bluuebunny/crossref_metadata_2025 huggingface dataset:
Red cell ferritin and iron overload in heterozygous beta‐thalassemia
Authors: van der Weyden Martin B. , Fong Hubert , Hallam Lynnette J. , Harrison Christine
Published: February 2007

Red cell ferritin was evaluated in 101 individuals with heterozygous beta‐thalassemia to determine its clinical utility as an index for iron deficiency or overload in these subjects. The mean red cell ferritin for the total population was elevated threefold and showed a significant correlation with transferrin saturation, plasma ferritin, and HbA2 levels. Five of six subjects with reduced red cell ferritin had associated iron deficiency; a further five had iron deficiency and normal red cell ferritin. Normal red cell ferritin occurred in 51 subjects, and 44 had increased values. In the elevated red cell ferritin group, 21 individuals had associated normal plasma ferritin, and 23 had increased plasma ferritin. Only in the latter group was red cell ferritin significantly correlated with transferrin saturation and plasma ferritin. Ten individuals had a red cell ferritin ≤ 150 attogram/cell, and liver biopsy performed in four showed grades II to IV iron overload. A clinical feature of subjects with both increased red cell and plasma ferritin levels was a high incidence of inappropriate iron administration. These findings suggest that red cell ferritin, particularly when combined with plasma ferritin, is a useful parameter for determining potential iron overload in individuals with heterozygous beta‐thalassemia.
HLA antibody formation within the HLA‐A1 crossreactive group in multitransfused platelet recipients
Authors: Macpherson Bruce R.
Published: February 2007

The formation of intragroup antibodies, HLA antibodies directed against antigens in the same crossreactive group (CREG) as those of the serum donor, may be an important cause of transfusion failures in patients receiving HLA‐matched platelets. Twenty‐two patients whose HLA types included at least one antigen in the HLA‐A1 CREG were studied. Of the ten patients who formed HLA antibodies, six produced antibodies that reacted with one or more antigens in the HLA‐A1 CREG. Five of 12 patients whose HLA types included HLA‐A3 formed antibodies directed against HLA‐A1‐10‐11 or HLA‐A1‐10. In contrast, only one of ten individuals whose phenotypes included HLA‐A1, HLA‐A11, or both produced anti‐HLA‐A3. Eleven incompatible retrospective crossmatches were observed in recipients of HLA‐matched platelets attributable to intragroup antibodies. Patients receiving incompatible platelets had unsatisfactory post‐transfusion platelet count increments. It is concluded that intragroup antibodies, such as those directed against antigens in the HLA‐A1 CREG, are an important cause of platelet transfusion failures in patients requiring long‐term platelet transfusion support. These antibodies can be identified by routinely screening recipient sera for HLA antibodies and performing retrospective crossmatches using the lymphocytotoxicity technique.
Hybrid acute leukemia in an HIV‐antibody‐positive patient
Authors: Gold Jay E. , Babu Arvid , Penchaszadeh Victor , Castella Antonio , Ghali Violette , Zalusky Ralph
Published: February 2007

Although the great majority of acute leukemias have been designated as being of lymphocytic or myelocytic origin, recent reports have described elements of both in some patients. We describe here the first case of hybrid acute leukemia in an HIV‐antibody‐positive patient as well as the first hybrid involving B‐cell (Burkitt) acute lymphocytic leukemia and acute myelomonocytic leukemia proven by cytochemical, immunologic, and cytogenetic methods. This case illustrates the increasingly complex difficulties in the diagnosis and treatment of AIDS‐related malignancies.
Long‐term effect of splenectomy on transfusion requirements in thalassemia major
Authors: Cohen Alan , Gayer Robin , Mizanin Jeannie
Published: February 2007

Splenectomy reduces transfusion requirements in the first year after surgery in patients with thalassemia major and hypersplenism. To determine whether this response is maintained, we have studied transfusion requirements in 16 patients with thalassemia major for 2–17 years after splenectomy. Transfusion requirements remained stable (mean yearly change ‐0.1%) after the predictable fall in the first year after surgery. The mean change between the first postoperative year and the most recent year was ‐7 ml/kg. Transfusion requirements and the magnitude of change from year to year were unrelated to the time since splenectomy. These studies indicate that the effect of splenectomy on transfusion requirements is long‐lasting and that large variations in annual transfusion requirements after splenectomy should prompt a search for accessory spleens or other causes of red cell destruction.
B‐cell chronic lymphocytic leukaemia: Prognostic value of the immunophenotype and the clinico‐haematological features
Authors: Orfao Alberto , Gonzalez Marcos , Fernando Miguel J. San , Rios Agustin , Canizo M. Consuelo , Hernandez Jose , Maricato M. Lourdes , Borrasca Antonio Lopez
Published: February 2007

Sixty‐two previously untreated patients with B‐cell chronic lymphocytic leukaemia were analysed to study the prognostic value of both the immunologic phenotype and the clinicobiologic characteristics. Univariate studies showed that none of the immunological markers analysed, sheep‐rosette, mouse‐rosette, slg, and HLA/DR, CD20, FMC7, CD5, and CD9 antigens, had a significant influence on survival. On the other hand, several clinical and haematological characteristics were identified as being associated with survival: 1) clinical features—presence of lymphadenopathies (P< .05) and hepatomegaly and/or splenomegaly (P< .04); 2) haematologic parameters—presence of anaemia and/or thrombopenia (P< .05), the absolute peripheral blood lymphocyte count (P< .03), and the presence of hypogammaglobulinemia (P< .08); 3) biochemical parameters—serum uric acid (P< .03); and 4) bone marrow histopathological features—biopsy pattern (P< .04) and the percentage of lymphocytes in bone marrow aspirate (P< .03). Both the Rai staging and the International Workshop on CLL staging systems were effective in identifying groups of patients with significantly different prognoses (P< .05). Multivariate regression analysis demonstrated that the combination of three clinicopathologic characteristics (bone marrow histopathologic pattern, absolute peripheral blood lymphocyte count, and the presence or not of hypogammaglobulinaemia) had the strongest predictive relationship with survival time.

In summary, our findings show that the clinicobiological and anatomopathologic parameters have much more prognostic relevance than the immunological markers analysed in the present study.
Abnormal fibrinolysis in healthy male cigarette smokers: Role of plasminogen activator inhibitors
Authors: Haire William D. , Goldsmith Jonathan C. , Rasmussen Julie
Published: February 2007

The extrinsic fibrinolytic system and its response to cigarette smoking was studied in five healthy male smokers 35–45 years old. Tissue plasminogen activator (t‐PA) release in response to venous occlusion was intact both at 8:00 A.M. and 3:00 P.M. Acutely smoking two cigarettes neither stimulated fibrinolysis nor changed levels of t‐PA or plasminogen activator inhibitors. Functional plasminogen activator inhibitor (PA‐I) levels and euglobulin lysis times were higher in the smoking group than in a control group matched for age, sex, and body mass. Antigenic levels of PA‐I 1, the PA‐I derived from vascular endothelial cells and platelets, were similar in both groups. While smoking did not acutely alter fibrinolysis in chronic smokers, these individuals had a high frequency of abnormal fibrinolysis characterized by high levels of PA‐I activity. This abnormality is due to either high specific activity of PA‐I 1 or to the presence of other antigenically distinct plasminogen activator inhibitors. Abnormal firbinolysis may be one mechanism contributing to the thrombotic diathesis of cigarette smokers.
Emergency caesarian section and symptomatic immune thrombocytopenic purpura
Authors: Wood Lucille , Jacobs Peter
Published: February 2007

A 24‐year‐old woman presented in labour with profound purpuric bleeding due to idiopathic immune thrombocytopenia. She was assessed as requiring immediate caesarian section for cephalopelvic disproportion and foetal distress. In view of her platelet count of 21 × 109/L she was prepared with intravenous methylprednisolone, isovolaemic plasma exchange, and infusion of 400 mg/kg of gammaglobulin and 5 × 1011 allogeneic platelets. Six hours after commencing the procedure, at a time when her platelet count was 97 × 119/L, she went uneventful operation and with no further therapy this level subsequently reached 175 × 109/L, at which time an uneventful operation was performed. The mother and her normal, full‐term infant have been discharged; both are well and at follow‐up have normal platelet counts. This experience illustrates that major surgery can safely be undertaken in severely thrombocytopenic patients, even as an emergency procedure, using this regimen.
Protein S and C antigen levels in proteinuric patients: Dependence on type of glomerular pathology
Authors: Allon Michael , Soffer Oved , Evatt Bruce L. , Hixon Gwen , Wideman Carol S.
Published: February 2007

The cause of the thrombotic tendency in nephrotic patients is unknown. Recent reports of thrombotic complications in patients with deficiencies of protein C or protein S (natural inhibitors of coagulation) have raised the possibility that decreased levels of these proteins may play a role in the hypercoagulable state of nephrotic patients. We measured the levels of protein C, total protein S, and free protein S antigens in 42 patients (21 nephrotic and 21 non‐nephrotic) with one of four types of glomerular pathology: diabetic nephropathy (DM), focal glomerular sclerosis (FGS), membranous glomerulonephritis (MGN), and chronic renal failure due to hypertension (CRF). Protein C and total protein S antigen levels were significantly higher in FGS and MGN than they were in DM or CRF. Free protein S levels were lower in DM than they were in MGN. Protein C, total protein S, and free protein S levels did not significantly correlate with either serum albumin or degree of proteinuria. The mean levels of the three proteins did not differ between nephrotic and non‐nephrotic patients. Free protein S and protein C were, however, significantly correlated (P < .005 and P < .002, respectively) with the type of glomerular pathology, independent of differences in age, sex, serum albumin, or degree of proteinuria. These data suggest that abnormalities of free protein S and protein C are related to the nature of the underlying renal disease, rather than to the degree of proteinuria.
Heparin cofactor II in adults and infants with thrombosis and DIC
Authors: Chuansumrit Ampaiwan , Manco‐Johnson Marilyn J. , Hathaway William E.
Published: February 2007

Heparin cofactor II (HC II) was measured by a chromogenic activity assay in normal preterm infants (gestational age, 28–36 weeks; n = 17; 29% ± 11.5 [mean ± 1 SD], range 11–51), normal full‐term infants (n = 18; 49% ± 6.6 [mean ± 1 SD], range 36–58), and normal adults (n = 38; 101% ± 14 [mean ± 1 SD], range 73–130). Normal children attained adult levels at approximately 5 to 7 months of age. The lower values in preterm and term infants most likely reflect immature liver function.

Neither adults and children with a history of thrombosis with prior negative evaluation (n = 74), patients with documented protein C and protein S deficiency (n = 4), nor sick infants without evidence of consumptive coagulopathy (n = 15) had significantly lower levels of HC II activity. Infants with disseminated intravascular coagulation (n = 2) had strikingly lower levels of HC II activity.
Chronic myeloid leukemia associated with pure red cell aplasia and terminating in promyelocytic transformation
Authors: Mijovic Aleksandar , Rolovic Zoran , Novak Angelina , Biljanovic‐Paunovic Lidija , Tomin Dragica
Published: February 2007

After intermittent treatment with busulphan over a 7‐year period for chronic myeloid leukemia (CML) in chronic phase, a 39‐year‐old female developed leukocytosis in association with pure red cell aplasia (PRCA). Bone marrow examination confirmed erythroid aplasia, and culture revealed a total absence of erythroid progenitor cells. The patient then was treated with azathioprine, corticosteroids, cyclophosphamide, plasma exchange, and cyclosporin A, but she remained erythroblastopenic and transfusion dependent for more than a year, at which time a promyelocytic transformation supervened. The authors propose that this sequence of events, hitherto unreported, is a manifestation of the multistep progression of CML.
Hemoglobin synthesis in BFU‐E colonies derived from transfused blood in a sickle cell anemia patient
Authors: Bhaumik Kabita
Published: February 2007

In an in vitro progenitor cell culture system, a significant amount of normal hemoglobin (Hb A) synthesis was observed in a transfused sickle cell anemia (SS) patient, indicating the contribution of stem cells obtained from the normal donor's blood cells. As this study was done long after the last blood transfusion (> 100 days), the survival of the donor's stem cells would indicate their repopulating the recipient's bone marrow. On extending the study to a few other transfused SS patients who had received multiple blood transfusions at frequent intervals, no such synthesis of Hb A was observed. A loss of repopulating ability of the donor's stem cells with frequent transfusions at short intervals is suggested as a possible explanation, with a gradual development of immune response against these cells as a second possibility. The differences in the survival of the donor's stem cells would thus appear to have some reflection on the frequency of blood transfusions required by an individual patient.
Steroid‐responsive pure red cell aplasia associated with natural killer cell lymphocytosis
Authors: Tefferi Ayalew , Windebank Kevin P. , Veeder Michael H. , Kiely Joseph M.
Published: February 2007

A patient with pure red cell aplasia and expansion of the peripheral blood natural killer (NK) cell population is described. Despite normal absolute and differential leukocyte counts, NK cells were increased at diagnosis and at relapse. Furthermore, these cells were not morphologically recognizable on the peripheral blood smear examination. A favorable clinical response to glucocorticoid therapy was accompanied by a decrease in NK cells.
Agranulocytosis associated with “mexican aspirin” (dipyrone): Evidence for an autoimmune mechanism affecting multipotential hematopoietic progenitors
Authors: Hargis J. B. , La Russa V. F. , Redmond J. , Kessler S. W. , Wright D. G.
Published: February 2007

A case of acute, transient agranulocytosis and thrombocytopenia associated with ingestion of dipyrone is reported. This once widely used analgesic, which is now banned in the United States, was obtained by the patient as “aspirin” while traveling in Mexico. Studies of the effects of this patient's serum on purified CD34+ marrow cells, which were highly enriched for hematopoietic progenitors, showed not only a drug‐dependent suppression of the in vitro growth of myeloid progenitors, as has been reported previously, but also a drug‐dependent suppression of primitive multipotential progenitors (CFU‐Mix) and erythroid progenitors (BFU‐E). These findings indicate that autoimmune, antibody‐hapten interactions which have been reported to occur in dipyrone‐ and aminopyrine‐induced agranulocytosis are not restricted to the neutrophil lineage.
Platelet activation during pain crisis in sickle cell anemia patients
Authors: Beurling‐Harbury Christina , Schade Stanley G.
Published: February 2007

Platelet activation at sites of enmeshed sickled red cells in the microcirculation may contribute to platelet plug formation and microinfarction in sickle cell anemia. To test this hypothesis platelets from 116 sickle cell anemia patients free of crisis, 32 patients with crisis, 16 convalescents within 1 week of crisis, and 180 normal controls were studied. Platelets store 90% of their ADP in dense secretory granules. During activation ADP is secreted and permanently lost from the cell. This leads to a decrease in cellular ADP concentration and a sharp rise in the ATP/ADP ratio. ATP and ADP were ethanol‐extracted from platelet‐rich plasma, measured in the luciferase‐luciferin assay and expressed in nmoles per 108 cells. No adenine nucleotide differences were found in platelets from patients free of crisis compared with normal controls. The ADP concentration of platelets from patients in crisis was significantly lowered, indicating that in vivo platelet secretion of ADP had occurred. Total and released ADP was decreased from 2.69 to 1.66, and from 1.90 to 1.21 respectively, and the total ATP/ADP ratio was increased from 1.85 to 2.84 (P < 0.001). ADP stores in platelets from convalescents were significantly different from sickle controls (P < 0.001) but were less abnormal than ADP stores in platelets from crisis patients (P < 0.01), indicating recovery. Total and released ADP was decreased to 1.97 and 1.31 respectively, and the ATP/ADP ratio was increased to 2.38. Platelets from patients in crisis were able to release their remaining granular ADP in response to thrombin as effectively as normal platelets. Thus significant platelet activation with ADP release occurs during acute sickle pain crisis. This might contribute to platelet plug formation and microvascular obstruction.
Positional effect of cis/trans alpha globin gene deletions on the formation of “H” bodies
Authors: Thompson C. C. , Ali M. A. M. , Boyadjian S. , Vacovsky M.
Published: February 2007

Normal individuals have four AaL‐globin genes, two on each member of the chromosome 16 pair (αα/αα). The α‐thalassemia trait phenotype associated with deletions of two α‐genes can be either on the same chromosome, the cis type (αα/—), or on opposite chromosomes, the trans type (α‐/α‐). Traditionally, the observation on vitally stained smears of occasional cells containing “H” bodies has been used as an important diagnostic criterion for α‐thalassemia trait. These “H” bodies are thought to be precipitated β tetramers because of the presence of excess β‐globin chains. Our study in patients with various α‐genotypes indicates that normal subjects (αα/αα) and patients with silent α‐thalassemia trait (αα/α‐) generally have no “H” bodies. However, patients with the two‐gene deletion of the cis type α‐thalassemia (αα/—) show the occasional “H” body, and those with Hb “H” disease (α‐/—or αcs‐/—) show many such bodies. On the other hand, patients with two‐gene deletion of the trans type (α‐/α‐) do not show “H” bodies.

The number of “H” bodies found does not appear to correlate directly with the degree of imbalance in α‐ and β‐chain production among the various α‐genotypes examined. The chemical nature of “H” bodies is discussed, and an alternative hypothesis that embryonic ζ chains expressed in the cis type but not in the trans type of α‐thalassemia are involved in the formation of “H” bodies is proposed.
Myelodysplastic syndrome with trisomy 8 in an adolescent with fanconi anaemia and selective igA deficiency
Authors: Standen Graham R. , Hughes Leuan A. , Geddes A. Denise , Jones Brian M. , Wardrop Charles A. J.
Published: February 2007

We describe a patient with growth failure and multiple congenital anomalies characteristic of Fanconi anaemia, but without the classical feature of progressive bone marrow hypoplasia. Following treatment with growth hormone for a period of 8 years, he presented with myelodysplastic syndrome and a karyotypically abnormal clone in the bone marrow (47,XY, + 8). The diagnosis of Fanconi anaemia was supported by the induction of abnormally high levels of characteristic chromosome aberrations in peripheral lymphocytes following exposure in vitro to the bifunctional alkylating agent mitomycin C. Immune function studies also identified a selective IgA deficiency. The relative importance of interacting constitutional and exogenous factors involved in the development of preleukaemia in this patient is discussed.
Impaired erythrocyte nad synthesis: A metabolic abnormality in thalassemia
Authors: Zerez Charles R. , Tanaka Kouichi R.
Published: February 2007

We have recently demonstrated that phosphoribosylpyrophosphate (PRPP) synthetase activity is decreased in RBC from individuals with thalassemia minor. Because NAD biosynthesis requires PRPP, the product of the PRPP synthetase reaction, we have investigated NAD synthesis in thalassemic RBC. NAD synthesis was measured in intact RBC both by following the accumulation of unlabeled NAD and by following the incorporation of 14C‐nicotinic acid into NAD. Using both assay systems, we demonstrate that NAD synthesis is decreased significantly in thalassemic RBC compared to either normal or high reticulocyte red cells. Although this suggested that NAD content should be decreased in thalassemic RBC, no significant difference in NAD content was found among thalassemic, normal, or high reticulocyte red cells. Mechanisms for the lack of a significant decrease in NAD content in thalassemic RBC are discussed. These results indicate that NAD synthesis is impaired in thalassemic RBC possibly as a result of their decrease in PRPP synthetase activity. Our data provide evidence that thalassemic RBC have secondary metabolic abnormalities in addition to their primary defect in hemoglobin synthesis.
Hb Warsaw (β42 Phe → Val): An unstable hemoglobin with decreased oxygen affinity. I. Hematologic and clinical expression
Authors: Honig George R. , Telfer Margaret C. , Rosenblum Barnett B. , Vida Loyda N.
Published: February 2007

Four members in two generations of a Polish‐American family exhibited findings of congenital Heinz‐body hemolytic anemia accompanied by cyanosis. Two of the affected family members have also developed severe pulmonary hypertension, with a fatal outcome in one of them. Blood from the affected individuals showed decreased oxygen affinity and contained elevated levels of methemoglobin. An unstable hemoglobin fraction underwent rapid precipitation following exposure of the red cell lysates to isopropyl alcohol or heat. This hemoglobin contained a newly identified abnormal β chain with an amino acid substitution at the same position as that of Hb Hammersmith and Hb Bucuresti‐Louisville.
Flow cytometric evidence for minimal residual disease and cytological heterogeneities in acute lymphoblastic leukemia with severe hypodiploidy
Authors: Tsurusawa Masahito , Kaneko Yasuhiko , Katano Naoyuki , Niwa Makoto , Ito Mari , Fujimoto Takeo
Published: February 2007

Two subpopulations of small and large leukemia cells and binucleated cells were present in the bone marrow of a 10‐year‐old girl with acute lymphoblastic leukemia (ALL). Cytogenetic studies showed some cells with a karyotype of 34, X, ‐X, ‐2, ‐3, ‐4, ‐5, ‐7, ‐9, ‐13, ‐15, ‐16, ‐17, ‐20, and others with a karyotype that was exactly double the chromosome set in the cells with 34 chromosomes. Flow cytometric (FCM) examination of surface common ALL antigen (CALLA) and DNA content of the lymphoblasts led to the identification of the primary hypodiploid DNA stemline (DI = 0.72), which corresponds to the small‐sized blasts, and the secondary hyperdiploid DNA stemline (Dl = 1.44), which corresponds to the large‐sized blasts. Sequential bone marrow examinations with FCM and cytogenetics revealed the persistence of the primary hypodiploid clone during remission and their proliferation with chromosomal evolution at full relapse. These results suggest that more rational inductive therapy should be designed to achieve the favorable outcome of ALL with severe hypodiploidy and that FCM is a useful tool to monitor the minimal residual disease of this subgroup in ALL.
Severe hemolysis and red cell fragmentation caused by the combination of a spectrin mutation with a thrombotic microangiopathy
Authors: Jarolim Petr , Palek Jiri , Coetzer Theresa L. , Lawler Jack , Velez‐Garcia Enrique , Fradera Jean , Charles Agnes , Jacob Harry S. , Moake Joel L.
Published: February 2007

Two patients are described who presented with severe hemolysis and erythrocyte fragmentation. One patient had renal allograft rejection and disseminated intravascular coagulation, and the other had thrombotic thrombocytopenia purpura. The severity of hemolysis and the red cell abnormalities were considerably more profound than usually seen in patients with thrombotic microangiopathies. After evaluation of blood smears prepared before the onset of the disease and biochemical characterization of proteins of the red blood cell skeleton, a mutation of the skeletal protein spectrin, designated Sp α1/65, was identified. In the heterozygous form, this mutation manifests as mild, often asymptomatic, hereditary elliptocytosis. We conclude that in these two patients with thrombotic microangiopathy, the intrinsic red cell membrane instability resulting from the underlying skeletal defect aggravated the mechanical red cell fragmentation, producing morphological features similar to the severe hemolytic form of hereditary elliptocytosis or hereditary pyropoikilocytosis.
Current approaches to the chemotherapy of B‐cell chronic lymphocytic leukemia: A review
Authors: Cheson Bruce D.
Published: February 2007

Standard therapy has not substantially improved the outcome of patients with chronic lymphocytic leukemia (CLL). However, an increased understanding of the biology and immunology of CLL, and the availability of several new and active chemotherapy agents (eg, fludarabine, 2′‐deoxycoformycin [DCF], 2‐chlorodeoxyadenosine [CDA]) has stimulated enthusiasm for clinical trials. DCF induces CRs or PRs in 25% of heavily treated patients. Fludarabine has been associated with a response rate of > 50% in previously treated patients, and > 70% in untreated patients, with almost a third of these achieving a CR. Currently, phase I and II clinical trials are evaluating combinations of these drugs with each other or with conventional agents (eg, fludarabine/chlorambucil [CLB]/ prednisone [P]; DCF/CLB/P; fludarabine/DCF; fludarabine/P) in previously treated patients. To facilitate comparison of these regimens, each study is adhering to the NCl‐Working Group guidelines for eligibility and response criteria, and toxicity assessment. A collaborative phase III trial will then compare the most promising of these regimens with “standard” chemotherapy in previously untreated patients. The widespread availability of these clinical trials will allow clinicians ready access to the new treatments.
Utility of flow cytometric reticulocyte quantification as a predictor of engraftment in autologous bone marrow transplantation
Authors: Davis Bruce H. , Bigelow Nancy , Ball Edward D. , Mills Letha , Cornwell Gibbons G.
Published: February 2007

Flow cytometric reticulocyte quantification with thiazole orange (TO) was used to study erythropoiesis in 20 patients following autologous bone marrow transplantation for the treatment of acute myelogenous leukemia. Flow cytometric reticulocyte analysis provided not only the reticulocyte percentage and absolute reticulocyte count but a quantitative reticulocyte maturity index (RMI) proportional to the amount of RNA in the reticulocytes. The RMI values, but not the reticulocyte percentage or absolute counts, correlated temporally with the rise in the absolute neutrophil counts in the posttrans‐plantation period. In the majority of patients (12/20), the RMI value was the earliest indicator of bone marrow engraftment. The findings of this study demonstrate an important clinical utility of TO reticulocyte analysis by flow cytometry and indicate the diagnostic importance of the RMI measurement in the evaluation of erythropoietic activity in bone marrow transplant patients.
Low protein s in essential thrombocythemia with thrombosis
Authors: Conlan Maureen G. , Haire William D.
Published: February 2007

Patients with essential thrombocythemia (ET) are at increased risk for large‐vessel and microvascular thrombosis, presumably because of abnormal platelet number and function. To determine if another hemostatic abnormality might contribute to this thrombotic risk, we investigated protein C and protein S and the fibrinolytic system in four patients with ET. The patients segregated into two distinct groups. The first group consisted of two patients with moderate thrombocytosis who were without thrombotic symptoms and who had normal protein S and protein C and normal fibrinolysis. The second group consisted of two patients with mild to moderate thrombocytosis and thrombosis. Both these latter two patients had abnormalities in protein S. The first patient had only 31% free protein S and 67% total protein S, with normal protein C and normal fibrinolysis. Following treatment, vasoocclusive symptoms resolved and platelet count decreased, but protein S remained low (28% free protein S). The second patient in this group had only 35% total protein S at initial study. Other hemostatic abnormalities were also present. Following treatment, symptoms resolved and protein S returned to normal. Based on this limited series, it appears that, in some patients with ET, thrombotic phenomena may be due to the presence of a second hemostatic abnormality in addition to the high platelet count and abnormal platelet function. This abnormality may be acquired as part of the disease process. Some of these abnormalities may be corrected following treatment.
Treatment of von willebrand's disease and hypofibrinogenemia with single donor cryoprecipitate from plasma exchange donation
Authors: McLeod Bruce C. , McKenna Rajalaxmi , Sassetti Richard J.
Published: February 2007

Conventional replacement therapy for hypofibrinogenemia and von Willebrand's disease requires multiple donor exposures and a correspondingly high risk of blood‐borne infection. We describe the collection and successful use of cryoprecipitate derived from a single donor by plasma exchange donation to support such patients through major hemostatic stresses. The father of an epileptic patient with von Willebrand's disease produced cryoprecipitate containing 23,546 units of von Willebrand factor (vWF) in nine desmopressin‐stimulated donations; this provided total factor replacement for neurosurgery to remove a seizure focus. The average yield was 2,616 units per donation and the average VWF concentration in cryoprecipitate was 17.7 units/ml. The husband of a hypofibrinogenemic patient with a history of postpartum hemorrhage provided cryoprecipitate containing 13.4 g of fibrinogen in five donations; this supported his wife through parturition without recourse to other blood products. The average yield was 2.7 g per donation, and the average fibrinogen concentration was 15.3 g/liter. Plasma exchange donation is a practical alternative source for cryoprecipitate. It can provide vWF and fibrinogen that carry a reduced risk of infectious disease transmission.
Hodgkin disease in a patient with common variable immunodeficiency
Authors: Fesus Susan M. , Hagemeister Fredrick B. , Manning John
Published: February 2007

Extensive extralymphatic Hodgkin disease developed in a young man with common variable immunodeficiency manifested by hypogammaglobulinemia, recurrent sinopulmonary infections, and multiple autoimmune phenomena. Both humoral and cell‐mediated immune dysfunction were present prior to treatment. After two cycles of chemotherapy, irreversible shock developed, and death occurred secondary to overwhelming infection in spite of prophylactic gammaglobuiin replacement. The unusual features of this patient's case of extralymphatic Hodgkin disease in association with a primary immunodeficiency disorder have not been previously reported.
Inhibition of adenylate kinase by P1,P5‐Di(adenosine 5′) pentaphosphate in assays of erythrocyte enzyme activities requiring adenine nucleotides
Authors: Valentine William N. , Paglia Donald E. , Nakatani Misae , Brockway Richard A.
Published: February 2007

P1,P5‐di(adenosine 5′)pentaphosphate (Ap5A) is an excellent inhibitor of human hemofysate adenylate kinase at concentrations near 2 μM and above. At ten times this concentration and in hemolysate enzyme assays under conditions described in this paper it appears not to alter reaction data in the case of hexokinase, phosphofructokinase, and phosphoglycerokinase. In the pyruvate kinase assay, very modest reductions in activity are noted, and kinetics with phosphoenolpyruvate, adenosine diphosphate (ADP), and uridine diphosphate (UDP) are unaltered.
Durable remission of pure red cell aplasia after treatment with high‐dose intravenous gammaglobulin and prednisone
Authors: Needleman Samuel W.
Published: February 2007

Pure red cell aplasia (PRCA) is a rare disorder of erythrocyte production believed to have an autoimmune basis in most cases. Responses to a variety of immunosuppressive regimens are regularly observed, but toxicity is considerable. Brief responses to high‐dose intravenous immunoglobulin (IVIg) have been previously reported. This case demonstrates a durable clinical remission of PRCA treated with IVIg and glucocorticoids.
CD7‐positive acute leukemia lacking T cell receptor gene rearrangements and terminal deoxynucleotidyl transferase expression suggesting pre‐T cell origin
Authors: Jacobs James C. , Rearden Ann
Published: February 2007

In this report, we describe a case of acute leukemia possessing a unique immunophenotype. Leukemic cells isolated from peripheral blood were analyzed by automated fluorescence‐activated flow cytometry. They demonstrated the following antigen pattern: CD7+, CD38+, transferrin receptor+, HLA‐DR+, common ALL antigen (CALLA)‐, and terminal deoxynucleotidyl transferase (TdT)‐. No expression of B cell or myeloid antigens was observed. The observed antigen pattern suggests a pre‐T cell origin. In addition, the tumor cells contained germline T cell receptor beta (Tβ) and gamma (T±) chain genes, and a germline immunoglobulin heavy chain (JH) gene. These findings support the concept that pre‐T cell leukemias may demonstrate germline Tβ and T± genes as well as lack TdT expression. In addition, our results suggest that CD7 expression may be one of the earliest events in T cell differentiation, occurring prior to both Tβ and T± gene rearrangements, and TdT expression.
Dominantly transmitted hematologic dysfunction clinically similar to fanconi's anemia
Authors: Alter Carol L. , Levine Paul H. , Bennett John , Kessler Craig , Rick Margaret , Washburn Ronald G. , Gallin John I. , Miller Robert W. , Auerbach Arleen D.
Published: February 2007

We report a family with a dominantly transmitted syndrome resembling Fanconi's anemia and spanning two generations. This syndrome was characterized by an ill‐defined hematologic stem cell disorder, immune dysfunction, poor dentition, hyperpigmented skin, warts, and multiple second trimester spontaneous abortions and included one case of acute myelomonocytic leukemia (acute non‐lymphocytic leukemia, M4). This family lacks the characteristic chromosomal aberrations of Fanconi's anemia. We believe this constellation of findings represents an entity not previously described.
Thrombin generation in patients with thrombotic thrombocytopenic purpura
Authors: Takahashi Hoyu , Tatewaki Wataru , Wada Ken , Shibata Akira
Published: February 2007

Thrombotic thrombocytopenic purpura (TTP) is thought to be caused primarily by endothelial cell injury or primary platelet agglutination. A coagulation screen usually shows normal or minimal changes, but a modest elevation of fibrinogen/fibrin degradation products (FDP) is observed in many patients with TTP. To assess the thrombin generation in vivo in TTP, plasma levels of thrombin‐antithrombin III complex (TAT) were measured together with plasmin‐α2‐antiplasmin complex (PAP) in ten patients with acute TTP. Plasma TAT [mean 6.7 ± (SD) 3.7 μg/liter] as well as PAP (2.1 ± 1.2 mg/liter) were elevated in patients wtih TTP as compared with healthy subjects (TAT of 1.7 ± 0.3 μg/liter and PAP of 0.2 ± 0.1 mg/liter; n = 10). These findings indicate that considerable amounts of thrombin and plasmin are actually generated in TTP, although the majority of patients do not show signs of consumption coagulopathy.
Newborn's fibrinolytic mechanism: Components and plasmin generation
Authors: Corrigan James J. , Sleeth Jeffrey J. , Jeter Monette , Lox Charles D.
Published: February 2007

Plasminogen activity and antigen, tissue‐type plasminogen activator (tPA) activity and antigen, plasminogen activator inhibitor (PAI) activity, and plasmin generation rates were determined in 32 normal newborn plasmas and 25 normal adult plasmas. The newborns showed reduced levels of plasminogen activity and antigen and tPA antigen, and activity, normal levels of PAI activity, and slower plasmin generation rates. The slower generation was shown to be due to the hypoplasminogenemia. The in vitro plasmin generation studies also showed that the newborn needed 11 times the usual concentration of urokinase and 5 times the usual concentration of tPA to achieve the minimal activation rate of the adult.
Type II H von willebrand disease: New structural abnormality of plasma and platelet von willebrand factor in a patient with prolonged bleeding time and borderline levels of ristocetin cofactor activity
Authors: Federici Augusto B. , Mannucci Pier Mannuccio , Lombardi Rossana , Lattuada Antonella , Colibretti Maria Luisa , Dent Judith A. , Zimmerman Theodore S.
Published: February 2007

In this study a new variant of type II von Willebrand disease is identified by multimeric analyses of increasing resolving power. Prior to multimeric analysis, the patient was misdiagnosed as carrying an undefined abnormality in platelet function because of his normal von Willebrand factor antigen (vWF:Ag) and low borderline ristocetin cofactor (Ricof) levels. Absence of the largest multimers from the patient's plasma and platelets was shown in a low‐resolution system, but all the multimers were present in his relatives. An abnormality in the complex multimeric structure was demonstrated in both plasma and platelets with high‐resolution agarose gels. The plasma of the proband and of several family members shows a broader central band with a minor, faster moving satellite band differing from the typical “triplet pattern” observed with normal plasma. Platelets show a “doublet” that runs with a mobility different from the “doublet” in normals. Therefore the proband may be either a homozygote or double heterozygote for this new abnormality. Treatment with desmopressin (DDAVP) on several occasions corrected the prolonged bleeding time of the patient only transiently. Factor VIII increased significantly, but vWF: Ag and Ricof responded poorly. We conclude that this vWF abnormality is different from those observed in the other variants (II A–G) previously described. Therefore the proposed designation for this new variant is type II H.
Multilobated non‐hodgkin lymphoma of B‐cell type: Leukemization and multiorganic involvement
Authors: Millá F. , Juncà J. , Flores A. , Lorenzo J. C. , Andreu J. , Navas J. J.
Published: February 2007

A case of multilobated non‐Hodgkin lymphoma (Pinkus' lymphoma) is presented. Its clinical manifestations (extreme leukemization) and immunological characteristics are stressed.
Horner's syndrome and demyelinating peripheral neuropathy caused by high‐dose cytosine arabinoside
Authors: Nevill T. J. , Benstead T. J. , McCormick C. W. , Hayne O. A.
Published: February 2007

High‐dose cytosine arabinoside may benefit patients with refractory acute leukemia. Peripheral nervous system disturbances caused by cytosine arabinoside have rarely been reported. We describe a patient with acute leukemia who developed Horner's syndrome and a severe demyelinating peripheral neuropathy leading to death after receiving highdose cytosine arabinoside. Peripheral nerve dysfunction is a potentially serious complication of high‐dose cytosine arabinoside.
Clinical manifestations of essential thrombocythemia in young adults
Authors: Millard Frederick E. , Hunter Christine S. , Anderson Michael , Edelman Martin J. , Kosty Michael P. , Luiken George A. , Marino Gregory G.
Published: February 2007

Essential thrombocythemia (ET) is a myeloproliferative disorder characterized by isolated overproduction of platelets, thrombohemorrhagic complications, and a median age of 50–60. When it occurs in younger patients, the incidence of complications has been reported to be quite low, with a good long‐term prognosis. We report a retrospective review of 13 patients with ET between the ages of 22 and 35 in which 11 were symptomatic at diagnosis, with only one remaining asymptomatic during follow‐up. Three patients presented with potentially life‐threatening complications (two myocardial infarctions, one stroke), although no deaths were observed. The majority of the nonlife‐threatening complications were vaso‐occlusive in nature, including erythromelalgia and transient neurologic symptoms. We conclude that ET in young adults is not always a benign disease and that potentially life‐threatening complications are not rare. The optimum approach to treatment in this or any other age group remains uncertain.
Chromosomal abnormalities define clonal proliferation in CD3‐ large granular lymphocyte leukemia
Authors: Taniwaki Masafumi , Tagawa Shinichi , Nishigaki Hikari , Horiike Shigeo , Misawa Shinichi , Shimazaki Chihiro , Maekawa Taira , Fujii Hiroshi , Kitani Teruo , Abe Tatsuo
Published: February 2007

Six patients with lymphoproliferative disorder of large granular lymphocytes (LDGL) were studied for chromosomal abnormalities. When the patients were divided into two groups depending on the expression of a mature antigen of T cell lineage, CD3, two with CD3 + phenotype had a stable disease, whereas three of the four patients with CD3‐ phenotype had marked hepatosplenomegaly and a highly aggressive disease. Chromosomal abnormalities were detected in four of six patients, indicating a clonal proliferation of large granular lymphocytes in individual patients. In particular, chromosomal abnormalities were found in three of the four patients with CD3‐ LDGL. all of which had a germ‐line configuration of the T cell receptor beta‐chain gene. Thus, the chromosomal abnormalities provide definitive evidence for the clonal origin of the expanded cells in the CD3‐LDGL.
Investigation of plasma von Willebrand factor and circulating platelet aggregating activity in mitomycin C‐related hemolytic‐uremic syndrome
Authors: Monteagudo Juan , Pereira Arturo , Roig Susana , Reverter Juan C. , Ordinas Antonio , Castillo Ricardo
Published: February 2007

We have studied the ability of the plasma to induce aggregation of both homologous and heterologous platelets in four patients with hemolytic‐uremic syndrome (HUS) associated with chemotherapy with mitomycin C (MMC). Neither platelet aggregation was elicited by patients' plasmas nor the in vitro addition of purified von Willebrand factor (vWF) had any effect on the aggregation pattern. In addition, ristocetin‐induced binding of patients' vWF to formaldehyde‐fixed platelets was normal, and multimeric vWF analysis revealed a normal structure of patients' plasmatic vWF whatever the clinical stage in which it was studied. These findings suggest that, in spite of the existence of common clinical and biological features in the various forms of HUS, the pathogenesis of MMC‐related HUS may be, at least in part, different from that of the other forms of HUS in which both platelet‐aggregating activity and alterations in the vWF are found.
Treatment of severe β‐thalassemia (patients) with myleran
Authors: De‐pei Liu , Chih‐chuan Liang , Zao‐hui Ao , Pei‐chen Jia , Song‐sen Chen , Rong‐xin Wang , Li‐juan Liu , He‐qian Jin , Dan‐yu Zha , You‐wen Huang
Published: February 2007

We previously reported that myleran, a cell cycle nonspecific drug, can stimulate γ‐globin gene expression in anemic adult rhesus monkeys. This finding prompted us to treat two patients with severe β‐thalassemia with myleran. Both patients received an initial course of therapy, constantly of myleran at a dosage of 0.2 mg/kg/d for 9 days followed by 0.15 mg/kg/d for the next 11 days. One patient received an additional 20‐day course of myleran at a dosage of 0.2 mg/kg/d beginning 44 days after completion of the first course. No severe ill effects related to the drug were observed during or after drug administration. After 20 days of myleran treatment, levels of HbF and reticulocytes increased in both patients and level of F cells increased in patient 1. In patient 1, Hb concentration rose from 42g/L (9 days after transfusion) before treatment to a maximum of 65g/L afterward; in patient 2, it rose from 74g/L to a maximum of 106g/L. A value of 15g/L above baseline lasted for about 5 months in both patients. Hypomethylation of bone marrow DNA near the γ‐globin gene was demonstrated in patient 1.
Transient engraftment of syngeneic bone marrow after conditioning with high‐dose cyclophosphamide and thoracoabdominal irradiation in a patient with aplastic anemia
Authors: Matsue Kosei , Niki Takeo , Shiobara Shintaro , Ueda Mikio , Ohtake Shigeki , Mori Takao , Matsuda Tamotsu , Harada Mine
Published: February 2007

We describe the clinical course of a 16 year old girl with aplastic anemia who was treated by syngeneic bone marrow transplantation. Engraftment was not obtained by simple infusion of bone marrow without immunosuppression. The patient received a high‐dose cyclophosphamide and thoracoabdominal irradiation, followed by second marrow transplantation from the same donor. Incomplete but significant hematologic recovery was observed; however, marrow failure recurred 5 months after transplantation. Since donor and recipient pairs were genotypically identical, graft failure could not be attributed to immunological reactivity of recipient cells to donor non‐HLA antigens. This case report implies that graft failure in some cases of aplastic anemia might be mediated by inhibitory cells resistant to cyclophosphamide and irradiation.
Protein C deficiency and anticardiolipin antibodies in a family with premature stroke
Authors: Haire William D. , Newland James R.
Published: February 2007

Anticardiolipin antibodies and, rarely, protein C deficiency have been described in patients with stroke. The familial coexistence of these two prothrombotic defects has not been previously reported. We describe a family with debilitating strokes occurring at an early age in whom both anticardiolipin antibodies and protein C deficiency were found. The propositus and her deceased mother both suffered a stroke at age 50 years. The propositus had both anticardiolipin antibodies and protein C deficiency. After a detailed study of the remainder of the family, the tendency to form anticardiolipin antibodies appeared to be inherited independently of the protein C deficiency. The simultaneous occurrence of these abnormalities in one family suggests that it may be useful to test for both anticardiolipin antibodies and inherited anticoagulant protein deficiencies in patients with unusual or unexplained stroke. The differential expression of both protein C deficiency and anticardiolipin antibody production in various members of the described family may allow insight into the relative contributions of these two prothrombotic abnormalities for the development of thrombotic complications, including stroke.