Main Causes of Correction on aPTT Mixing Test
Correction on an aPTT mixing test indicates coagulation factor deficiency, where the normal plasma provides the missing clotting factors to normalize the prolonged aPTT. 1, 2
Primary Causes of Correction
Inherited Factor Deficiencies
- Hemophilia A (Factor VIII deficiency) is the most common inherited cause, presenting with isolated low Factor VIII activity and immediate correction on mixing studies 3, 2
- Hemophilia B (Factor IX deficiency) also corrects immediately when mixed with normal plasma 2
- Factor XI deficiency causes prolonged aPTT that corrects with normal plasma, though bleeding tendency is typically mild 4
- Factor XII deficiency produces extremely prolonged aPTT with complete correction on mixing, but notably causes no bleeding tendency whatsoever 5
Acquired Factor Deficiencies
- Von Willebrand disease presents with low Factor VIII levels (as VWF stabilizes Factor VIII in circulation) and corrects on mixing studies 3, 2
- Vitamin K deficiency can prolong aPTT when severe, correcting with normal plasma that contains adequate vitamin K-dependent factors 6, 5
- Liver disease causes multiple factor deficiencies that correct on mixing, though often affects both PT and aPTT 6
Interpretation Algorithm
Immediate Mixing Study Results
- Correction immediately after mixing (Rosner index <11%) indicates factor deficiency rather than inhibitor presence 2, 7
- The normal plasma in the 1:1 mix provides sufficient clotting factors to normalize the aPTT if deficiency is the sole problem 1, 8
Critical Caveat
- Immediate correction does not completely exclude acquired hemophilia A, so if clinical bleeding is present, proceed with Factor VIII inhibitor workup (Bethesda assay) regardless of mixing study correction 2, 7
- Both factor deficiency and lupus anticoagulant can coexist, so lupus anticoagulant testing should still be performed even when mixing corrects 2
Follow-Up Testing After Correction
Specific Factor Assays Required
- Measure Factor VIII activity level as the first priority, since Factor VIII deficiency is the most clinically significant cause 2, 7
- If Factor VIII is isolated and low, distinguish between hemophilia A and von Willebrand disease by measuring VWF:RCo and VWF:Ag 3
- Perform specific factor assays for factors IX, XI, and XII to identify the exact deficiency, as this facilitates accurate diagnosis and management 1
Exclude Confounding Variables
- Rule out heparin contamination by checking thrombin time or reviewing medication history, as heparin can artifactually prolong aPTT 2, 7
- Consider warfarin effect and defer testing until INR <1.5, or wait 1-2 weeks after discontinuation if INR is 1.5-3.0 2, 7
- Multiple factor deficiencies prolong aPTT more than single factor deficiency, requiring different interpretation thresholds 9
Common Pitfalls to Avoid
- Do not assume correction excludes all pathology: approximately 40% of patients show evidence of both deficiency and inhibitor on comprehensive testing 9
- Artifactual results occur in 5% of cases, including issues with blood draw technique, sample processing, or laboratory error 6
- Lupus anticoagulant can cause artifactual lowering of factor levels through phospholipid inhibition in the assay; repeat at higher dilutions if suspected 2
- Patient stress, recent exercise, pregnancy, or inflammatory illness can falsely elevate Factor VIII and VWF levels, potentially masking mild deficiencies 3