摘要:

AbstractElevation of free cytoplasmic calcium is the common pathway of platelet activation, leading to shape change, shedding of platelet microparticles (PMP), aggregation, and secretion of internal granules, including expression of CD62p on the surface. Platelet activation is well documented in unstable angina (UA) and acute myocardial infarction (MI). We investigated the following markers of platelet activation in 55 patients undergoing coronary angiography for suspected CAD: free cytoplasmic calcium, [Ca2+]cyt, PMP, CD62p expression, and platelet/leukocyte (P/L) interaction. [CA2+]cytwas measured by Fluo‐3 and the other measurements were by flow cytometry. Patients were classified into three groups: unstable angina (UA, n = 11), recent myocardial infarction (MI, n = 11), and patient controls (CTL, n = 33). Blood was drawn before infusion of heparin through femoral lines at the time of catheterization for assays.Results:(1) PMP values were significantly higher in both UA and MI than in CTL,P<0.05. There was no difference between UA and MI. (2) P/L interaction was significantly elevated only in UA,P<0.05. (3) CD62p expression on free platelets did not differ significantly between any of the three groups. (4) The resting [Ca2+]cyt, thrombin‐induced CA2+influx, and release of CA2+from internal stores were all significantly higher in platelets from the combined patient group (UA + MI) than in the patient group,P<0.001Conclusions:Results on calcium hemostasis and PMP were significantly different in patients with acute coronary syndromes than those with stable angina or no coronay ischemia; this may reflect underlying pathophysiology of acute coronary ischemia. P/L interaction was higher only in the UA group, suggesting a role of leukocytes in the UA. Am. J. Hematol. 54:95–101, 1997 © 1997 Wiley‐L

ISSN:0361-8609    

DOI:10.1002/(SICI)1096-8652(199702)54:2<95::AID-AJH1>3.0.CO;2-Z

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

年代:1997

数据来源: WILEY

摘要:

AbstractThrombotic thrombocytopenic purpura (TTP) is characterized by micro‐angiopathic hemolytic anemia (MAHA), thrombocytopenia, neurological symptoms, renal involvement, and fever. We describe our experience in 70 serially encountered TTP patients in the last decade who were treated with a standard therapeutic plasma exchange (TPE) protocol. Seventy percent of the patients were females. The median age of the patients was 43 years (range: 8–80). Sixty patients (85.7%) had a complete response to TPE therapy. This represented 91% of 66 who received at least one TPE. Ten patients died, two patients died before and two during the first plasma exchange. The median number of TPEs performed was nine (range: 1–85). Thirty‐five (58%) out of 60 responded to 3–9 TPEs, and 25 (42%) required 10–34 TPEs for the response. The median total plasma volume exchanged was 28 liters (range: 2.7–250 L) and the mean plasma volumes exchanged during each prodcedure was 3.2 (SD ± 1.09 L). The patients were classified into early responders (ER) and late responders (LR). ERs had a mean platelet count of 180 × 109/L by Day 5, mean LDH of 643 IU/L by Day 7, and required median of seven TPEs. LRs had a mean platelet count of 122 × 109/L by Day 5, mean LDH of 885 IU/L by Day 7, and required median of 19 TPEs (P= 0.001). The platelet counts were significantly higher (P= 0.01–0.03) in ERs on Days 1, 3, and 5 as compared to LRs but the LDH did not differ significantly. Seventy‐seven percent of LRs had exacerbation of TTP and 18% had relapse as compared to 7% each in ERs. Thirteen patients were in coma/semicoma at presentation. Out of these, six died, making coma a bad prognostic indicator. Five of the seven survivors in coma had received two single‐plasma volume exchanges on Day 1. In conclusion, 91% of TTP patients had an excellent response to plasma exchange therapy with FFP. Coma/semicoma appears to be a bad prognostic indicator. LRs needed prolonged treatment with a greater number of patients experiencing exacerbation and relapse of TTP as compared to ERs. Am. J. Hematol. 54:102–107, 199

ISSN:0361-8609    

DOI:10.1002/(SICI)1096-8652(199702)54:2<102::AID-AJH2>3.0.CO;2-0

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

年代:1997

数据来源: WILEY

摘要:

AbstractTo establish a simple computer program for the laboratory diagnosis of anemia and related diseases, multivariate analyses were applied to the results of routine hematological laboratory tests obtained from 48 patients and 51 healthy volunteers. The patients studied were limited to those who had not been treated hematologically by the time of their first visit to our hospital, and their first data obtained in our laboratory were analyzed. Final diagnoses were aplastic anemia (AA) in 21, myelodysplastic syndrome (MDS) in 14, iron deficiency anemia (IDA) in 3, polycytemia vera (PV)in 3, and idiopathic thrombocytopenic purpura (ITP) in 7. Eight parameters, WBC, RBC, Hb, Ht, MCV, MCH, MCHC, and PLT, were transformed to normal distribution and then applied to principal component analysis to evaluate their independence. Very close relationships were observed between Ht and Hb, and between MCV and MCH. One each of these pairs was selected by discriminant analysis and two sets, RBC, MCH, Hb, PLT, and WBC, and RBC, MCV, Ht, PLT, and WBC, were obtained. Two canonical components gave good discrimination of these five diseases and also of normal subjects. When disease prediction was made using this analysis, 37 of 48 patients (77.1%) were predicted correctly, and furthermore, when two disease predictions were allowed, all patients were diagnosed properly. Some overlaps were observed in this two‐dimensional coordinate system, especially of AA and MDS, and also with normal subjects. To improve the system further, the additional parameters of age and sex were added to construct a three‐dimensional analysis which resulted in much clearer discrimination. The whole procedure described is being developed with subjects who are not taking medication. Subsequently, the general application of this analytical procedure should be limited to only those not on medications. In conclusion, this is in essence a demonstration project; however, this trial of laboratory diagnosis using routine hematological laboratory results appears to be promising. Further extension of the study by increasing numbers of patients and disorders studied, including secondary anemias, will allow the design of diagnostic software for use with personal computers at the sites of primary care. Am. J. Hematol. 54:108–117, 1997 © 1997 Wiley‐

ISSN:0361-8609    

DOI:10.1002/(SICI)1096-8652(199702)54:2<108::AID-AJH3>3.0.CO;2-0

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

年代:1997

数据来源: WILEY

摘要:

AbstractAdult respiratory distress syndrome (ARDS) and disseminated intravascular coagulation (DIC) are serious complications of sepsis. Thrombomodulin, an important endothelial anticoagulant, binds thrombin to generate activated protein C (APC). To determine whether thrombomodulin purified from human urine (urinary thrombomodulin, UTM) is useful for the treatment of DIC and ARDS in sepsis, we examined the effect of UTM on endotoxin (ET)‐induced coagulation abnormalities and pulmonary vascular injury in rats. Intravenous administration of UTM prevented the ET‐induced pulmonary accumulation of leukocytes and the increase in pulmonary vascular permeability, as well as ET‐induced histological changes such as leukocyte infiltration and pulmonary interstitial edema. On the other hand, dansyl‐Glu‐Gly‐Arg‐chloromethyl ketone‐treated factor Xa (DEGR‐Xa), a selective inhibitor of thrombin generation, did not prevent these effects of ET. UTM did not prevent ET‐induced pulmonary accumulation of leukocytes and pulmonary vascular injury in rats pretreated with DEGR‐Xa. Our findings suggest that UTM attenuates ET‐induced coagulation abnormalities and pulmonary vascular injury. Furthermore, the latter effect may be dependent on the capacity of UTM to activate protein C. Am. J. Hematol. 54:118–1

ISSN:0361-8609    

DOI:10.1002/(SICI)1096-8652(199702)54:2<118::AID-AJH4>3.0.CO;2-#

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

年代:1997

数据来源: WILEY

摘要:

AbstractLimited evidence suggests increased efficacy of rhG‐CSF by subcutaneous (SQ) compared with intravenous (IV) administration. To examine the possibility that rapid elimination of IV rhG‐CSF could substantially shorten the duration of systemic exposure and could explain a difference in pharmacodynamics, we characterized the pharmacokinetic profile of IV rhG‐CSF for comparison to that previously reported for SQ administration. Twelve children were randomly assigned to receive 10 or more days of IV rhG‐CSF at dosages of 5 or 10 μg/kg a day beginning 24 hr after chemotherapy. Enzyme‐linked immunosorbent assay (ELISA) was used to measure rhG‐CSF concentrations in timed serum samples on days 1 and 10. Pharmacokinetic parameters were estimated by nonlinear, least squares regression. All serum concentration‐time profiles were best described by a two‐compartment model of elimination. Mean t1/2βvalues ranged from 3.68 ± 0.86 to 22.4 ± 12.0 hr. ANC was correlated with log CLT(r= 0.72,P<0.05), and inversely with log dose‐adjusted AUC (r= −0.75,P<0.05) and log dose‐adjusted Cmax(r= −0.65,P<0.05). Estimated duration of serum rhG‐CSF concentrations above 1 ng/ml exceeded 24 hr for all but the 5 μg/kg cohort on day 1. Pharmacokinetic parameters of IV rhG‐CSF are similar to those previously reported for SQ administration in children treated with myelosuppressive cancer chemotherapy. Daily IV administration should be suitable alternative route of administration in this patient population. Am. J. Hematol. 54:124

ISSN:0361-8609    

DOI:10.1002/(SICI)1096-8652(199702)54:2<124::AID-AJH5>3.0.CO;2-Z

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

年代:1997

数据来源: WILEY

摘要:

AbstractSurvivors of allogeneic marrow transplants are immunodeficient for at least 1 year after grafting. Multiple defects of immunity have been found; however, it is not known which defect primarily accounts for the high infectious morbidity of these patients. Twenty‐nine allograft recipients who were in complete remission of the original disease were examined for the following parameters of immunity at 1 year after transplant: infection score (gauging the number and severity of infections within the 6 months prior to the annual exam), serum total IgM, IgG, and IgA, anti‐Haemophilus influenzae IgG, anti‐Streptococcus pneumoniae IgG, skin test reactivity, and the blood counts of B cells, CD4+T cells, CD8+T cells, and their subsets. THe only parameter inversely correlated with the infection score was CD4+T cell count (P= 0.005 in univariable analysis,P= 0.06 in multivariable analysis). We conclude that infectious morbidity of long‐term transplant survivors is related to the reconstitution of CD4+T cells. Am. J. Hematology 54:131–138, 1997 © 1997 Wiley

ISSN:0361-8609    

DOI:10.1002/(SICI)1096-8652(199702)54:2<131::AID-AJH6>3.0.CO;2-Y

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

年代:1997

数据来源: WILEY

摘要:

AbstractAcquired von Willebrand's disease (AvWD), an adult‐onset bleeding diathesis, has most commonly been found in patients with an underlying lymphoproliferative disease or monoclonal gammopathy. Other malignancies, autoimmune diseases, hypothyroidism, and drugs have also been associated with AvWD. We have included an illustrative case history of a patient with a bleeding diathesis consistent with AvWD and a monoclonal gammopathy who required emergent cardiac surgery. Our review of the literature determined that most cases of AvWD are due to a circulating antibody that combines with the high molecular weight multimers (HMWM) of von Willebrand factor (vWF). These vWF multimer‐antibody complexes are subsequently cleared from the circulation either by the reticuloendothelial system or by adsorption onto tumor cells. Clearance of the HMWM of vWF thus results in extremely low functional levels and variable antigenic levels. Mixing studies which are traditionally used to diagnose factor inhibitors are useful only if removal of vWF‐antibody complexes can be accomplished in vitro. Treatment with intravenous immunoglobulin has recently been shown to be the most effective therapy for patients with an underlying lymphoproliferative disorder or monoclonal gammopathy. This therapeutic strategy is based on the observed immune complex clearance phenomenon that appears to be operative in most cases. Other AvWD‐associated diseases require treatment specifically directed at the underlying disorder. Am. J. Hematol. 54:139–145, 1997 © 1997 Wiley

ISSN:0361-8609    

DOI:10.1002/(SICI)1096-8652(199702)54:2<139::AID-AJH7>3.0.CO;2-Y

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

年代:1997

数据来源: WILEY

ISSN:0361-8609    

DOI:10.1002/(SICI)1096-8652(199702)54:2<146::AID-AJH8>3.0.CO;2-X

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

年代:1997

数据来源: WILEY

摘要:

AbstractParoxysmal nocturnal hemoglobinuria (PNH) is a rare clonal stem‐cell disorder in which blood cells lack complement inhibiting membrane proteins, and become susceptible to complement‐mediated injury, leading to chronic intravascular hemolysis and pancytopenia. Glucocorticoids have been a mainstay of therapy. For patients refractory to glucocorticoids and requiring blood transfusions, an alternative therapy is needed. We studied danazol therapy in 5 patients refractory to other treatments. Four of the 5 benefited, showing rise in hematocrit and eventual cessation of transfusion requirements. Remissions lasted ≥2 years in 3 and 10 years in 1 patient. Danazol was well‐tolerated without serious side effects. Danazol appears to be a good alternative treatment in PNH. Am. J. Hematol. 54:149–154, 1997 © 1997 Wiley

ISSN:0361-8609    

DOI:10.1002/(SICI)1096-8652(199702)54:2<149::AID-AJH9>3.0.CO;2-X

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

年代:1997

数据来源: WILEY

摘要:

AbstractWe report on 2 cases of chronic relapsing thrombotic thrombocytopenic purpura, in which anti‐phospholipid antibodies were also found. The first patient was felt to have the anti‐phospholipid antibody syndrome, while the second patient had anti‐phospholipid antibodies without clinical manifestations of the anti‐phospholipid antibody syndrome. We discuss chronic relapsing thrombotic thrombocytopenic purpura and the anti‐phospholipid antibody syndrome. Furthermore, we introduce the possibility of an association between chronic relapsing thrombotic thrombocytopenic purpura and the presence of anti‐phospholipid antibodies. Am. J. Hematol. 54:155–159, 1997 © 1997 W

ISSN:0361-8609    

DOI:10.1002/(SICI)1096-8652(199702)54:2<155::AID-AJH10>3.0.CO;2-E

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

年代:1997

数据来源: WILEY