Assessment of a cohort of primarily pediatric patients with a presumptive diagnosis of type 1 von Willebrand disease with a novel high shear rate, non-citrated blood flow device.

BACKGROUND: A precise approach to the diagnosis of von Willebrand disease (vWD) remains elusive. One important reason is that vWD is a blood flow-related disorder: a vW Factor-platelet GPIb binding defect exists in this condition under the high shear-rate (> 1000 sec-1 in whole blood; > 3000 sec-1 in PRP) conditions of physiologic blood flow which exist in the arterioles of mucous membranes, from which most bleeding in vWD occurs. METHODS: We therefore studied 28 patients (mean 18.9 yrs) with vWD, diagnosed according to the 2007 NHLBI clinical guidelines, and 26 healthy controls (mean 17.5 yrs). Blood was collected into a plastic tube containing 4 U/ml FC dalteparin, 1.75 µg/ml of the Tab (anti-CD41) monoclonal antibody directed against platelet GPIIb, and 1.0 µg/ml of an ALEXA 555-conjugated rabbit anti-mouse second antibody. Within 30-90 min, the blood was then withdrawn at 667 and 1330 sec(-1) through a special flow chamber allowing for real-time epifluorescence digital videomicroscopy of platelets interacting with a microfibrillar collagen substrate. With MetaMorph software (Universal Imaging) we quantified the percent area (PA) covered by and total volume (TV) of adherent platelet aggregates within a 435 µm × 580 µm field of view. RESULTS: At 667 sec(-1) after 1 min PA and TV were similar for patients and controls, but at 1330 sec(-1) PA was 9.32 ± 4.21 (mean ± SD) for patients, a value lower (p < 0.001) than the 12.8 ± 3.39 for controls. TV was (1.43 ± 0.91) x 10(4) for patients, a value also lower (p < 0.001) than the (2.22 ± 0.77) x 10(4) for controls. PA or TV was below the 2.5th percentile for controls in 10 patients (36%) and both PA and TV were below the 2.5th percentile in eight. CONCLUSIONS: The novel flow device found that PA and TV were significantly reduced under high shear stress in vWD patients compared to normal controls. However, there was some overlap between the vWD and the control group, suggesting that some vWD patients had normal platelet adhesion/aggregation under the conditions studied. Further study with a higher shear rate appears indicated.

Cerebral fractional anisotropy score in trauma patients: a new indicator of white matter injury after trauma.

OBJECTIVE: Previous studies evaluating quantitative cerebral white matter diffusion anisotropy indexes have shown alteration in patients after trauma. To date, no clinically applicable scale exists by which to gauge and test the relevance of these findings. We propose the cerebral fractional anisotropy score in trauma (C-FAST) as an index of white matter injury, and we correlate C-FAST with several predictor and outcome variables. MATERIALS AND METHODS: Fifteen patients were randomly selected from the trauma surgery service. Thirty control patients were randomly selected from the emergency department. All patients were subjected to MRI evaluation, including a diffusion-weighted sequence. Data extracted from the record of each subject included Glasgow Coma Scale, revised trauma score, Abbreviated Injury Scale, initial head CT results, patient disposition, length of hospital stay, and length of stay in intensive care unit. Region of interest measurements were made in fractional anisotropy maps in each of 12 white matter regions. Univariate statistics and a two-tailed t test were performed on the raw fractional anisotropy data. Data were then dichotomized using thresholds from univariate statistics. A C-FAST score was devised from the dichotomized data. Logistic regression analyses were performed among the C-FAST, outcome, and predictor data. RESULTS: Good correlation was noted between the C-FAST and death, hospital stay greater than 10 days, and intensive care unit stay greater than 5 days. Correlation with discharge to rehabilitation facility was good when adjusted for age and sex. Glasgow Coma Scale, revised trauma score, and Abbreviated Injury Scale show good correlation as predictors of a critical C-FAST. CONCLUSION: The C-FAST is a promising index derived from MRI diffusion fractional anisotropy measurements that shows successful correlation with outcome and predictor variables. A larger investigation is needed to verify the validity and stability of the correlations.