membrane particles

Question 8

What is the consequence of Constant high levels of antibodies (due to unknown deficiency of the immune system)?

Answer 8

A) inhibiting of fibrinolytic or anticoagulant protein-phospholipid complexes
B) facilitating of clotting via effect on blood coagulation cell receptors

Question 9

Phospholipid dependent reactions of haemostasis, Apparent contradiction in APS diagnostics

Answer 9

Question 10

Treatment for APS

Answer 10

-70% of patients are asymptomatic: treatment is not needed
-after thrombosis: long-term anticoagulant treatment (coumarins) INR (PTR): 2,5-3,5 (plus heparin on the first few days)
-in pregnancy: heparin+aspirin

Question 11

Molecular mechanism of Ethanol gelation test

Answer 11

Question 12

Study of the stability of fibrin
-> What are mechanisms?

Answer 12

1. fibrinogen+thrombinfibrin
2. time+glutaraldehydecovalent crosslink between Lys-s (Schiff-base)
   (in vivo FXIIIa: isopeptide links between Lys-s & Glu-s)(also covalent )
3. Urea: dissolves noncovalently polymerised fibrin (tube 1), but not
   covalently crosslinked fibrin (tube 2)

Question 13

Fibrin forming and stabilization

Answer 13