bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased response of erythroid progenitors to interleukin‐3 in sickle cell anemia: CFU‐E‐like behavior of circulating erythroid progenitors in liquid culture
Authors: Isoyama Keiichi , Baliga Surendra , Shah Arvind , Mankad Vipul N.
Published: February 2007

Erythroid progenitors circulating in peripheral blood and their response to erythropoietin (EPO), interleukin‐3 (IL3), and phytohemagglutinin‐stimulated, lymphocyte‐conditioned medium (PHALCM) were assessed in sickle cell anemia (SCA) patients and controls. SCA patients have significantly higher numbers of circulating burst‐forming unit–erythroid (BFU‐E) compared with controls (mean ± SEM, 940.27 ± 129.11 per ml and 86.56 ± 19.74 per ml, respectively; P < 0.0001). At low doses of EPO, BFU‐E‐derived colonies were significantly increased in SCA patients compared with controls (each P < 0.05). The EPO dose required to produce 50% of maximum colony numbers was 47 times greater in control subjects than in SCA patients. Moreover, in 11 of 17 patients with SCA, spontaneous BFU‐E‐derived colonies were formed without added erythropoietin. This phenomenon was not observed in control subjects (P = 0.035). PHALCM developed from mononuclear cells of SCA patients had significantly greater stimulatory effect than did that derived from controls regardless of the source of target cells (each P < 0.05). A two‐step study of IL3 sensitivity of erythroid progenitors was conducted. First, in a liquid culture system, circulating erythroid progenitors of SCA patients and controls were incubated in the presence of varying doses of IL3. During a second step, CFU‐E‐like colonies were observed in methylcellulose cultures of these cells. The mean numbers of colony‐forming unit‐erythroid (CFU‐E)‐like colonies was significantly higher in SCA patients compared with control subjects at low doses of IL3 (each P < 0.02). The increased response of erythroid progenitors to IL3 and the increased production of hemopoietic growth factors (IL3 or non‐IL3) contribute to the hemopoietic response in SCA patients. These mechanisms and increased sensitivity of the BFU‐E to EPO may explain lower than expected EPO levels in SCA patients.
Effect of tranexamic acid on platelet ADP during extracorporeal circulation
Authors: Soslau Gerald , Horrow Jan , Brodsky Isadore
Published: February 2007

Seventeen adults received the antifibrinolytic drug tranexamic acid during cardiac surgery utilizing extracorporeal circulation (ECC). In 8 patients, drug administration began prior to skin incision (pre‐ECC); infusions commenced after ECC and protamine administration in another 9 patients (post‐ECC). Compared with the post‐ECC group, the pre‐ECC group exhibited less bleeding via mediastinal drains (420 vs. 655 mL/12 h median, P = 0.024), decreased frequency of the presence (≥10 γg/mL) of fibrin split products (P < 0.05), and greater platelet dense granule content of adenosine diphosphate after surgery (15.47 vs. 4.05 nmoles/mg protein median, P = 0.021).

Follow‐up in vitro study of tranexamic acid inhibition of plasmin‐induced platelet activation utilizing normal human platelet rich plasma and porcine plasmin revealed a 13‐fold lower concentration of tranexamic acid for 50% inhibition when plasmin was preincubated with the drug (1.2 γg/mL, 95% CI = 1.13 – 1.60 γg/mL) compared to when platelet rich plasma was preincubated with the drug (16 γg/mL, 95% CI = 7.3 – 99. γg/mL). Plasmin inactivated with tranexamic acid retained its ability to inhibit thrombininduced platelet activation, thus suggesting that tranexamic acid inhibits plasmin's catalytic activity and not its binding to platelets.

Both clot lysis and platelet dysfunction may contribute to bleeding after ECC. Tranexamic acid blocks plasmin‐induced partial platelet activation during ECC, thus preserving platelet function and promoting hemostasis after ECC.
Small bowel hematoma in a hemophiliac as a cause of pseudoappendicitis: Diagnosis by ct imaging
Authors: McCoy Harry E. , Kitchens Craig S.
Published: February 2007

Acute abdominal pain in a hemophiliac should be approached as hemorrhage until proven otherwise. With factor replacement available, a conservative approach can be taken as opposed to immediate exploratory surgery. Diagnostic imaging can define areas of hemorrhage. We report a case of “pseudoappendicitis” in a hemophiliac with terminal ileum circumferential bowel wall hematoma diagnosed by CT with the initial diagnostic scan. Factor replacement resulted in resolution of the signs and symptoms of the pseudoappendicitis and follow‐up CT scan revealed resolution of the hematoma. A review of the literature reveals few CT documented circumferential bowel wall hematomas with limited clinical histories and no cases with follow‐up scans after conservative management.
Application of a monoclonal antibody specific for the δ chain of hemoglobin A2 in the diagnosis of β thalassemia
Authors: Shyamala M. , Kiefer Charles R. , Moscoso Hugo , Garver Fred A.
Published: February 2007

We have developed a murine monoclonal antibody (mAb) specific for the δ chain of hemoglobin (Hb) A2 that does not cross‐react with α, β, or γ chains. The mAb reacted with Hb P‐Nilotic (β δ hybrid), but not with Hb Lepore‐Boston (δ β hybrid), indicating an epitope consisting of positions 116 (Arg) and 117 (Asn) or 125 (Gin) and 126 (Met) of the δ chain. By using this antibody, we have established a simple and rapid enzyme‐linked immunosorbent assay (ELISA) for the detection and quantification of Hb A2 in adult, cord, and fetal hemolysates. We analyzed 70 adult, 8 newborn, and 19 fetal hemolysates from normal subjects and those with various hemoglobinopathies. The mean percentage of Hb A2 was 2.5 for normal adults, 5.4 for β thalassemic (β thai) heterozygotes, and <0.1% in β thal fetal samples. We were able to distinguish and characterize certain phenotypes of β thai patients such as β thai heterozygotes, β° thai homozygotes, and Cβ° thal, and Cβ° thal double heterozygotes with the aid of this and other mAbs we have generated. This technique is a valuable addition to current methods for the diagnosis of β thai based on quantification of Hb A2.
Hemophagocytic syndrome: A cause of pancytopenia in human ehrlichiosis
Authors: Abbott Kevin C. , Vukelja Svetislava J. , Smith Craig E. , McAllister C. Kenneth , Konkol Keith A. , O'rourke Timothy J. , Holland Cynthia J. , Ristic Miodrag
Published: February 2007

A 67‐year‐old white man with human ehrlichiosis infection complicated by pancytopenia, hemophagocytic syndrome, disseminated intravascular coagulopathy and septic shock is presented. The patient had been on a three‐week camping trip to California, Colorado, Utah, and New Mexico. The diagnosis of human ehrlichiosis was confirmed by sixteenfold rise in antibody titer to Ehrlicha canis, and supported by the characteristic cytoplasmic inclusions. Human ehrlichiosis should be considered in the differential diagnosis in patients with fever and cytopenia associated with hemophagocytosis. Pancytopenia associated with ehrlichiosis is transient; however, it may be severe, and appears to be associated with destruction of normal blood elements.
Lupus anticoagulant associated with primary malignant lymphoplasmacytic lymphoma of the spleen: A report of four patients
Authors: Ciaudo M. , Horellou M. H. , De Carbonnieres C. , Conard J. , Samama M. , Audouin J.
Published: February 2007

Primary lymphoma of the spleen is characterized by predominant splenomegaly. Lymphoplasmacytic malignant lymphoma of the spleen, of low malignancy in the Kiel classification, low and intermediate grade in the National Cancer Institute Working Formulation (NCIWF), is rare. It is often associated with a monoclonal immunoglobulin M (IgM).

Four patients presenting with primary splenic lymphoma of plasmacytic type associated with a high level of monoclonal IgM and a lupus anticoagulant (LA) are described. This association has not previously been reported. In contrast with the usual heterogeneity of LA, this LA is relatively homogeneous with an important prolongation of the prothrombin time (>18 see for a control of 12), more prolonged partial thromboplastin time (PTT) of the mixture patient + control plasma than PTT of the patient plasma. Despite the important coagulation abnormalities, none of these four patients has presented any hemorrhagic or thrombotic complications, even during major surgery such as splenectomy.

The lupus‐like anticoagulant effect ran parallel with the monoclonal IgM. Survival, after splenectomy and chemotherapy, appears to be favourable: three patients are alive with survivals of ≧7 years. The follow‐up is as yet too short for the last patient.
Hemoglobin constant spring in bangkok: Molecular screening by selective enzymatic amplification of the α2‐globin gene
Authors: Thonglairoam V. , Fucharoen S. , Tanphaichitr V. S. , Pung‐amritt P. , Embury S. H. , Winichagoon P. , Wasi P.
Published: February 2007

Hemoglobin Constant Spring (Hb CS) is a hemoglobin variant with an elongated α‐globin chain secondary to a chain termination mutation. The diagnosis of HbCS by electrophoresis is difficult because it is present in very low amounts in the red cells of heterozygotes. Selective enzymatic amplification of the α2‐globin gene and allele‐specific hybridization for Hb CS gene provided accurate diagnosis of Hb Constant Spring. We have used this approach to detect the αcs mutation in the cord blood that contained all four α‐globin genes but had Hb Bart on electrophoresis. The αcs mutation was found in six subjects whose Hb Bart levels were 3.0, 3.2, 3.7, 4.0, 4.9, and 9.8%. The latter also had −α mutation on the other chromosome, giving rise to the genotype αcsα/−α, which produced high Hb Bart. The gene frequency for αcs in the Thai calculated from a total of 406 cord blood studied in Bangkok was found to be ∼0.008.
Relationship Between Cell‐Cycle State of Erythroid Progenitors and Fetal Hemoglobin Synthesis
Authors: Isoyama Keiichi , Baliga Surendra , Shah Arvind , Mankad Vipul N.
Published: February 2007

DNA‐synthesis state of circulating burst forming unit‐erythroid (BFU‐E) was evaluated in patients with sickle cell anemia and correlated with percent of fetal hemoglobin synthesized in the BFU‐E‐derived cells. Percentage of S‐phase BFU‐E inversely correlated with percent fetal hemoglobin synthesized in the BFU‐E‐derived cells (simple linear correlation coefficient, r = −0.8, P = 0.0302; polynomial regression, R = ‐0.99, P = 0.0002). This observation is of relevance to our understanding of the relationship between the developmental stage of the erythroid progenitors and expression of globin genes.
Circulating CD34+ cells: An adverse prognostic factor in the myelodysplastic syndromes
Authors: Sullivan Sally A. , Marsden Katherine A. , Lowenthal Raymond M. , Jupe David M. , Jones Michael E.
Published: February 2007

As part of an epidemiological survey of myelodysplastic syndromes (MDS) in southern Tasmania, 62 MDS patients identified over a 2 year period were tested for the presence of CD34, the human progenitor cell antigen (HPCA), in their peripheral blood. The results were correlated with transformation to acute myeloid leukemia (AML) and patient survival, and CD34+ status was compared as a prognostic indicator with Bournemouth score, cytogenetics, and CFU‐GM colony growth which were also assessed. Circulating CD34+ cells were found in 23 of the 62 MDS patients; 9 of the 23 patients with circulating CD34+ cells transformed to AML, as compared with none of the 39 CD34 negative patients (P < 0.0001); and 11 of the 23 patients with circulating CD34+ cells were dead at the end of the 2 year period, as opposed to 6 of the 39 with no CD34+ cells (P < 0.03). The Bournemouth score was also significantly associated with transformation to AML (P < 0.0001) and poor survival (P < 0.04). These were the only significant associations of the possible prognostic factors studied with either transformation or survival. In summary, the presence of circulating CD34+ cells was significantly associated with both progression to AML and poor survival and was found to be a better prognostic indicator than cytogenetics or CFU‐GM colony growth.
Survival of hemophilic males with acquired immunodeficiency syndrome with and without risk factors for AIDS other than hemophilia
Authors: Holman Robert C. , Rhodes Phillip H. , Chorba Terence L. , Evatt Bruce L.
Published: February 2007

Between January 1, 1981, and June 30, 1990, 1,514 hemophilia‐associated acquired immunodeficiency syndrome (AIDS) cases in males were diagnosed in the United States. In 1,394, hemophilia was reported as the sole risk factor. For an additional 120, other risk factors were reported: of 101 of these, 40 had homosexual/bisexual activity, 53 had a history of intravenous drug use, and 8 had both of these risk factors. We examined the demographic data and the survival data of two principal groups: males for whom hemophilia was the sole reported risk factor for human immunodeficiency virus (HIV) exposure, and hemophilic males for whom homosexual/bisexual activity, intravenous drug use, or both of these additional risk factors were reported. The survival curves showed marginal differences between the hemophilia‐only and the multiple risk groups; the median survival times were 13.1 and 14.6 months, with the cumulative probability of survival at 1 year as 52.7% and 54.0%, respectively. Kaposi's sarcoma was among AIDS indicator diseases more commonly found in the multiple risk factor group. Pneumocystis carinii pneumonia was the sole reported diagnosis indicative of AIDS for 34.4% of those in the hemophilia‐only group, compared with 20.8% of those with multiple risk factors. The principal demographic difference between the two groups was the age distribution; those in the multiple risk factor group were primarily between 20 and 44 years of age. Restricting the analysis to those between 20 and 44 years resulted in a slightly longer survival time in the hemophilia‐only group and no appreciable difference between the disease distributions and survival curves of the two groups. © 1992 Wiley‐Liss, Inc.
DNA methylation patterns of the γδβ‐globin genes in human fetal and adult erythroid tissues
Authors: Loo L. S. L. , Cauchi M. N.
Published: February 2007

An investigation of the correlation between the γ→β‐globin switch and DNA methylation was carried out. The restriction patterns obtained with methylation‐sensitive and ‐insensitive enzymes indicated hypomethylation in the promoter region of the γ‐globin genes in fetal liver DNA but high methylation of the same region in all other samples (except in the presence of an elevated erythroblast count or leukemia). All samples appeared to be partially hypomethylated at the 5′ end of the δ‐globin gene and hypomethylated at the 3′ region of the β‐globin gene. Although consistent with a role for DNA methylation in globin gene regulation, the results also suggest that other factors besides methylation may be required for regulation of the level of expression, and switching of the globin genes. © 1992 Wiley‐Liss, Inc.
Acute undifferentiated leukemia (AUL): A case report and a proposed system of classification
Authors: Shende Ashok C. , Bonagura Vincent R. , Cheah Marc S. C. , Lanzkowsky Philip
Published: February 2007

This report describes a case of HLADR+, CD34‐ acute undifferentiated leukemia (AUL) diagnosed in an 18‐year‐old male. A definition of AUL and a system for its classification are proposed on the basis of the current state of knowledge about phenotypic features of AUL cells and their clonal counterparts that exist during early stages of normal hematopoiesis. © 1992 Wiley‐Liss, Inc.
Reduced expression of CD20 antigen as a characteristic marker for chronic lymphocytic leukemia
Authors: Almasri Nidal M. , Duque Ricardo E. , Iturraspe Jose , Everett Eric , Braylan Raul C.
Published: February 2007

The surface antigens expressed by the cells of chronic lymphocytic leukemia (CLL) are well known. Most CLL are monoclonal B‐cell lymphoproliferative disorders characterized by the coexpression of B‐cell antigens and CD5, an antigen present predominantly on T cells. Very little attention, however, has been paid to the quantitative characteristics of the expression of B‐cell antigens in CLL. In this study, we used flow cytometry to analyze the expression of CD20, a well‐known B‐cell‐associated antigen, in lymphocytes from 42 cases of CLL and its tissue counterpart, small lymphocytic lymphoma (SLL), and compared the results with results obtained from the analysis of 21 follicular lymphomas, 20 hyperplastic reactive nodes, and 26 samples of normal peripheral blood. The intensity of CD20 expression in the CLL/SLL cells was significantly lower than that of B cells in the other categories. This antigen expression abnormality does not appear to be a universal phenomenon in CLL/SLL, since CD19, another pan‐B antigen, was expressed in CLL/SLL at levels higher than those in follicular lymphomas and comparable to those in reactive lymph nodes. These results indicate that the low CD20 expression can be used as a marker for CLL/SLL. The few cases exhibiting intense CD20 expression may represent a biologically different disease. CLL/SLL cells faintly expressing CD20 also show concomitant low CD5 expression in a manner not observed in normal CD5‐expressing B cells. © 1992 Wiley‐Liss, Inc.
Relationship of thrombohemorrhagic complications to endothelial cell function in patients with chronic myeloproliferative disorders
Authors: Friedenberg W. R. , Roberts R. C. , David D. E.
Published: February 2007

Thrombotic and hemorrhagic disorders are common complications of the myeloproliferative disorders. Endothelial cells release both procoagulant and profibrinolytic factors, which may contribute to these hemorrhagic or thrombotic complications. The pre‐ and postvenous stasis levels of the procoagulant and profibrinolytic factors produced by endothelial cells were correlated with the occurrence of complications in polycythemia rubra vera (PRV) patients (n = 29) and essential thrombocythemia (ET) patients (n = 17) compared with normal patients (n = 17). Tissue plasminogen activator (tPA) activity, plasminogen activator inhibitor (PAI) activity, von Willebrand's factor (vWF) activity and antigen (vWF:Ag), and factor VIII activity were measured. The resting tPA activity was significantly higher in the two disease groups compared with normal controls, but no difference between the levels of tPA and either complication within the disease groups was observed. Significantly elevated tPA following venous stasis was observed in the patients of both disease groups who had bleeding complications. Significant decreases, compared with the normal group, in both resting and postvenous stasis levels of PAI were observed in the disease groups regardless of complication history. The subjects from both disease groups with thrombotic complications had significantly elevated resting vWF and both resting and postvenous stasis vWF:Ag levels compared with normal controls. The endothelial cell is likely to be responding to abnormal hemastasis rather than being primarily involved in the genesis of a hyper‐ or hypocoaguable state. © 1992 Wiley‐Liss, Inc.
Reduction in tissue iron stores with a new regimen of continuous ambulatory intravenous deferoxamine
Authors: Olivieri Nancy F. , Davis Susan A. , Liu Peter P. , Berriman Ann Marie , Tyler Beverley J. , Francombe William H.
Published: February 2007

A new regimen of 24‐hr ambulatory continuous intravenous infusion of deferoxamine (CIV OFO) through central venous ports was instituted in nine patients aged (mean ± SD) 22.4 ± 5.8 years over a period of 15.7 ± 7.3 months. Central venous infusion sites were changed weekly in the clinic, eliminating the necessity for reconstitution of DFO and needle Insertion at home. Because CIV DFO could be interrupted only by medical personnel, patient compliance was documented accurately; patients administered 93.0% ± 3.2% of CIV DFO prescribed. Mean urinary iron excretion on CIV DFO (66.8 ± 50.4 mg/24 hr) was significantly greater than that quantitated during 12‐hr equivalent‐dose subcutaneous DFO infusions (23.4 ± 18.3 mg/24 hr; P < 0.025). Mean serum ferritin declined by 71% over the treatment period (P < 0.005). This regimen confers the advantages of uninterrupted exposure to DFO, is associated with excellent patient compliance, and should be considered in any patient with severe iron overload and erratic compliance with DFO. © 1992 Wiley‐Liss, Inc.
CD5 B lymphocyte antigen in monoclonal gammopathy
Authors: Bataille RÉGis , Duperray Christophe , Zhang Xue Guang , Brochier Jean , Klein Bernard
Published: February 2007

Because B lymphocytes bearing the CD5 antigen have been involved in many B‐cell malignancies, we have investigated the presence of the CD5 B‐cell antigen on B and plasma cells in monoclonal gammopathy. Quantification of CD5 B cells was made in the peripheral blood of seven individuals with monoclonal gammopathy of undetermined significance (MGUS) and in that of 21 patients with multiple myeloma (MM). The bone marrow of ten patients with MM was also studied. Patients with progressive MM presented a significant reduction in both B and CD5 B lymphocytes (i.e., percentages and absolute numbers), when compared with individuals with MGUS and patients with stable MM. These latter individuals and patients did not differ from healthy donors. No CD5 B cells were found in the bone marrow of patients with MM. Moreover, no CD5 antigen could be detected on eight freshly established human myeloma cells lines including six totally dependent on Interleukin‐6. However, it was weakly expressed on two standard myeloma cell lines not requiring exogenous interleukin‐6 (i.e., RPMI 8226 and U 266). In conclusion, our data show mainly an overall reduction of the polyclonal CDS B lymphocytes similar to what is observed for the other polyclonal B lymphocytes in patients with active MM. Finally, the expression of the CDS antigen human myeloma cell lines is not constant. © 1992 Wiley‐Liss, Inc.
Inefficacy of intravenous immunoglobulin in patients with low‐risk thrombotic thrombocytopenic purpura/hemolytic‐uremic syndrome
Authors: Finazzi Guido , Bellavita Piero , Falanga Anna , Viero Piera , Barbui Tiziano
Published: February 2007

Objective: To assess the efficacy of intravenous immunoglobulin (IVIG), in comparison with plasma exchange (PE), in the treatment of patients with thrombotic thrombocytopenic purpura/hemolytic‐uremic syndrome (TTP/HUS). © 1992 Wiley‐Liss, Inc.

Design: Prospective, nonrandomized comparative study.

Setting: Hematology department in a general hospital.

Patients: 17 consecutive adult patients, six of them pregnant, with diagnosis of TTP/ HUS. Three had a severity score at diagnosis ≦4 and were treated with IVIG and 14 had a severity score of ≧5 and/or were pregnant and received PE. The response was evaluated after 5 days of therapy.

Results: Complete remission was obtained in 0/3 cases treated with IVIG and 10/14 (71%) with PE (Fisher's exact test P = 0.05). Three patients died for widespread TTP‐HUS, and four had persistent disease. In three of the four resistant patients, complete remission was obtained by further PE but not by further IVIG. The overall remission rate was 76% (13/17).

Conclusions: Our study does not confirm the utility of IVIG in the management of TTP‐HUS, as suggested by earlier single case reports. © 1992 Wiley‐Liss, Inc.
Proliferation of abnormal bone marrow histiocytes, an undesired effect of granulocyte macrophage‐colony‐stimulating factor therapy in a patient with hurler's syndrome undergoing bone marrow transplantation
Authors: Lang Eric , Cibull Michael L. , Davey Diane D. , Gallicchio Vincent S. , Jean Henslee‐Downey P. , Harder Edward J. , Messino Michael J.
Published: February 2007

Granulocyte macrophage‐colony‐stimulating factor (GM‐CSF) has shown promise as a means of alleviating leukopenia associated with a wide variety of disorders. It is currently undergoing evaluation as an adjunct to bone marrow transplantation but its use in patients with metabolic disorders, such as Hurler's syndrome (HS), has not been explored. We followed bone marrow morphology in a 2‐year‐old male with HS who received up to 8 μg/kg GM‐CSF per day because of failure of allogeneic bone marrow engraftment. Both premortem and postmortem bone marrow sampling revealed almost complete replacement of the marrow space by sheets of histiocytes demonstrating metachromatic cytoplasmic granules. Such cells were present in far greater numbers than are usually seen in untreated patients with HS or patients with HS undergoing successful bone marrow transplantation without GM‐CSF. Moreover, the in vitro culture of bone marrow from a second HS patient showed a GM‐CSF dose‐related increase in colony formation up to a dose of 250 units/ml. Microscopic examination of these colonies showed a high percent‐age of histiocytes identical to those seen in the patient's bone marrow. These observations suggest that caution should be exercised when considering administration of CSFs to patients with HS and similar metabolic storage diseases. © 1992 Wiley‐Liss, Inc.
Intrathoracic extramedullary hematopoietic tumor in hemoglobin H disease
Authors: Wu Jin‐Hou , Shih Lee‐Yung , Kuo Tseng‐Tong , Lan Ray‐Shee
Published: February 2007

We report a Chinese patient with hemoglobin H (Hb H) disease who developed intrathoracic extramedullary hematopoiesis (EMH) 17 years following splenectomy for a blunt abdominal injury. The patient initially presented with extreme hyperbilirubinemia and multiple intrathoracic tumors. Hb H disease was diagnosed after investigation, and the marked jaundice, which declined gradually after supportive treatment, was attributed to his chronic hemolysis superimposed on an acute hepatitis C virus infection. A biopsy of the intrathoracic tumors revealed an EMH. Intrathoracic EMH, which is usually encountered in patients with β‐thalassemia and hereditary spherocytosis, has never been reported in Hb H disease. In areas where thalassemia is prevalent, EMH should be considered in the differential diagnosis of patients who have chronic anemia with asymptomatic intrathoracic tumor to avoid unnecessary surgical interventions. © 1992 Wiley‐Liss, Inc.
Alpha granule proteins in type I von Willebrand's disease
Authors: McKeown Laurie P. , Williams Sybil B. , Shafer Brenda , Murray Natalie , Gralnick Harvey R.
Published: February 2007

Platelet von Willebrand factor (vWf) is located in the alpha granules. Individuals with type I von Willebrand's disease (vWd) with prolonged bleeding times are best discriminated from those who have normal bleeding times by the normal level of platelet vWf ristocetin cofactor activity (vWf activity) and, to a lesser extent, by their platelet vWf antigen content. We have studied the content of adhesive proteins and platelet factor‐4 (PF‐4), and β‐thromboglobulin (βTG) in the platelet alpha granules of types I and III vWd patients to determine if other alterations in alpha granule contents or proteins occur in vWd. We found that type I vWd patients with prolonged or normal bleeding times could not be differentiated on the basis of their platelet levels of βTG, PF‐4, fibronectin, or fibrinogen. The levels of the alpha granule constituents in the type I vWd patient were similar to normal except for the platelet fibrinogen concentration. Patients with type I vWd, regardless of the level of platelet vWf activity or antigen, had increased levels of platelet fibrinogen. The patients with type III vWd who had undetectable levels of platelet and plasma vWf also had increased levels of platelet fibrinogen. In our study we could not attribute the variation in the platelet vWf activity and antigen in type I vWd to the size of the alpha granule pool as determined by the measurement of other alpha granule proteins. The mechanism(s) of increased platelet fibrinogen in these vWd patients is at present unknown. © 1993 Wiley‐Liss, Inc.
Unusually large von willebrand factor multimers preferentially promote young sickle and nonsickle erythrocyte adhesion to endothelial cells
Authors: Wick Timothy M. , Moake Joel L. , Udden Mark M. , McLntire Larry V.
Published: February 2007

Sickle red blood cells (RBC) suspended with endothelial cell (EC)‐derived unusually large (UL) von Willebrand factor (vWF) multimers, but not large plasma vWF forms, adhered to human venous EC under shear flow conditions. When sickle RBC were separated by density gradient centrifugation, fractions rich in less dense RBC were the most adhesive to EC in the presence of ULvWF. Incubation of sickle RBC with monoclonal antibodies against platelet surface receptors GPlb or GPIIb/llla, or with the integrin receptor agonist Arg‐Gly‐Asp‐Ser (RGDS) decreased the ULvWF‐mediated sickle RBC adhesion to EC 84%, >99%, and 90%, respectively. When incubated with EC before the flow studies, anti‐GPIb antibody and RGDS inhibited the ULvWF‐mediated sickle RBC adhesion to EC.

ULvWF also promoted the adhesion to EC of nonsickle RBC (HbAA) from patients with an increased proportion of young erythrocytes. When the EC supernatant was depleted of most vWF forms, young nonsickle RBC adhesion decreased by 90%. Preincubation of young nonsickle RBC with anti‐GPIb antibody, anti‐GPIIb/llla antibody, or RGDS inhibited the ULvWF‐mediated young RBC adhesion to EC by 47%, 88%, and 92%, respectively.

These data indicate that (1) low‐density erythrocyte fractions enriched in young sickle or young nonsickle RBC are capable of binding ULvWF multimers via GPIb‐like and GPIIb/IIIa‐like receptors; (2) the RBC vWF receptors are lost or modified as erythrocytes age in the circulation; and (3) ULvWF/RBC complexes also bind to EC via a GPIb‐like receptor. © 1993 Wiley‐Liss, Inc.
8;21 translocation and multilineage involvement
Authors: Kwong Y. L. , Ching L. M. , Liu H. W. , Lee C. P. , Pollock A. , Chan L. C.
Published: February 2007

The translocation (8;21)(q22;q22) is commonly associated with acute myeloid leukemia (AML) M2 according to the French‐American‐British (FAB) classification. We describe 11 cases of t(8;21) diagnosed by strict FAB criteria. Six cases were diagnosed as AML M2, 3 cases as AML M4, 1 case as refractory anemia with excess of blasts in transformation, and 1 case as Philadelphia chromosome negative chronic myeloid leukemia in acceleration. Translocation (8;21) could thus occur in a wider variety of hematological abnormalities. Accordingly, we propose that t(8;21) may involve different hemopoietic lineages.
Primary plasmacytoma of generalized lymph nodes: A long survivor
Authors: Matsushima Takafumi , Murakami Hirokazu , Tamura Jun'Ichi , Sawamura Morio , Naruse Takuji , Tsuchiya Jun
Published: February 2007

Extramedullary plasmacytomas are occasionally seen in the course of multiple myeloma; however, primary plasmacytomas are unusual. Most of the primary plasmacytomas arise in the upper respiratory system, but a plasmacytoma of the lymph nodes is very rare. A case of a 56‐year‐old female with primary plasmacytoma in the lower mandibular, cervical, axillary, and para‐aortic lymph nodes accompanied by IgA Kappa paraproteinemia is described. After ten courses of combination chemotherapy with cyclophosphamide and prednisolone, she obtained complete response. However, 6 years later, she had a relapse of plasmacytoma in the generalized lymph nodes. She received ten treatments of melphalan‐prednisolone and again obtained complete response. She has remained well without chemotherapy or recurrent signs for 9 years. It is considered that conventional chemotheapy can be useful for primary plasmacytoma of generalized lymph nodes.
CD34+ and CFU‐GM progenitors are significantly decreased in sivsmm9 infected rhesus macaques with minimal evidence of direct viral infection by polymerase chain reaction
Authors: Hillyer Christopher D. , Lackey Dixon A. , Villinger Francois , Winton Elliott F. , McClure Harold M. , Ansari Aftab A.
Published: February 2007

Hematologic abnormalities in the peripheral blood and bone marrow are associated with human immunodeficiency and simian immunodeficiency virus (HIV, SIV) infection. The reasons for these abnormalities remain unclear. Bone marrow specimens collected from uninfected animals (Group A, Controls) and from rhesus macaques experimentally infected with SIVsmm9 during the asymptomatic stage (Group B, SIV+ “well”) and during the clinically ill stage (Group C, SIV+ “sick”), underwent a variety of in vitro assays of hematopoiesis. Colony forming unit‐granulocyte/macrophage (CFU‐GM) per plate growth was 46.7 ± 7.7, 31.9 ± 8.4 and 6.5 ± 5.0 (means ± sd, P <.02 each mean compared to the others) in the 3 groups respectively. Burst forming unit‐erythroid (BFU‐E) growth was similarly decreased in bone marrow samples from the SIV+ animals. There was no change in the number of CFU‐GM per plate with the removal of plastic adherent or T‐cell mononuclear cell fractions. There was no increase in CFU‐GM per plate growth with the addition of low dose GM‐CSF (1 or 5 ng/mL) though there was a near 67% increase (48 to 80 CFU‐GM per plate) with the addition of 100 ng/mL recombinant rhesus IL‐3 and 100 ng/mL GM‐CSF in SIV+ 'sick' animals. Variation in frequency of CD34+ progenitor cells in SIV+ animals was seen, with 3.0% CD34 cells in SIV− controls, 4.9% CD34+ cells in SIV+ 'well' animals and 0.5% CD34+ progenitor cells in SIV+ 'sick' monkeys (P <.01, each mean compared to the others). Finally, there was minimal evidence of SIV sequences by polymerase chain reaction in pooled cultured CFU‐GM, and no evidence in flowcytometrically sorted CD34+ progenitor cells from selected animals. Thus, the SIV seropositive rhesus monkey appears to have similar hematopoietic aberrations as are found in HIV infected human subjects and may be an excellent model for studying the interaction of lentiviruses on the kinetics of blood formation.
Hereditary thrombophilia among 217 consecutive patients with thromboembolic disease in Jordan
Authors: Awidi A. S. , Abu‐Khalaf M. , Herzallah U. , Abu‐Rajab A. , Shannak M. M. , Abu‐Obeid T. , Al‐Taher I. , Anshasi B.
Published: February 2007

This is a four‐year prospective study on patients admitted or referred with thromboembolic disease to Jordan University Hospital or to the Thrombosis/Haemostasis Laboratory at the University of Jordan. The aim of the study was to find the relative prevalence of hereditary thrombophilia. For the purpose of this work, hereditary thrombophilia was diagnosed in the absence of an acquired cause of thrombophilia in addition to two of the following: 1) positive family history of thrombophilia, 2) confirmed same deficiency in a closely related family member, 3) the deficient protein is constantly below 2 SD of the normal mean on repeated testing. All ages were admitted to the study. Acquired systemic factors or local factors known to cause thrombosis or affect the levels of proteins opposing thrombosis were excluded.

There were a total of 217 patients (102 males and 115 females) with confirmed throm‐boembolic disease. Their mean age was 34 years. A total of 49 patients (26 males and 23 females) fulfilled the criteria of hereditary thrombophilia. There were 17 cases of protein C deficiency (PC), 15 protein S deficiency (PS), 10 antithrombin III deficiency (ATIII), 3 dyfibrinogenemia, 2 heparin cofactor II deficiency, and 2 plasminogen defects. In this group most of the thrombosis was venous. A positive family history was obtained in 65.3% of patients with hereditary thrombophilia. Twenty‐seven additional relatives with deficiency were identified upon family studies. The calculated prevalence of hereditary thrombophilia in Jordan is put at 1/25,000. Screening for PC, PS, and ATIII is advocated in young patients who have thromboembolic disease, especially when there is a positive family history of thrombosis. © 1993 Wiley‐Liss, Inc.
Recombinant interferon α‐2b in the treatment of polycythemia vera
Authors: Cimino Renato , Rametta Vincenzo , Matera Carmela , Mele Giuseppina , Mettivier Vincenzo , Ferrara Felicetto
Published: February 2007

We studied the effects of recombinant α2‐b interferon (α2‐b IFN) in a dose of 3 × 106U intramuscularly three times a week for 1 year in 13 patients affected by polycythemia vera (PV) previously treated with phlebotomy only. Response to treatment was evaluated by reduction of the number of phlebotomies required to retain normal hematocrit value. Ten out of 13 patients (77%) responded to treatment; in 4 of them the exigency of phlebotomy was completely eliminated. In all responders a concomitant decrease of platelet count and splenomegaly was obtained. Treatment was well tolerated and side effects were easily controlled. We conclude that α‐IFN may represent an attractive therapeutic option in the management of the proliferative stages of PV. © 1993 Wiley‐Liss, Inc.
Hemoglobin D Ibadan‐β° thalassemia: Detection by neonatal screening and confirmation by electrospray‐ionization mass spectrometry
Authors: Lane Peter A. , Witkowska H. Ewa , Falick Arnold M. , Houston Marva L. , McKinna James D.
Published: February 2007

We describe an infant with hemoglobin D Ibadan‐β° thalassemia whose hemoglobinopathy was initially detected by neonatal screening. This previously undescribed condition was confirmed by family studies and by globin chain analysis by mass spectrometric techniques. The case illustrates the importance to neonatal screening programs of confirmatory testing and of linkage with reference laboratories capable of globin chain analysis. Hematologic studies at 36 months of age suggested that the presence of hemoglobin D Ibadan had no deleterious effect on this child with heterozygous β° thalassemia. © 1993 Wiley‐Liss, Inc.
Coincidental polycythemia vera and multiple myeloma: Case report and review
Authors: Fink Laura , Bauer Frank , Perry James J.
Published: February 2007

Polycythemia vera (PCV) and multiple myeloma are both clonal disorders of hematopoietic stem cells. The simultaneous occurrence of these diseases in an individual patient is rare. A case of synchronous PCV and smoldering myeloma is presented and the literature is reviewed. The issues of clinical importance in this unusual case include the mechanisms of anemia in multiple myeloma, the difficulty in using anemia as a parameter on which to base the initiation of therapy for myeloma, and the risks of treatment‐induced leukemia and myelodysplasia. © 1993 Wiley‐Liss, Inc.
Synergistic effect of storage pool deficient platelets and low plasma von willebrand factor on the severity of the hemorrhagic diathesis in hermansky‐pudlak syndrome
Authors: Witkop Carl J. , Bowie E. J. Walter , Krumwiede Marlys D. , Swanson Jane L. , Plumhoff Elizabeth A. , White James G.
Published: February 2007

A study of 565 Puerto Rican patients with storage pool deficient (SPD) Hermansky‐Pudlak syndrome (HPS) demonstrated that most HPS patients had minor bleeding episodes while others had repeated, severe hemorrhagic episodes requiring transfusion. The severity of bleeding in these latter patients could not be attributed to their SPD alone. As swine with SPD platelets and low von Willebrand factor antigen (vWF:Ag) have more severe hemorrhages than pigs with either defect alone, 146 albino patients and 46 normally pigmented patients were examined for their level of vWF:Ag. The risk of SPD HPS patients having severe, repeated bleeding episodes increased when vWF:Ag fell below 70 U/dL. Family studies indicated that low vWF:Ag levels were more frequently associated with O blood group than from a gene suppressing production or release of vWF1. HPS patients should be tested for vWF:Ag levels. © 1993 Wiley‐Liss, Inc.
Disseminated mycobacterium avium‐intracellulare infection in a patient with myelodysplastic syndrome (refractory anemia)
Authors: Tsukada Hiroko , Chou Takaaki , Ishizuka Yasuo , Ogawa Osamu , Saeki Takako , Ito Satoshi , Wakabayashi Masaya , Hayashi Naoki , Arakawa Masaaki
Published: February 2007

A 31‐year‐old woman presented with fever and arthralgla. Despite treatment with antimicrobials and cortlcosteroids, her symptoms persisted. A diagnosis of myelodysplastic syndrome (MDS)‐refractory anemia (RA) was made by pancytopenia, dysplasia, and trisomy 8. Cultures of bone marrow, blood, and gastric juice showed Mycobacterium aviumintraceliuiare (MAI). She was treated with antimycobacterial drugs and recombinant human G‐CSF/M‐CSF and showed an initial response, but spike fever recurred and pancytopenia progressed. Hepatospienomegaly and marked retroperitoneal lymphade‐nopathy were revealed, indicating further dissemination of MAI. Treatment with recombinant human GM‐CSF and very‐low‐dose cytosine arabinoside, was started but was not effective. This case showed significant reduction in peripheral blood 1‐lymphocytes, especially the CD4+ population, and low immunoglobulin levels. immunodeficiency state associated with long‐term steroid therapy and MDS seemed to contribute to the development of the disseminated infection with MAI. © 1994 Wiley‐Liss, Inc.
Deep vein thrombosis in a 13‐year‐old boy with hereditary protein S deficiency and a review of the pediatric literature
Authors: Blanco A. , Bonduel M. , Peñalva L. , Hepner M. , Lazzari M.
Published: February 2007

We report a 13‐year‐old boy with hereditary deficiency of protein S, who developed a deep vein thrombosis of the lower limb after a varicella with severe cutaneous lesions.

Hereditary protein S deficiency is an established cause of thrombophllia; however thrombotic events are seldom described in pediatric patients. A review of previous literature revealed 35 cases, 16 girls and 19 boys, with a first episode below of the age of 18 years old (x = 10y). The 57% of the patients had venous thrombosis, 20% arterial thrombosis, and 14% both and in 9% the type of thrombosis was not reported. Predisposing factors were referred In only 12 cases. The deficiencies can be classified as type 1 in 25 patients and type III in 8. © 1994 Wiley‐Liss, Inc.
Enhancement of pain control with ketorolac tromethamine in patients with sickle cell vaso‐occlusive crisis
Authors: Perlin Elliott , Finke Helga , Castro Oswaldo , Rana Sohail , Pittman Jerome , Burt Robert , Ruff Carol , McHugh Dennis
Published: February 2007

Twenty one patients with sickle cell disease admitted to the hospital with the pain of vaso‐occlusive crisis (VOC) were treated by continuous IV infusion of ketorolac or normal saline for up to 5 days. All patients received supplemental IM injections of meperidine, 100 mg, as necessary, but not more frequently than every 3 hr. Over the 5 days the ketorolac treated patients (KT) required 33% less meperidine than did the placebo treated patients (PL), P = 0.04, and had significantly better pain relief as assessed by categorical, visual analog, and pain relief scales. By the end of 5 days infusions had been discontinued in six KT and one PL. The time to discontinuation of the infusion was significantly shorter in KT, (P = 0.009). The median duration of hospital stay from the start of treatment was 3.3 days for KT and 7.2 days for PL, P = 0.027. Adverse events were mainly related to the digestive system. This study showed that continuous infusion of ketorolac significantly reduced total meperidine requirement and that the analgesia produced by this combination was superior to that produced by meperidine alone. Further evaluation of this drug in the management of sickle cell VOC is warranted. © 1994 Wiley‐Liss, Inc.
Reticulated platelet counts in patients undergoing autologous bone marrow transplantation: An aid in assessing marrow recovery
Authors: Romp Katherine G. , Peters William P. , Hoffman Maureane
Published: February 2007

Thiazole orange (TO) is a fluorescent dye that is commonly used for flow cytometric measurement of erythrocytic reticulocytes. This technique has also been validated for counting “reticulated” platelets, as a measure of bone marrow thrombopoietic activity. Patients with an established diagnosis of idiopathic thrombocytopenic purpura (ITP) have been reported to have a three‐ to five‐fold increase in the percent of circulating reticulated platelets. The current study was conducted to determine if platelet reticulocyte counts predicted recovery of bone marrow thrombopoietic activity following autologous bone marrow transplantation. We found an increase in the percent of circulating reticulated platelets preceding recovery of the platelet count; then, as the patients' platelet counts rose, the percent reticulated platelets fell. In patients with prolonged thrombocytopenia, a persistent increase in the proportion of reticulated platelets suggested a consumptive process, as opposed to failure of engraftment. Moderate transfusion of platelet concentrates did not interfere with the ability of the platelet reticulocyte measurements to detect increased thrombopoietic activity. Platelet transfusions did obscure any decrease in the proportion of reticulated platelets. Our results show that platelet reticulocyte counts could be useful in monitoring the recovery of marrow function following autologous bone marrow transplantation. © 1994 Wiley‐Liss, Inc.
Tissue factor in plasma of patients with disseminated intravascular coagulation
Authors: Takahashi Hoyu , Satoh Naoaki , Wada Ken , Takakuwa Etsuko , Seki Yoshinobu , Shibata Akira
Published: February 2007

Recently it has been shown that tissue factor (TF), an important trigger for initiating blood coagulation, is present in the circulating plasma. In order to assess the clinical implications of TF in plasma, plasma concentration of TF was quantitated in 65 patients with disseminated intravascular coagulation (DIC). The mean concentration of plasma TF was elevated in patients with DIC at presentation as compared with healthy subjects (446 ± SD 536 pg/ml vs. 138 ± 51 pg/ml, P < 0.001). Abnormally high levels were found only in 46.2% of the patients, predominantly in patients with non‐hematological solid tumors and acute leukemia. Plasma TF did not correlate with hemostatic markers of DIC such as thrombinantithrombin III complex, prothrombin fragment 1 + 2, plasmin‐α2‐plasmin inhibitor complex, FDP, D‐dimer, or fibrinogen. Serial determinations of plasma TF demonstrated that plasma TF changes roughly in parallel with the course of DIC in most patients with elevated TF at presentation of DIC. These findings suggest that plasma TF is potentially valuable for monitoring the progress of DIC in a limited population of patients. © 1994 Wiley‐Liss, Inc.
Fat embolism syndrome associated with asthma and sickle cell‐β+‐thalassemia
Authors: Johnson K. , Stastny J. F. , Rucknagel D. L.
Published: February 2007

A 25‐year‐old African‐American man with sickle cell‐β+‐thalassemia presented with acute asthma of 2 days' duration. The asthma was well controlled by 48 hr, and parenteral medications were changed to oral bronchodilators and steroids. Sixty hours after presentation, he developed pain similar to that of sickle cell vasooclusion, for which he received small amounts of analgesics. He died approximately 84 hours after presentation. Autopsy showed extensive marrow necrosis and massive fat embolism. This is the first reported case of fat embolism syndrome associated with this genotype, the mildest of the clinically significant sickle cell hemoglobinopathies. The relationship between these etiologic factors and indications for transfusions are discussed. © 1994 Wiley‐Liss, Inc.
α‐thalassemia‐1 (— −‐CAL mutation) in a Spanish family
Authors: Villegas A. , Sanchez J. , Gonzalez F. A. , Carreño D. L. , Ropero P.
Published: February 2007

We have detected a second family (five members affected) with a large (32 kb) deletion involving the α1, α2, ψα1, ψα2,ψζ1, and ζ‐globin genes. This mutation has been previously described in Calabria, Italy, in a child and his mother and has been named α‐thalassemia −‐ −‐CAL. © 1994 Wiley‐Liss, Inc.