Lab: hypercoagulability assays (lupus anticoagulant, protein C/S, HIT studies, molecular)

6 ASCP MLS practice questions on Lab: hypercoagulability assays (lupus anticoagulant, protein C/S, HIT studies, molecular), part of Hematology. The first 6 are below; the first 5 with answers and explanations (tap Show answer after you have chosen), the rest in Learn with a free account.

1. Question 1 · Hard

   A 36-year-old woman had an unprovoked deep vein thrombosis 6 months ago. She stopped rivaroxaban 4 weeks ago and takes no hormones or other anticoagulants. Thrombophilia results: modified APC resistance ratio 1.6 (reference above 2.0); factor V Leiden genotyping heterozygous; protein C activity 102% and antithrombin activity 98% (reference 70-140%). Protein S: clot-based activity 38% (reference 60-140%), free antigen 91% (reference 60-140%), total antigen 104% (reference 70-140%). What is the best interpretation of her protein S results?

   1. AFalsely low activity caused by factor V Leiden
   2. BType III protein S deficiency
   3. CResidual rivaroxaban lowering the activity
   4. DType II (functional) protein S deficiency

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   Answer: A · Falsely low activity caused by factor V Leiden

   The clot-based protein S assay measures how much the patient's protein S helps added activated protein C to prolong a clotting time. Factor Va Leiden resists cleavage by activated protein C, so the clotting time lengthens less and protein S activity reads falsely low. With normal free and total antigen, this interference is the best explanation; type II deficiency can be diagnosed only once factor V Leiden and other interferences are excluded. Type III deficiency would show a low free antigen with a normal total antigen. Rivaroxaban would prolong clotting times and falsely raise, not lower, the activity, which is one reason many laboratories use free protein S antigen as the first test.

   • B: Type III shows a low free antigen with a normal total antigen; her free antigen is normal.
   • C: Factor Xa inhibitors prolong clotting times and falsely raise clot-based protein S activity.
   • D: Type II deficiency is diagnosed only after factor V Leiden and other interferences are excluded.

2. Question 2 · Medium

   Thrombophilia testing 3 months after stopping warfarin: protein C activity (chromogenic) 36% (reference 70-140%), protein C antigen 94% (reference 70-140%), liver tests normal. The most likely diagnosis is:

   1. AType I protein C deficiency
   2. BType II protein C deficiency
   3. CFactor V Leiden effect
   4. DResidual warfarin effect

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   Answer: B · Type II protein C deficiency

   Protein C activity is measured first because it detects both kinds of inherited deficiency. A low activity with a normal antigen means the protein is made in normal amounts but works poorly, which defines type II deficiency. In type I, activity and antigen are reduced together. Warfarin, liver disease and acute thrombosis all lower protein C, so they must be excluded before calling a deficiency inherited.

   • A: Type I deficiency lowers activity and antigen together.
   • C: Factor V Leiden can affect clot-based assays, but not chromogenic ones.
   • D: The warfarin effect is gone well before 3 months after stopping.

3. Question 3 · Hard

   A 35-year-old woman taking rivaroxaban for an unprovoked DVT is tested for lupus anticoagulant. The dRVVT normalized ratio is 1.45 (positive above 1.20). The best interpretation of this result is:

   1. AA confirmed lupus anticoagulant
   2. BHeparin in the sample
   3. CPossibly a rivaroxaban effect
   4. DAcquired factor X deficiency

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   Answer: C · Possibly a rivaroxaban effect

   Rivaroxaban and other factor Xa inhibitors prolong the dRVVT screen more than the confirm step, which can produce a false-positive ratio. ISTH guidance therefore advises against lupus anticoagulant testing during DOAC therapy. The options are to retest after the drug has been stopped long enough, or to treat the sample with a DOAC-removal agent such as activated charcoal before testing. A positive result in a patient on a DOAC is reported with a comment, not as a confirmed lupus anticoagulant.

   • A: A drug effect must be excluded before the result can be called a lupus anticoagulant.
   • B: Most dRVVT reagents neutralize heparin, and she is not taking heparin.
   • D: Factor X deficiency prolongs screen and confirm equally, so the ratio stays normal.

4. Question 4 · Hard

   A 70-year-old woman on unfractionated heparin after hip surgery has a platelet fall from 280 to 120 × 10^3/µL (120 × 10^9/L) on day 7; her 4Ts score is 5 (intermediate). A PF4-heparin IgG ELISA gives an optical density of 0.62 (positive at 0.40 or more). Which test best confirms HIT?

   1. APlatelet-associated IgG assay
   2. BPolyspecific PF4-heparin ELISA
   3. CLupus anticoagulant testing
   4. DSerotonin release assay

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   Answer: D · Serotonin release assay

   PF4-heparin immunoassays are very sensitive, so a negative result makes HIT unlikely, but they also detect many antibodies that do not activate platelets. A weakly positive optical density such as 0.62 is often found without true HIT. The serotonin release assay is a functional test: patient serum releases labelled serotonin from donor platelets at low heparin concentrations, and high heparin suppresses the release. While the result is pending, heparin is stopped and a non-heparin anticoagulant is given.

   • A: Platelet-associated IgG is nonspecific and is not used to diagnose HIT.
   • B: A polyspecific assay also detects IgA and IgM, which makes it less specific.
   • C: Lupus anticoagulant tests do not detect heparin-dependent antibodies.

5. Question 5 · Easy

   Which pair of tests do ISTH guidelines recommend for detecting a lupus anticoagulant?

   1. AdRVVT and an LA-sensitive aPTT
   2. BPT and thrombin time
   3. CFibrinogen and D-dimer
   4. DAnticardiolipin and anti-β2-glycoprotein I

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   Answer: A · dRVVT and an LA-sensitive aPTT

   Lupus anticoagulants vary in which phospholipid-dependent test they prolong, so ISTH advises two tests based on different principles: the dilute Russell viper venom time and an aPTT made sensitive with low phospholipid and a silica activator. Each is run as screen, mix and confirm steps, and a positive result in either test is enough. Anticardiolipin and anti-β2-glycoprotein I antibodies are measured separately by immunoassay. A positive result is repeated after at least 12 weeks to show persistence.

   • B: The PT and thrombin time are insensitive to most lupus anticoagulants.
   • C: Fibrinogen and D-dimer do not detect phospholipid-dependent inhibitors.
   • D: These immunoassays detect related antibodies but not lupus anticoagulant activity.

6. Question 6 · Medium

   A thrombophilia workup shows a modified APC-resistance ratio of 1.5 (reference above 2.0), with normal protein C, protein S and antithrombin. Which test should follow?

   1. AProtein C antigen assay
   2. BFactor V Leiden (R506Q) genotyping
   3. CProthrombin G20210A genotyping
   4. DFactor V activity assay

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