The prothrombin time (PT) and activated partial thromboplastin test (aPTT) are common screening tests for the coagulation cascade. If one or both of these tests is abnormal, retesting of the sample after addition of normal plasma can help separate a deficiency state from the presence of an inhibitor.
"Mixing" studies: If a screening test is abnormal, then a 50:50 mixture of the patient's sample with normal plasma is prepared and tested.
(1) If the problem is a deficiency of a coagulation factor: Usually only about 10% of a coagulation factor is required for a normal test. Addition of normal plasma is sufficient to raise the factor level to sufficient to normalize the test.
(2) An inhibitor will not be affected by the addition of a source of coagulation factors and the test will remain prolonged.
|
Result |
Corrected in Mixing Studies |
Not Corrected in Mixing Studies |
|
PT abnormal, PTT normal |
Factor 7 deficiency |
Factor 7 inhibitor lupus-like inhibitor |
|
PT normal, PTT abnormal patient bleeding |
Factor 8 deficiency (including von Willebrand's disease) Factor 9 deficiency Factor 11 deficiency |
Factor 8 inhibitor Factor 9 inhibitor Factor 11 inhibitor nonspecific (anti-phospholipid) heparin |
|
PT normal, PTT abnormal patient clinically normal |
as above, plus: Factor 12 deficiency deficiency prekallikrein deficiency HMW kininogen |
as above, plus: Factor 12 inhibitor
|
|
PT and PTT both abnormal |
multiple factor deficiency fibrinogen deficiency Factor 2 deficiency Factor 5 deficiency Factor 10 deficiency |
Factor 2 inhibitor Factor 5 inhibitor Factor 10 inhibitor nonspecific (anti-phospholipid) heparin |
Limitations:
• A low concentration of an inhibitor may be sufficient to prolong a test in the patient sample, but may be too low to prolong the 50:50 mixture sample. Thus, the mixing studies are more effective when the screening test is 1.5 times the upper limit of the reference range as compared to only a few seconds prolonged.
• Normal control material should not be used for mixing studies since this may have been modified by the manufacturer.
• Finding a laboratory to test for deficiencies of prekallikrein or HMW kininogen may be difficult.
• Some immune inhibitors require incubation of the mixed sample before the inhibition is apparent.
Specialty: Hematology Oncology, Clinical Laboratory
ICD-10: ,
