The relationship between acidosis and coagulopathy has long been described in vitro and in trauma patients, but not yet in orthotopic liver transplantation (OLT). The association of metabolic ...acidosis with coagulopathy and with transfusion requirements was evaluated in patients submitted to OLT. Changes in acid-base and coagulation parameters were analyzed by repeated measures. Regression analyses adjusted for sex, age, model for end stage liver disease (MELD) score, and baseline values of hemoglobin, fibrinogen, international normalized ratio, platelets determined the association of acid-base parameters with coagulation markers and transfusion requirement. We included 95 patients, 66% were male, 49.5% of the patients had hepatocellular carcinoma and the mean MELD score was 20.4 (SD 8.9). The values of all the coagulation and acid-base parameters significantly changed during OLT, particularly in the reperfusion phase. After adjustments for baseline parameters, the decrease in pH and base excess (BE) values were associated with a decrease in fibrinogen levels (mean decrease of fibrinogen level = 14.88 mg/dL per 0.1 unit reduction of pH values and 3.6 mg/dL per 1 mmol/L reduction of BE levels) and an increase in red blood cells transfusion (2.16 units of RBC per 0.1 unit reduction of pH and 0.38 units of RBC per 1 mmol/L reduction of BE levels). Among multiple factors potentially associated with adverse outcomes, decreasing pH levels were independently associated with the length of hospitalization but not with in-hospital mortality. Metabolic acidosis is independently associated with decreased fibrinogen levels and increased intraoperative transfusion requirement during OLT. Awareness of that association may improve treatment strategies to reduce intraoperative bleeding risk in OLT.
Introduction: Cardiac failure is a main cause of morbidity and mortality in patients with thalassemia major (TM) who are receiving regular blood transfusion due to iron overload. So, effective and ...adequate iron chelation is extremely important. Deferoxamine (DFO), the most widely used iron chelator, has poor compliance. Combined therapy with Deferiprone (DFP) increases chelation efficacy, decreases iron-induced complications, improves compliance increasing survival in thalassemia.
Objectives: Assessment of efficacy and safety in combined chelation with DFP and DFO in thalassemic patients with iron overload.
Methods and results: We have 50 thalassemia major patients in 4 Brazilian Centers (Boldrini Hospital, Sao Paulo Hematology Center, HEMEPAR and FAMEMA) receiving combined chelation therapy with follow up to three years. DFP (75–100 mg/kg/daily) and DFO (30–60 mg/kg, 4–7 days/week) are being administered during one to three years. Median age of this group is 21,5 y/o (range 8–35), with 48% female. Median age to start regular transfusions was 12 months (range 2–140) and to begin chelation therapy was 57 months (range 17–216). All patients were screened for Hepatitis C and 26% had positive sorology and/or PCR. Statistical analysis were made with Spearman test and Fisher test. All patients, except two, did cardiac and liver MRI in the initial phase of the study, resulting in 60,5% with cardiac iron overload (T2*<20ms), being severe in 31,2%. Assessment of liver iron concentration (LIC) showed 95,7% with liver iron overload (>3ug/g dry weight), being severe in 17,4%. During follow up, only 43 patients (86%) was screened with MRI. From these, 67,4% had cardiac iron overload (severe in 32,5%) and 78,6% had liver iron overload (severe in 11,9%). Mean serum ferritin before and after three years were 3095,7 ±1934,5 ng/ml and 2373,9±1987,6 ng/ml, respectively. Our data showed positive correlation between serum ferritin, LIC and ALT, even in initial data and after combined chelation therapy (p<0,001), but there is no correlation between cardiac T2* and LIC and between cardiac T2* and ferritin. DFP adverse events included 8% agranulocytosis, 22% neutropenia, 20% arthralgia and 38% gastric intolerance. DFO adverse events were 2,6% deafness, 2,0% cataract and 12% growth deficit. Hepatic toxicity was found in 6%, but without necessity to stop treatment. Compliance in this group was excellent in 48%, good in 22% and poor in 30%.
Conclusions: This is the first multicenter study to evaluate combined chelation therapy in Brazil based on cardiac MRI and LIC. Most patients had cardiac and hepatic iron overload probably because they began iron chelation lately, due to difficult access to iron chelators in the past. Cardiac iron overload didn't have correlation with ferritin and LIC and these data need more understanding. Age of initial regular blood transfusion, increased transfusional requirement, inadequate chelation or delayed chelation may play a role in this question. Combined therapy with DFO and DFP is effective to decrease serum ferritin and LIC. Follow up and improving compliance may decrease cardiac iron overload. Adverse events are similar to literature. Combined therapy is safety in TM patients with transfusional iron overload.
COVID-19 can result in severe lung injury. It remained to be determined why diabetic individuals with uncontrolled glucose levels are more prone to develop the severe form of COVID-19. The molecular ...mechanism underlying SARS-CoV-2 infection and what determines the onset of the cytokine storm found in severe COVID-19 patients are unknown. Monocytes and macrophages are the most enriched immune cell types in the lungs of COVID-19 patients and appear to have a central role in the pathogenicity of the disease. These cells adapt their metabolism upon infection and become highly glycolytic, which facilitates SARS-CoV-2 replication. The infection triggers mitochondrial ROS production, which induces stabilization of hypoxia-inducible factor-1α (HIF-1α) and consequently promotes glycolysis. HIF-1α-induced changes in monocyte metabolism by SARS-CoV-2 infection directly inhibit T cell response and reduce epithelial cell survival. Targeting HIF-1ɑ may have great therapeutic potential for the development of novel drugs to treat COVID-19.
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•Elevated glucose levels regulate viral replication and cytokine production in monocytes•Glycolysis sustains CoV-2-induced monocyte response and viral replication•mtROS/HIF-1α is necessary for CoV-2 replication and monocyte cytokine production•Monocyte-derived cytokines drive T cell dysfunction and epithelial cell death
Diabetic people with uncontrolled blood glucose levels have a greater risk to develop severe COVID-19 disease. Codo et al. show that elevated glucose levels and glycolysis promote SARS-CoV-2 (CoV-2) replication and cytokine production in monocytes through a mitochondrial ROS/hypoxia-inducible factor-1α dependent pathway, resulting in T cell dysfunction and epithelial cell death.
Abstract 4052
Poster Board III-987
Frequent transfusions of red blood cells are considered standard therapy for patients with β-thalassemia. However, this can lead to transfusional iron overload and ...subsequent end-organ damage with decrease in life-expectancy. Ferritin is the most widely available non-invasive method for assessing iron stores and iron overload in chronically transfused patients. However, it can also be elevated in inflammatory conditions. MRI has been proposed as a non-invasive method for detection and quantification of iron stores in specific organs. Most studies utilizing MRI for detection of iron overload have focused on the heart and liver, and it is unknown if MRI could satisfactory detect iron overload in other potentially involved organs such as pancreas.
To evaluate and correlate the level of iron accumulation in different organs and serum ferritin concentrations for 6 months before imaging studies in patients with β-thalassemia receiving chronic transfusion therapy.
MRI was used to asses iron content in three different organs (heart, liver, and pancreas) in patients with a diagnosis of β-thalassemia. Validation of the MRI technique was done by determining liver iron concentration (LIC) from 11 liver biopsies. LIC was determined by atomic absorption spectrometry and was correlated with liver T2* measurement obtained with MRI. There was a significant, curvilinear, inverse correlation between liver T2* MRI measurements and the LIC by Pearson′s method (r =-0.878, p=0.001). We used Pearson′s coefficient of correlation to assess association between T2* measurements among different organs (heart, liver and pancreas) and between organs and serum ferritin levels.
We evaluated 115 patients with a diagnosis of β-thalassemia that were receiving chronic transfusion therapy. Mean age was 21,25 years (range 7-54 years) and 43% were male. Mean T2* value in the liver was 3.91 ± 3.95 ms, indicating significant liver siderosis (T2*<6.3ms) in most patients (92.1%). Mean value of myocardial T2* was 24.96 ± 14.17 ms and the incidence of cardiac siderosis (T2*<20ms) was 36%. Additionaly, 19% of the patients (22/115) had severe cardiac siderosis (T2* <10ms). Mean T2* value in pancreas was 11.12 ± 11.20 ms, and pancreatic iron deposition (T2* < 21ms) was found in 83.5% of patients. There was no significant correlation between liver and pancreas iron overload (r =0.249), and liver and myocardial iron overload (r =0.149). There was a moderate correlation among pancreas and myocardial iron overload (r =0.546; p=0.001). Mean serum ferritin level was 2,676.5 +/- 2,051.7 ng/mL (range 59-12,362 ng/mL). There was no significant correlation among ferritin serum level and liver, heart and pancreas T2* values (r =-0.397; r =-0.220; r =-0.295).
Iron overload of liver, heart and pancreas, measured by MRI T2*, could not be predicted by ferritin levels in patients with β-thalassemia. Pancreatic iron overload can be measured by MRI, but we could not predict pancreatic hemosiderosis by detection of iron overload in others organs (except for a moderate correlation among pancreas and heart iron overload). Given that direct calibration of MRI with pancreas biopsies is not possible, further studies are necessary to validate this technique.
No relevant conflicts of interest to declare.
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