Is there consensus on anticoagulation strategies for free flaps in H&N procedures/does the literature support one management approach over another?

Comment by InpharmD Researcher

The available literature does not demonstrate a clear consensus on the optimal anticoagulation strategy for free flap reconstruction in head and neck surgery, nor does it consistently support any one management approach over another for improving flap survival. Routine therapeutic anticoagulation, including unfractionated heparin, low-molecular-weight heparin, and aspirin-based regimens, has not been shown to consistently reduce flap thrombosis or flap failure compared with standard care. In contrast, several analyses have reported an increased risk of hematoma and bleeding, particularly with unfractionated heparin and higher-intensity anticoagulation regimens, while the benefit of adding aspirin remains uncertain. Although some retrospective studies have reported favorable outcomes with specific intraoperative or postoperative heparin protocols, these findings have not been consistently reproduced and are largely limited by retrospective study designs. Consequently, current evidence generally supports standard pharmacologic venous thromboembolism prophylaxis when indicated based on patient risk, rather than routine flap-directed anticoagulation, with anticoagulation strategies individualized according to the balance between thrombotic and bleeding risk.
Background

A 2017 systematic review and consensus statement from the Enhanced Recovery After Surgery (ERAS) Society provided a comprehensive perioperative care protocol for patients undergoing major head and neck cancer surgery with free flap reconstruction. Key recommendations include preoperative carbohydrate loading, pharmacologic venous thromboembolism (VTE) prophylaxis, perioperative antibiotics for clean-contaminated procedures, and opioid-sparing multimodal analgesia. The authors note that these patients are at moderate to high risk of VTE due to the combined risks of cancer and major surgery, and that pharmacologic thromboprophylaxis (e.g., low-molecular-weight heparin) reduces VTE incidence but must be individualized because of an associated increase in bleeding risk. Additionally, no pharmacologic agents have been shown to reduce free flap anastomotic thrombosis or flap necrosis, and the routine use of antithrombotic agents for flap preservation is not supported by human evidence. [1]

A 2019 clinical review examined controversies surrounding microvascular free tissue transfer in head and neck cancer reconstruction, with a focus on patient selection and perioperative management strategies. The review critically evaluated postoperative practices, including antibiotic duration and the use of antithrombotic therapy. Although postoperative aspirin, heparin, and other antithrombotic agents are commonly used to maintain anastomotic patency, the authors concluded that evidence supporting improved flap outcomes is limited, and some studies suggest that routine VTE prophylaxis alone may be sufficient. The review also notes that while pharmacologic VTE prophylaxis may increase the risk of flap hematoma, the overall benefits of preventing VTE generally outweigh this risk in appropriately selected patients. [2]

A 2026 systematic review and network meta-analysis evaluated postoperative antithrombotic strategies in microvascular free flap reconstruction of the head and neck. This comprehensive review incorporated data from 54 predominantly retrospective studies encompassing 17,773 patients to assess the efficacy and safety of various antithrombotic regimens, including aspirin (ASA), LMWH, intravenous and subcutaneous unfractionated heparin (IV and SC UFH), dextran, and prostaglandin E1 (PGE1). The analysis revealed that no antithrombotic regimen consistently reduced the risk of flap loss or thrombosis compared to no prophylaxis. ASA was associated with the lowest estimated absolute risk for both total and partial flap failures, although these findings did not translate into statistically significant superiority over no prophylaxis, while IV UFH significantly increased the risk of hematoma (OR 4.18; 95% CI, 1.36-13.22). LMWH was noted to modestly raise the reoperation rate when compared to no prophylaxis (OR 2.25; 95% CI, 1.00-5.01). These findings underscore the limited benefit of routine anticoagulation in improving flap-related outcomes and suggest a need for more individualized prophylactic strategies. The authors also noted that the overall quality of evidence was moderate, with most included studies being retrospective, highlighting the need for adequately powered prospective comparative studies. The study highlights the necessity for further prospective research to establish evidence-based guidelines, emphasizing the challenge of balancing thrombosis prevention with bleeding risk in clinical practice. [3]

A 2018 review presented the available evidence for thromboprophylaxis in otolaryngology or head and neck surgeries. Subcutaneous heparin appears to not be associated with increased adverse flap outcomes, based on individual studies. However, a cited meta-analysis reported a significantly increased risk of hematoma, despite reducing the risk of flap loss by 35%. A combination of subcutaneous heparin and aspirin is frequently reported in practice but may increase complication rates and the benefit of aspirin remains suspect. There is limited information regarding intravenous heparin in head and neck surgery, but some studies related to free tissue transfer suggest an increased risk of bleeding complications with heparin drips and continuous infusions at doses above 500 U/hour. Low-molecular-weight heparin has also demonstrated a similar and potentially lower risk of bleeding complications versus unfractionated heparin, while other studies suggest inferiority. Because of this, the use of low-molecular-weight heparin remains controversial and requires further investigation. [4]

A 2022 systematic review and meta-analysis evaluated the effectiveness of anticoagulation therapy in improving outcomes for microvascular free flap reconstruction following head and neck surgery. This comprehensive analysis included eight studies, comprising both randomized controlled trials and observational cohort studies, which collectively examined 3531 free flaps used in head and neck reconstruction. The primary focus was on perioperative complications, such as free flap thrombosis and failure, while secondary outcomes included bleeding complications requiring additional intervention. The findings of the 2022 review indicated that none of the assessed anticoagulation interventions statistically improved free flap outcomes. Moreover, the pooled analysis from the included studies revealed that prophylactic use of therapeutic doses of anticoagulants significantly increased the risk of hematoma and bleeding complications [RR 2.98 (1.47-6.07), p = 0.003] compared to control groups. Unfractionated heparin (UFH) consistently heightened the risk of complications without reducing the incidence of flap thrombosis and failure. Based on the lack of benefit in reducing free flap failure along with a significant risk of bleeding complications, the authors recommend limiting anticoagulation to standard prophylactic use of low-molecular-weight heparin in the perioperative setting without additional anticoagulation. [5]

A multicenter, individual patient data meta-analysis investigated the effectiveness of postoperative anticoagulants to improve survival after free radial forearm flap (FRFF) in head and neck reconstruction. A total of four studies were available for meta-analysis (n= 759 FRFF procedures). Anticoagulants used in procedures included aspirin (12%), low-molecular-weight dextran (18.3%), unfractionated heparin (28.1%), low-molecular-weight heparin (49%), and prostaglandin-E1 (2.1%); there were 31% of patients who did not receive anticoagulation. Outcomes evaluated included flap failure, defined as flap failure with or without revision surgery, and flap complications including bleeding, wound infection, seroma, fistula formation, and (partial) flap failure. Pooled analysis indicated that initial flap failure occurred in 90 (12%) patients. The rate of flap failure was significantly greater with heparin (odds ratio [OR] 3.99; 95% CI 1.579 to 10.082; p= 0.003) and LMWH (OR 5.429; 95% CI 1.671 to 17.64; p= 0.005) compared to no anticoagulation. No difference in flap failure was reported between aspirin or low-molecular-weight dextran and no anticoagulation. Further, the univariate analysis determined anticoagulation use resulted in significantly more flap failure (OR 2.6; 95% CI 1.1 to 6.4; p <0.05), specifically with aspirin and heparin/LMWH, and flap complications (OR 2.2; 95% CI 1.1 to 4.1; p <0.05) compared to no anticoagulation use. [6]

A 2015 meta-analysis investigated the efficacy and safety of heparin or low-molecular-weight heparin (LMWH) along with other antithrombotics for the development of various flap complications, including flap failure and pedicle thrombosis. Heparin and LMWH were grouped together due to their comparable antithrombotic activity. Four clinical trials (N= 1,796) were analyzed which reported a non-significant but lower risk of total flap loss in the heparin and LMWH group versus comparator (relative risk [RR] 0.65; 95% CI 0.25 to 1.69). The risk of thrombosis was also not significantly lower in the heparin and LMWH group (RR 0.84; 95% CI 0.07 to 8.70). However, the risk of hematoma was significantly greater in the heparin group (4.15-fold increased risk) although limited data prevented investigation in the LMWH group. While the majority of studies were head and neck surgeries, other upper extremity sites were also included in the meta-analysis, limiting the applicability of results to the specific population. [7]

A 2018 meta-analysis that included 2,048 free-flap surgery procedures in the head and neck determined there to be no significant difference in the occurrence of flap loss (RR 1.25; 95% CI 0.85 to 1.81; p= 0.26) and thromboembolic events (RR 1.05; 95% CI 0.74 to 1.48; p= 0.79) when anticoagulation was utilized compared with no anticoagulation. Additionally, the risk of hematoma was significantly higher when anticoagulation was utilized compared to when no anticoagulation was used (RR 2.02; 95% CI 1.08 to 3.76; p= 0.03). These results indicate the lack of benefit of postoperative anticoagulation therapy for reducing the risk of flap loss and thromboembolic events in free-flap surgery in the head and neck. It should be noted that this analysis is limited due to the inclusion of only retrospective studies. [8]

A 2014 meta-analysis focused on heparin for the prevention of flap loss during head, neck, and upper extremity surgery. Data was limited to 4 studies of which were divided into two categories: heparin versus aspirin and high-dose heparin/dalteparin versus low-dose heparin/dalteparin. The two studies comparing heparin versus aspirin reported a combined OR of 2.003 (95% CI 0.976 to 4.109; p= 0.058) which was not significantly different. The high-dose versus low-dose study reported an OR of 7.810 (95% CI 1.859 to 32.808; p= 0.005) which indicates significantly greater odds of flap loss rates in patients receiving high doses of heparin and dalteparin. Individually, the single study focused on heparin reported an OR of 11.00 which significantly associates high-dose heparin with a greater flap loss rate (p= 0.011). The single dalteparin study trended towards association but was not significant (OR 4.691; p= 0.181). The findings are limited due to the limited number of studies and statistical power. [9]

Background References: [1] Dort JC, Farwell DG, Findlay M, et al. Optimal Perioperative Care in Major Head and Neck Cancer Surgery With Free Flap Reconstruction: A Consensus Review and Recommendations From the Enhanced Recovery After Surgery Society. JAMA Otolaryngol Head Neck Surg. 2017;143(3):292-303. doi:10.1001/jamaoto.2016.2981
[2] Abouyared M, Katz AP, Ein L, et al. Controversies in free tissue transfer for head and neck cancer: A review of the literature. Head Neck. 2019;41(9):3457-3463. doi:10.1002/hed.25853
[3] Uralov D, De Virgilio A, Canali L, et al. Postoperative Antithrombotic Strategies in Head and Neck Free Flap Reconstruction: A Systematic Review and Network Meta-Analysis. Head Neck. 2026;48(3):893-917. doi:10.1002/hed.70158
[4] Abraham M, Badhey A, Hu S, et al. Thromboprophylaxis in Head and Neck Microvascular Reconstruction. Craniomaxillofac Trauma Reconstr. 2018;11(2):85-95. doi:10.1055/s-0037-1607068
[5] Dawoud BES, Kent S, Tabbenor O, Markose G, Java K, Kyzas P. Does anticoagulation improve outcomes of microvascular free flap reconstruction following head and neck surgery: a systematic review and meta-analysis. Br J Oral Maxillofac Surg. 2022;60(10):1292-1302. doi:10.1016/j.bjoms.2022.07.016
[6] Swartz JE, Aarts MC, Swart KM, et al. The value of postoperative anticoagulants to improve flap survival in the free radial forearm flap: a systematic review and retrospective multicentre analysis. Clin Otolaryngol. 2015;40(6):600-609. doi:10.1111/coa.12425
[7] Lee KT, Mun GH. The efficacy of postoperative antithrombotics in free flap surgery: a systematic review and meta-analysis. Plast Reconstr Surg. 2015;135(4):1124-1139. doi:10.1097/PRS.0000000000001100
[8] Liu J, Shi Q, Yang S, Liu B, Guo B, Xu J. Does Postoperative Anticoagulation Therapy Lead to a Higher Success Rate for Microvascular Free-Tissue Transfer in the Head and Neck? A Systematic Review and Meta-Analysis. J Reconstr Microsurg. 2018;34(2):87-94. doi:10.1055/s-0037-1606346
[9] Pan XL, Chen GX, Shao HW, Han CM, Zhang LP, Zhi LZ. Effect of heparin on prevention of flap loss in microsurgical free flap transfer: a meta-analysis. PLoS One. 2014;9(4):e95111. Published 2014 Apr 21. doi:10.1371/journal.pone.0095111
Literature Review

A search of the published medical literature revealed 9 studies investigating the researchable question:

Is there consensus on anticoagulation strategies for free flaps in H&N procedures/does the literature support one management approach over another?

Level of evidence

C - Multiple studies with limitations or conflicting results  Read more→


Please see Tables 1-9 for your response.

Postoperative Management of Antithrombotic Medication in Microvascular Head and Neck Reconstruction: A Comparative Analysis of Unfractionated and Low-Molecular-Weight Heparin

Design

Single-center, retrospective analysis

N= 266

Objective

To compare low-dose unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) in perioperative thrombosis prophylaxis

Study Groups

UFH (n= 87)

LMWH (n= 179)

Inclusion Criteria

Patients with ablative surgical procedures and microvascular flap transplantation that received postoperative therapy with either low-dose UFH (500 IU/h) or LMWH (20/40 mg daily)

Exclusion Criteria

Did not receive low-dose UFH or LMWH protocol

Methods

The operating surgeon decided whether to administer either low-dose UFH or subcutaneous LMWH after surgery. Intravenous low-dose UFH was given as a 500 IU/h infusion. LMWH was given per standard protocol with enoxaparin. Each individual's risk of thrombosis was assessed and those with low peri- and postoperative thrombosis risk received 20 mg of enoxaparin once a day. Patients with medium to high thrombosis risk (e.g., obesity) received 40 mg of enoxaparin once a day. Other anticoagulants that would influence the coagulation time were not administered.  Flap surveillance was performed at a 2 hour interval during the first 5 days by an experienced and trained ENT resident supervised by the microvascular surgeon.

Duration

 

Procedure completed: January 2004 to July 2017 

Outcome Measures

Primary: Total frequency of transplant thrombosis and number of flap failures

Secondary: Occurrence of peri- and postoperative complications (minor complications defined as treatable with sufficient conservative therapy; major complications defined as requiring surgical revision)

Baseline Characteristics

  

UFH (n= 87)

LMWH (n= 179)

 p-value

Age, years

 57.9 ± 11.2 59.7 ± 10.5 0.202

Male

 72 (82.8%) 138 (77.1%) 0.288

Location of Primary

Oral Cavity

Oropharynx

Hypopharynx

Larynx

Other


16 (18.4%)

41 (47.1%)

16 (18.4%)

3 (3.4%)

11 (12.6%)


27 (15.1%)

95 (53.1%)

24 (13.4%)

14 (7.8%)

19 (10.6%)

0.443

-

-

-

-

-    

Tumor Stage 

T1

T2

T3

T4

n= 82

11 (13.4%)

23 (28.1%)

28 (34.1%)

20 (24.4%)

n= 174

16 (9.2%)

68 (39%)

49 (28.2%)

41 (23.6%)

0.317   

-

-

-

-

Peripheral artery occlusive disease

Fontaine 1

Fontaine 2

Fontaine 3


3 (3.5%)

0

1 (1.1%)


3 (1.7%)

1 (0.6%)

1 (0.6%)

0.797

-

-

-

Coronary heart disease

10 (11.5%)

14 (7.8%)

 0.298

Activated partial thromboplastin time 

31.1 ± 4.4

32.1 ± 7.3

 0.261

Prothrombin time

91.2 ± 10.4

94.4 ± 9.5

 0.095

Results

Endpoint

UFH (n= 87)

LMWH (n= 179)

 p-value

Flap thrombosis

Total rate

Arterial 

Venous


8 (9.2%) 

3 (3.5%) 

5 (5.7%)


17 (9.5%) 

2 (1.1%) 

15 (8.4%)


0.767 

0.040 

0.445

Time to thrombosis, hours

 29.8 ± 66.5 63.9 ± 100.7 0.227
Total flap loss 3 (3.4%) 12 (6.7%)

0.280

Partial flap loss

 5 (5.7%) 4 (2.2%) 0.134

Postoperative Bleeding

Minor

Major


3 (3.4%) 

4 (4.6%)


8 (4.5%) 

12 (6.7%)


0.688

0.498

Hematoma formation

Minor 

Major


12 (13.8%) 

4 (4.6%)


22 (12.3%) 

7 (3.9%)


0.731 

0.792

Salivary fistula 

Minor 

Major


9 (10.3%) 

4 (4.6%)


22 (12.3%) 

12 (6.7%)


0.632 

0.498
Overall revision rate 18 (20.7%)

36 (20.1%)

  0.912
Pulmonary artery embolism

1 (1.1%)

 0 (0%) --

5-year overall survival

 66.7% 70.1% 0.420

There were no cases of deep vein thrombosis or heparin-induced thrombocytopenia reported.

Adverse Events

 No significant difference in adverse events between UFH and LMWH groups. No cases of heparin-induced thrombocytopenia or allergic reactions. One case of pulmonary artery embolism in the UFH group.

Study Author Conclusions

The free-flap survival rate using low-dose UFH seems to be equivalent to LMWH regimens without compromising the postoperative outcome. Consequently, for risk-adapted thrombosis prophylaxis, either LMWH or UFH can be administrated.

Critique

The study provides valuable insights into the comparative effectiveness of UFH and LMWH in microvascular head and neck reconstruction. However, the retrospective design and lack of randomization may introduce selection bias. The study's strength lies in its comprehensive analysis of a large cohort, but the absence of a control group without anticoagulation limits the ability to assess the absolute benefit of anticoagulation therapy. Additionally, the study does not address long-term outcomes beyond the immediate postoperative period
Table 1 References:
[10] Sievert M, Goncalves M, Tamse R, et al. Postoperative management of antithrombotic medication in microvascular head and neck reconstruction: a comparative analysis of unfractionated and low-molecular-weight heparin. Eur Arch Otorhinolaryngol. 2021;278(5):1567-1575. doi:10.1007/s00405-020-06219-w

Aspirin, Heparin, and Ischemia Time in Microvascular Free Flap Surgery - Their Influence and an Optimal Anticoagulation Protocol

Design

Retrospective, observational, quasirandomized cohort study 

N= 178

Objective

To develop and optimize a new anticoagulation protocol using aspirin (ASA) and unfractionated heparin (UH) for intraoperative and immediate postoperative administration in the intensive care unit (ICU)

Study Groups

Group I (n= 42)

Group II (n= 44)

Group IIIa (n= 32)

Group IIIb (n= 26)

Group IV (n= 34)

Inclusion Criteria

All microvascular free flap surgeries performed at a single center in Germany between 2013 and 2018

Exclusion Criteria

N/A

Methods

This was a single-center study from a German hospital that stratified groups based on the time the microvascular free flap surgery was conducted. These time frames correspond to different anticoagulation protocols at the institution. 

Group I consisted of surgeries prior to 2015 with random anticoagulation.

Group II comprised of surgeries from January 2015-August 2016. At that time, the anticoagulation protocol included an intraoperative bolus of UFH 5,000 IU followed by continuous UFH with a goal activated partial thromboplastin time (aPTT) of 60-80 seconds.

Groups IIIa and IIIb consisted of surgeries from September 2016-May 2018. Both groups were given an intraoperative UFH 5,000 IU bolus. However, Group IIIa (free soft tissue flaps) followed with UFH 1 mL/hr with no target aPTT while Group IIIb (free bone flaps) followed with continuous UFH and a target aPTT of 60-80 seconds. 

Group IV comprised of surgeries from May 2018-December 2018. The anticoagulation protocol called for an intraoperative bolus of ASA 300 mg and UFH 20 IU/kg followed by UFH 1 mL/hr with no target aPTT and ASA 100 mg/day.

Once patients were transferred to the floor, UFH was replaced with enoxaparin 40-60 mg once daily and ASA was continued at 100 mg/day until discharge. Notably, patients who received two or more flaps at different time points were listed multiple times.

Duration

 2013 to 2018

Outcome Measures

Rate of flap loss; complications rates including bleeding, hematoma, and problems with anastomosis; important blood values within patient groups

Baseline Characteristics

  

Group 1 (n= 42)

Group 2 (n= 44)

 Group IIIa (n= 32) Group IIIb (n= 26) Group IV (n= 34)

Age, years

 59.3 ± 14.1 64.5 ± 11.3 65.3 ± 13.7 61.5 ± 14.1 66.9 ± 9.7

Flap performed

Radial forearm flap

Latissimus dorsi flap

Free fibula flap

Iliaic crest flap

Scapula

Anterolateral thigh (ALT)

 

59.5%

23.8%

16.7%

2.3%

 -

-

 

23.9%

10.9%

10.9%

23.9%

28.2%

2.2% 

 

65.6%

25%

-

-

-

9.4% 

 

6.1%

15.2%

21.2%

39.4%

18.1%

- 

 

36.9%

13.1%

-

36.9%

10.5%

2.6% 

Arterial anastomosis

Superior thyroid artery

Facial artery

Lingual artery

Others

 

76.7%

9.3%

7%

7% 

 

51.1%

35.6%

8.9%

4.4% 

 

40.6%

37.5%

12.5%

9.4% 

 

10.7%

57.1%

14.3%

17.9% 

 

35.3%

52.9%

5.9%

5.9%

Venous anastomosis

Jugular vein

Facial vein

Others

 

90.5%

7.1%

2.4% 

 

68.2%

27.3%

4.5% 

 

50%

34.4%

15.6% 

 

46.4%

39.3%

14.3%

 

56.8%

43.2%

-

Of the total (N= 178) patients, 41% of patients were female and the average ischemia time was 129.2 ± 65.1 minutes.

Results

 

Group 1 (n= 42)

Group 2 (n= 44)

Group IIIa (n= 32)

 Group IIIb (n=26) Group IV (n= 34)

Loss of free flap

 14.3% 9.1% 6.23% 15.4% 5.9%

Bleeding

 2.4% 11.4% 18.8% 3.9% 11.8%

Hematoma

 2.4% 20.5% 18.8% 23.1% 5.9%

Problems with anastomosis

 16.7% 13.6% 12.5% 27% 14.7% 

Hemoglobin, g/dL

Preoperative

Postoperative

 

13.3 ± 2

10.1 ± 1.6

 

12.9 ± 1.6

9.1 ± 1.8

 

12.9 ± 2

10.1 ± 1.6

 

12.7 ± 1.5

8.9 ± 0.8

 

13.1 ± 1.8

9.1 ± 1.3

aPTT at ICU, s

 38.4 ± 12.2 49.5 ± 13.8 46.6 ± 16.3 55.7 ± 11.8 44.12 ± 10

Adverse Events

 Prolonged ASA administration increased complication rates after 72 hours. Higher doses of UFH (>500 IU/h) increased the risk of hematoma and anastomosis problems.

Study Author Conclusions

 A combined anticoagulation regime of ASA and UFH is effective in reducing flap loss and complications in microvascular surgery. Prolonged ASA administration and high doses of UFH should be avoidedA combined anticoagulation regime of ASA and UFH is effective in reducing flap loss and complications in microvascular surgery. Prolonged ASA administration and high doses of UFH should be avoided.

Critique

The study provides valuable insights into optimizing anticoagulation protocols in microvascular surgery. However, the retrospective design and lack of randomization may introduce bias. The study's findings may not be generalizable to other surgical settings or patient populations.
Table 2 References:
[11] Rothweiler R, Gerlach V, Voss P, et al. Aspirin, heparin and ischemia time in microvascular free flap surgery - their influence and an optimal anticoagulation protocol. J Stomatol Oral Maxillofac Surg. 2022;123(5):e556-e562. doi:10.1016/j.jormas.2022.03.001
Continuous administration of heparin during free flap surgery for head and neck tumors reduces the risk of pulmonary embolism
Design

Retrospective case-control analysis

N= 92
Objective To investigate the impact of different anticoagulation protocols on the incidence of pulmonary embolism (PE) in patients with head and neck tumors who underwent microvascular flap reconstruction
Study Groups

6 h postop: 10,000 IU UFH/24 h (n= 46)

3 IU UFH and 6 h postop aPTT (n= 46)
Inclusion Criteria Patients suffering from head and neck tumors who received at least one free flap reconstruction at the Department of Oral and Maxillofacial Surgery at the University Medical Center of Göttingen
Exclusion Criteria Not specified
Methods Two anticoagulation strategies were evaluated: one group received 10,000 IU of UFH administered over 24 hours starting 6 h postoperatively for one week. The other group received 3 IU of UFH per kilogram of total body weight per hour at the onset of surgery until 6 h after surgery. The aPTT target was set at 50 to 60 seconds for one week. The aPTT was monitored four times daily in the ICU and once daily after transfer to the normal ward
Duration Not specified
Outcome Measures Primary: Incidence of pulmonary embolism (PE) Secondary: Incidence of bleeding requiring intervention, revision rate of vascular anastomoses, graft loss
Baseline Characteristics   6 h postop: 10,000 IU UFH/24 h (n= 46) 3 IU UFH and 6 h postop aPTT (n= 46)
Female 23 (50%) 23 (50%)
Age (range), years 66 (15-89) 66.1 (37-91)
Surgery time (range), hours 9.9 (6.1-18.1) 9.5 (4.2-15.1)
Forearm flap 16 (34.8%) 16 (34.8%)
Fibula flap 14 (30.4%) 14 (30.4%)
Anterolateral thigh flap 12 (26.1%) 12 (26.1%)
Scapula flap 4 (8.7%) 4 (8.7%)
Results   6 h postop: 10,000 IU UFH/24 h (n= 46) 3 IU UFH and 6 h postop aPTT (n= 46)
Pulmonary embolism* 8 (17.4%) 3 (6.5%)
Secondary bleeding 2 (4.3%) 6 (13%)
Revision anastomosis 7 (15.2%)  2 (4.3%) 
Loss of graft 2 (4.3%)  3 (6.5%)
*Significant difference (p >0.05)
Adverse Events The incidence of postoperative bleeding requiring surgical intervention increased from 4.3% to 13% in the group receiving intraoperative heparinization, although this change did not reach statistical significance.
Study Author Conclusions The intraoperative administration of UFH is effective in significantly reducing the risk of PE in patients with head and neck tumors undergoing free flap reconstruction. Further research is needed to optimize anticoagulation protocols that balance thromboembolic prevention and the risk of bleeding complications.
Critique The study provides valuable insights into anticoagulation protocols for reducing PE risk in free flap surgeries. However, the retrospective design and small sample size may limit the generalizability of the findings. Additionally, the study did not specify the duration of follow-up, which could impact the assessment of long-term outcomes. Further prospective studies are needed to confirm these findings and establish guidelines for anticoagulation in this context.
Table 3 References:
[12] Goldstein K, Holdorf F, Lier M, et al. Continuous administration of heparin during free flap surgery for head and neck tumors reduces the risk of pulmonary embolism. Oral Maxillofac Surg. 2026;30(1):62. Published 2026 Mar 25. doi:10.1007/s10006-026-01545-5
Impact of perioperative anticoagulation management on free flap survival in reconstructive surgery: a retrospective analysis
Design

Retrospective, single-center study

N= 489
Objective To investigate the role of anticoagulation and perioperative practices in free flap reconstructive surgery and their impact on surgical outcomes
Study Groups

Intraoperative UFH (n= 222)

No intraoperative UFH (n= 127)

Postoperative Heparin (n= 261)

Postoperative Heparin + Aspirin (n= 67)

Postoperative Aspirin only (n= 3)
Inclusion Criteria All adult patients undergoing microvascular flap transplantation at the University Hospital Cologne between 2009 and 2020
Exclusion Criteria Patients with intra- or postoperative demise before flap healing
Methods Patients were divided based on intraoperative (UFH or no UFH) and postoperative anticoagulation management (UFH only, Aspirin and UFH, Aspirin only). Intraoperative UFH was administered at 20 IU/kg. Postoperative UFH was initiated with an infusion pump at 500 IU/h, followed by PTT-controlled dosing every four hours for the first three days. Data were collected from electronic hospital information systems and medical records
Duration 2009 to 2020
Outcome Measures

Primary: Flap survival

Secondary: Relationship between anticoagulation protocols, PTT values, and flap survival
Baseline Characteristics   Total (n= 489) Flap loss (n= 71) Flap survival (n= 418) p-value
Age, years 62 (53.8–72) 61 (52–70) 62 (54–72) 0.36
Male 263 (53.8%) 42 (59.2%) 221 (52.9%) 0.33
Hypertension 195 (40.3%) 29 (40.9%) 166 (40.2%) 0.92
Peripheral artery disease 28 (5.8%) 6 (8.5%) 22 (5.3%) 0.32
Nicotine history 97 (20%) 15 (21.1%) 82 (19.9%) 0.81
Diabetes mellitus 67 (13.8%) 8 (11.3%) 59 (14.3%) 0.50
Head/Neck reconstruction 50 (10.2%)  12 (17%)  38 (9.1%) NS
Results   Total (n= 489) Flap loss (n= 71) Flap survival (n= 418) p-value
Intraoperative Heparin 222 (63.6%) 23 (46.9%) 199 (66.3%) 0.01
PTT day 1 (sec.) 31.2 (7.7) 29.3 (5.5) 31.5 (8.0) 0.03
Adverse Events No significant difference in flap survival between patients treated with heparin alone and those treated with both heparin and aspirin. Aspirin without additional heparin was used in only three patients, with flap loss occurring in two of these cases
Study Author Conclusions Intraoperative UFH and PTT-guided postoperative management are crucial for improving free flap survival. Standardized anticoagulation protocols are essential for enhancing outcomes in free flap reconstructive surgery.
Critique The study's retrospective nature and diverse patient cohort with various flap types are limitations. The absence of data for some patients limited the final analysis to 349 patients. The small sample size in the aspirin-only group prevented significant statistical findings. The decision for anticoagulation regime was based on individual preference without a clear protocol, highlighting the need for a prospective multicenter study.
Table 4 References:
[13] Torabi S, Overbeek R, Dusse F, et al. Impact of perioperative anticoagulation management on free flap survival in reconstructive surgery: a retrospective analysis. BMC Anesthesiol. 2025;25(1):106. Published 2025 Feb 26. doi:10.1186/s12871-025-02975-6

The Role of Anticoagulation Regimen on Flap Outcome in Microvascular Head and Neck Reconstruction
Design

Retrospective cohort study

N= 300
Objective To measure and compare flap compromise associated with 3 different anticoagulation protocols: intravenous unfractionated heparin (IV-UFH), subcutaneous UFH (SC-UFH), and SC-UFH plus ASA
Study Groups

IV-UFH (n= 47)

SC-UFH (n= 176)

SC-UFH + ASA (n= 77)
Inclusion Criteria Histologically confirmed head and neck cancer; treatment plan involving ablative surgery; undergoing surgery after providing written consent; free flap reconstruction performed on the same day as the ablative surgery
Exclusion Criteria Only received antithrombotic stocking during and after surgery; had a prior adverse reaction to heparin or ASA; did not receive the anticoagulation agent in the dosage specified for the study groups; declined to participate in the study
Methods Subjects were allocated to 3 treatment groups based on clinical criteria: SC-UFH (5000 IU every 8 hours), IV-UFH (500 IU/hour via continuous infusion adjusted based on partial thromboplastin time), or SC-UFH + ASA (80 mg daily). Flap outcome was assessed as compromised or not. 
Duration March 2013 to January 2023
Outcome Measures Flap outcome (compromised or not), postoperative complications (hematoma formation, mortality)
Baseline Characteristics   IV-UFH (n= 47) SC-UFH (n= 176) SC-UFH + ASA (n= 77)
Age, years  49.21 ± 18.79 45.73 ± 16.13 53.70 ± 19.35
Male 34 (72.3%) 109 (61.9%) 59 (76.6%)

Cancer type

Tongue

Gingiva SCC of Maxilla

Gingiva SCC of Mandible

Lip

Other

 

9 (19.1%)

9 (19.1%)

17 (36.2%)

5 (10.6%)

7 (15%)

 

73 (41.5%)

11 (6.3%)

53 (30.1%)

29 (16.5%)

10 (5.7%)

 

17 (22.1%)

12 (15.6%)

30 (38.9%)

11 (14.3%)

7 (9.1%)
Operation time, hours  10.07 ± 2.12 9.28 ± 1.74 10.31 ± 2.02
ICU stay, days  4.87 ± 2.49 3.86 ± 1.72 3.71 ± 2.20
Results   SC-UFH (n= 176) IV-UFH (n= 47) SC-UFH + ASA (n= 77) p-value
Flap compromise 12 (6.8%) 11 (23.4%) 5 (6.5%) <0.01
Hematoma formation 8 (4.5%) 7 (14.9%) 3 (3.9%) 0.03
Mortality 4 (2.3%) 2 (4.3%) 6 (7.8%) 0.1
Adverse Events Subjects administered IV-UFH had significantly increased risks of hematoma formation (RR = 3.28, 95% CI [1.25 to 8.57]). See above for more details. 
Study Author Conclusions Postoperative thrombosis in head and neck microsurgery remains a significant risk factor for poor outcomes. SC-UFH administration may be a practical approach to managing these risks compared to intravenous administration; however, the choice of anticoagulation protocol is not associated with the flap compromise. 
Critique The study's retrospective design limits the ability to exclude all confounders, and the lack of randomization may introduce bias. The study was conducted in a single teaching hospital, which may limit the generalizability of the findings. Additionally, the heterogeneous population of head and neck cancer patients reconstructed with various flap types limits specific recommendations regarding superior anticoagulation regimens based on flap types. 
Table 5 References:
[14] Mouzannar S, Jalaeefar A, Shirkhoda M, et al. The Role of Anticoagulation Regimen on Flap Outcome in Microvascular Head and Neck Reconstruction. J Oral Maxillofac Surg. 2025;83(4):467-475. doi:10.1016/j.joms.2024.12.011

Perioperative anticoagulation in free microvascular flaps – a comparison of different prophylactic regimes in oncologic reconstructive surgery
Design

Retrospective study

N= 355
Objective To compare three different heparin protocols with regard to postoperative complications in free tissue transfer for oncologic head and neck surgery
Study Groups

500 IU/h unfractionated heparin (UFH) (n= 87)

Low-molecular-weight heparin (LMWH) once daily (n= 179)

LMWH once daily with additional immediate preoperative administration (n= 89)
Inclusion Criteria Patients with oncological surgery and microvascular flap transplantation who received perioperative antithrombotic therapy with either low-dose UFH, LMWH started postoperatively, or LMWH applied perioperatively with additional administration on the morning of surgery
Exclusion Criteria Patients who did not receive the low-dose UFH or LMWH protocol, or those with cardiac risk factors or UFH/LMWH at therapeutic doses
Methods Retrospective analysis of free flap transplants from 2004 to 2023. Patients were divided into three groups based on the type of perioperative antithrombotic prophylaxis: low-dose UFH (500 IU/hour), LMWH started postoperatively (20/40 mg daily), or LMWH applied perioperatively with additional administration on the morning of surgery. 
Duration January 2004 to April 2023
Outcome Measures Primary: Incidence of postoperative bleeding and hematoma, appearance of flap thrombosis, incidence of postoperative systemic complications
Baseline Characteristics  

500 IU/h UFH

(n= 87)

LMWH once daily

(n= 179)

LMWH + additional preoperative administration

(n= 89)
Female 15 (17.2%) 41 (22.9%) 22 (24.7%)
Age, years 57.9 ± 11.2 59.7 ± 10.5 62 ± 9.9
Smoking 70 (80.1%) 143 (79.9%) 62 (69.6%)
Alcohol 34 (35.8%) 73 (40.8%) 29 (32.6%)
Heart failure 16 (18.4%) 14 (7.8%) 1 (1.1%)
Results  

500 IU/h UFH

(n= 87)

LMWH once daily

(n= 179)

LMWH + additional preoperative administration

(n= 89)

 p-value
Total flap loss 3 (3.4%) 12 (6.7%) 8 (8.9%) 0.323
Partial flap loss 5 (5.7%) 4 (2.2%) 0 (0%) 0.048

Postoperative bleeding

Major

Minor

 

4 (4.6%)

3 (3.4%)

 

12 (6.7%)

8 (4.5%)

 

5 (5.6%)

0 (0%)

 

0.784

0.127

Hematoma formation  

Major

Minor

 

4 (4.6%)

12 (13.8%)

 

7 (3.9%)

22 (12.3%)

 

2 (2.2%)

10 (11.2%)

 

0.660

0.874
Total rate for flap thrombosis  8 (9.2%) 17 (9.5%) 8 (8.9%) 0.990
Adverse Events Postoperative bleeding occurred in 8.7% of patients, with no significant difference between groups. Hematoma formation requiring revision was found in 3.7% of patients. Postoperative hematoma was identified as a significant influencing factor for venous pedicle thrombosis (OR 3.602; p = 0.001).
Study Author Conclusions The three anticoagulation regimens appear to be equivalent therapy for the prevention of thrombosis without significant differences in postoperative bleeding. The use of LMWH with additional preoperative administration can be administered in free flap reconstruction.
Critique The study's retrospective design and non-randomized selection of perioperative anticoagulation regimens may introduce selection bias. However, the large sample size and long observation period strengthen the findings. The lack of a negative control group limits the ability to prove the superiority of anticoagulant therapy over no thromboprophylaxis. Additionally, the absence of monitoring for postoperative anticoagulants is a limitation.
Table 6 References:
[15] Tamse HR, Koch M, Mueller SK, et al. Perioperative anticoagulation in free microvascular flaps - a comparison of different prophylactic regimes in oncologic reconstructive surgery. Eur Rev Med Pharmacol Sci. 2024;28(10):3532-3541. doi:10.26355/eurrev_202405_36288

Effect of Perioperative Antithrombotics on Head and Neck Microvascular Free Flap Survival After Anastomotic Revision
Design

Retrospective review

N= 843
Objective To determine if antithrombotic therapy improves head and neck microvascular free flap survival following anastomotic revision
Study Groups All patients (n= 843)
Inclusion Criteria Patients who underwent microvascular free tissue transfer to the head and neck between August 2013 and July 2021 at the University of Alabama at Birmingham, University of Colorado, and University of California Irvine
Exclusion Criteria Not specified
Methods Perioperative use of anticoagulation, antiplatelets, intraoperative heparin bolus, tissue plasminogen activator (tPA), vasopressor use, and leech therapy were collected. The primary endpoint was free flap failure. Analyses of free flaps that underwent anastomotic revision with or without thrombectomy were performed
Duration August 2013 to July 2021
Outcome Measures Free flap failure, impact of antithrombotic therapy on flap survival after anastomotic revision
Baseline Characteristics   All patients (n= 834) Anastomotic revision (n= 42)
Age, years 63 62
Female 217 (26%) 14 (33.3%)

Race

White

Black

Other

 

688 (82.4%)

63 (7.5%)

69 (8.3%)

 

34 (81%)

2 (4.8%)

6 (14.2%)

Smoking

Current

Former

Never

 

229 (27.6%)

299 (36%)

303 (36.5%)

 

13 (31%)

16 (38%)

13 (31%)

Alcohol

Current

Former

Never

 

249 (30%)

64 (7.7%)

518 (62.3%)

 

13 (31%)

2 (4.8%)

27 (64.2%)
Results   All patients (n= 843) Anastomotic revision (n= 42) p-value
Free flap failure rate 4.0% (n= 34) 47.6% (n= 20) <0.0001
Pedicle anastomosis revision rate 5.0% (n= 42) -- --
Revision of both artery and vein -- 75% of failures 0.008
The use of antithrombotic therapy, whether in the form of aspirin, prophylactic anticoagulation, or therapeutic anticoagulation, did not significantly enhance free flap survival. 
Adverse Events Not specified
Study Author Conclusions In cases of microvascular free tissue transfer pedicle anastomotic revision, the use of antithrombotic therapy does not appear to significantly change free flap survival outcomes.
Critique The study provides valuable insights into the role of antithrombotics in free flap survival after anastomotic revision. However, the retrospective design and the small number of flaps within the anastomotic revision group limit the strength of the conclusions. Additionally, the lack of a standardized protocol for antithrombotic use across institutions may introduce variability in the results. 
Table 7 References:
[16] Bishop JL, Vasudev M, Garcia N, et al. Effect of Perioperative Antithrombotics on Head and Neck Microvascular Free Flap Survival After Anastomotic Revision. Otolaryngol Head Neck Surg. 2023;168(6):1353-1361. doi:10.1002/ohn.295
Assessment of BMI and Venous Thromboembolism Rates in Patients on Standard Chemoprophylaxis Regimens After Undergoing Free Tissue Transfer to the Head and Neck
Design

Retrospective review of a prospectively collected cohort

N= 765
Objective To assess the association between BMI and postoperative VTE and hematoma rates in patients treated with prophylactic enoxaparin 30 mg BID
Study Groups

BMI ≥30 (n= 190)

BMI <30 (n= 575)
Inclusion Criteria Patients undergoing H&N reconstruction with free flaps that received fixed-dose subcutaneous enoxaparin 30 mg BID postoperatively
Exclusion Criteria Patients who obtained enoxaparin later than postoperative day 1, treated with heparin drip intraoperatively, or received a chemoprophylaxis regimen other than enoxaparin 30 mg BID
Methods Retrospective review of medical records from 2012 to 2022. Patients received enoxaparin 30 mg BID starting from postoperative day 1. Outcomes included VTE, hematoma, and flap pedicle thrombosis within 30 days of surgery. Univariate and multivariable regression models were used to evaluate associations between BMI and outcomes
Duration January 2012 through March 2022
Outcome Measures

Primary: Incidence of VTE, hematoma, and flap pedicle thrombosis within 30 days of surgery

Secondary: Association between BMI and these outcomes
Baseline Characteristics   Total (N= 765)
Female 262 (34.24%)
Mean age, years 60.85 ± 12.64
Mean BMI, kg/m2 26.36 ±6.29
Obese (BMI ≥30) 190 (24.84%)
Caprini score ≥9 84 (10.98%)
FTT with osseous component 235 (30.72%)
Results   Total (n= 765) BMI ≥30 (n= 190) BMI <30 (n= 575)
VTE incidence 3.92% (30 patients) 6.8% (13 patients) 3.0% (17 patients)
Hematoma incidence 5.09% (39 patients) 3.7% (7 patients) 5.6% (32 patients)
Flap pedicle thrombosis incidence 6.53% (50 patients) 5.3% (10 patients) 7.0% (40 patients)
Adverse Events No specific adverse events reported beyond the primary outcomes of VTE, hematoma, and flap pedicle thrombosis.
Study Author Conclusions This cohort study found that obesity was associated with an increased risk of VTE in patients after microvascular H&N reconstruction and while on standard postoperative chemoprophylaxis regimens. This association may suggest insufficient VTE prophylaxis in this group and a potential indication for weight-based dosing.
Critique The study provides valuable insights into the association between BMI and VTE risk in patients undergoing H&N reconstruction. However, it is limited by its retrospective design and single-center setting, which may affect the generalizability of the findings. Additionally, the study did not explore alternative dosing strategies for enoxaparin, which could be beneficial for patients with varying BMI.

 

Table 8 References:
[17] Saadoun R, Bengur FB, Moroni EA, et al. Assessment of BMI and Venous Thromboembolism Rates in Patients on Standard Chemoprophylaxis Regimens After Undergoing Free Tissue Transfer to the Head and Neck. JAMA Otolaryngol Head Neck Surg. 2022;148(11):1051-1058. doi:10.1001/jamaoto.2022.2551
Testing a New Anticoagulation Method for Free Flap Reconstruction of Head and Neck Cancers
Design

Interventional study

N= 30
Objective To evaluate a new protocol for anticoagulation therapy and its effect on flap survival and complications
Study Groups All patients (N= 30)
Inclusion Criteria Patients with advanced head and neck cancer undergoing extensive surgical resection and reconstruction by microvascular free flap between 2013 and 2014
Exclusion Criteria Not specified
Methods Patients received aspirin (100 mg/day) for 5 days and enoxaparin (40 mg/day subcutaneously) for 3 days postoperatively. Various types of free flaps were used, and perfusion status was monitored by tissue color observation and pin prick test.
Duration

2013 to 2014

Follow-up: 3 weeks
Outcome Measures

Primary: Flap survival

Secondary: Need for re-exploration, venous and arterial thrombosis
Baseline Characteristics   All patients (N= 30)
Male 21 (70%)
Mean age, years (range) 45.06 (16 to 70)
History of previous chemoradiation 9 (30%)
Results   All patients (N= 30)
Complete necrosis or loss of flap 0%
Need for re-exploration 3 (10%)
Impaired venous flow leading to re-exploration 1 (3.3%)
Adverse Events No complete necrosis or loss of flap observed. Re-exploration needed in 3 patients (10%), with 2 due to hematoma and 1 due to impaired venous flow.
Study Author Conclusions The aspirin-enoxaparin short-term protocol may be a good choice after free flap transfer in reconstruction of head and neck surgical defects, achieving a 100% success rate in flap survival.
Critique The study's small sample size and lack of a control group limit the generalizability of the findings. Further studies with larger sample sizes and randomized controlled trials are needed to validate the results.

 

Table 9 References:
[18] Karimi E, Arrestant SHS, Jafari M, Hagh AB. Testing a New Anticoagulation Method for Free Flap Reconstruction of Head and Neck Cancers. Clinical and Experimental Otorhinolaryngology 2016; 9(4): 370-373. DOI: 10.21053/ceo.2015.01781