Central retinal vein thrombosis as an initial manifestation of heterozygous protein C deficiency: case report

Trombose da veia central da retina como manifestação inicial da deficiência de proteína C na forma heterozigótica: relato de caso

RELATOS DE CASOS

Central retinal vein thrombosis as an initial manifestation of heterozygous protein C deficiency - Case Report

Trombose da veia central da retina como manifestação inicial da deficiência de proteína C na forma heterozigótica - Relato de Caso

Rodrigo Pessoa Cavalcanti LiraI, ¹; Gustavo Araújo CovoloII, ²; Wilson Nadruz JúniorIII, ³; Carlos Eduardo Leite ArietaIV, ⁴

^IDoutor em Ciências Médicas pela Universidade Estadual de Campinas, UNICAMP

^IIPós-graduando nível Mestrado do Curso de Pós-graduação em Ciências Médicas da Universidade Estadual de Campinas, UNICAMP

^IIIPós-graduando nível Doutorado do Curso de Pós-graduação em Clínica Médica da Universidade Estadual de Campinas, UNICAMP

^IVProfessor Assistente Doutor do Departamento de Oftalmo-Otorrinolaringologia da UNICAMP

^{Endereço para correspondência}

ABSTRACT

The purpose of this paper is to report a case of central retinal vein thrombosis associated with isolated heterozygous protein C deficiency. Acute occlusion of the central retinal vein presents as one of the most dramatic pictures in ophthalmology. It is often a result of both local and systemic causes. A rare systemic cause is heterozygous protein C deficiency, and it usually occurs in combination with other thrombophilic conditions. This case highlights that isolated heterozygous protein C deficiency may be the cause of central retinal vein thrombosis and underscores the importance of its screening in young patients with this ophthalmologic disease.

Keywords: Retinal vein thrombosis; Protein C deficiency; Case report

RESUMO

O objetivo deste estudo é relatar um caso de trombose da veia central da retina associada à deficiência isolada de proteína C na forma heterozigótica. Oclusão aguda da veia central da retina é um dos mais dramáticos quadros oftalmológicos. Geralmente resulta tanto de fatores locais como sistêmicos. Uma causa sistêmica rara é a deficiência de proteína C na forma heterozigótica, ocorrendo usualmente associada a outras trombofilias. Este caso mostra que deficiência isolada de proteína C na forma heterozigótica pode ser a causa da trombose da veia central da retina e reforça a importância de sua investigação em pacientes jovens com esta doença ocular.

Descritores: Trombose venosa retiniana; Deficiência proteína C; Relato de caso

Thrombophilic conditions may be associated with retinal vein thrombosis. The most common is activated protein C resistance, but its deficiency is also described in some patients. We report a case of central retinal vein thrombosis associated with isolated heterozygous protein C deficiency.

CASE REPORT

A 34-year-old white woman was admitted to our institution with a sudden decrease of visual acuity in the right eye. She did not present ocular pain, photophobia, fever or any other local or systemic complaint. The patient had no personal or familial history of eye disease, systemic hypertension, diabetes mellitus, thrombophilia, malignancy or use of oral contraceptive pills. At examination, blood pressure measurement was 114 x 73 mmHg. Visual acuity in the right eye (OD) was 20/25 and left eye (OS) was 20/20 with best correction. In both eyes, slit-lamp biomicroscopic findings were normal, without pupillary defects, and intraocular pressure was 15 mmHg. Ophthalmoscopy of the right eye revealed occlusion of the central retinal vein with venous engorgement, few flame-shaped hemorrhages, blurring of optic disc margins and rare cotton-wool spots. In the left eye, ophthalmoscopy was normal. Angiography of OD showed a nonischemic central retinal vein occlusion (Figure 1), and of OS was normal. Biochemistry and hematology tests were otherwise normal. Erythrocyte sedimentation rate was 7 mm/h. Immunological tests for rheumatoid factor, lupus anticoagulant, as well as tests for nuclear, DNA, phospholipid and neutrophil cytoplasmic antibodies were negative. A DNA analysis showed no mutation for factor V, prothrombin or MTHFR genes. Plasma levels of protein S and antithrombin III were normal. Plasma level of protein C was 58% (normal 70-140%), compatible with the diagnosis of heterozygous protein C deficiency. Heparin anticoagulation was promptly instituted and warfarin then introduced. One month later, visual acuity of the right eye was 20/20 and complete improvement in ophthalmoscopic findings was noted. Neither parents nor children were available for ocular and systemic examination.

COMMENT

Acute occlusion of the central retinal vein is one of the most dramatic pictures in ophthalmology. It is often a result of both local and systemic causes^(1-2). An increased risk for central retinal vein occlusion is found in patients with systemic hypertension, diabetes mellitus, open-angle glaucoma, and thrombophilic conditions^(1-3).

Although there is no consensus, referring patients younger than 50 years old with central retinal vein occlusion to thrombophilia screening seems to be appropriate^(1-4). A cost-effective approach would be to screen initially for activated protein C resistance, because the test for this disease is relatively easy to perform and provides good differentiation between normal and resistant subjects. If this test is negative, then the patient should be screened for lupus anticoagulant, anticardiolipin antibody, protein C, protein S, and antithrombin III deficiencies^(1-2).

Activated protein C resistance is the most common inherited hypercoagulable state associated with venous thrombosis. It is usually caused by a single point mutation in the factor V gene referred to as factor V Leiden^(1,4-5). This condition has been frequently associated withcentral retina vein occlusion^(1-2,5). In contrast, protein C deficiency is an uncommon cause of venous thrombosis^(6-8). Its inherited deficiencies are either heterozygous or homozygous, with levels of protein C around 50% and 1%, respectively (normal 70-140%). Although homozygous deficiencies of protein C tend to result in severe neonatal thrombotic disease, heterozygous deficiencies result in milder thrombotic tendencies^(1,6-7). Patients with the heterozygous form who have already suffered an episode of thrombosis may be treated with long-term anticoagulation, but each patient should be considered on an individual basis⁽⁸⁾. This disorder seems to represent an autosomal dominant trait, although its penetrance is variable^(4,6).

There are few reports of central retinal vein occlusion associated with protein C deficiency^(3,9-10), and they usually occur in combination with other thrombophilic conditions. This case highlights that isolated heterozygous protein C deficiency may be the cause of central retinal vein thrombosis and underscores the importance of its screening in young patients with this ophthalmologic disease.

Recebido para publicação em 24.07.2001

Aceito para publicação em 05.08.2002

Nota Editorial:Pela análise deste trabalho e por sua anuência na divulgação desta nota, agradecemos ao Dr. Ayrton Roberto Branco Ramos.

• 1. Vine AK, Samama MM. The role of abnormalities in the anticoagulant and fibrinolytic systems in retinal vascular occlusions. Surv Ophthalmol 1993; 37:283-92.
• 2. Greiner K, Hafner G, Dick B, Peetz D, Prellwitz W, Pfeiffer N. Retinal vascular occlusion and deficiencies in the protein C pathway. Am J Ophthalmol 1999;128:69-74.
• 3. Tekeli O, Gursel E, Buyurgan H. Protein C, protein S and antithrombin III deficiencies in retinal vein occlusion. Acta Ophthalmol Scand 1999;77:628-30.
• 4. Rosendaal FR. Venous thrombosis: a multicausal disease. Lancet 1999; 353:1167-73.
• 5. Willianson TH, Rumley A, Lowe GD. Blood viscosity, coagulation, and activated protein C resistance in central retinal vein occlusion: a population controlled study. Br J Ophthalmol 1996;80:203-8.
• 6. Reitsma PH. Protein C deficiency: from gene defect to disease. Thrombosis and haemostasis 1997;78:344-50.
• 7. Nizzi FA Jr, Kaplan HS. Protein C and S deficiency. Semin Thromb Hemost 1999;25:265-72.
• 8. Sanson BJ, Simioni P, Tormene D et al. The incidence of venous thromboembolism in asymptomatic carriers of a deficiency of antithrombin, protein C, or protein S: a prospective cohort study. Blood 1999;94:3702-6.
• 9. Bertram B, Remky A, Arend O, Wolf S, Reim M. Protein C, protein S, and antithrombin III in acute ocular occlusive diseases. Ger J Ophthalmol 1995; 4:332-5.
• 10. Krüger K, Anger V. Occlusion ischémique de la veine centrale de la rétine et déficit en protéine C. J Fr Ophtalmol 1990;13:369-71.

¹

Doutor em Ciências Médicas pela Universidade Estadual de Campinas, UNICAMP

²

Pós-graduando nível Mestrado do Curso de Pós-graduação em Ciências Médicas da Universidade Estadual de Campinas, UNICAMP

³

Pós-graduando nível Doutorado do Curso de Pós-graduação em Clínica Médica da Universidade Estadual de Campinas, UNICAMP

⁴

Professor Assistente Doutor do Departamento de Oftalmo-Otorrinolaringologia da UNICAMP

Publication Dates

• Publication in this collection
  28 Mar 2003
• Date of issue
  Jan 2003

History

• Accepted
  05 Aug 2002
• Received
  24 July 2001