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Topical fresh frozen plasma and heparin treatment of ligneous conjunctivitis in a Canadian hospital setting

      A 73-year-old Caucasian female was referred with a 3-year history of a recurrent enlarging, white, vascularised plaque of the left upper and lower lids following a severe viral systemic illness. The presenting biopsy revealed ligneous conjunctivitis, which had been treated with topical steroids and surgical debulking. Although the lower lid lesion resolved, the upper lid lesion recurred soon after each treatment. She was otherwise healthy, and lacked other mucous membrane lesions. The family history was negative for plasminogen deficiency.
      Examination revealed best-corrected visual acuity (BCVA) of 20/60 on the right and 20/100 on the left. The left upper eyelid had a thick, yellow-white, woody pseudomembranous lesion across the entire length of the tarsal conjunctiva. This was associated with significant anterior stromal scarring and vascularisation in the superior and central cornea (Fig. 1A). Laboratory investigations revealed plasminogen deficiency (0.19 U/mL, normal 0.78 to 1.29 U/mL).
      Figure thumbnail gr1
      Fig. 1Pretreatment: large woody, yellow, pseudomembrane along the entire length of the left upper tarsal conjunctiva (A). Six months posttreatment: resolution of ligneous conjunctivitis. Residual left upper tarsal conjunctival scarring with no evidence of recurrence (B).
      Successful treatment with topical plasminogen has been reported,
      • Heidemann D.G.
      • Williams G.A.
      • Hartzer M.
      • Ohanian A.
      • Citron M.E.
      Treatment of ligneous conjunctivitis with topical plasmin and topical plasminogen.
      although commercial preparations are not available in North America. With the support of the transfusion medicine laboratory and pharmacy department, this patient was nevertheless successfully managed with surgical excision (histology in Fig. 2) followed by 6 weeks of topical frozen plasma
      • Tabbara K.F.
      Prevention of ligneous conjunctivitis by topical and subconjunctival fresh frozen plasma.
      • Watts P.
      • Suresh P.
      • Mezer E.
      • et al.
      Effective treatment of ligneous conjunctivitis with topical plasminogen.
      (FP) and heparin
      • Lee W.B.
      • Himmel K.
      Fresh frozen plasma treatment of ligneous conjunctivitis: use of heparin and allogeneic serum.
      eye drops. At 6-months follow-up, she has not had any recurrence of ligneous conjunctivitis (Fig. 1B).
      Figure thumbnail gr2
      Fig. 2Ligneous conjunctivitis showing ulcerated conjunctiva lined by fibrin forming a pseudomembrane with underlying granulation tissue with acute and chronic inflammation (25×) (A). Conjunctival stroma containing abundant dense eosinophilic “amyloid-like” material surrounded by numerous neutrophils (100×) (B).
      Topical FP was prepared from a 250 mL unit of group AB frozen plasma supplied to the pharmacy and registered as having been issued to the patient for traceability.
      • Schott D.
      • Dempfle C.
      • Beck P.
      • et al.
      Therapy with a purified plasminogen concentrate in an infant with ligneous conjunctivitis and homozygous plasminogen deficiency.
      This was thawed in a warm water bath and aliquoted under sterile conditions into 3 mL bottles within 8 hours of primary thaw, thereby minimizing any plasminogen loss before refreezing at −20°C, and permitting an unadjusted expiry date on labelling for ongoing frozen storage.
      A frozen bottle was dispensed daily to the patient, with instructions to rethaw at room temperature for 40 minutes, after which home use continued for a 24-hour period with intercurrent refrigeration (at 2°-8°C) until discard. For the heparin eye drops, preservative-free heparin sodium (10 000 units/mL) was diluted with saline to a concentration of 5000 units/mL, and packaged into sterile drop bottles. For both the FP and heparin drops, sterility testing was carried out.
      The treatment regimen for both topical FP and heparin was hourly (alternating) while awake for 6 weeks postsurgery and every 2 hours (alternating) overnight for the first 48 hours. Additionally, 0.1% dexamethasone sodium phosphate and tobramycin (Tobradex, Alcon, Forth Worth, TX) four times per day was given for the first week, then switched to dexamethasone 0.1% (Maxidex, Alcon) four times per day for the remaining 5 weeks. At 6-month follow-up, BCVA remained at 20/100. The left upper tarsal conjunctiva was scarred, but without recurrence.
      Ligneous conjunctivitis is an often unremitting condition despite treatment. We have illustrated that within the Canadian hospital setting, it is possible to manage these patients successfully with topical FP and heparin with the coordinated efforts of the blood bank and pharmacy for quality preparation and storage.

      References

        • Heidemann D.G.
        • Williams G.A.
        • Hartzer M.
        • Ohanian A.
        • Citron M.E.
        Treatment of ligneous conjunctivitis with topical plasmin and topical plasminogen.
        Cornea. 2003; 22: 760-762
        • Tabbara K.F.
        Prevention of ligneous conjunctivitis by topical and subconjunctival fresh frozen plasma.
        Am J Ophthalmol. 2004; 138: 299-300
        • Watts P.
        • Suresh P.
        • Mezer E.
        • et al.
        Effective treatment of ligneous conjunctivitis with topical plasminogen.
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        • Lee W.B.
        • Himmel K.
        Fresh frozen plasma treatment of ligneous conjunctivitis: use of heparin and allogeneic serum.
        Cornea. 2009; 28: 122-123
        • Schott D.
        • Dempfle C.
        • Beck P.
        • et al.
        Therapy with a purified plasminogen concentrate in an infant with ligneous conjunctivitis and homozygous plasminogen deficiency.
        New Engl J Med. 1998; 339: 1679-1686