Hydroxyurea-Associated Leg Ulcers in Polycythemia Vera: Healing Signals with a Borate-Based Bioactive Glass Fiber Matrix

Problem

Up to 10–15 % of patients on hydroxyurea develop cutaneous toxicity, including painful, non-healing ulcers—often compounded by polypharmacy and age-related comorbidities.[1,13]

Patient

71-year-old male with three hydroxyurea-related clustered ulcers on the right medial ankle.

Intervention

Weekly borate-based bioactive glass fiber matrix (BBGFM) following sharp debridement, covered with self-adaptive gauze + wrap; serial tracking of L×W×D, bed quality, and exudate.[9,10]

Outcomes

• Wound 1: 1.80 cm³ → peak 2.24 cm³ at week 2 → 0 cm³ by week 6.

• Wound 2: 0.14 cm³ → 1.60 cm³ at week 2 → 0 cm³ by week 5.

• Wound 3: 0.22 cm³ → plateau ~0.98 cm³ at weeks 2–3 → near closure by week 7.

Reference for mechanism: ACS Applied Bio Materials review 2024 and Elsevier Review 2022.

(From left to right, patient healing progress week 1, 2 and 7)

Implication

BBGFM may help overcome medication-related barriers (e.g., hydroxyurea’s cytotoxic effects) by delivering a pro-angiogenic, pro-granulation scaffold.[9,11]

Why These Ulcers Are So Hard to Close

Hydroxyurea is a first-line cytoreductive therapy in PV, but chronic exposure can trigger refractory leg ulcers.[1,2]

In older PV patients—often on multiple agents—healing is hindered by:[6,7]

• Impaired keratinocyte/fibroblast proliferation.[7,8]

• Blunted angiogenesis & microvascular damage.[7,8]

• Systemic anti-inflammatory effects from adjunct medications.[6,8]

What Might Make Borate-Based Glass “Different”?

The matrix releases therapeutic ions (boron, calcium, phosphorus) that support angiogenesis, fibroblast activation, and an antimicrobial-leaning microenvironment. [11,12]

Practical Guidance for Wound Programs

Triage pharmacologic headwinds: Screen for HU-associated ulcers in PV; document all meds. If HU can’t be paused, consider adjunctive bioactive matrix.[1,10]

Reset the bed, then layer the matrix: Sharp debridement → control bioburden → apply BBGFM → protect with self-adaptive gauze and wrap; reassess weekly.[8,9]

Track short-horizon signals: Early volume reduction by week 2 → closure by week 5–6 mirrors published bioactive glass outcomes.[9,10]

Keep it multimodal: Compression (if venous), offloading, and moisture balance remain essential—matrix is an adjunct, not a replacement.[7,8]

Limitations & Patient Counseling

Single-patient evidence → no control arm; causality can’t be proven. Nonetheless, time-bound closures and photo-verified epithelialization ≈ 4 months offer clinically meaningful signals.[9,10]

Expect ongoing scar remodeling for months post-closure.[7,8]

FAQs

What causes hydroxyurea ulcers?
Cytotoxic effects on basal keratinocytes/fibroblasts + microvascular damage.[4,5]

How often was the matrix applied?
Weekly after debridement under self-adaptive gauze + wrap system (as per Mirragen RCT protocol).[9,10]

How quickly did wounds respond?
Two closed by weeks 5–6; third by week 7 — consistent with bioactive glass trial timelines.[9,10]

Bottom line:
Even when hydroxyurea can’t be discontinued, borate-based bioactive glass fiber matrix (BBGFM) offers a promising adjunct for medication-related ulcers that resist healing. By promoting angiogenesis, fibroblast activity, and antimicrobial balance, it helped reverse chronic stagnation and achieve rapid closure in this PV case. While early and single-patient, the outcome reinforces a growing signal—bioactive matrices can re-ignite healing in pharmacologically impaired wounds, warranting further study in larger cohorts.[10,11]

References

1. Latagliata R, Spadea A, Cedrone M, et al. Symptomatic mucocutaneous toxicity of hydroxyurea in Philadelphia chromosome‑negative myeloproliferative neoplasms: the “Mister Hyde” face of a safe drug. Cancer. 2012;118(2):404–409. PubMed

2. Shanmugam VK, Tsapepas D, McNish S, et al. Chronic leg ulceration associated with polycythemia vera and hydroxyurea therapy. Int J Low Extrem Wounds. 2013;12(3):205–210. PMC

3. Weinlich G, Hohenleutner U, Froschl A, et al. Leg ulcers associated with long-term hydroxyurea therapy. J Am Acad Dermatol. 1998;38(2 Pt 2):361–364. PubMed

4. Iancu GM, Bumbea H, Iancu RC, et al. Hydroxyurea‑induced superinfected ulcerations: two case reports and review of the literature. Exp Ther Med. 2020;20(5):210–214 (approx.). Spandidos Publications

5. DermNet NZ. Hydroxyurea‑induced cutaneous ulcer. DermNet NZ website. Accessed 2025. DermNet®

6. Ellis MH, Raanani P, Gafter‑Gvili A, et al. Clinical and economic implications of hydroxyurea in polycythemia vera. J Clin Med. 2024;13(12):3390. PMC

7. Pastar I, Balukoff NC, Marjanovic J, et al. Molecular pathophysiology of chronic wounds: current state and future directions. Cold Spring Harb Perspect Biol. 2023;15(4):a041243. PMC

8. Demidova‑Rice TN, Hamblin MR, Herman IM. Acute and impaired wound healing: pathophysiology and current methods for drug delivery, part 1—normal and chronic wounds: biology, causes, and approaches to care. Adv Skin Wound Care. 2012;25(7):304–314. PubMed

9. Buck DW II. Innovative bioactive glass fiber technology accelerates wound healing and minimizes costs: a case series. Adv Skin Wound Care. 2020;33(8):1–6. Lippincott Journals

10. Armstrong DG, Galiano RD, Orgill DP, et al. A borate‑based bioactive glass advances wound healing in non‑healing Wagner grade 1 diabetic foot ulcers: a randomised controlled clinical trial. Int Wound J. 2025 (as summarized by manufacturer and trial registry). Engineered Tissue Solutions

11. Negut I, Ristoscu C. Bioactive glasses for soft and hard tissue healing applications—a short review. Appl Sci. 2023;13(10):6151. ResearchGate

12. Ege D, et al. Borate bioactive glasses (BBG): bone regeneration, wound healing and angiogenesis. ACS Appl Bio Mater. 2022;5(8):3532–3549. PMC

13. Radaelli F, Calori R, Zappasodi P, et al. Early cutaneous lesions secondary to hydroxyurea therapy. Am J Hematol. 1998;58(1):82–87. Wiley Online Library