How we diagnose and manage altered oxygen affinity hemoglobin variants.

Altered oxygen affinity variant hemoglobins (Hbs) are caused by mutations of the globin genes. Changes in Hb oxygen affinity shift the oxygen dissociation curve, and can be identified by abnormal p50 measurements of patient red blood cells. Variants are categorized as either low oxygen affinity (high p50) or high oxygen affinity (low p50).

Clinical evaluation of a hemochromatosis next-generation sequencing gene panel.

Background: Next-generation sequencing of an iron metabolism gene panel could identify pathogenic mutations, improving on standard hemochromatosis genetic testing and providing a molecular diagnosis in patients with suspected iron overload.

Methods: A next-generation sequencing panel of 15 genes with known roles in iron metabolism was constructed. A total of 190 patients were sequenced: 94 from a tertiary hemochromatosis clinic and 96 submitted for HFE testing with biochemical evidence of iron overload [elevated ferritin (>450 μg/L) or transferrin saturation (>55%)] obtained from a chart review.

A 13-question approach to resolving serological discrepancies in the transfusion medicine laboratory.

Laboratory professionals, consultants, and treating physicians may encounter discrepancies in serological testing results for numerous reasons; identifying the reason(s) for the presence of an unexpected antibody or antigen can be challenging. A question-based approach can be useful in identifying the underlying cause of the discrepancy. We describe a new approach to serological problems in a transfusion-service laboratory.

Periprocedural heparin bridging in patients receiving vitamin K antagonists: systematic review and meta-analysis of bleeding and thromboembolic rates.

Background: Periprocedural bridging with unfractionated heparin or low-molecular-weight heparin aims to reduce the risk of thromboembolic events in patients receiving long-term vitamin K antagonists. Optimal periprocedural anticoagulation has not been established.

Methods And Results: MEDLINE, EMBASE, and Cochrane databases (2001-2010) were searched for English-language studies including patients receiving heparin bridging during interruption of vitamin K antagonists for elective procedures.

Specificity in substrate and cofactor recognition by the N-terminal domain of the chaperone ClpX.

Clp ATPases are a unique group of ATP-dependent chaperones supporting targeted protein unfolding and degradation in concert with their respective proteases. ClpX is a representative member of these ATPases; it consists of two domains, a zinc-binding domain (ZBD) that forms dimers and a AAA+ ATP-binding domain that arranges into a hexamer. Analysis of the binding preferences of these two domains in ClpX revealed that both domains preferentially bind to hydrophobic residues but have different sequence preferences, with the AAA+ domain preferentially recognizing a wider range of specific sequences than ZBD.