Mean Hemoglobin Decrease Research Articles

Macitentan: Endothelin receptor antagonist

Macitentan: Endothelin receptor antagonist

Analysis of the factors affecting blood loss in percutaneous nephrolithotomy: A registry of the Spanish Association of Urology in the supine position

ObjectivePercutaneous nephrolithotomy (PCNL) is the minimally invasive procedure of choice for removing renal stones larger than 2cm. This study has aimed to identify the different variables that might influence decrease of hemoglobin during the surgery performed in supine position. Materials and methodsA prospective, multicenter, observational study of supine PCNL, based on the Spanish Association of Urology database, was analyzed. The different preoperative and postoperative factors that might affect the decrease of hemoglobin were assessed: demographics and anthropometric data, comorbidities, size and location of the stones, anatomical variants and technical aspects of the procedure. ResultsFrom September 2008 to December 2012, 397 supine PCNL procedures performed in 15 Spanish centers were registered. Mean hemoglobin decrease was 2.3±1.5g/dl and overall blood transfusion rate was 5.5%. No statistically significant differences were found between genders, body mass index (BMI) and age in terms of blood loss. There were also no differences between patients with cardiovascular, hypertensive, diabetic and anticoagulant treatment background. Blood loss was not significantly influenced by stone size and location. Technical aspects of the procedure as operative time (>120min ≤), access to the pelvi-caliceal system (ultrasound, fluoroscopy), percutaneous tract dilation technique (Alken, balloon or Amplatz) or placement of nephrostomy (tube versus tubeless) were not associated with differences in pre-op/post-op hemoglobin. Only multiple percutaneous tracts (≥2) and middle calix access were statistically significantly (P=.03 and P=.01) related with less blood loss. ConclusionsPCNL in supine position is a minimally invasive procedure for removal of large (≥2cm) and multiple renal stones, with a low incidence of blood loss and minimal transfusion rate. Multiple percutaneous tracts and middle calix puncture were the only statistically significant variables associated with decrease in hemoglobin levels.

Ribavirin suppresses erythroid differentiation and proliferation in chronic hepatitis C patients.

Combination therapy with pegylated interferon (pegIFN) plus ribavirin (RBV) is the standard of care for chronic hepatitis C. One of the major treatment-related side effects is anaemia, attributed to RBV-induced haemolysis. However, haemolysis biomarkers are not present in all patients supporting the existence of other pathogenetic mechanisms. We studied the role of RBV in inducing haemolysis and its effects on erythropoiesis. In 18 hepatitis C virus (HCV) genotype 2 patients treated with pegIFN-alpha-2a (180 mcg/week) plus RBV (800 mg/day) for 24 weeks and in 10 hepatitis B virus (HBV) patients treated with pegIFN-alpha-2a (180 mcg/week) for 48 weeks, haemolysis was assessed by serum LDH, haptoglobin and reticulocyte count. Erythropoiesis was evaluated both ex vivo, analysing the clonogenic activity of patients' erythroid progenitors, as well as in vitro adding pegIFN and RBV to liquid cultures obtained from CD34+ cells of healthy volunteers. The majority of patients developed anaemia; the week 4 mean haemoglobin decrease was greater in HCV than in HBV patients (1.7 vs 0.47 g/dL, P = 0.01). Only three HCV patients (17%) and no HBV patients showed signs of haemolysis. The 15 nonhaemolytic HCV patients and all HBV patients showed a delay in erythroid differentiation, with a reduction in colony number and a relative increase in undifferentiated colony percentage. Haemolytic HCV patients had an increase in colony number at week 4 of therapy. In vitro, erythroid cell proliferation and differentiation were inhibited by both pegIFN and RBV. Both pegIFN and RBV have an inhibitory effect on erythroid proliferation and differentiation.

Emergent Intervention Criterias for Controlling Sever Bleeding after Percutaneous Nephrolithotomy

Objectives. To determine when emergent intervention for bleeding after percutaneous nephrolithotomy (PCNL) is required. Methods. We reviewed analysis data of 850 patients who had undergone PCNL in our center. Blood transfusion was needed for 60 (7%) patients during and/or after surgery. We routinely performed followup of the urine output per hour, blood pressure, and hemoglobin levels after PCNL. Five (0.6%) of them had severe bleeding that emergent intervention was needed. Results. The mean age of the 5 patients who had emergent surgery due to severe bleeding was 42.2 (19–56) years. Mean duration of surgery was 44.75 (25–65) minutes. Mean stone size was 27 (15–38) mm. Mean decrease of hemoglobin was 4.8 (3.4–5.8) ng/dL, and unit of transfused blood was 4.4 (3–6). Mean blood pH was 7.21. There were metabolic acidosis and anuria/oliguria in all these patients. One of 5 patients suffered from cardiopulmonary arrest because of massive bleeding four hours after the PCNL, and despite cardiac resuscitation, he died. Hemorrhaging was controlled by open surgery in the other 4 patients. Two patients experienced cardiac arrest during the open surgery but they responded to cardiac resuscitation. There were no metabolic asidosis and anuria/oliguria, and bleeding was managed only with blood transfusion for the other 55 patients. Conclusion. Severe bleeding after PCNL is rare and can be mortal. If metabolic asidosis and anuria/oliguria accompanied the drop of hemoglobin, emergent surgical intervention should be performed because vascular collapse may follow, and it may be too difficult to stabilise the patient.

Análisis de los factores que influyen en la pérdida hemática en la nefrolitotomía percutánea: registro de la Asociación Española de Urología sobre la posición supina

ObjectivePercutaneous nephrolithotomy (PCNL) is the minimally invasive procedure of choice for removing renal stones larger than 2cm. This study has aimed to identify the different variables that might influence decrease of hemoglobin during the surgery performed in supine position. Material and methodsA prospective, multicenter, observational study of supine PCNL, based on the Spanish Association of Urology database, was analyzed. The different preoperative and postoperative factors that might affect the decrease of hemoglobin were assessed: demographics and anthropometric data, comorbidities, size and location of the stones, anatomical variants and technical aspects of the procedure. ResultsFrom September 2008 to December 2012, 397 supine PCNL procedures performed in 15 Spanish centers were registered. Mean hemoglobin decrease was 2.3±1.5g/dl and overall blood transfusion rate was 5.5%. No statistically significant differences were found between genders, body mass index (BMI) and age in terms of blood loss. There were also no differences between patients with cardiovascular, hypertensive, diabetic and anticoagulant treatment background. Blood loss was not significantly influenced by stone size and location. Technical aspects of the procedure as operative time (> 120min ≤), access to the pelvi-caliceal system (ultrasound, fluoroscopy), percutaneous tract dilation technique (Alken, balloon or Amplatz) or placement of nephrostomy (tube versus tubeless) were not associated with differences in pre-op/post-op hemoglobin. Only multiple percutaneous tracts (≥2) and middle calix access were statistically significantly (P=.03 and P=.01) related with less blood loss. ConclusionsPCNL in supine position is a minimally invasive procedure for removal of large (≥2cm) and multiple renal stones, with a low incidence of blood loss and minimal transfusion rate. Multiple percutaneous tracts and middle calix puncture were the only statistically significant variables associated with decrease in hemoglobin levels.

Initial report of microperc in the treatment of pediatric nephrolithiasis

Background/PurposeTo report the first technical feasibility and safety of microperc in the treatment of pediatric nephrolithiasis. MethodsA multicenter prospective trial was initiated and microperc was performed in 19 children from four different centers. In all cases, 4.85-Fr all-seeing needle was used to access the collecting system under direct vision. Stone fragmentation was performed using a 200-μm holmium: YAG laser fiber either through the same needle sheath or an 8-Fr microsheath. Patient- and procedure-related factors and perioperative and postoperative parameters were analyzed. ResultsThe mean age of the children was 7.5±4.4years. Mean stone size was 14.8±6.8mm. Conversion to Mini-PNL was required in two patients because of optical default in one and the high stone burden in the other. The mean hospital stay was 1.8±0.8days and the mean hemoglobin decrease was 0.1mg/dl. The overall stone-free rate at 1month was 89.5%. In one patient with obstructed ureteropelvic junction, intravasation of the irrigation fluid has led to abdominal distention and managed with percutaneous drainage intraoperatively. No other postoperative complication was recorded and no ancillary procedure was required. ConclusionsMicroperc is a safe and effective procedure in the treatment of pediatric kidney stones.

Minimally Invasive Surgery for Patients with Bulky Bladder Stones and Large Benign Prostatic Hyperplasia Simultaneously: A Novel Design

Objective: To determine the efficacy and safety of a novel minimally invasive design for treating bulky vesical calculi and large benign prostatic hyperplasia (BPH) simultaneously. Methods: 76 patients with large bladder stones (>4 cm) and large BPH (≥50 cm³) were treated from August 2008 to January 2011. 38 patients (group 1) underwent transurethral cystolithotripsy followed by transurethral resection of the prostate (TURP), 38 patients (group 2) received percutaneous cystolithotripsy within a laparoscopic entrapment bag and TURP by two surgeons simultaneously. 72 patients were followed up for 1 year. Patient demographics, perioperative parameters and follow-up data were compared. Results: Patient baseline characteristics were comparable in the two groups. In group 1, 3 patients converted to open surgery and received blood transfusion, 4 patients had postoperative fever, 2 had residual stones and 1 developed urethral stricture postoperatively. In group 2, the mean total operative and the operative times for stone management were 71.6 and 30.1 min, respectively, the mean hemoglobin decrease was 0.80 g/dl, no patients received blood transfusion and no complications occurred, significantly superior to group 1. Conclusions: Percutaneous cystolithotripsy using a laparoscopic entrapment bag associated with TURP by two surgeons simultaneously is a highly effective, safe and minimally invasive method for managing large vesical calculi and large BPH.

Total Tubeless Versus Standard Percutaneous Nephrolithotomy: A Meta-Analysis

The aim of this meta-analysis was to evaluate the efficacy and safety of total tubeless percutaneous nephrolithotomy (PCNL) versus standard PCNL. MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and the Chinese Biomedical Literature Database were researched. Randomized controlled trials (RCTs) and clinically controlled trials (CCTs) comparing total tubeless PCNL (tubeless and stentless) versus standard PCNL were included in this review. The related studies that met the inclusion criteria were included in the meta-analysis. Two reviewers independently assessed the quality of each included studies and extracted data. RevMan 5.1. was used for meta-analysis. Five RCTs and four CCTs were included, involving a total of 652 patients. All patients were divided into the total tubeless PCNL group and the standard PCNL group. The pooled results showed that the total tubeless PCNL group significantly reduced the hospital stay [weighted mean difference (WMD) -1.09 (95% confidence intervals, 95% CI -1.33, -0.85)] and analgesic requirement [standardized mean difference (SMD) -0.59 (95% CI -0.96, -0.23)]. There was no statistically significant difference in the operation time [WMD -4.14 (95% CI -8.27, -0.01)], mean hemoglobin decrease [-0.07 (95% CI -0.20, 0.06)], fever [relative risk (RR) 0.53 (95% CI 0.16, 1.69)], transfusion [RR 0.86 (95% CI 0.40, 1.85)], prolonged urinary drainage [RR 0.58 (95% CI 0.08, 4.09)], and ancillary procedure [extracorporeal shockwave lithotripsy, RR 0.84 (95% CI 0.29, 2.41), second-look PCNL RR 1.18 (95% CI 0.49, 2.89)]. According to the study design, the subgroup analyses were performed; most results were consistent with the overall findings, except the one that evaluated the analgesic requirement in the CCT subgroup. Total tubeless PCNL is a safe and effective procedure. It significantly reduced the hospital stay, analgesic requirement, and the time to return to normal activity without increasing complications. However, further randomized trials are needed to confirm these findings.

前立腺肥大症に対する120 W・HPSを用いた光選択式前立腺蒸散術PVPの初期経験

We examined the safety and efficacy of photo-selective vaporization of the prostate (PVP) using a 120-W high-performance system (HPS) for benign prostatic hyperplasia (BPH). We prospectively reviewed the records of 25 patients who had undergone PVP using a 120-W HPS in our institution. Patients were evaluated pre-operatively, and at 2 weeks and 1, 3, and 6 months postoperatively. The mean age was 73.6 years, and the mean estimated preoperative prostate volume was 51.5 ml. Laser vaporization was performed successfully in all 25 patients. The operating time was 104 +/- 29 minutes. The mean decrease in hemoglobin was 0.6 g/dl on post-operative day 1. The International Prostate Symptom Score (IPSS), QOL score, maximum flow rate, and residual urine volume were significantly improved 2 weeks after the procedure. There were no serious complications during the peri-operative period, and no patients were transfused. PVP using a 120-W HPS was shown to be an effective, safe procedure for patients with BPH and lower urinary tract symptoms.

Clinical Experience with Tranexamic Acid during Primary Total Hip Arthroplasty

We examined whether a single 1-gram preoperative dose of tranexamic acid (TXA) was effective in reducing 1) allogeneic blood transfusion, 2) haemoglobin (Hb) decreases, and 3) perioperative blood loss following primary total hip arthroplasty (THA) and resurfacing hip arthroplasty (RHA). One hundred and thirty-two patients (88 THA, 44 RHA; 66M, 66F; mean age = 58.2 years) who received TXA were compared with a control group matched for starting Hb, body mass index (BMI), age and gender. For the THR, transfusion rates were 4.5% and 19.3% for the TXA and control groups, respectively (p = 0.001) with no difference for the resurfacing patients. The mean overall Hb decrease was significantly lower in the TXA treatment groups for both THA and RHA patients (p<0.0001 and p = 0.01 respectively). 1 g of tranexamic acid administered preoperatively significantly reduced the mean decrease in haemoglobin as well as risk of transfusion.

Can the Availability of Unrestricted Financial Support Improve the Quality of Care of Thalassemics in a Center with Limited Resources? A Single Center Study from India

Comprehensive management of thalassemia demands a multidisciplinary approach, sufficient financial resources, carefully developed expertise of the care givers, as well as significant compliance on the patients’ part. Studies exploring the utility of unrestricted financing within the existing infrastructure, for the management of thalassemia, particularly in the context of a developing country, are scarce. This study aimed to assess the impact of sponsored comprehensive care compared to the routine care of thalassemics provided at Institute of Haematology and Transfusion Medicine, Kolkata, India. Two hundred and twenty patients were selected for the study and distributed in two arms. Regular monthly follow up was done including a Health Related Quality of Life (HRQoL) assessment with SF 36 v2 (validated Bengali version). Patients receiving sponsored comprehensive care showed a significant improvement in the mean hemoglobin levels and decrease in mean ferritin. HRQoL assessment revealed a better score in the physical domain though the mental health domain score was not significantly better at nine months. Unrestricted financial support in the form of comprehensive care has a positive impact on the thalassemia patients in a developing country not only in terms of clinical parameters but also in health related quality of life.

Clinical spectrum and severity of hemolytic anemia in glucose 6-phosphate dehydrogenase–deficient children receiving dapsone

AbstractDrug-induced acute hemolytic anemia led to the discovery of G6PD deficiency. However, most clinical data are from isolated case reports. In 2 clinical trials of antimalarial preparations containing dapsone (4,4′-diaminodiphenylsulfone; 2.5 mg/kg once daily for 3 days), 95 G6PD-deficient hemizygous boys, 24 G6PD-deficient homozygous girls, and 200 girls heterozygous for G6PD deficiency received this agent. In the first 2 groups, there was a maximum decrease in hemoglobin averaging −2.64 g/dL (range −6.70 to +0.30 g/dL), which was significantly greater than for the comparator group receiving artemether-lumefantrine (adjusted difference −1.46 g/dL; 95% confidence interval −1.76, −1.15). Hemoglobin concentrations were decreased by ≥ 40% versus pretreatment in 24/119 (20.2%) of the G6PD-deficient children; 13/119 (10.9%) required blood transfusion. In the heterozygous girls, the mean maximum decrease in hemoglobin was −1.83 g/dL (range +0.90 to −5.20 g/dL); 1 in 200 (0.5%) required blood transfusion. All children eventually recovered. All the G6PD-deficient children had the G6PD A− variant, ie, mutations V68M and N126D. Drug-induced acute hemolytic anemia in G6PD A− subjects can be life-threatening, depending on the nature and dosage of the drug trigger. Therefore, contrary to current perception, in clinical terms the A− type of G6PD deficiency cannot be regarded as mild. This study is registered at http://www.clinicaltrials.gov as NCT00344006 and NCT00371735.

Tranexamic Acid Reduces Blood Loss During Percutaneous Nephrolithotomy: A Prospective Randomized Controlled Study

Bleeding is a significant morbidity associated with percutaneous nephrolithotomy. This study was conducted to evaluate the safety and efficacy of the antifibrinolytic agent tranexamic acid in reducing blood loss in patients undergoing percutaneous nephrolithotomy. A total of 200 patients undergoing percutaneous nephrolithotomy were randomized into 2 equal groups. Patients in the tranexamic acid group received 1 gm tranexamic acid at induction followed by 3 oral doses of 500 mg during 24 hours, while those in the control group did not receive tranexamic acid. The patient demographics and clinical data of the 2 groups were compared. Baseline patient demographics were similar in both groups. Mean hemoglobin decrease in the tranexamic acid group was significantly lower than that of the control group (1.39 vs 2.31 gm/dl, p <0.0001). Mean operative time in the tranexamic acid group was significantly lower than that in the control group (48.3 vs 70.8 minutes, p <0.0001). The stone clearance rate was similar in both groups (91% vs 82%, p = 0.06). The blood transfusion rate was lower in the tranexamic acid group (2% vs 11%, p = 0.018), as was the complication rate (33% vs 59%, p <0.0001). Two patients with a solitary functioning kidney in the tranexamic acid group required ureteral stenting to relieve anuria due to clot obstruction. The use of tranexamic acid in percutaneous nephrolithotomy is safe, and is associated with reduced blood loss and a lower complication rate.

Minimized perfusion circuits: an alternative in the surgical treatment of Jehovah’s Witnesses

Jehovah's Witnesses present a challenge to cardiac surgeons, as quality of care is not only defined by mortality and morbidity, but also by the avoidance of blood transfusions. Over the last years, minimized perfusion circuits (MPC) have contributed substantially to the achievement of this goal in our clinic. Presented is a retrospective analysis of our experience. Twenty-nine Jehovah's Witnesses, aged 69 ± 10 years, have undergone cardiac surgery with a MPC in our institution since 2005. The ROCsafe (reservoir optional circuit) MPC was used in most of these patients (n=27) as it offers the unique possibility of a speedy integration of a reservoir in the event of a major air leak, thereby, negligating any safety concerns. There was no in-hospital or 30-day postoperative mortality. Mean ICU stay was 1.6 ± 2 days with a mean intubation time of 11.3 ± 9.1 hrs. Postoperative complications included one myocardial infarction with accompanying low cardiac output, one stroke, one transient delirium, one idiopathic thrombocytopenia and three re-operations (one sternal infection, one postoperative bleeding and one delayed tamponade). The mean postoperative hospital stay was 9.9 ± 2.3 days. Mean decrease in hemoglobin was 2.1 ± 1.3 g/dl during cardiopulmonary bypass and 3.4 ±1.4 g/dl at discharge. The lowest postoperative hemoglobin level was 9.3 ±1.8 (Range 6-12.9). These encouraging results emphasize the role MPCs can play in optimizing the quality of patient care. We hope that this report can serve as a stimulus for similar experiences.

Blood loss and complications following carotid endarterectomy in patients treated with clopidogrel

This study assessed the effect of uninterrupted antiplatelet therapy on perioperative blood loss and complications in patients undergoing carotid endarterectomy. The files of 107 consecutive patients (mean age 69.5 ± 9 years; range 47-88; 78 men) who underwent carotid endarterectomy were reviewed. Twenty-six patients had been treated with clopidogrel (16 of whom were on combined clopidogrel and aspirin treatment) and compared with non-clopidogrel patients. Antiplatelet treatment was continued until the day of surgery without interruption. Perioperative blood loss and complications were studied. The mean hemoglobin decrease was 1.64 ± 1.2 mg/dL and was not significantly affected by clopidogrel. Surgical time was significantly longer among patients treated with clopidogrel (205 ± 52 minutes on combined treatment and 201 ± 68 minutes on clopidogrel alone versus 165 ± 33 minutes, P < 0.0001). Postoperative complications were similar for all groups and included five strokes, five neck hematomas, one nerve injury and one wound infection. In conclusion, patients treated with clopidogrel before carotid endarterectomy can be expected to have prolonged surgical time. Large cohorts are required to determine whether these patients have more complications.

Holmium Laser Enucleation of the Prostate: A Modified Enucleation Technique and Initial Results

Although holmium laser enucleation of the prostate has been proven to be an excellent technique for the treatment of benign prostatic hyperplasia, it has not been widely applied due to technical difficulties and longer operative time. We modified the current technique of enucleation and present our initial experience. A total of 189 patients with benign prostatic hyperplasia underwent prostatectomy with our modified technique for holmium laser enucleation of the prostate. Intraoperative and postoperative data were prospectively collected. For followup International Prostate Symptom Score, quality of life, maximal flow rate and post-void residual urine were recorded. Mean±SD preoperative prostate volume was 78.1±24.3 cc and 60.9±39.2 gm tissue were enucleated. Mean operative and enucleation times were 54.7±21.1 and 36.5±16.3 minutes, respectively. Mean serum hemoglobin decrease was 0.98±0.72 gm/dl. Mean catheter time was 1.2±0.5 days and mean postoperative hospital stay was 4.9±3.4 days. Serious complications were not observed. Three patients complained of transient stress incontinence which resolved within 3 months. Significant improvement occurred in International Prostate Symptom Score, quality of life, maximal flow rate and post-void residual urine volume at 3 and 6-month followup compared with the preoperative baseline. The modified holmium laser enucleation of the prostate technique is effective and safe when treating benign prostatic hyperplasia.

Narrow Band Imaging Cystoscopy and Bipolar Plasma Vaporization for Large Nonmuscle-invasive Bladder Tumors—Results of a Prospective, Randomized Comparison to the Standard Approach

To evaluate the efficacy of narrow band imaging (NBI) cystoscopy associated with bipolar plasma vaporization (BPV) in cases of large nonmuscle-invasive bladder tumors (NMIBTs) compared with white light cystoscopy (WLC) and monopolar transurethral resection of bladder tumors (TURBTs). A total of 220 cases with ≥ 1 bladder tumor >3 cm determined by abdominal ultrasonography, computed tomography, and flexible WLC were included in the present trial. The patients in the first arm underwent WLC and NBI cystoscopy followed by BPV, and the patients in the second arm underwent only WLC and TURBT. The patients with NMIBTs underwent standard repeat TUR at 4 weeks and follow-up urinary cytology and WLC at 3, 6, 9, and 12 months. The carcinoma in situ, Stage pTa, and overall NMIBT detection rates were significantly improved for NBI compared with WLC. BPV provided lower obturator nerve stimulation and bladder wall perforation rates and significantly reduced the mean hemoglobin decrease, catheterization period, and hospital stay compared with TURBT. The repeat TUR overall and primary site residual tumor rates were significantly decreased in the NBI-BPV group (6.3% vs 17.5% and 4.2% vs 13.4%, respectively). The overall and other site 1-year recurrence rates were significantly reduced in the NBI-BPV series (7.9% vs 17.8% and 3.4% vs 12.2%, respectively). NBI cystoscopy significantly improved the diagnostic accuracy in cases of large NMIBTs, and BPV emphasized superior efficacy and safety compared with TURBT. This combined approach provided a lower residual tumor rate at repeat TUR and a reduced 1-year recurrence rate.

The use of novel hemostatic sealant (Tisseel®) in laparoscopic myomectomy: a case–control study

This is the first case-control study on the use of a fibrin sealant (Tisseel) on uterine suture during laparoscopic myomectomy (LM), with the primary endpoint to evaluate the intraoperative bleeding and postoperative blood loss. In addition, we evaluated the time required to achieve hemostasis using Tisseel and how much it can influence operative time. From December 2009 to January 2011, consecutive patients older than 18 years with symptomatic isolate intramural myoma with maximal diameter B6 cm and ≥ 4 cm and with a sonographically diagnosed free myometrium margin ≥ 0.5 cm were included in the study. We selected from our institute's database a group of consecutive patients with homogeneous features of the study group, who underwent laparoscopic myomectomy without Tisseel application. Fifteen women with symptomatic myoma were enrolled in the study (group A). Regarding the control group (group B), we selected a homogenous group of 15 patients with the same preoperative characteristics of the study group. Mean operative time was 47.7 min and 62.1 min, for groups A and B respectively (p < 0.05). Mean time required to achieve complete haemostasis was 195.5 s in group A and 361.8 in control group B (p < 0.0001). Mean estimated blood loss was 111.3 mL and 230 mL in groups A and B, respectively (p < 0.05). Mean hemoglobin decrease was 1.36 g/dL and 2.04 g/dL in groups A and B, respectively (p < 0.05). The use of Tisseel during LM may represent a valid alternative solution for obtaining hemostasis, reducing intra- and postoperative bleeding. Furthermore, it may help the surgeon to obtain a rapid healing of the injured surfaces, probably reducing the use of electrocoagulationand traumatisms.

Hemolytic Anemia Following Intravenous Immunoglobulin Administration: A Cluster of Suspected Cases

Abstract 4332 Background:Hemolytic anemia caused by the passive transfer of isoagglutinins, typically anti-A or anti-B antibodies, is a rare and likely under-recognized complication of intravenous immunoglobulin (IVIG) therapy. The Immunohematology Reference Laboratory at Mayo Clinic Rochester has detected 12 cases of passively acquired isoagglutinins following IVIG administration during the first seven months of this calendar year (January-July 2011). This frequency of detection is much higher than that seen over the three prior calendar years, when only two cases were detected. Given this “cluster” of isoagglutinin detection, we analyzed these 12 cases to determine the clinical significance of this finding as well as characteristics of resulting cases of hemolytic anemia. Materials/Methods:Charts of patients identified as having passively acquired isoagglutinins following IVIG therapy were analyzed for evidence of a significant drop in hemoglobin (defined as >1 g/dL) as well as evidence of hemolysis (elevated lactate dehydrogenase, reticulocytosis, spherocytosis, decreased haptoglobin, indirect hyperbilirubinemia, hemoglobinemia and hemoglobinuria). Cases with a >1 g/dL drop in hemoglobin and two or more of the above findings consistent with hemolysis were considered “confirmed” cases. Those with passively acquired isoagglutinins but without evidence of hemolysis or with an alternative explanation for anemia were considered “asymptomatic”, and cases without a full hemolytic evaluation but still clinically suspicious were categorized as “suspected” cases. Results:Passively acquired isoagglutinins were detected in 11 patients following 12 separate treatments with IVIG (one patient had antibodies noted after two separate treatment episodes >3 weeks apart). Four of these 12 cases were categorized as “confirmed” cases, five as “suspected” and three as “asymptomatic”. The indication for IVIG use was a neurologic disorder in three of the four confirmed cases, with immune thrombocytopenic purpura (ITP) being the indication in the other case. In suspected cases, ITP was the indication in four of the five cases, with the fifth patient carrying a diagnosis of Kawasaki's disease. During the 7 month period reviewed, 250 unique patients were treated with IVIG, meaning 1.6% of patients (4/250) had confirmed IVIG-associated hemolytic anemia and another 1.6% (4 patients; 5 events) had suspected hemolytic anemia during this period.The mean decrease in hemoglobin was 4.1 g/dL in confirmed cases (range 1.3–7.1 g/dL) and 2.7 g/dL in suspected cases (range 1.7–4.2 g/dL). Eight of nine patients reviewed had blood type A positive; the other was B positive. The median time from initiation of therapy to hemoglobin nadir was eight days in confirmed and three days in suspected cases. The mean dose of IVIG administered in confirmed cases was 300 g (range 180–400 g) and was 162 g (range 50–300 g) in suspected cases. Red cell transfusion was required in three of the four confirmed cases. Privigen™ was the IVIG product utilized in all four confirmed and the first three suspected cases. After removal of Privigen™ from the Mayo Clinic formulary given concerns regarding these cases, two suspected cases of IVIG-associated hemolytic anemia occurred with Gamunex-C™, including one in a patient who previously suffered confirmed hemolysis after receipt of Privigen™. Conclusions:Hemolytic anemia is a rare complication of therapy with IVIG. The rate of hemolytic anemia following IVIG administration over the evaluated period is consistent with previous reports, but it should be noted that these cases were detected without the aid of an active surveillance policy, indicating the actual rate of hemolytic anemia associated with IVIG use was likely greater than that detected by this review. Our series suggests that those with blood type A may be at increased risk for this complication; further work is ongoing to better define risk factors for development of this potentially significant complication of IVIG therapy. Disclosures:Off Label Use: IVIG use in various off-label indications.

Final Results From a Phase II Trial with the First in Class Recombinant Polyclonal Antibody Product Rozrolimupab in Primary Immune Thrombocytopenia

Abstract 527▪▪This icon denotes a clinically relevant abstract Background:Rozrolimupab is the first in-class fully human, recombinant antibody mixture for the treatment of ITP. Rozrolimupab comprises 25 unique human antibodies with documented binding capacity to the Rhesus D antigen on red blood cells, and constitutes a promising, modern counter-part to the blood-derived immunoglobulin products currently used in the treatment of ITP. The antibody mixture constituting rozrolimupab is produced by a novel single batch manufacturing strategy. Objectives and Endpoints:The objectives of the trial were to investigate the safety and efficacy of a single dose of rozrolimupab in RhD positive, non-splenectomized adult patients with primary ITP. The primary endpoint was incidence and severity of Adverse Events (AEs) during the 6-week trial period. Secondary endpoints included identification of the optimal dose of rozrolimupab and percentage of patients responding to treatment at 72 hours, 7 and 15 days. Methods:Patients from 27 sites in 11 countries were enrolled in this dose escalation (75 μg/kg – 300 μg/kg), multicentre, open label trial. Inclusion criteria included confirmed presence of thrombocytopenia with two individual pre-dose platelet counts of < 30 × 109/L. The patients received a single iv dose of rozrolimupab, and were followed for 6 weeks with frequent evaluations for safety and efficacy. Response was defined as platelet count ≥ 30 ×109/L and increase in platelet count from baseline by > 20 × 109/L. Results:A total of 61 ITP patients were treated with rozrolimupab: 75 μg/kg (11 patients), 100 μg/kg (10 patients), 125 μg/kg (10 patients), 150 μg/kg (5 patients), 200 μg/kg (6 patients), 250 μg/kg (6 patients) and 300 μg/kg (13 patients). Data from the 300 μg/kg cohort were not available for this abstract, but will be included in the final presentation.Given the small size of this study, the dose cohorts differed in a number of baseline characteristics. 60–90% of patients were females in all dose cohorts except in the 75 μg/kg cohort where 73% were males. Median platelet count before trial entry ranged from 11.5 to 22.3 × 109/L, and median time from first ITP diagnosis ranged from 5 to 68 months. In the individual dose groups, up to 83% of the patients responded at day 7. Up to 50% and 60% of the patients responded at 24 and 72 hours, respectively, and some responses lasted for the duration of the 6 weeks follow up period. Platelet responses also included patients who had baseline platelet counts below 10 ×109/L. A total of 51 AEs considered related to trial drug were reported in 20 patients. The most frequently reported adverse reactions were headache (7 events in 5 patients) and pyrexia (5 events in 4 patients). All but 2 of the adverse reactions (one headache, one extravascular haemolysis) were of mild or moderate intensity. Four of the 51 adverse reactions were categorized as Serious Adverse Events: One mild haemoglobin decrease in the 100 μg/kg cohort, one extravascular haemolysis in the 200 μg/kg cohort (mentioned above) and two mild to moderate, transient increases in D-dimer with no clinical symptoms in the 250 μg/kg cohort. Laboratory data showed a mean maximum decrease in haemoglobin ranging from 1.1 g/dL to 2.7 g/dL in individual cohorts with a slight dose dependency. A drop in haemoglobin of ≥ 3 g/dL was seen in 2 patients, one of 3.1 g/dL in the 100 μg/kg cohort and one of 4.5 g/dL in the 200 μg/kg cohort. Conclusions:Rozrolimupab is well tolerated with a favourable safety profile. In the individual dose groups, up to 83% of patients responded at day 7 including patients who had baseline platelet counts below 10 ×109/L. Final safety and efficacy data from all dose groups in the completed Phase II trial of rozrolimupab in primary ITP patients will be presented. Disclosures:Wiktor-Jedrzejczak:Celgene: Honoraria; Janssen-Cilag: Honoraria; Novartis: Honoraria, Research Funding. Flensburg:Symphogen: Employment. Petersen:Symphogen: Employment.