Bilateral Macular Hemorrhage Caused by Azathioprine-Induced Aplastic Anemia in a Corneal Graft Recipient

Sudhir, Rachapalli R.; Rao, Srinivas K; Shanmugam, Mahesh P; Padmanabhan, Prema

doi:10.1097/00003226-200210000-00016

Cited by 22 publications

(4 citation statements)

References 12 publications

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“…The present experiments were therefore carried out to characterize the effects of AZA treatment on the haematopoietic system of the mouse, and compare these changes to those reported in man. AZA was selected as a drug of choice for these studies because, as well as causing a profound pancytopenia, AZA may also induce a pure red cell aplasia (Old et al 1978;Pruijt et al 1996;Thompson & Gales 1996;Al-Uzri et al 2003), and aplastic anaemia (Lawson et al 1984;Sudhir et al 2002). Furthermore, we have been planning experiments directed towards the development of a mouse model of drug-induced aplastic anaemia, and are considering studies with AZA administered as a second haemotoxic agent to mice pretreated with the anti-cancer agent busulphan (Gibson et al 2003;Turton et al 2006).…”

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confidence: 99%

The haemotoxicity of azathioprine in repeat dose studies in the female CD‐1 mouse

Molyneux

Gibson

Chen

et al. 2008

Int J Experimental Path

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Azathioprine (AZA) is a cytotoxic immunosuppressive drug used in the prevention of rejection in organ transplants and the treatment of auto-immune diseases. However, AZA is haemotoxic causing significant bone marrow depression. The present studies were to characterize the haemotoxicity of AZA in the female CD-1 mouse. In Experiment 1, a dose-ranging study, with AZA gavaged daily for 10 days, clinical evidence of toxicity was evident at 125 mg/kg and above. Experiment 2 was a dose-response study with AZA gavaged daily for 10 days at 40-120 mg/kg. At day 1 after the final dose, AZA induced a dose-related pancytopaenia, reduced femoral marrow cellularity, increases in serum levels of the cytokine fms-like tyrosine kinase 3 ligand, reduction in granulocyte-monocyte colony-forming units and erythroid colonies, and increased bone marrow apoptosis. Histology demonstrated hepatocyte hypertrophy, thymic atrophy, reduced splenic extramedullary haemopoiesis, and reduced cellularity of sternal bone marrow. In Experiment 3, AZA was dosed for 10 days at 100 mg/kg with autopsies at 1, 3, 9, 22, 29, 43 and 57 days postdosing. At 1, 3 and 9 days, haematological parameters reflected changes in Experiment 2. At 22/29 days, many blood parameters were returning towards normal; at 43/57 days, most parameters compared with controls. However, there was some evidence of a persistent (i.e. residual/late-stage) mild reduction in RBC and erythroid progenitor cell counts at day 43/57. We conclude that the CD-1 mouse provides an acceptable model for the haemotoxicity of AZA in man.

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confidence: 99%

The haemotoxicity of azathioprine in repeat dose studies in the female CD‐1 mouse

Molyneux

Gibson

Chen

et al. 2008

Int J Experimental Path

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“…CsA side effects have been reported in corneal graft rejection patients [6,26]. A rare association between azathioprine-induced aplastic anemia and bilateral macular hemorrhage in one corneal graft recipient has been reported [32]. MMF may produce gastrointestinal distress, hepatotoxicity, aplastic anemia, lymphoma and skin carcinoma.…”

Section: Resultsmentioning

confidence: 99%

Management of Corneal Graft Rejection – A Case Series Report and Review of the Literature

Nguyẽ̂n¹,

Barte²,

Shinada³

et al. 2010

J Clinic Experiment Ophthalmol

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“…Clinical features: Anemia, neutropenia and thrombocytopenia result in fatigue, pallor recurrent infections, mucosal hemorrhage, menorrhagia, petechiae, and rarely SPE [7]. Retinal and vitreous hemorrhage, neovascularization, and cotton-wool spots have also been reported [60][61][62].…”

Section: Coagulation Disorders Aplastic Anemiamentioning

confidence: 99%

Spontaneous Periocular Ecchymosis in Children: Differential Diagnosis and Current Trends in Evaluation and Management

Kavoussi¹,

Pasco²,

Mears³

et al. 2014

J Clin Exp Ophthalmol

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While periocular ecchymosis commonly develops following surgery or traumatic injury to the orbit, the spontaneous appearance of periocular ecchymosis in children can indicate the presence of life-threatening conditions including pediatric malignancies (neuroblastoma, rhabdomyosarcoma, leukemia) and hematologic disorders (aplastic anemia, thrombocytopenia). Vascular malformations (capillary hemangioma, lymphangioma, orbital varix), inflammatory conditions (orbital myositis, amyloidosis), pertussis, and Blue rubber bleb nevus syndrome are benign differential considerations with visual complications in certain instances. Since spontaneous periocular ecchymosis (SPE) can be encountered by pediatric subspecialists both within and outside ophthalmology, the authors present a review of the current literature integrating the clinical features, latest diagnostic investigations, and updates in management for the entities that cause spontaneous periocular ecchymosis in children. A comprehensive and current understanding of the differential diagnosis elicited by this unique ocular finding will aid the clinician in managing long-term visual consequences and coordinating with appropriate pediatric subspecialists.

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Bilateral Macular Hemorrhage Caused by Azathioprine-Induced Aplastic Anemia in a Corneal Graft Recipient

Abstract: This report highlights the serious ocular and systemic complications that can occur following the use of systemic immunosuppressants after ophthalmic surgery.

Cited by 22 publications

References 12 publications

The haemotoxicity of azathioprine in repeat dose studies in the female CD‐1 mouse

The haemotoxicity of azathioprine in repeat dose studies in the female CD‐1 mouse

Management of Corneal Graft Rejection – A Case Series Report and Review of the Literature

Spontaneous Periocular Ecchymosis in Children: Differential Diagnosis and Current Trends in Evaluation and Management

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