Vitamin K deficiency may account for roughly 30% of all coagulopathy referrals, surpassing inherited causes as the leading driver of abnormal bleeding diagnoses, according to a recent review.
Investigators highlighted that a factor (F) II/FIIE ratio of less than 0.86, or an absolute difference of FIIE minus FII of greater than 0.045 U/mL, had strong specificity for diagnosing vitamin K deficiency even in the presence of liver disease. In the 2025 International Society on Thrombosis and Haemostasis scoring revision, a total disseminated intravascular coagulation (DIC) score of 5 or greater was found to correlate with overt DIC, with D-dimer levels more than seven times the upper normal limit earning three diagnostic points. Among rare disorders, FXIII deficiency occurred in approximately one in 3 million patients, with a minimum factor XIII activity of 31% required to prevent bleeding. Combined FV and FVIII deficiency (F5F8D) had an estimated prevalence of one in 2 million, while specific F5 mutations (F5 Atlanta, F5 East Texas, and F5 Amsterdam) prolonged the prothrombin time (PT) by 5 to 13 seconds and activated partial thromboplastin time (APTT) by 15 to 22 seconds without factor deficiency.
The investigators designed a structured diagnostic approach using first-line laboratory screening tests—including PT, international normalized ratio, APTT, thrombin time, and Clauss fibrinogen assay—to differentiate common and rare bleeding disorders. The investigators emphasized that acquired vitamin K deficiency and liver disease remain the predominant causes of coagulopathy, whereas lupus anticoagulant and DIC accounted for smaller but clinically significant proportions. PT/international normalized ratio prolongation was shown to be the most sensitive initial marker for vitamin K deficiency because of the short half-life of FVII, whereas concurrent PT and APTT prolongations indicated multiple vitamin K–dependent F deficiencies (II, IX, X).
Liver disease–related coagulopathy, observed more frequently among hospitalized patients, produced reduced levels of FVII, FXI, and FXII and lower fibrinogen concentrations with disease progression, but typically preserved FVIII synthesis. The International Society on Thrombosis and Haemostasis 2025 scoring revisions improved diagnostic performance for DIC by integrating platelet counts, fibrinogen levels, and D-dimer thresholds.
“The diagnosis of rarer conditions requires strategic consideration of more specialized investigations that are appropriate for investigating a patient's bleeding problem before concluding that the cause must be a ‘bleeding problem of unknown cause’,” noted study authors Rabab Al Dawood, of the Hamilton Health Sciences at the McMaster University Medical Center at the Hamilton Regional Laboratory Medicine Program as well as the Department of Pathology and Molecular Medicine at the Health Science Center at McMaster University, and Catherine P. M. Hayward, of the Department of Medicine at the Health Science Center at McMaster University.
The authors have no conflicts of interest.
Source: Pathology