摘要:

AbstractA functional factor X deficiency is described which caused pronounced reduction in the in vitro activation of the extrinsic system while marginally affecting the in vitro activation of the intrinsic pathway. All studies were normal with the exception of a prolonged PT, an elevated factor X antigen, and low factor X activity. Western blot analysis revealed the presence of two factor X species. The abnormal molecule was of higher molecular weight. Interestingly, there was no bleeding associated with this deficiency. The biochemical basis of this defect is currently under investigation. ©1995 Wiley‐Liss, I

ISSN:0361-8609    

DOI:10.1002/ajh.2830480102

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

年代:1995

数据来源: WILEY

摘要:

AbstractIn this study we have defined the spectrum of the β‐thalassemia mutations, the β‐thalassemia haplotypes, and the genotype‐to‐phenotype correlations in a large number of patients with different β‐thalassemia conditions. Seventeen different (β‐thalassemia mutations were detected which included one chromosome each with Hb Dhonburi and Hb Lepore. Five alleles, namely, codon 39 (C→T), IVS‐l‐110 (G→A), IVS‐l‐6 (T C), IVS‐ll‐745 (C→G), and IVS‐l‐1 (G→A), account for 90% of all β‐thalassemia mutations in 846 thalassemic chromosomes studied.Haplotyping for a large number of subjects showed that the five common mutations are linked to a few haplotypes. The presence of milder mutations, mainly IVS‐l‐6 (T C), in about 19% of our patients explains some of the clinical variables. Among the 37 patients with thalassemia of intermediate severity, only 6 were homozygous or compound heterozygous for two severe alleles. The type of β‐thalassemia is the main factor responsible for differences in the phenotypic expression of the disease in patients with Hb S‐β‐thalassemia; patients with Hb S‐β+‐thalassemia are less severely affected than those with Hb S‐β°‐thalassemia. The five most frequent mutations hav

ISSN:0361-8609    

DOI:10.1002/ajh.2830480103

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

年代:1995

数据来源: WILEY

摘要:

AbstractAbnormal antithrombin III (AT III) was found in a 30‐year‐old woman who suffered from recurrent thrombosis during pregnancy and the postpartum period. Among her family members, only her father had recurrent episodes of deep vein thrombosis of the lower extremities, from his youth. The antithrombin and antifactor Xa heparin cofactor activities of the proposita's plasma were 61% and 42% of normal, respectively. The progressive antithrombin and antifactor Xa activities were also decreased to 55% and 58% of normal, respectively. The immunoreactive level of AT III was within the normal range (23.1 mg/dl). Analysis of the proposita's plasma by crossed immunoelectrophoresis in the presence or absence of heparin and by affinity chromatography on heparin‐Sepharose revealed that the proposita's AT III had apparently normal affinity for heparin. Nucleotide sequencing of 7 exons of the proposita's AT III gene amplified by polymerase chain reaction (PCR) disclosed that the second base of codon 393 comprised both G and A, indicating Arg393‐His conversion. The base sequences of exons 1,2,3a, 3b, 4, and 5 were normal, excluding any other mutation. These findings indicated that the proposita's AT III was a variant of AT III at the thrombin binding site and that the proposita was a heterozygote for the abnormality. Heparin affinity of purified abnormal AT III from the proposita's plasma was demonstrated to be increased upon affinity chromatography using heparin‐Sepharose, suggesting that the mutation (Arg393‐His) per se could possibly increase the affinity of antithrombin III for heparin.For this variant AT III (Arg393‐His), the name AT III Kumamoto II is proposed. ©1995 W

ISSN:0361-8609    

DOI:10.1002/ajh.2830480104

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

年代:1995

数据来源: WILEY

摘要:

AbstractSickle cell disease pathophysiology is mediated by acute and chronic impairment of cell flexibility due to the formation of intracellular sickle hemoglobin (Hb S) polymer as cells are partially deoxygenated in the microcirculation. We have recently developed a method to measure the relationship between the formation of intracellular polymerized Hb S and cell filtration. In this study, we have used this method to examine whether sickle cell morphology, independent of Hb S polymer fraction, had an effect on cell rheology. We primarily use sickle trait (AS) and Hb S‐β+‐thalassemia (S‐β+‐thal) erythrocytes with low hemoglobin F levels, which have normal membranes and few or no dense cells, to remove these confounding effects. We find that the relationship between filtration and the percentages of each “type” of morphological deformation of AS erythrocytes was different from that of the S‐β+‐thal erythrocytes. In addition, we find that while the filtration of AS erythrocytes as a function of oxygen saturation was similar, whether measured during deoxygenation or reoxygenation, the relationship between the percentages of each type of deformed erythrocyte and oxygen saturation demonstrated hysteresis during oxygenation‐deoxygenation experiments. Transmission electron microscopy, for both elongated and irregularly shaped cells, showed that similarly distorted cells could have very different amounts and alignment of polymer. These results suggests that cell morphology per se is not strongly related to filtration, whereas calculated intracellular Hb S polymer fraction predicts loss of filtration of AS and S‐β+‐thal erythrocytes well. Measured or calculated polymer fraction values would appear to be a better parameter for the study of sickle cell disease pathophysiology and response to treatment than cell morphology studi

ISSN:0361-8609    

DOI:10.1002/ajh.2830480105

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

年代:1995

数据来源: WILEY

摘要:

AbstractRecombinant human granulocyte colony‐stimulating factor (rhG‐CSF) and erythropoietin (rhEPO) were used to treat patients with aplastic anemia (AA). In terms of effects on erythrocyte recovery, the combined use of rhG‐CSF and rhEPO showed a favorable response in 6 of 14 (42.9%) patients with moderate AA following 10 weeks treatment and in 3 of 14 (21.4%) patients thereafter. However, the response was poor in patients with severe AA (3/13). A favorable response in severe AA was observed in 1 of 13 (7.7%) patients following 10 weeks treatment and in 2 of 13 (15.4%) patients thereafter. The overall effect on erythrocytes was observed in 44.4% patients. A dose of 400 μ/m2G‐CSF was sufficient to cause an increase in neutrophil count and 100 IU/kg rhEPO appeared to be sufficient to cause an increase in erythrocyte count. In 6 of 27 (22.2%) patients, a trilineage response was observed. Interestingly, a delayed and long‐lasting effect was obtained in 5 of 27 (18.5%) patients. These results suggest that rhG‐CSF can synergize with rhEPO in erythrocyte response, especially in patients with

ISSN:0361-8609    

DOI:10.1002/ajh.2830480106

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

年代:1995

数据来源: WILEY

摘要:

AbstractWe report a new case of severe bleeding diathesis due to an acquired inhibitor of fibrin crosslinking. The patient, an 80‐year‐old woman, was admitted to the hospital for a massive subcutaneous hematoma, with severe anemia requiring red cell transfusion; a subsequent retroperitoneal hematoma developed 2 weeks later. Coagulation studies were normal except for a thromboelastographic pattern suggestive of FXIII deficiency. Clot solubility test was abnormal even after 1: 1 mix with normal plasma. Immunochemical studies confirmed the presence of a monoclonal IgG lambda inhibitor directed against FXIII activity (type II FXIII inhibitor). The patient IgG fraction selectively inhibited FXIII transamidating activity but did not inhibit the thrombin‐mediated activation of FXIII. The patient was treated with high doses of FXIII concentrate to overcome the inhibitor and immunosuppressive therapy with cyclophosphamide and discharged in good conditions.High doses of commercially available FXIII appear to be a safe and effective method of controlling acute episodes of bleeding in patients with acquired FXIII deficiency. ©1995 Wiley‐L

ISSN:0361-8609    

DOI:10.1002/ajh.2830480107

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

年代:1995

数据来源: WILEY

摘要:

AbstractSecondary leukaemia following treatment of M3 acute promyelocytic leukaemia (APL) is a rare event. We describe a patient in remission following chemotherapy for APL who relapsed with M2 acute non‐lymphoblastic leukaemia (ANLL). The original t(15;17) (q22; q21) chromosome translocation was lost and replaced by a clone containing a dic(5;17) (q11; p11) abnormality. Southern genomic analysis demonstrated re‐arrangements of the retinoic acid receptor α (RARα) and PML genes in the APL blasts at presentation but not in the M2 ANLL marrow at relapse. The significance of unbalanced 5;17 translocations as markers for therapy‐related secondary leukaemia is discussed. ©1995 Wiley

ISSN:0361-8609    

DOI:10.1002/ajh.2830480108

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

年代:1995

数据来源: WILEY

摘要:

AbstractA patient with a history of partial gastrectomy presented with severe anemla, neutropenia, intestinal malabsorption, and was found to be severely copper‐deficient. The anemia and neutropenia corrected promptly with the administration of intravenous cupric chloride. This case suggests that partial gastrectomy with or without intestinal malabsorption can result in copper deficiency and should be considered in differential diagnosis of severe anemia and neutropenia. ©1995 Wiley‐Liss,

ISSN:0361-8609    

DOI:10.1002/ajh.2830480109

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

年代:1995

数据来源: WILEY

摘要:

AbstractThe effect of supplementing induction chemotherapy with recombinant human granulocyte‐macrophage colony‐stimulating factor (rhGM‐CSF) was studied in a randomized trial of 18 patients with acute myeloid leukemia (AML). Ten patients received rhGM‐CSF, starting on day one to three before chemotherapy and continued for a maximum of 21 days after the start of induction treatment. Unexpected adverse effects of rhGM‐CSF and chemotherapy combination included a transient decline in plasma coagulation factors II, VII, and X (5 of 5 patients) and an increased transcapillary escape rate of albumin (in 3 of 3 patients tested). The decline in coagulation factors was prevented in subsequent patients by prophylactic treatment with vitamin K. Although the small number of patients studied may not allow a definite conclusion, caution with regard to liver function should be shown in combining rhGM‐CSF with intensive chemotherapy. ©1995 Wil

ISSN:0361-8609    

DOI:10.1002/ajh.2830480110

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

年代:1995

数据来源: WILEY

摘要:

AbstractEighty‐eight percent (38/43) patients of intestinal tuberculosis showed significant hyperaggregation of platelets (P<0.001). Serum and plasma from 15 patients when incubated with normal platelets caused hyperaggregation. Gel filtered platelets from 2 patients suspended in normal plasma showed hyperaggregation of platelets with arachidonic acid. Tubercular protein had no effect on platelet aggregation. A role of hyperactive platelets in chronic inflammatory response is discussed. ©1995 Wiley‐Liss,

ISSN:0361-8609    

DOI:10.1002/ajh.2830480111

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

年代:1995

数据来源: WILEY