Heparin has been used to treat burn patients since the 1960s. It is believed to have anti-inflammatory and wound healing properties. However, the evidence for its efficacy is poor. A 2018 study found heparin improved burn wound healing compared to saline, but larger studies are needed. Most reviews find a lack of strong evidence due to flaws in study design and missing data. A recent trial of nebulized heparin in burns was stopped early due to low enrollment and safety concerns. While heparin may help superficial burns, there is little evidence it benefits deep burns. Further research is still needed before recommending heparin treatment for burns.

1. Heparin
in Burns
BY Linus Lay Pharm.D. Candidate University of
Rhode Island Class of 2022
3/1/2021

2. Agenda
1. Overview of Heparin
2. Heparin in clinical practice
3. Burn patient overview
4. Heparin in Burn patients
5. Medication Administration
6. Research studies and Analysis
7. Discussion and Conclusion

3. What is Heparin?
• Heparin is an anticoagulant/blood thinner used to prevent blood clots from forming in
specific blood diseases including Venous Thromboembolism (VTE) and cardioembolic
stroke prophylaxis.
• Heparin’s chemical structure is a glycosaminoglycan, a complex carbohydrate that is
isolated from porcine (pig) intestinal mucosa or bovine (cattle) lung.
• The injectable drug is widely used around the world in clinical practice as deep vein
thrombosis (DVT) (900,000 patients/year), dialysis (370,000 patients/year), IV and
central line flushing, and surgical procedures including over half-million per year
cardiac surgeries.
Heparin Market Report. (n.d.). University of Arkansas. Retrieved February 22, 2021, from
https://research.uark.edu/documents/techventures/tech_docs/heparin_market_report.pdf

4. Products and dosage forms available
FDA “how supplied” (porcine
intestinal mucosa)
• Heparin sodium (unfractionated [UFH])
• In 0.45% or 9% sodium chloride
• In 5% dextrose injection
Heparin sodium, for intravenous use. (n.d.) Retrieved on February 24, 2021 on
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/017029s140lbl.pdf

5. Heparin shortage
FDA Drug Shortages. (n.d.). Retrieved 22, 2021 from https://www.accessdata.fda.gov/scripts/drugshortages/dsp_ActiveIngredientDetails.cfm?AI=Heparin Sodium and Sodium
Chloride 0.9per Injection&st=c#
Heparin Injection. (February 10, 2021). Retrieved 22, 2021 from https://www.ashp.org/Drug-Shortages/Current-Shortages/Drug-Shortage-Detail.aspx?id=353

6. Heparin in medical practice
• UFH is administered intravenously or subcutaneously depending on indication
• VTE Prophylaxis: 5,000 units SubQ every 8 to 12 hours
• VTE Treatment: continuous IV infusion based on weight (80 units/kg bolus Max 10,000units,
then 18 units/kg/hr Max 2,000 units/hr)
• Activated partial thromboplastin time (aPTT) can be measured after 6 hours of initial
heparin bolus to adjust dosing and measure therapeutic effect.
• aPTT every 6 hours until stable in therapeutic range range (1.5-2.5 times control), then at least
every 24 hours.
• Other heparin-based products are available including low-molecular weight heparin
(LMWH) or fondaparinux (Arixtra).
• UFH is mostly used than LMWH due to high antithrombin effect and is fully reversible with an
antidote (protamine sulfate)
Lexicomp Online, Lexi-Drugs, Hudson, Ohio: UpToDate, Inc.; 2021; February 24, 2021.
Smythe, Maureen A et al. “Guidance for the practical management of the heparin anticoagulants in the treatment of venous thromboembolism.” Journal of thrombosis and thrombolysis vol.
41,1 (2016): 165-86. doi:10.1007/s11239-015-1315-2

7. Special monitoring/nursing considerations
• Monitor CBC daily for 3 days, then every 2-3 days for 2 weeks for signs
and symptoms of bleeding (hemoglobin/hematocrit)
• If bleeding occurs during treatment, stop heparin (and other anticoagulants)
• Protamine sulfate (1mg per 100 units of UFH; Max 50mg, lasts 2hrs) can be
given to fully reverse bleeding side effects.
• Heparin is also know to cause heparin-induced thrombocytopenia (HIT),
an immune-mediated reaction where platelet count drops to
<100,000/mm3 after five days of UFH initiation.
• Treatment requires stopping all heparin, followed by administering direct
thrombin inhibitors (DTI) or fondaparinux to prevent thrombosis
• After platelet count returns to >100,000/mm3, warfarin and parenteral
anticoagulants can be started until minimal INR is achieved for 2 days.
Smythe, Maureen A et al. “Guidance for the practical management of the heparin anticoagulants in the treatment of venous thromboembolism.” Journal of thrombosis and thrombolysis vol. 41,1
(2016): 165-86. doi:10.1007/s11239-015-1315-2
Ahmed, I et al. “Heparin induced thrombocytopenia: diagnosis and management update.” Postgraduate medical journal vol. 83,983 (2007): 575-82. doi:10.1136/pgmj.2007.059188

8. ISMP HIGH ALERT
MED
“…unfractionated heparin, low-
molecular weight heparin, and
warfarin. When used or omitted in
error, anticoagulants can cause
life-threatening or fatal bleeding
or thrombosis.”- ISMP 2007
Institute for Safe Medication Practice (ISMP) and Vermont Oxford Network, “High-Alert Medication Feature: Anticoagulant Safety Takes Center
Stage In 2007,” 2007. Available at https://www.ismp.org/resources/high-alert-medication-feature-anticoagulant-safety-takes-center-stage-2007

9. Burn Patients

10. What classifies as a
burn patient?
Human & Health Services (HHS) defines a burn as
“the partial or complete destruction of skin
caused by some form of energy, usually thermal
energy.”
• Burn severity is determined by total body
surface area (TSBA)
• “Burns >20-25% TBSA require IV fluid
resuscitation”
• “Burns >30-40% TBSA fatal without treatment”
• Burns are staged between Superficial and
Deep, and further placed between degrees of
burns
• Stage 1 & 2 superficial burns (1st to 2nd degrees)
can be self-treatable
• Stages 3 & 4 deep burns (2nd to 4th degrees)
are medically referred.
Burn triage and treatment - thermal injuries - chemm. (n.d.). Retrieved February 24, 2021, from
https://chemm.nlm.nih.gov/burns.htm

11. Annual Burn Statistics
Death rate from fires and burns. (2017). Retrieved February 24, 2021, from https://ourworldindata.org/grapher/fire-death-rates?tab=chart
Burn Accident and Injury Statistics. (August 27, 2013). Retrieved February 24, 2021, from https://www.swoperodante.com/burn-accident-and-injury-statistics/
• Estimated annual
burn injury
hospitalizations:
40,000 (30,000 at
burn treatment
centers) -2013
data

12. Why use heparin on burns?
• Since 1960s, large doses of heparin sodium (20,000 to 100,000 units BID, TID, or q6hrs) were
administered parenterally, topically, and nebulized on clinical burn patients, yielding positive
therapeutic results.
• Reports of relived pain, enhanced healing, and smooth skin
• Fewer resuscitation fluids, fewer lung and intestinal complications, and fewer infections.
• Theory that heparin’s mechanism of actions on burns included:
1. anti-inflammatory activity (which was not well understood),
2. restore blood flow and revascularize ischemic tissue through enhanced vascular growth,
3. and inhibit degrading enzymes (elastase and proteinases) to enhance wound healing
Masoud M, Wani AH, Darzi MA. Topical heparin versus conventional treatment in acute burns: A comparative study. Indian J Burns 2014;22:43-50
Saliba, M J Jr et al. “Large burns in humans. Treatment with heparin.” JAMA vol. 225,3 (1973): 261-9.
Saliba MJ Jr. Heparin in the treatment of burns: a review. Burns. 2001 Jun;27(4):349-58. doi: 10.1016/s0305-4179(00)00130-3. PMID: 11348743.

13. Medication Preparation and Administration
• Parental route: 20,000 units/mL concentration SubQ heparin (UFH) at a
non-burned-skin site through a number 30 gauge needle.
• For moderate to severe burns approximately 20 000 units (1 ml) to 30 000 units (1.5
ml) per 15% BSA size was used SC for adults and one-half that dose for children
under age 5.
• After first infusion, diminishing doses every 4–12 h, then day 2 usually every 12h.
• Heparin was also administered in pulmonary burns to preserve lung
structure and improve lung function.
• Given aerosolized inhalations of 5,000-25,000 units heparin
Saliba MJ Jr. Heparin in the treatment of burns: a review. Burns. 2001 Jun;27(4):349-58. doi: 10.1016/s0305-4179(00)00130-3. PMID: 11348743.
Lioton gel. (August 11, 2020). Retrieved February 25, 2021 on https://www.lybrate.com/medicine/lioton-gel

14. Medication Preparation and Administration (cont.)
• Topical route: 5,000 units/mL concentration of commercial heparin solution placed
within a 5 or 10 cc syringe with a 30 gauge needle attached, topically sprayed or
dripped onto raw burn surfaces and inserted into burn blisters (after the blister had
been ruptured with the needle and the burn fluid had drained out).
• Process repeated 2 to 4 times every 5min (total 20-30 min).
• Total burn-day 1 topical dose averaged 100,000 units per 15% BSA size, in two or three
divided doses, more initially and less later.
• No topical dosage form of heparin is currently available in the USA, though topical gels
(Lioton 1000 units/g gel) are manufactured in Europe for superficial thrombophlebitis
(inflammation of vein walls).
Saliba MJ Jr. Heparin in the treatment of burns: a review. Burns. 2001 Jun;27(4):349-58. doi: 10.1016/s0305-4179(00)00130-3. PMID: 11348743.
Lioton gel. (August 11, 2020). Retrieved February 25, 2021 on https://www.lybrate.com/medicine/lioton-gel

15. Role of Heparin in superficial burns
• A 2018 pilot study compared 40 patients with superficial first and
second degree burns; one group was treated with heparin
irrigation (n=20) and the control group was treated with 100mL
saline irrigation (n=20).
• Heparin topical application: 100,000 IU per 15% burn surface area
(BSA) per day in 3 to 4 divided doses
• At week 4 results,
• Burn healing significant difference (80% vs 5%, p=0.023)
• Necrotic tissue prevention significant(50% vs. 40%; p=0.024)
• Granulation tissue presence singnificant (85% vs. 65%; p= 0.06)
• Limitations included small sample size, expensive use of heparin,
and no analysis of scar cosmesis and sepsis-related parameters.
Vijayakumar C, Prabhu R, Senthil Velan M, Muthu Krishnan V, Kalaiarasi R, T S. Role of Heparin Irrigation in the Management of Superficial Burns
with Special Reference to Pain Relief and Wound Healing: A Pilot Study. Cureus. 2018 Aug 17;10(8):e3157. doi: 10.7759/cureus.3157. PMID:
30349764; PMCID: PMC6193569.
 p value <0.05 was considered to be statistically significant.

16. Vijayakumar C, Prabhu R, Senthil Velan M, Muthu Krishnan V, Kalaiarasi R, T S. Role of Heparin Irrigation in the Management of Superficial Burns
with Special Reference to Pain Relief and Wound Healing: A Pilot Study. Cureus. 2018 Aug 17;10(8):e3157. doi: 10.7759/cureus.3157. PMID:
30349764; PMCID: PMC6193569.
Figure 2: Patient satisfaction
score in dressing
• Difference (p˃0.05) was not
statistically significant
Figure 1: VAS score for pain
• Difference between both
groups on seventh
day(p=0.321) was not
significant
Figure 3: Length of hospital stay
• Difference (p=0.74) was not
statistically significant

17. Lack of evidence in heparin therapy for
burns?
• In a systemic review conducted in 2006, 19 abstracted articles did not contain strong evidence for
therapeutic efficacy of heparin in burns.
• Quality of evidence is poor due to contradictions or missing important research data
• Selection bias: half of articles did not report patient recruitment or participation rate
• No statistical comparisons were performed in half of the articles.
• A recent 2020 randomized clinical trial of nebulized heparin in inhalation trauma burn patients
was prematurely discontinued due to low recruitment and expensive heparin costs.
• Serious respiratory problems occurred in the heparin group and withheld treatment along with
increased blood sputum and bleeding risks reported.
Glas, Gerie J et al. “Nebulized Heparin in Burn Patients with Inhalation Trauma-Safety and Feasibility.” Journal of clinical medicine vol. 9,4 894. 25 Mar. 2020,
doi:10.3390/jcm9040894
Oremus, Mark et al. “The uses of heparin to treat burn injury.” Evidence report/technology assessment ,148 (2006): 1-58.
Oremus, Mark et al. “A systematic review of heparin to treat burn injury.” Journal of burn care & research : official publication of the American Burn Association vol. 28,6 (2007):

18. Oremus, Mark et al. “A systematic review of heparin to treat burn injury.” Journal of burn care & research : official publication of the American Burn Association vol. 28,6
(2007): 794-804. doi:10.1097/BCR.0b013e3181599b9b

19. Pros and Cons of Heparin use in burns
Pros
• Medical studies suggest heparin can
reduce mortality, improve graft and
wound healing, and provide pain relief.
• Research shows heparin is beneficial in
superficial burns, yet little evidence that
heparin works on deep burns.
• Opens new heparin research for
different dosage forms for specific
indications.
Cons
• Lack of evidence and significant
differences from control groups to prove
therapeutic benefit.
• Waste of heparin resources on
hospitalized injury that requires a huge
amount of heparin.
• 20,000 units/mL q12hrs subQ for burns
vs. 10,000 units/mL q12hrs subQ for VTE
prophylaxis
• Worsen heparin shortage
Glas, Gerie J et al. “Nebulized Heparin in Burn Patients with Inhalation Trauma-Safety and Feasibility.” Journal of clinical medicine vol. 9,4 894. 25 Mar. 2020,
doi:10.3390/jcm9040894
Oremus, Mark et al. “The uses of heparin to treat burn injury.” Evidence report/technology assessment ,148 (2006): 1-58.
Oremus, Mark et al. “A systematic review of heparin to treat burn injury.” Journal of burn care & research : official publication of the American Burn Association vol. 28,6 (2007):

20. Discussion and Conclusion
• Where do we go from here?
• Clinical studies believe heparin can be used to treat burns, yet the evidence
is not strong enough to support indication.
• Until further research is conducted, heparin should not be used as
recommended treatment for burns compared to other burn treatments
available.
• Non-inferior studies to compare heparin better than normal saline or topical
anesthetics for burn management.
• In conclusion, unless urgent or emergency, healthcare providers should
caution the use of heparin in off-labeled burn treatment.

21. References
1. Heparin Market Report. (n.d.). University of Arkansas. Retrieved February 22, 2021, from https://research.uark.edu/documents/techventures/tech_docs/heparin_market_report.pdf
2. Heparin sodium, for intravenous use. (n.d.) Retrieved on February 24, 2021 on https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/017029s140lbl.pdf
3. FDA Drug Shortages. (n.d.). Retrieved 22, 2021 from https://www.accessdata.fda.gov/scripts/drugshortages/dsp_ActiveIngredientDetails.cfm?AI=Heparin Sodium and Sodium Chloride 0.9per Injection&st=c#
4. Heparin Injection. (February 10, 2021). Retrieved 22, 2021 from https://www.ashp.org/Drug-Shortages/Current-Shortages/Drug-Shortage-Detail.aspx?id=353
5. Lexicomp Online, Lexi-Drugs, Hudson, Ohio: UpToDate, Inc.; 2021; February 24, 2021.
6. Smythe, Maureen A et al. “Guidance for the practical management of the heparin anticoagulants in the treatment of venous thromboembolism.” Journal of thrombosis and thrombolysis vol. 41,1 (2016): 165-86. doi:10.1007/s11239-015-1315-2
7. Ahmed, I et al. “Heparin induced thrombocytopenia: diagnosis and management update.” Postgraduate medical journal vol. 83,983 (2007): 575-82. doi:10.1136/pgmj.2007.059188
8. Institute for Safe Medication Practice (ISMP) and Vermont Oxford Network, “High-Alert Medication Feature: Anticoagulant Safety Takes Center Stage In 2007,” 2007. Available at https://www.ismp.org/resources/high-alert-medication-feature-
anticoagulant-safety-takes-center-stage-2007
9. Burn triage and treatment - thermal injuries - chemm. (n.d.). Retrieved February 24, 2021, from https://chemm.nlm.nih.gov/burns.htm
10. Death rate from fires and burns. (2017). Retrieved February 24, 2021, from https://ourworldindata.org/grapher/fire-death-rates?tab=chart
11. Burn Accident and Injury Statistics. (August 27, 2013). Retrieved February 24, 2021, from https://www.swoperodante.com/burn-accident-and-injury-statistics/
12. Masoud M, Wani AH, Darzi MA. Topical heparin versus conventional treatment in acute burns: A comparative study. Indian J Burns 2014;22:43-50
13. Saliba, M J Jr et al. “Large burns in humans. Treatment with heparin.” JAMA vol. 225,3 (1973): 261-9.
14. Lioton gel. (August 11, 2020). Retrieved February 25, 2021 on https://www.lybrate.com/medicine/lioton-gel
15. Glas, Gerie J et al. “Nebulized Heparin in Burn Patients with Inhalation Trauma-Safety and Feasibility.” Journal of clinical medicine vol. 9,4 894. 25 Mar. 2020, doi:10.3390/jcm9040894
16. Oremus, Mark et al. “The uses of heparin to treat burn injury.” Evidence report/technology assessment ,148 (2006): 1-58.
17. Oremus, Mark et al. “A systematic review of heparin to treat burn injury.” Journal of burn care & research : official publication of the American Burn Association vol. 28,6 (2007): 794-804. doi:10.1097/BCR.0b013e3181599b9b
18. Saliba, M J Jr. “Heparin in the treatment of burns: a review.” Burns : journal of the International Society for Burn Injuries vol. 27,4 (2001): 349-58. doi:10.1016/s0305-4179(00)00130-3
19. Vijayakumar, Chellappa et al. “Role of Heparin Irrigation in the Management of Superficial Burns with Special Reference to Pain Relief and Wound Healing: A Pilot Study.” Cureus vol. 10,8 e3157. 17 Aug. 2018, doi:10.7759/cureus.3157