bluuebunny/crossref_metadata_2025 huggingface dataset:
Factor VII deficiency
Authors: Ragni Margaret V. , Lewis Jessica H. , Spero Joel A. , Hasiba Ute
Published: February 2007

This report describes three patients with factor (F) VII deficiency: two adult siblings and an unrelated 5½‐month‐old child who succumbed after several central nervous system (CNS) hemorrhages. This event prompted a review of the literature concerning the incidence and characteristics of intracranial hemorrhage in congenital F VII deficiency.

Of 138 patients reported to have F VII deficiency, only 75 were considered to have a true deficiency. There was a 1:1 sex distribution with a 19% incidence of consanguinity in the 63 families which these 75 patients represented.

CNS hemorrhage occurred in 12 of the 75 proven factor‐deficient patients – an incidence of 16.0%. There was a 1.4:1 female predominance in this group, with a 44.4% incidence of consanguinity in their nine families. Except for one patient with hypertension, there was no history of preceding trauma or previous underlying CNS abnormality, though head trauma with a difficult vaginal delivery may have occurred in five infants. Diagnostic lumbar puncture or ventricular tap revealed bloody, xanthochromic cerebrospinal fluid in five.

Five patients with F VII deficiency developed a CNS hemorrhage prior to 1 week of age, and none survived. Seven patients older than 1 week of age suffered such an event, and four of these survived. It is concluded that the greatest risk factor for development of CNS hemorrhage is trauma related to the birth process.
von Willebrand disease associated with familial thrombocytopenia and increased ristocetin‐induced platelet aggregation
Authors: Takahashi Hoyu , Nagayama Reizo , Hattori Akira , Ihzumi Toshio , Tsukada Tsuneyasu , Shibata Akira
Published: February 2007

Two cases of von Willebrand disease (vWD) associated with familial thrombocytopenia were reported. The proband (daughter) and her father showed thrombocytopenia with large platelets and decreased von Willebrand factor activity (VIIIR:WF). Factor VIII procoagulant activity (VIII:C) and factor VIII‐related antigen (VIIIR:AG) were normal, but both patients revealed an increased ristocetin‐induced platelet aggregation and a qualitative abnormality of the factor VIII protein, which was characterized by fast electrophoretic mobility of VIIIR:AG and an abnormal elution of factor VIII‐related activities on Sepharose 2B. DDAVP was hemostatically effective even in this thrombocytopenic patient undergoing a dental extraction.
An antigen expressed by cells of the myelo‐monocytic lineage
Authors: Foon Kenneth A. , Billing Ronald J. , Fitchen John H. , Belzer Michael , Drew S. Ian , Terasaki Paul I.
Published: February 2007

We describe an antigen(s) characterized by a heteroantiserum raised in rabbits against mature human granulocytes. This antigen was found on neutrophils, monocytes, platelets, acute and chronic myelocytic leukemia cells and on granulocyte‐macrophage progenitor cells grown in agar. It was not found on lymphocytes, eosinophils, erythrocytes, or erythroid progenitor cells. On the basis of tissue distribution and absorption studies, the antigen (tentatively designated the “myelo‐monocytic” antigen) is distinct from antigens previously identified on human neutrophils. Restriction of the “myelo‐monocytic” antigen to normal and malignant cells of the myelo‐monocytic series suggests that it may represent a normal differentiation antigen of the myelomonocytic lineage.
Karyotypic patterns and their clinical significance in polycythemia vera
Authors: Testa J. R. , Kanofsky J. R. , Rowley J. D. , Baron J. M. , Vardiman J. W.
Published: February 2007

We studied a series of 34 polycythemia vera (PV) patients to determine the incidence of chromosome abnormalities and their relationship to leukemic transformation. Metaphase chromosomes from bone marrow or unstimulated peripheral blood were examined with conventional stain and, in 20 patients, also with banding techniques. The overall incidence of clonal abnormalities in first samples was 44% (15 of 34 patients), with a higher incidence in patients who had received prior therapy. The most frequent abnormalities were long‐arm deletion of No. 5 (5q‐; four patients), gain of all or most of a No. 8 (five patients), gain of all or most of a No. 9 (four patients), and long‐arm deletion of No. 20 (three patients); these sometimes occurred in combination. Some of the PV patients who had cytogenetic abnormalities early in the disease have had long survivals without developing leukemia. For example, one patient has been 48, XX, +8, +9 in sequential samples obtained over the last 15 years. Five patients developed acute myeloblastic leukemia (AML); each had a complex chromosomal pattern. Two of these five patients were cytogenetically normal during the polycythemic phase; the change in karyotype occurred with the leukemic transformation. Three AML patients were studied only in the leukemic phase. Three AML patients had a 5q‐, and a fourth showed loss of a B‐group chromosome. Evolutionary changes in the karyotype during the disease course and the occurrence of a 5q‐appear to be associated with a terminal phase of PV.
The anemia of senescence
Authors: Lipschitz D. A. , Mitchell C. O. , Thompson C.
Published: February 2007

A study of 196 healthy geriatric females and 26 males confirmed the high prevalence of anemia in this population. Forty‐two females (21.4%) had a hematocrit of less than 36% and nine (34%) of the males had a value of less than 40%. A careful evaluation, including a therapeutic trial of oral iron in some subjects, made a diagnosis of iron deficiency anemia in only three and the anemia of chronic disease could be diagnosed in two. No subject had folate or B12 defiency and hemolytic anemia was not present. Thus, in most of these subjects, the lower hematocrit was not due to commonly recognized causes. Further evaluation revealed a high prevalence of leukopenia in this population; 30% having counts less than 5 × 103/μd and 10% having values less than 4 × 10−3/ μl. Of most importance, leukocyte counts were significantly lower in anemic subjects in whom a high incidence of neutropenia was also demonstrated. This suggests that the mechanisms of the unexplained anemia and neutropenia is an overall reduction in hematopoietic cell numbers. This conclusion is consistent with the observation that many aged subjects have a decreased ability to mount an adequate leukocyte response to infection. These findings suggest that the presence of anemia marks an overall reduction in hematopoietic reserve and provides a clue to those aged subjects at greatest risk of an inadequate response to stress.
A simplified method for monitoring heparin therapy at the bedside: The activated whole blood clotting time
Authors: Forman Walter B. , Bayer Gerald
Published: February 2007

Twelve patients receiving heparin during hemodialysis had coagulation parameters monitored using the whole blood clotting time (WBCT), activated partial thromboplastin time (APTT), plasma heparin levels and activated whole blood clotting time (AWBCT). The AWBCT, performed with a battery‐powered portable incubator/timer, correlated with both the corresponding WBCT and the plasma heparin levels. However, the correlation between the AWBCT and the APTT was quite poor. This assay is simply performed, inexpensive, and reproducible. It is recommended as an excellent method for monitoring heparin therapy.
Trace metals in hematopoiesis
Authors: Deur Charles J. , Stone Marvin J. , Frenkel Eugene P.
Published: February 2007

The trace metals represent an extremely small part of the total mass of the organism. In spite of this, these elements appear to play major roles in metabolism. At the level of the hematopoietic system, specific roles can be identified for iron, copper, zinc, and cobalt. Other trace metals appear to play less clearly defined roles in hematopoiesis but clearly are involved by virtue of a number of interactions at the level of absorption, intermediary metabolism, or modulation of toxicity. Still other trace metals, such as lithium, appear to have a therapeutic role in altering production of granulocytes, by an as yet unidentified mechanism.
Epinephrine potentiation of arachidonate‐induced aggregation of cyclooxygenase‐deficient platelets
Authors: Rao Gundu H. R. , White James G.
Published: February 2007

Evaluation of platelet physiology, biochemistry, ultrastructure, and function in a young woman without history of hemorrhagic problems revealed that her platelets were deficient in cyclooxygenase activity. Her citrate platelet‐rich plasma (C‐PRP) responded monophasically when stirred with aggregating agents in the same manner as aspirin‐treated normal C‐PRP, but could be irreversibly aggregated by high concentrations of thrombin, collagen, and ADP. Her platelets did not aggregate when stirred with AA at concentrations as high as 2 mM. Ultrastructure and levels of serotonin and adenine nucleotides were normal. Amounts of 14C‐AA released after stirring with thrombin were similar to normal cells. However, evaluation of prostaglandin synthesis after stirring with 14C‐AA revealed no evidence of endoperoxide or thromboxane production, although products of the lipoxygenase pathway were produced in normal amounts. Aggregation in response to AA was completely corrected after mixing with 10% normal C‐PRP. However, equal volumes of her C‐PRP and normal aspirin‐treated C‐PRP did not respond to AA, whereas 10% normal platelets combined with aspirin‐treated cells corrected aggregation to AA. Since epinephrine pretreatment corrects the response of dog platelets that are not aggregated by AA, we evaluated the influence of epinephrine on her platelets. Preexposure to 5 μM epinephrine, a concentration that gave only primary waves of aggregation, resulted in normalization of her response to AA, even though correction was not associated with the generation of endoperoxides or thromboxanes. The results may explain why patients with platelet cyclooxygenase deficiency have mild or absent bleeding symptoms.
Factor‐X deficiency in amyloidosis: A critical review
Authors: Greipp Philip R. , Kyle Robert A. , Bowie E. J. Walter
Published: February 2007

Thirty cases of amyloidosis with factor‐X deficiency, including six of our own, were reviewed. Modest deficiency of factor X was often associated with severe bleeding. In many of the cases, clinical bleeding could not be accounted for by deficiency of factor X alone. Other hemostatic defects were found in these patients and probably contributed to the bleeding. Modes of treatment, including the empiric use of corticosteroids and splenectomy, were discussed in light of current knowledge of pathogenesis of this unusual blood clotting disorder. This involves the interaction of amyloid fibrils and blood clotting factors.
Idiopathic thrombocytopenic purpura and graves disease
Authors: Valenta Lubomir J. , Treadwell Thomas , Berry Richard , Elias Alan N.
Published: February 2007

A 31‐year‐old black woman was studied who, at the age of 12 years, underwent splenectomy for a bleeding disorder due to idiopathic thrombocytopenic purpura (ITP). More than 20 years after the first signs of her bleeding disorder, the patient developed signs of Graves disease. This condition was treated with 131I with resulting hypothyroidism. The rare combination of ITP and Graves disease was considered to be a manifestation of two separate autoimmune diseases. For the second time in the literature, HLA typing was performed in a patient with such a disease combination, and it was found to be of the group A23, A28, and B17. This is different from B8, which is most frequently found in both isolated ITP and Graves disease. Possible racial factors may be involved. It is concluded that more cases of such combined disease need to be studied before possible genetic patterns can be established.
Nonsteroidal anti‐inflammatory drugs in the treatment of hemophilic arthropathy
Authors: Thomas Patricia , Hepburn Bonnie , Kim Hugh C. , Saidi Parvin
Published: February 2007

This study was undertaken to investigate the safety and efficacy of nonaspirin, nonsteroidal anti‐inflammatory drugs (NSAIDs) in controlling the pain and stiffness of hemophilic arthropathy. Data were collected from eight adult hemophilic patients in successive double‐blind controlled studies using choline magnesium trisalicylate (CMT) and ibuprofen (IPF). In seven patients, neither drug consistently affected bleeding times, platelet aggregation studies, frequency of joint hemorrhages, or frequency of factor infusions. In one patient, platelet aggregation appeared to be affected by CMT and bleeding time became markedly prolonged after IPF therapy. Three patients taking CMT and four patients taking IPF reported greater relief of pain and stiffness with the drugs than with placebos. Our results suggest that IPF and CMT can benefit the hemophiliac and that they can be used safely in most hemophilic patients under closely supervised conditions.
Coexistence of gaucher disease and philadelphia positive chronic granulocytic leukemia
Authors: Shinar E. , Leibovitz Gershon Z. ‐Ben , Leiserowitz R. , Matzner Y. , Yatziv S. , Polliack A.
Published: February 2007

A patient with coexistent Gaucher disease and Philadelphia positive chronic granulocytic leukemia (CGL), who subsequently developed myeloblastic leukemia, is described. The diagnosis of CGL was established according to standard clinical, morphological, biochemical, and cytogenetic data, while the diagnosis of true Gaucher disease was based on biochemical data and the presence of Gaucher cells with typical ultrastructural features in the bone marrow and spleen. Enzyme studies showed low activity of ceramide‐β‐glucosidase in the patient's peripheral blood leukocytes, skin fibroblasts, and splenic tissue and the presence of increased amounts of ceramide‐β‐glucoside in the spleen.

This case is reported in order to draw attention to the possible coexistence of these two diseases in the same patient, as opposed to the well‐recognized finding of “Gaucher‐like” cells in the bone marrow of patients with CGL. Enzyme studies enable distinction between these two situations.
Indications for platelet transfusion in children with acute leukemia
Authors: Murphy Scott , Litwin Samuel , Herring Leonard M. , Koch Penelope , Remischovsky Judith , Donaldson Milton H. , Evans Audrey E. , Gardner Frank H.
Published: February 2007

In an attempt to determine the indications for platelet transfusion in thrombocytopenic patients, we randomized 56 children with acute leukemia to one of two regimens of platelet transfusion. The prophylactic group received platelets when the platelet count fell below 20,000 per mm3 irrespective of clinical events. The therapeutic group was transfused only when significant bleeding occurred and not for thrombocytopenia alone. The time to first bleeding episode was significantly longer and the number of bleeding episodes were significantly reduced in the prophylactic group. The survival curves of the two groups could not be distinguished from each other. Prior to the last month of life, the total number of days on which bleeding was present was significantly reduced by prophylactic therapy. However, in the terminal phase (last month of life), the duration of bleeding episodes was significantly longer in the prophylactic group. This may have been due to a higher incidence of immunologic refractoriness to platelet transfusion. Because of this terminal bleeding, comparison of the two groups for total number of days on which bleeding was present did not show a significant difference over the entire study period.
Osmotic error in erythrocyte volume determinations
Authors: Beautyman William , Bills Terry
Published: February 2007

Because of osmotic effects erythrocytes suspended in their native plasma do not have the same volume as the same erythrocytes suspended in Isoton. The discrepancy varies depending upon the osmolality and composition of the native plasma and the length of time the cells have been suspended in Isoton. Consequently, the MCV recorded in an electronic particle counter (Coulter in this case) may differ markedly from the true in vivo MCV. A similar error affects the Coulter hematocrit, which is calculated from the MCV and the erythrocyte count. This matrix effect should be taken into account in any laboratory quality assurance program.
Mixed myeloid—lymphoid colonies in a patient with polycythemia vera
Authors: Beckman Barbara , Anderson William F. , Beltran G. , Chen I. , Fisher James W.
Published: February 2007

Peripheral blood mononuclear cells from a patient with polycythemia vera were cultured in a methylcellulose system employing human serum. Electron microscopy documented the appearance of mixed colonies containing lymphocytes, granulocytes, megakaryocytes, and erythrocytes. In vitro culture characteristics were similar to those seen for other patients with polycythemia vera, ie, colonies grew in the absence of added erythropoietin or other pathway‐specific regulators. Plating efficiency was linearly related to the number of cells plated, which supports the concept that each colony arose from a single cell. The appearance of mixed myeloid—lymphoid colonies points to the existence of a primitive stem cell capable of giving rise to multiple hematopoietic cell lines.
Simultaneous detection of two mechanisms of immune destruction of penicillin‐treated human red blood cells
Authors: Yust Israel , Frisch Bertha , Goldsher Naomi
Published: February 2007

Two separate processes of putative red‐cell destruction in penicillin‐induced immune hemolysis were measured simultaneously by a rapid (3 hour) assay utilizing 51Cr‐labelled red blood cells (RBC). Antibody‐dependent, cell‐mediated cytotoxicity (ADCC) was estimated by release of 51Cr; and antibody‐dependent phagocytosis (ADPh) by quantitation of 51Cr uptake into mononuclear phagocytes as well as by counts of engulfed RBC. Attacking cells were obtained by Ficoll‐Hypaque separation of peripheral blood from normal donors. Phagocytosis as well as lysis were proportional to anti‐penicillin antiserum concentration, to incubation time, and to the concentration of the attacking cells. Enrichment of mononuclear phagocytes in the attacking cell population by albumin gradient separation led to an increase in phagocytosis as well as in cytotoxicity. Depletion of mononuclear phagocytes resulted in a decline in both processes. Dilution of antiserum abolished ADCC but affected ADPh only slightly. Iodoacetate as well as colchicine inhibited both activities. These results indicate that both processes may be operative in the immune destruction of RBC in vivo.
The generation of antibody diversity
Authors: Rose David R.
Published: February 2007

By their nature, antibody molecules exhibit a wide range of binding specificities. The antigen‐binding properties of the antibody reside entirely in the amino‐terminal portion of the molecule, termed the variable domain. Structurally, the combining site specificity is determined by the amino‐acid residues within 6 short lengths, 3 each in the heavy and light chains, of unusually variable sequence. The hypervariability of 2 of these lengths arises from the somatic recombination of short gene segments into a single stretch of mRNA which encodes the entire variable region of 1 polypeptide chain. For example, a V gene segment that codes for most of the variable portion of a light chain, can combine with one of a number of much shorter J gene segments to create the complete variable region gene. In heavy chain genes, a third element, the D gene segment, increases the potential for diversity even further. A mechanism has been proposed by which variability occurs at the point where 2 gene segments join. Thus, a large part of the generation of antibody diversity occurs in the somatic recombination of small genetic elements.
Kinetic alterations of the red cell membrane phosphatase in α‐ and β‐Thalassemia
Authors: Morlé L. , Dorléac E. , Alloisio N. , Jaccoud P. , Colonna P. , Bachir D. , Delaunay J.
Published: February 2007

We studied the red cell membrane neutral phosphatase, which is part of the Na+K+ ATPase, in several types of oxidative hemolytic anemias. We used an artificial substrate, the p‐nitrophenylphosphate. In controls and in patients heterozygous for various unstable hemoglobins (Hb Hope, Hb Köln, or Hb Hammersmith), the kinetics were of the Michaelis‐Menten type. On the contrary, in nearly all patients with α‐ or β‐thalassemia, the kinetics displayed an abnormally biphasic character. The apparent Michaelis constant (KMapp) was significantly decreased. The biphasic character correlated with the imbalance of globin chain synthesis. The β‐mercaptoethanol markedly increased Vmax in controls, but had little effect on the biphasic kinetics. Omission of K+abolished the biphasic kinetics. The abnormal kinetics failed to appear with another artificial substrate, the 4‐methylum‐belliferylphosphate, nor did it appear with ATP, the natural substrate. In vitro, H2O2 treatment of normal and thalassemic red cells was unable to induce or exaggerate, respectively, the biphasic kinetics, but generated alterations of a different nature. We suggest that the various kinetic alterations of the phosphatase in thalassemic syndromes originate from the imbalance of globin chain synthesis. However, the involvement of an oxidative process remains to be demonstrated.
Emperipolesis of neutrophils by dysmorphic megakaryocytes
Authors: Parmley R. T. , Kim T. H. , Austin R. L. , Alvarado C. S. , Ragab A. H.
Published: February 2007

Neutrophil engulfment by megakaryocytes was observed within 20 to 30% of megakaryocytes from two children: one with metastatic rhabdomyosarcoma, the other with fever of unknown origin. Other cell types and neutrophil precursors were not observed within megakaryocytes. Only late megakaryocytes were involved in the process, and often these cells appeared vacuolated or degenerating at the light and electron microscope level. Ultrastructurally the engulfed neutrophils were intact and were within the open canalicular system of the megakaryocyte cytoplasm. No evidence of neutrophil granule exocytosis could be demonstrated in ultrastructural morphologic and peroxidase preparations; however, many neutrophils appeared to be endocytosing portions of the megakaryocyte cytoplasm. The phenomenon could not be transferred to normal marrow incubated with patient serum or plasma. Thus, our patients differ from previous observations of emperipolesis in: 1) the extreme frequency of the observation; 2) the selective involvement of neutrophils; and 3) the association of the anomaly with dysmorphic and/or disrupted megakaryocytes. These observations are consistent with a neutrophil response to altered and/or injured megakaryocytes.
Successful treatment of thrombotic thrombocytopenia purpura by vincristine
Authors: Schreeder Marshall T. , Prchal Josef T.
Published: February 2007

Two patients with thrombotic thrombocytopenia purpura (TTP) are described in whom vincristine administration appeared to play a role in successful outcomes. The first patient with chronic TTP responded partially to plasma exchange followed by plasma infusion and transiently to splenectomy, but developed a complete long lasting remission after a single injection of intravenous vincristine. The second patient developed a complete remission following vincristine administration and plasma exchange. Although vincristine's mechanism of action in TTP is obscure, we suggest that vincristine is effective in the treatment of this infrequent and often fatal disease.
Paroxysmal nocturnal hemoglobinuria terminating in TdT‐positive acute leukemia
Authors: Katahira Jun'Ichi , Aoyama Masako , Oshimi Kazuo , Mizoguchi Hideaki , Okada Michiko
Published: February 2007

A case of paroxysmal nocturnal hemoglobinuria (PNH) which developed terminal transfer‐ase (TdT)‐positive leukemia 5 years after the diagnosis of PNH was studied. Most of the leu‐kemic cells were suggestively lymphoid by cytochemistry and electron microscopy, and TdT‐positive by immunofluorescence studies. The development of acute lymphoblastic leukemia during the course of PNH suggests that in PNH the clonal abnormality may involve lymphoid cells as well as myeloid cells, thus raising the possibility of the disease being a disorder of the pluripotential stem cell.
Transcobalamin II deficiency associated with unusual bone marrow findings and chromosomal abnormalities
Authors: Rana Sohail R. , Colman Neville , Goh Kong‐Oo , Herbert Victor , Klemperer Martin R.
Published: February 2007

A female infant presented at seven weeks of age with failure to thrive, progressively severe pancytopenia, hypogammaglobulinemia and, mucosal ulceration. Bone marrow morphology showed severed megaloblastic changes in the myeloid series with a shift to the left and an increased number of blasts with abnormal morphology. Erythroid precursors and megakaryocytes were markedly decreased. Cytogenetic studies showed marked aneuploidy and increased chromosomal breakage. Treatment with high doses of vitamin B12 resulted in a dramatic clinical response with hematological values becoming normal. The patient's serum showed absence of transcobalamin II, and very little TC I and TC III binding. The patient's parents had only half the lower limits of normal transcobalamin II. QUSO G‐32 was used for separation of transcobalamins, and the results were confirmed by Sephacryl S‐300. This case illustrates the usefulness of QUSO in the rapid diagnosis of transcobalamin II deficiency.
Alpha chain and gamma chain abnormal hemoglobins in newborn babies: Structural and genetic aspects
Authors: Nakatsuji T. , Carver J. , Wilson J. B. , Lam H. , Reese A. L. , Nagle S. , Miwa S. , Huisman T. H. J.
Published: February 2007

Structural studies and quantitative analyses were conducted on the hemoglobin of 55 newborn babies. Seven α chain variants (G‐Philadelphia, Montgomery, Inkster, I‐Philadelphia, Matsue‐Oki, Winnipeg, and O‐Indonesia) were present in 26 heterozygous new‐borns (17 black, eight Caucasian, and one Indonesian). The relative amount of the αx containing abnormal Hb F of the Hb G‐Philadelphia and Hb Winnipeg babies was less than observed in heterozygous adults, which may indicate a decreased rate of assembly of the αx‐γ dimer over that of the αx‐β dimer. Of the 29 newborns with γ chain variants, 16 were Caucasian babies; of these 15 had a Hb Aγ F‐Hull heterozygosity and one a Hb GγF‐Marietta heterozygosity. Six black babies were heterozygous for Hb AγF‐Texas‐I and six for Hb GγF‐Port Royal. One Japanese baby had a heterozygosity for AγF‐Iwata and a second was heterozygous for ATF‐Yamaguchi. Quantitative analyses of the isolated normal Hb F0 as well as an evaluation of the relative amounts of the Hb Fx in the red cell lysates gave data useful for a speculation of the genetic condition in each of these babies. It was concluded that the babies with the Hbs F‐Texas‐I, F‐Iwata, F‐Hull, and F‐Marietta were simple heterozygotes with either the Gγ,Aγ/Gγ,AγN or the Gγ,Aγ/Gγx,Aγ genic arrangement. The babies with Hb F‐Port Royal had a Gγ,GγxGγ,Aγ arrangement, which may result from a (to be determined) gene conversion. The newborn baby with Hb F‐Yamaguchi has the Gγ,Aγ/Aγ/TN.—. genic arrangement, suggesting the presence of three distinctly different γ chain genes of which one, the AγT‐X gene, produces an Aγ chain (with threonyl at position γ75 and an Asn at position γ80) at a level usually seen for Gγ rather than Aγ chains. These studies were greatly facilitated by the use of high pressure liquid chromatographic methods.
Pericardial tamponade associated with myeloid metaplasia
Authors: Bubley Glenn , Come Patricia , MacDougall Don , Thurer Robert , Goldberg Joan
Published: February 2007

A 32‐year‐old white male with agnogenic myeloid metaplasia developed pericardial tamponade shortly after elective splenectomy. Tamponade was relieved by pericardiocentesis but recurred, necessitating partial pericardiectomy. Following surgery and a course of radiation therapy to the heart, there was no further significant reaccumulation of fluid. Pathologic evaluation demonstrated foci of extramedullary hematopoiesis in the pericardium. To our knowledge, pericardial tamponade has not previously been reported as a biopsy‐proven complication of myeloid metaplasia.
Essential thrombocythemia: A clonal disorder of hematopoietic stem cell
Authors: Singal Usha , Prasad Ananda S. , Halton David M. , Bishop Carter
Published: February 2007

We studied 5 patients with essential thrombocythemia utilizing glucose‐6‐phosphate dehydrogenase (G‐6‐PD) enzyme as a cell marker for determining clonality. One of the patients was found to be heterozygous for isoenzymes B and A in the nonhaemopoietic tissues such as fibroblasts, but manifested only isoenzyme type B in the erythrocytes, neutrophils, and platelets. Our studies support the concept that essential thrombocythemia is a clonal disorder arising in a multipotent stem cell.
Interaction of protamine sulfate with thrombin
Authors: Cobel‐Geard Richard J. , Hassouna Houria I.
Published: February 2007

Protamine sulfate (salmine), a basic protein with a molecular weight of 4,626 ± 109, is a known antiheparin agent which in the absence of heparin demonstrates an anticoagulant activity. To date, much work has been done to elucidate the interaction of heparin with thrombin and its physiologic inhibitor, Antithrombin III (ATIII). Little is known, however, about the mechanism of anticoagulant action of protamine sulfate and its mode of thrombin inactivation. We provide information about the interaction of protamine sulfate with purified, labeled thrombin and ATIII through binding experiments in which protamine is shown to inhibit the inactivation of thrombin by ATIII. Furthermore, we show in clotting assays that protamine sulfate has an inhibitory effect on thrombin in the conversion of fibrinogen to fibrin, and that this inhibition is concentration dependent, partial, and reversible.
Abnormalities of the spleen and liver in patients with hemophilia
Authors: Meyer William H. , Levin Jack , Ness Paul M. , Bell William R. , Douglass Kenneth H. , Camargo Edwaldo E. , Zinkham William H.
Published: February 2007

Previous studies have demonstrated functional and histologic abnormalities of the liver, and, more recently, splenomegaly in patients with hemophilia. Since these observations usually were derived from hemophiliacs who had received intensive replacement therapy, the question was posed as to whether the frequency of splenic and hepatic abnormalities was secondary to the amount of therapy utilized. In this study, a variety of tests were employed to evaluate spleen and liver size and function to determine if abnormalities in these organs correlated with the intensity of the transfusion program. The study group was comprised of 25 hemophiliacs (mean factor replacement—18,361 U/year; median factor replacement—12,920 U/year). Over 70% of our patients had elevations of aspartate and alanine aminotransferase. Immunoglobulin and complement levels were normal in most subjects. Ninety‐six percent had evidence of exposure to hepatitis B virus. Liver‐spleen imaging suggested significant hepatic abnormalities in most of the patients as evidenced by inhomogeneity of tracer uptake in the liver in 33% and relatively increased colloid uptake in the spleen in 90%. Splenomegaly (palpable spleen or enlargement on liver‐spleen imaging) was detected in 40% of our patients, and tended to occur in the more frequently transfused patients. These findings indicate that significant abnormalities of the spleen and liver can occur in hemophiliacs who have received moderate amounts of replacement therapy and that liver‐spleen imaging may be a useful method for monitoring the development of hepatic and splenic abnormalities.
Transient erythroblastopenia of childhood: Varied pathogenesis
Authors: Freedman Melvin H. , Saunders E. Fred
Published: February 2007

The mechanism of anemia in four patients with transient red cell aplasia of childhood (“erythroblastopenia”) was studied at the time of diagnosis by assessing the colony growth of marrow erythroid progenitors in methylcellulose tissue cultures. Marrow from Patient 1 yielded high normal numbers of BFU‐E colonies that were completely abolished on addition of autologous serum or IgG. Patient 2 had normal BFU‐E growth that markedly declined when autologous serum or IgM was added to the cultures, but growth remained unchanged with added autologous IgG or peripheral blood mononuclear cells (PBMC). Marrow from Patient 3 yielded low CFU‐E and BFU‐E numbers with standard plating techniques, but colonies strikingly increased when marrow fractions from an albumin density gradient were cultured. PBMC from Patient 3 suppressed control marrow CFU‐E and BFU‐E, but serum had no effect. Patient 4 had normal CFU‐E and BFU‐E that increased with autologous serum and remained unchanged with autologous PBMC. We conclude that the red cell aplasia in Patients 1, 2, and 3 was due to suppressed erythropoiesis via IgG, IgM, and cell‐mediated inhibition, respectively. In contrast, in Patient 4 no immune mechanism was demonstrated. Whereas transient red cell aplasia has a uniform clinical presentation, there are at least four pathogenetic mechanisms that can be detected in vitro.
Migration of human leukocytes from soft agarose droplet: A simplified method for studying chemotaxis and spontaneous migration
Authors: Barak Yigal , Karov Yocheved , Levin Stanley
Published: February 2007

Studies of in vitro chemotaxis and spontaneous migration of human leukocytes using the accepted method with the Boyden‐chamber‐filter are troublesome, because of the need for specially constructed vessels as well as the difficulties caused by the use of membrane filters. We describe a new and simplified method for measuring human leucocyte chemotaxis, which is a modification of the recently described underagarose migration method and which is based upon spontaneous migration of cells from a soft agarose droplet and in response to a chemotactic gradient. We examined suspensions of leukocytes, purified granulocytes, and mononuclear cells from 10 healthy normal adults and from 10 samples of cord blood using E Coli O111B4 endotoxin‐activated human serum as attractant. Our results showed that the mean chemotactic indices (C.I.‐chemotaxis/migration) for purified granulocytes and for mononuclear cells from normal individuals were 3.0 ± 1.2 and 2.7 ± 1.5, respectively. Chemotaxis was significantly reduced when unwashed leukocytes were studied, indicating a detrimental effect of autologous plasma on leukocytic response to a chemotactic stimulus in this system. Cord blood cells showed normal spontaneous migration, but significantly decreased chemotaxis. This preliminary report shows that the technique is simple, rapid, and reproducible, and can detect abnormalities of chemotaxis in both granulocytes and mononuclear cells.
Red cell adenylate kinase deficiency associated with hereditary nonspherocytic hemolytic anemia: Clinical and biochemical studies
Authors: Miwa Shiro , Fujii Hisaichi , Tani Kenzaburo , Takahashi Keisuke , Takizawa Takenori , Igarashi Takashi
Published: February 2007

We report here a case of red cell adenylate kinase (AK) deficiency associated with hereditary hemolytic anemia. The proband is a 10‐year‐old Japanese girl. Her physical and mental development was normal. She has shown moderate to mild hemolytic anemia since the neonatal period and hepatosplenomegaly. The red cell AK activity was 44% of normal. Contents of red cell glycolytic intermediates and adenine nucleotides were normal when compared with a comparable reticulocyte‐rich control. Glucose consumption and lactate formation were normal. Hexose monophosphate shunt activity was somewhat lower than that of a comparable reticulocyte‐rich control. There were no significant differences in the contents of adenine nucleotides between the younger and older red cells of the patient. Enzymatic characterization by hemolysate revealed that the patient's AK had an increased Michaelis constant for adenosine diphosphate and slight thermal instability. The patient's enzyme migrated approximately half‐way between the AK 1 and AK 2 position on starch‐gel electrophoresis. The mode of inheritance of this case is obscure. The mechanism of hemolysis might be a structural gene mutation that caused altered electrophoretic and kinetic properties.
Mechanism of defibrination in humans after envenomation by the eastern diamondback rattlesnake
Authors: Kitchens Craig S. , van Mierop Lodewyk H. S.
Published: February 2007

We prospectively studied the hemostatic system of ten persons bitten by the Eastern diamondback rattlesnake (Crotalus adamanteus) during 1978–1980. Blood was drawn when the patients arrived in the emergency room and every 6 hr thereafter. All envenomated victims developed incoagulable blood (defined by a thrombin time ≥ 120 sec, normal < 20 sec). Platelet counts and plasma levels of antithrombin III and factors II and VIII were not drastically altered, which distinguished this disorder from classic disseminated intravascular coagulation. Fibrinogen levels were markedly decreased (mean coagulable level of 0 mg/dl and antigenic levels of 99 mg/dl). Plasminogen levels were 20% of normal, alpha‐2‐plasminogen inhibitor was 17% of normal, and plasminogen activator was 20 times normal. Levels of fibrin degradation products peaked at a mean of 7,680 μg/ml. The magnitude and duration of the coagulopathy were proportional to the clinical severity of envenomation. Treatment with antivenin blunted the coagulopathy. Because venom from the Eastern diamond‐back rattlesnake does not directly activate plasminogen, we conclude that coagulopathy following envenomation by that reptile appears to be due to partial proteolysis of fibrinogen with secondary activation of plasminogen by released plasminogen activator, probably of endothelial orgin.
Hereditary disorders of red cell enzymes in the embden‐meyerhof pathway
Authors: Miwa Shiro
Published: February 2007

Recent advances about hereditary disorders of red cell enzymes in the Embden‐Meyerhof glycolytic pathway and Rapoport‐Luebering cycle are discussed with a stress on pyruvate kinase deficiency, because it is the most common and most intensively studied disorder among them. Broad genetic heterogeneity exists in all the known erythroenzymopathies. Recently, the primary structure of normal human red cell phosphoglycerate kinase has been determined and single amino acid substitutions of four mutant phosphoglycerate kinases have been clarified by Yoshida et al. These studies allowed analysis of structure‐function relationships at the molecular level to be carried out more precisely than was previously possible. It is the consensus of the investigators working in this field that the pathogenesis in three‐quarters of the congenital nonspherocytic hemolytic anemia patients remains unknown even after adequate red cell enzyme studies and isopropanol test for unstable hemoglobin have been done. This simply means that much studies remain to be worked out in this field.
Studies on abnormal polymorphonuclear neutrophils in acute myelogenous leukemia: Clinical significance and changes after chemotherapy
Authors: Suda T. , Onai T. , Maekawa T.
Published: February 2007

In patients with acute myelogenous leukemia (AML), 34 out of 35 patients (97%) had cytochemically abnormal polymorphonuclear neutrophils (PMN). Some interesting regularity was noted in the appearance of cytochemical abnormalities of the PMNs. When peroxidase (PO) activity was low, both alkaline phosphatase (AP) and chloroacetate esterase (CAE) activities were also low (group A). When PO activity was normal, if AP activity was low, CAE activity tended to be high (group B) and if AP activity was high, CAE activity tended to be low (group C). Complete remission rate of group B (65%) seemed to be better than that of group C (20%) and group A (25%) although the differences was not statistically significant. In these patients, the number of peripheral leukemic blasts and PMNs showed a significant positive correlation (r = 0.69, p < 0.005). Furthermore, patients with higher circulating PMN counts (more than 2 × 109/L) had a significantly worse prognosis than patients with lower counts (p < 0.05). These rather unexpected findings strongly suggest that cytochemically abnormal PMNs are progeny of AML blasts. The change in the proportion of abnormal PMNs associated with chemotherapy were studied in 21 patientas during the remission induction period. Abnormal PMNs disappeared from the circulation in patients who achieved complete remission. In contrast, abnormal PMNs persisted throughout the remission induction period in patients who failed to achieve complete remission.
Serum‐free light chain analysis by crossed immunoelectrophoresis: Correlation with plasmapheresis in light chain disease nephropathy
Authors: McLeod Bruce C. , Viernes Ann L. , Sassetti Richard J.
Published: February 2007

The technique of crossed immunoelectrophoreis (X‐IEP) has been used to quantify free monoclonal light chains (LC) directly in the serum of patients with light chain disease, without preliminary gel or membrane filtration of serum to separate whole immunoglobulin. LC concentration is proportional to the area under an immunoprecipitin peak formed by LC in the patient's serum and an anti‐LC antibody of appropriate specificity. Light chains of beta electrophoretic mobility can be processed in the standard X‐IEP technique at pH 8.6. Light chains of gamma mobility must be processed in a modified technique using a pH of 5.0 and a carbamylated antiserum in the second dimension gel. Dose response curves obtained from the method in serial dilution experiments with sera from 18 patients gave correlation coefficients ± 0.99. Replicate measurements of absolute LC concentration on the same specimens were within ± 10%. The method can also detect polymerized light chains. Serum light chain levels were measured during the course of plasmapheresis therapy in three patients with light chain disease and renal failure. Light chain levels were shown to fall after plasmapheresis and to rise rather rapidly in the interval between treatments.
Waldenström macroglobulinemia terminating in acute leukemia: A report of three cases
Authors: Horsman Douglas E. , Card Robert T. , Skinnider Leo F.
Published: February 2007

Acute leukemia was observed to develop in three patients with Waldenstöm marcroglobulinemia. Each patient had been treated with cytotoxic drug therapy. Pancytopenia preceded the onset of the terminal leukemia in two of the three cases. The acute leukemias were all of acute myelogenous type. All of the patients died soon after the development of the terminal leukemia. A number of recent reports have documented acute terminal leukemia in patients with macroglobulinemias and multiple myeloma, as well as other malignant and nonmalignant diseases. The role of the cytotoxic drugs, especially chlorambucil, cyclophosphamide, and melhalan, in leukemogenesis has been raised by these recent reports.
Heinz‐body anemia: “Bite Cell” variant— A light and electron microscopic study
Authors: Ward Patrick C. J. , Schwartz Burton S. , White James G.
Published: February 2007

Light and scanning electron microscopic studies of blood from five patients with drug‐induced oxidant hemolysis are presented. None of the patients had a previous history of hemolytic disease and laboratory studies indicated no evidence of either glucose‐6‐phosphate dehydrogenase (G6PD) deficiency or unstable hemoglobinopathy. Although the red cell deformities in our patients overlapped to some extent with those reported in patients with microangiopathic hemolytic anemia (MAHA) and in patients with G6PD deficiency undergoing oxidant hemolysis, striking differences were also observed. Cell fragments, commonly found in patients with MAHA, and eccentrocytes, frequently found in patients with G6PD deficiency undergoing oxidant hemolysis, were seldom found in blood samples from the five patients in this study. Bite cells were extremely common in our patients. They are rare in patients with either of the above disorders. An awareness of the morphologic abnormalities detailed in this report may help characterize the nature of a hemolytic process so that appropriate therapy can be initiated.
Leukocyte alkaline phosphatase: Another organ‐specific alkaline phosphatase
Authors: Miller Donald M. , Yang Angela , Liepman Marcia
Published: February 2007

We have used enzyme specific inhibitors and heat inactivation to distinguish Leukocyte alkaline phosphate (LAP) from other organ‐specific alkaline phosphatases as well as to compare LAP from normal granulocytes and leukemic cells with elevated LAP. The heat inactivation and inhibition curves of LAP are quite different from those of other organ‐specific alkaline phosphatases. The inhibition curves and heat inactivation characteristics of LAP from normal granulocytes and that obtained from chronic granulocytic leukemia (CGL) blast phase cells with elevated LAP are identical. These data suggest that LAP is distinct from other organ‐specific alkaline phosphatases, particularly placental alkaline phosphatase. We also conclude that the LAP present in cells with elevated levels is very similar or identical to that of normal granulocytes.
Splenectomy for thrombocytopenia in chronic lymphocytic leukemia
Authors: Merl Stuart A. , Theodorakis Michael E. , Goldberg Jack , Gottlieb Arlan J.
Published: February 2007

The role of peripheral platelet destruction as a reversible etiology of thrombocytopenia in chronic lymphocytic leukemia (CLL) was evaluated in nine patients with CLL and refractory thrombocytopenia who underwent splenectomy. The patients' ages ranged from 54 to 74 years. Progressive thrombocytopenia refractory to antineoplastic agents and corticosteroids had been present for a mean of 23.4 months. The platelet counts were 4,000–57,000/μl, and were generally higher in those patients with larger spleens. The spleens ranged from 180 to 4050 gm.

Seven patients responded completely to splenectomy, achieving platelet counts > 150,000/μl, and in one other patient, the count rose to > 100,000/μl. The platelet count of one patient failed to respond to surgery. Those patients with massive splenomegaly developed higher, more rapidly rising platelet counts postoperatively. No operative mortality was encountered. Median hospitalization was seven postoperative days. All patients experienced an increased sense of well‐being. Median follow‐up time is 9 months.
Acquired partial deletions of the long arm of chromosome 5 in hematologic disorders
Authors: Wisniewski Lawrence P. , Hirschhorn Kurt
Published: February 2007

We have analyzed the data on 105 patients reported with a deletion of part of the long arm of chromosome 5 in the presence of hematologic disease. The major conditions associated with this abnormality are refractory anemia, polycythemia vera, and acute myelogenous leukemia, as well as the occasional occurrence of several other problems.