Aggressive Transfusion Research Articles

Extensive ecchymosis and retroperitoneal hemorrhage due to acquired hemophilia-A following influenza vaccination: A case report.

Acquired hemophilia-A (AHA) is a rare but potentially life-threatening impaired coagulation disorder characterized by the development of autoantibodies against clotting factor VIII. Only a few case reports have been experienced with influenza vaccine-triggered AHA. Here, we report a case of severe hemorrhagic disorder due to AHA following influenza vaccine, which was successfully treated. The patient presented to the emergency department because of several severe, progressively worsening bruises after receiving the influenza vaccination. Consequently, the patient required intubation due to nasal-oral bleeding, which compromised the airway, and retroperitoneal hemorrhage with shock also developed. AHA was confirmed through a coagulation factor assay, including coagulation activity and antibody testing, which is possibly triggered by influenza vaccination. Low-dose cyclophosphamide and hydrocortisone were prescribed until activated partial thromboplastin time showed normal levels. Coagulation factor VIIa was administered, and aggressive blood transfusion was carried out concurrently to address the blood loss. The upper airway bleeding subsided and bleeding tendencies had been corrected to normal. The patient was smoothly weaned from the ventilator and recovered from critical illness. She was then discharged on the 19th day. The activated partial thromboplastin time mixing test can be performed immediately to establish the initial differential diagnosis and treatment plan for severe coagulopathy. AHA may be triggered by vaccination, with the hypothesis of activation of autoantibodies and molecular mimicry; this mechanism should be further studied.

Blood failure: traumatic hemorrhage and the interconnections between oxygen debt, endotheliopathy, and coagulopathy.

This review explores the concept of "blood failure" in traumatic injury, which arises from the interplay of oxygen debt, the endotheliopathy of trauma (EoT), and acute traumatic coagulopathy (ATC). Traumatic hemorrhage leads to the accumulation of oxygen debt, which can further exacerbate hemorrhage by triggering a cascade of events when severe. Such events include EoT, characterized by endothelial glycocalyx damage, and ATC, involving platelet dysfunction, fibrinogen depletion, and dysregulated fibrinolysis. To manage blood failure effectively, a multifaceted approach is crucial. Damage control resuscitation strategies such as use of permissive hypotension, early hemorrhage control, and aggressive transfusion of blood products including whole blood aim to minimize oxygen debt and promote its repayment while addressing endothelial damage and coagulation. Transfusions of red blood cells, plasma, and platelets, as well as the use of tranexamic acid, play key roles in hemostasis and countering ATC. Whole blood, whether fresh or cold-stored, is emerging as a promising option to address multiple needs in traumatic hemorrhage. This review underscores the intricate relationships between oxygen debt, EoT, and ATC and highlights the importance of comprehensive, integrated strategies in the management of traumatic hemorrhage to prevent blood failure. A multidisciplinary approach is essential to address these interconnected factors effectively and to improve patient outcomes.

Pituitary and Pancreatic Iron Is Present at an Early Age in Transfused Patients with Alpha Thalassemia Major

Introduction Alpha thalassemia major is generally fatal in utero or shortly after birth without aggressive red cell transfusion therapy both pre- and postnatally. The Society for Maternal-Fetal Medicine has released evidence-based practice guidelines for the diagnosis and management of fetal anemia, largely focused on red cell alloimmunization, with intrauterine transfusion typically starting at 18 weeks gestational age.((SMFM) et al., 2015) Early initiation of intrauterine transfusion allows quick correction of anemia and a prolonged reduction of hemoglobin Bart's concentration leading up to birth.(Chmait, Baskin, Carson, Randolph, & Hamilton, 2015) Long-term transfusion regimens postnatally invariably lead to iron overload, which can lead to organ dysfunction.(Taher & Saliba, 2017) Minimal data is currently available regarding the pattern of iron overload in young patients with alpha thalassemia major given the rarity of the disease itself and variations in iron overload monitoring. Methods We reviewed patients with alpha thalassemia major treated at our center who had iron overload evaluations prior to 10 years of age. Diagnoses were confirmed by genetic testing. Iron deposition measurements were collected using multiple gradient echo pulse sequences on 1.5 Tesla magnets. Results Six subjects were included in the study. All but one subject received several intrauterine transfusions and were delivered at term. The last subject did not receive any intrauterine transfusions and was born at 24 weeks gestational age. Subjects were routinely transfused postnatally to keep fast migrating hemoglobin below 10%. Initial MRI was done prior to 4 years of age and as early as 1.5 years. All subjects had moderate to severe iron overload based on liver iron concentration (LIC) by R2* MRI, which decreased significantly after starting chelation in the four subjects who had subsequent MRI assessments (Figure 1A). Pancreatic iron was also elevated in all subjects, and none had cardiac siderosis. All but one subject had pituitary R2 by Z-score for age and sex greater than 2 in the coronal and sagittal planes, indicating pituitary siderosis, but none had pituitary volume loss (Figure 2B). Discussion This study shows significant extrahepatic iron deposition (pancreas, pituitary) at a very young age indicating exposure to toxic reactive ferrous iron (Fe 2+). The pancreas is known to load temporally before the heart.(Noetzli, Papudesi, Coates, & Wood, 2009) None of the subjects in this study had cardiac iron by MRI, probably reflecting slower cardiac loading and lowering of Fe 2+ by chelation. It is very rare to have cardiac loading from transfusion in patients less than 2 years old.(Berdoukas et al., 2013) It is reassuring that none of the patients had pituitary volume loss, which has been associated with pituitary dysfunction,(Noetzli et al., 2012) although we know very little about pituitary function and iron in very young children. Our observation that some subjects had loading at 1.5 years old suggests there is significant circulating Fe 2+ in this population and the pituitary may be at risk. Chelation is rarely started prior to 2 years of age due to concerns about theoretical effects of chelation on neurodevelopment.(Coates, 2019) Despite significant levels of iron overload seen in initial assessments, hepatic iron rapidly improved with chelation despite aggressive red cell transfusion in this cohort. There are many unknowns here, including effects of prenatal iron exposure from transfusion, the extent to which iron seen by MRI signifies organ damage, and response of extrahepatic iron to chelation. However, the effects of iron deficiency on brain development are well documented(Idjradinata & Pollitt, 1993; Lozoff et al., 2013) and the possible effects of chelators on the newborn/infant brain could be serious. Long-term pituitary iron data are still needed to support earlier implementation of iron chelation in this population.

The Case Files

A patient presented after a cardiac cath with a football-sized mass in her groinFigure 1.: Axial CT angiography demonstrating right anterior thigh hematoma measuring 11.9 cm by 15.4 cm by 21 cm with active arterial extravasation (arrow).FigureFigureFigureA 56-year-old woman presented with shortness of breath and a cough she had had for a month. She also had associated orthopnea, paroxysmal nocturnal dyspnea, and dyspnea on exertion. A workup revealed an NSTEMI and new systolic heart failure, dilated cardiomyopathy (estimated ejection fraction 18%), and a sizable left ventricular apical thrombus on echocardiogram. Cardiac catheterization was performed and complicated by stable focal dissection of the right femoral artery and external iliac artery. She was discharged home on warfarin and enoxaparin for the LV thrombus. The patient returned to the ED one week later with symptoms of right groin pain and generalized lethargy, and she was in hypovolemic shock and had a massive right groin mass. Bedside ultrasound of the mass revealed a large hyperechoic fluid collection prompting resuscitation with two units of packed red blood cells to treat suspected hemorrhagic shock. She was also started on norepinephrine infusion for blood pressure and MAP support. Anticoagulation reversal was administered with 10 mg of vitamin K and one unit of FFP. CT angiography of the mass was obtained (Figures 1 and 2), and the patient was immediately taken to the OR for right femoral groin exploration for suspected right femoral artery injury with active arterial extravasation.Figure 2.: Coronal CT angiography demonstrating right anterior thigh hematoma with active arterial extravasation (arrow).Massive Hematoma The patient was diagnosed with post-catheterization femoral artery dissection with massive hematoma and active hemorrhage. She presented with hypotension, progressing to hypovolemic shock requiring aggressive fluid resuscitation, blood transfusion, vasopressors, and anticoagulation reversal. CT angiography showed a mixed density hematoma measuring 11.9 cm by 15.4 cm by 21 cm, and a small central focus of contrast blush. The patient was taken to the OR, where the surgeon found a hematoma the size of a football, which is roughly 17 cm in diameter and roughly 28 cm long. The hematoma was evacuated, and the femoral artery and external iliac arteries were repaired. Hematomas are the most common complication after cardiac catheterization. One review found that the incidence of femoral hematomas was 2.8 percent while active femoral and retroperitoneal bleeds were even lower at 0.6 percent and 0.3 percent, respectively. Dissection of the femoral or iliac arteries is also extremely rare, with an incidence of 0.46 percent. (Glob J Health Sci. 2012;4[1]:65; https://bit.ly/42TUAv5.) A large multicenter cohort study investigating vascular complications following endovascular cardiac procedures found that the incidence of major vascular complications was only 1.6 percent, defined as major hematoma (>10 cm), unstable bleeding, retroperitoneal hematoma, pseudoaneurysm, and arteriovenous fistula within a 48-hour periprocedural window. (Rev Lat Am Enfermagem. 2018;26:e3060; https://bit.ly/3lXFhRx.) The study also found that most vascular complications took place within six hours of surgery, making this patient's prolonged presentation even more unexpected. Most hematomas are self-limited, but larger ones with bleeding can cause hemodynamic instability. This patient was on anticoagulation for an LV thrombus, which likely complicated the bleeding. This case highlighted the importance of physician awareness of an emergent, rare presentation of a common hospital procedure—the cardiac cath. Clinical suspicion, especially in the periprocedural setting, rapid identification of the bleeding source, and immediate imaging make the diagnosis. Patients who continue to deteriorate despite resuscitative efforts require operative management. (StatPearls. Jan. 16, 2023; http://bit.ly/3nnkmaL.) Share this article on Twitter and Facebook. Access the links in EMN by reading this on our website: www.EM-News.com. Comments? Write to us at [email protected].

Association between perioperative plasma transfusion and in-hospital mortality in patients undergoing surgeries without massive transfusion: A nationwide retrospective cohort study.

An aggressive plasma transfusion is associated with a decreased mortality in traumatic patients requiring massive transfusion (MT). However, it is controversial whether non-traumatic or non-massively transfused patients can benefit from high doses of plasma. We performed a nationwide retrospective cohort study using data from Hospital Quality Monitoring System, which collected anonymized inpatient medical records from 31 provinces in mainland China. We included the patients who had at least one record of surgical procedure and received red blood cell transfusion on the day of surgery from 2016 to 2018. We excluded those receiving MT or diagnosed with coagulopathy at admission. The exposure variable was the total volume of fresh frozen plasma (FFP) transfused, and the primary outcome was in-hospital mortality. The relationship between them was assessed using multivariable logistic regression model adjusting 15 potential confounders. A total of 69319 patients were included, and 808 died among them. A 100-ml increase in FFP transfusion volume was associated with a higher in-hospital mortality (odds ratio 1.05, 95% confidence interval 1.04-1.06, p < 0.001) after controlling for the confounders. FFP transfusion volume was also associated with superficial surgical site infection, nosocomial infection, prolonged length of hospital stay, ventilation time, and acute respiratory distress syndrome. The significant association between FFP transfusion volume and in-hospital mortality was extended to the subgroups of cardiac surgery, vascular surgery, and thoracic or abdominal surgery. A higher volume of perioperative FFP transfusion was associated with an increased in-hospital mortality and inferior postoperative outcomes in surgical patients without MT.

Preoperative Transfusion in Sickle Cell Disease Children Undergoing Adenotonsillectomy.

To perform a systematic review and meta-analysis comparing two pre-operative transfusion regimens (conservative versus aggressive) in children with sickle cell disease(SCD) undergoing adenotonsillectomy in terms of post-operative complications, complications related to SCD and transfusion related complications. A literature review was performed through PubMed, EMBASE, Cochrane, and Ovid databases using the following phrases: (Adenotonsillectomy OR Tonsillectomy) AND (Sickle Cell Disease OR Sickle Cell Trait). Using predetermined inclusion and exclusion criteria, seven articles were selected for systemic review and two control trials were included in meta-analysis. Out of a total of 3,146 results, seven articles were selected for review and two controlled trials were included in the meta-analysis. There was no statistically significant difference in the rate of primary and secondary hemorrhage between the aggressive and conservative transfusion regimens (RR = 3.1, CI = 0.84-11.4, p-value = 0.089). The rate of sickle cell disease related complications including vaso-occlusive crisis and acute chest syndrome was also not statistically significant between the two transfusion groups (RR = 1.4, CI = 0.7-2.8, p-value = 0.339). Even though, the transfusion related complications did not reach statistical significance, there was a higher complication rate in the group receiving aggressive blood transfusion. In SCD children undergoing adenotonsillectomy, an aggressive transfusion regimen that focuses on reducing the Hemoglobin S ratio to below 30% has not been shown to be more effective in reducing post-operative complications when compared to a conservative transfusion regimen. Therefore, it is reasonable to utilize a conservative transfusion regimen, thereby reducing the transfusion-associated risks.

Step by step transfusion timeline and its challenges in trauma: A retrospective study in a level one trauma center.

Hemorrhagic shock is the leading cause of preventable early death in trauma patients. Transfusion management is guided by international guidelines promoting early and aggressive transfusion strategies. This study aimed to describe transfusion timelines in a trauma center and to identify key points to performing early and efficient transfusions. This is a monocentric retrospective study of 108 severe trauma patients, transfused within the first 48 h and hospitalized in an intensive care unit between January 2017 and May 2019. One hundred and eight patients were transfused with 1250 labile blood products. Half of these labile blood products were transfused within 3 h of admission and consumed by 26 patients requiring massive transfusion (≥4 red blood cells [RBC] within 1h). Among these, the median delay from patient's admission to labile blood products prescription was -11 min (-34 to -1); from admission to delivery of labile blood products was 1min (-20 to 16); and from admission to first transfusion was 20 min (7-37) for RBC, 26 min (13-38) for plasma, and 72 min (51-103) for platelet concentrates. The anticipated prescription of labile blood products and the use of massive transfusion packs and lyophilized plasma units were associated with earlier achievement of high transfusion ratios. This study provides detailed data on the transfusion timelines and composition, from prescription to initial transfusion. Transfusion anticipation, use of preconditioned transfusion packs including platelets, and lyophilized plasma allow rapid and high-ratio transfusion practices in severe trauma patients.

Optimizing transfusion therapy for survivors of Haemoglobin Bart's hydrops fetalis syndrome: Defining the targets for haemoglobin-H fraction and "functional" haemoglobin level.

Owing to the unique pathophysiology of anaemia in haemoglobin Bart's hydrops fetalis (HBHF), a transfusion strategy based on beta-thalassemia guidelines is suboptimal for chronically transfused HBHF patients. A more aggressive transfusion aimed at reducing the proportion of non-functional HbH and improving the "functional" haemoglobin (f-Hb) can lead to reduced haemolysis and improved tissue oxygenation. However, the optimal transfusion targets for these parameters are not yet defined. In this retrospective, longitudinal study on four chronically transfused patients with HBHF, we used receiver operating characteristic curves to find a pre-transfusion f-Hb of 106g/l and a HbH of 16.1% to be the optimal thresholds to achieve a normal soluble transferrin receptor and lactate dehydrogenase, respectively.

Cerebral venous sinus thrombosis-associated hemorrhage in vaccine-induced immune thrombotic thrombocytopenia: Catastrophic outcome if delayed diagnosis and treatment

The authors reported the clinical course of a 58-year-old female suffering from cerebral venous sinus thrombosis associated with hemorrhage after the ChAdOx1 nCov-19 vaccination. Emergent decompressive craniectomy was performed, and aggressive blood transfusion was given. Nevertheless, progressive intracerebral hemorrhage and thrombocytopenia developed. A delayed diagnosis was made on a rare complication of vaccine-induced immune thrombotic thrombocytopenia (VITT) with a positive result of anti-platelet factor 4 antibodies (PF4 Ab). The patient died 4 days postoperative due to brainstem failure.

S2621 When Do You Use an Aggressive Exchange Blood Transfusion Strategy to Treat Acute Hepatic Sequestration in Sickle Cell Disease?: A Case Report

S2621 When Do You Use an Aggressive Exchange Blood Transfusion Strategy to Treat Acute Hepatic Sequestration in Sickle Cell Disease?: A Case Report

Anemia in Cardiovascular Disease: Marker of Disease Severity or Disease-modifying Therapeutic Target?

In this review paper, we examine the latest evidence regarding the use of iron supplementation, erythropoiesis-stimulating agents (ESAs), and blood transfusions as therapeutic targets for anemia to mitigate morbidity and mortality in patients with cardiovascular disease. Intravenous ferric carboxymaltose (FC) injections in heart failure (HF) have resulted in improved self-reported patient symptoms; higher exercise capacity, as measured by 6-min walk test distance in anemic patients; and lower re-hospitalization rates in iron deficient patients. Darbepoetin alfa has shown evidence of improved Kansas City Cardiomyopathy Questionnaire scores. No mortality benefits have been noted thus far with FC injections or darbepoetin in HF, with an increase in adverse events with darbepoetin. Aggressive transfusions (Hg < 10g/dL) are not associated with improved outcomes in cardiovascular disease. Quality of life metrics, rather than mortality, appear to improve with IV FC and ESA use in HF. More studies are required to see if these treatments have a role in coronary artery disease. Current evidence suggests that anemia is a marker of underlying disease severity, with a limited role in disease modification. Further studies are required to solidify our understanding of this topic.

Continuous Platelet Transfusion As a Potential Desensitization Regimen in HLA Class I Alloimmune-Mediated Platelet Refractoriness

Background: The development of HLA antibodies is responsible for 4-8% of platelet transfusion refractoriness (PTR). The presence of HLA antibodies is a clinical complication that is generally managed by the selection of products that are negative for the antigens cognate to the patient's antibodies. Often, this selection is facilitated by targeted recruitment of donors with known HLA types. However, for very broadly HLA-alloimmunized patients, compatible products may be exceedingly scarce or completely unavailable, precluding the ability to consistently provide products the patient will likely increment to and benefit from. Here we describe a case of a patient with severe aplastic anemia (platelet count chronically <1 K/uL) and platelet transfusion refractoriness secondary to broad HLA-alloimmunization (98% PRA). HLA compatible products were unavailable due to the patient's rare HLA type and breadth of antibodies, and attempts at procuring compatible products via multiple national agency searches were unsuccessful. Thus, the patient could only be supplied with HLA incompatible products, which yielded insufficient post-transfusion platelet corrected-count increments (CCI). Her course was eventually complicated by multifocal intracranial hemorrhages, necessitating ICU admission with aggressive platelet transfusion support, immune-targeting therapy consisting of IVIg, and aminocaproic acid and recombinant activated factor VIIa.Methods: A continuous platelet infusion, or “platelet drip,” was employed in order to provide platelet transfusion support in the face of her severe thrombocytopenia with profound refractoriness. This consisted of consecutive transfusions of 4-6 equivalent unit apheresis platelet products (“doses”) transfused over 4 hours with a 15 minute post-transfusion CBC obtained from Q8 to Q12 hours to assess platelet increments. This ultimately resulted in 24-30 equivalent unit platelet product infusions/day.Results: Two days into the continuous platelet infusion, the patient began incrementing appropriately to occasional platelet products (CCI>>5) and, consequently, the infusions were able to sustain a platelet count >10K/uL, with a range of 20-70 K/uL, over the subsequent week. The improved counts, along with the patient's improved clinical condition and stable imaging findings showing resolving intracranial hemorrhages, allowed the transfusion support to be goal-directed targeting a prophylactic platelet threshhold of 10K/uL. Continued monitoring of the patient's CCIs enabled the identification of permissive antigens (i.e., allogeneic platelets with HLA antigens predicted to be incompatible with the patient's serum by solid-phase testing but were found to result in satisfactory increments); this knowledge allowed progressive widening of her permissive donor pool and enabled continued prophylactic support as needed. After three weeks the patient was able to be discharged from the ICU.Subsequent HLA class I antibody screens using flow-cytometry based single antigen bead (SAB) technology revealed progressive decrease in the patient's mean fluorescence intensity for most of her antibody specificities, with the majority of her class I A antibodies falling to undetectable or near-undetectable levels (while previously >5000 MFI). Simple regression analysis (RStudio 1.0.153, R version 3.4.1) was used to test to how level of exposure to individual HLA platelet antigens (as measured by the number of doses with a given antigen) affected subsequent MFI levels. The results of the regression indicate that pre MFI and exposure explain 70.6% of the variance (R2=0.706, F(2,78)=93.7, p=<2.2e-16). It was found that exposure is a significant predictor of decreased MFI (b=-107.20, p=0.01422). High initial MFI was strongly associated with high subsequent MFI (b=0.75, p= <2.2e-16).Conclusions: This data raises the possibility that large bolus platelet infusions could not only be of immediate therapeutic benefit in patients with HLA-alloimmune-mediated platelet refractoriness, but may also accelerate the evanescence of the responsible antibodies. Further research is warranted to explore this possibility, and to ascertain the potential magnitude of this effect in comparison to competing factors such as natural evanescence and/or B-cell immunosuppressive or immunomodulatory therapies. DisclosuresNo relevant conflicts of interest to declare.

Weight Gain during Induction Therapy of Acute Promyelocytic Leukemia Patients: A Preventable Problem

Introduction:Differentiation syndrome can be a major complication of all-trans retinoic acid (ATRA) and/or arsenic trioxide (ATO) therapy in acute promyelocytic leukemia (APL) patients. The incidence of DS in studies varies widely and reported between 2-27% mainly due to the definition used for the diagnosis of DS. Dyspnea, unexplained fever, weight gain greater than 5 kg, unexplained hypotension, acute renal failure, and presence of infiltrates and/or pleural, pericardial effusions on chest radiographs are regarded as the signs and symptoms associated with DS. Four or more of these criteria is required for a diagnosis of severe DS but any single criteria is not diagnostic. Weight gain of 5 kg is seen in up to 38% of moderate DS (2-3 criteria) and 68% of severe DS patients. APL patients characteristically have a bleeding tendency at presentation requiring aggressive transfusion support that leads to fluid overload and weight gain unless meticulously monitored. Herein we report our observations with weight gain in APL patients during induction period.Methods:Chart review of APL patients managed between 01/2006 and 04/2017 was conducted and patients who gained more than 5kg from baseline at admission were identified. Patients from 09/2013 to 04/17 were managed on an algorithm designed to reduce induction mortality in APL patients and care was provided by physicians dedicated to the management of this disease. The outcomes in these patients was compared to those prior to implementation of the algorithm. The algorithm was a two-page set of guidelines directed at preventing or treating the major causes of early death including meticulous monitoring of the weight as well as aggressive diuresis in the event of weight gain. Institutional review board approval was obtained. for this review.Results:130 patients were managed during this time period. 57 patients (trial group TG) were managed on the algorithm while 73 (pre-trial, PG) were managed prior to this implementation. Median age was higher in trial patients 48 vs 45 years, range being 21-81 in TG vs 19-80 in PG. Median WBC was (4.2 vs 2.7) and high risk (WBC > 10,000/mm3) were higher in the PG vs TG. Median platelet counts were similar. The predominant induction combination was ATRA with chemotherapy in PG (66%) whereas ATRA/Arsenic combination was used in the TG (75%). Median weight gain in the TG was less than PG. (3.15 vs 3.5 kg, range 0-12.8kg vs 0-35 kg). 3 patients in the PG and 1 in the TG did not get treatment and were discharged with comfort care. Excluding these patients, 26 % of patients in TG and 38% in PG gained more than 5kg. The mortality was higher in the PG group at 38% in those that gained more than 5 kg compared to 20 % in the TG. In contrast, the mortality was lower in both TG and PG patients with weight gain <5 Kg at 7.1% and 7.4%. Five patients in the PG group did not have follow up weights checked but there was documentation that would satisfy definition of severe DS and all 5 patients died between 4-14 days after admission. The incidence of severe DS was also lower in trial patients (6% vs 18%).Conclusions:Management of APL patients utilizing an algorithm might lead to better monitoring of complications like weight gain and preventing fluid overload seen during the treatment of APL. The impact of the weight gain on outcomes in comparison to other variables that might impact survival in our cohort will be evaluated further. DisclosuresKota:Incyte: Consultancy; Leukemia Lymphoma Society: Research Funding; Takeda Pharmaceuticals: Consultancy; Xcenda: Consultancy; Pfizer: Consultancy; Novartis: Consultancy. Arellano:Cephalon Oncology: Research Funding.

Could Transfusion be Restricted for Acute Promyelocytic Leukemia in the Era of Diffetentiating Agents?

BACKGROUNDWith the advent of differentiating agents (DA) like all-trans-retinoic-acid (ATRA), and arsenic trioxide (ATO), acute promyelocytic leukemia (APL) has become one of the best prognostic type of acute myeloid leukemia (AML) even in the under-developed countries. In Myanmar, APL is recognized as a common form of AML and managing APL in the resource limited setting particularly for aggressive transfusion support according to current guidelines is difficult and therefore transfusion requirement of APL treated in our center were analyzed with an aim to find evidence for restrictive transfusion policy. MATHODSCases of APL complicated by disseminated intravascular coagulation (DIC) treated during November 2014 to April 2017 were retrospectively reviewed in this study. All cases were treated with combined ATRA and ATO and conventional chemotherapy was added in high risk patients and those who developed rapid rise in white cell counts. Recommended target platelet count of 30-50 x 109/L and fibrinogen level of 100-150 mg/dl were maintained only for WHO grade 3 to 4 bleeding while the rest were transfused with platelet target of 20 x 109/L and fixed dose of FFP 2 -4 units per day until bleeding subsided. Prophylactic platelet was given for counts below 10 x 109/L. RESULTSAmong 33 APL admitted during two and half year's period, 29 presented with evidence of DIC, of them 4 had already developed intracerebral haemorrhage at presentation and died within 24 hours. In remaining molecularly confirmed 25 patients with APL, 14 males and 11 females, with median age of 28 years (range 12 -58) with initial performance status of 3 to 4 in 8 cases (32%) were classified as low, intermediate and high risk in 1 (4%), 13 (52%) and 11 (44%) cases respectively. Presenting blood counts were median hemoglobin - 5.9 mg/dl (3.2 - 10.6), median white cell count 7.23 x 109/L (0.43 - 110.8) and median platelet count 29 x 109/L (2 - 121). Regarding coagulation profile median PT - 15.6 second (9.9 - 21), median APTT - 28.4 second (20 - 46), median fibrinogen 160 mg/dl (82 - 900) and median D-Dimer - 8700 ng/ml (1917 - 19166). Median lowest platelet was 6 x 109/L (2 - 37) and median days of platelet count less than 10 x 109/L and less than 20 x 109/L were 4 days (0 - 10) and 8 days (2 - 26) respectively. Median number blood products transfused were of 6 units (3 - 12) of red cell, 10 units (6 - 15) of platelets and 10 unit (4 - 24) of FFP in total for each patient. Most bleeding and DIC subsided within first week and there were no haemorrhagic death during induction. CONCLUSIONRestricted transfusion policy may be possible in APL provided close monitoring of clinical and laboratory parameters and transfusion of blood products are tailored according to the risk and clinical condition. DisclosuresNo relevant conflicts of interest to declare.

Serum Ferritin Underestimates Liver Iron Concentration in Patients with Homozygous Alpha-0 Thalassemia

Background: Homozygous α0-thalassemia (Hemoglobin Bart's hydrops fetalis, HBHF) results from deletion of all α-globin genes. Similar to patients with transfusion-dependent beta-thalassemia (TDT-β), survivors of HBHF require life-long transfusions which over time will inevitably lead to significant tissue iron overload (IO). We have recently reported that the underlying disease process in HBHF is different from that of TDT-β (Amid A. et al. Blood, 2016). Unlike TDT-β, hemolysis is the major pathophysiologic process in HBHF and chronically transfused HBHF patients continue to have significant erythropoietic activity and tissue hypoxia (with increased serum erythropoietin) due to the indegenous nonfunctional hemoglobin-H. In addition, almost all survivors of HBHF would have commenced their transfusion therapy in-utero, potentially resulting in earlier IO compared to their TDT-β counterparts. Considering these differences, we hypothesized that the pattern of IO in patients with HBHF would likely differ from those with TDT-β.Methods: Following research ethics board approval, we retrospectively collected longitudinal data on transfusion and chelation history, serum ferritin, and liver iron concentration (LIC) measured by MRI or biopsy, in 7 HBHF (5 males; mean age: 7.3 years) and 14 TDT-β (8 males; mean age: 11.1 years) patients. None of the HBHF or TDT-β patients were splenectomized. Corresponding pairs of serum ferritin and LIC assessment (defined as measurements of not more than two weeks apart with no transfusions in between) were used to calculate ferritin-to-LIC ratios. All patients were treated with the same transfusion protocol to maintain pre-transfusion hemoglobin of >90 g/L and LIC of <5 mg/g of dry liver weight, until 2014. Since April 2014, five patients with HBHF have been commenced on a more aggressive transfusion strategy to decrease the nonfunctional HbH, suppress erythropoiesis, increase tissue oxygenation, and reduce hemolysis. We used linear mixed models to assess the associations between serum ferritin, LIC, and ferritin-to-LIC ratio with age, disease type (HBHF vs. TDT-β), chelation type, and method of LIC assessment. Correlations within a subject and between different ages were effectively accounted for in this model.Results: At 12 month of age, chelation-naïve HBHF patients had significantly higher serum ferritin level reflecting earlier IO compared to chelation-naïve TDT-β patients [1242.4 μg/dL (SD 419.4) vs. 418.3 μg/dL (SD 113.3), p<0.001]. On longitudinal assessments in both chelated HBHF and TDT-β patients, ferritin was significantly correlated with LIC (ρ = 0.88, p <0.001 and ρ = 0.46, p <0.001, respectively). Serum ferritin was significantly lower in HBHF vs. TDT- β [849 μg/dL (SD 573) vs. 2036 μg/dL (SD 1495), p<0.001] but there was no difference in LIC between the two groups [9.68 mg/g (SD 5.73) vs. 8.63 mg/g (SD 7.99), p=0.48]. Consequently, HBHF patients had significantly lower ferritin-to-LIC ratios [86.8 (SD 33.2) vs. 308.5 (SD 182.4), p<0.0001]. In addition, in the HBHF patients, serum ferritin-to-LIC ratio was corrolated with reticulocyte count (ρ = 0.41, p <0.042). In two mixed model analyses that included age, disease type, and method of LIC assessement or chelation type as variable of interset, disease type remained a highly signifiant predictor of serum ferritin-to-LIC ratio (p<0.0001). However, after the implementation of aggressive transfusion strategy (and suppression of erythropoeitic activity and improvement of tissue oxygenation) in HBHF patients, ferritin-to-LIC ratios were significantly higher [304.2 (SD 121.5) vs. 86.87 (SD 33.2), p=0.0003], becoming similar to ratios in TDT-β patients (p=0.88).Conclusion: Patient with HBHF are at-risk of significant IO early in life which poses potential challenges with iron chelation at an early age. Furthermore, in these patients, ferritin significantly underestimates LIC. This finding has important implications for clinical care and surveillance of IO in these patients, especially in areas with limited resources where non-invasive assessement of LIC (MRI) may not be widely available. The lower ferritin-to-LIC ratio observed in HBHF patients and its relation to erythropoietic activity indirectly suggest that in addition to transfusional iron loading, increased gastrointestinal absorption of iron due to suppressed hepcidin may also contribute to siderosis in these patients. DisclosuresNo relevant conflicts of interest to declare.

Cerebrovascular Infarcts in the Setting of Disseminated Intravasulcar Coagulation As Presenting Symptom in Acute Promyelocytic Leukemia

Introduction:Patients with newly diagnosed Acute Promyelocytic Leukemia (APL) commonly present with disseminated intravascular coagulation (DIC) that can lead to hemorrhagic insult. Hematologists caring for APL patients understand that aggressive transfusion support with platelets, cryoprecipitate, and fresh frozen plasma must be initiated to correct the underlying DIC. Rarely, a patient with APL will present with arterial thrombosis in the setting of DIC and little is known about how to best manage these patients.On review of the literature, five cases were described where patients with newly diagnosed APL presented with CNS arterial thrombosis; 3 patients are alive with neurologic deficit and 2 are dead. (Table 1).We have experience with three patients diagnosed with APL who presented with cerebrovascular infarct. We report our experience to heighten awareness of this unusual presentation of this rare type of leukemia.Methods:Chart review was conducted with IRB approval on three patients with known diagnosis of APL who presented to Emory University with signs and symptoms of stroke who were found to have ischemic cranial events. Demographics, past medical history, and treatment regimen for both infarction and APL were collected.Case Series:Patient 1- 21-year-old male who presented to an outlying hospital with expressive aphasia. MRI scan showed large right temporoparietal infarction. Labs showed WBC 21.6, platelets 9,000, low fibrinogen, elevated PT and elevated d-dimer. High-risk APL was confirmed and ATRA and IV dexamethasone were started. Heparin drip was initiated to decrease risk of further ischemic insult. Worsening neurologic symptoms 4 days later led to a repeat MRI scan, which showed progressive right sided infarct and a new infarct in the left distal territory of the middle cerebral territory and expired shortly thereafter. Images 1 and 2 show infarcts on day 2 and 6 of admission.Patient 2- 55-year-old female with presented with dysarthria and altered mental status. CT head showed left middle cerebral infarction and was immediately given tPA. Her admission labs showed WBC 37.6, platelets 48,000, PT 19, aPTT 35.3, Fibrinogen 67 and a diagnosis of high risk APL was established. She was induced with ATRA, Idarubicin and ATO and discharged in hematologic remission with no neurologic deficit.Patient 3- 59 year old female, Jehovah's Witness, with multiple comorbidities presented with shortness of breath. Influenza A and PE were diagnosed and oseltamivir and warfarin was initiated. New left arm tingling prompted a brain MRI scan that showed multifocal bilateral acute infarcts. She was discharged with anticoagulation but readmitted 5 days later with a WBC of 38.4 and platelets 19,000. CT head showed progression of all the infarcts. APL was diagnosed and ATRA and ATO was started but she refused transfusions and died of neurologic deterioration.Conclusions:Our case series review is consistent with the previous literature. The mortality in patients with APL presenting with CNS arterial thrombosis is extremely high. Since it is a rare occurrence in a rare malignancy, not enough is known on the best management strategy. More dedicated observation and research is warranted on this topic to improve outcomes in this otherwise very curable malignancy. [Display omitted] DisclosuresArellano:Cephalon Oncology: Research Funding. Kota:Takeda Pharmaceuticals: Consultancy; Xcenda: Consultancy; Leukemia Lymphoma Society: Research Funding; Incyte: Consultancy; Novartis: Consultancy; Pfizer: Consultancy.

An Ovine Model of Hemorrhagic Shock and Resuscitation, to Assess Recovery of Tissue Oxygen Delivery and Oxygen Debt, and Inform Patient Blood Management.

Aggressive fluid or blood component transfusion for severe hemorrhagic shock may restore macrocirculatory parameters, but not always improve microcirculatory perfusion and tissue oxygen delivery. We established an ovine model of hemorrhagic shock to systematically assess tissue oxygen delivery and repayment of oxygen debt; appropriate outcomes to guide Patient Blood Management. Female Dorset-cross sheep were anesthetized, intubated, and subjected to comprehensive macrohemodynamic, regional tissue oxygen saturation (StO2), sublingual capillary imaging, and arterial lactate monitoring confirmed by invasive organ-specific microvascular perfusion, oxygen pressure, and lactate/pyruvate levels in brain, kidney, liver, and skeletal muscle. Shock was induced by stepwise withdrawal of venous blood until MAP was 30 mm Hg, mixed venous oxygen saturation (SvO2) < 60%, and arterial lactate >4 mM. Resuscitation with PlasmaLyte® was dosed to achieve MAP > 65 mm Hg. Hemorrhage impacted primary outcomes between baseline and development of shock: MAP 89 ± 5 to 31 ± 5 mm Hg (P < 0.01), SvO2 70 ± 7 to 23 ± 8% (P < 0.05), cerebral regional tissue StO2 77 ± 11 to 65 ± 9% (P < 0.01), peripheral muscle StO2 66 ± 8 to 16 ± 9% (P < 0.01), arterial lactate 1.5 ± 1.0 to 5.1 ± 0.8 mM (P < 0.01), and base excess 1.1 ± 2.2 to -3.6 ± 1.7 mM (P < 0.05). Invasive organ-specific monitoring confirmed reduced tissue oxygen delivery; oxygen tension decreased and lactate increased in all tissues, but moderately in brain. Blood volume replacement with PlasmaLyte® improved primary outcome measures toward baseline, confirmed by organ-specific measures, despite hemoglobin reduced from baseline 10.8 ± 1.2 to 5.9 ± 1.1 g/dL post-resuscitation (P < 0.01). Non-invasive measures of tissue oxygen delivery and oxygen debt repayment are suitable outcomes to inform Patient Blood Management of hemorrhagic shock, translatable for pre-clinical assessment of novel resuscitation strategies.

Association of perioperative red blood cell transfusions with all-cause and cancer-specific death in patients undergoing surgery for gastrointestinal cancer.

464 Background: Perioperative anemia and red blood cell (RBC) transfusions are common in patients undergoing gastrointestinal cancer surgery. To adequately balance the risks and benefits of transfusion, clinicians must understand the potential effect of transfusions on long-term outcomes. Methodologic issues have limited previous studies exploring the association between RBC transfusion and survival in this specific patient population. Our objective was to determine, among patients who have undergone gastrointestinal cancer resection, if perioperative RBC transfusions are associated with higher risk of all-cause and cancer-specific death. Methods: In this population-based retrospective cohort study, we used administrative datasets containing routinely collected data from Ontario, Canada. Patients who underwent gastrointestinal cancer resection between January 1, 2007 and March 31, 2019 and survived at least 90 days postoperatively were eligible for inclusion. All-cause death from the ninetieth post-operative day was compared between groups using Kaplan-Meier methods and Cox proportional hazards models. Cancer-specific death was compared using competing risk methods. Regression adjusted for potential confounders. Sensitivity analyses, including the E-value, evaluated the robustness of estimates. Results: We identified 74,962 patients (mean age, 67.7 years; 55.4% male; 79.7% colorectal cancer) who underwent resection for gastrointestinal cancer and survived at least 90 days after surgery. Over a median follow-up of 4.1 years (interquartile range 1.9-5.0 years), patients who received RBC transfusions demonstrated increased hazards of all-cause and cancer-specific death relative to patients who were not transfused (hazard ratio: 1.39, 95% confidence interval 1.34 to 1.44; cause-specific hazards ratio: 1.36, 1.30 to 1.43). The adjusted risk of all-cause death was higher in early follow-up intervals (3-6 months post-operatively) but remained elevated in each subsequent interval over 5 years. Conclusions: RBC transfusion among patients with gastrointestinal cancer is associated with increased all-cause death; this persisted over time suggesting a long-term effect of perioperative transfusion. These findings should help clinicians balance the risks and benefits of transfusion and highlight the need for well-designed, multicenter randomized trials to determine if aggressive transfusion avoidance protocols could improve patient survival after gastrointestinal cancer surgery.

Cholecystectomy in Sickle Cell Anemia Patients: Perioperative Outcome of 364 Cases From the National Preoperative Transfusion Study

AbstractCholecystectomy is the most common surgical procedure performed in sickle cell anemia (SCA) patients. We investigated the effects of transfusion and surgical method on perioperative outcome. A total of 364 patients underwent cholecystectomy: group 1 (randomized to aggressive transfusion) 110 patients; group 2 (randomized to conservative transfusion) 120 patients; group 3 (nonrandomized nontransfusion) 37 patients; and group 4 (nonrandomized transfusion) 97 patients. Patients were similar except group 3 patients were more likely to be female, over 20 years old, smokers, and more healthy by American Society of Anesthesiologists (ASA) physical status score. Total complication rate was 39%: sickle cell events 19%; intraoperative or recovery room events 11%; transfusion complications 10%; postoperative surgical events 4%; and death 1%. Group 3 patients had the highest incidence of sickle cell events (32%). Open cholecystectomies were performed in 58% and laparoscopic in 42%. Laparoscopic patients were younger and more healthy by ASA score. Laparoscopic patients had longer anesthesia time (3.2 v 2.9 hours), but shorter hospitalization time (6.4 days v 9.8). Complications were similar between these two groups. We conclude that SCA patients undergoing cholecystectomy have a high perioperative morbidity, and the incidence of sickle cell events may be higher in patients not preoperatively transfused. We recommend a conservative preoperative transfusion regimen, and we encourage the use of the laparoscopic technique for SCA patients undergoing elective cholecystectomy.

Early re-laparotomy for patients with high-grade liver injury after damage-control surgery and perihepatic packing.

PurposeThe likelihood of re-bleeding after damage-control surgery (DCS) and perihepatic packing for high-grade liver injuries is a major concern. Thus, although early re-laparotomy tends to be recommended, we conducted this study to evaluate the feasibility of performing definite laparotomy within ≤ 48 h in this clinical population.MethodsThe subjects of this retrospective study were 65 patients (n = 24, ≤ 48-h group; n = 41, > 48-h group) who underwent DCS and perihepatic packing. The primary outcome was the rate of repacking for bleeding during re-laparotomy and the secondary outcomes were mortality and length of stay in the intensive care unit (ICU).ResultsThe ≤ 48-h group had a higher rate of angioembolization and transfusion of red blood cells (RBCs), fresh frozen plasma, and platelets, but the rates of repacking and mortality were not significantly different between the groups. However, the incidence of pneumonia and ventilation support requirement were significantly lower in the ≤ 48-h group than in the > 48-h group.ConclusionThe re-laparotomy performed within ≤ 48 h after DCS and perihepatic packing is feasible for patients with high grade liver injury, using angioembolization and aggressive transfusion, as required. Early re-laparotomy reduces the need for prolonged ventilator support and the incidence of ventilator-associated pneumonia.