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Biomedical subjects

G L Salvagno

Publications and source records attributed to G L Salvagno.

6 recordsLinked to original sources
PubMed2007

Impact of different inhibitor reactivities with commercial factor VIII concentrates on thrombin generation.

In order to describe the haemostatic role of a variation in inhibitor reactivity with different factor VIII (FVIII) concentrates, we have compared inhibitor titres against a panel of FVIII concentrates and correlated titre with the capacity to inhibit thrombin generation. Three plasma-derived concentrates were tested in vitro in mixing experiments with inhibitor plasmas from 11 patients with severe haemophilia A: Fanhdi, which contains von Willebrand factor (VWF) with a final ratio of approximately 1:1 (VWF IU per IU FVIII:C); Haemate-P with a ratio of 2.5:1 and Hemofil-M containing only trace amounts of VWF. In addition, the recombinant FVIII concentrate Kogenate Bayer containing no VWF was included. Inhibitor titres and the capacity to generate thrombin were measured. A statistically significant difference in measured titres was found with the highest titres recorded against Hemofil-M. The inhibitor titres needed to inhibit 50% maximum thrombin generation were the lowest for Kogenate Bayer and the highest and similar for Fanhdi and Haemate-P with intermediate titres needed for inhibition of Hemofil-M. In this study, the thrombin generation assay provides additional indications for the role of VWF in the treatment of patients with inhibitors. The VWF-containing concentrates Fanhdi and Haemate-P, added to FVIII-deficient plasma with the presence of inhibitor, generate more thrombin than do the purified concentrates Hemofil-M and Kogenate Bayer.

Antigen-Antibody Reactions↗
PubMed2006

The influence of the tourniquet time on hematological testing for antidoping purposes.

Hematological manipulation to optimize aerobic performances is a serious problem in elite and professional sports and the approach to identify blood doping is as yet challenging. In most cases, the current strategy contemplates a first stage of analysis, based on the application of arbitrary threshold for hemoglobin or hematocrit, followed by second-generation blood tests, or the adoption of an individual hematological passport. To establish the influence of preanalytical variables on the athletes' hematological profile, we compared hemoglobin, hematocrit, and reticulocytes count in 27 male professional cyclists after a mean time of 2.30 +/- 0.12 tourniquet holding. Statistically significant differences were observed for hematocrit (+ 2.4 %; p < 0.001) and hemoglobin measurements (+ 1.4 %; p < 0.001), but not for the reticulocytes count (- 1.9 %; p = 0.170). In 4 out of 27 cases (15 %), the variability of the hematocrit measurement exceeded the 4.1 % desirable analytical quality specification for total error. Results of the present investigation further highlight the risk that unfulfillment of rigorous and standardized procedures for collection of blood specimens might increase the number of false positive testing and might lead to inappropriate sanctioning of a minority of clean athletes with hematocrit or hemoglobin values naturally elevated. Owing to the minor biological variability and the lesser susceptibility to variation of the preanalytical phase, the hemoglobin concentration might be a more suitable parameter than hematocrit for inclusion within laboratory testing to identify blood doping.

Doping in Sports↗
PubMed2006

Evaluation of platelet turnover by flow cytometry.

The number of circulating newly produced platelets depends on the thrombopoietic capacity of bone marrow as well as platelet removal from the bloodstream. Flow cytometric analysis with thiazole orange (TO), a fluorescent dye that crosses platelet membranes and binds intracellular RNA, has been used to measure circulating reticulated platelets (RPs) with high RNA content as an index of platelet turnover. We first assessed the specificity of TO flow cytometry and then applied this method in the diagnosis of thrombocytopenia caused by impaired platelet production or increased destruction. We also explored the utility of TO flow cytometry to predict thrombocytopoiesis after chemotherapy-induced bone marrow aplasia. Venous blood, anticoagulated with K(2)EDTA, was incubated with 0.6 microg/ml TO plus an anti-GPIIIa monoclonal antibody. The mean percentage of RPs in control subjects (n = 23) was 6.13 +/- 3.09%. RPs were 10.41 +/- 9.02% in patients (n = 10) with hematological malignancies during aplasia induced by chemotherapy and a significant increase in RPs (35.45 +/- 6.11%) was seen in the recovery phase. In 10 patients with idiopathic thrombocytopenic purpura, the percentage of TO positive platelets was 67.81 +/- 18.79 (P < 0.001 vs. controls). In patients with thrombocytopenia associated with hepatic cirrhosis (n = 21; 21.04 +/- 16.21%, P < 0.001 vs. controls) or systemic lupus erythematosus (n = 6, 29.08 +/- 15.57%; P < 0.001 vs. controls) increases in TO-stained platelets were also observed. Measurement of TO positive platelets may be a reliable tool for the laboratory identification of platelet disorders, with a higher sensitivity than measurement of platelet volume. Measurement of RPs may also prove useful to recognize the underlying pathogenetic mechanisms in thrombocytopenia.

Adolescent↗
PubMed2006

Venous stasis and routine hematologic testing.

Prolonged venous stasis, as generated by a long tourniquet placement, produces spurious variations in several measurable analytes. To verify to what extent venous stasis influences routine hematologic testing, we assessed routine hematologic parameters, including hemoglobin, hematocrit, red blood cell count (RBC), main cell hemoglobin (MHC), main cell volume (MCV), platelet count (PLT), main platelet volume (MPV), white blood cell count (WBC) and WBC differential on the Advia 120 automated hematology analyzer in 30 healthy volunteers, either without venous stasis (no stasis) or after application of a 60 mmHg standardized external pressure by a sphygmomanometer, for 1 (1-min stasis) and 3 min (3-min stasis). Although the overall correlation between measures was globally acceptable, the mean values for paired samples were significantly different in all parameters tested, except MCV, MHC, PLT, MPV, eosinophils, basophils and large unstained cells after 1-min stasis and all parameters except MCV, MHC, MPV and basophils after 3-min venous stasis. As expected RBC, hemoglobin and hematocrit displayed a significant trend towards increase, whereas WBC and the WBC subpopulations were decreased. Difference between measurements by Bland and Altman plots exceeded the current analytical quality specifications for desirable bias for WBC, RBC, hemoglobin, hematocrit, lymphocytes and monocytes in samples collected after either 1- and 3-min stasis. These results provide clear evidence that venous stasis during venipuncture might produce spurious and clinically meaningful biases in the measurement of several hematologic parameters, prompting further considerations on the usefulness of adopting appropriate preventive measures for minimizing such influences.

Adult↗
PubMed2006

Tyr2105Cys mutation in exon 22 of FVIII gene is a risk factor for the development of inhibitors in patients with mild/moderate haemophilia A.

We report the case of a patient with mild haemophilia A, due to a Tyr2105Cys mutation in exon 22 of the C1 domain, who developed a high-titre factor VIII inhibitor (maximum titre 1600 BU) with recurrent severe haemorrhages and fatal intracranial bleeding. Based on published data, it appears that although this mutation occurs rarely in patients with mild or moderate haemophilia A, it is frequently associated with the development of high-titre inhibitors.

Blood Coagulation Factor Inhibitors↗