• 1

    Ramsey DT. Ligneous conjunctivitis in four Doberman Pinschers. J Am Anim Hosp Assoc 1996;32:439447.

  • 2

    Mingers AM, Heimburger N, Zeitler P, et al. Homozygous type I plasminogen deficiency. Semin Thromb Hemost 1997;23:259269.

  • 3

    Mingers AM, Philapitsch A, Zeitler P, et al. Human homozygous type I plasminogen deficiency and ligneous conjunctivitis. APMIS 1999;107:6272.

    • Search Google Scholar
    • Export Citation
  • 4

    Schuster V, Seidenspinner S, Zeitler P, et al. Compound-heterozy-gous mutations in the plasminogen gene predispose to the development of ligneous conjunctivitis. Blood 1999;93:34573466.

    • Search Google Scholar
    • Export Citation
  • 5

    Schuster V, Zeitler P, Seregard S, et al. Homozygous and com-pound-heterozygous type I plasminogen deficiency is a common cause of ligneous conjunctivitis. Thromb Haemost 2001;85:10041010.

    • Search Google Scholar
    • Export Citation
  • 6

    Tefs K, Gueorguieva M, Klammt J, et al. Molecular and clinical spectrum of type I plasminogen deficiency: a series of 50 patients. Blood 2006;108:30213026.

    • Search Google Scholar
    • Export Citation
  • 7

    Drew AF, Kaufman AH, Kombrinck KW, et al. Ligneous conjunctivitis in plasminogen-deficient mice. Blood 1998;91:16161624.

  • 8

    Lanevschi A, Kramer JM, Greene SA, et al. Evaluation of chromogenic substrate assays for fibrinolytic analytes in dogs. Am J Vet Res 1996;57:11241130.

    • Search Google Scholar
    • Export Citation
  • 9

    Tabbara KF. Prevention of ligneous conjunctivitis by topical and subconjunctival fresh frozen plasma. Am J Ophthalmol 2004;138:299300.

    • Search Google Scholar
    • Export Citation
  • 10

    Watts P, Suresh P, Mezer E, et al. Effective treatment of ligneous conjunctivitis with topical plasminogen. Am J Ophthalmol 2002;133:451455.

    • Search Google Scholar
    • Export Citation
  • 11

    Schuster V, Seregard S. Ligneous conjunctivitis. Surv Ophthalmol 2003;48:369388.

  • 12

    Shimabukuro M, Iwasaki N, Nagae Y, et al. Ligneous conjunctivitis: a case report. Jpn J Ophthalmol 2001;45:375377.

  • 13

    Holland EJ, Chan CC, Kuwabara T, et al. Immunohistologic findings and results of treatment with cyclosporine in ligneous conjunctivitis. Am J Ophthalmol 1989;107:160166.

    • Search Google Scholar
    • Export Citation
  • 14

    Shigekiyo T, Tomonari A, Uno Y, et al. Danazol therapy in hypoplasminogenemia. Thromb Haemost 1992;68:233234.

  • 15

    Lottenberg R, Dolly FR, Kitchens CS. Recurring thromboembolic disease and pulmonary hypertension associated with severe hypoplasminogenemia. Am J Hematol 1985;19:181193.

    • Search Google Scholar
    • Export Citation
  • 16

    Koh KK, Mincemoyer R, Bui MN, et al. Effects of hormone-re-placement therapy on fibrinolyis in postmenopausal women. N Engl J Med 1997;336:683690.

    • Search Google Scholar
    • Export Citation
  • 17

    Conard J, Gompel A, Pelissier C, et al. Fibrinogen and plasminogen modifications during oral estradiol replacement therapy. Fertil Steril 1997;68:449453.

    • Search Google Scholar
    • Export Citation
  • 18

    van Baal WM, Emeis JJ, van derMooren MJ, et al. Impaired pro-coagulant-anticoagulant balance during hormone replacement therapy? A randomized, placebo-controlled 12-week study. Thromb Haemost 2000;83:2934.

    • Search Google Scholar
    • Export Citation
  • 19

    Meijers JC, Middeldorp S, Tekelenburg W, et al. Increased fibrinolytic activity during use of oral contraceptives is counteracted by an enhanced factor XI-independent down regulation of fibrinolysis: a randomized cross-over study of two low-dose oral contraceptives. Thromb Haemost 2000;84:914.

    • Search Google Scholar
    • Export Citation
  • 20

    Teresa Sartori M, Saggiorato G, Pellati D, et al. Contraceptive pills induce an improvement in congenital hypoplasminogenemia in two unrelated patients with ligneous conjunctivitis. Thromb Haemost 2003;90:8691.

    • Search Google Scholar
    • Export Citation
  • 21

    Riis RC. Small animal ophthalmology: self-assessment picture tests in veterinary medicine. London: Mosby-Wolfe, 1994;1994

  • 22

    Borel MG. Un nouveau syndrome oculo-palpebral. Ann Ocul (Paris) 1934;171:207222.

  • 23

    Mingers AM, Philapitsch A, Schwarz HP, et al. Polymorphonuclear elastase in patients with homozygous type I plasminogen deficiency and ligneous conjunctivitis. Semin Thromb Hemost 1998;24:605612.

    • Search Google Scholar
    • Export Citation
  • 24

    Hidayat AA, Riddle PJ. Ligneous conjunctivitis: a clinicopathologic study of 17 cases. Ophthalmology 1987;94:949959.

  • 25

    Pfannkuch F, Schmidt R, Schmidt B, et al. Morphologic studies of the pathogenesis of ligneous conjunctivitis. Klin Monatsbl Augenheilkd 1987;190:4045.

    • Search Google Scholar
    • Export Citation
  • 26

    Rao SK, Biswas J, Rajagopal R, et al. Ligneous conjunctivitis: a clinicopathologic study of 3 cases. Int Ophthalmol 1998;22:201206.

  • 27

    Scully C, Gokbuget AY, Allen C, et al. Oral lesions indicative of plasminogen deficiency (hypoplasminogenemia). Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2001;91:334337.

    • Search Google Scholar
    • Export Citation
  • 28

    Chai F, Coates H. Otolaryngological manifestations of ligneous conjunctivitis. Int J Pediatr Otorhinolaryngol 2003;67:189194.

  • 29

    Heidemann DG, Williams GA, Hartzer M, et al. Treatment of ligneous conjunctivitis with topical plasmin and topical plasminogen. Cornea 2003;22:760762.

    • Search Google Scholar
    • Export Citation
  • 30

    Ciftci E, Ince E, Akar N, et al. Ligneous conjunctivitis, hydrocephalus, hydrocele, and pulmonary involvement in a child with homozygous type I plasminogen deficiency. Eur J Pediatr 2003;162:462465.

    • Search Google Scholar
    • Export Citation
  • 31

    Cohen SR. Ligneous conjunctivitis: an ophthalmic disease with potentially fatal tracheobronchial obstruction. Laryngeal and tracheobronchial features. Ann Otol Rhinol Laryngol 1990;99:509512.

    • Search Google Scholar
    • Export Citation
  • 32

    Rubin A, Buck D, MacDonald MR. Ligneous conjunctivitis involving the cervix. Case report. Br J Obstet Gynaecol 1989;96:12281230.

  • 33

    Aslan AT, Ozcelik U, Dogru D, et al. Congenital hydrocephalus as a rare association with ligneous conjunctivitis and type I plasminogen deficiency. Neuropediatrics 2005;36:108111.

    • Search Google Scholar
    • Export Citation
  • 34

    Schott D, Dempfle CE, Beck P, et al. Therapy with a purified plasminogen concentrate in an infant with ligneous conjunctivitis and homozygous plasminogen deficiency. N Engl J Med 1998;339:16791686.

    • Search Google Scholar
    • Export Citation
  • 35

    Girard LJ, Veselinovic A, Font RL. Ligneous conjunctivitis after pingueculae removal in an adult. Cornea 1989;8:724.

  • 36

    De Cock R, Ficker LA, Dart JG, et al. Topical heparin in the treatment of ligneous conjunctivitis. Ophthalmology 1995;102:16541659.

  • 37

    Demarmels Biasiutti F, Sulzer I, Stucki B, et al. Is plasminogen deficiency a thrombotic risk factor? A study on 23 thrombophilic patients and their family members. Thromb Haemost 1998;80:167170.

    • Search Google Scholar
    • Export Citation
  • 38

    Melikian HE. Treatment of ligneous conjunctivitis. Ann Ophthalmol 1985;17:763765.

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Ligneous conjunctivitis secondary to a congenital plasminogen deficiency in a dog

Nancy S. Johnstone McLean DVM1, Daniel A. Ward DVM, PhD, DACVO2, Diane V. H. Hendrix DVM, MS, DACVO3, Robert L. Donnell DVM, PhD, DACVP4, and Marcia R. S. Ilha DVM, MS5
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  • 1 Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996.
  • | 2 Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996.
  • | 3 Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996.
  • | 4 Department of Pathobiology, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996.
  • | 5 Department of Pathobiology, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996.

Abstract

Case Description—A 7-month-old 16.6-kg (36.5-lb) sexually intact female Golden Retriever was evaluated because of progressive severe bilateral membranous conjunctivitis, oral lesions, nasal discharge, and cough.

Clinical Findings—Histologic examination of conjunctival biopsy specimens revealed findings consistent with ligneous conjunctivitis. Circulating plasminogen activity was repeatedly low, and congenital plasminogen deficiency was identified as the underlying cause of the ocular, oral, and respiratory lesions.

Treatment and Outcome—Topical and subconjunctival administrations of fresh frozen plasma (FFP), topical administration of cyclosporine, and oral administration of azathioprine had no effect on the conjunctival membranes. Excision of the membranes followed by intensive treatment with topical applications of heparin, tissue plasminogen activator, corticosteroid, and FFP and IV administration of FFP prevented membrane regrowth. Intravenous administration of FFP increased plasma plasminogen activity to within reference limits, improved respiratory and oral lesions, and resulted in weight gain; discontinuation of this treatment resulted in weight loss, signs of depression, and worsening of lesions. After euthanasia because of disease progression, necropsy findings included mild hydrocephalus; multifocal intestinal hemorrhages; and fibrinous plaques in the oral cavity, nasopharynx, trachea, esophagus, and pericardium. Microscopically, the plaques were composed of fibrin and poorly organized granulation tissue. Fibrin thrombi were present within vessels in the lungs, oral cavity, and trachea.

Clinical Relevance—In dogs, congenital plasminogen deficiency can occur and may be the underlying cause of ligneous conjunctivitis. A combination of surgical and medical treatments may improve conjunctival membranes, and administration of FFP IV appears to be effective in treating nonocular signs of plasminogen deficiency.

Abstract

Case Description—A 7-month-old 16.6-kg (36.5-lb) sexually intact female Golden Retriever was evaluated because of progressive severe bilateral membranous conjunctivitis, oral lesions, nasal discharge, and cough.

Clinical Findings—Histologic examination of conjunctival biopsy specimens revealed findings consistent with ligneous conjunctivitis. Circulating plasminogen activity was repeatedly low, and congenital plasminogen deficiency was identified as the underlying cause of the ocular, oral, and respiratory lesions.

Treatment and Outcome—Topical and subconjunctival administrations of fresh frozen plasma (FFP), topical administration of cyclosporine, and oral administration of azathioprine had no effect on the conjunctival membranes. Excision of the membranes followed by intensive treatment with topical applications of heparin, tissue plasminogen activator, corticosteroid, and FFP and IV administration of FFP prevented membrane regrowth. Intravenous administration of FFP increased plasma plasminogen activity to within reference limits, improved respiratory and oral lesions, and resulted in weight gain; discontinuation of this treatment resulted in weight loss, signs of depression, and worsening of lesions. After euthanasia because of disease progression, necropsy findings included mild hydrocephalus; multifocal intestinal hemorrhages; and fibrinous plaques in the oral cavity, nasopharynx, trachea, esophagus, and pericardium. Microscopically, the plaques were composed of fibrin and poorly organized granulation tissue. Fibrin thrombi were present within vessels in the lungs, oral cavity, and trachea.

Clinical Relevance—In dogs, congenital plasminogen deficiency can occur and may be the underlying cause of ligneous conjunctivitis. A combination of surgical and medical treatments may improve conjunctival membranes, and administration of FFP IV appears to be effective in treating nonocular signs of plasminogen deficiency.

Contributor Notes

The authors thank Dr. Marjory Brooks for performing the plasminogen activity assays.

Address correspondence to Dr. Ward.