Renal infarction in a patient with von Willebrand disease

Won Kim1, Sang Yong Lee2, Soo Wan Kim3, Jae Yong Kwak1, Sung Kyew Kang1 and Sung Kwang Park1

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 34–38 s). Coagulation factor tests showed factor VIII 28.9% (our laboratory normal 60–140%), von Willebrand factor (vWF)-related antigen 35% (normal 50–160%), vWF ristocetin cofactor 32.2% (normal 60–170%), factor XI 83% (normal 60–140%), protein S 81.8% (normal 55–140%), and protein C 98% (normal 60–150%). 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 1Go). 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 2Go). 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.



View larger version (110K):
[in this window]
[in a new window]
 
Fig. 1. No blood flow was found in the mid-portion of the rightkidney in colour-coded Doppler ultrasonography where hyperechogenicity had been seen with simple ultrasonography.

 


View larger version (110K):
[in this window]
[in a new window]
 
Fig. 2. Abdominal computed tomography at the level of the kidneyrevealed a wedge-shaped, sharply marginated, low-density lesion,which is highly suggestive of segmental, right renal infarction.

 

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 haemolytic–uraemic 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

  1. Bowen D, Dasani H, Yung B, Bloom A. Deep venous thrombosis and pulmonary embolism in a patient with type III von Willebrand's disease, protein C and antithrombin III deficiency. Br J Haematol1992; 81: 446–447[ISI][Medline]
  2. Pareti FI, Federici AB, Cattaneo M, Mannucci PM. Spontaneous platelet aggregation during pregnancy in a patient with von Willebrand disease type IIB can be blocked by monoclonal antibodies to both platelet glycoproteins Ib and IIb/IIIa. Br J Haematol1990; 75: 86–91[ISI][Medline]
  3. Mannucci PM, Lombardi R, Bader R et al. Studies of the pathophysiology of acquired von Willebrand's disease in seven patients with lymphoproliferative disorders or benign monoclonal gammopathies. Blood1984; 64: 614–621[Abstract]
  4. Simone JV, Cornet JA, Abildgaard CF. Acquired von Willebrand's syndrome in systemic lupus erythematosus. Blood1968; 31: 806–812[ISI][Medline]
  5. McGrath KM, Johnson CA, Stuart JJ. Acquired von Willebrand disease associated with an inhibitor to factor VIII antigen and gastrointestinal telangiectasia. Am J Med1979; 67: 693–696[ISI][Medline]
  6. Petaja J, Rasi V, Myllyla G, Vahtera E, Hallman H. Familial hypofibrinolysis and venous thrombosis. Br J Haematol1989; 71: 393–398[ISI][Medline]




This Article
Extract
FREE Full Text (PDF)
Alert me when this article is cited
Alert me if a correction is posted
Services
Email this article to a friend
Similar articles in this journal
Similar articles in ISI Web of Science
Similar articles in PubMed
Alert me to new issues of the journal
Add to My Personal Archive
Download to citation manager
Disclaimer
Request Permissions
Google Scholar
Articles by Kim, W.
Articles by Park, S. K.
PubMed
PubMed Citation
Articles by Kim, W.
Articles by Park, S. K.