1 Department of Internal Medicine, 2 Diagnostic Radiology, Institute for Medical Sciences, Chonbuk National University Medical School, Chonju, 3 Department of Internal Medicine, Chonnam National University Medical School, Kwangju, South Korea
Sir,
Von Willebrand disease (vWD) is the most common inherited bleeding disorder. Because vWD is heterogeneous there are variable manifestations. Common symptoms include bleeding after surgery, spontaneous epistaxis, menorrhagia, and gastrointestinal or genitourinary bleeding. There are some reports of thrombosis in vWD: one case of deep-venous thrombosis and pulmonary embolism in a patient with type III vWD and protein C and antithrombin III deficiency, and one case of spontaneous platelet aggregation during pregnancy in vWD type IIB have been published [1,2]. However, renal infarction in vWD has not previously been reported in the English literature. We describe such a case.
Case.
A 16-year-old girl was admitted with gross haematuria and recent onset of pain, without radiation, in the right costolumbar area. The pain started 5 days before admission and was unremitting. The patient, her mother, and her mother's brother had histories of prolonged bleeding episodes and easy cutaneous bruising. There was no personal or family history of diabetes, hypertension, or renal disorder.
On admission, the patient's blood pressure was 120/80 mmHg, supine pulse 70 b.p.m., and axillary temperature 36.8°C. Physical examination revealed lower left abdominal tenderness. Urinalysis showed many red blood cells per high-power field and 2+ proteinuria, but was negative for white blood cells, crystals, and casts; culture was negative. Serum chemistries were remarkable for elevated aspartate aminotransferase (56 U/l), alanine aminotransferase (54 U/l), lactic dehydrogenase (839 U/l) (predominantly LDH-2 isoenzymes), and creatinine phosphokinase (380 U/l). Lactic dehydrogenase, creatinine phosphokinase, and proteinuria normalized during hospitalization. Bleeding time was 6 min and clotting time was 7 min. Prothrombin time was 100% (INR ratio 1.0) and partial thromboplastin time was 36.0 s (laboratory normal 3438 s). Coagulation factor tests showed factor VIII 28.9% (our laboratory normal 60140%), von Willebrand factor (vWF)-related antigen 35% (normal 50160%), vWF ristocetin cofactor 32.2% (normal 60170%), factor XI 83% (normal 60140%), protein S 81.8% (normal 55140%), and protein C 98% (normal 60150%). Von Willebrand multimeric analysis was normal, which is consistent with a type I pattern. The screening test for factor V Leiden was negative. Lupus anticoagulant, antiphospholipid and anticardiolipin antibodies, and homocystinuria were negative. Underlying neoplasm or septic emboli were also excluded.
Using colour-coded Doppler ultrasonography, no evidence of blood flow was found in the mid-portion of the right kidney, where hyperechogenicity had been seen with simple ultrasonography of the kidney (Figure 1). Abdominal computed tomography at the level of the kidney revealed a wedge-shaped, sharply marginated, low-density lesion near the mid-portion of the right kidney, which was highly suggestive of obstruction in the posterior division of the right renal artery (Figure 2
). The patient was treated with heparin and later converted to coumadin therapy for a 3-month treatment course. She has remained symptom-free for 6 months.
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Discussion.
We describe a case of renal infarction in vWD. vWD is a haemorrhagic disorder, while renal infarction is associated with thrombosis or atherosclerosis. The coexistence of these two conditions is very rare. We believe that this is the first report in the English literature of renal infarction in vWD.
Inherited abnormalities in vWD are associated with a defect of the vWF gene on chromosome 12. Acquired vWD has been described in patients with lymphoproliferative disorders, systemic lupus erythematosus, malignancies, vascular telangiectasia, and benign monoclonal gammopathy [35]. Our patient had no evidence of a primary or secondary hypercoagulable state. She had a positive family history of a bleeding tendency and her bleeding time was prolonged. The serum levels of factor VIII, vWF-related antigen, and vWF ristocetin cofactor were decreased. By vWF multimeric analysis, this case was diagnosed as type 1 vWD.
The association between thrombosis and vWD is rarely reported. Petaja et al. [6] and Bowen et al. [1] reported that deep-venous thrombosis had been observed in a patient with vWD and then in association with other risk factors for thrombosis. A case with spontaneous platelet aggregation during pregnancy in vWD type IIB was reported by Pareti et al. [2].
The pathogenesis of thromboembolic phenomenon in vWD is not well understood. It is known that vWF in the plasma compartment is essential for the development of arterial thrombosis and that it also contributes to the maintenance of bleeding time and hemostasis. Absence of large vWF multimers, seen in type 2A von Willebrand disease and in myeloproliferative disorders, is associated with bleeding tendency. In patients with vWF multimers of supranormal size, as seen in thrombotic thrombocytopenic purpura and haemolyticuraemic syndrome, there is an increased risk of thrombosis. The thromboembolism in vWD can be associated with coagulation abnormality, atherosclerosis, pregnancy, and aggregation of vWF multimers. In this case we did not find the exact cause of the renal infarction. However, an aggregation of high-molecular-weight multimers of vWF may be a cause of renal infarction in this case even though von Willebrand multimeric analysis is normal. Other possible causative factors in this case are localized vascular endothelial injury, thrombosis, and microaneurysm in the renal artery, which were not detected by ultrasonography.
We suggest that renal infarction can occur in vWD although it is a haemorrhagic disorder.
References