Retrospective evaluation of multidisciplinary perioperative hemostatic management in oral surgery for patients with hemophilia

Abstract

Objectives

This study evaluated the clinical efficacy and safety of an individualized, multidisciplinary perioperative hemostatic management coordinated by the Department of Pediatrics for oral and maxillofacial surgery in hemophilia patients at a single tertiary medical center.

Materials and Methods

We retrospectively reviewed 13 hemophilia patients (hemophilia A: 11; hemophilia B: 2) who underwent oral surgery under individualized multidisciplinary perioperative hemostatic management at Busan Paik Hospital, Inje University, between 2021 and 2025, including preoperative hospital admission, individualized clotting factor replacement, intravenous tranexamic acid, and preoperative confirmation of activated partial thromboplastin time (aPTT). The primary outcome was intraoperative and postoperative hemorrhagic complications.

Results

A total of 21 surgical cases (including 37 tooth extractions) were analyzed. Disease severity was severe in 7 patients (58.3%), moderate in 2 (16.7%), and mild in 3 (25.0%); one patient with undocumented factor activity was excluded. One inhibitor-positive patient was managed with activated prothrombin complex concentrate (FEIBA). By World Federation of Hemophilia classification, 16 cases (76.2%) were major and 5 (23.8%) minor procedures. The primary hemostasis success rate was 95.2% (20/21 cases), and the overall complication rate was 14.3% (3/21 cases): one readmission for delayed secondary hemorrhage (mild hemophilia B), one odontogenic cellulitis, and one minor intraoperative oozing in the inhibitor-positive patient. Mean hospital stay was 5.5±1.5 days (inpatients only, n=16/21; range 4-9). No uncontrolled major hemorrhage or mortality occurred.

Conclusion

In this small single-center retrospective series without a control group, individualized multidisciplinary perioperative hemostatic management was associated with favorable outcomes (success rate 95.2%; complication rate 14.3%). These descriptive findings suggest that multidisciplinary collaboration, perioperative confirmation of inhibitor status, and thorough discharge education may be important components of perioperative care in hemophilia patients, though they should not be interpreted as demonstrating the causal superiority of any single care model, pending prospective, controlled confirmation.

I. Introduction

Hemophilia A and B are X-linked recessive congenital bleeding disorders caused by deficiencies of coagulation factors VIII and IX, respectively, with a combined prevalence of approximately 1 in 5,000-10,000 males worldwide^1,2. Patients with hemophilia face a markedly increased risk of hemorrhagic complications during invasive procedures, including oral and maxillofacial surgery. Even minor procedures such as tooth extractions can lead to life-threatening hemorrhage if appropriate hemostatic measures are not implemented^3,4.

The oral environment promotes prolonged postoperative bleeding owing to the high fibrinolytic activity of saliva and local tissue plasminogen activators, which accelerate clot dissolution⁵. Precise measurement of factor activity, individualized replacement dosing, and continuous perioperative hemostatic monitoring are therefore mandatory in hemophilia patients undergoing oral surgery^1,6.

According to World Federation of Hemophilia (WFH) guidelines, minor oral surgery requires factor activity to be raised to 50%-80% of normal and maintained for 1-5 days postoperatively, combined with antifibrinolytic therapy with tranexamic acid; major surgery requires 80%-100% for 7 days¹. However, specific administration schedules and the integration of antifibrinolytic therapy vary considerably among institutions^7,8.

At our institution, a multidisciplinary model is in place in which the Department of Pediatrics leads preoperative hemostatic preparation, intraoperative monitoring, and postoperative factor management, while the Department of Oral and Maxillofacial Surgery performs the surgical procedures. This structured collaborative framework, in which a pediatric hematologist directs the overall hemostatic management, has not been systematically evaluated in the context of oral surgery for hemophilia patients in Korea^9,10. The aim of this study was to retrospectively describe clinical outcomes in hemophilia patients who underwent oral surgery under this multidisciplinary perioperative management, in which the Department of Pediatrics served as the coordinating unit for perioperative hemostatic care. In this study, clinical efficacy was defined as the case-wise absence of intraoperative and postoperative hemorrhagic complications, and safety was defined as the absence of thromboembolic events, serious adverse reactions to clotting factor products, or death. Given the limited number of complication events, potential factors associated with perioperative complications were explored descriptively rather than through formal inferential analysis.

II. Materials and Methods

1. Study design and patient selection

This study was conducted as a single-center retrospective cohort study. The research protocol was approved by the Institutional Review Board (IRB) of Busan Paik Hospital, Inje University (IRB no. BPIRB 2025-12-020), with a waiver of informed consent granted given the retrospective nature of the study. All procedures were performed in accordance with the ethical principles of the Declaration of Helsinki (2024 revision).

Patients with confirmed hemophilia A or B who underwent oral surgery under the multidisciplinary perioperative hemostatic management of the Departments of Pediatrics and Oral and Maxillofacial Surgery at Busan Paik Hospital, Inje University, between January 2021 and February 2025, were included. At our institution, the Department of Pediatrics serves as the institutional hemophilia treatment unit, providing specialized hemostatic care for all patients with hemophilia regardless of age, including both pediatric and adult populations. Inclusion criteria were: (1) confirmed hemophilia A or B by coagulation factor assay; (2) oral surgery performed under formal perioperative hemostatic management by the Department of Pediatrics; and (3) availability of adequate medical records. Cases in which surgery was performed without pediatric consultation, or in which medical records were insufficient, were excluded. One case requires clarification relative to these criteria. Case 4 had a confirmed diagnosis of hemophilia A but no baseline factor activity level in the retrievable records. This case was retained because perioperative dosing was guided by real-time clinical assessment and institutional weight-based dosing rather than a single baseline value. However, this case was excluded from severity-stratified analyses, and its inclusion is acknowledged as a limitation of case ascertainment.

2. Perioperative hemostatic management

All inpatients were admitted to the Department of Pediatrics the day before their scheduled surgery. Baseline investigations on the day of admission included complete blood count, prothrombin time, and activated partial thromboplastin time (aPTT). Coagulation factor assay and inhibitor screening (Bethesda assay) were not repeated at the time of this admission; because all patients were under regular follow-up at the Korea Hemophilia Foundation Hospital, these results were retrieved from that institution’s records and confirmed by the Department of Pediatrics through chart review as a mandatory component of the preoperative evaluation. Tranexamic acid (500 mg diluted in 100 mL normal saline, administered intravenously every 8 hours) was initiated from the day of admission and maintained throughout the hospital stay in inpatients; after discharge, oral tranexamic acid (250-500 mg three times daily) was continued, typically for approximately 7 days but ranging from 2 to 10 days depending on the clinical course.(Table 1) Outpatient cases—Patient 2 (Cases 3-4), Patient 7 (Cases 12-13), and Patient 9 (Case 16)—were managed with oral tranexamic acid only, without an intravenous component.

Table 1. Surgical cases, perioperative hemostatic management, and outcomes.

Case No.	Patient No.	Procedure	Preoperative aPTT (21.0-34.5) (sec)	Severity	Clotting factor & dose	TXA	Anesthesia	LOS (days)	Outcome
1	Patient 1	Surgical extraction #18, #48	28.0	Moderate	Adynovate 4,000 U preop→ 2,000 U qd×1d; 2,000 U q8h×2d	IV 500 mg q8h×3d (admission)→ PO 500 mg tid×5d at discharge	Local	4	Success
2	Patient 1	Surgical extraction #28, #38	27.6	Moderate	Adynovate 4,500 U preop→ 2,000 U qd×1d; 2,000 U q8h×2d; 2,000 U q12h×1d	IV 500 mg q8h×4d (admission)→ PO 500 mg tid×5d at discharge	Local	5	Success
3	Patient 2	Scaling; Simple extraction #45	26.6	Mild	GreenGene F 3,400 U preop→1,700 U qd×1d; 1,700 U q12h×3d	PO only: Transamin 500 mg (2 cap) tid×10d, started morning of procedure	Local	Outpt	Success
4	Patient 2	Implants #44,46,47 + GBR	27.2	Mild	GreenGene F 3,500 U preop→1,750 U qd×1d; 1,750 U q12h×3d	PO only: Transamin 500 mg (2 cap) tid×10d, started night before procedure	Local	Outpt	Success
5	Patient 3	Surgical extraction #28, #38	31.0	Mild	Rixubis 10,000 U preop→5,000 or 6,000 U q8h×3d; 5,000 U q12h×2d; 5,000 U qd×2d	IV 500 mg q8h×8d (admission)→ PO 500 mg tid×3d at discharge	Local	9	Delayed bleeding→readmission
6	Patient 3	Surgical extraction #18, #48	29.6	Mild	Rixubis 10,000 U preop→5,000 or 6,000 U q8h×2d; 5,000 U q12h×1d; 5,000 U qd×1d	IV 500 mg q8h×5d (admission)→ PO 500 mg tid×7d at discharge	Local	6	Success
7	Patient 4	Surgical extraction #28, #38	25.8	Unknown	Adynovate 3,000 U preop→1,500 U qd×1d; 1,500 U q8h×3d	IV 500 mg q8h×4d (admission)→ PO 250 mg tid×7d at discharge	Local	5	Success
8	Patient 4	Surgical extraction #18, #48	27.2	Unknown	Adynovate 3,000 U preop→1,500 U qd×1d; 1,500 U q8h×3d	IV 500 mg q8h×4d (admission)→ PO 500 mg tid×5d at discharge	Local	5	Success
9	Patient 5	Surgical extraction #18, #48	24.6	Severe	Adynovate 3,000 U preop→1,500 U qd×1d; 1,500 U q8h×2d; 1,500 U qd×1d	IV 500 mg q8h×4d (admission)→ PO 500 mg tid×7d at discharge	Local	5	Success
10	Patient 5	Surgical extraction #28, #38	26.1	Severe	Adynovate 3,000 U preop→1,500 U qd×1d; 1,500 U q8h×2d; 1,500 U qd×1d	IV 500 mg q8h×4d (admission)→ PO 500 mg tid×7d at discharge	Local	5	Success
11	Patient 6	Surgical extraction #18, #48	34.4	Severe	Afstyla 3,300 U preop→1,500 U q12h×1d; 1,500 U q8h×3d; 1,500 U q12h×2d; 1,500 U qd×2d	IV 500 mg q8h×8d (admission)→ PO 500 mg tid×2d at discharge	Local	9	Odontogenic infection→antibiotics
12	Patient 7	Simple extraction #63	Not performed	Mild	Advate 2,000 U preop; 2,000 U qd×1d (outpatient)	Outpatient, PO only: Transamin 250 mg qd×1d preop + 250 mg tid×7d postop	Local	Outpt	Success
13	Patient 7	Simple extraction #52, #53, #54	Not performed	Mild	Advate 2,000 U preop; 2,000 U qd×2d (outpatient)	Outpatient, PO only: Transamin 250 mg qd×1d preop + 250 mg tid×7d postop	Local	Outpt	Success
14	Patient 8	Surgical extraction #48	26.2	Severe	Advate 4,000 U preop→1,500 U q8h×3d, taper×2d	IV 500 mg q8h×4d (admission)→ PO 500 mg tid×7d at discharge	Local	5	Success
15	Patient 8	Surgical extraction #18, #28, #38	26.1	Severe	Advate 4,000 U preop→1,500 U q8h×3d, taper×2d	IV 500 mg q8h×4d (admission)→ PO 500 mg tid×7d at discharge	Local	5	Success
16	Patient 9	Simple extraction #23; root planing #22, #24	Not performed	Moderate	Advate 4,000 U preop; 4,000 U qd×1d (outpatient)	Outpatient, PO only: Transamin 500 mg (2 cap) tid×7d, started morning of procedure	Local	Outpt	Success
17	Patient 10	Scaling + curettage; simple extraction #31, #33	Not performed	Severe	FEIBA 6,680 U preop→6,680 U qd×1d; additional dose for oozing	IV 500 mg q8h×4d (admission)→ PO 500 mg tid×7d at discharge	Local	5	Minor oozing→additional FEIBA
18	Patient 11	Surgical extraction #28, #38	26.7	Severe	BeneFIX 11,000 U preop→5,000 U qd×1d; 5,000 U q12h×2d	IV 500 mg q8h×3d (admission)→ PO 500 mg tid×7d at discharge	Local	4	Success
19	Patient 11	Surgical extraction #48	27.3	Severe	BeneFIX 11,000 U preop→5,000 U qd×1d; 5,000 U q12h×2d	IV 500 mg q8h×3d (admission)→ PO 500 mg tid×7d at discharge	Local	4	Success
20	Patient 12	Cyst enucleation + apicoectomy #22	27.3	Severe	Green Mono 4,000 U preop→2,000 U q8h×3d	IV 500 mg q8h×4d (admission)	Local	5	Success
21	Patient 13	Surgical extraction #18, #28, #38, #48 (GA)	26.1	Severe	Advate 5,000 U preop→1,750+3,000 U qd postop; 1,750+3,000 U q8h×2d; 1,750+2000 U q8h×1d, 1,750 or 2,000 U q8h×1d, 1,750 U qd×1d	IV 500 mg q8h×6d (admission, under GA)→PO 500 mg tid×7d at discharge	General	7	Success

(GBR: guided bone regeneration, TXA: tranexamic acid, q: every, h: hours, d: days, QD: once daily, preop: immediately before surgery, U: international units, LOS: length of stay, IV: intravenous, PO: per oral, Outpt: outpatient [no inpatient admission])

All IV TXA was tranexamic acid injection (Shinpoong) 500 mg/5 mL given by slow intravenous push; all PO TXA was Transamin capsule 250 mg.

Clotting factor product doses were individualized based on body weight, baseline factor activity, hemophilia type and severity, and the target activity level determined by the attending pediatric hematologist. Patients with hemophilia A received recombinant factor VIII products (octocog alfa [Advate; Takeda], rurioctocog alfa pegol [Adynovate; Takeda], lonoctocog alfa [Afstyla; CSL Behring], or beroctocog alfa [GreenGene F; GC Biopharma]) or a plasma-derived product (Green Mono; GC Biopharma). Patients with hemophilia B received nonacog gamma (Rixubis; Takeda) or nonacog alfa (BeneFIX; Pfizer). The inhibitor-positive patient (Patient 10) received the bypassing agent anti-inhibitor coagulant complex (FEIBA; Takeda) (activated prothrombin complex concentrate, approximately 88 U/kg). On the morning of surgery, aPTT was measured 30 minutes after the loading dose in cases managed with standard factor concentrates (whether inpatient or outpatient), and surgery proceeded after the attending pediatrician confirmed that the overall clinical and laboratory picture was acceptable; aPTT fell within the institutional reference range (21.0-34.5 seconds) in all of these cases, and surgery proceeded accordingly without complications. This aPTT-based confirmation was not applicable to the outpatient cases or to the FEIBA-treated inhibitor-positive patient (Patient 10), for whom aPTT is not a valid hemostatic marker. Post-infusion coagulation factor activity levels were not directly measured; aPTT was used as a practical surrogate marker of hemostatic status and does not directly quantify factor VIII or IX activity, a limitation particularly relevant for patients with mild hemophilia or those receiving bypassing agents. Postoperative factor infusions were maintained at 8-hour intervals for the first two days and then tapered stepwise according to clinical assessment.

Local hemostatic measures included oxidized regenerated cellulose (Surgicel; Ethicon), wound closure with absorbable sutures, and pressure gauze dressing. Standard local anesthesia consisted of 2% lidocaine with 1:100,000 epinephrine.

3. Data collection

Data extracted from medical records included: patient number, sex, age at surgery, hemophilia type and severity, inhibitor status, type and number of surgical procedures, type of anesthesia (local/general), clotting factor product and dose, tranexamic acid use, pre- and postoperative aPTT values, intraoperative and postoperative complications, additional hemostatic interventions, length of stay (inpatients only), and 30-day postoperative course. Hemophilia severity was classified according to clotting factor activity level as severe (<1%), moderate (1%-5%), or mild (>5%), in accordance with the WFH guidelines. One patient (Patient 4) had no documented factor activity level in the available medical records and was therefore excluded from the severity distribution analysis. Accordingly, severity-based percentages were calculated using a denominator of 12 patients with documented factor levels.

According to the WFH guidelines for the management of hemophilia (3rd edition)¹, surgical procedures were classified as major or minor based on procedural complexity and the requirement for hemostatic support exceeding five consecutive days. Hemorrhagic complications were defined as: (1) intraoperative bleeding requiring unplanned additional hemostatic intervention; (2) primary postoperative bleeding within 24 hours; and (3) secondary delayed bleeding after 24 hours requiring emergency department visit, readmission, or unplanned additional factor administration. Primary hemostasis success was defined as the absence of both intraoperative bleeding requiring unplanned additional hemostatic intervention and primary postoperative bleeding within 24 hours. Accordingly, Case 17, in which minor intraoperative and early postoperative oozing required an additional dose of FEIBA to achieve hemostasis, was classified as a primary hemostasis failure despite the eventual absence of readmission.

4. Statistical analysis

Descriptive statistics were used throughout; continuous variables were expressed as mean±standard deviation or median (range), and categorical variables as frequency and percentage. Given the small number of complication events (n=3) and limited sample size, formal inferential statistical comparisons between subgroups were not performed. All subgroup comparisons are therefore descriptive and hypothesis-generating rather than confirmatory. IBM SPSS Statistics ver. 27.0 (IBM) was used for analysis.

III. Results

1. Patient demographics and hemophilia characteristics

A total of 13 patients (all male) were included, comprising 21 surgical cases. Age at the first surgical case ranged from 14 to 70 years (mean 34.5±19.9 years). Eleven patients had hemophilia A and two had hemophilia B. Severity distribution: severe in 7 patients (58.3%), moderate in 2 (16.7%), and mild in 3 (25.0%); factor level was undocumented in one patient (Patient 4). Patient 10 was confirmed inhibitor-positive (Bethesda titer 5.88 BU) and managed with FEIBA. Patient 9 had developed a transient inhibitor in 2019 (0.82 BU), which was confirmed negative on repeated testing from November 2019 to August 2023 (over 4 years); Advate was accordingly used at the time of surgery. Inhibitor screening was negative in all other patients. Patient demographics and hemophilia characteristics are presented in Table 2.

Table 2. Patient demographics and hemophilia characteristics.

Patient No.	Sex/Age (yr)	Diagnosis	Severity	Factor level (%)	Inhibitor	Inhibitor titer (BU)	Clotting factor product	Maintenance therapy
Patient 1	M/19	Hemophilia A	Moderate	1.7	Negative	-	Adynovate	2,000 U every 2-3 days
Patient 2	M/55	Hemophilia A	Mild	10.0	Negative	-	GreenGene F	PRN
Patient 3	M/18	Hemophilia B	Mild	10.0	Negative	-	Rixubis	4,000 U, 7×/4 weeks
Patient 4	M/18	Hemophilia A	Unknown1	Unknown1	Negative	-	Adynovate	PRN (procedure only)
Patient 5	M/18	Hemophilia A	Severe	0.7	Negative	-	Adynovate	2,000 U, 2×/week
Patient 6	M/36	Hemophilia A	Severe	0.5	Negative	-	Afstyla	1,500-2,000 U, 2-3×/week
Patient 7	M/14	Hemophilia A	Mild	10.0	Negative	-	Advate	PRN (procedure only)
Patient 8	M/34	Hemophilia A	Severe	0.2	Negative	-	Advate	2,250 U, 1-2×/week
Patient 9	M/70	Hemophilia A	Moderate	1.7	Negative2	-	Advate	PRN; Advate 4,000 U
Patient 10	M/70	Hemophilia A	Severe	0.7	Positive	5.88	FEIBA	PRN (inhibitor patient)
Patient 11	M/20	Hemophilia B	Severe	0.3	Negative	-	BeneFIX	9,000 U, 1×/week
Patient 12	M/45	Hemophilia A	Severe	0.3	Negative	-	Green Mono	1,000-1,250 U, 3×/week
Patient 13	M/32	Hemophilia A	Severe	0.2	Negative	-	Advate	2,500 U, 1-2×/week

(M: male, BU: Bethesda units, PRN: pro re nata [as needed], -: not available)

¹Patient 4: factor level not documented in available records.

²Patient 9: transient inhibitor in 2019 (0.82 BU); confirmed negative on repeated testing November 2019 to August 2023; Advate used at time of surgery.

Age is at the first surgical case.

2. Surgical procedures and anesthesia

The 21 surgical cases and corresponding hemostatic protocols are detailed in Table 1. Tooth extraction was the predominant procedure, accounting for 19 cases (90.5%), including surgical removal of impacted third molars and simple extraction of multiple teeth. Among the 21 cases, one involved dental implant placement at sites #44, #46, and #47 with simultaneous guided bone regeneration (GBR) (Patient 2), and one involved cyst enucleation with apicoectomy (Patient 12). Additionally, tooth extraction was performed in conjunction with periodontal treatment in Patients 9 and 10. One patient (Patient 13) underwent surgery under general anesthesia owing to an inability to tolerate local anesthesia because of severe gagging; all other procedures were performed under local anesthesia with 2% lidocaine containing 1:100,000 epinephrine.

3. Perioperative hemostatic management

Clotting factor products used were as follows: Recombinant factor VIII products: Advate (octocog alfa) in Patients 7, 8, 9, and 13; Adynovate (rurioctocog alfa pegol) in Patients 1, 4, and 5; Afstyla (lonoctocog alfa) in Patient 6; GreenGene F in Patient 2; and Green Mono in Patient 12. Factor IX products: Rixubis (nonacog gamma) in Patient 3 and BeneFIX (nonacog alfa) in Patient 11. FEIBA was administered at 88 U/kg in the inhibitor-positive patient (Patient 10). Preoperative loading doses varied according to the specific factor concentrate administered: Adynovate 47.5-55.2 IU/kg, GreenGene F 44.4-45.5 IU/kg, Rixubis 101.5-103.4 IU/kg, Afstyla 49.3 IU/kg, FEIBA 87.9 IU/kg, BeneFIX 133.0-134.6 IU/kg, Green Mono 50.6 IU/kg, and Advate 56.3-66.8 IU/kg. Postoperative factor infusions were maintained at 8-hour intervals for the first 2 days and subsequently tapered. Intravenous tranexamic acid (500 mg every 8 hours) was administered during the hospital stay in inpatients, with oral therapy continued after discharge for a duration individualized according to clinical course (median 7 days; range, 2-10 days).(Table 1) Outpatient cases were managed with oral tranexamic acid only: Patients 7 and 9 received a single preoperative factor infusion and a 7-day oral course, whereas Patient 2 (Cases 3-4) received a 10-day oral course together with scheduled pre- and post-procedure factor dosing. Preoperative aPTT, measured approximately 30 minutes after the loading dose, ranged from 24.6 to 34.4 seconds (institutional reference range, 21.0-34.5 seconds) among evaluable cases (Table 1); values were not obtained in three of the five outpatient cases (Cases 12, 13, and 16; Patients 7 and 9), which involved no factor-level monitoring, or in the FEIBA-treated inhibitor-positive patient (Patient 10), for whom aPTT is not a valid monitoring parameter. aPTT was measured in the remaining two outpatient cases (Patient 2, Cases 3-4), as these involved scheduled administration of clotting factor. All measured aPTT values fell within the institutional reference range (21.0-34.5 seconds), and surgery proceeded accordingly in each case without hemorrhagic complications.

4. Clinical outcomes

According to the WFH guidelines for the management of hemophilia (3rd edition)¹, surgical procedures were classified as major or minor based on procedural complexity and the requirement for hemostatic support exceeding five consecutive days. Of the 21 cases, 16 (76.2%) were classified as major procedures, including surgical extractions of molar teeth, dental implant placement with GBR, and cyst enucleation with apicoectomy. The remaining 5 cases (23.8%) were classified as minor procedures, comprising simple extractions of non-molar teeth, scaling, and root planing. The distribution of cases by hemophilia severity and procedure category is summarized in Table 3.

Table 3. Cross-tabulation of surgical cases by hemophilia severity and procedure category.

Diagnosis/severity	Patient (n)	Case (n)		Total cases	Complication (n)
		Minor	Major
Hemophilia A — Severe	6	1	7	8	2
Hemophilia A — Moderate	2	1	2	3	0
Hemophilia A — Mild	2	3	1	4	0
Hemophilia A — Unknown	1	0	2	2	0
Hemophilia B — Severe	1	0	2	2	0
Hemophilia B — Mild	1	0	2	2	1
Total	13	5 (23.8%)	16 (76.2%)	21	3 (14.3%)

(HA: hemophilia A, HB: hemophilia B, GBR: guided bone regeneration)

Classification based on WFH guidelines for the management of hemophilia, 3rd edition (2020)¹. Minor procedures (n=5): simple dental extraction of non-molar or <3 teeth, scaling, root planing. Major procedures: surgical extraction of molar teeth, extraction of ≥3 teeth, implant placement with GBR, cyst enucleation with apicoectomy.

The distribution of complications by procedure category and hemostasis outcome is presented in Table 4. Complications occurred in 2 of 16 major cases (12.5%) and 1 of 5 minor cases (20.0%). The overall primary hemostasis success rate was 95.2% (20/21 cases). The sole primary hemostasis failure (Case 17) occurred in the only inhibitor-positive patient undergoing a minor procedure. Case 17 (Patient 10) was classified as a failure of primary hemostasis due to intraoperative bleeding requiring an unplanned additional hemostatic intervention, and was counted as such in the calculation of the primary hemostasis success rate. In contrast, delayed secondary hemorrhage (Case 5, Patient 3) and odontogenic cellulitis (Case 11, Patient 6) were included as overall complications; however, they were considered successes in the calculation of the primary hemostasis success rate, as neither represented a failure of immediate intraoperative and postoperative bleeding control. Overall, complications were not concentrated in any single procedure category or disease severity subgroup, though the small sample size limits interpretation. Mean hospital stay was 5.5±1.5 days (inpatients only, n=16/21 cases; range 4-9 days). No cases of uncontrolled massive intraoperative hemorrhage, thromboembolic events, hypersensitivity reactions to clotting factor products, or mortality within 30 days were observed.

Table 4. Complication distribution by procedure category and hemostasis outcome.

Outcome	Minor (n=5)	Major (n=16)	Total (n=21)
Primary hemostasis success	4 (80.0%)	16 (100%)	20 (95.2%)
Primary hemostasis failure	1 (20.0%)	0 (0%)	1 (4.8%)
Overall complications	1 (20.0%)	2 (12.5%)	3 (14.3%)
Primary postop bleeding (<24 hours)	1	0	1
Delayed secondary hemorrhage (POD 10)	0	1	1
Non-hemorrhagic complication (cellulitis)	0	1	1
No complications	4 (80.0%)	14 (87.5%)	18 (85.7%)

(POD: postoperative day)

Primary hemostasis success=absence of intraoperative and primary postoperative bleeding (<24 hours) requiring unplanned hemostatic intervention.

Complications occurred in 3 cases (14.3%) and are described in detail in Table 5. Case 5 (Patient 3, mild hemophilia B): Following uneventful extraction of #28 and #38 and discharge, delayed secondary hemorrhage from the #28 extraction socket occurred on postoperative day 10 after consumption of hot food (rice soup). The patient was readmitted via the emergency department and managed with additional Rixubis infusions and local hemostatic measures for 3 days.

Table 5. Details of perioperative complications.

Case No.	Patient No.	Diagnosis	Severity	Procedure	Complication type	Timing	Management & outcome
5	Patient 3	Hemophilia B	Mild	Surgical extraction #28, #38	Delayed secondary hemorrhage	POD 10	Readmission; additional FIX (Rixubis)+local hemostasis; resolved within 3 days
11	Patient 6	Hemophilia A	Severe	Surgical extraction #18, #48	Odontogenic cellulitis (non-hemorrhagic)	POD 1	IV antibiotics (ceftriaxone+metronidazole+tobramycin)×7d; LOS extended to 9d; full recovery
17	Patient 10	Hemophilia A+inhibitor	Severe	Scaling+curettage; extraction #31, #33	Minor intraoperative/early postoperative oozing	Intraoperative	Additional FEIBA 88 U/kg same day; compression; resolved without readmission

(POD: postoperative day, FIX: coagulation factor IX, FEIBA: activated prothrombin complex concentrate, LOS: length of stay)

Case 11 (Patient 6, severe hemophilia A): Extraction of #18 and #48 was completed without intraoperative or immediate postoperative bleeding; however, progressive pain and swelling in the right perimandibular region developed from the evening of the extraction day. Neck computed tomography confirmed odontogenic cellulitis secondary to post-extraction infection, and intravenous antibiotics (ceftriaxone, metronidazole, and tobramycin) were administered for 7 days, extending the hospital stay to 9 days.

Case 17 (Patient 10, inhibitor-positive hemophilia A): Despite administration of FEIBA 88 U/kg instead of standard factor VIII products, minor oozing persisted intraoperatively and in the immediate postoperative period. An additional dose of FEIBA was administered approximately 6 hours after surgery, combined with compression, achieving hemostasis without readmission.

IV. Discussion

In this small single-center retrospective series, a structured multidisciplinary perioperative hemostatic management was associated with favorable hemostatic outcomes in hemophilia patients undergoing oral and maxillofacial surgery, with a primary hemostasis success rate of 95.2%. This finding is consistent with the published literature, in which complication rates for oral surgery in hemophilia patients range from 0% to 35%^3,4,7,11,12. Stratification of cases by procedure category revealed that major procedures accounted for 76.2% of cases (16/21), yet complications occurred in only 2 of these cases (12.5%). Notably, the sole primary hemostasis failure occurred in the only inhibitor-positive patient undergoing a minor procedure (Case 17), underscoring that inhibitor status, rather than procedural complexity alone, is the primary determinant of hemostatic risk. These findings are consistent with prior series reporting that adequate factor replacement and multidisciplinary management can mitigate hemorrhagic risk even in major oral surgical procedures^3,4,7. The small sample size precludes definitive subgroup comparisons, and these observations should be regarded as descriptive and hypothesis-generating. Additionally, the 21 cases encompassed procedures of considerably varying invasiveness pooled into a single success rate, which limits the interpretability of the overall outcomes.

This study offers several distinctive contributions to the existing literature on oral and maxillofacial surgery in hemophilia patients. First, it describes an institution-specific perioperative management model at a Korean tertiary medical center, in which a pediatric hematologist with expertise in hemophilia, rather than the operating surgeon, serves as the clinical lead and directs preoperative hemostatic preparation, intraoperative monitoring, and postoperative clotting factor adjustment for both pediatric and adult patients with hemophilia. This model reflects the actual clinical practice at our institution. Second, our protocol applied an individualized antifibrinolytic regimen consisting of tranexamic acid administered intravenously during the inpatient admission in most cases, with an oral-only regimen used in outpatient cases, followed by an oral tranexamic acid course after discharge, with duration tailored to the clinical course (typically around 7 days; range, 2-10 days), providing a flexible template that may be adapted by other institutions. Third, the cohort uniquely included and successfully managed an inhibitor-positive patient within the same structured protocol, extending the applicability of this framework beyond the more homogeneous populations described in most previous series.

Compared with previously published cohorts, our findings are broadly consistent with the reported experience, while highlighting differences in institutional structure and protocol design. Landart et al.⁷ described a 13-year single-center experience in patients with inherited bleeding disorders undergoing oral surgery under a hematologist-directed replacement protocol and likewise reported a low overall rate of bleeding complications. Givol et al.⁴, in a two-decade tertiary center experience, reported an overall low rate of bleeding complications, with only 40 delayed bleeding events (2%) occurring among 1,968 dental extractions and oral surgical procedures. However, in their study, neither the use of perioperative factor replacement therapy nor antifibrinolytic therapy was statistically significantly associated with the occurrence of bleeding, and the authors emphasized meticulous local surgical hemostatic technique as the key factor underlying the low bleeding rate. This study, too, did not specifically describe a perioperative management approach led by a pediatric hematologist. Ramos et al.⁸ demonstrated the feasibility of outpatient minor oral surgery in a series of 23 hemophilia patients managed with a structured perioperative factor replacement protocol combined with tranexamic acid, without requiring hospital admission, consistent with the outcomes observed in our own outpatient subgroup (Patients 2, 7, and 9). Peisker et al.¹², reporting 58 dental extractions in patients with hemophilia A and B, similarly emphasized an individualized, weight-based factor replacement protocol combined with systemic antifibrinolytic therapy and local hemostatic measures as central to minimizing hemorrhagic complications, in line with the present findings. Taken together, these comparisons support the concept that structured, multidisciplinary perioperative protocols are associated with favorable hemostatic outcomes across differing institutional models, while indicating that the specific contribution of our series lies in its multidisciplinary governance model coordinated by a pediatric hematologist, individualized antifibrinolytic regimen, and inclusion of an inhibitor-positive patient within a single protocol.

The cornerstone of the hemostatic management is maintaining adequate factor activity throughout the entire perioperative period. Preoperative aPTT assessment served as a practical safety check to help avoid proceeding under grossly inadequate hemostatic cover; however, the decision to proceed ultimately relied on the attending pediatrician’s overall clinical judgment rather than a rigid numeric cutoff. However, aPTT is a global coagulation screening assay and a surrogate marker of hemostatic status rather than a direct measure of factor VIII or IX activity; post-infusion factor activity levels were not measured in this cohort, which should be considered when interpreting the adequacy of hemostatic monitoring, particularly in patients with mild hemophilia or those receiving bypassing agents—as illustrated by the inhibitor-positive patient (Patient 10, Case 17) managed with FEIBA, for whom aPTT does not reliably reflect hemostatic status and monitoring instead relied on clinical assessment and Bethesda titer history. This reliance on a global, non-specific coagulation assay, combined with the attending pediatrician’s individualized clinical judgment rather than a uniform numeric threshold, introduces an element of subjectivity that may limit the reproducibility of this protocol in settings without dedicated hematology support. Individualized dosing calculations by a pediatric hematologist allow for a precise approach that accounts for patient-specific pharmacokinetics and clinical history^1,6.

Tranexamic acid plays a central role in this hemostatic management. By inhibiting the high fibrinolytic activity within the oral cavity, it reduces clot dissolution at extraction sites and decreases both the frequency of postoperative bleeding and the consumption of clotting factor products⁵. A Cochrane systematic review by van Galen et al.⁵ confirmed that antifibrinolytic agents significantly reduce post-extraction bleeding in hemophilia patients. The maintenance of tranexamic acid—administered intravenously during the inpatient stay in most cases and continued orally after discharge for a duration individualized according to clinical course (median 7 days; range, 2-10 days)—is believed to have contributed to the low complication rate¹³.

The delayed secondary hemorrhage in Case 5 (Patient 3, mild hemophilia B) was precipitated by a behavioral factor—consumption of hot food on postoperative day 10—highlighting the critical importance of thorough patient education regarding dietary and activity restrictions after discharge³. This was the only case requiring readmission in the present series and was controlled with additional Rixubis infusion and local hemostatic measures.

The odontogenic cellulitis in Case 11 (Patient 6, severe hemophilia A) was a non-hemorrhagic infectious complication. Delayed wound healing and accumulation of blood products at the extraction site in severe hemophilia may predispose to secondary infection¹⁴. Early initiation of antibiotic therapy and close surgical monitoring were essential for the timely management of this complication.

The management of the inhibitor-positive patient (Patient 10, Case 17) presented a unique challenge. Inhibitors are neutralizing antibodies that inactivate standard factor VIII products and develop in approximately 25%-30% of patients with severe hemophilia A¹⁵. Minor oozing was controlled with an additional same-day dose of FEIBA (88 U/kg) and local compression, with resolution achieved without readmission. This case reaffirms the necessity of confirming inhibitor status, through coordination with the patient’s hemophilia treatment center, prior to surgery in all hemophilia patients.

In Patient 9 (Case 16), who had a history of transient inhibitor, a transient factor VIII inhibitor arising in 2019 was confirmed negative on repeated testing over more than 4 years from November 2019 to August 2023; Advate was appropriately used for the outpatient procedure in January 2024. This case suggests that standard clotting factor products may be safely used in patients with a history of transient inhibitor formation after prolonged confirmed negativity, though limited to a single case.

Outpatient management of Patient 7 (mild hemophilia A, Cases 12 and 13) with a single preoperative Advate infusion and a 7-day course of oral tranexamic acid suggests that not all hemophilia patients require inpatient admission for oral surgery in carefully selected cases. Risk stratification according to disease severity, inhibitor status, and procedural complexity is important for appropriately calibrating the level of perioperative management^1,6,8.

Patient 2 (Case 4) involved dental implant placement at sites #44, #46, and #47 with simultaneous GBR in a patient with mild hemophilia A, included as part of a sequential treatment course following a prior simple extraction in the same patient (Case 3). We acknowledge that implant placement with GBR carries greater invasiveness than routine dental extraction, with distinct perioperative hemostatic implications including the risk of delayed hemorrhage at the GBR site. Notably, both the simple extraction (Case 3) and the implant placement with GBR (Case 4) in this patient were managed on an outpatient basis without overnight admission; given the greater invasiveness of GBR, this observation should be interpreted cautiously as a single-case finding rather than a general recommendation for outpatient management of comparable procedures. The patient received 3,500 IU of GreenGene F preoperatively followed by 1,750 IU every 12 hours for 3 days with tranexamic acid, and the procedure was completed without hemorrhagic complications. Although limited to a single case, this outcome suggests the feasibility of implant surgery with GBR in carefully selected, mild hemophilia patients under multidisciplinary perioperative hemostatic management. This single, favorable outcome in a patient with mild hemophilia must not be generalized into a routine recommendation for outpatient management of implant placement with GBR—or of other highly invasive procedures—in patients with moderate or severe hemophilia, inhibitors, or other elevated bleeding risk; in such patients, inpatient admission with close perioperative monitoring remains advisable pending further evidence. Dedicated prospective studies are warranted to establish evidence-based protocols for this more invasive procedure.

This study has several limitations. First, the retrospective single-center design limits generalizability. Second, the sample size was small overall, and subgroups of particular interest were especially limited — only 2 patients had hemophilia B and only 1 was inhibitor-positive — precluding meaningful subgroup analysis. Third, the absence of a control group prevents direct comparison with alternative approaches. Fourth, the small number of complications (n=3) precluded formal inferential statistics; all comparisons are descriptive and hypothesis-generating. Fifth, factor level was undocumented in Patient 4. Sixth, post-infusion coagulation factor activity levels were not directly measured; aPTT, used as a surrogate marker of hemostatic adequacy, may not fully reflect true factor activity, particularly in mild hemophilia or in the inhibitor-positive patient receiving bypassing therapy. These findings should therefore be regarded as promising observations from a small single-center series, and prospective multicenter studies are warranted to confirm them.

V. Conclusion

In this small single-center retrospective series of 21 surgical cases across 13 hemophilia patients, an individualized multidisciplinary perioperative hemostatic management was associated with favorable hemostatic outcomes, with a primary hemostasis success rate of 95.2% and an overall complication rate of 14.3%. Given the retrospective design, small sample size, and absence of a control group, these results should be interpreted as promising findings rather than definitive evidence of management efficacy. The findings suggest that multidisciplinary collaboration, perioperative confirmation of inhibitor status, and thorough patient education may be important components of perioperative management in this population. Prospective multicenter studies are warranted to confirm these observations.

Funding Statement

Funding No funding to declare.