Peripheral retinal neovascularization (Eales disease) associated with the factor V Leiden mutation.

PURPOSE: To illustrate a case of peripheral retinal neovascularization (Eales disease) in a patient who tested positive for the factor V Leiden mutation. METHODS: A 42-year-old woman had a 1-week history of blurred vision in her right eye. Her medical history was remarkable for a cerebrovascular accident. Ophthalmoscopy of the right eye disclosed a mild vitreous hemorrhage and a ridge of retinal neovascularization in the temporal periphery. The left fundus showed evidence of temporal retinal ischemia. A laboratory evaluation for hypercoagulability was positive for factor V Leiden mutation. RESULTS: Peripheral scatter laser photocoagulation was applied to the ischemic retina, and the neovascularization regressed. The patient began taking warfarin sodium to prevent further thrombotic events. CONCLUSION: A laboratory evaluation for coagulopathy, including the factor V Leiden mutation, should be added to the examination of patients with Eales disease, especially individuals with a history of a previous thrombotic event.

Arterial thromboembolic events in patients with the factor V Leiden mutation.

BACKGROUND: The factor V Leiden mutation affects 6% of the United States population and is known to be associated with venous thrombosis. We identify, herein, 30 individuals with the Leiden mutation and known arterial thromboembolic events. METHODS: The factor V mutation was assessed using polymerase chain reaction. RESULTS: In the 16 patients sustaining a cerebrovascular accident, the mean age was 44.1 and 11 (69%) were younger than 50. Similarly, the 13 patients presenting with an acute myocardial infarction were relatively young with a mean age of 45.5, and 9 (65%) patients presented at less than 50 years of age. Radiographic information was available for 19 patients in this study. No significant arterial atherosclerotic disease was demonstrated in 18 (95%) of these patients. CONCLUSIONS: This study demonstrates an association between the factor V Leiden mutation and the development of unexplained arterial thromboembolic events, especially in younger patients without existing atherosclerotic disease.

von Willebrand disease and bleeding in women.

Menorrhagia is a common health problem in women, particularly those with bleeding disorders. Little is known about the course of menorrhagia or other bleeding symptoms in women with the most common congenital bleeding disorder, von Willebrand disease (vWD). We determined the prevalence of menorrhagia, bleeding symptoms and coagulation abnormalities associated with vWD, including factor VIII activity, von Willebrand factor (vWF) antigen, ristocetin cofactor and bleeding time (BT), on a cohort of 38 females with type 1 vWD referred for diagnosis and medical care. Menorrhagia was the most common bleeding symptom in females with vWD, occurring in 93.1% of adult women. Menorrhagia was also the most common initial bleeding symptom, occurring in 53.1% of adult women in all of whom it began at menarche, median 14 years of age. There was a delay from initial bleeding symptoms, at median age 12 years, to diagnosis, at median age 16 years, P=0.0049. Although 94% undergoing surgery had previous bleeding, a vWD diagnosis was known preoperatively in only 6.2%, resulting in potentially preventable bleeding. In summary, menorrhagia is the most common bleeding symptom in females with vWD and begins at menarche. Obtaining a personal and family bleeding history promotes early diagnosis, potentially prevents postoperative bleeding, and improves the health of women with vWD.

Lipopolysaccharide induction of tissue factor expression in THP-1 monocytic cells. Protein-DNA interactions with the promoter.

Tissue factor, the cellular receptor for factor VII/VIIa, activates both the intrinsic and extrinsic pathways of blood coagulation. In this analysis we have used DNase I footprinting to map the sites of protein-DNA interaction along the promoter (-383 to +8) using nuclear extracts prepared from uninduced and lipopolysaccharide-induced THP-1 cells. We have identified six regions that interact with nuclear factors in both uninduced and induced extracts. Four footprints are contained within a region reported to confer base-line high level expression and lipopolysaccharide and serum induction. Two additional footprints map to a region reported to reduce basal transcription by 50%. The only qualitative change in the footprint pattern with uninduced and induced extracts is the appearance of two hypersensitive sites with uninduced extracts. In addition, changes in the level of protein- DNA binding are detected with only one probe by DNA mobility shift analysis. A combination of well characterized transcription factors (AP1), primarily lymphoid cell specific regulatory proteins (NF-kappa B- and/or Ets-1-related proteins), as well as additional, uncharacterized proteins appear to interact with these sequences. Our data suggest that post-translational modification of existing transcription factors, and not induction of new DNA-binding activity, mediates the lipopolysaccharide induction of tissue factor synthesis in THP-1 cells.

The factor V Leiden mutation: spectrum of thrombotic events and laboratory evaluation.

PURPOSE: This study aims to describe the spectrum of clinical thrombotic events and to compare the methods of laboratory evaluation for the newly described prothrombotic factor V Leiden mutation. METHODS: Specimens from 1376 patients with thrombotic events or their relatives were tested for the factor V Leiden mutation by polymerase chain reaction plus restriction digest from Jan. 1, 1995, to Mar. 31, 1996. Activated protein C (APC) resistance test data was available for 554 of these patients. Clinical information was available for 166 patients with the mutation. RESULTS: Of 1376 patients tested for factor V Leiden mutation, 270 (19.6%) were positive, with 12 homozygotes and 258 heterozygotes. Of 554 patients for whom APC resistance data was available, 221 (39.9%) had low APC resistance ratios (< or = 2.4); of these only 97 (43.9%) were factor V Leiden-positive. Among 333 samples with normal or elevated APC resistance ratios, 19 (5.7%) were later identified with the factor V Leiden mutation, despite the normal screening test. One hundred fourteen of 166 patients (68.7%) with the mutation had at least one thrombotic event, most commonly deep venous thrombosis and pulmonary embolus. Arterial cerebrovascular thrombotic events occurred in 11 patients (10%), and myocardial infarctions in eight (7%). The mean age of all patients with arterial thrombotic events was 45.4 years. CONCLUSIONS: The factor V mutation is a common cause of venous thromboses but may also be associated with the early presentation of arterial thrombotic events. The APC resistance test is a sensitive screening assay but has limitations of its specificity in clinical practice.