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Thromb Haemost
DOI: 10.1055/a-2798-3385
Invited Editorial Focus

Guiding Surgical Haemostasis in Inherited Factor VII Deficiency: Looking beyond Coagulation Factor Levels

Authors

  • Eva Soler-Espejo

    1   Department of Hematology, Hospital Clínico Universitario Virgen de la Arrixaca, University of Murcia, Instituto Murciano de Investigación Biosanitaria Pascual Parrilla (IMIB-Pascual Parrilla), Murcia, Spain
    2   Liverpool Centre of Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool Heart and Chest Hospital, Liverpool, United Kingdom

  • Vanessa Roldán 

    1   Department of Hematology, Hospital Clínico Universitario Virgen de la Arrixaca, University of Murcia, Instituto Murciano de Investigación Biosanitaria Pascual Parrilla (IMIB-Pascual Parrilla), Murcia, Spain

  • Francisco Marín 

    3   Department of Cardiology, Instituto Murciano de Investigación Biosanitaria Pascual Parrilla (IMIB-Pascual Parrilla), Hospital Clínico Universitario Virgen de la Arrixaca, University of Murcia, CIBERCV, Murcia, Spain

Funding Information This publication is part of Action 23042/GERM, funded by FSRM/10.13039/100007801.
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Inherited factor VII deficiency (FVIID) is the most frequent of the rare autosomal-recessive bleeding disorders. Its hallmark is the weak correlation between factor VII coagulant activity (FVII:C) and the clinical phenotype,[1] with individuals at comparable levels ranging from asymptomatic to experiencing life-threatening hemorrhage.[2] This variability complicates perioperative planning and has traditionally forced clinicians to rely on empirical thresholds that inadequately predict bleeding risk while balancing the competing hazards of hemorrhage and thrombosis.[3]

In this issue of Thrombosis and Haemostasis, García-Jaén et al[4] provide timely multicenter data that advance perioperative management in this disorder. Their cohort of 215 patients undergoing 380 procedures across 17 Spanish centers (2016–2024) constitutes the largest surgical series in FVIID to date. The study describes real-world use of tranexamic acid (TA) and recombinant activated factor VII (rFVIIa), and examines outcomes in relation to baseline FVII:C, bleeding history, and procedural risk—offering a pragmatic, phenotype-guided framework that moves beyond rigid factor-level cut-offs.

Most procedures were performed in patients with mild deficiency (FVII:C > 20 IU/dL), with fewer in moderate (10–20 IU/dL) or severe (<10 IU/dL) cases. rFVIIa prophylaxis was used in around 63% of high-risk (HR) and 43% of low-risk (LR) interventions, typically at 15 to 30 µg/kg every 4 to 6 hours for 1 to 3 days.[5] [6] Bleeding occurred in 12 procedures (3.1%), all in mild deficiency, and 92% in individuals with an International Society on Thrombosis and Haemostasis-Bleeding Assessment Tool (ISTH-BAT)[7] score ≥ 3 who had received no rFVIIa or only TA. No bleeding occurred in moderate or severe deficiency, all of whom received rFVIIa cover.

Multivariable analyses showed that treatment decisions were mainly driven by FVII:C level and surgical category, whereas bleeding correlated best with the combination of bleeding score and procedural risk.[8] These findings informed a simple algorithm: rFVIIa prophylaxis for all procedures in moderate and severe deficiency, and in mild deficiency only for HR surgery or LR procedures when the bleeding score ≥ 3. This model reproduced two-thirds of real-world practice and correctly identified most bleeding events.

While clinically robust, such universal prophylaxis in moderate deficiency invites reflection. Given the strong predictive value of individual bleeding phenotype, it remains uncertain whether all moderately deficient patients require replacement therapy for LR procedures. Some clinically quiescent individuals—particularly those without significant bleeding history—may be safely managed with antifibrinolytics alone, provided meticulous local hemostasis is ensured. Future prospective and registry-based studies will be essential to determine which subgroups truly require rFVIIa coverage.

The findings align with previous registry evidence. The STER registry[9] and other European cohorts[10] [11] have shown that clinical history and surgical type predict outcomes as well as—or better than—FVII:C activity, while Benlakhal et al[12] demonstrated that selected minor procedures can be performed safely without replacement in mild deficiency. Larger series confirm that integrating phenotype and procedural risk maintains bleeding rates below 5% with minimal thrombosis, reinforcing phenotype-based management. Within this context, García-Jaén et al[13] refine rather than redefine current paradigms—validating a phenotype-guided model and suggesting room for more individualized care in moderate deficiency.

A striking feature of the cohort is that all postoperative hemorrhages occurred in mild deficiency, none in severe—likely reflecting systematic rFVIIa use in severe cases and the presence of clinically fragile subgroups within the mild spectrum.[14] [15] Patients with significant bleeding histories—especially mucosal or gynecological bleeders—remain vulnerable during major or highly fibrinolytic surgery if inadequately protected, whereas asymptomatic individuals with low FVII:C levels may receive unnecessary replacement. The ISTH-BAT proved valuable: a score ≥ 3 identified nearly all bleeding cases and provided an objective, reproducible tool for perioperative assessment.

Beyond bleeding phenotype, comorbid factors also influence hemostatic balance. Advanced age, hepatic or renal dysfunction, concomitant antithrombotic or anti-inflammatory drugs,[16] [17] [18] and systemic inflammatory states may amplify bleeding risk, even in mild or moderate deficiency. Ethnic differences in bleeding patterns have also been reported.[19] [20] Optimal perioperative management must therefore integrate FVII:C, bleeding phenotype, procedural risk, and comorbidity.

Only one thrombotic event—a postoperative deep-vein thrombosis in a severely deficient patient undergoing major orthopedic surgery—was reported. Although isolated, it underscores the need for vigilance. Thrombotic risk with rFVIIa is generally low but increases with age, immobility, and higher cumulative doses.[6] [21] The regimen used—≤30 µg/kg for up to 3 days—reflects current best practice.

Despite its retrospective design, this study provides compelling real-world evidence supporting a phenotype-driven perioperative approach.[22] Its findings are particularly valuable for centers with limited experience in rare bleeding disorders, and their strong concordance with international data lends credibility to the proposed algorithm.[23]

Clinically, the implications are clear. For moderate and severe deficiency, rFVIIa prophylaxis remains appropriate for both low- and HR procedures but should be used at the lowest effective dose and duration. In mild deficiency, antifibrinolytic therapy and meticulous local measures generally suffice for LR surgery in patients with little or no bleeding history, whereas those with a bleeding score ≥ 3 or undergoing HR procedures should receive rFVIIa cover. This phenotype-guided strategy minimizes bleeding while avoiding unnecessary replacement, aligning with the broader shift toward personalized hemostatic medicine ([Fig. 1]).

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Fig. 1 Perioperative hemostatic risk assessment in inherited factor VII deficiency.

Beyond its clinical implications, García-Jaén et al's work[4] exemplifies the power of collaborative research in rare disorders. Integration of international registries will be pivotal to validate and refine the proposed algorithm, optimize dosing regimens, and assess long-term safety, cost-effectiveness, and patient-reported outcomes. As the field advances, emerging hemostatic assays and molecular tools may elucidate why patients with comparable FVII:C levels display such variable bleeding phenotypes.

Ultimately, this study represents a major advance in the surgical management of inherited FVIID. It convincingly demonstrates that effective hemostatic care should be guided not by factor levels alone, but by an integrated assessment of bleeding phenotype, procedural risk, and comorbidity—bridging the gap between laboratory metrics and real-world surgical outcomes.



Publication History

Received: 06 January 2026

Accepted: 27 January 2026

Accepted Manuscript online:
05 February 2026

Article published online:
18 February 2026

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