Coagulation and Clotting Flashcards

Question

Bethesda assay

Answer 1

- also called factor VIII inhibitor assay, anti-factor VIII antibody assay - Factor VIII is the most common factor to which antibodies arise - can be adapted to any factor - Anti-factor VIII antibodies have characteristic properties - they behave as inhibitors in coagulation screen assays (fails to correct with 1:1 mix, especially after 1-4 hour incubation - time dependance) - if factor assays are performed, factor VII will appear decreased and serial dilutions wills how progressively more factor VIII activity -------------- procedure: - make several dilutions of patient plasma with citrated saline - each mixed 1:1 with normal plasma and incubated for 1-2 hours - Factor VIII activity assays are then performed on each dilution - the dilution at which the factor VIII activity is 50% represents the inhibitor titer. - Bethesda units are the dilution factor for 50% activity (e.g.. 1:16 = 16 Bethesda units) - 5 the antibody cannot be overcome with high doses of human factor VIII. (use porcine factor VIII, activated prothrombin complex concentrate APCC, or recombinant factor VII NovoSeven

Answer 2

- D-dimers are formed by factor XIII when it cross links D regions of fibrin molecules - later, the fibrin clot is disassembled by plasmin, which is incapable of breaking up D-dimers - NOT formed in the plasmin-mediated degradation of fibrinogen, but rather released into circulation - Presence of D-dimer indicates that fibrin has been formed and then degraded - Assays for FDPs are a little less specific because they detect fibrin degrading products, fibrinogen degradation products, and D-dimer - most often increased in thrombosis and significant bleeding - may be elevated in atrial fibrillation and CHF - cirrhotic patients may have persistent elevation because of difficulty clearing - some cancers cause elevation (mucin-secreting adenocarcinomas) - DIC - widely applied to the diagnosis of venous thromboembolism and PE, negative predictive value is most useful, especially in patients with low pretest probability

Answer 3

- II, V, VII, VIII, IX, X, XI, XII - patient plasma is mixed with reagent plasma having a known factor deficiency - resulting PT or PTT is compared to standard curve, generated by plotting known factor levels against clotting times. - Factor VIII, IX, XI, and XII assays are PTT based - Factor II, VII, and X assays are PT based - Factor V can be either - serial dilutions are usually used - an inhibitor is suggested if serial dilutions result in an apparent increase in factor activity - isolated inherited factor deficiencies are less common than multiple acquired factor deficiencies (DIC, liver disease, coumadin)

Answer 4

- very similar to Thrombin time assay - excess thrombin is added to diluted patient's plasma - use standard curve to determine activity

Answer 5

Type 1 - quantitative decrease in vWF - mild to moderate bleeding - most common 70-80% of cases - normal molecules of factor Type 2 - qualitative deficiencies with functional abnormalities of vWF - quantity is often reduced too - 20-30% of cases - can be severe bleeding, but usually mild to moderate - Four subtypes - 2A - loss of high-molecular-weight multimers (defective assembly and secretion, or increased rate of proteolyzed) - 2B - mutations lead to increased binding of vWF to GP1b (platelet receptor) and resulting increased clearance of factor and platelets - "Platelet type" or "pseudo vWD" is rare disorder that is similar to type 2B, except the mutation in on the platelet GP1b gene instead of VWF gene. leads to increased binding and increased clearance - 2M - decreased function with normal sized multimers. impaired binding of vWF to GP1b - 2N - (normandy) mutations are located withing factor VIII binding site. Factor VIII half-life is shorter. vWF is normal. Often misdiagnosed as hemophilia A Type 3 - severe bleeding - very rare .5- 5.3 per million - quantitative deficiency so severe that vWF is often undetectable