Impact of iron supplementation on patient outcomes for women with abnormal uterine bleeding: a protocol for a systematic review and meta-analysis.

BACKGROUND: Abnormal uterine bleeding (AUB), which includes heavy menstrual bleeding (HMB), is a common condition placing women at increased risk for developing iron deficiency and iron deficiency anemia (IDA). Depletion of iron stores has negative implications on physical, social, and emotional health, as well as quality of life. Iron supplements are safe, effective, and readily available, while red blood cell (RBC) transfusions have inherent risks including infectious and immune reactions. Despite high prevalence of IDA among women with AUB, there are limited studies on the impact of iron therapies on patient outcomes. This systematic review and meta-analysis will evaluate the impact of iron supplementation on patient outcomes for women with AUB, when compared to combination therapy, no intervention, placebo, or standard of care. METHODS: We will conduct a systematic review and meta-analysis of randomized controlled trials and observational studies evaluating the impact of iron interventions on patient outcomes for women with AUB. Systematic literature searches will be conducted in major databases including MEDLINE, EMBASE, CENTRAL, CINAHL, and Web of Science. Studies assessing the impact of iron interventions on patient outcomes in women experiencing AUB, in comparison to combination therapy, no intervention, placebo, or standard of care, will be included in the review. Independent reviewers will screen for eligibility, assess risk of bias, and abstract data. Overall certainty of evidence for each outcome will be assessed using the GRADE approach. We will meta-analyze outcomes which are sufficiently homogeneous to summarize intervention effects and narratively synthesize nonhomogeneous outcomes. The main outcomes of interest are hemoglobin levels immediately prior to surgery and post-operatively, number of RBC transfusions, and adverse effects. Secondary outcomes will include length of hospital stay, intraoperative blood loss, adverse and side effects, quality of life, and iron indices. DISCUSSION: This review will evaluate the impact of iron interventions on patient outcomes in women with IDA secondary to AUB with focus on changes in hematological and iron indices, red blood cell utilization, quality of life, cost of treatment, and adverse events. The results will inform evidence-based clinical practice for the management of iron deficiency and IDA secondary to AUB. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019137282.

Direct oral anticoagulants for treatment of HIT: update of Hamilton experience and literature review.

Direct oral anticoagulants (DOACs) are attractive options for treatment of heparin-induced thrombocytopenia (HIT). We report our continuing experience in Hamilton, ON, Canada, since January 1, 2015 (when we completed our prospective study of rivaroxaban for HIT), using rivaroxaban for serologically confirmed HIT (4Ts score ≥4 points; positive platelet factor 4 [PF4]/heparin immunoassay, positive serotonin-release assay). We also performed a literature review of HIT treatment using DOACs (rivaroxaban, apixaban, dabigatran, edoxaban). We focused on patients who received DOAC therapy for acute HIT as either primary therapy (group A) or secondary therapy (group B; initial treatment using a non-DOAC/non-heparin anticoagulant with transition to a DOAC during HIT-associated thrombocytopenia). Our primary end point was occurrence of objectively documented thrombosis during DOAC therapy for acute HIT. We found that recovery without new, progressive, or recurrent thrombosis occurred in all 10 Hamilton patients with acute HIT treated with rivaroxaban. Data from the literature review plus these new data identified a thrombosis rate of 1 of 46 patients (2.2%; 95% CI, 0.4%-11.3%) in patients treated with rivaroxaban during acute HIT (group A, n = 25; group B, n = 21); major hemorrhage was seen in 0 of 46 patients. Similar outcomes in smaller numbers of patients were observed with apixaban (n = 12) and dabigatran (n = 11). DOACs offer simplified management of selected patients, as illustrated by a case of persisting (autoimmune) HIT (>2-month platelet recovery with inversely parallel waning of serum-induced heparin-independent serotonin release) with successful outpatient rivaroxaban management of HIT-associated thrombosis. Evidence supporting efficacy and safety of DOACs for acute HIT is increasing, with the most experience reported for rivaroxaban.

Design of the rivaroxaban for heparin-induced thrombocytopenia study.

Rivaroxaban is an ideal potential candidate for treatment of heparin-induced thrombocytopenia (HIT) because it is administered orally by fixed dosing, requires no laboratory monitoring and is effective in the treatment of venous and arterial thromboembolism in other settings. The Rivaroxaban for HIT study is a prospective, multicentre, single-arm, cohort study evaluating the incidence of new symptomatic venous and arterial thromboembolism in patients with suspected or confirmed HIT who are treated with rivaroxaban. Methodological challenges faced in the design of this study include heterogeneity of the patient population, differences in the baseline risk of thrombosis and bleeding dependent on whether HIT is confirmed or just suspected, and heterogeneity in laboratory confirmation of HIT. The rationale for how these challenges were addressed and the final design of the Rivaroxaban for HIT study is reviewed.