26 research outputs found
Prognostic Factors in Thrombotic Thrombocytopenic Purpura
No full textThrombotic Thrombocytopenic Purpura (TTP) is a rare disorder in which
ADAMTS13 deficiency, either congenital (cTTP) or acquired (immune-TTP),
leads to circulating ultra-large VWF multimers and microthrombi formation with
potentially catastrophic results. Alongside laboratory studies, the UK TTP
Registry was used to assess the prognostic impact of several variables.
312 immune mediated-TTP episodes were evaluated to assess the impact of
anti-ADAMTS13 antibody, ADAMTS13 antigen, troponin and neurological
symptoms on prognosis. A raised troponin conferred a sixfold increase in
mortality (12.1% vs 2.0%, p=0.04), whilst neurological symptoms increased the
risk ninefold (20% vs 2.2%, p<0.0001). Both antibody and antigen levels
affected outcomes with 27.3% mortality seen in those with antibody levels in the
highest quartile and antigen levels in the lowest quartile.
73 cTTP patients had genetic analysis. Mutation location affected onset age
with pre-spacer domain mutations more associated with earlier presentation
(p=0.0011). Prophylactic ADAMTS13 replacement despite normal blood counts
improved subacute symptoms such as headache, lethargy and abdominal pain
and decreased stroke incidence. In separate research, a shear flow assay was
developed to replicate ADAMTS13-VWF binding in cTTP. Analysis of 22
patients showed increase thrombus formation which improved with ADAMTS13
replacement and the addition of antiplatelet therapy to prophylactic regimens
appeared to offer the most comprehensive reduction in microthrombi formation.
For both cTTP and immune-TTP, neurological symptoms at presentation are an
especially important factor with an impact on long term morbidity. MRI scanning
of 131 patients after an acute event found those with neurological symptoms
were significantly more likely to have an abnormal cerebral MRI compared to a
headache only (80% vs. 18%, p<0·0001). An abnormal MRI was associated
with lower verbal and performance IQ, suggestive of functional decline (verbal
IQ 85 vs. 99, p=0·02, performance IQ 83 vs. 100, p=0·02)
Assessing thrombogenesis and treatment response in congenital thrombotic thrombocytopenic purpura
No full textDespite clinical remission and normal platelet counts, congenital TTP (cTTP) is associated with non-overt symptoms. Prophylactic ADAMTS13 replacement therapy such as plasma infusion (PI) prevents acute episodes and improves symptomatology. There is no current method to investigate disease severity or monitor the impact of treatment. We utilize a dynamic high shear flow assay to further understand disease pathophysiology and determine the impact of cTTP on symptomatology and therapy, despite normal platelet counts. Whole blood, under high shear, was run over collagen-coated channels, causing platelet adhesion to von Willebrand factor (VWF) multimers. The resulting surface coverage by platelet-VWF thrombus was assessed. The normal range was 6-39% in 50 controls. Twenty-two cTTP patients with normal platelet counts were evaluated. Median pre-treatment surface coverage was 89%, and PI reduced coverage to a median of 44% (p = 0.0005). Patients taking antiplatelets had further reduced coverage when combined with PI and improved non-overt symptoms such as headache, lethargy, and abdominal pain in 100% of patients compared to 74% with PI alone (p = 0.046). We use a dynamic assay to report increased in vitro platelet adhesion and aggregation and additionally demonstrate significantly decreased thrombi following PI, with levels in the normal range levels achieved in patients taking additional antiplatelet therapy
Improved SWMM Modeling for Rapid Pipe Filling Incorporating Air Behavior in Intermittent Water Supply Systems
No full textStormwater management model (SWMM) software has recently become a modeling tool for the simulation of intermittent water supply systems. However, SWMM is not capable of accurately simulating the air behavior in the pipe-filling phase, missing therefore a relevant factor during pipe pressurization. This work proposes the integration of a conventional accumulator model in the existing SWMM hydraulic model to overcome this gap. SWMM source code was modified to calculate the air piezometric head inside the pipe based on the system boundary conditions, and the air piezometric head was incorporated in the SWMM flow rate pressure component. Experimental data were collected during the rapid filling of a pipe system for three possible configurations that are likely to occur in intermittent water supply pipe systems: no air release, small air release, and large air release. Results show that the improved SWMM better describes the effect of the air behavior using the extended transport (EXTRAN) surcharge method when compared to the original SWMM. Results also show that the SLOT method with predefined slot width is not suitable for this purpose; thus, further research is needed to assess if an adjusted slot width could provide better results.Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Sanitary Engineerin
