Evaluation of the utility of the ISTH-BAT in haemophilia carriers: a multinational study.

INTRODUCTION: There has been increasing recognition in recent years that female carriers of haemophilia manifest abnormal bleeding; however, data on the use of bleeding assessment tools in this population are lacking. AIM: Our objective was to validate the ISTH-BAT in haemophilia carriers to describe bleeding symptoms and allow for comparisons with factor levels and other patient groups. METHODS: This was a prospective, observational, cross-sectional study performed by members of Global Emerging HEmostasis Panel (GEHEP). Unselected consecutive haemophilia carriers were recruited and a CRF and the ISTH-BAT were completed by study personnel. RESULTS: A total of 168 haemophilia carriers were enrolled: 155 haemophilia A and 13 haemophilia B. The mean age was 40 years (range: 20-82). Carriers had higher mean bleeding scores (BS) compared with age-matched controls (n = 46; 5.7 vs. 1.43; P < 0.0001) and Type 3 VWD OC (n = 32; 3.0; P = 0.009), but lower BS compared with women with Type 1 VWD (n = 83; 8.7; P < 0.0001). Fifteen carriers reported haemarthrosis, and of those six had normal FVIII/FIX levels. There was a significant but weak negative correlation between BS and factor level (Spearman's r2  = -0.36, P < 0.001). CONCLUSION: Our results show that haemophilia carriers experience abnormal bleeding, including haemarthrosis. Overall, BS in women with Type 1 VWD > haemophilia carriers > Type 3 VWD OC > controls. Understanding the performance of the ISTH-BAT in this population is a critical step in future research aimed at investigating the underlying pathophysiology of abnormal bleeding, with the ultimate goal of optimizing treatment.

Sudden death in a patient with chronic lymphocytic leukemia.

The authors describe a 51-year-old man with chronic lymphocytic leukemia who presented with respiratory distress and then died suddenly while in hospital. Autopsy revealed pulmonary leukostasis and a large intracardiac mass containing mostly mature lymphocytes and fibrin. Although leukostasis and lymphocyte thrombi have been described (albeit rarely) in chronic lymphocytic leukemia, an intracardiac "clot" has not. It seems plausible that this intracardiac mass caused the patient's death.

Crypt cell proliferative micronests in rectal carcinoids. An immunohistochemical study.

Gastrointestinal endocrine cells are situated both in the epithelium as well as in the subepithelium, especially in relation to enteric nerves. This has complicated efforts at delineating the histogenesis of gastrointestinal carcinoids. However, gastrointestinal carcinoids themselves are a heterogeneous group made up of various subsets, and as such may have different modes of origin. The present study investigated the histogenesis of rectal carcinoids because this has not been adequately addressed. Nine rectal carcinoids together with sex- and age-matched controls were stained with silver stains and various immunoreagents. The number of intraepithelial endocrine cells per unit length of mucosa in the carcinoid group was compared with the controls using the Student t test. Our results showed that there was no evidence of diffuse intraepithelial endocrine cell hyperplasia associated with these carcinoids. In six of the cases, however, there were focal areas where the carcinoids abutted onto the mucosal epithelium, and in another two cases there were focal areas depicting crypt cell proliferative micronests. These findings suggest that most conventional rectal carcinoids arise from localized areas of crypt cell proliferation rather than from diffuse areas of intraepithelial endocrine cell hyperplasia. Furthermore, rectal carcinoids appear to be constituted of a heterogenous population of endocrine cells rather than a monoclonal population of cells with each cell expressing a multiplicity of hormones.

A comparative immunohistochemical study of jejunoileal and appendiceal carcinoids. Implications for histogenesis and pathogenesis.

BACKGROUND: The purpose of this study was to determine the histogenesis of jejunoileal and appendiceal carcinoids and to ascertain whether this could be useful in further explaining the pathology of these neoplasms. METHODS: Eight cases each of multiple jejunoileal carcinoids and appendiceal carcinoids together with their respective age-matched and sex-matched controls were stained with silver stains, chromogranin A, serotonin, and S-100. Histomorphometric evaluations of the endocrine cells in the mucosa adjacent to the carcinoids were carried out and compared with the respective controls using the Student's t test. RESULTS: All the carcinoids from both groups stained for argyrophilia, argentaffinity, chromogranin A, and serotonin. Histomorphometric evaluations showed intraepithelial endocrine cell hyperplasia (IECH) in the jejunoileal carcinoid group (P = 0.007, chromogranin; P = 0.004, serotonin) but not in the appendiceal carcinoid group. On the other hand, subepithelial endocrine cell aggregates that were separate from the main tumor were seen in two cases of appendiceal carcinoids. With S-100, all appendiceal carcinoids showed intrinsic tumor positivity whereas the jejunoileal carcinoids did not. CONCLUSIONS: The finding of IECH with multiple jejunoileal carcinoids suggests that these carcinoids arise from a field effect. The absence of IECH with appendiceal carcinoids as well as their association with subepithelial endocrine cell aggregates and their intimate relationship with Schwann cell processes suggests that appendiceal carcinoids arise from a more discrete unit, the subepithelial neuroendocrine complex.