Head and Neck Free-Flap Reconstruction in Patients With Pre-Existing Coagulopathies: A Case Series

Introduction

Free tissue transfer is central to head and neck (H&N) reconstruction, offering functional and esthetic benefits. ¹ Thrombotic events—arterial or venous—are the dominant cause of flap loss, accounting for up to 85% of all failures despite overall failure rates of only 2% to 10%.^1-4 Predictors for thrombotic complications include diabetes, prior neck surgery, radiotherapy, and smoking.^2,5

Hypercoagulable states are recognized contributors to flap failure. ⁶ Inherited conditions (eg, Factor V Leiden, prothrombin G20210A, and protein C/S or antithrombin III deficiency) affect 5% to 8% of Western populations, while acquired coagulopathies (eg, malignancy-associated hypercoagulability, cirrhosis) are even more prevalent in surgical cohorts.^6-9 Their propensity for peri-anastomotic thrombosis renders patients a high-risk group during free-flap reconstruction.

Despite risks, data on H&N microvascular outcomes in this population are limited, and perioperative management lacks consensus. This case series describes perioperative courses and outcomes in patients with inherited coagulopathies—including thrombophilias—undergoing H&N free flaps, aiming to inform risk stratification and guide evidence-based perioperative protocols for this high-risk cohort.

Materials and Methods

Results

The cohort (n = 15) included 8 females, 7 males; median age 59 (range, 27-76) and BMI 26.3 kg/m² (range, 19.6-38.6). Common comorbidities included hypertension (60%), cardiac disease (33%), prior thromboembolic events (27%), chronic kidney disease (20%), diabetes mellitus, and chronic obstructive pulmonary disease (13% each; Table 1). Four were former smokers, and 1 was an active smoker. None had documented alcohol abuse or immobility. One patient (case #6) was taking oral contraceptive pills. The most common coagulopathies included sickle cell trait (n = 6, 40%) and Factor V Leiden (n = 4, 27%; Figure 1). One patient carried both sickle cell trait and heterozygous Factor V Leiden. Three cases were undiagnosed preoperatively.

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Table 1.

Demographic and Comorbidity.

Case	Sex	Age	BMI	Medical comorbidities	ASA class	Smoking history	Coagulopathy disorder	Indication	Free flap type
1	M	61	22.24	Prior thromboembolic disease (DVT, stroke, etc.)	IV	Never	Factor V Leiden	Malignancy	Lateral arm
2	F	59	34.70	Type II diabetes, hypertension	III	Former	Sickle cell trait	Malignancy	Lateral arm
3	F	76	28.58	Hypertension, chronic kidney disease, cardiac disease (heart failure, CAD, etc.), prior kidney transplant	III	Former	Sickle cell trait	Malignancy	Serratus
4	F	61	21.4	Hypertension, cardiac disease (heart failure, CAD, etc.)	III	Never	Systemic lupus erythematosus	Malignancy	Radial forearm
5	F	75	19.71	Hypertension, prior thromboembolic disease (DVT, stroke, etc.), cardiac disease (heart failure, CAD, etc.)	IV	Never	Prothrombin G20210a mutation	Malignancy	ALT
6	F	53	24.93	Sleep apnea	IV	Never	Sickle cell trait, Factor V heterozygous	Malignancy	Scapular tip
7	M	71	22.24	Type II diabetes, hypertension, chronic kidney disease, cardiac disease (heart failure, CAD, etc.), COPD	II	Never	Sickle cell trait	Malignancy	ALT
8	M	65	21.67	Cardiac disease (heart failure, CAD, etc.)	IV	Former	Factor V Leiden	Radiation fibrosis	Temporo-parietal fascia
9	F	33	35.3	None	III	Never	Factor V Leiden	Malignancy	ALT
10	F	56	26.53	Hypertension	III	Never	Sickle cell trait	Malignancy	Scapular tip
11	M	48	38.64	Hypertension, prior thromboembolic disease (DVT, stroke, etc.), chronic kidney disease	III	Never	Prothrombin G20210a mutation	Malignancy	Radial forearm
12	M	57	29.04	Hypertension	III	Never	Systemic lupus erythematosus	Malignancy	Latissimus
13	F	27	30.7	None	III	Never	Sickle cell trait	Benign mass	Fibular
14	M	53	19.6	Hypertension, COPD	IV	Current	Heparin-induced thrombocytopenia	Malignancy	ALT
15	M	66	26.3	Prior thromboembolic disease (DVT, stroke, etc.)	II	Former	Protein S deficiency	Malignancy	Scapular tip

Abbreviations: ALT, anterolateral thigh; COPD, chronic obstructive pulmonary disease.

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Figure 1.

Distribution of coagulopathy diagnoses.

Most reconstructions (93%) were oncologic, with 1 case addressing radiation fibrosis. Free flap types included anterolateral thigh (ALT, n = 4), scapular tip (n = 3), radial forearm (n = 2), lateral arm (n = 2), and single cases of serratus, latissimus dorsi, fibular, and temporoparietal fascia flaps (Table 1). Operative time ranged from 256 to 930 minutes, with available ischemia times from 52 to 216 minutes. Blood loss ranged from 50 to 800 mL (Table 2).

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Table 2.

Surgical, Coagulation, and Complication Data.

Case	Surgery, time (min)	Ischemia, time (min)	EBL (mL)	Preoperative AC	Intraoperative AC	Postoperative AC	Flap complication	Medical complications
1	535	-	300	UFH 5000 IU SC	Enoxaparin 40 mg SC at case end	Enoxaparin 40 mg SC daily through POD 4 → rivaroxaban 5 mg PO q24 h from POD 5	None	None
2	930	-	150	UFH 5000 IU SC	-	UFH 5000 IU SC q8 h throughout admission	None	None
3	256	90	100	Enoxaparin 40 mg SC	-	Enoxaparin 40 mg SC q24 h throughout admission	None	None
4	548	-	400	UFH 5000 IU SC	-	UFH 5000 IU SC q8 h throughout admission	None	None
5	361	52	50	Enoxaparin 30 mg SC	-	Enoxaparin 40 mg SC q24 h → apixaban 5 mg PO BID from POD 6	None	Aspiration pneumonia
6	625	-	800	UFH 5000 IU SC	-	UFH 5000 IU SC q8 h + ASA 325 mg PO q24 h throughout admission	Arterial and venous thrombosis, complete flap loss	None
7	629	58	200	UFH 5000 IU SC	Enoxaparin 40 mg SC at case end	Enoxaparin 40 mg SC q24 h + ASA 81 mg PO q24 h throughout admission	None	None
8	535	115	200	Enoxaparin 40 mg SC	Enoxaparin 40 mg SC intra-op	Enoxaparin 40 mg SC q24 h throughout admission	None	Urinary tract infection
9	589	-	300	UFH 5000 IU SC	-	Enoxaparin 40 mg SC q24 h throughout admission	Arterial and venous thrombosis, complete flap loss	None
10	610	168	450	Enoxaparin 40 mg SC		UFH 5000 IU SC q8 h throughout admission, ASA 325 mg PO q24 h	Infection	None
11	534	-	300	Enoxaparin 40 mg SC	-	Enoxaparin 40 mg SC q24 h throughout admission	None	None
12	602	170	300	Enoxaparin 40 mg SC	Enoxaparin 80 mg SC mid-case; 120 mg SC at case end	Enoxaparin 120 mg SC q12 h from POD 1 → apixaban 5 mg PO BID from POD 2; ASA 81 mg PO q24 h throughout admission	None	None
13	673	216	700	UFH 5000 IU SC		UFH 5000 IU SC q8 h throughout admission	None	None
14	490	116	100	Fondaparinux 2.5 mg	-	Fondaparinux 2.5 mg q24 h throughout admission	None	None
15	612	-	600	UFH 5000 IU SC	-	UFH 5000 IU SC q8 h throughout admission	None	None

Abbreviations: AC, anticoagulation; ALT, anterolateral thigh; ASA, aspirin; EBL, estimated blood loss; OR, operating room; PO, oral; POD, postoperative day; q8 h/q12 h, every 8/12 hours; SC, subcutaneous; UFH, unfractionated heparin.

Perioperative anticoagulation regimens varied across patients (Figure 2). Preoperatively, patients most commonly received either subcutaneous (SC) heparin (5000 units) or enoxaparin (30-40 mg). One patient received fondaparinux 2.5 mg due to heparin-induced thrombocytopenia. Four patients (26.7%) received additional intraoperative anticoagulation beyond heparinized saline flushes. Three patients received enoxaparin at case completion; 1 received it intraoperatively at mid-case and again at completion. Postoperatively, 3 patients (20.0%) transitioned to direct oral anticoagulants within a week. Three patients (20%) received aspirin, ranging from 81 to 325 mg daily. Heparin infusion protocols (5000 units every 8 hours) were employed in over one-third of cases (Table 2).

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Figure 2.

Anticoagulant transitions over perioperative phases.

The 2 patients (13.3%) who experienced vascular compromise also experienced complete flap loss due to both arterial and venous thrombosis. One of these patients was heterozygous for Factor V Leiden and had sickle cell trait, and the other had Factor V Leiden. Both received 5000 units of SC heparin preoperatively, and 1 patient continued this every 8 hours throughout admission, while the other received 40 mg of daily enoxaparin. In both, postoperative thrombosis caused flap loss despite revascularization efforts. In the first case, the patient developed flap compromise on postoperative day 3 (POD 3), prompting re-exploration, which revealed both arterial and venous thrombosis. The arterial anastomosis was revised from the facial to the superior thyroid artery, and the venous anastomosis was reestablished. However, extensive thrombosis of the jugular venous system precluded outflow, necessitating flap excision. A contralateral ALT flap was performed on POD 4, but partial flap necrosis required 2 subsequent returns to the operating room: first for local flap coverage and later for a medial sural artery perforator flap.

In the second case, flap compromise was noted on POD 6. Intraoperative findings again included arterial and venous clots. Arterial inflow was restored with intravenous (IV) unfractionated heparin (UFH), local tissue plasminogen activator injection, and thrombectomy. Despite these interventions, venous outflow could now be re-established, and the flap was sacrificed. The patient subsequently underwent a successful scapular-tip free flap reconstruction 1 year later.

The overall flap success rate was 80.0%. Postoperative blood transfusions were required in 6 patients (40.0%), and 4 patients (26.7%) received intraoperative transfusions. The median intraoperative transfusion volume was 425 mL (range, 250-1200 mL), and the median postoperative volume was 649 mL (range, 278-1300 mL). One patient (Case #13) required 1200 mL intraoperatively; 2 (Cases #9, #10) required >1100 mL postoperatively. Two patients (13.3%) experienced non-flap-related complications: 1 urinary tract infection and 1 case of aspiration pneumonia (Table 2).

Discussion

Despite high success rates, H&N reconstruction remains susceptible to failure—particularly with vascular compromise. ¹⁰ Coagulopathies, especially inherited hypercoagulable disorders, are increasingly recognized contributors to flap failure across all types of autologous reconstruction.^6,11,12 In a review of 1355 patients undergoing free flaps, 3.03% had hypercoagulable conditions, with flap loss rate exceeding 15%—much higher than the typical 1% to 2%.^1,13-15 Despite this elevated risk, no standardized protocol exists for screening or anticoagulation in patients with inherited coagulopathies. ¹⁶

In our series of 15 patients with documented inherited coagulopathies—including thrombophilias and other disorders such as lupus and heparin-induced thrombocytopenia—the flap failure rate was 13.3%. In both failures, re-exploration revealed arterial and venous thrombosis, despite anticoagulation. Salvage was unsuccessful, requiring secondary reconstruction with alternative free flaps, which succeeded. Notably, both patients with flap loss had Factor V Leiden mutations, and 1 had concurrent sickle cell trait—emphasizing the heightened thrombotic risk in patients with multiple prothrombotic factors. The 0% flap salvage rate observed in our cohort aligns with published literature demonstrating low salvage rates in inherited hypercoagulable states, particularly Factor V Leiden or multiple prothrombotic risk factors.^13,17 While timely re-exploration remains essential, intraoperative strategies such as systemic heparinization and complete mechanical thrombus removal have shown preliminary benefit. However, even these measures prove insufficient in patients with inherited coagulopathies. ¹⁸

Patients with H&N malignancies often present with compounding thrombotic risk factors, including advanced age, malignancy-associated hypercoagulability, history of tobacco/alcohol use, immobility, and prior radiation. ¹⁹ These baseline risks are exacerbated by coexisting inherited coagulopathies. Although the Enhanced Recovery After Surgery Society acknowledges the importance of thromboprophylaxis in free flap reconstruction, their 2017 guidelines note no pharmacologic regimen conclusively prevents microvascular thrombosis. ²⁰ While society guidelines provide recommendations for systemic Deep Vein Thrombosis/ Pulmonary Embolism (DVT/PE) prophylaxis, they do not address microvascular anastomotic thrombosis. ²¹ Amongst agents, low-molecular-weight heparin (LMWH) is favored for its safety profile. ¹⁹ A recent cohort study found no significant difference in flap compromise between patients receiving IV-UFH, SC-UFH, or SC-UFH combined with aspirin, suggesting that SC-UFH alone may be a safe, pragmatic option. ²² However, the optimal timing, intensity, and duration of anticoagulation remain debated. Meta-analyses suggest routine postoperative anticoagulation may not reduce thrombosis or improve flap survival, yet it increases bleeding risk.^23,24

There is no standardized anticoagulation protocol at our institution for free flap patients without coagulopathies. For oncologic reconstructions, patients typically receive 40 mg enoxaparin preoperatively, as most have a Caprini score ≥5. Postoperative regimens vary; some continue enoxaparin alone, while others add low-dose aspirin (81 mg daily). In our cohort, most patients received preoperative SC UFH. Intraoperative anticoagulation was selectively administered, often as enoxaparin at case completion. Postoperatively, >75% received SC-UFH or LMWH, and approximately one-third were treated with adjunctive aspirin. Importantly, no patients experienced clinically significant bleeding complications. Among the 2 patients with flap failure, neither received intraoperative anticoagulation, and postoperative regimens differed (one transitioned to LMWH, the other continued SC UFH).

Tailored anticoagulation strategies are crucial in patients with inherited coagulopathies undergoing microsurgical reconstruction. In H&N reconstruction, Faber et al described 3 cases of flap failure in undiagnosed Factor V Leiden patients undergoing H&N reconstruction. Implementation of a revised protocol—including preoperative enoxaparin (0.5 mg/kg daily), intraoperative IV heparin (1500 IU), and postoperative heparin infusion titrated to an activated Partial Thromboplastin Time (aPTT) of 45 seconds, followed by enoxaparin BID—resulted in successful salvage in all subsequent reconstructions. ¹⁷ In a broader analysis of various flap types, Wang et al found no outcome differences among 4 anticoagulation strategies, reinforcing that multidisciplinary planning may outweigh specific regimen choice. ¹³

Preoperative identification of inherited coagulopathies is essential to minimize thrombotic risk.^13,25 In our case series, among the 3 patients with previously undiagnosed coagulopathies, 2 experienced flap failure, underscoring the potential consequences of unrecognized hypercoagulable states. By contrast, among patients with known Factor V Leiden mutations, a structured screening protocol—including targeted questionnaires, coagulation panels, confirmatory genetic testing, and hematology referral—cut flap loss rates 10-fold. ²⁶

At our institution, preoperative screening is typically initiated by the anesthesia team and includes assessment of personal and family history of thromboembolic events. In lower extremity free flaps, Deldar et al employed a risk-stratified algorithm incorporating both clinical and laboratory-based coagulopathy work-up to guide anticoagulation, significantly reducing flap loss rates. ²⁷ These findings suggest that similar stratification strategies may be applied in H&N reconstruction to balance thrombotic and bleeding risks.

Hematology consultation and individualized anticoagulation regimens based on comprehensive coagulopathy work-ups have shown improved reconstructive outcomes.^13,28 However, the cost-effectiveness of routine screening remains a concern given the low prevalence of hereditary coagulopathies. ⁸ Even when risk is identified during preoperative evaluation, insufficient time often prevents confirmatory testing or hematology input before surgery. Targeted, risk-stratified screening protocols may offer a more practical balance between clinical benefit and cost, but optimizing their integration into preoperative workflows will be essential to maximize impact.

This study is one of the few focusing on H&N microsurgery outcomes in patients with inherited coagulopathies, offering insight into perioperative management. However, this study is limited by its retrospective, single-institution design and relatively small sample size, which may limit generalizability. The heterogeneity in anticoagulation regimens and timing reflects real-world variability but may confound comparisons. Larger, prospective studies are needed to better define optimal screening and anticoagulation protocols.

Collectively, this case series highlights the deleterious impact of inherited coagulopathies—particularly hypercoagulable disorders—on free flap viability in H&N reconstruction and underscores the need for evidence-based protocols. Early identification, multidisciplinary coordination, and individualized perioperative anticoagulation regimens are essential to optimize outcomes in this high-risk patient population.

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