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Abdul Mannan: APTT Mixing Studies Confuse a Lot of People
Dec 19, 2025, 05:54

Abdul Mannan: APTT Mixing Studies Confuse a Lot of People

Abdul Mannan, Consultant Haematologist at Betsi Cadwaladr University Health Board, shared on LinkedIn:

”APTT mixing studies confuse a lot of people.

Let me show you why the incubated step matters.

Factor VIII is thermally labile. At 37°C, it naturally decays over 1-2 hours.

This isn’t pathology—it’s normal biology.

But here’s the trick: this can look exactly like a time-dependent inhibitor if you’re not careful.

The solution? Run parallel tests.

Here’s what you need to know:

  • Test both immediate AND incubated samples (at 2 hours)
  • Compare patient plasma alone vs 1:1 mix with normal pooled plasma
  • Normal thermal decay: slight drift in both NPP and 1:1 mix
  • Time-dependent inhibitor: the 1:1 mix prolongs MORE than NPP control
  • Golden rule: If Δ(1:1 Mix) > Δ(NPP Control), think inhibitor

The pattern tells the story.

Normal FVIII lability shows similar small shifts in both tubes.

A true inhibitor shows clearly more prolongation in the mix than the control—it’s time AND temperature dependent, not just thermal drift.

Pro tip: Always use properly buffered conditions (Nijmegen-modified) for stability.

Thaw plasma promptly at 37°C and test without delay for routine assays. If you’re uncertain, measure

FVIII:C before and after incubation.

What’s the most challenging APTT mixing study pattern you’ve interpreted recently?”

Abdul Mannan: APTT Mixing Studies Confuse a Lot of People

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