The following results were obtained from a 55-year-old female following an uneventful cholecystectomy:

Parameter

Patient Value

Adult Normal Range

Prothrombin time (PT)

16.0 sec

12.0 – 16.5

International normalised ratio (INR)

1.2

0.9 – 1.3

Activated partial thromboplastin time

(APTT)

56.0 sec*

27.0 – 38.5

Fibrinogen

2.8 g/L

2.0 – 4.0

Platelet count

223 x 109/L

150 – 350

APTT mixing study

52 sec

a) List three causes of these results. What further blood tests would help to differentiate between them? (20% marks)

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College answer

  • Lupus Anticoagulant
  • Heparin contamination
  • Artefact

Other tests:

  • Repeat APTT
  • Thrombin Time, Reptilase assay, Anticardiolipin Ab.

Discussion

The history (cholecystectomy, etc) does not seem to serve much of a purpose here, as it dis not appear to have factored into the college's answer. In summary, this is an isolated raised APTT which does NOT reverse with a mixing study. The patient's blood, as it is mixed with a normal sample, makes the normal sample coagulopathic. There must be some sort of anticoagulant factor in it. Which one?

The three major candidates are:

  • Heparin
  • Heparin-like anticoagulants (eg. in malignancy)
  • Antiphospholipid syndrome (lupus anticoagulant)
  • Multiple myeloma paraprotein
  • Thrombolytic therapy and DIC, due to the presence of large amounts of fibrin degradation products which interfere with the polymerisation of fibrin (though in this case the fibrin level is normal)

The following tests are reasonable:

  • Test antiphospholipid antibodies
  • Heparinase assay:
    • The heparinase enzyme rapidly degrade heparin. If there is heparin in the sample and it is responsible for the raised APTT, the heparinase will reverse the coagulopathy.
  • If the patient has had no heparin, order a thrombin time and reptilase time.
    • Heparin will affect thrombin time but not reptilase time.
    • Heparin-like anticoagulants will also affect thrombin time but not reptilase time.
    • Weird disturbances of fibrinogen cleavage will elevate both thrombin and reptilase time, and these include excessive fibrin degradation byproducts, paraprotein, amyloidosis, and so forth.


 

References

References

Kamal, Arif H., Ayalew Tefferi, and Rajiv K. Pruthi. "How to interpret and pursue an abnormal prothrombin time, activated partial thromboplastin time, and bleeding time in adults." Mayo Clinic Proceedings. Vol. 82. No. 7. Elsevier, 2007.

DeMuro, J. P., and A. F. Hanna. "Trauma Induced Coagulopathy: Prevention and Intervention."Scand J Trauma Resusc Emerg Med 20.47 (2014): 4.

White, Julian. "Snake venoms and coagulopathy." Toxicon 45.8 (2005): 951-967.

Kashuk, Jeffry L., et al. "Primary fibrinolysis is integral in the pathogenesis of the acute coagulopathy of trauma." Annals of surgery 252.3 (2010): 434-444.

De Stefano, Valerio, Guido Finazzi, and Pier Mannuccio Mannucci. "Inherited thrombophilia: pathogenesis, clinical syndromes, and management [see comments]." Blood 87.9 (1996): 3531-3544.

Hunt, Beverley J. "Bleeding and coagulopathies in critical care." New England Journal of Medicine 370.9 (2014): 847-859.