Current state and potential applications of neonatal Fc receptor (FcRn) inhibitors in hematologic conditions.

The neonatal fragment crystallizable (Fc) receptor (FcRn) transports IgG across mucosal surfaces and the placenta and protects IgG from degradation. Numerous clinical trials are investigating therapeutic FcRn inhibition for various immune-mediated neuromuscular and rheumatologic conditions; however, FcRn inhibition also represents a potential therapy for IgG-mediated hematologic conditions (e.g., immune thrombocytopenia, autoimmune hemolytic anemia, immune thrombotic thrombocytopenic purpura, acquired hemophilia, red blood cell/platelet alloimmunization). Current evidence derived from both in vitro and in vivo studies suggests that FcRn inhibitors effectively reduce total IgG levels without impacting its production or altering the levels of other immunoglobulin isotypes. Moreover, the risk of serious adverse events, including serious infections, appears to be lower than that seen with other commonly used immunomodulatory/immunosuppressive therapies, albeit in the setting of limited clinical trial data. Ultimately, additional clinical trials that include varied patient populations are required prior to incorporating these agents into standard treatment algorithms for most hematologic conditions. However, based on the pathophysiology of IgG-mediated hematologic disorders and the mechanism of action of FcRn inhibitors, these agents may represent a future novel therapeutic strategy for patients with hematologic conditions caused by IgG antibodies.

The seasonal distribution of immune thrombotic thrombocytopenic purpura is influenced by geography: Epidemiologic findings from a multi-center analysis of 719 disease episodes.

Prior studies have suggested that immune thrombotic thrombocytopenic purpura (iTTP) may display seasonal variation; however, methodologic limitations and sample sizes have diminished the ability to perform a rigorous assessment. This 5-year retrospective study assessed the epidemiology of iTTP and determined whether it displays a seasonal pattern. Patients with both initial and relapsed iTTP (defined as a disintegrin and metalloprotease with thrombospondin type motifs 13 activity <10%) from 24 tertiary centers in Australia, Canada, France, Greece, Italy, Spain, and the US were included. Seasons were defined as: Northern Hemisphere-winter (December-February); spring (March-May); summer (June-August); autumn (September-November) and Southern Hemisphere-winter (June-August); spring (September-November); summer (December-February); autumn (March-May). Additional outcomes included the mean temperature in months with and without an iTTP episode at each site. A total of 583 patients experienced 719 iTTP episodes. The observed proportion of iTTP episodes during the winter was significantly greater than expected if equally distributed across seasons (28.5%, 205/719, 25.3%-31.9%; p = .03). Distance from the equator and mean temperature deviation both positively correlated with the proportion of iTTP episodes during winter. Acute iTTP episodes were associated with the winter season and colder temperatures, with a second peak during summer. Occurrence during winter was most pronounced at sites further from the equator and/or with greater annual temperature deviations. Understanding the etiologies underlying seasonal patterns of disease may assist in discovery and development of future preventative therapies and inform models for resource utilization.

Comparison of heel stick sample with placental blood sample for pretransfusion testing.

BACKGROUND: Published studies demonstrate that placental blood samples provide acceptable results for various laboratory tests, but these studies did not include pretransfusion testing. The aim of this study was to show concordance between heel stick and placental blood sample pairs for pretransfusion testing and to validate tube and gel method for placental samples. Using placental blood samples for pretransfusion testing potentially reduces the amount of blood collected from newborns for initial laboratory tests. STUDY DESIGN AND METHODS: Placental samples were collected for pretransfusion tests at birth from 32 newborns with less than 2000 g birthweight and less than 35 weeks to compare the results with the heel stick samples from the same newborns. ABO and D typing, direct antiglobulin test (DAT) with IgG, and antibody screen tests were performed on these sample pairs. For ABO and D typing both tube and gel methods were used to validate both methods for the placental samples. RESULTS: This study shows 100% concordance in 32 sample pairs for ABO, D, and DAT tests. Antibody screen results were compared on 29 sample pairs. All 28 sample pairs were concordant, but one placental blood sample was more sensitive to detect a weak maternal antibody than its corresponding heel stick sample was. CONCLUSION: The results of this study validated that placental blood samples can be used in place of heel stick samples and are suitable for pretransfusion testing. This study also validated ABO and D typing by tube and gel methods for placental samples.

Nitrous Oxide Abuse and Vitamin B12 Action in a 20-Year-Old Woman: A Case Report.

Herein, we report a case of a 20-year-old (ethnicity not reported) woman with a history of nitrous oxide abuse and clinical symptoms consistent with spinal cord subacute combined degeneration with associated low serum concentrations of vitamin B12, elevated methylmalonic acid levels, and radiologic evidence of demyelination of the dorsal region of the spinal column. The health of the patient improved dramatically with B12 supplementation. In this case, we discuss the interaction of nitrous oxide with the enzymatic pathways involved in the biochemistry of vitamin B12.