Reevesdalrymple9761

In a high-risk patient with subacute heparin-induced thrombocytopenia (HIT) type A (platelet count recovery following acute HIT but with persisting platelet-activating antibodies), in whom urgent cardiac surgery was required, a key clinical question arose could intraoperative heparin be given safely with "platelet anesthesia" provided with high-dose intravenous immunoglobulin (IVIG) plus cangrelor (ultra-short-acting antiplatelet agent)? This approach proved successful, without unexpected postoperative thrombocytopenia or thromboembolism. Selleck Cl-amidine In vitro studies confirmed that both IVIG and cangrelor contributed to perioperative inhibition of HIT antibody-induced platelet activation. Interestingly, despite the patient testing strongly positive in 4 HIT immunoassays (latex immunoturbidimetric assay and 3 enzyme-immunoassays), the serotonin-release assay (SRA) was consistently negative. Nevertheless, platelet-activating HIT antibodies were detectable using modified (platelet factor 4-enhanced) SRA. Our protocol of heparin rechallenge following IVIG/cangrelor provides both intraoperative and early postoperative inhibition of HIT antibody-induced platelet activation and is applicable to patients with circulating functional HIT antibodies requiring urgent heart surgery, including those with "SRA-negative HIT."

Centrifugation is commonly used as a first step to enrich biomarkers from blood. Biomarkers are separated on the basis of density and/or diameter. However, the centrifugation protocol affects the yield and purity of biomarkers, for example, isolation of platelets results in co-isolation with extracellular vesicles (EVs).

To assess the ability of rate zonal centrifugation (RZC) to separate platelets from co-isolated EVs.

Using a linear Optiprep gradient, RZC was able to separate a mixture of beads with different diameters but similar density. Next, RZC was applied to samples containing both platelets and platelet-derived EVs (n=3). After RZC, all fractions were collected and stained with anti-CD61-Alexa 488 to measure the concentrations of platelets and platelet-derived EVs by flow cytometry.

We confirm that RZC separates polystyrene beads with diameters of 140nm, 380nm and 1,000nm. Next, we show that the majority of platelets occur in fractions 8-19, whereas the majority of platelet-derived EVs are detectable in fractions 1-7. Furthermore, each fraction contains a different diameter range of platelets, which suggests that separation is indeed diameter based.

RZC can partially separate platelets from EVs.

RZC can partially separate platelets from EVs.

Patients with type 1 von Willebrand disease (VWD) undergo a desmopressin (DDAVP) responsiveness challenge at diagnosis to assess whether DDAVP reverses their coagulation deficits. Current practice assumes DDAVP responsiveness remains constant over the lifetime. In patients with type 1 VWD, VWF-related parameters increase with age. This study explores whether DDAVP responsiveness also differs with age in this population.

We conducted a retrospective chart review of 106 patients enrolled at our center since 1990. Our primary outcome was DDAVP responsiveness at 1hour after DDAVP challenge. Locally weighted scatterplot smoothing fit and Spearman correlation coefficients were used to study the relationship between age and DDAVP responsiveness. For female participants, we used the Kruskal-Wallis test to compare absolute and relative changes in DDAVP responsiveness at various ages.

We had 79 patients (56 female) with type 1 VWD with at least 1 DDAVP challenge. In women with type 1 VWD, the absolute change in Donsiveness prospectively to evaluate whether there is clinical utility in rechallenging postpubertal female patients with type 1 VWD.

Recurrent joint bleeding in hemophilia results in arthropathy and functional impairment. The relationship of arthropathy development and factor activity (FA) has not been reported in patients with FA levels <15%-20%.

During the Centers for Disease Control and Prevention Universal Data Collection, joint range-of-motion (ROM) measurements were taken at each comprehensive visit. Data were extracted from male patients with hemophilia (PWH) age ≥2years with baseline factor activity levels ≤40%, excluding those prescribed prophylaxis, and used to calculate a proportion of normal ROM (PN-ROM) measure. Data were analyzed using regression models.

There were 6703 eligible PWH with 30102 visits. PN-ROM declined with increasing age, and was associated with hemophilia severity, race/ethnicity, obesity, and viral illnesses. PWH ≥30years old with fFA ≤2% and those ≥50years old with FA ≤5% had mean PN-ROM values >10% less than controls; those ≥40years old with FA <1% had values >20% less than controls. In the multivariable analysis, subjects with <1% FA had a 0.43% greater decrease (-0.49 to -0.37, 95% confidence interval) in PN-ROM each year relative to those with 16%-40% factor activity. A less pronounced effect was seen with 1%-5% or 6%-9% FA.

The effect of FA on ROM loss is far greater than that of any of the other characteristics, especially with FA <10%. This emphasizes the need to maintain a high index of suspicion for arthropathy in individuals with moderate and low-mild hemophilia.

The effect of FA on ROM loss is far greater than that of any of the other characteristics, especially with FA less then 10%. This emphasizes the need to maintain a high index of suspicion for arthropathy in individuals with moderate and low-mild hemophilia.

Phenotypic von Willebrand disease (VWD) classification requires multiple tests including analysis of multimeric distributions von Willebrand factor (VWF) and evaluation of its structure. VWF multimer analysis is labor intensive, nonstandardized, and limited to specialized laboratories. A commercial semiautomatic assay, HYDRAGEL VW multimer assay (H5/11VWM, Sebia), has become available.

Establishment of reference ranges for H5/11VWM to improve VWD classification.

Implementation validation, establishment and validation of normal and pathological reference intervals (NRIs/PRIs), comparison with in-house method using 40 healthy volunteers and 231 VWD patients.

Qualitative and quantitative validation of NRI obtained sensitivity of 88% and 79%, respectively, for type 2. Comparison of the two methods showed an overall concordance of 86% with major conflicting results in all atypical 2B (n=7) and 50% 2M-GPIb (n=41) showing quantitative and qualitative multimeric loss, that was not detected with in-house method.