Low plasma protein Z levels are associated with an increased risk for perioperative bleedings

Eur J Haematol. 2018 May;100(5):403-411. doi: 10.1111/ejh.13031. Epub 2018 Mar 26.


Background and objectives: Protein Z (PZ) deficiency has been implicated both in bleeding diatheses and in thrombophilia. Considering its ambiguous nature and the conflicting clinical data so far, we set out to evaluate the impact of low PZ on perioperative bleeding in patients who underwent surgical (ENT) interventions involving a high risk of bleeding.

Patients and methods: After exclusion of other coagulation disorders, 154 Patients were stratified into quartiles according to PZ plasma concentrations to evaluate the relation between PZ and bleeding complications.

Results: Low PZ levels were associated with increased blood loss (P < .001), increased need for blood transfusions (P < .001), and a higher rate of surgical revisions (P = .009) in a concentration-dependent fashion. Low PZ caused earlier (within 24 hours) and repetitive bleedings (P = .005). The number of major bleeding episodes was significantly increased when low PZ was combined with bleeding history (P < .05). Finally, ROC analyses confirmed the predictive value of low PZ for bleeding complications and PZ-thresholds for clinical practice were determined.

Conclusions: Low PZ appears to be an underestimated risk factor for perioperative bleeding. Determination of PZ plasma concentrations might be useful in the preoperative workup in patients with a bleeding history, when detailed clotting analyses remain inconclusive.

Keywords: haemorrhage; protein Z; surgery.

MeSH terms

  • Adolescent
  • Adult
  • Biological Variation, Population
  • Biomarkers
  • Blood Coagulation
  • Blood Loss, Surgical
  • Blood Proteins*
  • Child
  • Female
  • Hemorrhage / blood*
  • Hemorrhage / diagnosis
  • Hemorrhage / etiology*
  • Humans
  • Male
  • Middle Aged
  • Perioperative Period*
  • ROC Curve
  • Reproducibility of Results
  • Risk Assessment
  • Risk Factors
  • Severity of Illness Index
  • Surgical Procedures, Operative / adverse effects*
  • Surgical Procedures, Operative / methods
  • Young Adult


  • Biomarkers
  • Blood Proteins
  • plasma protein Z