Skip to main content

Nebulized heparin reduces levels of pulmonary coagulation activation in acute lung injury

Previously in this journal, we published a phase 1 study of nebulized heparin in patients with acute lung injury [1]. Patients were administered heparin at doses of 50,000, 100,000, 200,000, or 400,000 U/day for 2 days, and bronchoalveolar lavage (BAL) fluid samples were taken at baseline and after the last heparin dose. The study demonstrated a trend to reduced coagulation activation (prothrombin fragments) in BAL fluid after the last dose of nebulized heparin [1].

Following publication of these data, we were offered the possibility of further analysis of the BAL fluid with additional markers of coagulation activation, including thrombin-antithrombin complexes (TATcs), fibrin degradation products (FDPs), and plasminogen activator activity (PAI-1) levels. We wish to publish the results of this further analysis. The 400,000 U/day group had one patient more than the same group in the previously published data.

We found that TATc and FDP levels were significantly reduced in patients treated with 400,000 U/day of nebulized heparin, but not PAI-1 (Figure 1 overleaf). We believe that these data are important as they demonstrate for the first time that nebulized heparin significantly reduces coagulation activation in the lungs of critically ill patients with acute lung injury. This may be important knowledge as inflammatory mechanisms related to coagulation activation, such as hyaline membrane formation and microvascular thrombosis, may mediate lung injury [2, 3].

Figure 1

Changes in markers of coagulation activation in bronchoalveolar fluid before and after 2 days of nebulized heparin. Each line represents a single patient (*P < 0.01, **P < 0.001, paired t test). FDP, fibrin degradation product; NS, not significant; PAI-1, plasminogen activator activity; TATc, thrombin-antithrombin complex.



bronchoalveolar lavage


fibrin degradation product


plasminogen activator activity


thrombin-antithrombin complex.


  1. 1.

    Dixon B, Santamaria JD, Campbell DJ: A phase 1 trial of nebulised heparin in acute lung injury. Crit Care. 2008, 12: R64-10.1186/cc6894.

    PubMed Central  Article  PubMed  Google Scholar 

  2. 2.

    Dixon B: The role of microvascular thrombosis in sepsis. Anaesth Intensive Care. 2004, 32: 619-629.

    CAS  PubMed  Google Scholar 

  3. 3.

    Blaisdell FW: Pathophysiology of the respiratory distress syndrome. Arch Surg. 1974, 108: 44-49.

    CAS  Article  PubMed  Google Scholar 

Download references

Author information



Corresponding author

Correspondence to Barry Dixon.

Additional information

Competing interests

The authors declare that they have no competing interests.

Authors’ original submitted files for images

Below are the links to the authors’ original submitted files for images.

Authors’ original file for figure 1

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Dixon, B., Schultz, M.J., Hofstra, J.J. et al. Nebulized heparin reduces levels of pulmonary coagulation activation in acute lung injury. Crit Care 14, 445 (2010).

Download citation


  • Heparin
  • Lung Injury
  • Plasminogen
  • Prothrombin
  • Acute Lung Injury