pRBC Units Research Articles

322: A comparison of intrauterine balloon deflation techniques in postpartum hemorrhage

Intrauterine balloon tamponade is a commonly used treatment for refractory postpartum hemorrhage (PPH). However, balloon deflation techniques at the time of tamponade removal have not been studied. The objective of this study was to compare gradual intrauterine balloon deflation versus all-at-once removal in women with PPH. Retrospective cohort study of women with PPH requiring intrauterine balloon tamponade from 2015-2018. Patients who had gradual balloon deflation (≥30 minutes from start of deflation to removal) were compared to those who had the balloon deflated and removed all-at-once. Clinical outcomes were assessed including estimated blood loss (EBL), decrease in hemoglobin, blood transfusion, need for additional invasive surgical procedures (i.e. uterine artery embolization, B-Lynch, hysterectomy), ICU admission and postpartum fever. The primary study outcome was a composite maternal morbidity of transfusion ≥4 units PRBC, disseminated intravascular coagulopathy (DIC), need for additional invasive surgical procedures or ICU admission. Chi-square, Mann Whitney U and multivariate logistic regression models were used for statistical analysis. Of 51 women with PPH and intrauterine balloon placement, 40 (78.4%) underwent gradual balloon deflation and 11 (21.6%) underwent all-at-once removal. The median duration of intrauterine balloon tamponade was 1100 minutes (150-2025 minutes), and did not differ between the two groups (1090 vs 1230 minutes, p=0.95). Within the gradual group, the median time from start of deflation to complete balloon removal was 150 minutes (30-510 minutes). Clinical outcomes are shown in the Table. Composite maternal morbidity was not statistically different between the gradual and all-at-once groups (25% vs 27.3%, p=0.88). Maternal age, parity, gestational age, BMI, mode of delivery, and neonatal weights did not differ between the two groups. The groups had similar rates of inductions, cesarean deliveries, multifetal pregnancies, episiotomies and postpartum fevers. There were no peripartum hysterectomies or maternal deaths. In women with refractory PPH requiring intrauterine balloon tamponade, gradual balloon deflation compared to all- at-once removal have similar clinical outcomes.

Variability of fluid administration during exploratory laparotomy for abdominal trauma

BackgroundApproximately 8% of traumatically injured patients require transfusion with packed red blood cells (pRBC) and only 1% to 2% require massive transfusion. Intraoperative massive transfusion was defined as requiring greater...

Safety and Efficacy, Including Event-Free Survival, of Deferasirox Versus Placebo in Iron-Overloaded Patients with Low- and Int-1-Risk Myelodysplastic Syndromes (MDS): Outcomes from the Randomized, Double-Blind Telesto Study

▪Background: MDS comprise a group of disorders characterized by bone marrow (BM) failure, cytogenetic and molecular alterations, and progression to acute myeloid leukemia (AML). Most lower-risk MDS patients (pts) eventually need chronic red blood cell (RBC) transfusions because of impaired hematopoiesis, resulting in iron overload (IO) that damages organ function and contributes to shortened survival. Though iron chelation therapy (ICT) has been consistently shown to improve outcomes in lower-risk MDS pts, most studies had limitations (eg retrospective analyses, registry studies, pts not stratified by performance status). As such, a prospective, controlled study of ICT and survival in Low/Intermediate (Int-1)-risk MDS pts was needed.Aims: TELESTO (NCT00940602) was a Phase II randomized, double-blind study that evaluated event-free survival (EFS) and safety of deferasirox (DFX) vs placebo (PBO) in Low/Int-1-risk MDS pts.Methods: Eligible pts were aged ≥18 yrs, had IPSS Low/Int-1-risk MDS (confirmed by BM examination within 6 months of study entry), serum ferritin (SF) >1000 ng/mL, transfusion history of 15-75 pRBC units, without cardiac, liver and renal abnormalities. Pts were randomized 2:1 to DFX (dispersible tablets; 10-40 mg/kg/day based on dosing guidelines) or PBO. Primary objective was to evaluate DFX and PBO for EFS, measured by a composite primary endpoint of time to first non-fatal event (related to cardiac and liver function and transformation to AML) or death, whichever occurred first; events were confirmed by an independent adjudication committee. With a planned sample size of 210 pts, no hypotheses were planned to be tested; statistical tests are exploratory, P values associated with treatment effect are nominal.Results: 225 pts were randomized to DFX (n=149) or PBO (n=76); 72.4% had Int-1 MDS, 60.9% were male, mean age was 61.0 yrs; baseline characteristics were balanced, but more pts in the DFX arm were aged ≥75 yrs (25.5% vs 17.1%). DFX and PBO pts received a mean of 20.28 and 20.27 international units of pRBC transfusions 6 months prior to randomization. Median time on treatment was longer with DFX vs PBO (587.5 vs 370.5 days); 43.9% and 25.0% of DFX and PBO pts received treatment for ≥2 yrs. Median EFS was prolonged by 349 days with DFX (1440 days; 95%CI 1167-1559) vs PBO (1091 days; 95%CI 820-1348): 36.4% risk reduction in EFS with DFX (P=0.015 [Figure 1]). Estimated EFS at 3 yrs was 61.5% (95%CI 52.2-69.6) with DFX and 47.3% (95%CI 31.8-61.3) with PBO. Events that occurred first with DFX (n=62; 41.6%) and PBO (n=37; 48.7%) included: worsening cardiac function (1.3 vs 2.6%); hospitalization for congestive heart failure (0.7 vs 3.9%); liver function impairment (0.7 vs 1.3%); progression to AML (6.7 vs 7.9%); death (32.2 vs 32.9%). Robustness of the positive treatment effect with DFX was confirmed by various sensitivity analyses, including censoring pts with premature treatment discontinuation and subsequent ICT.Median overall survival (OS) was 1907 days (95%CI: 1440-not estimable) with DFX and 1509 days (95%CI 1095-1804) with PBO; HR 0.832 (95%CI 0.54-1.28, P=0.200). ICT after study treatment discontinuation may have diluted any potential OS difference. SF declined over time with DFX and increased in the PBO arm (Figure 2).Most frequently reported AEs (≥20% in either arm) were diarrhea, pyrexia, upper respiratory tract infection, cough and increased blood creatinine. After adjustment for exposure, rates were: diarrhea (24.7 vs 23.9%), pyrexia (21.8 vs 18.7%), upper respiratory tract infection (16.7 vs 22.7%), cough (12.6 vs 11.3%) and increased blood creatinine (15.9 vs 0.9%) in the DFX and PBO arms, respectively. Most frequently reported severe AEs (≥5% in either arm) were anemia, pyrexia, thrombocytopenia and lung infection. When adjusted for the different exposure time, the rate of all severe AEs per 100 pt-yrs was overall comparable.Summary/conclusions: TELESTO is the first prospective, randomized study in Low/Int-1-risk MDS pts with IO to show ICT with DFX provides clinical benefit across multiple tissues, leading to longer EFS (including cardiac and liver events and transformation to AML) vs PBO. The safety profile was as expected, consistent with previous studies of DFX in adult MDS pts with IO. Considering the current treatment landscape, it is unlikely that a similar, randomized trial can be performed. These results support the use of DFX in Low/Int-1-risk MDS pts with IO. [Display omitted] DisclosuresAngelucci:Celgene: Honoraria, Other: Chair DMC; Vertex Pharmaceuticals Incorporated (MA) and CRISPR CAS9 Therapeutics AG (CH): Other: Chair DMC; Jazz Pharmaceuticals Italy: Other: Local ( national) advisory board; Roche Italy: Other: Local (national) advisory board; Novartis: Honoraria, Other: Chair Steering Comiittee TELESTO Protocol. Rodriguez:Novartis: Speakers Bureau. Dong:Novartis: Employment. Ghosh:Novartis: Employment. Bornstein:Novartis: Employment.

Outcomes After Massive Transfusion in Trauma Patients: Variability Among Trauma Centers

BackgroundExsanguinating trauma patients often require massive blood transfusion (defined as transfusion of 10 or more pRBC units within first 24 h). The aim of our study is to assess the outcomes of trauma patients receiving massive transfusion at different levels of trauma centers. MethodsTwo-y (2013-2014) retrospective analysis of the American College of Surgeons Trauma Quality Improvement Program. We included all adult trauma patients who received massive transfusion (MT) of blood. Outcome measures were mortality, hospital length of stay, intensive care unit–free and ventilator-free days, blood products received, and complications. ResultsWe analyzed a total of 416,957 patients, of which 2776 met the inclusion criteria and included in the study. Mean age was 40.6 ± 20 y, 78.3% were males and 33.1% of the injuries were penetrating. Median injury severity score [IQR] was 29 [18-40], median [IQR] Glasgow Coma Scale 10[4-15]. Mean packed red blood cells transfusion in the first 24 h was 20 ± 13 units and mean plasma transfusion was 13 ± 11 units. Overall in-hospital mortality was 43.5%. Receiving MT in level I trauma center was independently associated with lower rates of mortality (odds ratio [OR]: 0.75 [0.46-0.96], P < 0.001). Higher injury severity score (OR: 1.020 [1.010-1.030], P < 0.001) and increased units of packed red blood cells transfused (OR: 1.067 [1.041-1.093], P < 0.001) were independently associated with increased mortality. However, there was no association between teaching status, age, gender, emergency department vitals, and units of plasma transfused. ConclusionsHemorrhage continues to remain one of the most common cause of death after trauma. Almost half of the patients who received massive transfusion died. Patients who receive massive blood transfusion in a level I trauma centers have improved survival compared with level II trauma centers.

Management of Duodenal Varix With Coiling

We present a case of a 65-year-old male with past medical history of intravenous drug abuse, ETOH abuse and dependence, chronic HCV, and decompensated liver cirrhosis. He presented to our facility with complaints of bright red blood per rectum for one day, reporting approximately 6 episodes of large volume liquid red stool. Upon arrival to hospital, he had several episodes of hematochezia with hemodynamic instability. SBP was 80 and HR 110. Initial labs revealed a hemoglobin of 6.0 g/dl, HCT of 19%, MCV: 79.1u3, platelet count of 118 k/mm3, INR of 1.7, BUN of 14, and Cr of 0.53. His calculated MELD-Na at the time was 14. Patient was admitted to ICU and he was started on a protonix and octreotide drip, and transfused 2 units of PRBC. EGD was performed which revealed bright red blood in duodenum, and a serpiginous vessel in the duodenum which was believed to be a varix, with stigmata of recent bleed(white nipple sign). Varix was not actively bleeding at the time of endoscopy. Decision was made to send patient for urgent TIPS. However, after TIPS, the patient rebled, requiring 4 more units of PRBC. Doppler study of TIPS, revealed a patent TIPS shunt. Given the continued bleeding he was sent to interventional radiology, for coil embolization of the varix which ultimately resolved the bleeding. Duodenal varix bleeding is an uncommon cause of gastrointestinal bleeding in patients with portal hypertension but can cause severe and potentially fatal bleeding. Duodenal variceal bleeding can be treated surgically or non-surgically. Treatment of duodenal variceal bleeding includes endoscopic sclerotherapy, endoscopic ligation, and trans jugular intrahepatic portosystemic shunt (TIPS). Given the low incidence there is not one uniform means of treating duodenal varices. In patients that are poor surgical candidates TIPS procedure is generally safest, but it too has complications such as hepatic encephalopathy and restenosis of the stent which is common with incidence of 55-70%. Surgical options such as variceal ligation, duodenectomy have high rebleeding rates and usually require further interventions. Other options such as shunt surgery carry up to a 30% mortality and require good hepatic function which in most patients is compromised. Coil embolization has not been adequately studied or performed. We present a case of a patient with a large duodenal varix that was refractory to TIPS, and was eventually coiled with complete cessation of bleeding.2500_A Figure 1. EGD, showing large duodenal varix2500_B Figure 2. Large Varix shown under fluoroscopy2500_C Figure 3. Duodenal Varix status post coiling

Unmasking Jejunal Carcinoma With Dual Antiplatelet Therapy

Small bowel neoplasms are extremely rare, comprising less than 1-3% of all gastrointestinal cancers. Adenocarcinoma is the second most common type of tumor in the small bowel and most commonly present in the duodenum, followed by jejunum/ileum. Jejunal carcinomas are most likely to present with abdominal pain, obstruction and less commonly with gastrointestinal bleeding. This case outlines a patient with jejunal carcinoma presenting with a gastrointestinal bleed following an increase in dual antiplatelet therapy. A 66 year old male with a 45 pack-year history of smoking and coronary artery disease on dual antiplatelet therapy presented with melena and exertional dyspnea for two-week duration. Aspirin was increased 3 weeks ago from 81 mg to 325 mg due to a transient ischemic attack. Remaining review of symptoms were negative. The patient never had a previous endoscopy or colonoscopy. Upon admission, vital signs were stable and physical exam was benign. Labs resulted in a hemoglobin of 7g/dl with a normal hemoglobin three weeks ago. Other labs were unremarkable. He was transfused two units of pRBC's with appropriate response in hemoglobin. Endoscopy and colonoscopy were unrevealing. Pill capsule study showed active signs of bleeding in the mid/proximal small bowel and subsequent enteroscopy uncovered a bleeding ulcerated lesion (occupying 35% of the lumen) with a clot seen in the distal duodenum and proximal jejunum. Snare was used to unroof the clot and the bleeding subsided with epinephrine injection. CT of the abdomen and pelvis showed an incidental pancreatic cyst that was determined to be unrelated to the jejunal lesion. Tissue biopsy of jejunum showed poorly differentiated carcinoma. Follow-up enteroscopy revealed proximal jejunal ulcerated mass with central area of necrosis with biopsies confirming the previous results. Dual antiplatelets were discontinued at discharge and patient remains asymptomatic. Small bowel carcinoma most commonly occur in duodenum and less frequently in jejunum/ileum. Given their indolent nature, most of these cancers are diagnosed at advanced stages. The etiology of small bowel neoplasms is unknown, however certain risk factors include hereditary cancer syndromes, inflammatory bowel disease and tobacco. Our patient was asymptomatic with no constitutional symptoms until he presented with acute gastrointestinal bleeding following an increase in his dual antiplatelet therapy with the source being a jejunum carcinoma.2489_A Figure 1. Proximal jejunal ulcerated mass with central area of necrosis.2489_B Figure 2. H&E showing poorly differentiated jejunal carcinoma.2489_C Figure 3. Pill capsule endoscopy showing active bleeding in mid small bowel.

Acute Esophageal Necrosis: A Case Report

Acute esophageal necrosis, also known as black esophagus and necrotizing esophagitis, is a rare esophageal disease, characterized by diffuse inflammation and black appearance of the esophageal mucosa. It mainly affects the distal esophagus and discontinue at the gastroesophageal junction. Etiology is thought to be due to ischemia in the presence of acid reflux into the esophagus. The usual clinical presentation is hematemesis and melena. The mainstay of treatment is fluid resuscitation and proton pump inhibitors. Mortality rate is 13 to 35 %, mainly due to underlaying cause. We describe a case of Acute esophageal necrosis in a 60-year-old male. A 60-year-old male with a significant history of hypertension, coronary artery disease, diverticulosis, gastro esophageal reflux disease, indeterminate colitis. Two weeks prior to presentation he has severe watery diarrhea with no bleeding or melena. patient also has vomiting and had two episodes of presyncope. at the EC, he developed hematemesis, he was then admitted to ICU and given IV fluids, 2 units of PRBC, and IV proton punp inhibtors. Blood culture were negarive so septecmia was unlikely cause of his low blood pressure.Esophagogastroduodenoscopy Showed diffusely congested, black esophageal mucosa (image 1, 2) in the middle and lower thirds of the esophagus. These ulcerations stop at gastro esophageal junction. Biopsy was contraindicated because of the severe esophagitis. Gastrografin esophagogram showed no perforation. Patient was kept NPO and had parentral nutirion for 5 days, he was able to have liquid diet at the 6th day of his stay. A repeat endoscopy 12 days later showed almost complete healing of the esophagus with reflux esophagitis (image 3). subsequently patient clinical condition has improved and was discharged home after 18 days of hospital stay. The black esophagus is one of the rare esophageal diseases. In this case the probable cause was hypovolemic shock from severe diarrhea, and hemorrhage in the presecne of reflux disease. The underlying vascular diseases also put the patient at higher risk to develop necrotizing esophagitis. This patient was treated with early resuscitative management which resulted in significant improvement in endoscopic findings and the overall survival. The key factors which contributed to survival are early detection and aggressive management in the resuscitation as the cause of ischemia needs to be corrected in order to increase perfusion to the esophageal mucosa.1828_A Figure 1. Image showing gangrenous esophageal mucosa, the likely cause of patient's bleeding1828_B Figure 2. esophageal necrosis.1828_C Figure 3. Esophageal healing 12 days later.

SUBCLINICAL POLYCYTHEMIA VERA PRESENTING AS EXTENSIVE THROMBOSIS DUE TO MASSIVE TRANSFUSION

SESSION TITLE: Critical Care 1 SESSION TYPE: Med Student/Res Case Report PRESENTED ON: 10/09/2018 03:45 PM - 04:45 PM INTRODUCTION: Massive Transfusion Protocol (MTP) is used in patients with hemorrhagic shock. Iatrogenic polycythemia secondary to massive transfusion is exceedingly rare. We present first reported case of undiagnosed subclinical polycythemia vera (PV) which became manifest with extensive thrombosis, after massive transfusion. CASE PRESENTATION: 66-year-old male with history of hypertension and ischemic strokes, presented to the Emergency Department with hypovolemic shock due to lower gastrointestinal bleeding. Initial bloodwork showed a Hb of 6.2 gm/dL, Hct 19.1%, platelets-282 x 109/L, WBC 6.6 x 109/L, INR 2.7, aPTT 83.7s. He received 8 units of PRBC, 6 units of fresh frozen plasma, 6 units of platelets as well as human prothrombin complex concentrate to reverse coagulopathy. Patient was admitted to ICU and intubated for urgent endoscopy, which revealed an esophageal ulcer and gastritis. He was started on proton pump inhibitor and repeat labs showed Hb of 18 gm/dL, Hct 53.8%, platelets-546 x 109/L with INR of 1. On admission day 3, patient developed pulmonary infiltrate and BAL grew MRSA treated with vancomycin. Due to worsening ventilation, a CT scan was done which showed bilateral acute pulmonary embolism with right heart strain. Doppler venous ultrasound revealed deep vein thrombosis of both upper and lower extremities. He had Hb of 19.6 gm/dL, Hct 59.9%, platelets-450 x 109/L. Reviewing his history, he was noted to have baseline Hb of 14 to 16 gm/dL, Hct 40%, with one instance of Hb of 18 gm/dL, Hct 56. The previous cerebrovascular accident was found to be secondary to a carotid artery thrombus. Hematology was emergently consulted and anticoagulation with low intensity heparin was initiated inspite of GI bleeding. He underwent multiple bedside phlebotomies until his Hct was below 50%. CT abdomen showed mild splenomegaly. Serum erythropoietin initially was normal, but was low on repeat testing. Janus kinase 2 (JAK2) V617F mutation was present, confirming diagnosis of primary polycythemia. Upon discharge, he is to receive ASA, hydroxyurea and anticoagulation for the venous thrombosis. DISCUSSION: PV is a chronic myeloproliferative neoplasm that is associated with a JAK2 mutation in most cases. An elevation of hemoglobin/hematocrit>16.5/49 in men and 16/48 in women, a subnormal serum EPO level, and a JAK2 V617F mutation constitute the diagnostic criteria for PV. Thrombotic complications are a major cause of morbidity and mortality in polycythemia vera with a reported incidence of 12–39%1. CONCLUSIONS: Sustained elevation of Hb/Hct >16.5/49 after massive transfusion should raise the possibility of PV, prompting workup and a heightened concern for thrombosis. Recognition of subclinical polycythemia is extremely important in critical care setting as they share the same vascular risk as overt PV including risk of arterial and venous thrombosis. Reference #1: Cerquozzi S, Barraco D, Lasho T, Finke C, Hanson CA, Ketterling RP, Pardanani A, Gangat N, Tefferi A. Risk factors for arterial versus venous thrombosis in polycythemia vera: a single center experience in 587 patients. Blood Cancer J. 2017 Dec 27;7(12):662 DISCLOSURES: No relevant relationships by Paula Adamson, source=Web Response No relevant relationships by Shahla Bari, source=Web Response No relevant relationships by Donnie Carter, source=Web Response No relevant relationships by Marilyn Foreman, source=Web Response No relevant relationships by Swathi Sree Nutakki, source=Web Response

Esophageal Arteriovenous Malformation as a Cause of Significant Gastrointestinal Bleeding - Rare, but Potentially Easy to Treat

Gastrointestinal arteriovenous malformations (AVMs) are responsible for 2-5% of the cases of upper GI bleeding. The colon is the most common location (cecum >ascending colon). The Small intestine and stomach are the next most common sites with esophagus being a rare location as described below. The patient is a 51-year-old male presented with 3 episodes of gross hematemesis without any melena or hematochezia. He had a history of GERD, chronic hepatitis B without cirrhosis, and ESRD treated with peritoneal dialysis. He denied taking NSAIDs and there was no prior history of AVMs, hematemesis, PUD. On admission, vitals were stable and the exam was normal. Labs: Hemoglobin 5.5 g/dL, WBC count 9.5 K/CUMM, and platelets 244 K/CUMM. The last Hg value, 2 months before the current admission, was 10.3 gm/dL. PT and aPTT were normal. The patient received 1 unit of pRBC and was started on a PPI drip. Hematemesis resolved after the admission, but he required 2 more units of pRBC to maintain a Hg >7 mg/dL. On day 2, an EGD done by general surgery revealed a mid-esophageal AVM, but that was not cauterized due to the location. On day 4, another EGD by GI service revealed a 4 mm mid-esophageal AVM with a small central clean-based ulcer without active bleeding. Further EGD exam was normal and no other bleeding source was identified. Given the difficult location and esophageal wall motion from breathing, APC was not considered to be feasible. A complete obliteration of the AVM was done with a single endoscopic clip with satisfactory mucosal anchoring, and obliteration of the lesion. No further bleeding was reported on follow-up and Hg returned to usual 9-10 g/dL. This case represents an uncommon presentation of GI AVMs. Endoscopic therapy with APC is the most successful method of treatment, but hemostasis with clips can be used in cases where lesions are localized or APC is difficult to be performed as described here. The PubMed literature search returned a total of 10 cases of esophageal AVMs reported in combination with AVMs at other locations or as a part of a syndrome. On review of cases, AVMs were seen predominantly in males (7/9) compared to females (2/9) with age ranging from 22-76 years. Out of ten patients, only 3 cases of isolated esophageal AVMs were reported. This case provides evidence that although esophageal AVMs are rare in clinical practice, they should be considered in the differential in a case of upper GI bleeding, and timely intervention could be lifesaving.1764_A Figure 1. Arteriovenous malformation (AVM) in mid-esophagus.1764_B Figure 2. Arteriovenous malformation (AVM) in mid-esophagus after application of endoscopic clip

Supermassive Transfusion: A 15-Year Single Center Experience and Outcomes

The objective of this study was to determine the survival outcome associated with large-volume blood transfusion after trauma. This was a retrospective study at a Level I trauma center from January 2000 to December 2014 that included trauma patients who received ≥25 units packed red blood cell (pRBC) within the first 24 hours of hospital admission. Univariate and multivariable logistic regressions identified risk factors for mortality. Receiver operating characteristic curve analysis evaluated the ability of pRBC volume to predict mortality. Among 74,065 adults (≥18 years old), 178 patients (0.24%) received ≥25 units of pRBC in the first 24 hours, of which 142 (79.8%) received 25 to 49 units, 28 (15.7%) received 50 to 74 units, and 8 (4.5%) received ≥75 units. Overall, 92.2 per cent were male, mean age 33.9 (±14.0), mean Injury Severity Score 28.9 (±14.3), and median Glasgow Coma Scale score 12 (3-15). The overall mortality was 65.2 per cent and 64.1 per cent for those receiving 25 to 49 units, 64.3 per cent for 50 to 74 units, and 87.5 per cent for ≥75 units. In univariate analysis, female gender was associated with lower mortality [odds ratio (OR) 0.24, P = 0.025]. Decreasing Glasgow Coma Scale (OR 0.82, P < 0.001), increasing Injury Severity Score (OR 1.07, P < 0.001), and thoracotomy (OR 3.91, P < 0.001) were associated with higher mortality. There was no transfusion cutoff that was significantly associated with higher mortality.

Lead and Mercury Levels in Preterm Infants Before and After Blood Transfusions

Very low birth weight (VLBW) infants usually receive packed red blood cell unit (pRBC) transfusions. Heavy metal transfer via pRBCs is not widely discussed before. This study aimed to determine pre-/post-transfusion erythrocyte lead and mercury levels in infants and to correlate these levels to heavy metal concentrations in pRBCs. VLBW infants (n = 80), needing pRBC transfusion for the first time, were enrolled. Erythrocyte heavy metal levels were determined in pre-/post-transfusion blood samples and also in pRBC units. Mean lead and mercury levels in the pRBCs were found to be 16.3 ± 10.8 and 3.75 ± 3.23μg/L, respectively. Of the infants, 69.7% received lead above reference dose. Erythrocyte lead levels increased significantly after transfusions (10.6 ± 10.3 vs. 13 ± 8.5, p < 0.05) with significant correlated to amount of lead within pRBCs (r = 0.28). Mean pre-/post-transfusion erythrocyte mercury levels were 3.28 ± 3.08 and 3.5 ± 2.83μg/L, respectively (p > 0.05). There was a significant correlation between mean difference of mercury levels after transfusion and amount of mercury delivered by pRBCs (r = 0.28). Infants can be subject to high levels of lead and mercury through pRBC transfusions.

Rapid bedside rejuvenation of red blood cell with an autologous cell salvage device.

During storage, red blood cells (RBCs) undergo physicochemical changes which affect the quality, function, and invivo survival of transfused packed RBCs (pRBC). Changes include decreased 2,3-diphosphoglycerate (2,3-DPG) levels, decreased ATP, changes in mechanical properties and oxidative injury. RBC rejuvenation is a method used to increase levels of 2,3-DPG and ATP in pRBCs. This process requires incubating the pRBCs with a rejuvenation solution and subsequent washing. Standard blood bank protocols using the COBE 2991 Cell Processor require several hours of preparation. The objective of this study was to verify if a bedside protocol for rejuvenating pRBC and washing with the Sorin Xtra autologous cell salvage system could be used. Outdated pRBC units were obtained and rejuvenated in a model operating suite using a dry air incubator for 1h at 37°C. Six units of pRBCs were pre-diluted with saline (1000ml) and six units were not pre-diluted with saline. All units were washed with normal saline (1000ml) using an apheresis-design cell salvage device in manual mode and wash volume set to 3000ml. Samples were collected and analyzed for standard RBC quality parameters at baseline and post-wash. Total pRBC wash efficiency was 94% ± 12% at a final hematocrit of 67.7±5.9% while maintaining post-wash hemolysis 0.24±0.12 %. Pre-dilution prior to washing did not confer statistically significant differences in final RBC quality parameters with the notable exceptions of calculated hemolysis and supernatant potassium levels (P<0.05). The washing process can be completed within 10min. The post-wash RBC parameters are appropriate for immediate transfusion to patients.

Red tides: Mass casualty and whole blood at sea.

The U.S. Navy's casualty-receiving ships provide remote damage control resuscitation platforms to treat injured combatants deployed afloat and ashore. We report a significant mass casualty incident aboard the USS Bataan, and the most warm fresh whole blood (WFWB) transfused at sea for traumatic hemorrhagic shock since the Vietnam War. Casualty-receiving ships have robust medical capabilities, including a frozen blood bank with packed red blood cells (pRBC) and fresh frozen plasma (FFP). The blood supply can be augmented with WFWB collected from a "walking blood bank." Following a helicopter crash, six patients were transported by MV-22 Osprey to the USS Bataan. Patient 1 had a pelvic fracture, was managed with a pelvic binder, and received 4 units of pRBC, 2 units of FFP, and 6 units of WFWB. Patient 2, with a comminuted tibia and fibula fracture, underwent lower extremity four-compartment fasciotomy, and received 4 units of WFWB. Patient 3 underwent several procedures, including left anterior thoracotomy, aortic cross-clamping, exploratory laparotomy, small bowel resection, and tracheostomy. He received 8 units of pRBC, 8 units of FFP, and 28 units of WFWB. Patients 4 and 5 had suspected spine injuries and were managed nonoperatively. Patient 6, with open tibia and fibula fractures, underwent lower extremity four-compartment fasciotomy with tibia external fixation and received 1 unit of WFWB. All patients survived aeromedical evacuation to a role 4 medical facility and subsequent transfer to local hospitals. Maritime military mass casualty incidents are challenging, but the U.S. Navy's casualty-receiving ships are ready to perform remote damage control resuscitation at sea. Activation of the ship's walking blood bank to transfuse WFWB is essential for hemostatic resuscitations afloat. Study type: case series, level V.

Tolerability and efficacy of deferasirox in patients with transfusional iron overload: results from a German 2-year non-interventional study.

Iron overload (IOL) due to repetitive transfusions of packed red blood cells (pRBC) has a major impact on morbidity and mortality in patients with inherited bone marrow failure syndromes and hemoglobinopathies such as thalassemia and sickle cell disease. However, whether IOL influences the outcome of elderly patients with myeloid malignancies is not yet clear. Moreover, clinical trials have reported high drop-out rates during treatment with the oral iron chelator deferasirox (DFX). Here we report the results of a 2-year prospective observational study that aimed at describing the routine use of DFX in patients with hematological malignancies with regard to safety, efficacy and handling of the drug in a routine setting. A total of 406 patients were included. 58% of the patients were male. Most of the patients had myelodysplastic syndromes (MDS) (68%) and myeloproliferative neoplasms (MPN) (14%). Median time from first transfusion to study enrollment was 1.1 years (0-25.5 years) and most patients were chelation naive (91%) at enrollment. With regard to transfusion burden, most of the patients were moderately or mildly transfusion-dependent with 53% receiving 2-4 and 27% receiving less than 2 units of pRBC per month. Serum ferritin decreased from a mean of 2305 μg/l (± 1449 μg/l) to a mean of 1910 μg/l (± 1529 μg/l) at 24 months. There was no substantial change in transfusion-dependence during the observation period. Dose adjustments were reported in 48% of the patients with dose-escalation strategies being the most frequent reason for dosage increases (49%). The median observation time was 355days (5-1080days). Median duration of exposure to DFX was 322days (2-1078days). Two-hundred and ninety (72%) patients discontinued the trial prematurely after a median time of 235days (1-808days). Death (29%) and adverse events (23%) were the main reasons for discontinuation. Eleven percent of the patients discontinued treatment due to sufficient decrease in serum ferritin. Most frequent adverse events were decrease in creatinine clearance (22%), increase in serum creatinine (18%) and diarrhea (16%). This descriptive trial confirms the efficacy of DFX in decreasing the serum ferritin. Moreover, the high drop-out rates seen in prospective trials are recapitulated in this study, which can be attributed to adverse events in a substantial proportion of patients.

In vitro quality control analysis after processing and during storage of feline packed red blood cells units

BackgroundDuring the storage of packed red blood cells (pRBC), packed cell volume (PCV), bacterial contamination and percentage of haemolysis [percentage of free haemoglobin (HGB) in relation to the total HGB] are important quality parameters. Both PCV and haemolysis are indicators of the cellular integrity of stored units. There are no published experimental studies that evaluated these parameters during storage of feline pRBC using SAGM (adenine, dextrose, mannitol and sodium chloride) as the additive solution. The present study aims to (1) evaluate the quality of feline pRBCs stored in SAGM; (2) test for the semi-closed system’s suitability for use and risk of bacterial contamination; (3) establish the maximum storage time that may be appropriate to meet the criteria established by the United States Food and Drug Administration (US-FDA) guidelines for human blood banking; and (4) evaluate the need to calculate the percentage of haemolysis prior to the administration of units stored for more than 4 weeks.Four hundred eighty nine feline pRBC units were analyzed. Bacterial culture, PCV and percentage of haemolysis were determined within 6 h after processing (t0). One hundred and eighty units were re-tested for haemolysis and PCV after 29–35 days of storage (t1) and 118 units after 36–42 days (t2).ResultsBacterial contamination was not detected in any pRBC unit. Mean PCV at t0 was 52.25% (SD: ±5.27) and decreased significantly (p < 0.001) during storage to 48.15% (SD: ±3.79) at t1 and to 49.34% (SD: ±4.45) at t2. Mean percentage of haemolysis at t0 was 0.07% (SD: ±0.06) and increased significantly (p < 0.001) to 0.69% (SD: ±0.40) at t1 and to 0.81% (SD: ±0.47) at t2. In addition, 13.88% and 19.49% of pRBC units exceeded 1% haemolysis at t1 and t2, respectively.ConclusionsAccording to the US-FDA guidelines for human blood banking that recommend a maximum of 1% haemolysis, the results of this study show that all feline pRBC units with less than 24 h of shelf life have low levels of haemolysis. However, units preserved up to 28 days can only be administered if tested for haemolysis before use, since 13.88% units exceeded the 1% limit. The semi-closed system was considered safe for use as bacterial contamination was not detected in any pRBC unit.

Use of Logistic Regression to Determine Parameter Ability for Recovery Prediction in Experimental Rat Hemorrhagic Shock Model

IntroductionHemorrhagic shock (HS) severely decreases oxygen (O2) delivery and induces cardiovascular collapse. It is of interest for clinicians to estimate the potential of recovery during the early onset of a shock event as that would determine whether resources should be expended in environments of material shortage such as warzones and low resource communities. Multiple parameters, such as mean arterial pressure (MAP) and heart rate, are traditionally monitored during shock as a means of estimating the potential for recovery. In this study we used a logistic regression model to determine the ability of systemic hemodynamics, cardiac function, and blood gas parameters in determining the ability of successful HS recovery.MethodsPacked red blood cells (pRBCs) stored in AS‐3 after leukorfiltration were created from donor Sprague‐Dawley rats. pRBC units were randomly stored under either 1) conventional; 2) anaerobic; or 3) anaerobic/hypercapnic conditions. Rats (150–200g) were hemorrhaged to 50% of blood volume, held in hypovolemia for 30 minutes, and resuscitated to recover blood pressure to 90% pre‐hemorrhage with pRBC stored for either 1 or 3 weeks. Systemic hemodynamic, cardiac function, and blood gas parameters were monitored during shock and resuscitation. The percent resuscitation (%Res) corresponding to the percentage of the animal's original blood volume infused at the end of recovery, was used to create two classes of subjects with %Res=50% (equivalent to approximately 5 blood units) set as the threshold. A binary classification, logistic regression model was created with all measured parameters as features, and trained on random instances. The weights with an above threshold contribution assigned to each parameter after an L2 norm cost function minimization were extracted and matched with the corresponding features creating a reduced feature vector. A Monte Carlo approach was applied for n=100 trials of the previously described procedure to get a distribution of the most commonly selected features. The performance of the new feature vector was assessed by another logistic regression model with a 5‐ fold cross‐validation.ResultsThe top 3 features chosen by the model in order of increasing number of occurrences were: lactate 30 minutes into shock, mean arterial pressure 30 minutes into shock and contractility (dp/dtmax) at baseline. The model trained using these three features had a mean cross‐validation accuracy of 90.2%, significantly above the 66.9% accuracy (p&lt;0.001) for a baseline classifier trained with random features. A final test set accuracy of 88.5% was obtained.ConclusionsIt has been shown that a logistic regression model can be effectively used for the determination of important parameters for the prediction of successful recovery after shock in an experimental rat hemorrhagic shock model.Support or Funding InformationNIH: R01 HL126945, NIH: T32 HL105373This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Compensatory Reserve Index: Performance of A Novel Monitoring Technology to Identify the Bleeding Trauma Patient

Hemorrhage is one of the most substantial causes of death after traumatic injury. Standard measures, including systolic blood pressure (SBP), are poor surrogate indicators of physiologic compromise until compensatory mechanisms have been overwhelmed. Compensatory Reserve Index (CRI) is a novel monitoring technology with the ability to assess physiologic reserve. We hypothesized CRI would be a better predictor of physiologic compromise secondary to hemorrhage than traditional vital signs. A prospective observational study of 89 subjects meeting trauma center activation criteria at a single level I trauma center was conducted from October 2015 to February 2016. Data collected included demographics, SBP, heart rate, and requirement for hemorrhage-associated, life-saving intervention (LSI) (i.e., operation or angiography for hemorrhage, local or tourniquet control of external bleeding, and transfusion >2 units PRBC). Receiver-operator characteristic (ROC) curves were formulated and appropriate thresholds were calculated to compare relative value of the metrics for predictive modeling. For predicting hemorrhage-related LSI, CRI demonstrated a sensitivity of 83% and a negative predictive value (NPV) of 91% as compared with SBP with a sensitivity to detect hemorrhage of 26% (P < 0.05) and an NPV of 78%. ROC curves generated from admission CRI and SBP measures demonstrated values of 0.83 and 0.62, respectively. CRI identified significant hemorrhage requiring potentially life-saving therapy more reliably than SBP (P < 0.05). The CRI device demonstrated superior capacity over systolic blood pressure in predicting the need for posttraumatic hemorrhage intervention in the acute resuscitation phase after injury.

Intraoperative blood transfusion in pediatric patients undergoing renal transplant-Effect of renal graft size.

In pediatric RT, donor allograft size often exceeds the expected recipient norms, especially in younger recipients. An "oversize" graft might not only present a technical- and space-related challenge, but may possibly lead to increased demands in perioperative volume requirements due to the disparity between donor and recipient in renal blood flow. We evaluated transfusion practices at a single tertiary institution with special consideration of kidney graft size, hypothesizing that oversize graft kidneys might lead to a quantifiable increased need of blood transfusion in smaller recipients. Retrospective analysis of all patients who underwent pediatric RT from January 2004 to June 2014 at a tertiary pediatric centre was performed. Variables analyzed included patient age, weight, pre- and postoperative Hb concentration, graft size, EBL, amount of intraoperative blood transfusion, and preoperative use of erythropoietin. Based on graft size in relation to patient's age, a SMR and an OvR were identified. A subcohort of age-matched pairs was used to allow for comparison between groups. We calculated the expected procedure- and transfusion-induced changes in Hb and compared these changes to the observed difference in pre- vs postoperative Hb to assess the influence of graft size on transfusion requirements. RT was performed in 188 pediatric recipients during the study period. In the matched cohort, percentage of transfused patients during transplantation in the OvR group was more than double compared with SMR (89% vs 39%, P<.001); similarly, the median number of transfused PRBC units in OvR was 1, while the median of SMR did not receive transfusion (P<.001). The difference between expected (calculated) and observed change in Hb was significantly higher in OvR with a median of 1.9g/dL compared with SMR with a median of 1.0g/dL (P=.026). Correspondingly, the calculated median volume taken up by a regular size kidney was significantly higher with 213mL compared with 313mL (P=.031) taken up by an oversize graft kidney. Median estimated intraoperative blood loss was significantly higher in OvR than in SMR (6.9mL/kg, vs 5.3mL/kg, respectively; P=.04). Median postoperative Hb was similar among groups (10.4g/dL vs 10.6g/dL for SMR vs OvR, respectively). Transplantation of an oversized kidney in pediatric RT recipients is associated with a quantifiable higher need for blood transfusion. This may be caused by a higher intraoperative EBL and/or greater blood volume sequestered by the larger renal allograft and requires further evaluation.

An analysis of the efficacy and safety of direct oral anticoagulants (DOACs) in gastrointestinal cancer-associated venous thromboembolism (GI-CAVTE).

505 Background: Two major trials and meta-analysis of patients (pts) with active cancer and VTE suggests that apixaban (A) and rivaroxaban (R) showed similar efficacy to enoxaparin and warfarin while having less associated major bleeding. GICA is associated with a higher incidence of VTE compared to other tumors. Moreover, bleeding complications of DOACs are not well defined in GICA pts. We compared the efficacy and safety of DOACs in pts with active GICA and VTE at the University of Arizona Cancer Center (UACC). Methods: A retrospective chart review of pts receiving DOACs with GICA and VTE treated at UACC was performed (11/2013-02/2017). GICA subgroup extracted from clinical trial delineations followed: active cancer, defined as cancer diagnosed at any stage +/- 6 months of VTE diagnosis. Efficacy outcomes were recurrent DVT, nonfatal pulmonary embolism (PE), or fatal PE. Safety outcomes for major bleeding were Hg drop of ≥2 g/dL, transfusion of ≥2 units of PRBC, bleeding in a critical site, or bleeding contributing to death. Fisher exact test is used for testing the difference in categorical variables for p-value &lt; 0.05. Results: Our review included pts on A (n = 28) and R (n = 34). Pts had similar baseline characteristics compared to AMPLIFY (n = 81) and pooled-EINSTEIN (n = 71). Recurrent VTE at 6 months were 7.1% and 2.9% for pts on A and R, respectively. VTE historical comparison to AMPLIFY (3.7%) and EINSTEIN (2.8%) showed no significant difference. Major bleeding at 6 months were 7.1% and 14.7% for A and R, respectively, compared to 2.3% AMPLIFY / 2.8% EINSTEIN. R had the one recurrent non-fatal PE event and a significantly worse safety profile with 2 fatal bleeds (hemopericardium and upper GI bleed) and 2 critical bleeding sites (subarachnoid hemorrhage and retroperitoneal) [p = 0.0348], whereas A had non-significant of the before stated. Conclusions: To our knowledge, this is the first retrospective analysis to present long-term outcome data of DOACs in pts with GICA and VTE, which showed a similar risk of recurrent VTE and worse safety profile with R versus A. This data warrants further prospective clinical analysis of the efficacy and safety of DOACs in pts with GICA and VTE.

Efficacy and safety of pasireotide-LAR for the treatment of refractory bleeding due to gastrointestinal angiodysplasias: results of the ANGIOPAS multicenter phase II noncomparative prospective double-blinded randomized study.

Background:Gastrointestinal angiodysplasias (GIADs) could be responsible for recurrent bleeding and severe anemia. Somatostatin analogs could reduce transfusion requirements in these patients but no randomized controlled study is available. The main objective of the ANGIOPAS phase II double-blinded randomized, noncomparative study was to assess the effectiveness of pasireotide-LAR in reducing transfusion requirements in patients with refractory GIADs bleeding.Methods:A total of 22 patients with transfusion requirements ⩾6 units of packed red blood cells (pRBCs) during the 6 months prior to inclusion were randomized to receive pasireotide-LAR 60 mg (n = 10) or placebo (n = 12) every 28 days for 6 months. Patients were then followed for an additional 6 months after stopping treatment.Results:The pasireotide-LAR and placebo groups were equivalent for age, sex, comorbidities and transfusion requirement during the reference period (median 13 and 9.5 pRBCs). A 50 and 83% success rate (success defined as a decrease of at least 30% of transfused pRBCs) was observed in the pasireotide-LAR arm in the Intent to Treat (ITT) and per protocol (PP) analysis respectively. The need for transfusion during the intervention period was 3 pRBC units in the pasireotide-LAR group (range 0–26) and 11.5 pRBC units in the placebo group (range 0–23). Overall, three cases with glycemic control impairment were observed in the pasireotide-LAR group including one de novo diabetes.Conclusion:This double-blinded noncomparative randomized phase II study suggests, for the first time, the effectiveness of pasireotide-LAR 60 mg every 28 days to decrease the transfusion requirement in patients with recurrent bleeding due to GIADs.