Improving Transplant-free Survival With Low-volume Plasma Exchange to Treat Children With Rodenticide Induced Hepatotoxicity.

Background: In a prior report, no patient with rodenticidal hepatotoxicity who met Kochi criteria (MELD score ≥36 or baseline INR ≥6 with hepatic encephalopathy) (PMID: 26310868) for urgent liver transplantation survived with medical management alone. Plasma exchange (PLEX) may improve survival in these patients. Objectives: We describe our experience with low-volume PLEX (PLEX-LV) in treating rodenticide ingestion induced hepatotoxicity in children. Methods: From prospectively collected database of rodenticidal hepatotoxicity patients managed as in-patient with department of Hepatology from December 2017 to August 2021, we retrospectively studied outcomes in children (≤18 years). Hepatotoxicity was categorized as acute liver injury (ALI, coagulopathy alone) or acute liver failure (ALF, coagulopathy and encephalopathy). Kochi criteria was used to assess need for urgent liver transplantation. The primary study outcome was one-month survival. Results: Of the 110 rodenticidal hepatotoxicity patients, 32 children (females: 56%; age: 16 [4.7-18] years; median, range) constituted the study patients. The study patients presented 4 (1-8) days after poison consumption (impulsive suicidal intent:31, accidental:1). Twenty children (62%) had ALI [MELD: 18 (8-36)] and 12 (38%) had ALF [MELD: 37 (24-45)].All children received standard medical care, including N-acetyl cysteine; ALF patients also received anti-cerebral edema measures. None of the patient families opted for liver transplantation. Seventeen children (ALI: 6, ALF: 11) were treated with PLEX-LV (3 [1-5] sessions, volume of plasma exchanged per session: 26 [13-38] ml/kg body weight) and peri-procedure low dose prednisolone.At 1 month, 28 of the 32 children (87.5%) were alive (4 ALF patients died). Of 10 children who met Kochi listing criteria for urgent liver transplantation, two children were ineligible for PLEX-LV (due to hemodynamic instability) and of the remaining 8 children treated by PLEX-LV, 6 (75%) survived. Conclusions: PLEX-LV shows promise as an effective non-liver transplant treatment in children with rodenticidal hepatotoxicity.

Total arch replacement with extended branched stented anastomosis frozen elephant trunk repair for type A dissection improves operative outcome.

Objective: Emergency surgical repair is the standard treatment for acute aortic dissection type A. However, the surgical risk of total arch replacement remains high. The Viabahn Open Revascularization TEChnique has been used for supra-aortic reconstruction during total arch replacement. This Cleveland Clinic technique is called "branched stented anastomosis frozen elephant trunk repair." Our total arch replacement with reconstructed extended branched stented anastomosis frozen elephant trunk repair requires no unnecessary cervical artery exposure. We compared the outcomes of extended branched stented anastomosis frozen elephant trunk repair and conventional total arch replacement in acute aortic dissection type A. Methods: We compared the clinical course of patients undergoing total arch replacement using sutureless direct branch vessel stent grafting with frozen elephant trunk (extended branched stented anastomosis frozen elephant trunk repair) for acute aortic dissection type A with patients undergoing conventional total arch replacement. For the procedure, the aortic arch was transected circumferentially distal to the brachiocephalic artery origin. Frozen elephant trunk was fenestrated by heating with a cautery, and the self-expandable stent graft was delivered into the branch vessels through the fenestration. Results: Of 58 cases, 21 and 37 were classified in the extended branched stented anastomosis frozen elephant trunk repair and conventional total arch replacement groups, respectively. The times (minutes) of selective antegrade cerebral perfusion (75 ± 24, 118 ± 47), total operation (313 ± 83, 470 ± 151), and cardiopulmonary bypass (195 ± 46, 277 ± 96) were significantly better in the extended branched stented anastomosis frozen elephant trunk repair group (P < .001). Six surgical deaths occurred: 2 (9%) in the extended branched stented anastomosis frozen elephant trunk repair group and 4 (10%) in the conventional total arch replacement group. In all cases, only 1 patient (2%) in the conventional total arch replacement group had a branch artery-related complication during the postoperative follow-up period. In the extended branched stented anastomosis frozen elephant trunk repair group, blood product use significantly decreased (P < .05). Conclusions: Extended branched stented anastomosis frozen elephant trunk repair has shown comparable safety and efficacy to conventional total arch replacement and can be used for acute aortic dissection type A emergency repair. It optimizes true lumen perfusion and facilitates supra-aortic artery remodeling.

Targeting repair of the vascular endothelium and glycocalyx after traumatic injury with plasma and platelet resuscitation.

Severely injured patients with hemorrhagic shock can develop endothelial dysfunction, systemic inflammation, and coagulation disturbances collectively known as the endotheliopathy of trauma (EOT). Shedding of the endothelial glycocalyx occurs early after injury, contributes to breakdown of the vascular barrier, and plays a critical role in the pathogenesis of multiple organ dysfunction, leading to poor outcomes in trauma patients. In this review we discuss (i) the pathophysiology of endothelial glycocalyx and vascular barrier breakdown following hemorrhagic shock and trauma, and (ii) the role of plasma and platelet transfusion in maintaining the glycocalyx and vascular endothelial integrity.

Autologous blood transfusion in acute type A aortic dissection decreased blood product consumption and improved postoperative outcomes.

Objective: To evaluate the effect of autologous blood use on blood product consumption and outcomes after acute type A aortic dissection repair. Methods: From 2010 to October 2020, 497 patients underwent open acute type A aortic dissection repair, including those with autologous blood harvesting before cardiopulmonary bypass and transfusion after cardiopulmonary bypass (autologous blood transfusion [ABT], n = 397) and without autologous blood harvesting and transfusion (No-ABT, n = 100). The median ABT volume was 900 mL. Using propensity score matching, 89 matched pairs were identified based on age, sex, body mass index, preoperative hemoglobin, acute preoperative stroke, previous cardiac surgery, and cardiogenic shock. Results: After propensity score matching, both groups were similar in demographic characteristics and aortic procedures. The ABT group required significantly less intraoperative transfusion of blood products (6 vs 11 units; P < .0001), including packed red blood cells (2 vs 4), fresh frozen plasma (2 vs 4), platelets (2 vs 2), and cryoprecipitate (0 vs 1); and combined intraoperative and postoperative transfusion (9 vs 13; P < .001). ABT was protective against intra- and postoperative blood product transfusion (odds ratio, 0.28; P = .01). The ABT group had significantly less sepsis, acute renal failure requiring dialysis, reintubation, and shorter intubation times and postoperative lengths of stay. Operative mortality was 6.7% in the ABT group versus 13% in the No-ABT group (P = .14). The midterm survival was similar between the 2 groups (5 year: 76% vs 74%). ABT had a hazard ratio of 0.81 for midterm mortality (P = .41). Conclusions: Autologous blood transfusion was associated with better short-term outcomes and could be used routinely for acute type A aortic dissection repair. External multicenter prospective validation would be warranted.

A case report of two siblings with hypertyrosinemia type 1 presenting with hepatic disease with different onset time and severity.

Hereditary tyrosinemia type 1 (HT1) is an autosomal recessive disorder caused by a defect in fumarylacetoacetate hydroxylase (FAH) encoded by the FAH gene. Patients with HT1 disorder present with increased blood tyrosine, succinyl acetoacetate, and succinyl acetone levels, and develop clinical manifestations including liver failure, kidney tubular dysfunction, growth failure, rickets, pseudo-porphyric crises, and hepatocellular carcinoma. We encountered two siblings with HT1. Among the siblings, the elder brother developed acute liver failure with coagulopathy at the age of 2 months and was rescued by liver transplantation (LT) following combination therapy with continuous hemodiafiltration and plasma exchange. The younger sister was followed up from the prenatal period for signs of HT1 due to prior history of the condition in her sibling. She was initially considered a carrier of HT1 owing to the lack of overt signs of the disease and negative urine screening for succinyl acetone (SA). She was eventually diagnosed with HT1 because of liver disorder at 9 months of age, associated with a positive urine SA result. Her disease state was controlled by treatment with nitisinone (NTBC). DNA analysis of both siblings identified heterozygous status for a previously reported FAH pathogenic allele (c.782C > T) and a novel likely pathogenic variant (c.688C.G). The siblings have stable lives with no developmental delay or impaired growth. NTBC treatment is effective in preventing the progression of liver and kidney diseases. However, even in cases treated without LT, clinicians should follow up the clinical outcomes over long term, as patients may require LT when developing complications, such as hepatocellular carcinoma.

Alterations in heparan sulfate proteoglycan synthesis and sulfation and the impact on vascular endothelial function.

The glycocalyx attached to the apical surface of vascular endothelial cells is a rich network of proteoglycans, glycosaminoglycans, and glycoproteins with instrumental roles in vascular homeostasis. Given their molecular complexity and ability to interact with the intra- and extracellular environment, heparan sulfate proteoglycans uniquely contribute to the glycocalyx's role in regulating endothelial permeability, mechanosignaling, and ligand recognition by cognate cell surface receptors. Much attention has recently been devoted to the enzymatic shedding of heparan sulfate proteoglycans from the endothelial glycocalyx and its impact on vascular function. However, other molecular modifications to heparan sulfate proteoglycans are possible and may have equal or complementary clinical significance. In this narrative review, we focus on putative mechanisms driving non-proteolytic changes in heparan sulfate proteoglycan expression and alterations in the sulfation of heparan sulfate side chains within the endothelial glycocalyx. We then discuss how these specific changes to the endothelial glycocalyx impact endothelial cell function and highlight therapeutic strategies to target or potentially reverse these pathologic changes.

The endothelial glycocalyx in critical illness: A pediatric perspective.

The vascular endothelium is the interface between circulating blood and end organs and thus has a critical role in preserving organ function. The endothelium is lined by a glycan-rich glycocalyx that uniquely contributes to endothelial function through its regulation of leukocyte and platelet interactions with the vessel wall, vascular permeability, coagulation, and vasoreactivity. Degradation of the endothelial glycocalyx can thus promote vascular dysfunction, inflammation propagation, and organ injury. The endothelial glycocalyx and its role in vascular pathophysiology has gained increasing attention over the last decade. While studies characterizing vascular glycocalyx injury and its downstream consequences in a host of adult human diseases and in animal models has burgeoned, studies evaluating glycocalyx damage in pediatric diseases are relatively few. As children have unique physiology that differs from adults, significant knowledge gaps remain in our understanding of the causes and effects of endothelial glycocalyx disintegrity in pediatric critical illness. In this narrative literature overview, we offer a unique perspective on the role of the endothelial glycocalyx in pediatric critical illness, drawing from adult and preclinical data in addition to pediatric clinical experience to elucidate how marked derangement of the endothelial surface layer may contribute to aberrant vascular biology in children. By calling attention to this nascent field, we hope to increase research efforts to address important knowledge gaps in pediatric vascular biology that may inform the development of novel therapeutic strategies.

Endothelial glycocalyx degradation during sepsis: Causes and consequences.

The glycocalyx is a ubiquitous structure found on endothelial cells that extends into the vascular lumen. It is enriched in proteoglycans, which are proteins attached to the glycosaminoglycans heparan sulfate, chondroitin sulfate, dermatan sulfate, keratan sulfate, and hyaluronic acid. In health and disease, the endothelial glycocalyx is a central regulator of vascular permeability, inflammation, coagulation, and circulatory tonicity. During sepsis, a life-threatening syndrome seen commonly in hospitalized patients, the endothelial glycocalyx is degraded, significantly contributing to its many clinical manifestations. In this review we discuss the intrinsically linked mechanisms responsible for septic endothelial glycocalyx destruction: glycosaminoglycan degradation and proteoglycan cleavage. We then examine the consequences of local endothelial glycocalyx loss to several organ systems and the systemic consequences of shed glycocalyx constituents. Last, we explore clinically relevant non-modifiable and modifiable factors that exacerbate or protect against endothelial glycocalyx shedding during sepsis.

A multicenter analysis of the role of prophylactic transfusion of blood products in patients with cirrhosis and esophageal varices undergoing endoscopic band ligation.

BACKGROUND & AIMS: Prophylactic administration of platelets and fresh frozen plasma (FFP) has been recommended in patients with cirrhosis with low platelets and/or prolonged international normalized ratio (INR) without scientific evidence to support this practice. In this analysis, we evaluated the use of prophylactic administration of blood products in outpatients with cirrhosis undergoing endoscopic band ligation (EBL). METHODS: This is a multicenter retrospective analysis of consecutive EBL procedures in patients with cirrhosis at 4 hospitals in Spain from 01/2010-01/2017. FFP and/or platelet transfusion were given at the discretion of the physician if INR was >1.5 and/or platelet count <50x109/L. Patient demographics, endoscopic findings, bleeding events after EBL, and the use of prophylactic FFP or platelets were recorded. RESULTS: A total of 536 patients underwent 1,472 EBL procedures: 72% male; main etiology HCV and alcohol (72%); median MELD score 11; Child-Pugh A/B/C (59/33/8%). EBL procedures were performed for primary (51%) or secondary (49%) prophylaxis. A median of 2 procedures per patient were performed.1-4 FFP and/or platelets were administered in 41 patients (7.6%). The prophylactic transfusion protocol was followed in 16% and 28% of procedures with high INR and/or low platelets, respectively. Post-EBL bleeding occurred in 26 out of 536 patients (4.8%) and in 33 out of 1,472 procedures (2.2%). Bleeding was due to post-EBL ulcers in 21 patients and due to band dislodgment in 5. In 6 patients, bleeding occurred within 24 hours and in the remaining patients it occurred within 2 weeks after EBL. In those that bled, 7 met criteria for transfusion (2 for FFP and 5 for platelets), of whom only 1 received FFP and 4 received platelets; the remaining 19 patients did not meet criteria for transfusion. There was no association between INR or platelet count and bleeding events. Univariate and multivariate analysis revealed that Child-Pugh and MELD scores were risk factors for post-EBL bleeding. CONCLUSIONS: The incidence of post-EBL bleeding is low and is associated with advanced liver disease. Post-EBL bleeding was not related to baseline INR/platelet count and most outpatients with post-EBL bleeding did not meet criteria for prophylactic transfusion. LAY SUMMARY: Patients with chronic liver disease or cirrhosis and enlarged veins (varices) of the esophagus that can potentially bleed commonly need an endoscopy to treat these varices with elastic rubber bands (endoscopic band ligation). Some patients have low platelet counts or prolonged coagulation tests. This analysis of 4 centers evaluated the use of prophylactic administration of blood products in outpatients with cirrhosis undergoing endoscopic band ligation. The results showed that bleeding after band ligation is uncommon and that if bleeding occurs it does not seem to be related with coagulation tests or the administration of blood products to prevent bleeding after band ligation of esophageal varices.

Balloon-occluded antegrade transvenous obliteration of rectal varices: A case report.

Patients with liver cirrhosis frequently experience rectal variceal bleeding subsequent to portal hypertension. Unlike gastroesophageal variceal bleeding, a well-established guideline does not exist in terms of management of bleeding rectal varices. A 75-year-old male with non-alcoholic-steatohepatitis induced cirrhosis presented with a 3-day history of severe rectorrhagia. Considering patient's clinical history, TIPS was not performed and thus, a novel endovascular technique termed balloon-occluded antegrade transvenous obliteration was considered. Under conscious sedation, an occlusion was made through balloon catheter by sclerotic agents including air/sodium tetradecyl sulfate/Lipiodol. After the procedure, and in the 6 months follow up period the patient's hemodynamic status was stable and he recovered without any serious complications. Balloon-occluded antegrade transvenous obliteration is a feasible and safe modality for treating rectal varices bleeding and could be used as an alternative approach in patients with contraindications to traditional treatments.

Conventional versus miniaturized cardiopulmonary bypass: A systematic review and meta-analysis.

Objective: A meta-analysis of randomized controlled trials was performed to compare the effects of miniaturized extracorporeal circulation (MECC) and conventional extracorporeal circulation (CECC) on morbidity and mortality rates after cardiac surgery. Methods: A comprehensive literature search was conducted using Ovid, PubMed, Medline, EMBASE, and the Cochrane databases. Randomized controlled trials from the year 2000 with n > 40 patients were considered. Key search terms included variations of "mini," "cardiopulmonary," "bypass," "extracorporeal," "perfusion," and "circuit." Studies were assessed for bias using the Cochrane Risk of Bias tool. The primary outcomes were postoperative mortality and stroke. Secondary outcomes included arrhythmia, myocardial infarction, renal failure, blood loss, and a composite outcome comprised of mortality, stroke, myocardial infarction and renal failure. Duration of intensive care unit, and hospital stay was also recorded. Results: The 42 studies eligible for this study included a total of 2154 patients who underwent CECC and 2196 patients who underwent MECC. There were no significant differences in any preoperative or demographic characteristics. Compared with CECC, MECC did not reduce the incidence of mortality, stroke, myocardial infarction, and renal failure but did significantly decrease the composite of these outcomes (odds ratio, 0.64; 95% confidence interval [CI], 0.50-0.81; P = .0002). MECC was also associated with reductions in arrhythmia (odds ratio, 0.67; 95% CI, 0.54-0.83; P = .0003), blood loss (mean difference [MD], -96.37 mL; 95% CI, -152.70 to -40.05 mL; P = .0008), hospital stay (MD, -0.70 days; 95% CI, -1.21 to -0.20 days; P = .006), and intensive care unit stay (MD, -2.27 hours; 95% CI, -3.03 to -1.50 hours; P < .001). Conclusions: MECC demonstrates clinical benefits compared with CECC. Further studies are required to perform a cost-utility analysis and to assess the long-term outcomes of MECC. These should use standardized definitions of endpoints such as mortality and renal failure to reduce inconsistency in outcome reporting.

Sepsis Following Liver Biopsy in a Liver Transplant Recipient: Case Report and Review of Literature.

Percutaneous liver biopsy is a relatively safe procedure with low complication rates. Infections following liver biopsy are uncommon and can lead to a poor outcome. There are limited data on liver biopsy-related infections among liver transplant (LT) recipients. Also, there is a paucity of data regarding the use of prophylactic antibiotics in LT patients undergoing percutaneous liver biopsy. We report a case of systemic sepsis following percutaneous liver biopsy in a LT recipient with choledochojejunal anastomosis. This was followed by severe rejection and deterioration of liver function and recurrence of primary sclerosing cholangitis (PSC) to the extent that he has been listed for retransplantation. This case report emphasizes the potential risk of sepsis in LT recipients with bilioenteric anastomosis undergoing percutaneous liver biopsy. This increased risk may warrant periprocedural broad spectrum antibiotic prophylaxis, in this subgroup of patients.

Sickle Hepatopathy.

Sickle hepatopathy is an umbrella term describing various pattern of liver injury seen in patients with sickle cell disease. The disease is not uncommon in India; in terms of prevalence, India is second only to Sub-Saharan Africa where sickle cell disease is most prevalent. Hepatic involvement in sickle cell disease is not uncommon. Liver disease may result from viral hepatitis and iron overload due to multiple transfusions of blood products or due to disease activity causing varying changes in vasculature. The clinical spectrum of disease ranges from ischemic injury due to sickling of red blood cells in hepatic sinusoids, pigment gall stones, and acute/chronic sequestration syndromes. The sequestration syndromes are usually episodic and self-limiting requiring conservative management such as antibiotics and intravenous fluids or packed red cell transfusions. However, rarely these episodes may present with coagulopathy and encephalopathy like acute liver failure, which are life-threatening, requiring exchange transfusions or even liver transplantation. However, evidence for their benefits, optimal indications, and threshold to start exchange transfusion is limited. Similarly, there is paucity of the literature regarding the end point of exchange transfusion in this scenario. Liver transplantation may also be beneficial in end-stage liver disease. Hydroxyurea, the antitumor agent, which is popularly used to prevent life-threatening complications such as acute chest syndrome or stroke in these patients, has been used only sparingly in hepatic sequestrations. The purpose of this review is to provide insights into epidemiology of sickle cell disease in India and pathogenesis and classification of hepatobiliary involvement in sickle cell disease. Finally, various management options including exchange transfusion, liver transplantation, and hydroxyurea in hepatic sequestration syndromes will be discussed in brief.

Outcome of Conservative Therapy in Coronavirus disease-2019 Patients Presenting With Gastrointestinal Bleeding.

BACKGROUND/OBJECTIVE: There is a paucity of data on the management of gastrointestinal (GI) bleeding in patients with Coronavirus disease -2019 (COVID-19) amid concerns about the risk of transmission during endoscopic procedures. We aimed to study the outcomes of conservative treatment for GI bleeding in patients with COVID-19. METHODS: In this retrospective analysis, 24 of 1342 (1.8%) patients with COVID-19, presenting with GI bleeding from 22nd April to 22nd July 2020, were included. RESULTS: The mean age of patients was 45.8 ± 12.7 years; 17 (70.8%) were males; upper GI (UGI) bleeding: lower GI (LGI) 23:1. Twenty-two (91.6%) patients had evidence of cirrhosis- 21 presented with UGI bleeding while one had bleeding from hemorrhoids. Two patients without cirrhosis were presumed to have non-variceal bleeding. The medical therapy for UGI bleeding included vasoconstrictors-somatostatin in 17 (73.9%) and terlipressin in 4 (17.4%) patients. All patients with UGI bleeding received proton pump inhibitors and antibiotics. Packed red blood cells (PRBCs), fresh frozen plasma (FFPs) and platelets were transfused in 14 (60.9%), 3 (13.0%) and 3 (13.0%), respectively. The median PRBCs transfused was 1 (0-3) unit(s). The initial control of UGI bleeding was achieved in all 23 patients and none required an emergency endoscopy. At 5-day follow-up, none rebled or died. Two patients later rebled, one had intermittent bleed due to gastric antral vascular ectasia, while another had rebleed 19 days after discharge. Three (12.5%) cirrhosis patients succumbed to acute hypoxemic respiratory failure during hospital stay. CONCLUSION: Conservative management strategies including pharmacotherapy, restrictive transfusion strategy, and close hemodynamic monitoring can successfully manage GI bleeding in COVID-19 patients and reduce need for urgent endoscopy. The decision for proceeding with endoscopy should be taken by a multidisciplinary team after consideration of the patient's condition, response to treatment, resources and the risks involved, on a case to case basis.

Partial warfarin reversal prior to hip fracture surgical intervention in geriatric trauma patients effects on blood loss and transfusions.

BACKGROUND: Warfarin reversal is typically sought prior to surgery for geriatric hip fractures; however, patients often proceed to surgery with partial warfarin reversal. The effect of partial reversal (defined as having an international normalized ratio [INR] > 1.5) remains unclear. METHODS: This was a retrospective cohort study. Geriatric patients (≥65 y/o) admitted to six level I trauma centers from 01/2014-01/2018 with isolated hip fractures requiring surgery who were taking warfarin pre-injury were included. Warfarin reversal methods included: vitamin K, factor VIIa, (a)PCC, fresh frozen plasma (FFP), and the "wait and watch" method. An INR of ≤ 1.5 defined complete reversal. The primary outcome was the volume of blood loss during surgery; other outcomes included packed red blood cell (pRBC) and FFP transfusions, and time to surgery. RESULTS: There were 135 patients, 44% partially reversed and 56% completely reversed. The median volume of blood loss was 100 mL for both those completely and partially reversed, p = 0.72. There was no difference in the proportion of patients with blood loss by study arm, 95% vs. 95%, p > 0.99. Twenty-five percent of those completely reversed and 39% of those partially reversed had pRBCs transfused, p = 0.08. Of those completely reversed 5% received an FFP transfusion compared to 14% of those partially reversed, p = 0.09. There were no statistically significant differences observed for the volume of pRBC or FFP transfused, or for time to surgery. CONCLUSIONS: Partial reversal may be safe for blood loss and blood product transfusions for geriatric patients with isolated hip fractures. Complete warfarin reversal may not be necessary prior to hip fracture surgery, especially for mildly elevated INRs.

Is anticoagulation reversal necessary prior to surgical treatment of geriatric hip fractures?

OBJECTIVE: Hip fracture surgery in geriatric patients on anticoagulants may increase the risk for blood loss. Anticoagulation reversal may lower these risks; however, data on blood loss and transfusions are limited. The study purpose was to compare outcomes between hip fracture patients 1) not on anticoagulants 2) whose anticoagulants were reversed, and 3) whose anticoagulants were not reversed. METHODS: This four-year retrospective cohort study at six Level 1 Trauma Centers enrolled geriatric patients (≥65) with isolated hip fractures. The primary outcome was total hospital blood loss (ml). Secondary outcomes: hospital length of stay (HLOS) and volume of packed red blood cells (pRBC) transfusions (ml). Statistical analyses included: Fisher's, chi-squared, Kruskal-Wallis, linear mixed-effect and logistic regression. Bonferroni adjusted alpha = 0.025. RESULTS: Of the 459 patients, 189 (41%) were not on anticoagulants, 186 (41%) were reversed, and 84 (18%) were not reversed. The LS mean (SE) blood loss was 134 ml (12) for not reversed patients and 159 (17) for reversed patients; no significant difference compared to those not on anticoagulants [138 (12)], p-diff = 0.14 and 0.83, respectively. The LS mean (SE) HLOS was significantly longer for the reversed patients, 7.7 (0.4) days, when compared to those not on anticoagulants, 6.8 (0.4), p = 0.02, and when compared to those not reversed, 6.3 (0.6), p = 0.01. There was no significant difference in pRBC transfusions. CONCLUSION: Not reversing anticoagulants for geriatric hip fractures was not associated with increased volume of blood loss or transfusions when compared to those reversed. Delayed surgery for anticoagulant reversal may be unnecessary and contributing to an increased HLOS.

Data on the application of early coagulation support protocol in the management of major trauma patients.

This article provides additional data on the application of early coagulation support protocol in the management of major trauma patients. Data come from a retrospective analysis reported in the article "Early coagulation support protocol: a valid approach in real-life management of major trauma patients. Results from two Italian centres" [1]. Data contain information about the relationship between differences in resource use and mortality outcomes, and patient demographic and clinical features at presentation. Furthermore, a comparison between resource consumption, the probability of multiple transfusions and the mortality outcomes among propensity-score matched patients is reported.

Fresh frozen plasma for on-demand hereditary angioedema treatment in South Africa and Iran.

BACKGROUND: International guideline-recommended on-demand treatments for hereditary angioedema (HAE) include: C1-esterase inhibitor (plasma-derived or recombinant), or bradykinin-receptor antagonists. In most low- and middle-income countries (LMIC) these products are not registered or are unaffordable. Solvent-detergent, fresh or freeze-dried plasma therapy is thus the only available on-demand treatment in these settings; but published data on efficacy and safety are limited. This study evaluated the efficacy and safety of on-demand plasma treatment of acute HAE in two LMICs. METHODS: A retrospective folder or patient registry review of acute swelling episodes necessitating emergency room attendance amongst known HAE patients was conducted at treatment centers in South Africa and Iran. Data collected included the site of angioedema, timing and amount of fresh frozen plasma (FFP) administered, time-to-resolution, hospital length of stay and adverse events. RESULTS: There were 176 acute swelling episodes amongst 43 HAE patients; 98 were treated with FFP. The face, upper airway, and abdomen were involved in 15.3% (15/98), 53.1% (52/98) and 29.6% (29/98) of episodes treated with FFP respectively. Median (interquartile range ([IQR]) of FFP administered was 400 (280-560) mLs. In all episodes except two, FFP led to resolution, with median (IQR) hours to resolution 4 (2-12). Five transfusion reactions occurred, with one case of anaphylaxis and no deaths; giving an adverse reaction rate of 5%. Differences between South Africa and Iran included: (1) proportion of HAE type II(2) median (IQR) hours to FFP administration and hospitalization, (3) number of intubations after FFP infusion. Healthcare cost for FFP treatment was USD369- 791 in South Africa and USD275-550 in Iran, largely influenced by hospital length of stay. CONCLUSIONS: Plasma (fresh-frozen) remains the only available effective on-demand treatment for acute HAE in many countries. FFP is effective and safe, but time-to-resolution is slower and adverse events are more frequent than published data on targeted therapies. Overall healthcare cost of FFP approaches that of targeted therapies - now available through global access programs - when hospitalization is prolonged.

Addition of Somatostatin After Successful Endoscopic Variceal Ligation Does not Prevent Early Rebleeding in Comparison to Placebo: A Double Blind Randomized Controlled Trial.

BACKGROUND: Efficacy of endoscopic sclerotherapy in controlling acute variceal bleeding is significantly improved when vasoactive drug is added. Endoscopic variceal ligation (EVL) is superior to sclerotherapy. Whether efficacy of EVL will also improve with addition of somatostatin is not known. We compared EVL plus somatostatin versus EVL plus placebo in control of acute variceal bleeding. METHODS: Consecutive cirrhotic patients with acute esophageal variceal bleeding were enrolled. After emergency EVL, patients were randomized to receive either somatostatin (250 mcg/hr) or placebo infusion. Primary endpoint was treatment failure within 5 days. Treatment failure was defined as fresh hematemesis ≥2 h after start of therapy, or a 3 gm drop in Hb, or death. RESULTS: 61 patients were enrolled (EVL plus somatostatin group, n = 31 and EVL plus placebo group, n = 30). The baseline characteristics were similar. Within the initial 5-day period, the frequency of treatment failure was similar in both the groups (EVL plus somatostatin group 8/31 [26%] versus EVL plus placebo group 7/30 [23%]; P = 1.000). The mortality was also similar in the two groups (3/31 [10%] vs. 3/30 [10%]; P = 1.000). Baseline HVPG ≥19 mm Hg and active bleeding at index endoscopy were independent predictors of treatment failure. CONCLUSIONS: Addition of somatostatin infusion to EVL therapy does not offer any advantage in control of acute variceal bleeding or reducing mortality. The reason for this may be its failure to maintain sustained reduction in portal pressure for five days. Active bleeding at index endoscopy and high baseline HVPG should help choose early alternative treatment options. Trial registered with ClincalTrials.gov vide NCT01267669.

Helicopter In-flight Resuscitation with Freeze-dried Plasma of a Patient with a High-velocity Gunshot Wound to the Neck in Afghanistan - A Case Report.

Massive hemorrhage with coagulopathy is one of the leading causes of preventable death in the battlefield. The development of freeze-dried plasma (FDP) allows for early treatment with coagulation-optimizing resuscitation fluid in the prehospital setting. This report describes the first prehospital use of FDP in a patient with carotid artery injury due to a high-velocity gunshot wound (HVGSW) to the neck. It also describes in-flight constitution and administration of FDP in a Medevac Helicopter. Early administration of FDP may contribute to hemodynamic stabilization and reduction in trauma-induced coagulopathy and acidosis. However, large-scale studies are needed to define the prehospital use of FDP and other blood products.