"Macro transcobalamin causing raised vitamin B12: Case-based laboratory investigation".

Determination of plasma vitamin B12 (B12) is a frequently requested laboratory analysis, mainly employed to establish B12 deficiency. However, an increased level of B12 is a common unexpected finding that may be related to an increased concentration of one of the B12 binding proteins, haptocorrin or transcobalamin. This paper describes the extensive laboratory evaluation of a patient with an elevated level of plasma B12 with various well-established assays.

Comparison of the direct antiglobulin test and the eluate technique for diagnosing haemolytic disease of the newborn.

Objective: The direct antiglobulin test (DAT) is an important tool for identification of haemolytic disease of the newborn (HDN) caused by erythrocyte immunization. Although this test has been used for decades, accurate insights into its diagnostic properties and optimal use in the diagnosis of HDN are limited. We aimed to gain more insight into the diagnostic properties of the DAT for HDN by comparing it with erythrocyte eluate screening.

INR vs. thrombin generation assays for guiding VKA reversal: a retrospective comparison.

Background: Prothrombin complex concentrate (PCC) is used to reverse vitamin K antagonist (VKA)-induced anticoagulation. Prothrombin time-derived international normalized ratio (INR) measurements are widely used in determining the required PCC dose, but this approach requires reappraisal. The aim of the present study was to determine the added value of the thrombin generation assay (TGA) compared with the INR in guidance of VKA reversal by PCC.

[Thalassaemia diagnostics].

The thalassaemias are characterised by quantitative aberrations in the production of the globin chains that make up haemoglobin, and are a subgroup of the haemoglobinopathies. In this LabQuiz we show how thalassaemia carrier status can be indicated in the results of regular laboratory tests, and discuss the laboratory diagnostics that can confirm or rule out thalassaemia. In these two cases we will present a man of Moroccan descent, and two brothers of Filipino descent, all with anaemia and microcytosis.

Management and outcome of 35 cases with foetal/neonatal alloimmune neutropenia.

Aim: The aim of this study was to provide an overview of foetal/neonatal alloimmune neutropenia (FNAIN), together with advice on the clinical management.

Methods: Neutrophil serology in the Netherlands is centralised at Sanquin Diagnostic Services. We examined FNAIN cases between January 1, 1991, and July 1, 2013, to determine the number of cases diagnosed, the relationship with human neutrophil antigen (HNA) antibody, the clinical presentation and therapeutic interventions.

[The diagnostic value of NT-proBNP in heart failure: in depth analysis].

A 77-year-old man with dyspnoea was suspected to have a decompensatio cordis by the general practitioner. A diuretic was prescribed. Additional radiological and laboratory investigation (e.

Introduction of a new cobalamin (vitamin B12) assay: lessons from a flawed validation study.

Background: Plasma vitamin B12 [cobalamin (Cbl)] concentrations are usually measured as a screening marker for vitamin B12 deficiency. Siemens Healthcare Diagnostics has introduced Cbl assays for various platforms, i.e.

Abundance of the long pentraxin PTX3 at sites of leukocytoclastic lesions in patients with small-vessel vasculitis.

Objective: The prototypical tissue pentraxin PTX3 inhibits phagocytosis of late apoptotic polymorphonuclear leukocytes (PMNs) by macrophages. Levels of PTX3 parallel disease activity in small-vessel vasculitis. Small-vessel vasculitis is often characterized by leukocytoclasia, a phenomenon of accumulation of nuclear remnants from unscavenged PMNs in or near the vessel wall.

Activation, apoptosis, and clearance of neutrophils in Wegener's granulomatosis.

Wegener's granulomatosis (WG) is strongly associated with the presence of antineutrophil cytoplasmic autoantibodies (ANCAs). Within WG these ANCAs are usually (80-90%) directed against the azurophilic enzyme proteinase 3, the so called PR3-ANCA. A pathophysiological role for these autoantibodies, supported by numerous in vitro and in vivo studies, is specifically based on their capacity to bind and activate neutrophils and potentially may damage vessels.

Human anti-neutrophil cytoplasm autoantibodies to proteinase 3 (PR3-ANCA) bind to neutrophils.

Background: Recently, the in vivo pathogenic role of anti-neutrophil cytoplasm autoantibodies (ANCA) in ANCA-associated vasculitis has been challenged by Abdel-Salam et al. In their report, they observed that ANCA directed against proteinase 3 (PR3) cannot bind to their target autoantigen PR3 on circulating neutrophils (PMN). Here we present evidence that human PR3-ANCA do specifically bind to PMN that express PR3 on their membrane.

The prototypic tissue pentraxin PTX3, in contrast to the short pentraxin serum amyloid P, inhibits phagocytosis of late apoptotic neutrophils by macrophages.

Objective: Phagocytosis of apoptotic cells can be facilitated by complement components and short pentraxins, such as serum amyloid P (SAP). In contrast, the long pentraxin PTX3 was shown to inhibit phagocytosis of apoptotic Jurkat cells by dendritic cells and to bind late apoptotic polymorphonuclear leukocytes (PMNs). Recently, levels of the pentraxin PTX3 were shown to parallel disease activity in small-vessel vasculitis, which is often characterized by leukocytoclasia, a persistence of leukocyte remnants in the vessel wall.

Constitutive membrane expression of proteinase 3 (PR3) and neutrophil activation by anti-PR3 antibodies.

Antineutrophil cytoplasm autoantibodies with specificity for proteinase 3 (PR3) are thought to play a major role in the pathogenesis of Wegener's granulomatosis (WG), presumably by their potential to activate neutrophils. In patients with WG, high expression of PR3 on the surface of nonprimed neutrophils is associated with an increased incidence and rate of relapse. In this study, we analyzed the functional significance of constitutive PR3 expression for neutrophil activation as induced by anti-PR3 antibody.