In 41 diabetics (27 type I, 14 type 11) and in 23 healthy controls the number of glycoprotein (GP)
Increased functional properties of diabetic platelets might be already conditioned during thrombopoiesis in the stem cell system. This hypothesis was studied by recording the distribution characteristics of the peripheral platelet pool in 218 diabetic patients versus 51 controls. Furthermore, platelet membrane coating with the stem cell marker glycoprotein IB was analyzed in 41 diabetic subjects and compared to 23 healthy volunteers. A consistent, significant shift of the volume distribution to larger platelets was found in diabetics: Mean platelet volume (MPV) - 7.9 +/- 0.9 versus 7.2 +/- 0.8 [fl]; Megathrombocyte index (MTI) - 20.4 +/- 2.8 versus 18.1 +/- 2.5 [fl]. These deviations were present in all patient subsets, however did not correlate to parameters of glucose metabolism. Whole blood platelet count was increased in the patient group; 195.0 +/- 59.5 versus 184.0 +/- 37.5 x 10(3) plts/ul. Coating with glycoprotein IB receptors correlated significantly to platelet size in platelets of both controls and diabetics (r normal = 0.52 +/- 0.07; r diabetic = 0.46 +/- 0.1). The quantitative expression of glycoprotein IB was significantly enhanced in the diabetic group: 54,500 x 1.28 +/- 1 versus 39,100 x 1.3 +/- 1 molecules per platelet. In conclusion, these findings strongly support the assumption of diabetic stem cell dysfunction of the megakaryocytic series and progenitor cells resulting in platelets with primarily increased potency to adhere and aggregate in diabetes mellitus.
'Ex vivo' testing of functional platelet properties using conventional techniques reflects the overall behaviour of the whole platelet population in the sample under investigation. Since many functional aspects depend on ultrastructural constituents which may vary from one cell to another, multiparameter single cell analysis of platelets may be advantageous in providing direct insight into deviations at the cellular level relevant to the pathophysiology of disease states such as bleeding disorders or thrombophilia. Immunolabelling with monoclonal antibodies against membrane antigens has been combined with flowcytometry to provide a standardized, highly specific and sensitive analytical tool. The assay has been optimized for simultaneous two colour fluorescence staining, and this allows the testing of whole blood to provide a quick monitoring method for the differential diagnosis of thrombasthenic diseases like Bernard Soulier's syndrome or Glanzmann's thrombasthenia in which typical staining patterns lack the specific fluorescence for glycoproteins Ib and IIb/IIIa respectively. Also changes in the antigenicity of the outer membrane of activated platelets are detectable with monoclonal antibodies against specific antigenic epitopes such as thrombospondin (a secretion marker) or α-granule and lysosomal proteins (extrusion markers). However, for detection of activated platelets in diseases associated with a prethrombotic state, the procedures for immunolabelling platelets with monoclonal antibodies and instrumental detection sensitivity remain to be optimized. After further development, flowcytometric assays of the functional status of individual platelets may be superior to the measurement of the indirect plasma markers such as platelet factor 4 or β-thromboglobulin for routine diagnosis of the prethrombotic state.
Background. The prognostic significance of tumor DNA ploidy in patients with cancer of the pancreas has not been defined because conflicting results have been reported. Methods. DNA content was measured in 56 ductal adenocarcinomas of the pancreas. DNA ploidy status was evaluated by flow cytometry in nuclei isolated from paraffin‐embedded tumor tissues. Results. An abnormal DNA stemline was observed in 27 (48%) patients. The percentage of aneuploid tumors was significantly increased in tumors classified as Stage III/IV (53%) compared with those classified as Stage I (22%). A borderline significant association existed between DNA ploidy and radicality of surgery (P = 0.08). The median survival of patients with diploid carcinomas was 6.9 months (standard error, ±0.9) in comparison to 4.5 ± 1.2 months for patients with aneuploid tumors (P = 0.013 by generalized Wilcoxon test; P = 0.023 by generalized Savage test). Although a selection bias cannot be excluded, survival of patients with a radical resection was longer than that of patients with a nonradical resection (P = 0.0008 and P = 0.0085, respectively). In addition, presence of distant metastasis (P = 0.0006 [Wilcoxon test] and P = 0.033 [Savage test]) could be identified as a prognostic factor. In a Cox regression model, results of surgery and DNA ploidy were independent prognostic variables. Conclusions. Because DNA ploidy has a significant impact on prognosis in pancreatic cancer, it should be used as a variable for stratified randomization of patients in therapeutic trials.
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