Myelodysplastic syndromes and chronic myelomonocytic leukemia are blood disorders characterized by ineffective hematopoiesis and progressive marrow failure that can transform into acute leukemia. The DNA methyltransferase inhibitor 5-azacytidine (AZA) is the most effective pharmacological option, but only ∼50% of patients respond. A response only manifests after many months of treatment and is transient. The reasons underlying AZA resistance are unknown, and few alternatives exist for non-responders. Here, we show that AZA responders have more hematopoietic progenitor cells (HPCs) in the cell cycle. Non-responder HPC quiescence is mediated by integrin α5 (ITGA5) signaling and their hematopoietic potential improved by combining AZA with an ITGA5 inhibitor. AZA response is associated with the induction of an inflammatory response in HPCs in vivo. By molecular bar coding and tracking individual clones, we found that, although AZA alters the sub-clonal contribution to different lineages, founder clones are not eliminated and continue to drive hematopoiesis even in complete responders.
Iron deficiency and anaemia are common in pregnancy. Audit data from our tertiary obstetrics unit demonstrated 22% of maternity patients experiencing a postpartum haemorrhage received a transfusion; a third of whom were anaemic on admission intrapartum. Australian Patient Blood Management (PBM) Module 5 Obstetrics guidelines focuses on maximising red cell mass at the time of delivery and reducing the reliance on transfusion as a salvage therapy to treat blood loss. A clinical practice improvement partnership began in February 2015 and completed in April 2016; which aimed to implement systems to improve antenatal identification and management of iron deficiency, and improve postpartum anaemia management. In order to develop change strategies, reasons for poor detection and correction of iron deficiency in the antenatal period were identified following a quality improvement methodology. Education was delivered to maternity healthcare providers. Standardised algorithms and an oral iron prescription handout were developed and piloted. Follow-up audit, staff and patient feedback, and other hospital data were collected to measure outcomes. The rate of anaemia on admission intrapartum fell from 12.2% in 2013 to 3.6% in 2016 following the introduction of unselective ferritin screening and other antenatal interventions. Sixty to 70% of maternity patients screened each month had iron deficiency. The algorithms aided staff to become confident in blood test interpretation and management of iron deficiency and anaemia. Patients found the oral iron prescription handout helpful. Additionally, single unit transfusions significantly increased from 35.4% to 50% (p=0.037) over the project timeframe. This project demonstrated the potential to improve patient blood management in obstetrics, reduce anaemia and transfusions by active antenatal interventions.
Rh D prophylaxis has increased positive DAT results, which may increase the number of unnecessary bilirubin measurements. A low or high DAT grade is strongly predictive of whether an infant does or does not require phototherapy. However, an intermediate DAT requires concomitant bilirubin measurements to determine phototherapy requirements.
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