Uncontrolled Bleeding Following Punch Biopsy

“Bleeding is the most common complication following punch biopsy [1] . Risk of bleeding is greater when the site of the biopsy is outside the trunk , though bleeding may occur at any site…”

Case

A 72 year old female with past medical history significant for B-cell lymphoma, cervical cancer, malignant splenic rupture, prior streptococcal sepsis, fibrocystic breast dysplasia, hypertension, TIA, carotid artery stenosis, osteoporosis, and generalized anxiety disorder presents to the Emergency Department with a chief complaint of uncontrolled bleeding from the site of a right breast biopsy.

Approximately 6 hours prior to presentation the patient received a punch biopsy of an abnormal lesion concerning for possible malignancy. She notes taking aspirin 81 mg daily but states that she did not take it on the day of the procedure, as instructed. She denies taking anticoagulation medications or other antiplatelet agents. She reports that the initial procedure was uncomplicated and that she was discharged with a dressing to the biopsy site made of steri-strips, 4x4 gauze, and a transparent dressing, as well as a linen breast binder. While recovering at home she noted that the binder and dressing had become saturated with blood, prompting her to apply direct pressure, which was not sufficient to control the bleeding, and present to the Emergency Department. 

On dressing take down, the patient’s post-procedural dressing was noted to be saturated with blood. A large, external blood clot formed beneath the transparent dressing, causing the dressing to pull away from the patient's skin and for blood to saturate the binder. Slow, non-pulsatile, bleeding was present at the site of the biopsy. The wound was explored through its entire depth with a cotton tip applicator and noted to be shallow, no deeper than 2cm. The bleeding was controllable with direct pressure and the patient was given fresh gauze and instructed to apply firm direct pressure to the site for 10 minutes. 

On re-evaluation, the wound continued to bleed. 10 mL of lidocaine with 1% epinephrine were injected throughout the biopsy site and surrounding soft tissue and direct pressure was re-applied for 10 minutes. 

On re-evaluation, the wound continued to bleed. Gauze soaked in 5% tranexamic acid was applied to the wound and direct pressure was re-applied. On re-evaluation in 10 minutes, the wound was hemostatic. A pressure dressing was applied to the site of the biopsy. The patient was discharged and directed to follow up with the physician who performed the procedure the next day. 

Discussion

Bleeding is the most common complication following punch biopsy [1] . Risk of bleeding is greater when the site of the biopsy is outside the trunk , though bleeding may occur at any site [1] . Frequently, patients will have been instructed to briefly hold anticoagulation to decrease risk of post procedural bleeding. The literature suggests that there may be no differences in bleeding risk in patients who did not take anticoagulation medicine the day of the procedure. The medication regimen most associated with bleeding risk following dermatosurgery are combination regimens and novel oral anticoagulants [2] . 

Achieving Hemostasis:

Dermato-oncologic procedures often occur in areas which resist methods of hemorrhage commonly applied in trauma surgery such as tourniquet application, aortic cross clamping etc. Regardless of the mechanism of hemorrhage, the basic principles of hemorrhage control apply. First line use of direct pressure is safe, requires few resources, and may be sufficient to yield hemostasis. If direct pressure is insufficient, pharmacologic and surgical management may be warranted.

Pharmacologic options:

Adrenergic Agents

Epinephrine functions as a vasoconstrictor by its action on alpha-1 receptors. An increase in capillary bed tone functions to decrease blood loss. [3]  Local injection of epinephrine diluted in lidocaine are particularly useful as they achieve dual function of analgesia and hemostasis. The literature suggests that a 1:50,000 ratio of epinephrine to lidocaine provides optimal clinical efficacy in dermatosurgery. [4]  Another accessible local vasoconstrictor which may be applied locally to achieve hemostasis is oxymetazoline, a selective alpha-1 agonist and partial alpha 2 agonist. As alpha-1 receptors are dominant in capillary beds and alpha-2 vasodilatory action is limited by oxymetazoline partial agonism, oxymetazoline can be similarly helpful to epinephrine in establishing local hemostasis. [5] 

Transexamic Acid

While the only FDA approved use of transexemic acid (TXA) is menorrhagia and short-term therapy in people with hemophilia, off-label usage of TXA abounds, though the data that supports its use is fraught. TXA theoretically promotes hemostasis by its action as a reversible competitive inhibitor to the lysine receptor on plasminogen. This action prevents activated plasminogen from binding to the fibrin matrix , thereby decreasing natural processes of clot breakdown. [6]  This clot stabilizing effect is demonstrated in the above case, and topical TXA is frequently used in this manner in trauma surgery [7] , obstetrics [8] , otolaryngology [9]  and more. [10] 

If a patient’s bleeding presents with hemodynamic instability, in addition to blood product resuscitation, systemic TXA may be a reasonable option. The literature suggests that systemic TXA administration is not associated with major adverse effects , at least in trauma patients where its use is well studied. [7]  The OBGYN literature additionally suggests no increase in thromboembolic events following iv TXA administration. [11] 

2-Octyl Cyanoacrylate

2-Octyl cyanoacrylate is a cyanoacrylate ester most often used as a wound closure adhesive. [12] monomers of 2-octyl cyanoacrylate quickly polymerize in an exothermic reaction that binds to the most superficial epithelium.  This creates a physical matrix which facilitates clot development, while mild increase in temperature during polymerization like promotes protein coagulation and clot development. [13] The use of 2-OC in decreasing bleeding following Moh’s surgery has been demonstrated in the literature. [14] 2-octyl cyanoacrylate has also been shown to have intrinsic anti-microbial activity against gram-positive (including methicillin-resistant Staphylococcus aureus) and non-pseudomonas gram-negative bacteria. [15] 

Caustic Agents

Topical caustics such as aluminum chloride, ferric sulfate (Monsel's solution) silver nitrate, and zinc chloride are reasonable tools to promote hemostasis. Topical caustics work by coagulating proteins which in turn yields thrombus formation and hemostasis. These agents may be briefly painful when applied, and caustic agents, specifically silver nitrate, may lead to skin discoloration. [16]  As such, alternative techniques are often preferred.

Pro-coagulant Dressings

Non-caustic hemostatic dressings create a physical mesh that facilitates platelet aggregation and coagulation. A variety of materials have been explored that function as hemostatic dressings including gauze, microporous polysaccharide spheres, hydrophilic polymers with potassium salts (HPPS), oxidized regenerated cellulose and microfibrillar collagens. Many of these materials may not be readily available in the Emergency Department, limiting their utility. 

Zeolites describe microporous, crystalline aluminosilicate materials and may be embedded in gauze and used as a physical matrix that promotes clot formation.  These preparations are often readily available in the Emergency Department and are widely used in trauma surgery, pre-hospital, and military arenas as a means of promoting local hemostasis. Another type of pro-coagulant dressing which may be available is kaolin impregnated gauze. Kaolin is a clay-silicate mineral which initiates the clotting process by transforming Factor XII to aXII. The active form of Factor XII then activates Factor XI and pre-kallikrien, leading to clot formation. [16] 

Sutures

If a bleeding blood vessel is identified or hemostasis is not achieved, suture placement may be indicated. A variety of suture techniques and materials are reasonable for achieving hemostasis, a guide to laceration technique and options can be reviewed here. [17]  Absorbable sutures offer a convenience and patient comfort factor which may favor their use. The figure of eight stitch is a common preferred technique, as the mechanics of the stitch create tension over a greater area of tissue as compared to the simple interrupted stitch. In addition, the figure of eight holds greater tensile strength than the simple interrupted, contributing to the effectiveness of achieving hemostasis with this stitch. Staples are also an option and share similar mechanical characteristics to the figure 8 which promote hemostasis, namely, higher compressive forces applied. 

Cautery

Bleeding has been shown to be easily controllable with the use of cautery. Prior to electricity, heated metal was frequently employed by proceduralists seeking hemostasis. Electrocautery is often readily available in the Emergency Department. Electrocautery applies a current to a metal with high resistance which produces heat, and in turn causes tissue necrosis and vascular coagulation. [18]  The resultant tissue necrosis may delay wound healing or lead to unfavorable cosmetic outcomes. As such, alternative methods are often preferred.


Author: Keaton Cameron-Burr, MD, is a fourth year emergency medicine resident at Brown University/Rhode Island Hospital.

Faculty Reviewer: Kristina McAteer, MD, is an attending emergency medicine physician at Rhode Island Hospital and Newport Hospital.


References

  1. Yasui Y, Kato H, Oda T, Nakamura M, Morita A. Complications and risk factors of punch biopsy: A retrospective large-scale study. J Dermatol. 2023;50(1):98-101. doi:10.1111/1346-8138.16585

  2. Iyengar S, Yeager DG, Cohen JL, Ozog DM. Update and Review of Bleeding Considerations in Dermatologic Surgery: Anticoagulants and Antiplatelets. Dermatol Surg. 2020;46(2):192-201. doi:10.1097/DSS.0000000000002266

  3. Dalal R, Grujic D. Epinephrine. [Updated 2023 May 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK482160/

  4. Shoroghi M, Sadrolsadat SH, Razzaghi M, et al. Effect of different epinephrine concentrations on local bleeding and hemodynamics during dermatologic surgery. Acta Dermatovenerol Croat. 2008;16(4):209-214.

  5.  National Center for Biotechnology Information. PubChem Compound Summary for CID 4636, Oxymetazoline. https://pubchem.ncbi.nlm.nih.gov/compound/Oxymetazoline. Accessed June 3, 2024.

  6. Chauncey JM, Wieters JS. Tranexamic Acid. [Updated 2023 Jul 24]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK532909/

  7. Ackery A, Rizoli S. Tranexamic acid for trauma-related hemorrhage. CMAJ. 2014;186(15):E587. doi:10.1503/cmaj.131741

  8. Burns, Rebecca MD; Kucera, Calen MD; Parsons, Arlene MD; Bannon, Lindsey MD. Case Report: Topical Tranexamic Acid as Novel Treatment of Refractory Bleeding After Excisional Cervical Procedure [27G]. Obstetrics & Gynecology 131():p 82S, May 2018. | DOI: 10.1097/01.AOG.0000533377.51247.49

  9. Zirk M, Zinser M, Buller J, et al. Supportive topical tranexamic acid application for hemostasis in oral bleeding events - Retrospective cohort study of 542 patients. J Craniomaxillofac Surg. 2018;46(6):932-936. doi:10.1016/j.jcms.2018.03.009

  10. Collier C, Sidhu G, Solvang K, Chan S. 63 Topical Use of Tranexamic Acid in the Emergency Department. Annals of Emergency Medicine. Research Form Abstract 78(4) October 2021. https://doi.org/10.1016/j.annemergmed.2021.09.072

  11. Pacheco, Luis D. MD; Hankins, Gary D. V. MD; Saad, Antonio F. MD; Costantine, Maged M. MD; Chiossi, Giuseppe MD; Saade, George R. MD. Tranexamic Acid for the Management of Obstetric Hemorrhage. Obstetrics & Gynecology 130(4):p 765-769, October 2017. | DOI: 10.1097/AOG.0000000000002253

  12. CLOSURE Medical Corporation. Summary of safety and effectiveness data (Dermabond®). Food and Drug Administration1998 Accessed May 2024 from https://www.accessdata.fda.gov/cdrh_docs/pdf/P960052b.pdf 

  13. Perera AGN, Tavarez MM. 2-Octyl Cyanoacrylate. [Updated 2024 Jan 25]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK532293/

  14. Waldman R, Chiaravalloti A, Whalen J,  Jinna S. A Novel Approach to the Use of 2-Octyl Cyanoacrylate to Reduce Postoperative Hemorrhage After Mohs Micrographic Surgery. Dermatologic Surgery 47(2):p 277-279, February 2021. | DOI: 10.1097/DSS.0000000000002838

  15. Rushbrook JL, White G, Kidger L, Marsh P, Taggart TF. The antibacterial effect of 2-octyl cyanoacrylate (Dermabond®) skin adhesive. J Infect Prev. 2014;15(6):236-239. doi:10.1177/1757177414551562

  16. Glick, Jaimie B.; Kaur, Ravneet R.; Siegel, Daniel. Achieving hemostasis in dermatology-Part II: Topical hemostatic agents. Indian Dermatology Online Journal 4(3):p 172-176, Jul–Sep 2013. | DOI: 10.4103/2229-5178.115509

  17. Forsch RT, Little SH, Williams C. Laceration Repair: a Practical Approach. Am Fam Physician. 2017;95(10):628-636. Accessed May 2024 https://www.aafp.org/pubs/afp/issues/2017/0515/p628.pdf

  18.  Hajilo P, Imani B, Zandi S, Mehrafshan A. Comparing the intraoperative and postoperative complications of the scalpel and electrocautery for severing the inner layers of the lumbar disc during discectomy surgery. Front Surg Sec Neurosurgery, September 28 2023 Volume 10 - 2023 https://doi.org/10.3389/fsurg.2023.1264519.