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Chokri Ben Lamine: The Two-Hit Model of TRALI
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Jul 7, 2026, 20:58

Chokri Ben Lamine: The Two-Hit Model of TRALI

Chokri Ben Lamine, Assistant Consultant at King Faisal Specialist Hospital and Research Center, shared a post on X:

“1.TRALI – transfusion-related acute lung injury 

Acute hypoxemia with non-cardiogenic pulmonary edema during or within 6h of transfusion.

Key DDx: TACO leads to hydrostatic and cardiogenic edema.

2.2019 definition matters

  • TRALI type I: no ARDS risk factor
  • TRALI type II: ARDS risk factor or mild ARDS, but respiratory status worsens temporally after transfusion.

Think ‘transfusion-triggered permeability edema.’

3.Pathogenesis is not one pathway

TRALI may be driven by:

  • anti-HLA and anti-HNA antibodies
  • biological response modifiers: lipids, proteins, extracellular vesicles

Final common pathway: ROS causes endothelial injury, leading to alveolar leak..

4.Classic 2-hit model

  • 1st hit: patient illness causes endothelial activation and neutrophil priming
  • 2nd hit: transfused antibodies or BRMs trigger neutrophil activation

Result: ROS burst causes pulmonary capillary leak

5.Antibody-mediated TRALI

Common culprits:

  •  anti-HLA class I
  • anti-HLA class II
  • anti-HNA antibodies

But antibody detection alone is not enough; need antigen–antibody concordance.

6.Six proposed pathways 

  • Two-hit neutrophil activation
  • Monocyte with neutrophil dependent
  • Endothelium–FcR–platelet–NET pathway
  • Direct monocyte activation
  • Direct endothelial activation
  • Endothelium–complement–monocyte pathway

7.NETs may amplify injury 

Neutrophils can release NETs, which interact with platelets and worsen endothelial damage.

DNase and NET-disruption reduced TRALI severity in experimental models.

Clinical translation still uncertain.

8.Why male-predominant plasma?

Prevention aims to reduce exposure to donor leukocyte antibodies.

Strategies include:

  • male-predominant plasma
  • HLA and HNA antibody screening
  • solvent or detergent plasma
  • platelet additive solutions

9.Treatment is supportive 

No proven targeted therapy yet.

Practical approach:

  • stop transfusion
  • notify blood bank
  • oxygen and ventilatory support
  • avoid unnecessary diuretics unless TACO possible
  • investigate donor antibodies when feasible

10.Pearl

  • TRALI is permeability edema, not volume overload.
  • TACO improves with diuresis; TRALI needs respiratory support and haemovigilance investigation.
  • When unsure: treat urgently, report immediately, and reassess volume and cardiac status.”

Other posts featuring Chokri Ben Lamine on Hemostasis Today.

Acute hypoxemia anti-HLA anti-HNA ARDS Blood Cardiology Chokri Ben Lamine Extracellular Vesicles Health Hematology Hemostasis News Hemostasis Today lipids Medicine proteins pulmonary edema TRALI
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