What studies are available with alternate injection sites (especially arms) for enoxaparin injections?

Comment by InpharmD Researcher

Available evidence evaluating subcutaneous enoxaparin injection sites other than the abdomen is limited and somewhat inconsistent. The arm, thigh, and deltoid have been studied as alternative sites, with most studies reporting no significant differences in bruising or hematoma formation compared with the abdomen. However, some evidence suggests the abdomen may be associated with less bruising and pain, while limited data indicate the deltoid may produce less bruising than the abdomen. The prescribing information recommends alternating injections between the left and right anterolateral and posterolateral abdominal wall but does not address administration in the arm or thigh. Importantly, available studies evaluated primarily local injection-site reactions and did not assess the anticoagulant efficacy or clinical effectiveness of enoxaparin when administered at alternative sites. Overall, the abdomen remains the preferred injection site, although limited evidence suggests the arm and thigh may be reasonable alternatives when abdominal administration is not feasible.
Background

A 2025 scoping review assessed subcutaneous injection techniques for low-molecular-weight heparin, including enoxaparin, and identified four studies comparing injection sites. Across these studies, abdominal injections were compared with the arm, deltoid, and thigh. One randomized controlled trial (Table 1) reported fewer hematomas at 72 hours with abdominal administration compared with the arm (p= 0.027), and another study (Table 2) found significantly smaller bruise size at 48 hours in the abdomen versus the arm (p<0.001). A separate study comparing abdomen and thigh injections of subcutaneous heparin reported higher pain in the thigh with no difference in bruising. In contrast, one within-subject study (Table 3) found smaller bruising at 72 hours with deltoid injections compared with the abdomen (p= 0.02) and concluded that the deltoid is more appropriate than the abdomen to minimize bruising. Overall, the review reports inconsistent findings across studies, with limited evidence suggesting the abdomen may be associated with fewer local adverse effects compared with other sites, but further research is needed. [1]

A 2021 systematic review and meta-analysis evaluated whether the site of subcutaneous LMWH injection influences the incidence and severity of local bruising and pain. Eleven studies, including randomized controlled and self-controlled trials, were analyzed. The authors found that subcutaneous injection in the abdominal area resulted in a lower incidence of bruising compared to the arm (risk ratio [RR] 0.76; 95% confidence interval [CI] 0.64 to 0.90; p<0.05; I²= 52%). However, the difference in bruising size between the abdominal and arm areas was only marginally significant (standardized mean difference [SMD] 0.08; 95% CI -0.45 to 0.62; p> 0.05; I² = 85%). When comparing the abdomen to the thigh, no significant difference in bruising size was observed (SMD -0.16; 95% CI -0.34 to 0.22; p> 0.05; I²= 32%). The severity of pain was lower with abdominal injections than with arm injections (RR 0.57; 95% CI 0.48 to 0.67; p<0.05; I²= 81%), although the intensity of pain between the two sites was not significantly different (mean difference -1.64; 95% CI -4.36 to 1.08; p> 0.05; I²= 99%). Based on these findings, it was concluded that the abdomen is the preferred site for subcutaneous LMWH injection, as it may reduce both local side-effects and patient discomfort. However, several limitations were noted, including inconsistent reporting of injection protocols, variation in outcome assessment timing, and potential biases in self-controlled trials. Due to these limitations, future large-scale randomized controlled trials should be conducted to confirm and strengthen the findings. [2]

Background References: [1] Wong AKC, Chu RYK, Nan Y, et al. Injection Techniques to Reduce Adverse Effects of Subcutaneous Low-Molecular-Weight Heparin Among Patients With Cardiovascular Diseases: A Scoping Review. J Adv Nurs. 2025;81(11):7361-7373. doi:10.1111/jan.16475
[2] Li Y, Dong S, Wang P, Sun J, Jiang H, Liu F. Influence of low-molecular-weight heparin injection sites on local bruising and pain: A systematic review and meta-analysis. J Clin Pharm Ther. 2021;46(3):688-697. doi:10.1111/jcpt.13323
Relevant Prescribing Information

Administration [1]
Subcutaneous Injection Technique:
Position patients in a supine position for enoxaparin sodium injection administration by deep subcutaneous injection.
Do not expel the air bubble from the prefilled syringes before the injection, to avoid the loss of drug.
Do not inject into skin that has bruises or scars. Do not inject through clothes.
Alternate injection sites between the left and right anterolateral and left and right posterolateral abdominal wall.
Introduce the whole length of the needle into a skin fold held between the thumb and forefinger; hold the skin fold throughout the injection. To minimize bruising, do not rub the injection site after completion of the injection.

Relevant Prescribing Information References: [3] Enoxaparin sodium injection. Prescribing information. Fresenius Kabi USA, LLC; 2026.
Literature Review

A search of the published medical literature revealed 5 studies investigating the researchable question:

What studies are available with alternate injection sites (especially arms) for enoxaparin injections?

Level of evidence

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


Please see Tables 1-5 for your response.

Ecchymosis and/or haematoma formation after prophylactic administration of subcutaneous enoxaparin in the abdomen or arm of the critically ill patient
Design

Randomised, two-arm clinical trial (injection in the abdomen vs the arm)

N= 301
Objective To evaluate the adverse events, ecchymosis and/or haematoma after the administration of prophylactic subcutaneous enoxaparin in the abdomen vs the arm in the critically ill patient
Study Groups

Abdomen (n= 149)

Arm (n= 141)
Inclusion Criteria Patients receiving prophylactic enoxaparin, admitted >72 h, with no liver or haematological disorders, a body mass index (BMI) >18.5, not pregnant, of legal age and with no skin lesions
Exclusion Criteria Patients who died or were transferred to another hospital before completing the evaluation
Methods Randomised, prospective and blind trial in a multipurpose intensive care unit. Enoxaparin was administered subcutaneously in the abdomen or arm. The injection site was selected at random. The administration followed the best evidence from the bibliography and manufacturer's instructions. Ecchymosis and/or haematoma were evaluated at 12, 24, 48, and 72 hours after injection.
Duration July 2014 to January 2017
Outcome Measures

Primary: Incidence of ecchymosis and haematoma

Secondary: Size of haematomas after 72 hours
Baseline Characteristics   Abdomen (n= 149) Arm (n= 141)
Women 51 (34.2%) 50 (35.5%)
Age, years 67 ± 15 69 ± 14
Stay, days 12 (7-26) 13 (8-25)

BMI, kg/m2        

          < 20 (slim)

          20-25 (normal)

          25-30 (overweight)

          30-40 (obesity)

          > 40 (morbid obesity)

 

2 (1.3%)

41 (27.5%)

63 (42.3%)

38 (25.5%)

5 (3.4%)

 

2 (1.4%)

35 (24.8%)

71 (50.4%)

30 (21.3%)

3 (2.1%)
SAPS II 42 ± 16 41 ± 16
Deaths 9 (6%) 10 (7.1%)

Dose administered

          20 mg

          40 mg

          60 mg

 

39 (26.2%)

109 (73.2%)

1 (0.7%)

 

29 (20.6%)

109 (77.3%)

3 (2.1%)

Antiaggregants

 34 (22.8%)   30 (21.3%)
Abbreviations: BMI: body mass index; SAPS: Simplified Acute Physiologic Score-II
Results   Abdomen (n= 149) Arm (n= 141) p-value
Ecchymosis 66 (44.3%) 72 (51.1%) 0.249
Haematoma 9 (6.0%) 14 (9.9%) 0.221
Area of haematoma at 72 h, mm2 2 (1-5.25) 20 (5.25-156) 0.027
Adverse Events No significant differences in the incidence of ecchymosis and haematoma between abdomen and arm. However, the size of haematomas was significantly larger in the arm after 72 hours.
Study Author Conclusions In our patient cohort, prophylactic subcutaneous enoxaparin administered in the abdomen causes fewer haematomas after 72 hours than when administered in the arm. The incidence rate of ecchymosis and haematoma was lower than the published incidence in critically ill patients, although patients receiving anti-platelet agents present a higher risk of injury. No relationship was observed in relation to BMI.
Critique The study provides valuable insights into the administration of enoxaparin in critically ill patients, highlighting the abdomen as a preferable site to reduce haematoma size. However, the study's findings may be limited by its single-center design and the exclusion of patients with certain conditions, which could affect the generalizability of the results. Additionally, the study did not explore the impact of different injection techniques on the outcomes.
Table 1 References:
[4] Jareo-Collado R, Snchez-Snchez MM, Fraile-Gamo MP, et al. Ecchymosis and/or haematoma formation after prophylactic administration of subcutaneous enoxaparin in the abdomen or arm of the critically ill patient. Formacin de equimosis y/o hematoma tras la administracin profilctica de enoxaparina subcutnea en abdomen o brazo en pacientes crticos. Enferm Intensiva (Engl Ed). 2018;29(1):4-13. doi:10.1016/j.enfi.2017.11.001
Comparing the Effect of Duration and Site of Subcutaneous Injection of Enoxaparin on Pain Intensity and Bruising Size in Patients Admitted to Cardiac Care Units
Design

Randomized clinical trial

N= 60
Objective To compare the effect of duration and site of subcutaneous injection of enoxaparin on pain intensity and bruise size in patients admitted to cardiac care units
Study Groups

30-second injection group (n= 30)

15+5-second injection group (n= 30)
Inclusion Criteria Adult patients; no neuromuscular disease or known skin disease and coagulation disorder; no type 1 or type 2 insulin-treated diabetes; no swelling, sores, scratches, redness in the injection site; body mass index between 18.5 and 30
Exclusion Criteria Death, discharge before 48 hours, intravenous anticoagulation for any reason, need for subcutaneous injection other than enoxaparin in the abdomen and arms
Methods Participants were randomly assigned to two groups: 30-second injection and 15+5-second injection. Enoxaparin was injected subcutaneously in the abdomen and arm according to the doctor's prescription (40 or 60 mg). Pain intensity was measured immediately after injection using VAS, and bruise size was measured 24 and 48 hours after injection with a clear millimeter ruler. Data were analyzed using SPSS version 21
Duration Data collection in 2019
Outcome Measures

Primary: Pain intensity and bruise size

Secondary: Comparison of injection sites (abdomen vs. arm)
Baseline Characteristics   30-s injection (n= 30) 15+5-s injection (n= 30)
Age, years  62.86 ± 6.41 62.03 ± 7.54
Women 53.3% 43.3%

Reason for hospitalization

          Acute coronary syndrome

          Myocardial infarction

          Other

 

40%

43%

17%

 

50%

30%

20%
Results   30-s injection (n= 30) 15+5-s injection (n= 30) p-value

Pain intensity 

          Abdomen

          Arm

 

6.9 ± 0.2

4.72±0.3

 

53.5 ± 0.3

43.93 ± 0.4

 

<0.001

<0.001

Bruise size after 24 hours 

          Abdomen

          Arm

 

1.99 ± 8.03

2.56 ± 9.03

 

2.87 ± 10.93

3.27 ± 12.13

 

<0.001

<0.001

Bruise size after 48 hours 

          Abdomen

          Arm

 

3.07 ± 15.76

3.40 ± 17.96

 

3.64 ± 18.36

6.30 ± 20.46

 

0.004

0.061
Adverse Events See results
Study Author Conclusions The 30-second injection technique resulted in a significant decrease in pain intensity and bruise size due to the subcutaneous injection of enoxaparin. The extent of bruising in the abdominal site was less than the arm, so the abdomen is recommended for subcutaneous injection of enoxaparin.
Critique The study provides valuable insights into the impact of injection duration and site on pain and bruising, but the small sample size and single-center design may limit the generalizability of the findings. Additionally, the subjective nature of pain assessment could introduce bias. Further studies with larger sample sizes and diverse populations are recommended.
Table 2 References:
[5] Sarani H, Navidian A, Tabas EE, Mendi AA. Comparing the Effect of Duration and Site of Subcutaneous Injectionof Enoxaparin on Pain Intensity and Bruising Size in PatientsAdmitted to Cardiac Care Units. Journal of Internal Medicine Today. 2020; 26(4): 348-3
Low-Molecular Weight Heparin and Complications of Subcutaneous Injection: How Important Is Injection Site Selection?
Design

Within-subject, quasi-experimental study

N= 41
Objective To compare pain and bruising associated with subcutaneous injection of the LMWH enoxaparin at two sites: abdomen and deltoid
Study Groups All patients (n= 41)
Inclusion Criteria Patients hospitalized in the Coronary Care Unit, able to communicate verbally in Persian, able to rate pain intensity, and have orders to receive enoxaparin twice a day
Exclusion Criteria History of hematologic diseases, coagulation problems, acute kidney failure, and scars or bruises at the injection sites
Methods Patients received two subcutaneous injections of enoxaparin, one in the abdomen and one in the deltoid (arm), 12 hours apart. Pain was assessed using the Visual Analog Scale immediately, 48 hours, and 72 hours after each injection. Bruising size was measured with a flexible ruler 48 and 72 hours after each injection. Comparison of pain and bruising was completed with independent t test and repeated measures test.
Duration March to September 2014
Outcome Measures Primary: Pain intensity and bruising size at 48 and 72 hours after injection
Baseline Characteristics   All patients (n= 41)
Age, years (range) 40-75
Female 23 (56.1%) 

Diagnosis

          Acute coronary syndrome

          Heart failure

          Myocardial infarction

          Hypertension

 

28 (68.3%)

6 (14.6%)

6 (14.6%)

1 (2.4%)
Results   Arm Abdomen p-value

Pain 

          Immediately after injection

          48 hours after injection

          72 hours after injection

 

44.32%

43.74%

42.39%

 

38.68%

39.26%

40.61%

 

0.2

0.35

0.7

Bruising 

          48 hours after injection

          72 hours after injection

 

36.44%

35.63 %

 

46.56%

47.37%

 

0.051

0.02
Adverse Events See results
Study Author Conclusions Findings of this study suggested the deltoid is a more appropriate injection site for LMWH than the abdomen to minimize bruising.
Critique The study's within-subject design allowed for control of confounding factors, but the small, nonrandomized sample and lack of bioavailability assessment limit generalizability. The sequence of injections was not randomized, which could introduce bias in pain reporting. The study focused on a specific patient population, limiting applicability to other groups.
Table 3 References:
[6] Babaieasl F, Yarandi H, Moosazadeh M, Kheradmand M. Low-Molecular Weight Heparin and Complications Of Subcutaneous Injection: How Important Is Injection Site Selection? Medsurg nursing. 2018;27(3):191-194. Accessed July 18, 2024.
Assessment of Three Sites in Terms of Bruising in Subcutaneous Heparin Administration
Design

Quasi-experimental design and randomized

N= 60
Objective To investigate the occurrence of bruising after subcutaneous heparin injection administered to three sites
Study Groups All patients (n= 60)
Inclusion Criteria Age between 30 and 65 years; no scar, incision, lipodystrophy or infection symptom at the sites where the injection is performed; no allergy history; and receipt of clexane (0.6 cc or 0.4 cc) treatment
Exclusion Criteria Not specified
Methods Subcutaneous heparin injections were administered in the arm, abdominal, and thigh areas of 60 patients. Enoxaparin was used as the intervention material. Bruise sizes were assessed using a bruise measurement tool 48 and 72 hours after the injection. Data were analyzed using one-way ANOVA and independent sample t-test
Duration October 2012 to February 2013
Outcome Measures

Primary: Occurrence and size of bruising at different injection sites

Secondary: Comparison of bruise sizes based on age and gender
Baseline Characteristics   All patients (n= 60)

Age

          30-47

          48-65

 

10 (16.7%)

50 (83.3%)
Female 30 (50.0%)

Service

          Chest Service

          Neurology Service

 

27 (45.0%)

33 (55.0%)
Results   48 Hours After Injection Size of Bruising (mm2) 72 Hours After Injection Size of Bruising (mm2)
Abdomen 62.52 ± 202.21 42.63 ± 156.84
Arms 13.62 ± 35.73 6.23 ± 17.74
Thigh 28.91 ± 185.20 26.00 ± 181.82
Adverse Events See results
Study Author Conclusions These three sites (abdomen, arm, and thigh) showed no differences in terms of occurrence of bruise, and no particular site is superior.
Critique The study was limited by its small sample size and lack of detailed exclusion criteria. The quasi-experimental design may limit the generalizability of the findings. Further studies with larger sample sizes are recommended to determine the most reliable site for reducing bruising after subcutaneous heparin injection.
Table 4 References:
[7] Ciftci B, Avsar G. Assessment of three sites in terms of bruising in subcutaneous heparin administration. International Journal of Caring Sciences, 2016; 9(3), 923-931
The Effect of Two Types of Subcutaneous Heparin Injections on Pain, Ecchymosis, Hematoma and Drug Absorption: A Quasi‐Experimental Study
Design

Quasi-experimental study

N= 122
Objective To investigate the effect of two types of subcutaneous low-molecular weight heparin (LMWH) injections on pain, ecchymosis, hematoma, and drug absorption rates
Study Groups

Tissue‐releasing technique (TRT; n= 68)

Tissue‐pinching technique (TPT; n= 54)
Inclusion Criteria Being on an LMWH type of medication according to a treatment plan recommended by a physician; Being over 18 years of age; Having no communication problems; Not having undergone a surgical procedure involving the injection site; Having been hospitalised for at least 4 days after heparin therapy; Volunteering; The area other than the last injection area was preferred for injection
Exclusion Criteria Having an incision, scar tissue, lipodystrophy, ecchymosis, or hematoma on the injection site; Being allergic to heparin; Being pregnant; Not being on medications incompatible with heparin; Having a hematological disease or coagulation disorder; Being on blood thinners other than subcutaneous heparin; Having received a subcutaneous injection on the same site 24 h ago; Declining to participate
Methods Participants were divided into two groups based on subcutaneous tissue thickness. Group TRT received LMWH injections using the tissue-releasing technique, while Group TPT received injections using the tissue-pinching technique. Injections were administered into the arm or abdomen. Ultrasonography was used to measure subcutaneous tissue thickness before injections. Pain, ecchymosis, hematoma, and drug absorption were monitored for 3 days post-injection.
Duration September 2021 to May 2022
Outcome Measures

Primary: Prevalence of pain, ecchymosis, and hematoma

Secondary: Drug absorption rates
Baseline Characteristics   Tissue-releasing (n= 68) Tissue-pinching (n= 54)
Age, years 64.5 (57.75−71.25) 65 (57.75−74)
Female 36 (52.9%) 26 (48.1%)

BMI, kg/m2

          Underweight

          Normal weight

          Overweight

          Obese

 

3 (4.4%)

24 (35.3%)

12 (17.6%)

29 (42.6%)

 

0

18 (33.3%)

10 (18.5%)

26 (48.1%)

Drug dosage

          0.4 mL

          0.6 mL

 

49 (72.1%) 

19 (27.9%) 

 

41 (75.9%)

13 (24.1%)

SC injection site

          Right arm

          Left arm

          Right abdomen

          Left abdomen

 

16 (23.5%) 

18 (26.5%) 

19 (27.9%) 

15 (22.1%) 

 

11 (20.4%)

16 (29.6%)

8 (14.8%)

19 (35.2%)
Abbreviations: BMI, body mass index; SC, subcutaneous 
Results   Tissue-releasing (n= 68) Tissue-pinching (n= 54) p-value
Pain 3 (11.1%) 2 (5.9%) 0.463
Ecchymosis 2 (3.7%) 1 (1.5%) 0.427
Hematoma 4 (14.8%) 1 (2.9%) 0.096

Drug absorption 

          Arm

          Abdomen

 

70.3%

100%

 

94.2%

100%

0.086

-

-
Adverse Events No significant difference in the prevalence of pain, ecchymosis, and hematoma between the groups. Abdominal injections caused no complications.
Study Author Conclusions The tissue-releasing and tissue-pinching techniques are not superior to each other in terms of drug absorption, pain, ecchymosis, and hematoma. The abdominal region is recommended for injections when subcutaneous tissue thickness is less than 15.96 mm. Nurses should consider BMI before choosing the injection site and technique.
Critique The study provides valuable insights into the effects of different injection techniques on complications and drug absorption. However, the quasi-experimental design and sample-specific results limit generalizability. The study did not use a simple random sampling method, which may introduce bias. Additionally, the study's reliance on self-reported data for pain assessment could affect the accuracy of the findings.
Table 5 References:
[8] Bayram SB, Gulnar E, Calskan N, et al. The Effect of Two Types of Subcutaneous Heparin Injections on Pain, Ecchymosis, Hematoma and Drug Absorption: A Quasi-Experimental Study. J Eval Clin Pract. 2025;31(1):e14266. doi:10.1111/jep.14266