Mitral regurgitation is associated with similar loss of von Willebrand factor large multimers but lower frequency of anemia compared with aortic stenosis.

Background: Various cardiovascular diseases cause acquired von Willebrand syndrome (AVWS), which is characterized by a decrease in high-molecular-weight (large) von Willebrand factor (VWF) multimers. Mitral regurgitation (MR) has been reported as a cause of AVWS. However, much remains unclear about AVWS associated with MR. Objectives: To evaluate VWF multimers in MR patients and examine their impact on clinical characteristics. Methods: Moderate or severe MR patients (n = 84) were enrolled. VWF parameters such as the VWF large multimer index (VWF-LMI), a quantitative value that represents the amount of VWF large multimers, and clinical data were prospectively analyzed. Results: At baseline, the mean hemoglobin level was 12.9 ± 1.9 g/dL and 58 patients (69.0%) showed loss of VWF large multimers defined as VWF-LMI < 80%. VWF-LMI in patients with degenerative MR was lower than in those with functional MR. VWF-LMI appeared to be restored the day after mitral valve intervention, and the improvement was maintained 1 month after the intervention. Seven patients (8.3%) had a history of bleeding, 6 (7.1%) of whom had gastrointestinal bleeding. Gastrointestinal endoscopy was performed in 23 patients (27.4%) to investigate overt gastrointestinal bleeding, anemia, etc. Angiodysplasia was detected in 2 of the 23 patients (8.7%). Conclusion: Moderate or severe MR is frequently associated with loss of VWF large multimers, and degenerative MR may cause more severe loss compared with functional MR. Mitral valve intervention corrects the loss of VWF large multimers. Gastrointestinal bleeding may be relatively less frequent and hemoglobin level remains stable in MR patients.

von Willebrand factor Ristocetin co-factor activity to von Willebrand factor antigen level ratio for diagnosis of acquired von Willebrand syndrome caused by aortic stenosis.

Background: Severe aortic stenosis (AS) causes acquired von Willebrand syndrome by the excessive shear stress-dependent cleavage of high molecular weight multimers of von Willebrand factor (VWF). While the current standard diagnostic method is so-called VWF multimer analysis that is western blotting under nonreducing conditions, it remains unclear whether a ratio of VWF Ristocetin co-factor activity (VWF:RCo) to VWF antigen levels (VWF:Ag) of <0.7, which can be measured with an automated coagulation analyzer in clinical laboratories and is used for the diagnosis of hereditary von Willebrand disease. Objectives: To evaluated whether the VWF:RCo/VWF:Ag is useful for the diagnosis of AS-induced acquired von Willebrand syndrome. Methods: VWF:RCo and VWF:Ag were evaluated with the VWF large multimer index as a reference, which represents the percentage of a patient's VWF high molecular weight multimer ratio to that of standard plasma in the VWF multimer analysis. Results: We analyzed 382 patients with AS having transaortic valve maximal pressure gradients of >30 mmHg, 27 patients with peripheral artery disease, and 46 control patients free of cardiovascular disease with osteoarthritis, diabetes, and so on. We assumed a large multimer index of <80% as loss of VWF large multimers since 59.0% of patients with severe AS had the indices of <80%, while no control patients or patients with peripheral artery disease, except for 2 patients, exhibited the indices of <80%. The VWF:RCo/VWF:Ag ratios, measured using an automated blood coagulation analyzer, were correlated with the indices (rs = 0.470, P < .001). When the ratio of <0.7 was used as a cut-off point, the sensitivity and specificity to VWF large multimer indices of <80% were 0.437 and 0.826, respectively. Conclusion: VWF:RCo/VWF:Ag ratios of <0.7 may indicate loss of VWF large multimers with high specificity, but low sensitivity. VWF:RCo/VWF:Ag ratios in patients with AS having a ratio of <0.7 may be useful for monitoring the loss of VWF large multimers during their clinical courses.

Cyclosporine A for chemotherapy-resistant subcutaneous panniculitis-like T cell lymphoma with hemophagocytic syndrome.

Subcutaneous panniculitis-like T cell lymphoma (SPTL) is a rare subtype of non-Hodgkin lymphoma for which a definitive therapeutic strategy has not been established yet. We report a case of chemotherapy-resistant SPTL with hemophagocytic syndrome (HPS) which was successfully treated with cyclosporine A (CsA) plus methylprednisolone (mPSL), and also reviewed 11 SPTL cases treated with CsA, previously reported in the literature. Our patient was a 38-year-old female with SPTL. The disease progressed despite conventional chemotherapy using cytotoxic agents including alkylators, anthracyclins or purine analogues, and, after 2 months of chemotherapy, was eventually complicated by HPS and disseminated intravascular coagulation (DIC). CsA (4 mg/kg/day) plus mPSL treatment dramatically improved HPS with DIC, reduced subcutaneous tumors within 2 weeks, and finally induced complete remission (CR) after 3 months. Currently, the patient has maintained CR while being treated with CsA for 12 months. In addition to our case, 9 of 11 SPTL cases were successfully treated with CsA, and 8 were induced to CR. Time to first response to CsA was within 2 weeks in most cases, regardless of prior treatment or the co-occurrence of HPS. Our case and this first comprehensive review on CsA for SPTL suggest that CsA may constitute a candidate treatment strategy for SPTL.

Length of vancomycin administration for treatment of clostridium difficile-associated diarrhea may depend on presentation of colonic ulcer.

BACKGROUND/AIMS: Clostridium difficile-associated diarrhea (CDAD) is a notorious iatrogenic infection with typical endoscopic features consisting of pseudomembranes (PMs). Concomitant colonic ulcers are sometimes endoscopically detected. We hypothesized that length of vancomycin (VCM) administration for treatment depends on presentation of colonic ulcer. METHODOLOGY: We investigated retrospectively endoscopic findings and total number of days of vancomycin administration for patients who showed evidence of C. difficile toxin A or PMs at our hospitals. We excluded CDAD cases with inflammatory bowel disease. RESULTS: Sixteen patients were diagnosed as having CDAD. All patients receiving endoscopic examination presented PMs. Two cases had PMs in the transverse and small intestine. The patients with ulcers needed 5-28 days of administration of VCM, while all those without ulcers except one were cured within seven days. CONCLUSIONS: Our results suggest that ulcer may be a factor of poor prognosis, and we recommend endoscopic examination for all patients with CDAD for identification of poor prognostic groups.

Risk factors for infection in haematology patients treated with rituximab.

OBJECTIVES: Although rituximab therapy is not considered to be closely associated with infection, there have been reports of serious infections in patients treated with rituximab. We performed a statistical retrospective analysis to clarify the risk factors for infection in patients receiving rituximab therapy. METHODS: A retrospective study of data from clinical records was performed that targeted haematology patients treated at our university hospital between April 2003 and October 2006. We selected 63 patients with CD20-positive lymphoma whose peripheral blood immunoglobulin levels had been measured within 6 months before and after rituximab therapy. Logistic regression analysis was used to investigate the risk factors for serious infection in these patients. RESULTS: The three risk factors identified were: 1) reduction in IgM after administration of rituximab [odds ratio (OR) = 1.032, confidence interval (CI) = 1.007-1.057; P = 0.009], 2) duration of rituximab therapy [OR = 0.962, CI = 0.932-0.994; P = 0.021] and 3) G-CSF administration [OR = 4.825, CI = 1.411-16.495; P = 0.012]. CONCLUSIONS: Rituximab therapy may be associated with infection, indicating the need for sequential monitoring of IgM levels and identification of the optimal interval between rituximab cycles.

Absence of pseudomembranes in Clostridium difficile-associated diarrhea in patients using immunosuppression agents.

OBJECTIVE: Clostridium difficile is a major cause of diarrhea in hospitalized patients. Although pseudomembranes are crucial evidence for diagnosis of C. difficile-associated diarrhea (CDAD), some cases do not show any pseudomembranes. The aim of this study was to verify the hypothesis that pseudomembranes are not generated in immunosuppressed patients because of the absence of immunoreactions. MATERIAL AND METHODS: We investigated the endoscopic findings of patients with ulcerative colitis (UC) or who had received hematopoietic stem cell transplantation, and who presented with C. difficile toxin A and had undergone colonoscopy between April 2002 and July 2007 at our institutes. Results. In 4 patients the diagnosis was UC and C. difficile infection, and in another 4 patients the diagnosis was CDAD after hematopoietic stem cell transplantation. None of these cases showed pseudomembranes. Shallow ulcers were found in all four cases with UC. Only non-specific findings were obtained for the CDAD patients after hematopoietic stem cell transplantation. CONCLUSIONS: Pseudomembranes, the typical evidence for CDAD, were not detected in any patients using immunosuppressive agents. Additional bacterial examination is therefore essential when UC becomes exacerbated and when patients present with diarrhea after hematopoietic stem cell transplantation, even in the absence of pseudomembranes.

Protein-losing enteropathy in a case of nodal follicular lymphoma without a gastrointestinal mucosal lesion.

Protein-losing enteropathy (PLE) is characterized by gastrointestinal loss of serum protein. It is usually caused by hypersecretion from a tumor, ulcer, or long standing lymphangiectasia. However, we report a 47-year-old man of peritoneal nodal follicular lymphoma who developed PLE with none of them. Oozing of whitish fluid from duodenal bulbar mucosa was endoscopically seen, resulting in continuous loss of protein. Chemotherapy was effective and PLE was rapidly diminished. Nodal lymphoma lesion was considered to disturb lymphatic flow and to regurgitate it to duodenal mucosa. To our knowledge, this is the second report of a lymphoma patient presenting PLE without a gastrointestinal mucosal lesion.