bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low blood counts: immune mediated, idiopathic, or myelodysplasia
Authors: Valent Peter 
Published: October 2019

AbstractTraditionally, cytopenias are classified as deficiency mediated, immune mediated, BM failure induced, renal, or idiopathic, with the latter including the so-called idiopathic cytopenias of undetermined significance (ICUS). Clinical findings, symptoms, blood counts, BM findings, and other laboratory parameters are usually sufficient to reveal the type and cause of a marked cytopenia. However, in patients with chronic mild cytopenia, it may be a challenge for the physician to establish a correct diagnosis. In such patients, laboratory features and findings often reflect a diagnostic interface, so that criteria that are otherwise robust may hardly be applicable or are not helpful. Even if the BM is examined, the diagnosis often remains uncertain in these patients. In addition, more than one potential cause of cytopenia may be present, especially in the elderly. A myelodysplastic syndrome (MDS) or another BM disorder, but also an overt autoimmune or other inflammatory disease, may develop during follow-up in these patients. A key problem is that in an early phase of MDS, most laboratory and clinical signs are “nonspecific.” One of the very few reliable peripheral blood parameters distinguishing between an early or “pre-phase” of MDS and most other causes of a mild cytopenia are the numbers of circulating colony-forming progenitor cells. In addition, flow cytometric and molecular investigations may sometimes assist in the delineation between clonal and reactive conditions underlying mild cytopenias. This review provides an overview of diagnostic approaches and algorithms for patients with mild unexplained cytopenia(s).
Anemias beyond B12 and iron deficiency: the buzz about other B's, elementary, and nonelementary problems
Authors: Green Ralph 
Published: October 2019

AbstractThe term “unexplained anemia” appears frequently in a request for a hematology consultation. Although most anemia consultations are fairly routine, they occasionally represent challenging problems that require an amalgam of experience, insight, and a modicum of “out-of-the-box” thinking. Problem anemia cases and pitfalls in their recognition can arise for one of several reasons that are discussed in the cases presented herein. “Anemias beyond B12 and iron deficiency” covers a vast domain of everything that lies beyond the commonly encountered anemias caused by simple deficiencies of 2 currently major hematologically relevant micronutrients. However, even these deficiencies may be obscured when they coexist or are not considered because of misleading distractions. They may also be mistakenly identified when other less common nutrient deficiencies occur. I present herein case examples of such situations: a young patient with pancytopenia and schistocytes who was responsive to plasmapheresis, but in whom pernicious anemia was not suspected because of ethnicity and age; a bicytopenic patient with anemia and myelodysplastic features caused by copper deficiency after gastric reduction surgery; and a patient with BM hypoplasia and a dimorphic blood smear who was found to have paroxysmal nocturnal hemoglobinuria. These “pearls” represent but 3 examples of the many varieties of problems in anemia diagnosis and are used to illustrate potential pitfalls and how to avoid them.
Perioperative management of patients on chronic antithrombotic therapy
Authors: Ortel Thomas L. 
Published: October 2019

AbstractPerioperative management of antithrombotic therapy is a situation that occurs frequently and requires consideration of the patient, the procedure, and an expanding array of anticoagulant and antiplatelet agents. Preoperative assessment must address each patient's risk for thromboembolic events balanced against the risk for perioperative bleeding. Procedures can be separated into those with a low bleeding risk, which generally do not require complete reversal of the antithrombotic therapy, and those associated with an intermediate or high bleeding risk. For patients who are receiving warfarin who need interruption of the anticoagulant, consideration must be given to whether simply withholding the anticoagulant is the optimal approach or whether a perioperative “bridge” with an alternative agent, typically a low-molecular-weight heparin, should be used. The new oral anticoagulants dabigatran and rivaroxaban have shorter effective half-lives, but they introduce other concerns for perioperative management, including prolonged drug effect in patients with renal insufficiency, limited experience with clinical laboratory testing to confirm lack of residual anticoagulant effect, and lack of a reversal agent. Antiplatelet agents must also be considered in the perioperative setting, with particular consideration given to the potential risk for thrombotic complications in patients with coronary artery stents who have antiplatelet therapy withheld.
Atypical hemolytic uremic syndrome: what is it, how is it diagnosed, and how is it treated?
Authors: Nester Carla M. , Thomas Christie P. 
Published: October 2019

Abstract
Atypical hemolytic uremic syndrome (aHUS) is a rare syndrome of hemolysis, thrombocytopenia, and renal insufficiency. Genetic mutations in the alternate pathway of complement are well recognized as the cause in more than 60% of patients affected by this thrombotic microangiopathy. The identification of aHUS as a disease of the alternate pathway of complement enables directed therapeutic intervention both in the acute and chronic setting and may include one or all of the following: plasma therapy, complement blockade, and liver transplantation. Because aHUS shares many of the presenting characteristics of the other thrombotic microangiopathies, and confirmatory genetic results are not available at the time of presentation, the diagnosis relies heavily on the recognition of a clinical syndrome consistent with the diagnosis in the absence of signs of an alternate cause of thrombotic microangiopathy. Limited understanding of the epidemiology, genetics, and clinical features of aHUS has the potential to delay diagnosis and treatment. To advance our understanding, a more complete characterization of the unique phenotypical features of aHUS is needed. Further studies to identify additional genetic loci for aHUS and more robust biomarkers of both active and quiescent disease are required. Advances in these areas will undoubtedly improve the care of patients with aHUS.
Thromboprophylaxis in nonsurgical patients
Authors: Streiff Michael B. , Lau Brandyn D. 
Published: October 2019

AbstractVenous thromboembolism (VTE) is an important cause of preventable morbidity and mortality in medically ill patients. Randomized controlled trials indicate that pharmacologic prophylaxis reduces deep venous thrombosis (relative risk [RR] = 0.46; 95% confidence interval [CI], 0.36-0.59) and pulmonary embolism (RR = 0.49; 95% CI, 0.33-0.72) with a nonsignificant trend toward more bleeding (RR = 1.36; 95% CI, 0.80-2.33]. Low-molecular-weight heparin (LMWH) and unfractionated heparin are equally efficacious in preventing deep venous thrombosis (RR = 0.85; 95% CI, 0.69-1.06) and pulmonary embolism (RR = 1.05; 95% CI, 0.47-2.38), but LMWH is associated with significantly less major bleeding (RR = 0.45; 95% CI, 0.23-0.85). LMWH is favored for VTE prophylaxis in critically ill patients. New VTE and bleeding risk stratification tools offer the potential to improve the risk-benefit ratio for VTE prophylaxis in medically ill patients. Intermittent pneumatic compression devices should be used for VTE prophylaxis in patients with contraindications to pharmacologic prophylaxis. Graduated compression stockings should be used with caution. VTE prevention in medically ill patients using extended-duration VTE prophylaxis and new oral anticoagulants warrant further investigation. VTE prophylaxis prescription and administration rates are suboptimal and warrant multidisciplinary performance improvement strategies.
In elderly patients with AML, which patients should be considered fit or unfit for standard induction therapy?
Authors: Swords Ronan , Santini Valeria 
Published: October 2019

Abstract
A 75-year-old man visits his primary care physician for a routine checkup and a complete blood count reveals pancytopenia. BM examination confirms the diagnosis of acute myeloid leukemia. No dysplastic features were noted and his karyotype results are pending. The patient has well-controlled hypertension and his last hospital admission was 20 years ago for repair of a rotator cuff injury. His Eastern Cooperative Oncology Group performance status is 0/4 and he has no cognitive impairment. You believe the patient is fit for standard acute myeloid leukemia induction, but you are concerned because of his older age and you are considering less-intensive approaches.
Defining minimal residual disease in acute myeloid leukemia: which platforms are ready for “prime time”?
Authors: Grimwade David , Freeman Sylvie D. 
Published: October 2019

Abstract
The past 40 years have witnessed major advances in defining the cytogenetic aberrations, mutational landscape, epigenetic profiles, and expression changes underlying hematological malignancies. Although it has become apparent that acute myeloid leukemia (AML) is highly heterogeneous at the molecular level, the standard framework for risk stratification guiding transplant practice in this disease remains largely based on pretreatment assessment of cytogenetics and a limited panel of molecular genetic markers, coupled with morphological assessment of bone marrow (BM) blast percentage after induction. However, application of more objective methodology such as multiparameter flow cytometry (MFC) has highlighted the limitations of morphology for reliable determination of remission status. Moreover, there is a growing body of evidence that detection of subclinical levels of leukemia (ie, minimal residual disease, MRD) using MFC or molecular-based approaches provides powerful independent prognostic information. Consequently, there is increasing interest in the use of MRD detection to provide early end points in clinical trials and to inform patient management. However, implementation of MRD assessment into clinical practice remains a major challenge, hampered by differences in the assays and preferred analytical methods employed between routine laboratories. Although this should be addressed through adoption of standardized assays with external quality control, it is clear that the molecular heterogeneity of AML coupled with increasing understanding of its clonal architecture dictates that a “one size fits all” approach to MRD detection in this disease is not feasible. However, with the range of platforms now available, there is considerable scope to realistically track treatment response in every patient.
Extracellular RNA released due to shear stress controls natural bypass growth by mediating mechanotransduction in mice
Authors: Lasch Manuel , Kleinert Eike Christian , Meister Sarah , Kumaraswami Konda , Buchheim Judith-Irina , Grantzow Tobias , Lautz Thomas , Salpisti Sofia , Fischer Silvia , Troidl Kerstin , Fleming Ingrid , Randi Anna M. , Sperandio Markus , Preissner Klaus T. , Deindl Elisabeth 
Published: October 2019

Key PointsShear stress–induced release of RNA from endothelial cells is crucial for initiation of arteriogenesis by controlling mechanotransduction. Extracellular RNA is essential for VWF release from endothelial cells initiating the inflammatory process driving arteriogenesis.
OBSERVATIONS ON THE EFFECT OF MASSIVE DOSES OF IRON GIVEN INTRAVENOUSLY TO PATIENTS WITH HYPOCHROMIC ANEMIA
Authors: GOETSCH ANNE TOMPKINS , MOORE CARL V. , MINNICH VIRGINIA 
Published: October 2019

Abstract
Massive doses of iron (from 0.608 to 1.32 Gm. as colloidal terric hydroxide or colloidal ferric oxide) were given intravenously in single infusions to 8 different patients with hypochromic microcytic anemia. One patient was given a second injection after an interval of four months, so that nine administrations were made. The following observations were made:
1. The reticulocyte response was higher in each instance than would be expected in oral therapy. In 3 additional patients in whom injection had to be discontinued after 0.070, 0.180, and 0.123 Gm. of elemental iron had respectively been given, the reticulocyte rises were higher than were the average responses reported by Heath18 after optimal oral therapy. This at least suggests that "optimal" oral therapy does not provide a maximal stimulus to outpouring of reticulocytes from the bone marrow. Comparable doses of iron given to 3 control subjects with normal hemoglobin levels did not cause a reticulocytosis.
2. The average rate of hemoglobin regeneration per 100 cc. of blood per day was 0.224 Gm.; the lowest value was 0.16 Gm. and the highest 0.27 Gm. These figures were calculated for the rise that occurred from the day of iron administration to the time at which the rate of hemoglobin increase was obviously becoming slower. Since correction was not made for blood loss in 3 of the patients during the period of regeneration, the figures for the rate of hemoglobin formation are lower than they otherwise would have been. Even so they are distinctly greater than those usually obtained following oral therapy (table 2), but no greater than is found in an occasional patient given iron by mouth. The data suggest that the fastest rate of hemoglobin regeneration that can be stimulated by iron in subjects with hypochromic anemia approximates 0.3 Gm. per 100 cc. per day.
3. Calculations indicated that from 71.8 to 99.7 per cent of the injected iron was apparently used for the synthesis of hemoglobin. These figures are likewise lower than they would have been if several of the patients had not lost blood during the recovery period. The observation of other workers that parenterally administered iron is almost completely retained by the body and converted into hemoglobin was therefore confirmed.
4. Toxic reactions to the injected iron are described in detail. They were severe in all but two instances, and in 3 patients were so alarming that injection of iron had to be discontinued. There can be no doubt that the reactions to iron parenterally administered in large doses are great enough to contra-indicate use of this measure as a therapeutic procedure.
ERYTHROBLASTOSIS FETALIS IN THE FIRST-BORN
Authors: LEVINE PHILIP , WALLER R. K. 
Published: October 2019

Abstract
The incidence of fatal forms of erythroblastosis fetalis in the first-born can be diminished by the simple measure of transfusing all Rh negative female patients, even as infants, with Rh negative blood. Once a female patient is found to be Rh negative, all subsequent transfusions must be carried out with Rh negative blood. The indications are that sufficient human anti-Rh serums will become available for the more extensive Rh tests required for the prevention of iso-immunization by transfusion.
HEMATOLOGICAL CHANGES FOLLOWING THE ADMINISTRATION OF LARGE DOSES OF QUINACRINE HYDROCHLORIDE
Authors: MUSHETT CHARLES W. , SIEGEL HENRY 
Published: October 2019

Abstract
The administration of quinacrine to rats, mice, rabbits, hamsters, guinea-pigs, dogs, monkeys, chickens, and ducks results in definite hematological changes. Peculiar basophilic inclusions, usually associated with vacuoles, appear in the cytoplasm of lymphocytes of all nine species following drug therapy. Inclusions of a similar nature are seen in erythrocytes of the rat, mouse, and hamster and rarely in monocytes of the rat.
The rat shows an anemia, polynucleosis, lymphopenia, and monocytosis after quinacrine dosing. None of the other species develop a leukocytosis or monocytosis, but they sometimes show a polynucleosis and lymphopenia after quinacrine therapy. Leukopenia occurs in the monkey and occasionally in the dog following the use of this drug.
THE BLOOD GROUPS, SUBGROUPS, AND RH FACTOR OF THE MAPUCHE INDIANS OF THE PROVINCE OF CAUTÍN, CHILE
Authors: S. L. SANDOVAL , HENCKEL C. , GIVOVICH L. 
Published: October 2019

Abstract
The authors present a sero-anthropological study of 205 Mapuche Indians from Cautín (Chile). There were 86.8 per cent of group O, 8.3 per cent of subgroup A1, 0.5 per cent of subgroup A2, 3.4 per cent of group B, and 1.0 per cent of subgroup AB.
The 3.4 per cent group B in the series may be due to crossing with whites or to the fact that this group was always present in Mapuches even before contact with whites.
The frequency of the standard Rh factor percentage is very high (98.6 per cent) but not 100 per cent as in the data of North American investigators.
Severe Para-Aminosalicylic Acid Hypersensitivity
Authors: CANNEMEYER W. , THOMPSON J. R. , LICHTENSTEIN M. R. 
Published: October 2019

Abstract
A severe form of hypersensitivity to para-aminosalicylic acid in patients with tuberculosis was studied. The blood picture, lymph node biopsies, and imprints are described. The similarities between this hypersensitivity to a simple chemical and infectious mononucleosis and infectious hepatitis are discussed. The possibility is suggested that some of the findings in viral diseases are due to hypersensitivity to chemical substances derived from the virus rather than to infection per se.
Studies on Human Myoglobin
Authors: SINGER KARL , ANGELOPOULOS BASIL , RAMOT BRACHA 
Published: October 2019

Abstract
The problem whether patients with sickle cell anemia have not only a pathologic (type S) hemoglobin, but also an abnormal myoglobin, was investigated by means of spectroscopic and electrophoretic methods. Purified, hemoglobin-free met-myoglobin preparations, obtained from normal adults and from individuals with sickle cell anemia, were compared. No differences could be detected with either technic.
The electrophoretic studies revealed that adult met-myoglobin moves faster in an acid than in an alkaline buffer. Regardless of the buffer used, adult met-myoglobin moves always slower than either met-hemoglobin A or S. The met-compounds of hemoglobin A and S move faster than their respective oxy-compounds in an acid medium, but slower in an alkaline medium.
Immunologic Studies of Hemoglobins
Authors: RUCKNAGEL DONALD L. , CHERNOFF AMOZ I. 
Published: October 2019

Abstract
Changes in the concentration of fetal hemoglobin in maternal blood during pregnancy and after delivery were studied in 91 pregnant women. Significant elevations of fetal hemoglobin were detected in the blood of ten women during the second trimester of pregnancy; these values fell toward normal during the ensuing pregnancy and post partum periods. In no instance could a rise in fetal hemoglobin be detected after delivery. The significance of these observations is discussed; it is suggested that acute hormonal changes early in pregnancy may be responsible for the reactivation of a fetal erythropoietic anlage with the resultant production by the mother of erythrocytes containing fetal hemoglobin. The method used was not sensitive enough, however, to detect minute amounts of fetal blood which may have crossed the placental barrier.
An In Vitro Study of Antileukemic Serum
Authors: THOMPSON JOHN S. 
Published: October 2019

Abstract
1. A rabbit anti-DBA2-mouse-induced lymphogenous leukemia serum was prepared that contained antibodies to normal lymphocytic and to leukemic lymphocytic antigens, as determined by the complement fixation test of Thornton and his associates.
2. When this antiserum was incubated with normal lymphocytic antigen, all of its complement fixing activity was removed except that which reacted with the leukemic tissue. It appears that an antibody or group of antibodies was produced which was specific for this leukemia.
3. An antiserum to lymphogenous leukemia, induced in DBA2 mice, given prophylactically or therapeutically, did not significantly protect other DBA2 mice that had been inoculated with a transplantable leukemia of the same cell type.
4. The failure to induce leukemia in young, DBA2 female mice by painting them with 20-methylcholanthrene in benzene is reported.
Hemoglobin C Disease
Authors: HARTZ WILSON H. , SCHWARTZ STEVEN O. 
Published: October 2019

Abstract
1. The cases of four Negro patients with splenomegaly and targeting of the red cells are reported.
2. Electrophoretic analysis of the hemoglobin in these cases revealed type C hemoglobin exclusively.
3. An analysis of the genetic, clinical, and hematologic manifestations was made.
4. For convenience, the name hemoglobin C disease has been given to the mild hemolytic syndrome observed in these patients.
5. Electrophoretic recognition of hemoglobin C by filter paper and Tiselius technics is illustrated.
6. Differential diagnosis is discussed with special attention directed to the mild form of Mediterranean anemia.
Studies on Abnormal Hemoglobins
Authors: SINGER KARL , SINGER LILY , GOLDBERG SEYMOUR R. 
Published: October 2019

Abstract
(1) Four Negro patients with mild sickle cell-thalassemia disease (heterozygous for the genes for S hemoglobin and for thalassemia) are described. In contrast to reports in the literature, some of these patients are only mildly anemic, or not anemic at all. In three, the values for MCV and MCH are decreased, but in one, all hematologic indices are normal. All four individuals show leptocytosis and elevated reticulocyte levels.
(2) Hemoglobin analyses, consisting of a combination of electrophoresis and the alkali denaturation technic, demonstrate the S + A + F pattern in three, and the S + A pattern in the fourth. These patterns are considered pathognomonic for sickle cell-thalassemia disease. They may be sharply differentiated from the S + F pattern, encountered in classical (homozygous) sickle cell anemia, and from the A + S pattern found in the heterozygous sickle cell trait. The various types of hemoglobin are reported in the sequence of their quantitative representation in the hemolysate. Hemoglobin analysis is indispensable for the recognition of the different types of sickle cell disease.
(3) Evidence is cited that clinically almost asymptomatic sickle cell-thalassemia disease is probably not too rare in the American Negro population.
(4) The genetic aspects of the production of fetal hemoglobin are discussed. It is postulated that the production of fetal hemoglobin is also under genetic control. The genes for fetal hemoglobin are not alleles of the genes for normal adult hemoglobin and are physiologically almost completely suppressed by the latter. Pathologic genes may render this suppression incomplete.