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Low-Molecular Weight Heparin and Complications of Subcutaneous Injection: How Important Is Injection Site Selection?

Low-molecular weight heparin (LMWH) (e.g., enoxaparin [Lovenox[R]]) is used widely to reduce patients' risk of harmful clot formation. It has several potential advantages: reliable anticoagulant effect, lower incidence of heparin-induced thrombocytopenia, and a simple subcutaneous administration that permit short-term and long-term treatment (Palese, Aidone, Dante, & Pea, 2013). However, more than 90% of subcutaneous injections of LMWH by nurses lead to pain and bruising (Akbari Sari, Janani, Mohammady, & Nedjat, 2014).

Subcutaneous injection usually is selected when slow, continuous medication absorption is desired. The medication is injected into fat and connective tissue underlying the dermis, where there is less blood flow and as a result slower medication absorption. The umbilical region of the abdomen, and lateral arms and thighs are considered appropriate sites for subcutaneous injection (Akbari Sari et al., 2014). Research has found the occurrence and size of bruising, as well as pain of subcutaneous injection, can be influenced by multiple actions. These include appropriate selection of injection site and needle size, injection duration, aspiration of the syringe before injection, application of local dry heat, and massage after the injection (Amaniyan, Varaei, Vaismoradi, Haghani, & Sieloff, 2016; Avsar & Kasikci, 2013; Balci Akpinar, 2013; Pourghaznein, Azimi, & Jafarabadi, 2014; Sendir, Buyukyilmaz, Zelik, & Taskopru, 2015).

Because patient safety and quality of care are primary nursing concerns, nurses are accountable for taking steps to prevent and limit such side effects through appropriate medication administration.

Significance of Research

The thicker subcutaneous tissue (>25 mm) and larger surface area of the abdominal wall are believed to reduce the risk of extravasation of enoxaparin (Avsar & Kasikci, 2013). However, abdominal wall hematomas and fetal rectus sheath hematoma have been reported in multiple studies related to subcutaneous injection (Hatjipetrou, Anyfantakis, & Kastanakis, 2015; Miguel-Gomez, Fonda-Pascual, Carrillo-Gijon, & Munoz-Zato, 2016; Salemis et al., 2014).

Although healthcare professionals and drug manufacturers consider the abdomen the best location for enoxaparin injection, clinical observations show patients typically experience bruising in this area (Avsar & Kasikci, 2013; Hatjipetrou et al., 2015; Miguel-Gomez et al., 2016). Bruising, which results from the escape of blood from damaged blood vessels into subcutaneous tissues, may limit possible sites for future injections. It also may cause unpleasant experiences that can lead patients to reject treatment due to reduced trust in nurses' competence to perform the injections, anxiety, and disruption of body image (Palese et al., 2013). Furthermore, pain resulting from medication administration can contribute to physical and psychological discomfort (Pourghaznein et al., 2014) because patients usually associate pain with skin tissue injury and bruising that appears later. By reducing pain and bruising experienced with LMWH, nurses can build more trusting relationships with patients, reduce anxiety, and promote a healthy body image in patients.

Purpose of Research

The purpose of this study was to compare pain and bruising associated with subcutaneous injection of the LMWH enoxaparin at two sites: abdomen and arm.

Literature Review

An extensive literature search was conducted using CINAHL, PubMed/Medline, and EBSCO. Key words included LMWH, enoxaparin, bruising, pain, and subcutaneous injection. All relevant work for 2012-2016 published in English in peer-reviewed journals was included. Of 38 identified studies, 16 articles related to the study topic were selected for review.

All selected studies indicated subcutaneous injection of LMWH is related to adverse effects, such as bruising, pain, induration, and hematoma formation. The majority of studies examined the effect of injection duration on the occurrence of bruising and pain. For example, a quasi-experimental study by Ahmadi, Ahmadi, Saadati, and Mehrpour (2016) used a sample of 86 patients admitted to the Cardiology Department to investigate the effect of increasing injection time on pain intensity and bruising. Subjects first received 10-second injections and 24 hours later received 30-second injections. Then bruising size and pain intensity were measured 48 and 72 hours after each method of injection. The size of bruising caused by the 30-second injection was significantly less than that of the 10-second injection (p<0.05). Pain intensity also was significantly different between the two injection methods (p=0.005).

Available studies found slow injection decreases pain and bruising size caused by LMWH injection (Palese et al., 2013; Pourghaznein et al., 2014). However, results of a systematic review showed limited difference in pain and bruising sizes following slow versus fast injection (Akbari Sari et al., 2014). The systematic review included 15 full-text articles, one of which was a randomized controlled trial (RCT). Results of the RCT (N=50) showed bruising sizes were smaller with slow injection (18.76 [+ or -] 9.32 mm) compared to fast injection (109.2 [+ or -] 468.66 mm) at 48 hours follow up.

The authors' search found four studies that considered application of cold and/or heat to decrease side effects (Amaniyan et al., 2016; Balci Akpinar, 2013; Batra, 2014; Sendir et al., 2015). Amaniyan and colleagues (2016) conducted an RCT to investigate effect of cold and alternating cold pack and hot packs (1060 minutes) on the size of bruising at the enoxaparin injection site. Presence of bruising was assessed 24, 48, and 72 hours after injections. Repeated measures of analyses of variance (RMANOVA) were used to compare bruising in different groups. Results indicated application of cold and hot packs decreased bruising compared to application of only a cold pack at 48 and 72 hours (both p<0.01).

Sendir and co-authors (2015) examined the effect of injection duration and use of a cold compress on bruising size and pain intensity. Authors employed three experimental groups: 30-second injection duration (group A); 30-second injection duration and 5-minute local application of a dry cold compress before and after injection (group B); and 10-second injection with no dry cold application (group C). Injection duration and cold compress use were evaluated using RMANOVA. Results showed significant differences in pain and bruising over time among study groups (p<0.05). The percentage of bruising was 70% in group C, 40% in group A, and 35% in group B. The mean pain intensity was 2.20 [+ or -] 2.04, 2.50 [+ or -] 2.67, and 5.00 [+ or -] 4.18 in groups A, B, and C respectively. Subcutaneous injection duration of 30 seconds and 5-minute local dry cold application was effective in decreasing pain intensity and bruising size. Subcutaneous injection duration of 30 seconds and 5-minute local dry cold application was effective in decreasing pain intensity and bruising size.

Few studies indirectly compared various injection sites to reduce pain and bruising while examining different methods of injection. Pourghaznein and colleagues (2014) conducted a quasi-experimental study to compare four methods of subcutaneous heparin injection on pain and bruising in abdomen and thighs: 10-second injection; 10-second injection and waiting 10 seconds before withdrawing needle; 15-second injection and waiting 5 seconds before withdrawing needle; and 5-second injection and waiting 15 seconds before withdrawing needle. Results indicated a significant difference among bruising in all methods and both sites (p<0.05). However, authors reported no significant differences in bruising between abdomen and thigh for all four methods. Pain intensity did not differ by method but was significantly higher in the thigh than abdomen (p<0.05).



Participants were recruited from patients hospitalized in the Coronary Care Unit of a university hospital in Babol, Northern Iran, in March-September 2014. All patients who met inclusion criteria were eligible for the study: able to communicate verbally in the local language (Persian) and rate their pain intensity, and have orders to receive enoxaparin twice a day. Patients with a history of hematologic diseases, coagulation problems, or acute kidney failure, and those with scars or bruises at the injection sites were excluded. Written informed consent as approved by Babol University of Medical Sciences Ethics Committee was obtained from all subjects by a trained nurse responsible for enoxaparin injection. Patients' demographic data (age, gender identity, diagnosis) were collected by the researcher after patient consent was received.


In this quasi-experimental study, subjects served as their own controls. Each subject received two injections from the same nurse in the abdomen and arm, with the second injection completed 12 hours after the first. Administering an injection at both sites allowed researchers to control for confounding factors (e.g., age, gender identity, co-morbid diseases). A qualified trained nurse injected the prefilled enoxaparin for all patients. The same nurse also assessed pain and bruising in all patients.

The first subcutaneous injection was administered in the lateral abdomen about 5 cm from the umbilicus. The second dose of enoxaparin was injected subcutaneously into the deltoid 12 hours later. Injection technique was the same for both sites. First, injection sites were disinfected with alcohol wipes outwardly and left to dry. The needle then was inserted at a 90[degrees] angle for the abdomen and 45[degrees]-90[degrees] for the deltoid, depending on presence of subcutaneous fat, while the skin was pinched. After injection, the needle was removed smoothly and the site was pressed slightly with cotton wool. All patients were told not to rub or massage injection sites, which were circled and labeled with waterproof marker. The circled areas had an average diameter of 5 cm.


A Visual Analog Scale (0-10 mm) was used to assess subjects' pain immediately, and at 48 and 72 hours after each injection. Pain intensity was identified by the patients (0=no pain, 10=most severe pain imaginable). The clinical nurse who administered the injection recorded each patient's intensity score. The nurse also measured the size of bruising with a flexible ruler at 48 and 72 hours after each injection.

Procedures for Data Analysis

Data were analyzed using SPSS 21 (IBM Corp.; Armonk, NY). Comparison of pain and bruising at the sites was analyzed by independent t test; mean of pain and bruising at injection sites was compared by repeated measures test.


This is the first study comparing side effects of enoxaparin injection in the abdomen and arm. Of 41 patients (ages 40-75) who participated in this study, 56.1% (n=23) were female. Acute coronary syndrome (68.3%, n=28), heart failure (14.6%, n=6), myocardial infarction (14.6%, n=6), and hypertension (2.4%, n=1) were the most prevalent patient diagnoses. See Table 1 for comparison of pain and bruising at the two injection sites. The mean score of pain in deltoid and abdomen did not differ significantly at any assessed time. However, a marginally significant difference was found between bruising by site after 48 hours (p=0.051). In addition, a significant difference was found in bruising at the two sites after 72 hours (p=0.02). In both instances, bruising in the abdomen was greater than in the deltoid.

Repeated measurements showed significant differences in pain at different times in arms and abdomens, with pain after 72 hours being significantly lower than pain immediately after injection in both sites (see Table 2). The same pattern was seen for bruising after 48 and 72 hours. The size of bruising was significantly different after 48 and 72 hours in both sites (see Table 3). Mean of pain in the arm was greater than in the abdomen at all assessed times, but mean of bruising in abdomen was significantly greater than in the arm (see Tables 1 & 2).


Researchers investigated the most frequent sides effects of subcutaneous injection of LMWH (pain and bruising), and their relation to two injection sites (abdomen and deltoid). Techniques used for injection in this study have been suggested to decrease bruising in subcutaneous LMWH injections (Batra, 2014). However, no clear consensus existed regarding a superior injection technique.


Researchers did not assess the bioavailability of enoxaparin because both injections were done in the same patients. Because subjects were all Caucasian and had a diagnosis of cardiovascular disease, generalizability of the findings is limited to similar groups. The lack of generalizability also is related to the small, nonrandomized sample, with its unequal number of male and female subjects. Finally, the sequence of administering the injection should have been randomized to avoid introducing bias into pain data.

Nursing Implications

Nurses and others who administer LMWH (e.g., patients, family members) should be educated about risks of abdominal injection and select the best injection techniques to avoid tissue injury, especially if patients have chronic diseases or need long-term administration of LMWH. Because risk of abdominal wall bruising and serious hemorrhage is higher in older adults and thin patients (Agarwal, Lamani, Goudar, Kalburgi, & Bhavi, 2017; Chung, 2016), use of the deltoid for LMWH injection for these groups can help improve quality of care and minimize unpleasant and stressful experiences. Findings of this study suggested nurses can consider the deltoid as a potential site for injection of enoxaparin.

Recommendations for Future Research

Pain and bruising are less significant clinically than development of venous thromboembolism from ineffective anticoagulation. Therefore, bioavailability of enoxaparin after injection should be assessed through additional research. To confirm this study's results, further large-scale RCTs are warranted.


Current practice for administration of subcutaneous LMWH in the abdomen causes major side effects, such as bruising and pain (Akbari Sari et al., 2014). Findings of this study suggest the deltoid is a more appropriate injection site than the abdomen to reduce bruising. Nurses should be introduced to techniques that can reduce bruising. Reduction of adverse effects can enhance the availability of sites for future injections.

Acknowledgments: The researchers express their gratitude to the Management and Nursing offices of the study hospital (Beheshti Hospital), and patients who participated in this study. The authors also would like to express their sincere appreciation to Ms. Maryam Sohrabi and Masomeh Saberian, staff nurses in the Coronary Care Unit at Beheshti Hospital, for their enthusiastic work throughout the data collection of this study.

Note: This study was supported in part by the Research Center of Babol University of Medical Sciences, Babol, Iran.


The abdominal area has been considered the best location for subcutaneous injection of low-molecular weight heparin (LMWH); however, clinical observations indicated patients may experience bruising and pain after abdominal administration. The purpose of this study was to compare these adverse effects when LMWH was administered at two different sites (lateral abdomen and deltoid).


Forty patients in a coronary care unit participated in this within-subject, quasi-experimental study. The Visual Analog Scale (0-10 mm) was used to assess subjects' pain intensity immediately, 48 hours, and 72 hours after each injection. The size of bruising was measured using a flexible ruler 48 and 72 hours after each injection. Comparison of pain and bruising at different sites was completed with independent t test, and the mean results of pain and bruising assessments were compared by repeated measures test.


The mean score of pain at the two injection sites did not differ significantly at any of the three assessments. However, the difference in bruising size between deltoid and abdomen was marginally significant after 48 hours (p=0.051). A significant difference in bruising size at the two injection sites was found after 72 hours (p=0.02).


Findings of this study suggested the deltoid is a more appropriate injection site for LMWH than the abdomen to minimize bruising.


Agarwal, S., Lamani, Y.P., Goudar, B.V., Kalburgi, E.B., & Bhavi, B.K. (2017). Rectus sheath haematoma secondary to enoxaparin injection: A rare case report. Journal of Clinical Diagnostic Research, 11(3), PD11-PD12. doi:10.7860/JCDR/2017/23849.9589

Ahmadi, M., Ahmadi, R., Saadati, Z., & Mehrpour, O. (2016). The effect of extended injection of subcutaneous heparin on pain intensity and bruising incidence. Electron Physician, 8(7), 2650-2654. doi:10.19082/2650

Akbari Sari, A., Janani, L., Mohammady, M., & Nedjat, S. (2014). Slow versus fast subcutaneous heparin injections for prevention of bruising and site-pain intensity. The Cochrane Database of Systematic Review, CD008077. doi:10.1002/14651858.CD008077.pub3

Amaniyan, S., Varaei, S., Vaismoradi, M., Haghani, H., & Sieloff, C. (2016). Effect of local cold and hot pack on the bruising of enoxaparin sodium injection site: A randomized controlled trial. Contemporary Nurse, 52(1), 30-41. doi:10.1080/10376178.2016.1190289

Avsar, G., & Kasikci, M. (2013). Assessment of four different methods in subcutaneous heparin applications with regard to causing bruise and pain. International Journal of Nursing Practice, 19(4), 402-408. doi:10.1111/ijn.12079

Balci Akpinar, R. (2013). The effect of local dry heat pack application on recovering the bruising associated with the subcutaneous injection of heparin. Journal of Clinical Nursing, 22(17-18), 2531-2535. doi:10.1111 /jocn. 12216

Batra, G. (2014). Application of ice cube prior to subcutaneous injection of heparin in pain perception and ecchymosis of patients with cardiovascular problems. The Nursing Journal of India, 105(4), 155-159.

Chung, K.T. (2016). Intra-abdominal hematoma following enoxaparin injection. Clinical Medicine Insights Case Report, 9, 35-38. doi:10.4137/CCRep.S17881

Hatjipetrou, A., Anyfantakis, D., & Kastanakis, M. (2015). Rectus sheath hematoma: A review of the literature. International Journal of Surgery, 13, 267-271. doi :10.1016/j.ijsu.2014.12.015

Miguel-Gomez, L., Fonda-Pascual, P., Carrillo-Gijon, R., & Munoz-Zato, E. (2016). Bullous hemorrhagic dermatosis probably associated with enoxaparin. Indian Journal of Dermatology, Venereology and Leprology, 82(3), 319-320. doi :10.4103/0378-6323.175915

Palese, A., Aidone, E., Dante, A., & Pea, F. (2013). Occurrence and extent of bruising according to duration of administration of subcutaneous low-molecularweight heparin: A quasi-experimental case-crossover study. Journal of Cardiovascular Nursing, 28(5), 473-482.

Pourghaznein, T, Azimi, A.V., & Jafarabadi, M.A. (2014). The effect of injection duration and injection site on pain and bruising of subcutaneous injection of heparin. Journal of Clinical Nursing, 23(7-8), 1105-1113.

Salemis, N.S., Oikonomakis, I., Lagoudianakis, E., Boubousis, G., Tsakalakis, C., Sourlas, S., & Gourgiotis, S. (2014). Enoxaparininduced spontaneous massive retroperitoneal hematoma with fatal outcome. American Journal of Emergency Medicine, 32(12), 1559. doi:10.1016/j.ajem. 2014.05.026

Sendir, M., Buyukyilmaz, F., Qelik, Z., & Taskopru, I. (2015). Comparison of 3 methods to prevent pain and bruising after subcutaneous heparin administration. Clinical Nurse Specialist, 29(3), 174-180.

Faezeh Babaieasl, MSN, is PhD Candidate, School of Nursing, Wayne State University, Detroit, MI.

Hossein Yarandi, PhD, is Professor, School of Nursing, Wayne State University, Detroit, MI.

Mahmood Moosazadeh, PhD, is Assistant Professor, Health Sciences Research Center, Addiction Institute, Mazandaran University of Medical Sciences, Sari, Iran.

Motahareh Kheradmand, PhD, is Assistant Professor, Health Sciences Research Center, Addiction Institute, Mazandaran University of Medical Sciences, Sari, Iran.
TABLE 1. Comparison of Frequency of Pain and Bruising
by Injection Site

                                       Arm    Abdomen   p Value
                                       (%)      (%)

                 Immediately          44.32    38.68      0.2
               after injection
Pain       48 hours after injection   43.74    39.26     0.35
           72 hours after injection   42.39    40.61      0.7
Bruising   48 hours after injection   36.44    46.56     0.051
           72 hours after injection   35.63    47.37     0.02

TABLE 2. Mean of Pain by Injection Site Using Repeated
Measures ANOVA

Site       After Injection       48 Hours after

Arm       4.2 [+ or -] 3.02    2.24 [+ or -] 1.7
Abdomen   1.75 [+ or -] 1.06   3.44 [+ or -] 2.64

Site       72 Hours after     p Value

Arm       1.98 [+ or -] 1.6    0.00
Abdomen   1.66 [+ or -] 1.6    0.00

TABLE 3. Mean of Bruising by Injection Site Using Repeated
Measures ANOVA

Site         48 Hours after        72 Hours after      p Value
               Injection              Injection

Arm        5.0 [+ or -] 10.62    5.0 [+ or -] 10.88     0.01
Abdomen   14.51 [+ or -] 16.61   15.34 [+ or -] 16.4    0.05
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Title Annotation:Research for Practice
Author:Babaieasl, Faezeh; Yarandi, Hossein; Moosazadeh, Mahmood; Kheradmand, Motahareh
Publication:MedSurg Nursing
Article Type:Report
Date:May 1, 2018
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