Hematology Commons^™

Functionalization Of Cd36 Cardiovascular Disease And Expression Associated Variants By Interdisciplinary High Throughput Analysis., Namrata Madan, Andrew R. Ghazi, Xianguo Kong, Edward S. Chen, Chad A. Shaw, Leonard C. Edelstein

Department of Medicine Faculty Papers

CD36 is a platelet membrane glycoprotein whose engagement with oxidized low-density lipoprotein (oxLDL) results in platelet activation. The CD36 gene has been associated with platelet count, platelet volume, as well as lipid levels and CVD risk by genome-wide association studies. Platelet CD36 expression levels have been shown to be associated with both the platelet oxLDL response and an elevated risk of thrombo-embolism. Several genomic variants have been identified as associated with platelet CD36 levels, however none have been conclusively demonstrated to be causative. We screened 81 expression quantitative trait loci (eQTL) single nucleotide polymorphisms (SNPs) associated with platelet CD36 expression …

Use Of Plasmapheresis And Immunosuppressants To Treat Diffuse Alveolar Hemorrhage In A Patient With Granulomatosis With Polyangiitis., Yasar Sattar, Ammu Thampi Susheela, Waqas Ullah, Norina Usman, Fnu Zafrullah

Abington Jefferson Health Papers

Granulomatosis with polyangiitis (GPA) is a systemic granulomatous inflammatory disease characterized by small-to-medium vessel vasculitis due to Central Anti-Neutrophil Cytoplasmic Antibody (C-ANCA). GPA commonly involves the lungs and the kidneys. Among the pulmonary manifestations, diffuse alveolar hemorrhage (DHA) is a rare presentation of GPA that can present with hemoptysis leading to acute onset of anemia and hemodynamic instability. An active diagnostic workup including serologic titer of C-ANCA, imaging, intensive care, and aggressive immunosuppression is the key to DAH management. We report a case of DAH secondary to GPA that presented with hemoptysis leading to severe anemia, initially resuscitated symptomatically and …

Horizontal Rna Transfer Goes Deep: Platelet Consumption And Microrna Utilization By Vascular Smooth Muscle Cells., Lawrence E. Goldfinger, Leonard C. Edelstein

Department of Medicine Faculty Papers

No abstract provided.

A Prospective, Multi-Center, Randomized Comparison Of Iron Isomaltoside 1000 Versus Iron Sucrose In Patients With Iron Deficiency Anemia; The Ferwon-Ida Trial., Michael Auerbach, David Henry, Richard J. Derman, Maureen M. Achebe, Lars L. Thomsen, John Glaspy

Global Health Articles

Iron deficiency anemia (IDA) is prevalent, and intravenous iron, especially if given in a single dose, may result in better adherence compared with oral iron. The present trial (FERWON-IDA) is part of the FERWON program with iron isomaltoside 1000/ferric derisomaltose (IIM), evaluating safety and efficacy of high dose IIM in IDA patients of mixed etiologies. This was a randomized, open-label, comparative, multi-center trial conducted in the USA. The IDA patients were randomized 2:1 to a single dose of 1000 mg IIM, or iron sucrose (IS) administered as 200 mg intravenous injections, up to five times. The co-primary endpoints were adjudicated …

Gpvi Inhibitor As Antitumor Gateway Drug., Lawrence E. Goldfinger

Department of Medicine Faculty Papers

In this issue ofBlood, Volz et al establish a potential antitumor strategy byexploiting the selective requirement for platelets to maintain vascular in-tegrity within the tumor microenvironment.1Their work demonstrates, forthefirst time, that functional inhibition of platelet-specific surface receptorglycoprotein (GP) VI, using F(ab9)2fragments to avoid platelet clearance,increases intratumoral hemorrhage and concomitant tumor cell apoptosis, aswell as enhanced accumulation of chemotherapeutic drugs. These effectswork additively to inhibit tumor growth, achieving results similar to thoseachieved by platelet depletion.

Quantitative Sensory Testing In Children With Sickle Cell Disease: Additional Insights And Future Possibilities., Robin E. Miller, Dawn S. Brown, Scott W. Keith, Sarah E. Hegarty, Yamaja Setty, Claudia M. Campbell, Suzanne M. Mccahan, Suhita Gayen-Betal, Hal Byck, Marie Stuart

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Quantitative sensory testing (QST) is used in a variety of pain disorders to characterize pain and predict prognosis and response to specific therapies. In this study, we aimed to confirm results in the literature documenting altered QST thresholds in sickle cell disease (SCD) and assess the test-retest reliability of results over time. Fifty-seven SCD and 60 control subjects aged 8-20 years underwent heat and cold detection and pain threshold testing using a Medoc TSAII. Participants were tested at baseline and 3 months; SCD subjects were additionally tested at 6 months. An important facet of our study was the development and …

Survival Probability In Patients With Sickle Cell Anemia Using The Competitive Risk Statistical Model., Emilia Matos Do Nascimento, Clarisse Lopes De Castro Lobo, Basilio De Bragança Pereira, Samir K. Ballas

Cardeza Foundation for Hematologic Research

The clinical picture of patients with sickle cell anemia (SCA) is associated with several complications some of which could be fatal. The objective of this study is to analyze the causes of death and the effect of sex and age on survival of Brazilian patients with SCA. Data of patients with SCA who were seen and followed at HEMORIO for 15 years were retrospectively collected and analyzed. Statistical modeling was performed using survival analysis in the presence of competing risks estimating the covariate effects on a sub-distribution hazard function. Eight models were implemented, one for each cause of death. The …

Sickle Cell Disease And Variation In The Par4 Receptor, Matthew Lankiewicz, Steven E. Mckenzie, Leonard Edelstein, Stephanie Renna

Phase 1

Sickle cell disease disproportionately affects African Americans in the U.S. Much can still be learned regarding determinants of frequency and severity of painful vaso-occlusive episodes in these patients. It has been reported that a variant in PAR4 (protease-activated receptor 4) has a unique distribution among African Americans. One variant (Thr120) is hyperactive, while the other (Ala120) is hypoactive. This receptor is present on platelets, vascular cells, and nociceptors. We wish ultimately to test the hypothesis that sickle cell patients with the hyperactive PAR4 receptor have greater pain severity. A genotype-phenotype correlation would have prognostic value. An adequately powered study to …

Transcriptional Activation Of The Mir-17-92 Cluster Is Involved In The Growth-Promoting Effects Of Myb In Human Ph-Positive Leukemia Cells., Manuela Spagnuolo, Giulia Regazzo, Marco De Dominici, Andrea Sacconi, Andrea Pelosi, Etleva Korita, Francesco Marchesi, Francesco Pisani, Alessandra Magenta, Valentina Lulli, Iole Cordone, Andrea Mengarelli, Sabrina Strano, Giovanni Blandino, Maria G. Rizzo, Bruno Calabretta

Department of Cancer Biology Faculty Papers

MicroRNAs, non-coding regulators of gene expression, are likely to function as important downstream effectors of many transcription factors including MYB. Optimal levels of MYB are required for transformation/maintenance of BCR-ABL-expressing cells. We investigated whether MYB silencing modulates microRNA expression in Philadelphia-positive (Ph+) leukemia cells and if MYB-regulated microRNAs are important for the "MYB addiction" of these cells. Thirty-five microRNAs were modulated by MYB silencing in lymphoid and erythromyeloid chronic myeloid leukemia-blast crisis BV173 and K562 cells; 15 of these were concordantly modulated in both lines. We focused on the miR-17-92 cluster because of its oncogenic role in tumors and found …

Drugs For Preventing Red Blood Cell Dehydration In People With Sickle Cell Disease., Srikanth Nagalla, Samir K. Ballas

Cardeza Foundation for Hematologic Research

BACKGROUND: Sickle cell disease is an inherited disorder of hemoglobin, resulting in abnormal red blood cells. These are rigid and may block blood vessels leading to acute painful crises and other complications. Recent research has focused on therapies to rehydrate the sickled cells by reducing the loss of water and ions from them. Little is known about the effectiveness and safety of such drugs. This is an updated version of a previously published review.

OBJECTIVES: To assess the relative risks and benefits of drugs to rehydrate sickled red blood cells.

SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic …

Iron Isomaltoside Is Superior To Iron Sucrose In Increasing Hemoglobin In Gynecological Patients With Iron Deficiency Anemia., Richard Derman, Eloy Roman, Gioi N. Smith-Nguyen, Maureen M. Achebe, Lars L. Thomsen, Michael Auerbach

Global Health Articles

No abstract provided.

Comorbidities In Aging Patients With Sickle Cell Disease., Samir K. Ballas

Cardeza Foundation for Hematologic Research

Sickle cell disease (SCD) in general and sickle cell anemia in particular is a highly complex disorder both at the molecular and clinical levels. Although the molecular lesion is a single-point mutation, the sickle gene is pleiotropic in nature causing multiple phenotypic expressions that constitute the various complications of the disease. Moreover, despite the fact that SCD is a chronic malady, its manifestations are both acute and chronic. The former include, among other things, the recurrent vaso-occlusive crises (its hallmark) and acute chest syndrome. The chronic complications include most commonly avascular necrosis and leg ulcers. Currently, survival of patients with …

Sickle Cell Disease: Classification Of Clinical Complications And Approaches To Preventive And Therapeutic Management., Samir K. Ballas

Department of Medicine Faculty Papers

Sickle cell disease (SCD) is an inherited disorder of hemoglobin structure that has no established cure in adult patients. Cure has been achieved in selected children with sickle cell anemia (SCA) using allogeneic bone marrow transplantation or cord blood transplantation. SCD is essentially a triumvirate of (1) pain syndromes, (2) anemia and its sequelae and (3) organ failure, including infection. Pain, however, is the hallmark of SCD and dominates its clinical picture throughout the life of the patients. The prevalence of these complications varies with age from infancy through adult life. However, pain, infections and anemia requiring blood transfusion occur …

Blood Rheological Abnormalities In Sickle Cell Anemia., Philippe Connes, Céline Renoux, Marc Romana, Manouk Abkarian, Philippe Joly, Cyril Martin, Marie-Dominique Hardy-Dessources, Samir K. Ballas

Department of Medicine Faculty Papers

This review focuses on the contribution of abnormal blood rheology in the pathophysiology of sickle cell anemia (SCA). SCA is characterized by a reduction of red blood cell (RBC) deformability but this reduction is very heterogeneous among patients. Recent works have shown that patients with the lowest RBC deformability (measured by ektacytometry) have enhanced hemolysis and would be more prone to develop several complications such as priapism, leg ulcers and glomerulopathy. In contrast, patients with the highest deformability, and not under hydroxyurea therapy, seem to develop more frequently vaso-occlusive like events. Although less studied, RBC aggregation properties are very different …

Targeting Cdk6 And Bcl2 Exploits The "Myb Addiction" Of Ph+ Acute Lymphoblastic Leukemia, Marco De Dominici, Patrizia Porazzi, Angela Rachele Soliera, Samanta A. Mariani, Sankar Addya, Paolo Fortina, Luke F. Peterson, Orietta Spinelli, Alessandro Rambaldi, Giovanni Martinelli, Anna Ferrari, Ilaria Iacobucci, Bruno Calabretta

Department of Cancer Biology Faculty Papers

Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph^þ ALL) is currently treated with BCR-ABL1 tyrosine kinase inhibitors (TKI) in combination with chemotherapy. However, most patients develop resistance to TKI through BCR-ABL1–dependent and –independent mechanisms. Newly developed TKI can target Ph^þ ALL cells with BCR-ABL1–dependent resistance; however, overcoming BCR-ABL1–independent mechanisms of resistance remains challenging because transcription factors, which are difficult to inhibit, are often involved. We show here that (i) the growth of Ph^þ ALL cell lines and primary cells is highly dependent on MYB-mediated transcriptional upregulation of CDK6, cyclin D3, and BCL2, and (ii) restoring their expression in MYB-silenced …

Mortality In Children, Adolescents And Adults With Sickle Cell Anemia In Rio De Janeiro, Brazil., Clarisse Lopes De Castro Lobo, Emilia Matos Do Nascimento, Leonardo José Carvalho De Jesus, Thiago Gotelip De Freitas, Jocemir Ronaldo Lugon, Samir K. Ballas

Cardeza Foundation for Hematologic Research

OBJECTIVE: To determine the mortality rate of children, adolescents and adults with sickle cell anemia in Rio de Janeiro, Brazil.

METHODS: The number of deaths, the mortality rate and the causes of deaths in patients with sickle cell anemia who were treated and followed up at our institution for 15 years were determined and compared to data available for the Brazilian population.

RESULTS: The overall number of deaths was 281 patients with a mortality rate of 16.77%. Survival probability was significantly higher in females. The number of deaths and the mortality rate were age-specific with a significant increase in the …

Transcutaneous Electrical Nerve Stimulation (Tens) For Pain Management In Sickle Cell Disease, Sudipta Pal, Ruchita Dixit, Soe Moe, Myron A. Godinho, Adinegara B.L. Abas, Samir K. Ballas, Shanker Ram, Uduman A.M. Yousuf

Cardeza Foundation for Hematologic Research

No abstract provided.

Beyond The Transition Of Adolescents And Young Adults With Sickle Cell Disease To Adult Care: Role Of Geography., Nina Anderson, James R. Eckman, Samir K. Ballas

Cardeza Foundation for Hematologic Research

No abstract provided.

Identification Of A Functional Genetic Variant Driving Racially Dimorphic Platelet Gene Expression Of The Thrombin Receptor Regulator, Pctp., Xianguo Kong, Lukas M. Simon, Michael Holinstat, Chad A. Shaw, Paul F. Bray, Leonard C. Edelstein

Cardeza Foundation for Hematologic Research

Platelet activation in response to stimulation of the Protease Activated Receptor 4 (PAR4) receptor differs by race. One factor that contributes to this difference is the expression level of Phosphatidylcholine Transfer Protein (PCTP), a regulator of platelet PAR4 function. We have conducted an expression Quantitative Trait Locus (eQTL) analysis that identifies single nucleotide polymorphisms (SNPs) linked to the expression level of platelet genes. This analysis revealed 26 SNPs associated with the expression level of PCTP at genome-wide significance (p < 5×10(-8)). Using annotation from ENCODE and other public data we prioritised one of these SNPs, rs2912553, for functional testing. The allelic frequency of rs2912553 is racially-dimorphic, in concordance with the racially differential expression of PCTP. Reporter gene assays confirmed that the single nucleotide change caused by rs2912553 altered the transcriptional potency of the surrounding genomic locus. Electromobility shift assays, luciferase assays, and overexpression studies indicated a role for the megakaryocytic transcription factor GATA1. In summary, we have integrated multi-omic data to identify and functionalise an eQTL. This, along with the previously described relationship between PCTP and PAR4 function, allows us to characterise a genotype-phenotype relationship through the mechanism of gene expression.

Improved Survival After Acute Graft-Versus-Host Disease Diagnosis In The Modern Era., Hanna J. Khoury, Tao Wang, Michael T. Hemmer, Daniel Couriel, Amin Alousi, Corey Cutler, Mahmoud Aljurf, Joseph H Antin, Mouhab Ayas, Minoo Battiwalla, Jean-Yves Cahn, Mitchell Cairo, Yi-Bin Chen, Robert Peter Gale, Shahrukh Hashmi, Robert J. Hayashi, Madan Jagasia, Mark Juckett, Rammurti T. Kamble, Mohamed Kharfan-Dabaja, Mark Litzow, Navneet Majhail, Alan Miller, Taiga Nishihori, Muna Qayed, Helene Schoemans, Harry C. Schouten, Gerard Socie, Jan Storek, Leo Verdonck, Ravi Vij, William A. Wood, Lolie Yu, Rodrigo Martino, Matthew Carabasi, Christopher Dandoy, Usama Gergis, Peiman Hematti, Melham Solh, Kareem Jamani, Leslie Lehmann, Bipin Savani, Kirk R. Schultz, Baldeep M. Wirk, Stephen Spellman, Mukta Arora, Joseph Pidala

Department of Medical Oncology Faculty Papers

A cute graft-versus-host disease remains a major threat to a successful outcome after allogeneic hematopoietic cell transplantation. While improvements in treatment and supportive care have occurred, it is unknown whether these advances have resulted in improved outcome specifically among those diagnosed with acute graft-versus-host disease. We examined outcome following diagnosis of grade II-IV acute graft-versus-host disease according to time period, and explored effects according to original graft-versus-host disease prophylaxis regimen and maximum overall grade of acute graft-versus-host disease. Between 1999 and 2012, 2,905 patients with acute myeloid leukemia (56%), acute lymphoblastic leukemia (30%) or myelodysplastic syndromes (14%) received a sibling …

The Role Of Platelet Microvesicles In Intercellular Communication., Leonard C. Edelstein

Cardeza Foundation for Hematologic Research

In recent years, there has been exponential growth in the interest in microvesicles, which is reflected by the number of publications. Initially referred to as "platelet dust" by Peter Wolf in 1967, platelet microvesicles (PMV) are now recognized as important mediators of intercellular communication. There are examples of PMV exerting physiological effects on almost all hematological and vascular cell types, including monocytes, macrophages, neutrophils, T-cells, endothelium cells, and smooth muscle cells (SMCs). PMV can exert these effects by multiple methods: extracellular signaling through receptors, transfer of surface molecules, and delivery of intracellular contents including miRNA. Recent work suggests a complex …

Pharmacological Interventions For Painful Sickle Cell Vaso-Occlusive Crises In Adults, Tess E. Cooper, Ian R. Hambleton, Samir K. Ballas, Philip J. Wiffen

Cardeza Foundation for Hematologic Research

This is the protocol for a review and there is no abstract. The objectives are as follows: To assess the analgesic efficacy, and adverse events, of pharmacological interventions used to treat acute painful sickle cell vaso-occlusive crises in adults, aged 18 and over, in any setting.

Treatment Of Dental Complications In Sickle Cell Disease., Priti Mulimani, Samir K. Ballas, Adinegara B L Abas, Laxminarayan Karanth

Cardeza Foundation for Hematologic Research

BACKGROUND: Sickle cell disease is the most common single gene disorder and the commonest haemoglobinopathy found with high prevalence in many populations across the world. Management of dental complications in people with sickle cell disease requires special consideration for three main reasons. Firstly, dental and oral tissues are affected by the blood disorder resulting in several oro-facial abnormalities. Secondly, living with a haemoglobinopathy and coping with its associated serious consequences may result in individuals neglecting their oral health care. Finally, the treatment of these oral complications must be adapted to the systemic condition and special needs of these individuals, in …

A Case-Control Genome-Wide Association Study Identifies Genetic Modifiers Of Fetal Hemoglobin In Sickle Cell Disease., Li Liu, Alexander Pertsemlidis, Liang-Hao Ding, Michael D Story, Martin H Steinberg, Paola Sebastiani, Carolyn Hoppe, Samir K. Ballas, Betty S Pace

Cardeza Foundation for Hematologic Research

Sickle cell disease (SCD) is a group of inherited blood disorders that have in common a mutation in the sixth codon of the β-globin (HBB) gene on chromosome 11. However, people with the same genetic mutation display a wide range of clinical phenotypes. Fetal hemoglobin (HbF) expression is an important genetic modifier of SCD complications leading to milder symptoms and improved long-term survival. Therefore, we performed a genome-wide association study (GWAS) using a case-control experimental design in 244 African Americans with SCD to discover genetic factors associated with HbF expression. The case group consisted of subjects with HbF≥8.6% (133 samples) …

Trends In Survival Of Chronic Lymphocytic Leukemia Patients In Germany And The Usa In The First Decade Of The Twenty-First Century., Dianne Pulte, Felipe A Castro, Lina Jansen, Sabine Luttmann, Bernd Holleczek, Alice Nennecke, Meike Ressing, Alexander Katalinic, Hermann Brenner

Cardeza Foundation for Hematologic Research

BACKGROUND: Recent population-based studies in the United States of America (USA) and other countries have shown improvements in survival for patients with chronic lymphocytic leukemia (CLL) diagnosed in the early twenty-first century. Here, we examine the survival for patients diagnosed with CLL in Germany in 1997-2011.

METHODS: Data were extracted from 12 cancer registries in Germany and compared to the data from the USA. Period analysis was used to estimate 5- and 10-year relative survival (RS).

RESULTS: Five- and 10-year RS estimates in 2009-2011 of 80.2 and 59.5%, respectively, in Germany and 82.4 and 64.7%, respectively, in the USA were …

Conjugate Haemophilus Influenzae Type B Vaccines For Sickle Cell Disease., Slimane Allali, Martin Chalumeau, Odile Launay, Samir K. Ballas, Mariane De Montalembert

Cardeza Foundation for Hematologic Research

BACKGROUND: People affected with sickle cell disease are at high risk of infection from Haemophilus influenzae type b. Before the implementation of Haemophilus influenzae type b conjugate vaccination in high-income countries, this was responsible for a high mortality rate in children under five years of age. In African countries, where coverage of this vaccination is still extremely low, Haemophilus influenzae type b remains one of the most common cause of bacteraemias in children with sickle cell disease. The increased uptake of this conjugate vaccination may substantially improve the survival of children with sickle cell disease.

OBJECTIVES: The primary objective was …

Safety And Efficacy Of Blood Exchange Transfusion For Priapism Complicating Sickle Cell Disease., Samir K. Ballas, David Lyon

Cardeza Foundation for Hematologic Research

BACKGROUND: Priapism is unwanted painful penile erection that affects about 36% of boys and men with sickle cell disease (SCD) most of whom have sickle cell anemia. Clinically, priapism could be stuttering, minor, or major. The first two types are mild, last < 4 h, are usually treated at home, have good prognosis with normal sexual function. The major type of priapism lasts >4 h, associated with severe pain, requires hospitalization; often does not respond to medical treatment and may require shunt surgery. Untreated major priapism and surgical intervention often cause impotence. In this study, we report our 15-year experience in treating adult patients with SCD and major priapism with blood exchange transfusion after being refractory to other medical therapies.

METHODS: …

The Paradox Of The Serrated Sickle Erythrocyte: The Importance Of The Red Blood Cell Membrane Topography., Samir K. Ballas, Philippe Connes

Cardeza Foundation for Hematologic Research

Red blood cell rheology and adhesiveness play a key role in the occurrence of vaso-occlusive like events in sickle cell anemia. The present paper reviews counter-intuitive findings supporting that rigid and serrated sickle red blood cells do not initiate vaso-occlusion. Instead, the less rigid red blood cells could initiate vaso-occlusion because of their increased adhesiveness to the vascular wall. We suspect that stiffness of sickle erythrocytes and the topography of RBC membrane are factors affecting adhesion to the endothelium.

Off-Target V(D)J Recombination Drives Lymphomagenesis And Is Escalated By Loss Of The Rag2 C Terminus., Martina Mijušković, Yi-Fan Chou, Vered Gigi, Cory R Lindsay, Olga Shestova, Susanna M Lewis, David B Roth

Cardeza Foundation for Hematologic Research

Genome-wide analysis of thymic lymphomas from Tp53(-/-) mice with wild-type or C-terminally truncated Rag2 revealed numerous off-target, RAG-mediated DNA rearrangements. A significantly higher fraction of these errors mutated known and suspected oncogenes/tumor suppressor genes than did sporadic rearrangements (p < 0.0001). This tractable mouse model recapitulates recent findings in human pre-B ALL and allows comparison of wild-type and mutant RAG2. Recurrent, RAG-mediated deletions affected Notch1, Pten, Ikzf1, Jak1, Phlda1, Trat1, and Agpat9. Rag2 truncation substantially increased the frequency of off-target V(D)J recombination. The data suggest that interactions between Rag2 and a specific chromatin modification, H3K4me3, support V(D)J recombination fidelity. Oncogenic effects of off-target rearrangements created by this highly regulated recombinase may need to be considered in design of site-specific nucleases engineered for genome modification.

Risk Factors Of Pulmonary Hypertension In Brazilian Patients With Sickle Cell Anemia., Clarisse Lopes De Castro Lobo, Emilia Matos Do Nascimento, Renato Abelha, Ana Maria Mach Queiroz, Philippe Connes, Gilberto Perez Cardoso, Samir K. Ballas

Cardeza Foundation for Hematologic Research

This study was a prospective cross-sectional cohort study of 125 patients with sickle cell anemia (SS) between the ages of 16 to 60 years. Enrolled patients were followed-up prospectively for 15 months. Demographic, clinical, hematological and routine biochemical data were obtained on all patients. Six-minute walk test and Doppler Echocardiography were performed on all patients. A tricuspid regurgitant jet velocity (TRJV) < 2.5 m/sec was considered normal, 2.5 ≤ TRJV ≤ 3.0 was considered mild-moderate and > 3.0 m/sec, severe. Patients with abnormal TRJV were significantly older and more anemic, had significantly higher lactate dehydrogenase (LDH) levels, reticulocyte count and incidence of death. The logistic multimodal model implemented for the 125 patients indicated that age was …