Graefe's Archive Ophthalmology lot Clinical and Experimental
Communications
© Springer-Verlag 1992 Graefe's Arch Clin Exp Ophthalmol (1992) 230:496-497
Vitreous, retinal and subretinal hemorrhages associated with von Willebrand's syndrome Takashi Shiono 1, Schin-ichi Abe 1, Tamaki Watabe 1, Michiru Noro 1, Makoto Tamai 1, Yasuyuki Akutsu 2, Masaaki Ishikawa 2, Sozo Suzuki 2, and Kazuo Mori 2 1 Department of Ophthalmology and 2 the Third Department of Internal Medicine, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendal 980, Japan Received September 17, 1991 / Accepted November 8, 1991
Abstract. Two patients with v o n Willebrand's s y n d r o m e had intraocular h e m o r r h a g e s w i t h o u t t r a u m a or neovascularization. A 13-year-old Japanese girl c o m p l a i n e d o f sudden spotted vision in her left eye. Vitreous, peripapillary retinal, a n d subretinal h e m o r r h a g e s were seen by o p h t h a l m o s c o p y in the affected eye. In addition, a 19year-old Japanese m a n h a d repeated vitreous h e m o r rhage a n d epistaxis. Also noted was gyrate a t r o p h y o f the c h o r o i d a n d retina. Analysis o f the coagulation-fibrinolysis system revealed decreased activities o f F a c t o r V I I I and v o n Willebrand's factor in b o t h patients. The a m o u n t o f v o n Willebrand's factor antigen also was decreased. These results suggested that the patients h a d von Willebrand's syndrome. The bleeding tendency in the disorder a p p e a r e d to be responsible for the p a t h o genesis o f the intraocular h e m o r r h a g e s seen in these patients.
Introduction Von Willebrand's syndrome, one o f the hereditary coagulation disorders [6], is characterized by an a b n o r m a l i t y or deficiency o f the v o n Willebrand's factor [2, 5, 7]. The clinical picture includes epistaxis, gastrointestinal bleeding, and m e n o r r h a g i a [6, 7]. The bleeding manifestations in the typical patient with v o n Willebrand's synd r o m e are relatively mild, a n d those w h o have the partial f o r m o f the disease m a y be virtually a s y m p t o m a t i c . We describe two patients with v o n Willebrand's s y n d r o m e w h o presented with vitreous, retinal, and subretinal hemorrhages. To o u r knowledge, this is the first report that shows the relationship between intraocular h e m o r r h a g e s and decreased v o n Willebrand's factor.
Correspondence to." T. Shiono
Case reports Case 1
A 13-year-old Japanese girl came to our eye clinic in April 1989 for sudden spotted vision in her fight eye. She had no history of blood dyscrasias or epistaxis. Her eye examination revealed the best corrected visual acuity of 20/30 in the right eye and 20/15 in the left eye. The slit-lamp examination showed a normal anterior segment and lens. The intraocular pressures by applanation tonomerry were normal in both eyes. Ophthalmoscopic examination showed vitreous, peripapillary retinal, and subretinal hemorrhages in her right fundus (Fig. 1). No abnormalities were found in her left eye. These findings were confirmed by fluorescein angiography (Fig. 2). A computer tomography scan showed no abnormalities in her head, orbits, or eyes. The intraocular hemorrhages without trauma led us test for blood dyscrasias in the patient. No abnormality was found in the following evaluations: white blood cell count, red blood cell count, hemoglobin, hematocrit, platelet count, bleeding time, prothrombin time (PT), thrombin time (TT), maximum platelet aggregation (ADP and collagen induced), and coagulation factors (II, V, VII, IX, X, XI, XII). Only a slightly prolonged kaolin-activated partial thromboplastin time (48.4 s; normal range 35.8 _-t-3.0, mean_+ SD) and decreased activity of Factor VIII (51% of normal) and of von Willebrand's factor (55% of normal) were observed. The amount of von Willebrand's factor antigen was also decreased (45 % of normal). After 3 months the hemorrhages disappeared, and her visual acuity improved to 20/15. Fluorescein angiography was performed to determine the causes of the hemorrhages. No abnormalities were found. No new hemorrhages were noted at 1 year or at 20 months after the initial examination.
Case 2
A 19-year-old Japanese man, who has been described in previous reports [3, 4], had repeated epistaxis and vitreous hemorrhages in both eyes. His clinical findings are briefly summarized here. At age 8 years, he was referred to our clinic. His fundus showed typical chorioretinal atrophy with scalloped margins at the periphery. Biochemical hyperornithinemia (12.95mg/100ml; normal 0.36-1.56 mg/100 ml) was noted. Ornithine aminotransferase activity was undetectable in extracts of his cultured skin fibroblasts. The diagnosis of typical gyrate atrophy of the choroid and retina was made. During the follow-up period, he had repeated epistaxis and vitreous hemorrhages. Blood analysis in 1990 disclosed that the following results were within the normal range: white blood
497
brand's syndrome is ,one of the hereditary coagulation disorders that shows manifestations of bleeding [6, 7]. The basic defect in yon Willebrand's syndrome is an abnormality or deficiency of von Willebrand's factor [2, 5, 7]. The disease is mostly inherited as an incomplete autosomal dominant trait, although the expressivity of the genetic abnormality is highly variable, even among members of a single family. Cases of autosomal recessive and X-linked recessive inheritance have also been reported. Clinical features range from mild to severe. In the severe forms of the disorder, hemarthroses and dissecting intramuscular hematoma may develop. In the mild forms, however, the clinical picture is dominated only by cutaneous and mucosal bleeding. Some patients may be virtually asymptomatic. The patient in our case i had vitreous, peripapillary retinal, and subretinal hemorrhages and a decreased level of von Willebrand's factor, which is compatible with type I yon Willebrand's syndrome [5]. She had no trauma or other systemic disorders. The patient in our case 2 [3, 4] had repeated vitreous hemorrhages and epistaxis and type Ivon Willebrand's syndrome. No trauma or other systemic disorders were reported, although he had gyrate atrophy of the choroid and retina. We believe, therefore, that intraocular hemorrhages in our patients were related to the decreased level of von Willebrand's factor. Recognition of the association of decreased von Willebrand's factor with intraocular hemorrhages could suggest specific therapeutic approaches. In severe cases, management should include the use of cryoprecipitate or concentrated Factor VIII containing von Willebrand's factor. We suggest that decreased von Willebrand's factor should be considered in some cases of vitreous; retinal, and subretinal hemorrhages without a history of trauma or neovascularization, particularly in the young patient.
Fig. 1. Vitreous, peripapillary retinal, and subretinal hemorrhages are seen in the right fundus of the patient in case 1 Fig. 2. Fluorescein angiography reveals hypofluorescence corresponding to the retinal and subretinal hemorrhages
cell count, red blood cell count, hemoglobin, hematocrit, platelet count, thrombin and prothrombin times, fibrinogen, Factors II, V, VII, IX, X, XI, XII, antithrombin III, and plasminogen. Observed were decreased activities of Factor VIII (43% of normal) and von Willebrand's factor (51.5% of normal). The amount of von Willebrand's factor antigen (47% of normal) was also decreased. The diagnosis of type I v o n Willebrand's syndrome was made.
Discussion
Retinal and vitreous hemorrhages occur in diseases of the hematopoietic system, such as anemia, leukemia, purpura, polycythemia, and hemophilia [1]. Von Wille-
References 1. Duke-Elder S (1967) Retinal hemorrhages. In: Duke-Elder S (ed) System of ophthalmology. Henry Kimpton, London, pp 137-150 2. Gralnick HR, Cregger MC, Williams SB (1982) Characterization of the defect of the factor VIII/von Willebrand factor protein in yon Willebrand's disease. Blood 59 : 542-548 3. Hayasaka S, Saito T, Nakajima H, Takaku Y, Shiono T, Mizuno K, Omura K, Tada K (1981) Gyrate atrophy with hyperornithinemia. Different types in responsiveness to vitamin B 6. Br J Ophthalmol 65:478-483 4. Takahashi O, Hayasaka S, Kiyosawa M, Mizuno K, Saito T, Tada K, Igarashi Y (1985) Gyrate atrophy of choroid and retina complicated by vitreous hemorrhage. Jpn J Ophthalmol 29:17(~ 176 5. Tuddenham EGD (1984) The varieties of von Willebrand's disease. Clin Lab Haematol 6:307-323 6. Willebrand EA von (1926) Hereditar pseudohamofil. Finsk Lakaresallsk Handl 68:87-112 7. Wintrobe MM (1981) von Willebrand's disease. In: Wintrobe MM (ed) Clinical hematology, 8th edn. Lea & Febiger, Philadelphia, pp 116%1175
Communications
© Springer-Verlag 1992 Graefe's Arch Clin Exp Ophthalmol (1992) 230:496-497
Vitreous, retinal and subretinal hemorrhages associated with von Willebrand's syndrome Takashi Shiono 1, Schin-ichi Abe 1, Tamaki Watabe 1, Michiru Noro 1, Makoto Tamai 1, Yasuyuki Akutsu 2, Masaaki Ishikawa 2, Sozo Suzuki 2, and Kazuo Mori 2 1 Department of Ophthalmology and 2 the Third Department of Internal Medicine, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendal 980, Japan Received September 17, 1991 / Accepted November 8, 1991
Abstract. Two patients with v o n Willebrand's s y n d r o m e had intraocular h e m o r r h a g e s w i t h o u t t r a u m a or neovascularization. A 13-year-old Japanese girl c o m p l a i n e d o f sudden spotted vision in her left eye. Vitreous, peripapillary retinal, a n d subretinal h e m o r r h a g e s were seen by o p h t h a l m o s c o p y in the affected eye. In addition, a 19year-old Japanese m a n h a d repeated vitreous h e m o r rhage a n d epistaxis. Also noted was gyrate a t r o p h y o f the c h o r o i d a n d retina. Analysis o f the coagulation-fibrinolysis system revealed decreased activities o f F a c t o r V I I I and v o n Willebrand's factor in b o t h patients. The a m o u n t o f v o n Willebrand's factor antigen also was decreased. These results suggested that the patients h a d von Willebrand's syndrome. The bleeding tendency in the disorder a p p e a r e d to be responsible for the p a t h o genesis o f the intraocular h e m o r r h a g e s seen in these patients.
Introduction Von Willebrand's syndrome, one o f the hereditary coagulation disorders [6], is characterized by an a b n o r m a l i t y or deficiency o f the v o n Willebrand's factor [2, 5, 7]. The clinical picture includes epistaxis, gastrointestinal bleeding, and m e n o r r h a g i a [6, 7]. The bleeding manifestations in the typical patient with v o n Willebrand's synd r o m e are relatively mild, a n d those w h o have the partial f o r m o f the disease m a y be virtually a s y m p t o m a t i c . We describe two patients with v o n Willebrand's s y n d r o m e w h o presented with vitreous, retinal, and subretinal hemorrhages. To o u r knowledge, this is the first report that shows the relationship between intraocular h e m o r r h a g e s and decreased v o n Willebrand's factor.
Correspondence to." T. Shiono
Case reports Case 1
A 13-year-old Japanese girl came to our eye clinic in April 1989 for sudden spotted vision in her fight eye. She had no history of blood dyscrasias or epistaxis. Her eye examination revealed the best corrected visual acuity of 20/30 in the right eye and 20/15 in the left eye. The slit-lamp examination showed a normal anterior segment and lens. The intraocular pressures by applanation tonomerry were normal in both eyes. Ophthalmoscopic examination showed vitreous, peripapillary retinal, and subretinal hemorrhages in her right fundus (Fig. 1). No abnormalities were found in her left eye. These findings were confirmed by fluorescein angiography (Fig. 2). A computer tomography scan showed no abnormalities in her head, orbits, or eyes. The intraocular hemorrhages without trauma led us test for blood dyscrasias in the patient. No abnormality was found in the following evaluations: white blood cell count, red blood cell count, hemoglobin, hematocrit, platelet count, bleeding time, prothrombin time (PT), thrombin time (TT), maximum platelet aggregation (ADP and collagen induced), and coagulation factors (II, V, VII, IX, X, XI, XII). Only a slightly prolonged kaolin-activated partial thromboplastin time (48.4 s; normal range 35.8 _-t-3.0, mean_+ SD) and decreased activity of Factor VIII (51% of normal) and of von Willebrand's factor (55% of normal) were observed. The amount of von Willebrand's factor antigen was also decreased (45 % of normal). After 3 months the hemorrhages disappeared, and her visual acuity improved to 20/15. Fluorescein angiography was performed to determine the causes of the hemorrhages. No abnormalities were found. No new hemorrhages were noted at 1 year or at 20 months after the initial examination.
Case 2
A 19-year-old Japanese man, who has been described in previous reports [3, 4], had repeated epistaxis and vitreous hemorrhages in both eyes. His clinical findings are briefly summarized here. At age 8 years, he was referred to our clinic. His fundus showed typical chorioretinal atrophy with scalloped margins at the periphery. Biochemical hyperornithinemia (12.95mg/100ml; normal 0.36-1.56 mg/100 ml) was noted. Ornithine aminotransferase activity was undetectable in extracts of his cultured skin fibroblasts. The diagnosis of typical gyrate atrophy of the choroid and retina was made. During the follow-up period, he had repeated epistaxis and vitreous hemorrhages. Blood analysis in 1990 disclosed that the following results were within the normal range: white blood
497
brand's syndrome is ,one of the hereditary coagulation disorders that shows manifestations of bleeding [6, 7]. The basic defect in yon Willebrand's syndrome is an abnormality or deficiency of von Willebrand's factor [2, 5, 7]. The disease is mostly inherited as an incomplete autosomal dominant trait, although the expressivity of the genetic abnormality is highly variable, even among members of a single family. Cases of autosomal recessive and X-linked recessive inheritance have also been reported. Clinical features range from mild to severe. In the severe forms of the disorder, hemarthroses and dissecting intramuscular hematoma may develop. In the mild forms, however, the clinical picture is dominated only by cutaneous and mucosal bleeding. Some patients may be virtually asymptomatic. The patient in our case i had vitreous, peripapillary retinal, and subretinal hemorrhages and a decreased level of von Willebrand's factor, which is compatible with type I yon Willebrand's syndrome [5]. She had no trauma or other systemic disorders. The patient in our case 2 [3, 4] had repeated vitreous hemorrhages and epistaxis and type Ivon Willebrand's syndrome. No trauma or other systemic disorders were reported, although he had gyrate atrophy of the choroid and retina. We believe, therefore, that intraocular hemorrhages in our patients were related to the decreased level of von Willebrand's factor. Recognition of the association of decreased von Willebrand's factor with intraocular hemorrhages could suggest specific therapeutic approaches. In severe cases, management should include the use of cryoprecipitate or concentrated Factor VIII containing von Willebrand's factor. We suggest that decreased von Willebrand's factor should be considered in some cases of vitreous; retinal, and subretinal hemorrhages without a history of trauma or neovascularization, particularly in the young patient.
Fig. 1. Vitreous, peripapillary retinal, and subretinal hemorrhages are seen in the right fundus of the patient in case 1 Fig. 2. Fluorescein angiography reveals hypofluorescence corresponding to the retinal and subretinal hemorrhages
cell count, red blood cell count, hemoglobin, hematocrit, platelet count, thrombin and prothrombin times, fibrinogen, Factors II, V, VII, IX, X, XI, XII, antithrombin III, and plasminogen. Observed were decreased activities of Factor VIII (43% of normal) and von Willebrand's factor (51.5% of normal). The amount of von Willebrand's factor antigen (47% of normal) was also decreased. The diagnosis of type I v o n Willebrand's syndrome was made.
Discussion
Retinal and vitreous hemorrhages occur in diseases of the hematopoietic system, such as anemia, leukemia, purpura, polycythemia, and hemophilia [1]. Von Wille-
References 1. Duke-Elder S (1967) Retinal hemorrhages. In: Duke-Elder S (ed) System of ophthalmology. Henry Kimpton, London, pp 137-150 2. Gralnick HR, Cregger MC, Williams SB (1982) Characterization of the defect of the factor VIII/von Willebrand factor protein in yon Willebrand's disease. Blood 59 : 542-548 3. Hayasaka S, Saito T, Nakajima H, Takaku Y, Shiono T, Mizuno K, Omura K, Tada K (1981) Gyrate atrophy with hyperornithinemia. Different types in responsiveness to vitamin B 6. Br J Ophthalmol 65:478-483 4. Takahashi O, Hayasaka S, Kiyosawa M, Mizuno K, Saito T, Tada K, Igarashi Y (1985) Gyrate atrophy of choroid and retina complicated by vitreous hemorrhage. Jpn J Ophthalmol 29:17(~ 176 5. Tuddenham EGD (1984) The varieties of von Willebrand's disease. Clin Lab Haematol 6:307-323 6. Willebrand EA von (1926) Hereditar pseudohamofil. Finsk Lakaresallsk Handl 68:87-112 7. Wintrobe MM (1981) von Willebrand's disease. In: Wintrobe MM (ed) Clinical hematology, 8th edn. Lea & Febiger, Philadelphia, pp 116%1175
