Lifetime Transfusion Burden and Transfusion-Related Iron Overload in Adult Survivors of Solid Malignancies.

BACKGROUND: Limited data exist on transfusion burden and transfusion-related iron overload in adult survivors of solid malignancies. METHODS: Hospital-specific cancer registry data of patients with solid tumor receiving systemic anticancer treatment between January 2008 and September 2009 at the Oncology Department of the Leiden University Medical Center (The Netherlands) were retrieved and cross-referenced with red blood cell (RBC) transfusion records. Individual lifetime transfusion burden was captured in April 2015. Multitransfused long-term survivors with serum ferritin >500 µg/L were subsequently screened for hepatic and cardiac iron overload using 1.5 Tesla magnetic resonance imaging. RESULTS: The study population consisted of 775 adult patients with solid cancer (45.2% male; median age, 58 years; >75% chemotherapy-treated), 423 (54.6%) of whom were transfused with a median of 6.0 RBC units (range 1-67). Transfusion triggers were symptomatic anemia or hemoglobin <8.1-8.9 g/dL prior to each myelosuppressive chemotherapy cycle. We identified 123 (15.9%) patients across all tumor types with a lifetime transfusion burden of ≥10 RBC units. In the absence of a hemovigilance program, none of these multitransfused patients was screened for iron overload despite a median survival of 4.6 years. In 2015 at disclosure of transfusion burden, 26 multitransfused patients were alive. Six (23.1%) had hepatic iron overload: 3.9-11.2 mg Fe/g dry weight. No cardiac iron depositions were found. CONCLUSION: Patients with solid malignancies are at risk for multitransfusion and iron overload even when adhering to restrictive RBC transfusion policies. With improved long-term cancer survivorship, increased awareness of iatrogenic side effects of supportive therapy and development of evidence-based guidelines are essential. IMPLICATIONS FOR PRACTICE: In the presence of a restrictive transfusion policy, ∼30% of transfused adult patients with solid cancer are multitransfused and ∼50% become long-term survivors, underscoring the need for evidence-based guidelines for the detection and management of transfusion-related iron overload in this group of patients. In each institution, a hemovigilance program should be implemented that captures the lifetime cumulative transfusion burden in all patients with cancer, irrespective of tumor type. This instrument will allow timely assessment and treatment of iron overload in cancer survivors, thus preventing organ dysfunction and decreased quality of life.

Randomized trial of one-hour sodium bicarbonate vs standard periprocedural saline hydration in chronic kidney disease patients undergoing cardiovascular contrast procedures.

BACKGROUND: Guidelines advise periprocedural saline hydration for prevention of contrast induced-acute kidney injury (CI-AKI). We analysed whether 1-hour sodium bicarbonate hydration administered solely prior to intra-arterial contrast exposure is non-inferior to standard periprocedural saline hydration in chronic kidney disease (CKD) patients undergoing elective cardiovascular diagnostic or interventional contrast procedures. METHODS: We performed an open-label multicentre non-inferiority trial between 2011-2014. Patients were randomized to 1 hour pre-procedure sodium bicarbonate hydration (250 ml 1.4%, N = 168) or 4-12 hours saline hydration (1000 ml 0.9%, N = 165) prior to and following contrast administration (2000 ml of saline total). Primary outcome was the relative serum creatinine increase (%) 48-96 hours post contrast exposure. Secondary outcomes were: incidence of CI-AKI (serum creatinine increase>25% or >44µmol/L), recovery of renal function, the need for dialysis, and hospital costs within two months follow-up. RESULTS: Mean relative creatinine increase was 3.1% (95%CI 0.9 to 5.2%) in the bicarbonate and 1.1% (95%CI -1.2 to 3.5%) in the saline arm, mean difference 1.9% (95%CI -1.2 to 5.1%, p-non-inferiority <0.001). CI-AKI occurred in 11 (6.7%) patients randomized to sodium bicarbonate and 12 (7.5%) to saline (p = 0.79). Renal function did not fully recover in 40.0% and 44.4% of CI-AKI patients, respectively (p = 0.84). No patient required dialysis. Mean costs for preventive hydration and clinical preparation for the contrast procedure were $1158 for sodium bicarbonate vs. $1561 for saline (p < 0.001). CONCLUSION: Short hydration with sodium bicarbonate prior to elective cardiovascular diagnostic or therapeutic contrast procedures is non-inferior to standard periprocedural saline hydration in CKD patients with respect to renal safety and results in considerable healthcare savings. TRIAL REGISTRATION: Netherlands Trial Register (http://www.trialregister.nl/trialreg/index.asp), Nr NTR2699.

Association between micro particle-tissue factor activity, factor VIII activity and recurrent VTE in patients with acute pulmonary embolism.

Studies on the association between microparticle expressing tissue factor (MP-TF) activity, FVIII activity ( FVIII: C) and recurrent VTE yielded inconclusive results. We studied these associations in patients diagnosed with acute pulmonary embolism. Plasma levels of MP-TF and FVIII activity were measured in 277 patients with a first and 72 patients with a recurrent VTE. All patients were categorized based on the quintiles of MP-TF and FVIII activity in those with a single VTE. For both markers, odds ratios (ORs) for recurrent VTE were computed using patients in the lowest quintile as a reference group. No association was observed between MP-TF activity and recurrent VTE, with an OR of 1.4 (95 % CI 0.7-2.9) in the highest quintile of MP-TF activity. Compared with the reference group, patients in the highest quintile of FVIII: C were at increased risk of recurrent VTE, OR 4.2 (95 % CI 1.4-12.2). MP-TF activity was not associated with recurrent VTE whereas high FVIII: C levels were associated with a 4-fold increased risk of VTE recurrence. Future prospective studies are necessary to explore the potential of FVIII: C as a tool for risk stratification, either by itself or in combination with other pro-thrombotic markers.