摘要:

AbstractWe previously described an ELISA to measure the inhibition of platelet glycoprotein llb/IIIa (GPIIb/IIIa) binding to fibrinogen due to immune complexes and/or anti‐platelet antibodies from patients with immune thrombocytopenia (ITP) or HIV‐related ITP. Circulating immune complexes (CIC) were the main factor in the inhibition of GPIIb/IIIa binding to fibrinogen in HIV‐related ITP, whereas in non‐HIV ITP, inhibition was only partially due to CIC; anti‐platelet antibodies specific to GPIIIa were also shown to play a role. In this study, we correlated the rise in the platelet count after intravenous immunoglobulin (IVIG) infusion with the decrease in inhibition of fibrinogen binding to GPIIb/IIIa by the sera of patients with ITP and HIV‐related ITP. In the majority of the patients' sera tested, as the platelet count increased following the administration of IVIG, the degree of inhibition of GPIIb/IIIa binding to fibrinogen decreased. We also observed a decrease and/or disappearance of the antibodies specific to GPIIb and/or GPIIIa after IVIG administration. In HIV‐seronegative ITP patients, the decrease or disappearance of anti‐platelet antibodies directly correlated with the decreased inhibition of GPIIb/IIIa binding to fibrinogen by the 2% PEG supernatants of sera which contained anti‐platelet antibodies. These findings suggest that IVIG directly affects the binding of CIC and anti‐platelet antibodies to platelets and thereby improves platelet survival. Our results also suggest that the anti‐idiotypic effect may contribute to IVIG's therapeutic action. In contrast, in the HIV‐seropositive group, the decreased inhibition by PEG precipitates after IVIG administration was more strongly associated with an increase in the platelet count.

ISSN:0361-8609    

DOI:10.1002/ajh.2830440202

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

年代:1993

数据来源: WILEY

摘要:

AbstractWe examined vascular endothelial cell markers, thrombomodulin (TM), plasminogen activator inhibitor‐l (PAI‐I), tissue plasminogen activator (t‐PA), and von Willebrand factor, in 80 patients with disseminated intravascular coagulation (DIC). The levels of thrombin‐antithrombin III complex (TAT), plasmin‐α2 plasmin inhibitor complex (PIC) and FDP‐D‐dimer were significantly increased both before and after the onset of DIC, but were not correlated with organ failure or prognosis. However, the PIC/TAT ratio was lower in patients with poor prognosis than in those with good prognosis, and it was also lower in those with organ failure than in those without. Plasma TM, PAI‐I, and t‐PA levels were increased in DIC patients with organ failure or poor outcome, but were not significantly increased before the onset of DIC. We consider that the prognosis of patients with DIC might be related to organ failure or endothelial cell damage and that plasma levels of TM, PAI‐I, and t‐PA might be useful in the detection of these disorders and in assessing prognosis. A hypofibrinolytic state might enhance organ failure in patients with DIC.

ISSN:0361-8609    

DOI:10.1002/ajh.2830440203

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

年代:1993

数据来源: WILEY

摘要:

AbstractThe measurement of the number of platelets larger than 3 microns (megathrombocyte index) is the first element in the evaluation of thrombocytopenia. This is currently performed by counting the number of large platelets on the peripheral blood film. The MPV (mean platelet volume) is an automated measurement of the platelet volume. This study examines the mean values, correlations, sensitivity, specificity and the receiver operating characteristic curve (comparison of two tests) to determine which of these tests better separates the production state. For increased vs. decreased production, the MPV was 10.0 + 1.9 fL and 8.0 + 1.5 fL (P<.0001) respectively and the megathrombocyte index (MEGA) was 19.0 + 17.6% and 11.5 + 14.9% (P<.007) respectively. The correlation with the state of production was better for MPV (R= .47) than for MEGA (R= .20). For the MPV a sensitivity of 80% occurred with the MPV ⩾ 8.4 fL with a specificity of 71%. For a MEGA ⩾ 6%, the sensitivity was 80% but the specificity was 43%. For any MPV the sensitivity and specificity were better than for any MEGA. The Receiver Operating Characteristic Curve demonstrated that the MPV is a better test than the MEGA for separating the production into increased and decreased states. The MPV is a better test than the MEGA and will add to, but not replace, examination of the peripheral blood film in the diagnosis of thrombocytopenia. © 1993 Wiley‐Lis

ISSN:0361-8609    

DOI:10.1002/ajh.2830440204

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

年代:1993

数据来源: WILEY

摘要:

AbstractThis 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‐L

ISSN:0361-8609    

DOI:10.1002/ajh.2830440205

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

年代:1993

数据来源: WILEY

摘要:

AbstractWe found that patients with thrombotic thrombocytopenic purpura (TTP) have significantly elevated plasma thrombin antithrombin III complex (TAT) and FDP‐D‐dimer levels, while the plasmin‐α2 plasmin inhibitor complex (PIC) level was only slightly increased. The tissue‐type plasminogen activator (t‐PA) level was increased, but it was well correlated with the plasminogen activator inhibitor‐1 (PAl‐l) level. These findings suggest that hypercoagulable and hypofibrinolytic states coexist in these patients, in contrast to patients with disseminated intravascular coagulation, who exhibit coexisting hypercoagulable and hyperfibrinolytic states. Levels of vascular endothelial cell markers, such as PAl‐l, thrombomodulin (TM), and t‐PA, were increased at the onset of TTP, but the level of von Willebrand factor (vWF) antigen was not increased. The outcome in TTP patients was correlated with plasma t‐PA and TM levels but not with TAT or PIC. These results suggest that vascular endothelial cell markers, such as TM and t‐PA, are released from injured or stimulated endothelial cells, reflecting the degree of vascular endothelial damage, and that the main factor in the pathogenesis of TTP is vascular endothelial cell injury.

ISSN:0361-8609    

DOI:10.1002/ajh.2830440206

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

年代:1993

数据来源: WILEY

摘要:

AbstractWe developed a new monoclonal antibody directed against platelet myosin (NNKY6‐19). Using this antibody, we analyzed platelet cytoskeletal changes related to stimulation with thrombin and to long‐term storage. Immunoelectron microscopy showed increased binding of NNKY6‐19 to pseudopods and the open canalicular system during treatment with thrombin (0.1 U/ml) and during storage for 7 days. Flow cytometry also showed increased binding to platelets by NNKY6‐19 and an antiactin monoclonal antibody during storage. The binding of NNKY6‐19 showed an increase greater than that with the antiactin antibody after storage of platelets for 7 days and after thrombin treatment. These findings indicated that the increased binding of NNKY6‐19 had some relationship to changes in intracellular myosin and platelet morphology. Thus use of NNKY6‐19 allowed analysis of subtle changes related to platelet activation, which differed from those detected by antibodies against platelet glycoproteins or by the antiactin antibody. This antibody appears to provide a simple method for studying changes in platelet cytoskeletal and surface proteins. © 1993 W

ISSN:0361-8609    

DOI:10.1002/ajh.2830440207

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

年代:1993

数据来源: WILEY

摘要:

AbstractHypercholesterolemia is associated with an increased incidence of vascular complications. To assess the actual degree of activation of coagulation systems and vascular disorders in hypercholesterolemia, plasma levels of vascular endothelial cell markers, such as thrombomodulin (TM), tissue‐type plasminogen activator, plasminogen activator inhibitor‐l (PAl‐l), and von Willebrand factor, were measured in 51 patients with hypercholesterolemia. We also investigated the effects of Pravastatin, an inhibitor of 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase, on plasma lipid, lipoprotein a, and hemostatic markers. The mean plasma levels of thrombin‐antithrombin III complex (TAT), fibrinopeptide A (FPA), TM, and PAl‐I were significantly elevated in hypercholesterolemia. Of the hemostatic markers, only TM was significantly increased in patients with ischemic heart diseases (IHD). The mean concentration of total cholesterol and levels of TAT, FPA, PAI‐I, and TM were significantly reduced after the Pravastatin treatment. The PIC/TAT ratio was significantly increased in non‐IHD patients after treatment, this was not the case in IHD patients. These findings suggested the presence of a thrombogenic state and vascular endothelial cell disorders in hypercholesterolemia; such a state might well be related to hypofibrinolysis. ©

ISSN:0361-8609    

DOI:10.1002/ajh.2830440208

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

年代:1993

数据来源: WILEY

摘要:

AbstractAlthough a few studies have reported clonal cytogenetic changes in Hodgkin's disease (HD), their correlation with histologic groups is poorly defined. This is because of insufficient numbers of clonally abnormal cases ascertained in each of these studies, an inherent problem associated with the cytogenetic studies of HD. In this report we present results of pathologic, phenotypic, and genetic studies on 29 HD tumors consecutively ascertained by us and the results of a comprehensive analysis of the cytogenetic data available in the literature. In our series 75% of the tumors were positive for Epstein‐Barr virus (EBV) by polymerase chain reaction (PCR) assay. A higher frequency of EBV‐positive tumors showed clonal karyotypic abnormalities than the EBV‐negative tumors. Unlike the case in the previous reports, none of the 24 tumors studied by PCR showed the presence of t(14;18) (q32;q21)‐carrying cells. From the comprehensive analysis of the literature, we identified recurring nonrandom numerical changes, deletions, and chromosome breaks in HD. Some of these are associated either with nodular sclerosis or with mixed cellular histologies. A comparison of the pattern of these nonrandom cytogenetic changes in HD and those reported for non‐Hodgkin's lymphomas (NHL) identified common deletions and breaks between them. These common genetic lesions probably play a role in disease evolution. © 1993 Wiley

ISSN:0361-8609    

DOI:10.1002/ajh.2830440209

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

年代:1993

数据来源: WILEY

摘要:

AbstractPrimary systemic amyloidosis (AL) is a rare disorder characterized by production of an aberrant monoclonal light chain. This insoluble light chain, or a fragment thereof, deposits in tissues as amyloid and results in disruption of organ function and, ultimately, death. Although melphalan and prednisone were reported to benefit subsets of patients with the disease, many patients showed no benefit; the median survival with the disease is ∼2 years. There is a need to develop new agents for patients who fail to respond to a trial of cytotoxic chemotherapy. A study was undertaken of interferon alfa‐2 in the treatment of 15 patients with AL because of its reported benefits in the induction and maintenance therapy for patients with multiple myeloma, a disease that has many characteristics in common with AL. None of the patients showed any objective regression of their disease; the median survival of the entire group was 26.3 months. This survival is not superior to that reported with other agents used for this disease. We conclude that interferon alpha‐2 is not a valuable agent in the treatment of AL. © 1993 Wiley‐L

ISSN:0361-8609    

DOI:10.1002/ajh.2830440210

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

年代:1993

数据来源: WILEY

摘要:

AbstractWe report a 28‐year‐old‐Japanese male who had a skin tumor derived from variant type xeroderma pigmentosum (XP), combined with factor XI (FXI) deficiency and type IIB von Willebrand's disease (vWd). The patient had abnormal bleeding history on tooth extraction. FXI clotting activity (FXI:C) and antigen (FXI:Ag) were remarkably decreased (<0.01 U/ml,<0.02 U/ml, respectively). Factor VIII (FVIII) clotting activity, von Wiliebrand factor antigen (vWf :Ag), and ristocetin cofactor (RCoF) were 0.43 U/ml, 45%, and 57%, respectively. Ristocetin‐induced platelet agglutination (RIPA) revealed hyper‐aggregation compared with a normal control. Multimeric composition of vWf in plasma showed a reduction in high molecular weight forms. The family study revealed two other subjects with ho‐mozygous hereditary FXI deficiency and vWd, and five subjects with heterozygous FXI deficiency. The relationship between FXI deficiency and vWd is discussed and previously reported cases are reviewed. © 1993 Wil

ISSN:0361-8609    

DOI:10.1002/ajh.2830440211

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

年代:1993

数据来源: WILEY