摘要:

AbstractWe 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 of14C‐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 synthesi

ISSN:0361-8609    

DOI:10.1002/ajh.2830320102

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1989

数据来源: WILEY

摘要:

AbstractBolus Infusion of clotting factor concentrates remains the most common approach to the treatment or prevention of bleeding in patients with hemophilia. Although successful use of continuous infusion of such concentrates has been reported by several groups, this alternative treatment method has not achieved widespread popularity. We report here our experience in one hemophilia center with the use of continuous infusion of factor VIII and factor IX concentrates in 13 patients, 11 with hemophilia A, and 2 with hemophilia B. All patients were treated successfully for bleeding episodes (e.g., hemarthroses, intracranial, or gastrointestinal bleeding) or for surgical procedures (appendectomy, thoracotomy, etc.). Three patients with low titer factor VIII inhibitors were treated successfully with constant infusion therapy, requiring a mean dose of factor VIII concentrate 2.3 fold (8.20 u/kg/h) higher than that of the patients without inhibitors (3.63 u/kg/h) to maintain a circulating plasma level of factor VIII of 1 u/ml.The use of constant infusion of clotting factor concentrates is safe, efficacious, and more convenient than bolus therapy of factor concentrates and should be considered for hospitalized hemophilia patients requiring replacement therapy.

ISSN:0361-8609    

DOI:10.1002/ajh.2830320103

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1989

数据来源: WILEY

摘要:

AbstractCoagulo‐fibrinolytic factors were studied in five patients suffering from thrombotic thrombocytopenic purpura (TTP). The change in coagulation factors in the acute stage was mild compared with that found in disseminated intravascular coagulation (DIC). We observed a slight increase of fibrin‐fibrinogen degradation products (FDP) in the plasma of four patients during the acute stage of TTP, but the level of the D‐dimer remained within normal variation and was extremely low compared with that in 27 samples from patients with DIC showing the same level of FDP. At the same time, both antigen levels of tissue‐type plasminogen activator (t‐PA) and plasminogen activator inhibitor type 1 (PAI‐1) were elevated in three of the four patients tested. Although a similar change was recognized in DIC patients' plasma, the elevation of PAI‐1 in the acute stage of TTP was far higher than in overt DIC. The antigen levels of t‐PA and PAI‐1 were normal in remission, and a mild elevation of PAI‐1 was detected in one of the three patients during the early stage of TTP relapse. Enzymography revealed the appearance of free t‐PA and an increase of a substance with a 110 kD molecule, assumed to be a t‐PA and PAI‐1 complex, in TTP plasma in the acute stage, but the findings were normal for plasma from cases in remission and the early stage of relapse. Enzymography also showed a decrease of urokinase‐type plasminogen activator (u‐PA) only in the acute stage of TTP. These changes in the coagulo‐fibrinolytic factors in the acute stage of TTP suggest that fibrinogenolysis might be induced by t‐PA, released through vascular reaction at an uninvolved area of vascular lesions caused by platelet agglutinates, which would then release large amounts of PAI‐1 inhibiting t‐PA and u

ISSN:0361-8609    

DOI:10.1002/ajh.2830320104

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1989

数据来源: WILEY

摘要:

AbstractHemostatic changes were evaluated in ten patients with acute lymphoblastic leukemia and lymphoma who received chemotherapy with L‐asparaginase, vincristine, and prednisolone for 1 week. Following treatment, prothrombin time and activated partial thromboplastin time were significantly prolonged, while a marked decrease in fibrinogen levels was observed. The values for cross‐linked fibrin degradation products, however, remained within normal limits during treatment, which excluded the possibility of disseminated intravascular coagulation. The concentrations of coagulation inhibitors (antithrombin III, protein C, and protein S), plasminogen, and α2antiplasmin also significantly decreased; however, levels of both tissue‐type plasminogen activator and plasminogen activator inhibitor, which are synthesized in endothelial cells, increased during the treatment.Although a decrease was observed in concentrations of many coagulation factors, including subunits A and B of factor XIII, the activity and antigenicity of factor VII significantly increased following the treatment. From this study, we concluded that these hemostatic abnormalities caused by the administration of L‐asparaginase produced a labile condition that easily inclines to bleeding or th

ISSN:0361-8609    

DOI:10.1002/ajh.2830320105

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1989

数据来源: WILEY

摘要:

AbstractIn some patients with Philadelphia (Ph)‐chromosome positive acute lymphoblastic leukemias, breakpoints on chromosome 22 are reported to occur within the firstBCRintron. To analyze the breakpoints in chromosome 22 of Ph‐positive acute leukemia patients without rearrangement of the 5.8 kbbcr, we cloned the 3′ part of the firstBCRintron using a synthetic DNA probe. During the course of study, we mapped the region of the deletion/insertion of 1 kb that causes a restriction fragment length polymorphism (RFLP) and found a racial difference in the frequencies of the alleles giving rise to this RFLP. Analyses of the patients' samples indicated that breakpoints were located within the 8.5 kbEcoRI fragment of the firstBCRintron in two of five Ph‐positive acute leukemia patients. The data, together with the previous reports, indicate that breakpoints within this ∼50 kb intron are widely scattered, in contrast to those confined within the 5.8 kbbcrin chronic myelogenous

ISSN:0361-8609    

DOI:10.1002/ajh.2830320106

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1989

数据来源: WILEY

摘要:

AbstractPatients with liver disease frequently have multiple hemostatic abnormalities. Coagulation and fibrinolytic factors and inhibitors may decrease as the result of impaired synthesis and/or enhanced catabolism. In order to assess the actual degree of activation of coagulation and fibrinolytic systems in liver disease, plasma levels of thrombin‐antithrombin III complex (TAT) and plasmin‐α2‐antiplasmin complex (PAP) were measured together with cross‐linked fibrin derivatives (XDP), tissue‐type plasminogen activator (t‐PA), and plasminogen activator inhibitor (PAI‐1) in 31 patients with liver disease (five patients with acute hepatitis, seven with chronic hepatitis, nine with liver cirrhosis, and ten with hepatocellular carcinoma). Mean plasma levels of TAT (mean 4.2 ± SD 4.0 μg/L), PAP (0.7 ± 0.7 mg/L), and XDP (374 ± 518 μg/L) were significantly elevated in patients with liver disease as compared with normal subjects (TAT of 1.7 ± 0.3 μg/L, PAP of 0.2 ± 0.1 mg/L, and XDP of 30 ± 14 μg/L;P<0.005). Plasma concentrations of t‐PA and PAI‐1 antigens were also elevated. When plotted by the disease categories, the magnitude of elevations of these parameters was variable among subgroups. Patients with acute hepatitis had considerably higher TAT levels. The mean PAP values were relatively high in chronic hepatitis and hepatocellular carcinoma, in which an elevation of the t‐PA/PAI‐1 ratio was observed. Although clearance of TAT and PAP should be evaluated in the future, these findings suggest that excessive amounts of thrombin and plasmin are actually generate

ISSN:0361-8609    

DOI:10.1002/ajh.2830320107

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1989

数据来源: WILEY

摘要:

AbstractFour 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‐Loui

ISSN:0361-8609    

DOI:10.1002/ajh.2830320108

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1989

数据来源: WILEY

摘要:

AbstractTwo 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

ISSN:0361-8609    

DOI:10.1002/ajh.2830320109

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1989

数据来源: WILEY

摘要:

AbstractTwo 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

ISSN:0361-8609    

DOI:10.1002/ajh.2830320110

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1989

数据来源: WILEY

摘要:

AbstractA case report of squamous cell carcinoma in an epidermoid cyst of the spleen is diagnosed in a pregnant female. Elaboration on the clinical, radiological, and pathological findings is presented to emphasize the distinguishing features of benign and malignant cysts.

ISSN:0361-8609    

DOI:10.1002/ajh.2830320111

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1989

数据来源: WILEY