A variant form of Bernard-Soulier syndrome: mild haemostatic defect associated with partial platelet GPIb deficiency

Platelets from patients with Bernard-Soulier syndrome (BSS) are larger than normal and demonstrate characteristic aggregation abnormalities. A molecular defect involving platelet membrane glycoproteins has been established as the primary abnormality, and the major defect is described as an absence of GPIb, the receptor for von Willebrand factor, which prevents the adhesion of BSS platelets to damaged endothelium. Associated deficiencies of GPV and GPIX are also recognized. The overall clinical effect is a haemorrhagic tendency which, although variable, is severe at times in all patients. We report a child who presented with the typical morphological and aggregation abnormalities associated with BSS, but who had negligible bleeding problems. Further investigation revealed a significant but incomplete deficiency of GPIb and of GPV and GPIX. This case suggests that BSS may be a heterogeneous disorder with clinical consequences dependent on the extent and complexity of the platelet membrane glycoprotein deficiency.     

Anti-D (WinRho SD) treatment of children with chronic autoimmune thrombocytopenic purpura stimulates transient cytokine/chemokine production

Intravenous anti-D is often used in the treatment of autoimmune thrombocytopenic purpura (AITP), but little is known about its mechanisms of action. To investigate anti-D's potential in vivo mechanism(s) of action, a small group (N = 7) of children with chronic AITP was studied. The children initially received either 25 or 50 microg/kg of WinRho-SD in a four-cycle cross-over trial, and peripheral blood samples from the first and third cycles were assessed for cytokine levels at pre-treatment, 3 hr, 1 day, and 8 days post-treatment. Results showed that platelet counts significantly increased in all the children by day 8 post-treatment. Analysis of serum by ELISA showed that there was a significant but transient rise in both pro- and anti-inflammatory cytokine/chemokine levels (e.g., IL1RA, IL6, GM-CSF, MCP-1 alpha, TNF-alpha and MCP-1) by 3 hr post-treatment in both cycles which returned to baseline levels by 8 days post-treatment. These results suggest that anti-D administration may initially activate the RES in the form of cytokine/chemokine secretion, which is subsequently followed by an increase in platelet counts. It is possible that the induced cytokine/chemokine storm may have an effect on several physiological processes such as those mediating either adverse effects or potentially RES phagocytic activity.     

A systematic review of MR imaging as a tool for evaluating haemophilic arthropathy in children

Our purposes were to determine: (i) whether there is direct evidence that currently available MRI techniques are accurate for early diagnosis of pathological findings in haemophilic arthropathy; (ii) whether there is an MRI scoring system that best correlates with clinical/radiological constructs for evaluation of haemophilic arthropathy; (iii) whether there is an MRI scoring system that best correlates with clinical/radiological constructs for evaluation of haemophilic arthropathy. Articles were screened using MEDLINE (n = 566), EMBASE (n = 201), and the Cochrane Library (n = 1). Two independent reviewers assessed articles for inclusion under the overarching purposes of the review by using the Standards for Reporting of Diagnostic Accuracy (STARD) tool, and the quality of the studies were graded using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS‐2) tool. The electronic literature search retrieved 777 references (after duplicates were removed). A total of 32 studies were chosen for inclusion from the results of the search and review of bibliographical references. Using the STARD tool, seven studies were of excellent quality of reporting, and using the QUADAS‐2 tool, 10 studies were judged to be of adequate quality. There is ‘fair’ evidence to recommend MRI as an accurate test for detecting evidence of haemophilic arthropathy and the use of second or third generation MRI scales for assessing haemophilic arthropathy. However, there is no evidence that screening of early intra‐articular soft tissue bleed with MRI improves the functional status of joints over time.     

Intracranial haemorrhage in von Willebrand disease: a report on six cases

The incidence of intracranial haemorrhage (ICH) in von Willebrand disease (VWD) is not well documented. We describe our single centre experience regarding ICH in children with VWD and identify how such children presented and were managed. Thirty‐three head trauma events leading to medical attention occurred in 24 of 153 children with VWD followed in our institution. In only 15 of these were computed tomography (CT) imaging studies performed; seven in children with type 1 VWD, one in a child with type 2N VWD and seven in children with type 3 VWD. In six of these 15 episodes an ICH was identified: two children with type 1 VWD, one child with type 2N VWD and three children with type 3 VWD. In two of the 6 cases an ICH was only confirmed following a second CT scan. Neurological symptoms, including vomiting (noted in all six), headache, irritability, lethargy and/or alteration in the level of consciousness were present in all children with confirmed ICH. In contrast vomiting, irritability and alterations in level of consciousness were never present in those children without confirmed ICH. All three children with type 3 VWD who experienced an ICH were commenced on long‐term prophylaxis. ICH, although rare, does occur in children with VWD and particularly in children with type 3 VWD. A much larger cohort of patients with VWD experiencing an ICH is needed to make recommendations regarding treatment of such events, including the role of prophylaxis in patients with more severe forms of VWD.     

Compliance with consensus recommendations for the treatment of early stage breast carcinoma in elderly women

BACKGROUND: The goal of this study was to assess variations with age in the management of breast carcinoma and to identify determinants of care received. METHODS: A stratified random sample was selected among women age > or = 50 newly diagnosed with lymph node negative breast carcinoma in Quebec in 1988, 1991, and 1993. Information was abstracted from medical charts. Predictors of definitive locoregional treatment (total mastectomy with lymph node dissection or breast-conserving surgery with both axillary lymph node dissection and radiation therapy) were identified by multiple logistic regression analysis. RESULTS: Overall, 1174 patients age > or = 50 years with breast carcinoma were included. Women age > or = 70 years were much less likely to receive definitive locoregional treatment compared with women ages 50-69 years (48.7% vs. 83.5%; P < 0.0001). Older women were less likely to undergo surgery with breast preservation (76.7% vs. 86.3%; P < 0.0001), radiation therapy (54.7% vs. 90.5%; P < 0.0001), dissection of the axillary lymph nodes (55.6% vs. 86.3%; P < 0.0001), or chemotherapy (1.2% vs. 13.9%; P < 0.0001), but not treatment with tamoxifen (66.4% vs. 64.7%; P = 0.41). Adjusting for comorbidity and other characteristics related to the disease, the hospital, and the attending physician, age remained a strong determinant of the probability of receiving definitive locoregional treatment (odds ratio [OR], 0.14; 95% confidence interval [95% CI], 0.12-0.18 for women age > or = 70 years vs. women ages 50-69 years). The same association was observed when women who did not undergo lymph node dissection but who received systemic adjuvant treatment were considered to have received definitive therapy (OR, 0.13; 95% CI, 0.10-0.17) for women age > or = 70 years vs. women ages 50-69 years). CONCLUSIONS: Less aggressive patterns of care are provided to elderly breast carcinoma patients, independent of comorbidity. This could explain, at least in part, the sustained breast carcinoma mortality in this population.     

Intravenous Gamma-Globulin (Sandoglobulin®) Therapy in the Management of Four Patients with Immune Thrombocytopenic Purpura

We have used intravenous polyvalent intact gamma-globulin concentrate (Sandoglobulin®-immune globulin IV) in the management of 2 adults and 2 children with refractory immune thrombocytopenic purpura (ITP). Excellent responses were obtained in 2 children with chronic ITP as compared to no response in 2 adults with long-standing, severe ITP. The 2 adults who failed intravenous Sandoglobulin therapy had prolonged reticuloen-dothelial system (RES) clearance of autologous antibody-coated red blood cells before initiation of therapy as compared to normal RES clearance rates in the 2 children who responded to therapy. Blockade of the RES is one mechanism by which intravenous Sandoglobulin therapy may reverse thrombocytopenia in ITP — our observations suggest that patients who have impaired RES function before starting intravenous Sandoglobulin therapy may fail to respond to treatment. Continued studies are required to confirm these observations.     

Utility of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for dementia in a Japanese-American population

Ethnic diversity among older patients in Hawai'i is common; yet few data exist concerning the applicability of cognitive testing instruments in non-Caucasian populations. This project aimed to determine the specificity and sensitivity of the IQCODE for the detection of cognitive impairment in a Japanese-American population. Results confirm that the IQCODE is a valuable tool for primary care physicians to detect impairment in this population.     

Value of a cinefluoroscopic assessment of the Lillehei-Kaster prosthetic heart values

In order to assess the functioning of the pivoting disc of the Lillehei-Kaster prosthetic valve, a cinefluoroscopic technique using multiple angulations was developed. The disc was detected in 240 (99%) of the 242 valves studied (126 aortic, 107 mitral, and nine tricuspid valves). The maximal-opening angle of the disc was measured in 75% of the aortic but only 20% of the mitral valve prostheses in the 182 valve studies in which this was attempted. Prosthetic dysfucntions were suspected clinically in three aortic and three tricuspid valves and confirmed with the cinefluoroscopic technique. This cinefluoroscopic approach constitutes a rapid, noninvasive, and sensitive evalaution of the function of the Lillehei-Kaster prosthetic valve in the aortic position.