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Diagnosing protein S deficiency - Navigating challenges.

Rasmus Søgaard Hansen1, Peter H Nissen2, Julie Brogaard Larsen2

  • 1Department of Clinical Biochemistry, University Hospital of Southern Denmark, Esbjerg, Denmark; Unit for Thrombosis Research, Department of Regional Health Research, University of Southern Denmark, Esbjerg, Denmark.

Clinical Biochemistry
|May 26, 2025
PubMed
Summary

Diagnosing protein S deficiency is challenging, as initial tests can be misleading. This case shows that even with genetic screening, definitive diagnosis requires careful interpretation of coagulation assays and PROS1 gene variants.

Keywords:
Factor V LeidenInfarctionPregnancyProtein S deficiencyThrombophilia

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Area of Science:

  • Hematology
  • Clinical Diagnostics
  • Genetics

Background:

  • Protein S deficiency is a risk factor for venous thromboembolism.
  • Accurate diagnosis is crucial for appropriate anticoagulation management.
  • Challenges exist in interpreting thrombophilia testing results, particularly in the context of other genetic variants.

Observation:

  • A pregnant woman experienced adrenal infarction, prompting thrombophilia testing.
  • Initial testing revealed low protein S (PS) and protein C (PC) activity, along with heterozygosity for factor V Leiden (FVL).
  • Subsequent testing, including PROS1 gene sequencing, did not confirm protein S deficiency.

Findings:

  • Factor V Leiden (FVL) can falsely lower protein S (PS) activity measurements.
  • A common PROS1 variant was identified but deemed likely benign.
  • Repeated testing showed fluctuating protein S (PS) levels, ultimately not meeting diagnostic criteria for deficiency.

Implications:

  • This case underscores the complexity of diagnosing protein S deficiency.
  • Clear guidelines are needed for the clinical utility of PROS1 genetic testing.
  • Accurate interpretation of coagulation assays and genetic data is essential for patient management.