bluuebunny/crossref_metadata_2025_split huggingface dataset:
The relationship between increased platelet count and megakaryocyte size in bronchial carcinoma
Authors: Kristensen S. D. , Bath P. M. W. , Gladwin A.‐M. , Martin J. F. 
Published: March 2008

Summary.This study investigates megakaryocyte size in bronchial carcinoma and its relationship to platelet count, mean platelet volume and platelet function, the latter determined in vivo by measurement of the cutaneous bleeding time. Measurements were performed in 19 patients with bronchial carcinoma and 11 patients with a hiatus hernia (controls). Platelet count (335.123 v. 241 × 72.109/1) and megakaryocyte total area (772.135 v. 666.105μm2) (mean × standard deviation) were both significantly increased in patients with bronchial carcinoma when compared to controls whilst the bleeding time was shorter in the patient group (253.116 v. 321.80 s). Patients with bronchial carcinoma were older (60.2 ×8.4 v. 48.8 ×13.2 years) and smoked more heavily (760.511 v. 92.175 cigarette years) than controls. Megakaryocyte size, platelet count and bleeding time all correlated with smoking habit (r=0.395, P=0.031; r= 0.622, P<0.001; r=‐0.515, P=0.04 respectively). There were no statistically significant differences between the groups with respect to gender or mean platelet volume. When considering all patients, significant correlations existed between platelet count and megakaryocyte area (r= 0.400, P= 0.029), and bleeding time and megakaryocyte area (r=‐0.365, P= 0.047). The megakaryocyte nuclear and cytoplasmic areas were positively correlated (r=0–855, P<0.001). This study suggests that the elevated platelet count in patients with bronchial carcinoma is mediated by an increase in the size of bone marrow megakaryocytes although the results are compounded by the association between smoking and megakaryocyte/platelet parameters.
Factor VIII gene deletions in haemophilia A patients in Czechoslovakia
Authors: Křepelová Anna , Vorlová Zdena , Zavadil Jiŕí , Brdička Radim 
Published: March 2008

Summary.Genomic DNA from 90 Czechoslovak haemophilia A patients from 81 pedigrees was analysed by Southern blotting and hybridization with factor VIII cDNA probes. Three partial deletions of the factor VIII gene were identified and characterized: a 4.8 kilobase (kb) deletion eliminating exon 10 in one patient with severe haemophilia A without inhibitor, a 6.1 kb deletion eliminating the 3’ part of intron 13 and the 5’ part of exon 14 in two related severe haemophiliacs, but only one of them produced inhibitor, and a 4.6 kb deletion eliminating the 3’ part of intron 13 and the 5’ part of exon 14 in a severe haemophiliac with high‐titre inhibitor.Besides these three deletions, three different restriction site variants without apparent loss of DNA sequence were found.
Mechanisms of platelet aggregation by Streptococcus sanguis, a causative organism in infective endocarditis
Authors: Ford I. , Douglas C. W. I. , Preston F. E. , Lawless A. , Hampton K. K. 
Published: March 2008

Summary. The ability of certain strains of Streptococcus sanguis to aggregate human platelets in vitro may be related to their virulence in the pathogenesis of infective endocarditis. We have studied the mechanisms of aggregation of human platelets by S. sanguis strain NCTC 7863. Platelet aggregation follows incubation of S. sanguis cells with platelet‐rich plasma from normal, healthy adults, after a lag of 7–19 min. Platelet aggregation was accompanied by 5‐hydroxytryptamine release and thromboxane B2 production. Aggregation was prevented by aspirin and by EDTA. Platelets from two patients with Glanzmann's thrombasthenia did not respond to bacteria. Fixed, washed platelets resuspended in normal plasma were not agglutinated by S. sanguis.Blocking the glycoprotein Ib receptor with a monoclonal antibody inhibited aggregation of PRP. However, S. sanguis did not induce von Willebrand factor (vWF) binding to platelets; nor did the bacteria prevent ristocetin‐induced platelet agglutination or vWF binding. The aggregation response was not related to plasma vWF activity levels in normal subjects or in patients with von Willebrand's disease.The platelet response to S. sanguis therefore resembles true aggregation, requiring the cyclo‐oxygenase pathway and the presence of glycoprotein IIb/IIIa. The mechanism also involves glycoprotein Ib, but not apparently through irreversible binding of vWF.
PADGEM/GMP‐140 expression on platelet membranes from homozygous beta thalassaemic patients
Authors: Del Principe Domenico , Menichelli Adriana , Di Giulio Stefano , De Matteis Walter , Cianciulli Paolo , Papa Giuseppe 
Published: March 2008

Summary.Thromboembolic events, which are associated with significant morbidity and mortality, occur in betathalassaemia. We studied the expression of the platelet selectin PADGEM/GMP‐140 on intact cells from thalassaemic patients, as a marker ofin vivoplatelet activation. The mean of positive cells (%) was 38 · 143 · 20 · 65 in the patients versus 5 · 048 | 1 · 8 in the controls.n= 21.P< 0<001.No correlation was found between GMP‐140 expression and splenectomy, platelet counts, plasma ferritin and natural coagulation inhibitors. Instead an indirect correlation was found between GMP‐140 expression and HDL‐cholesterol. Moreover platelet activation was directly correlated with prebeta lipoproteins. Our data indicate that thalassaemic patients present anin vivoplatelet activation, which possibly depends on the dyslipidaemia, which is now regarded as a frequent feature of this disease.
High doses of intravenous recombinant erythropoietin for the treatment of anaemia in myelodysplastic syndrome
Authors: Goy A. , Belanger C. , Casadevall N. , Picard F. , Guesnu M. , Jaulmes D. , Poisson D. , Varet B. 
Published: March 2008

Summary. We studied the efficacy of high doses (100 000 IU intravenously (IV)/twice a week) of human recombinant erythropoietin (rHuEpo) in patients with transfusion dependent myelodysplastic syndromes (MDS). Rationale for such dose of IV Epo was the poor in vitro response of MDS erythroid progenitors (CFU‐E) to physiological concentrations of Epo, and the usual high endogenous serum Epo levels of MDS patients. Seventeen patients (nine males, eight females) were included, five refractory anaemia (RA), six RA with blasts excess (RAEB), five RA with ringed sideroblasts (RARS).Tolerance was good, except in three patients who experienced severe flu‐like syndrome after Epo injection. None of the patients showed hypertension or developed anti rHuEpo antibodies. Three patients (17.6%) with RAEB had 35–60% reduction of transfusion requirements. No progression of disease occurred. Percentage of erythroblasts, endogenous baseline Epo level and in vitro cultures of erythroid progenitors did not correlate with response to Epo treatment. This study shows that very high IV doses induce only seldom and partial improvement in the status of transfusion dependent MDS. This rate of response, not higher than described with lower dosage, probably represents the maximum expectable response to rHuEpo in this category of patients.
Immunotyping of blasts in refractory anaemia with excess of blasts
Authors: Oertel Joachim , Kleiner Sonja , Huhn Dieter 
Published: March 2008

Summary. A study of immunological markers was performed in 16 patients with newly diagnosed refractory anaemia with excess of blasts (RAEB) and RAEB in transformation (RAEB‐T) and in 12 other patients with acute myeloid leukaemia evolving from RAEB or RAEB‐T. Immunocytochemical investigation of bone marrow blasts was done using a modified indirect immunoperoxidase technique. This method permitted accurate morphological identification of blasts and other cells in bone marrow. The monoclonal antibodies used in RAEB and RAEB‐T samples were anti‐CD34, ‐c‐kit, ‐HLA‐DR and ‐CD13.The range of CD34 expression of blasts in RAEB samples was 1–14% (mean 6·2%) and in RAEB‐T samples 29–48% (mean 35·5%). CD34 positivity was detected in 3·94% (mean 47·4%) of the bone marrow blasts in acute myeloid leukaemia evolving from RAEB and RAEB‐T. Expression of c‐kit was demonstrated only in a low percentage of blast cells in RAEB, RAEB‐T and acute myeloid leukaemia following myelodysplasia. A high percentage (> 30%) of blasts in most patients with RAEB, RAEB‐T and acute myeloid leukaemia was HLA‐DR and CD13 positive. We observed the transformation from RAEB to acute myeloid leukaemia in three patients. The proportion of CD34 positive blasts increased to 25% and 32% in two patients. The third patient showed an unchanged percentage of CD34 positivity of blasts.These findings indicate that the CD34 positivity of blasts increases with the progression of myelodysplasia to RAEB‐T and acute myeloid leukaemia demonstrating the instability of the clonal defect in myelodysplasia.
Heparin‐induced thrombocytopenia and thrombosis: clinical and laboratory studies
Authors: Boshkov Lynn K. , Warkentin Theodore E. , Hayward Catherine P. M. , Andrew Maureen , Kelton John G. 
Published: March 2008

Summary. Heparin‐induced thrombocytopenia is one of the most common and important immunological complications of drug therapy. Most patients with heparin‐induced thrombocytopenia have isolated thrombocytopenia, which by itself seldom causes serious morbidity. However, a small proportion of patients also develop an acute arterial thrombotic episode which can be fatal. It remains uncertain why some patients have only isolated thrombocytopenia, whereas others have thrombotic complications. In this report we describe 53 patients with heparin‐induced thrombocytopenia in whom the diagnosis was confirmed using the platelet 14C‐serotonin release assay. The intent of the study was to look for laboratory or clinical characteristics that could be used to predict which patients will have the less serious thrombocytopenia and which patients will have thrombocytopenia plus thrombotic complications. The laboratory markers included AT‐III, protein C, protein S and heparin cofactor II. No serological result identified whether a patient was at risk of having isolated thrombocytopenia or an acute thrombotic event. However, during the acute thrombocytopenic episode, there was evidence of global activation of the coagulation cascade as evidenced by reductions in the level of protein C, heparin cofactor II and antithrombin III. Following resolution of the thrombocytopenia, these inhibitory factors returned to normal indicating that the thrombotic complications were not caused by a familial deficiency.We did observe a highly significant association (P < 0·001) between concomitant cardiovascular complications and the occurrence of an arterial thrombosis in patients with heparin‐induced thrombocytopenia. Recent surgery of any type was strongly associated with venous thrombi (P < 0·001). Our data suggest that heparin‐induced thrombocytopenia is a procoagulant disorder with thrombosis tending to occur at sites of pre‐existing pathology.
The clinical outcome of autoimmune thrombocytopenic purpura patients is related to their T cell immunodeficiency
Authors: Garcia‐Suarez J. , Prieto A. , Reyes E. , Manzano E. , Merino J. L. , Alvarez‐Mon M. 
Published: March 2008

Summary. In this work we have furthered the understanding of the alterations of T lymphocytes from 29 patients with active autoimmune thrombocytopenic purpura (ATP) and the clinical significance of their lymphocytes. An increased percentage of in vivo activated (CD25+ and DR+) T lymphocytes was found in ATP patients with respect to that found in 22 healthy controls. The function of these T cells measured as the proliferative response to polyclonal mitogenic signals is heterogeneously impaired in ATP patients. T lymphocytes from 65·5% (19/29) of the ATP patients showed a decreased proliferative response to these mitogenic signals. This functional alteration is associated with a redistribution of the T cell compartment in these patients' peripheral blood since a significant decrease of CD4+ T lymphocytes was found.We have also found that the impairment of the T cell function is different in the diverse clinical situations of the disease. Those with stable, untreated disease showed a marked decrease in the T cell proliferative response to mitogens. Furthermore, those patients who did not respond either to steroids or to splenectomy showed significantly reduced T lymphocyte blastogenesis after phytohaemagglutinin (PHA) stimulation in comparison to that found in responding patients.
Fixation with formaldehyde induces expression of activation dependent platelet membrane glycoproteins, P selectin (CD62) and GP53 (CD63)
Authors: Cahill M. R. , Macey M. G. , Newland A. C. 
Published: March 2008

Summary. Platelet activation in vivo is important in the pathogenesis of thrombosis. Accurate measurement is difficult due to artefactual in vitro preparation related activation. This can be overcome by using whole blood techniques, such as flow cytometry. However, there is little consensus on methods of platelet preparation, procedures for use of fixation, or the optimal types/amounts of fixative. The use of unfixed platelets has received little attention.We describe a series of experiments comparing platelet activation antigen expression detected by flow cytometry in fixed and unfixed samples. Formaldehyde increased the expression of both CD62 and CD63. We recommend that fixation with formaldehyde should not be used when studying platelet activation.
Blood platelet heterogeneity: evidence for two classes of platelets in man and rat
Authors: Behnke O. , Forer A. 
Published: March 2008

Summary. The platelet population of man and rat can be divided into two classes of about equal size on the basis of presence/absence of an acid phosphatase which acts on paranitrophenylphosphate (a PNPase), at pH 5. The cytochemical reaction product is in the platelet cytoplasmic matrix, without apparent association with organelles or membrane systems.We could not relate differences in staining to differences in function: all cells responded the same to activation by thrombin, ADP, or collagen, in fibrinogen binding to activated platelets, by endocytosis of fluid‐phase tracers, and in internalization of latex particles.With respect to possible physiological substrates for the PNP‐ase, there was no reaction product from β‐glycerophosphate, AMP, ADP, ATP, GTP, CMP, IMP, cAMP, creatine phosphate, and inositol phosphates, and the enzyme was not inhibited by 40 mm lithium. There was reaction product from tyrosine phosphate suggesting that the physiological substrate for PNP‐ase is tyrosine phosphate.In rat bone marrow, megakaryocytes also were of two classes, PNPase positive and PNPase negative, suggesting that different classes of platelets arise from different classes of megakaryocytes.
Autoantibodies directed against the epidermal growth factor‐like domains of thrombomodulin inhibit protein C activation in vitro
Authors: Oosting Janine D. , Preissner Klaus T. , Derksen Ronald H. W. M. , Groot Philip G. de 
Published: March 2008

Summary No consensus has been obtained about the question whether autoantibodies, in particular antiphospholipid antibodies (aPL), may cause thrombosis by inhibiting thrombomodulin (TM) mediated protein C activation. In order to clarify the mechanism by which autoantibodies inhibit TM‐mediated protein C activation, we have screened 12 patients with autoimmune diseases for the presence of circulating autoantibodies inhibiting TM function. In a cross‐sectional study we found that IgG fractions from two patients (who were aPL negative) inhibited TM mediated protein C activation in an assay system using purified components. A longitudinal study of six patients with a history of thrombosis of which two were aPL positive showed that all had at some time circulating antibodies inhibiting TM function, suggesting that the presence of these antibodies is transient.Three different TMs were used to identify the epitope of the antithrombomodulin antibodies (aTM): rabbit TM, which contains the entire TM molecule: Solulin, which contains the extracellular part of TM, and rEGF‐TM, which contains the six epidermal growth factor (EGF) domains of TM. We showed that the aTM inhibited protein C activation mediated by all three TMs, indicating that the aTM are directed against the region containing the EGF domains.When TM was incorporated in phospholipid vesicles, no inhibition by these aTM could be demonstrated. In addition, protein C activation mediated by cultured endothelial cells (EC) could not be inhibited by aTM. The lack of inhibition of TM in phospholipid vesicles and EC‐TM by aTM suggests that aTM only inhibit soluble TM.In conclusion, we demonstrated the transient presence of circulating autoantibodies directed against the region of TM containing the EGF domains in SLE patients with a history of thrombotic complications. We postulate that the presence of antibodies to soluble TM may be, in addition to aPL, a risk factor for the occurrence of thrombosis in patients with autoimmune diseases.
Analysis of multidrug‐resistance (MDR‐1) glycoprotein and CD56 expression to separate monoclonal gammopathy from multiple myeloma
Authors: Sonneveld P. , Durie B. G. M. , Lokhorst H. M. , Frutiger Y. , Schoester M. , Vela E. E. 
Published: March 2008

Summary Monoclonal gammopathy of undetermined significance (MGUS) is different from multiple myeloma (MM) by a low proliferation and by its indolent clinical course. In this study, two biological parameters were investigated which mark the transition from MGUS to MM, i.e. expression of the P‐170 glycoprotein associated with the multidrug resistance phenotype (MDR‐1) and expression of the natural killer cell antigen, CD56. Strong MDR‐1 expression was found in plasma cells of 32/38 untreated MGUS as compared with 33/105 untreated MM stage I–III (84%v 32%, P<0.001) and in 0/10 normal plasma cell samples. CD56 expression in high density was present in 43/57 analysed untreated MM but in none of 23 MGUS (78%v 0%P<0.0001). Plasma cells did characteristically show a low Ki‐67 proliferation index in 14/15 MGUS patients (mean 0.05%, range 0–0.2%) and a higher index in 25 analysed MM patients (mean 2.31%, range 1–7%, P<0.03).These data indicate that MDR‐1 expression together with absence of CD56 expression and a low proliferation index can be used to separate MGUS from MM.
Effect of antiphospholipid antibodies on procoagulant activity of activated platelets and platelet‐derived microvesicles
Authors: Galli M. , Bevers E. M. , Comfurius P. , Barbui T. , Zwaal R. F. A. 
Published: March 2008

We have recently described the in vitro mechanism of action of anticardiolipin (aCL) and lupus anticoagulant (LA) antibodies in patients with the antiphospholipid syndrome. LA antibodies inhibit coagulation reactions in plasma because they appear to recognize the complex of lipid‐bound (human) prothrombin, whereas aCL antibodies require β2‐glycoprotein I (β2‐GPI) for binding to anionic phospholipids. aCL antibodies can be divided into two subgroups, according to their behaviour in lipid‐dependent coagulation reactions: aCL‐type A enhances the anti‐coagulant effect of β2‐GPI, whereas aCL‐type B does not.In the present study we investigated the effect of purified aCL‐type A and B and of LA antibodies on the procoagulant activity of both Ca‐ionophore activated platelets and platelet‐derived microvesicles, using an assay system with highly purified bovine coagulation factors Xa, Va, and prothrombin from human and bovine origin. In the absence of β2‐GPI neither type of aCL was able to inhibit the prothrombinase activity of platelets or microvesicles. However, a strong and dose‐dependent inhibition of the prothrombinase activity of both platelets and platelet‐derived microvesicles was observed within a few minutes, when aCL‐type A antibodies were added in combination with β2‐GPI. This inhibitory effect was dependent also on the concentration of β2‐GPI. Conversely, no inhibitory effect of aCL‐type B antibodies on platelet‐ (or microvesicle) prothrombinase activity in the presence of β2‐GPI could be observed.LA antibodies were able to inhibit in a dose‐dependent way the procoagulant activity of activated platelets and platelet‐derived microvesicles. With two LA preparations this inhibition was only apparent when human prothrombin was used as substrate, while a third preparation exhibited its inhibitory effect both in the presence of human and bovine prothromin.The data indicate that, in the presence of their respective cofactors β2‐GPI and prothrombin, aCL and LA antibodies interact with the membrane of activated platelets and platelet‐derived microvesicles in a very similar way as previously observed for their interaction with anionic phos‐pholipid surfaces.
Iron status in red cell pyruvate kinase deficiency: study of Italian cases
Authors: Zanella Alberto , Berzuini Alessandra , Colombo Maria Bernadette , Guffanti Anna , Lecchi Lucilla , Poli Francesca , Cappellini Maria Domenica , Barosi Giovanni 
Published: March 2008

Summary. We investigated the iron status of 33 pyruvate kinase (PK) deficient patients, most of the cases reported in Italy. Serum ferritin (SF) was higher than the upper limit of the range of matched controls in 15/25 (60%) non‐transfused patients (median 228 μg/l, range 58–3160 v 43, 22–310). Liver siderosis and fibrosis were found in 8/9, and cirrhosis in two who died at age 39 and 42 of complications of iron overload.SF was independent of age, sex, or severity of haemolysis. The prevalence of HLA‐A3 antigen in PK deficient patients was not significantly different from that of our healthy population (29.6%v 23%). The HLA‐A3 positive, non‐transfused patients had significantly higher SF values than the HLA‐A3 negative ones (median 675 μg/l, range 340–3160 v 145, 58–400). A pedigree study of six high SF‐probands indicated that iron overload has a multifactorial pathogenesis. In particular, the association of PK deficiency‐induced haemolysis, splenectomy and an additional factor (heterozygosity for idiopathic haemochromatosis, ineffective erythropoiesis) leads to severe iron accumulation. We suggest that monitoring iron status would be useful in PK deficient patients, particularly in splenectomized and HLA‐A3 positive ones, to identify those at risk of iron overload and prevent the clinical consequences of iron accumulation.