Bilateral simultaneous central retinal vein occlusion (CRVO) caused by waldenstrom's macroglobulinaemia with acquired von willebrand's disease.

Abstract

Bilateral central retinal vein occlusion (CRVO) is rare. We report a case of bilateral simultaneous CRVO caused by Waldenstrom's macroglobulinaemia with acquired von Willebrand's disease. This case is unusual in that the paraprotein led to simultaneous bilateral thromboses but also possibly to an acquired coagulopathy (von Willebrand's disease). The incidence of fellow eye involvement in CRVO is reported to be 1%, with a higher rate when an underlying prothrombotic diathesis is present (e.g: hyperviscosity syndromes). However, CRVO as the initial presenting sign in these conditions is rare (Costen et al, 1999). A 67-year-old woman without visual symptoms was found to have bilateral retinal haemorrhages at a routine optometrist examination. She had a history of hypertension and was under investigation for lethargy, recurrent spontaneous bruising and epistaxis, and a previous spontaneous peri-orbital haemorrhage. She had two daughters born by Caesarian section and no prior history of a bleeding diathesis. Her corrected visual acuities were 6/9 OD (right eye) and 6/6 OS (left eye). Pupillary responses and intraocular pressures were normal and there was no evidence for rubeosis iridis. Fundoscopy revealed bilateral extensive-scattered retinal haemorrhages and venous tortuosity. Fluorescein angiography demonstrated a delayvenous filling in each eye (Fig 1A – right fundi and Fig 1B – left fundi). No ischaemic features were noted, but the presence of macular oedema was confirmed and a diagnosis of bilateral non-ischaemic CRVO was made. (A) Right fundi. Photograph of fluorescein angiography showing dilated and tortous veins and scattered retinal haemorrhages. (B) Left fundi. Photograph of fluorescein angiography showing dilated and tortuous veins and scattered retinal haemorrhages. There is also a macular oedema. Investigations revealed the following results: Hb 11·0 g/dl (11·5–16·5 g/dl), prothrombin time 21 s (control 13 s), activated partial thromboplastin time 50 s (control 30 s), factor VIII coagulant activity 30 IU/dl, factor V 34 IU/dl, factor VIII (von Willebrand factor, VWF) 20 IU/dl and factor VIII ristocetin cofactor 14 IU/dl (normal range 50–200 IU/dl), suggesting a diagnosis of von Willebrand's disease. Less relevant investigations showed: partial thromboplastin time 55·3 s (23·0–35·0 s), fibrinogen 1·45 g/l (1·5–4·5), IgG 2·6 g/l, IgA 0·6 g/l. Total protein at presentation was 138 g/l with albumin 39 g/l. Serum protein electrophoresis showed an IgM Kappa paraprotein of 70 g/l, with raised plasma viscosity [> 5 centipoises (cp)]. Bone marrow trephine biopsy was consistent with Waldenstrom's macroglobulinaemia/lymphoplasmacytoid lymphoma. The patient was managed with two plasmapheresis sessions, resulting in a normalization of the clotting factor profile. In addition, both the paraprotein level and plasma viscosity were reduced to 15·1 g/l and 1·96 cp respectively. Subsequent management included several courses of oral chlorambucil, and the patient remains in remission. Three months later, the corrected visual acuities had returned to 6/6 in each eye, with complete resolution of the macular oedema. Acquired von Willebrand's disease secondary to Waldenstrom's macroglobulinaemia is rare (Hennessy et al, 1998). There is a known association with the presence of autoimmune antibodies and clonal proliferation abnormalities. However, the aetiology of the deficiency of VWF in this disease remains unknown. Putative mechanisms include the formation of antibody–VWF complexes and the adsorption of VWF multimers to malignant haemopoietic cells (Simone et al, 1968; Mannucci et al, 1984). Waldenstrom's macroglobulinaemia is a rare and progressive neoplastic disorder associated with a raised monoclonal Ig paraprotein (IgM kappa type) (Avashia & Fath, 1989). The high molecular weight of IgM contributes to a raised serum viscosity. However, platelet function is also abnormal and bleeding times are often raised. Platelet aggregation and adhesiveness is abnormal as a result of non-specific coating by IgM M protein, which also binds to fibrin. This results in the formation of bulky primary clots that are incapable of retraction, promoting the formation of venous thrombosis, including CRVO (Hayreh et al, 1978). While CRVO is a well-recognized complication of paraproteinaemia and, on occasion, may be the presenting sign, this case is unusual in that the paraprotein led not only to simultaneous bilateral retinal vein thromboses, but also possibly to an acquired coagulopathy (von Willebrand's disease), manifesting as spontaneous recurrent epistaxis and bruising. Coagulation profiles in patients with CRVO should be performed as standard practice.