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H Wadenvik

Publications and source records attributed to H Wadenvik.

At least 55 records · Page 3Linked to original sources
PubMed1996

Diagnostic and differential criteria of essential thrombocythemia and reactive thrombocytosis.

Among the chronic myeloproliferative disorders essential thrombocythemia (ET) is known to be a distinct clinical entity in which an excessive number of morphologically and functionally abnormal platelets are produced. The clonal nature of the disease is well established. Based on a review of the literature the present authors propose the following novel criteria for the diagnosis of ET: A1. Platelet count in excess of 600 x 10(9)/L. A2. No increase in red-cell mass (RCM) in the presence of stainable iron in the bone marrow or failure of iron trial (RCM < 36 mL/kg in males and < 32 mL/kg in females; or RCM < 25% above mean normal predicted value*). A3. No Philadelphia chromosome. A4. Megakaryocytic hyperplasia (= increased megakaryocyte number and size) in histological sections of bone marrow and/or increased megakaryocytic ploidy (two-color flow cytometry); no collagen fibrosis. B1. Splenomegaly on isotopic scan or echogram. B2. Unstimulated growth of BFU-E and/or CFU-Meg present. B3. Normal ESR/fibrinogen. The diagnosis of ET is considered to be established if A1 + A2 + A3 + A4 or A1 + A2 + A3 + two B-criteria are fulfilled. (* Br J Haematol 1995; 89:748-756.)

Blood Sedimentation↗
PubMed1996

Naturally occurring IgG autoantibodies to platelet cytoskeleton tropomyosin.

We have observed that naturally occurring serum antibodies generated a 30 Kd band in a platelet immunoblot assay. The target protein had the same molecular weight (30 Kd) under nonreduced and reduced electrophoretic conditions, and could be immunoblotted from either autologous or homologous platelet lysates. Also, the 30 Kd reactive autoantibodies could be totally adsorbed by platelet cytoskeletons. From these data one likely candidate for the autoantibody target was the intracellular platelet protein tropomyosin. Indeed, a commercially available monoclonal anti-tropomyosin antibody reacted with proteins comigrating with this 30 Kd band; affinity purified human platelet tropomyosin was bound by the antibodies that recognized the 30 Kd protein. This body of evidence conclusively demonstrated that naturally occurring serum autoantibodies reacted with the platelet cyto-skeleton protein-tropomyosin. These tropomyosin specific antibodies were found in roughly the same percentage of sera from patients with chronic idiopathic thrombocytopenic purpura (ITP) as from normal individuals.

Adult↗
PubMed1995

The platelet-specific alloantigen PlA1 (HPA-1a): a comparison of flow cytometric immunophenotyping and genotyping using polymerase chain reaction and restriction fragment length polymorphism in a Swedish blood donor population.

BACKGROUND: There is an increasing interest in the development of rapid and reliable techniques for platelet alloantigen typing. STUDY DESIGN AND METHODS: By use of standardized flow cytometry and a specific human alloantiserum, 236 Swedish blood donors were immunophenotyped for the platelet-specific alloantigen, PlA1 (HPA-1a). RESULTS: Ten individuals (4.2%) had low fluorescence intensities and were considered PlA1-negative (HPA-1a-negative); all of them also demonstrated a PlA2/PlA2 (HPA-1b/1b) genotype in a polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) assay of the underlying DNA polymorphism. The remaining population had clear positive fluorescence and was regarded as PlA1-positive (HPA-1a-positive). The fluorescence distribution histogram among PlA1-positive (HPA-1a-positive) individuals was dome-shaped, and those individuals who were homozygous for PlA1 (HPA-1a) could not be distinguished from those who were heterozygous. This finding was further substantiated by PCR-RFLP analysis of the PlA1/PlA2 (HPA-1a/1b) genotype; a heterozygous genotype was found among those having a medium fluorescence intensity as well as among those having a strong fluorescence intensity. CONCLUSION: Flow cytometry is a valuable tool for large-scale detection of PlA1 (HPA-1a). However, flow cytometry based on only one antiserum cannot distinguish between homozygous and heterozygous carriers of PlA1 (HPA-1a). For zygosity testing and when platelets are difficult to obtain, the PCR-RFLP technique is the assay of choice.

Antigens, Human Platelet↗
PubMed1995

Evidence for a light chain restriction of glycoprotein Ib/IX and IIb/IIIa reactive antibodies in chronic idiopathic thrombocytopenic purpura (ITP).

To address the assumption of clonally restricted antibodies in immune thrombocytopenias we studied sera from 19 patients with chronic ITP known to possess antibodies reactive with glycoprotein (GP) Ib/IX and/or GPIIb/IIIa. These sera were re-analysed using the standard monoclonal antibody immobilization of platelet antigens (MAIPA) assay and 16 patients exhibited IgG antibodies reactive with GPIIb/IIIa; seven patients showed also a reactivity with GPIb/IX. Employing a light-chain-specific MAIPA assay, 75% (12/16) of these sera displayed GPIIb/IIIa-specific antibodies that were light chain restricted; only 13% (2/16) of the GPIIb/IIIa reactive sera showed a mixed kappa and lambda phenotype. A light-chain-restricted phenotype was also seen for the GPIb/IX reactive antibodies. To further substantiate these findings, the MAIPA assay was modified in order to avoid interference from human anti-mouse antibodies. A high frequency of light-chain restricted platelet antibodies was also found using the modified MAIPA technique. These results support the hypothesis of a clonal B-cell expansion in immune thrombocytopenias, producing antibodies with a restricted idiotype repertoire and reacting with a limited number of epitopes.

Adult↗
PubMed1995

Fab-mediated binding of glycoprotein Ib/IX and IIb/IIIa specific antibodies in chronic idiopathic thrombocytopenic purpura.

The antibody domain responsible for the interactions between platelet glycoproteins (GP) and serum IgG autoantibodies in patients with chronic idiopathic thrombocytopenic purpura (ITP) was studied. Sera from nine non-transfused ITP patients and 20 normal controls and a serum containing an anti-PlA1 antibody were employed. Serum, purified IgG and F(ab')2 fragments were prepared and their binding to platelet GPIb/IX and GPIIb/IIIa were analysed using a modified MAIPA assay and an antigen capture ELISA. In all experiments most of the autoantibodies studied behaved identically to the anti-PlA1 antibody in that the IgG-F(ab')2 fragments retained their ability to bind to the respective glycoprotein. Substituting the enzyme-conjugated secondary antibody (Fab specific), in the MAIPA assay, with an Fc specific antibody removed all reactivities observed against platelet GPs, produced by IgG-F(ab')2 fragments. Furthermore, in an antigen-capture ELISA, IgG autoantibodies against platelet GPIb/IX and/or GPIIb/IIIa were blocked preferentially by pre-incubating the ITP sera with a goat anti-human IgG (F(ab')2 specific) antibody, but not with an anti-Fc antibody. We conclude that these ITP patients produced antibodies specific for platelet GPIb/IX and/or GPIIb/IIIa, and that the autoantibody-platelet interaction was mediated by the classic Fab binding.

Adult↗
PubMed1995

Glycoprotein IIb/IIIa autoantigenic repertoire in chronic idiopathic thrombocytopenic purpura.

The objective of the present study was to further disclose the autoantigenic repertoire carried by the platelet glycoprotein (GP) IIb/IIIa complex. IgG-F(ab')2 fragments were prepared from two prototype ITP patients, and their ability to block the binding of GPIIb/IIIa reactive antibodies derived from other patients with ITP was evaluated using a modified MAIPA asay; a PlA1 alloantiserum and 20 normal sera were included as controls. It was found that the two prototype IgG-F(ab')2 fragments were each able to significantly block the binding of serum IgG to GPIIb/IIa in six (55%) and seven (64%) out of 11 patients with chronic ITP, respectively. No significant blocking effect was observed for IgG-F(ab')2 fragments prepared from normal subjects. Also, the binding of the PlA1 alloantiserum to its epitope on GPIIIa was not affected by any of the blocking IgG-F(ab')2 fragments exploited in the study. These data substantiate that in chronic ITP at least half of the GPIIb/IIIa reactive sera bind to homogenous autoepitopes.

Adolescent↗
PubMed1995

Antibodies against platelet GPIb/IX, GPIIb/IIIa, and other platelet antigens in chronic idiopathic thrombocytopenic purpura.

Antibodies involved in the pathogenesis of chronic idiopathic thrombocytopenic purpura (ITP) react most frequently with platelet glycoprotein (GP) Ib/IX and GPIIb/IIIa. However, uncertainty as to the specificity, frequency, and clinical significance of such antibodies still remains. By using a modified antigen-capture ELISA (MACE), an immunoprecipitation assay, and an immunoblot assay, sera from 60 patients with chronic ITP were analyzed. GP-specific antibodies were found in 50% (30/60) of the patients, with 14 patients having antibodies directed solely to GPIIb/IIIa, 8 holding antibodies specific only for GPIb/IX, and 8 possessing antibodies against both antigens. Serum antibodies were more frequently (p < 0.01) detected in either active and/or non-splenectomized ITP patients. Moreover, in patients displaying antibodies against GPIb/IX, significantly (p < 0.05) lower platelet counts were observed. Using the immunoblot assay, antibodies specific for a 30 kD platelet antigen were detected in 12 of 60 patients. This antigen could not be immunoprecipitated from surface labelled platelet membranes, indicating an intracellular location. We conclude that in chronic ITP, (1) the frequency of anti-GPIIb/IIIa antibodies is close to that of anti-GPIb/IX antibodies, (2) anti-GP antibodies are more likely to be detected in patients with an active disease status and, (3) a 30 kD internal platelet protein is another frequent antigen.

Adult↗
PubMed1995

Blood platelet activation and membrane glycoprotein changes during extracorporeal life support (ECLS). In vitro studies.

The aim of this study was to evaluate an in vitro model for investigation of platelet function parameters in an extracorporeal system. Two different perfusion pumps were compared, a roller pump (Polystan) and a centrifugal pump (Biomedicus). A continuous increase in glycoprotein (GP)1b-negative platelets was observed in both circuits. A marked increase of plasma beta-thromboglobulin thromboglobulin concentration and a decrease of the intracellular pool of serotonin was observed, indicating a marked release of alpha as well as of dense granules. The plasma concentration of glycocalicin increased in parallel with a reduced platelet surface expression of GP1b, suggesting that the loss of GP1b is caused by proteolysis rather than by a downregulation of this receptor protein. It is concluded that ECLS results in a pronounced platelet degranulation and causes changes of important membrane receptors which might explain some of the bleeding problems observed in patients treated with ECLS. No significant difference was noted between the roller pump and the centrifugal pump. Trial of strategies, e.g., protease inhibitors and nitric oxide to revert this untoward effect of ECLS are highly warranted.

Artificial Organs↗
PubMed1994

Peripheral and intrasplenic platelet kinetics and bone marrow megakaryopoiesis in alpha-2b-interferon treated hairy cell leukemia.

In eight patients with previously untreated hairy cell leukemia (HCL), by using 111In-labelled platelets and megakaryocyte quantitation, the splenic platelet pooling and the platelet production rate (P) were evaluated before and during alpha-2b-interferon (IFN) treatment. Both before and after 8 months of IFN therapy the spleen was shown to pool a sizeable amount of the total body platelet mass. The average splenic platelet pools, prior to and after 8 months of IFN, were 58 +/- 17 and 47 +/- 11%, respectively. At the time when treatment was initiated, the patients were heterogeneous as regards the spleen size, platelet kinetics, and the bone marrow morphology. Three patients had values for P below the 95th percentile for a group of healthy control subjects; following IFN therapy they displayed a substantial increase in P. In three other HCL patients, with the largest spleens, the pre-treatment P was normal, or slightly above the values seen for the control subjects. In these patients, changes in splenic platelet pool size, blood volume, and platelet mean life-span accounted for the increase in platelet count observed in response to IFN. The mean megakaryocyte number and volume per microliter bone marrow increased during IFN therapy, while the mean P remained slightly reduced. It is concluded that splenic platelet pooling would explain the previously described difference in platelet counts between splenectomized and non-splenectomized patients treated with IFN.

Adult↗
PubMed1993

Measurement of spleen size using gamma camera scintigraphy in essential thrombocythaemia.

By using gamma camera imaging the spleen size was determined in 33 consecutive patients with essential thrombocythaemia (ET) and in 33 consecutive patients with reactive thrombocytosis (RT). All ET patients were newly diagnosed and had not received myelosuppressive treatment prior to study; they all fulfilled the criteria for ET as established by the Polycythemia Vera Study Group. In both posterior and lateral projections, the spleen area in the group of ET patients was significantly larger than in the RT patients. The present study has shown that 39% of ET patients at diagnosis have splenic enlargement. Evaluation of spleen size is therefore a useful diagnostic test in patients presenting with unexplained thrombocytosis.

Adult↗
PubMed1992

Cigarette smoking increases thromboxane A2 formation without affecting platelet survival in young healthy females.

Smoking is a risk factor for the development of atherosclerotic cardiovascular disease, in men as well as in women. An increased urinary excretion of the thromboxane metabolite 2,3-dinorthromboxane B2 (Tx-M) has been observed in smokers of both genders, suggesting that cigarette smoking may facilitate cardiovascular disease via an action on the platelets. The present study addressed the hypothesis that the increased Tx-M excretion in female smokers reflects a true facilitation of platelet reactivity in vivo, rather than an increased destruction of the platelets. In healthy female volunteers (aged 20-46 years, 18 smokers and 17 non-smokers) platelet life-span and indices of platelet activity were determined, together with plasma levels of plasminogen activator inhibitor-1 (PAI-1), fibrinogen, peripheral blood cell counts and hematocrit. The urinary excretion of Tx-M was higher in smokers than in non-smokers (361 vs. 204 pg/mg creatinine, respectively, p < 0.05), while plasma and urinary beta-thromboglobulin, plasma platelet factor 4, platelet mean life-span and platelet production rate did not differ between the groups. PAI-1 activity, white blood cell count and hematocrit were higher in smokers than in non-smokers (p < 0.05). These data indicate that smoking facilitates platelet formation of thromboxane A2 without affecting platelet survival; i.e. it increases the activity of platelets without affecting their viability to a measurable extent. Such an increase in platelet activity, operating in parallel to a reduced fibrinolytic activity and a higher hematocrit and white blood cell count, may play an etiological role in smoking-induced cardiovascular disease in women.

Adult↗
PubMed1992

Dysplastic megakaryopoiesis with thrombocytopenia and chromosomal aberration.

A case of isolated thrombocytopenia with decreased platelet production and abnormal megakaryopoiesis is described. In the bone marrow, a chromosomally aberrant clone, 45,XX,-11,-18,+der (11;18)(11q13;18p11), was found. These findings indicate a myelodysplastic nature of the abnormal thrombocytopoiesis. The described case demonstrates the value of a bone marrow examination including histopathology with immunologic techniques to evaluate the megakaryopoiesis in thrombocytopenia and the interest of cytogenetic studies not only in instances with overt hematologic malignancies or complete myelodysplastic syndromes, but also when morphologic abnormalities occur in a single cell line.

Biopsy↗
PubMed1991

The effect of alpha-interferon on bone marrow megakaryocytes and platelet production rate in essential thrombocythemia.

In 10 patients with previously untreated essential thrombocythemia (ET), by using 111In-labeled platelets and megakaryocyte morphometry, the relation between platelet production rate and bone marrow megakaryocytes was evaluated before and during alpha-2b-interferon (IFN) therapy. A highly significant decrease in platelet count occurred during IFN therapy; the platelet counts, at baseline and after 2 and 6 months of IFN therapy, were 1,102 +/- 345 x 10(9)/L, 524 +/- 169 x 10(9)/L (P less than .0001), and 476 +/- 139 x 10(9)/L (P less than .0001), respectively. The decrement in platelet count was mainly a result of diminished platelet production rate, which at baseline and after 2 and 6 months of IFN therapy was 89 +/- 30 x 10(10) platelets/d, 53 +/- 18 x 10(10) platelets/d (P = .0033), and 45 +/- 20 x 10(10) platelets/d (P less than .0001), respectively. Also, a slight shortening of platelet mean life-span (MLS) was observed in response to IFN treatment; platelet MLS was 7.96 +/- 0.69 days at baseline and 6.68 +/- 1.30 days (P = .012) after 6 months of IFN therapy. IFN induced a significant decrease in bone marrow megakaryocyte volume; both megakaryocyte nuclear and cytoplasmatic volumes were affected. The mean megakaryocyte volume was 372 +/- 126 x 10(2) pL/microL at baseline and 278 +/- 147 x 10(2) pL/microL (P = .049) after 6 months of IFN therapy. However, the number of megakaryocytes did not show any significant change in response to IFN. It is concluded that alpha-IFN reduces platelet production rate and the peripheral platelet count in ET mainly through an anti-proliferative action on the megakaryocytes and to a considerably lesser degree by a shortening of platelet MLS.

Adult↗
PubMed1991

'Polycythaemia of stress' in subjects with Type A and Type B behaviour patterns.

To determine the importance of emotional stress for relative polycythaemia, we studied 11 subjects with the Type A and 11 subjects with the Type B behaviour patterns during short-term mental stress. All subjects were healthy, normotensive non-smoking young males aged 20-34 yr. without any medication. During rest there were no significant differences in heart rate, blood pressure, or plasma catecholamines between the two groups, but the A-group had significantly higher haemoglobin concentration (147 vs 140 g/l; p less than 0.005) and haematocrit (43.8 vs 42.1%: p = 0.05) than the B-group. In the whole group, there was a positive correlation between resting diastolic blood pressure and haemoglobin concentration (r = 0.53; p less than 0.05). In response to 10 min of mental arithmetic, haematocrit, haemoglobin and erythrocyte count rose approximately 2% (p less than 0.001 throughout). The stress-induced changes were not significantly different between the A- and B-groups. It is concluded that mild relative polycythaemia could be induced by acute emotional stress. In subjects with the Type A behaviour pattern a slight haemoconcentration is present already at rest, which further increases during stress.

Adult↗
PubMed1991

The in vivo kinetics of 111In- and 51Cr-labelled platelets: a comparative study using both stored and fresh platelets.

The in vivo kinetics of simultaneously injected 51Cr- and 111In-labelled platelets was investigated in 20 healthy male volunteers. The studies were carried out using both fresh platelets and platelets stored for 5 d at 22 degrees C; the disappearance of platelet-bound radioactivity was measured on whole blood samples as well as platelet pellets. Compared to 111In, the labelling efficiency was notably lower for 51Cr, and a higher amount of 51Cr was bound to contaminating red cells. As regards the fresh platelets, only small dissimilarities were observed in the in vivo kinetics obtained with the two labels. 51Cr yielded a slightly higher platelet recovery and longer T1/2 than 111In, when whole blood samples were used for calculations; no differences were seen when using platelet pellets. When stored platelets were studied, 51Cr gave significantly longer T1/2 and mean life-span (MLS) than did 111In. This difference was present for all mathematical models used for the calculation of MLS, and when whole blood samples as well as platelet pellets were employed. It was demonstrated that the estimation of MLS was also highly dependent upon techniques of blood sampling and curve fitting. Calculation, in which the initial data points were excluded, gave consistently longer MLS (P less than 0.0001), as compared to when all data points were included. Furthermore, when all survival studies were grouped together, calculations using platelet pellets gave a significantly (P less than 0.001) shorter platelet MLS than calculations using whole blood samples. It is concluded that both 51Cr and 111In are acceptable as radiolabels for both fresh and stored platelets. However, it appears that the viability of stored platelets may be influenced by the choice of label, and caution must be taken when these isotopes are used together in dual tracer experiments. Also, our results show that a meticulously standardized processing of blood samples and experimental data is required to enable interlaboratory comparisons of the results.

Adult↗
PubMed1991

Leukocyte removal filtration of platelet concentrates. A study of platelet loss using 111In-labelled platelets and dynamic gamma camera scintigraphy.

111In labelled platelets and gamma camera scintigraphy were used for the study of the platelet loss during leukocyte removal filtration of stored platelets. Two different filters were examined, Imugard IG500 and Pall PL100, and platelet pools containing varying number of platelet concentrates were filtered. It was found that a sizeable amount of the platelets was trapped within the filter. Some of the trapped platelets could be recovered by rinsing the filters with normal saline. The most appropriate rinsing volume to recover lost platelets seemed to match with the "dead space" volume within the filter. It is concluded that radiolabelled platelets and gamma camera scintigraphy appears to be an excellent method to investigate the dynamic events of platelet loss during leukocyte removal filtration. This technique should be well applicable for the study of technological advances in filter construction.

Blood Platelets↗
PubMed1991

Prevention of deep-vein thrombosis and pulmonary embolism after total hip replacement. Comparison of low-molecular-weight heparin and unfractionated heparin.

In a prospective, randomized, double-blind study, the efficacy and safety of a low-molecular-weight heparin were compared with those of unfractionated sodium heparin (standard heparin) in 136 patients who had elective total hip replacement. The patients received subcutaneous injection of either 5000 international units of low-molecular-weight heparin once daily or 5000 international units of standard heparin three times a day. Treatment with low-molecular-weight heparin began twelve hours before the operation, and treatment with standard heparin began two hours preoperatively; both regimens were continued for ten days. Twelve days postoperatively, bilateral ascending phlebography was performed in 122 patients, sixty-three in the treatment group that received low-molecular-weight heparin and fifty-nine in the treatment group that received standard heparin. Pulmonary scintigraphy was performed in 127 patients. Deep-vein thrombosis was diagnosed in forty-four patients: nineteen (30 per cent) of the sixty-three who received low-molecular-weight heparin and twenty-five (42 per cent) of the fifty-nine who received standard heparin. All but four patients, two from each treatment group, were asymptomatic. The difference in the total rate of thrombosis in the two groups was not significant (p = 0.189). However, thrombosis occurred in the thigh in only six (10 per cent) of the patients who received low-molecular-weight heparin but in eighteen (31 per cent) of those who received standard heparin, a significant difference (p = 0.011). Pulmonary embolism was detected in twenty-seven patients: eight (12.3 per cent) of those who received low-molecular-weight heparin and nineteen (30.6 per cent) of those who received standard heparin. Only three patients had clinical signs of embolism. Pulmonary embolism was significantly more frequent in the group that received standard heparin (p = 0.016). Total loss of blood and the total amount of blood that was transfused were significantly reduced in the patients who received low-molecular-weight heparin compared with those who received standard heparin. Prophylaxis was not discontinued because of hemorrhage in any patient. The efficacy of low-molecular-weight heparin was superior to that of standard heparin in the prevention of femoral thrombosis and pulmonary embolism, although the over-all incidence of deep-vein thrombosis was not statistically different.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗