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Biomedical subjects

G Lippi

Publications and source records attributed to G Lippi.

At least 19 recordsLinked to original sources

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↗

Relation between serum creatinine and body mass index in elite athletes of different sport disciplines.

OBJECTIVES: To document the relation between serum creatinine concentration and body mass index in elite athletes from five different sports, and to study potential differences among athletes performing different sports with different features and requirements. METHODS: Before the start of the competitive season, serum creatinine was measured in 151 elite athletes from five different sports: rugby (n = 44), soccer (n = 27), alpine skiing (n = 34), sailing (n = 22), cycling (n = 24). Pearson's correlation analysis was used to evaluate the relation between serum creatinine and body mass index (BMI). Analysis of variance and unpaired Student's t test were used to compare creatinine concentration and BMI in different sport disciplines. RESULTS: In the whole group of athletes, a positive correlation between serum creatinine and BMI was found (r = 0.48, p<0.001). Significant differences in creatinine concentration and BMI were found between athletes competing in different sports: their mean (SD) values were respectively 1.31 (0.12) mg/dl and 28.83 (2.41) for rugby players, 1.27 mg/dl (0.10) and 23.10 (1.01) for soccer players, 1.15 (0.11) mg/dl and 25.8 (1.50) for skiers, 1.08 (0.11) mg/dl and 26.93 (2.36) for sailors, and 0.91 (0.07)mg/dl and 21.33 (1.21) for cyclists. CONCLUSIONS: There is a correlation between creatinine concentration and BMI in elite athletes competing in different sports characterised by different kinds of training, competitive season, and involvement of aerobic and anaerobic metabolism. Interpretation of creatinine concentrations in male athletes should consider professional status as well as the specific sport performed. All athletes should be monitored with consecutive creatinine assessments, using as the baseline the concentration determined before the start of training and the competitive season, but taking into consideration the specific sport performed and the BMI until equations that include creatinine and factors that affect its concentration are used.

Adolescent↗

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↗

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↗

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↗

Cobalt chloride administration in athletes: a new perspective in blood doping?

Blood doping is an illegal and unfair way of enhancing athletic performance by increasing the oxygen carrying capacity of the blood. Currently used methods usually involve stimulation of erythropoiesis. Gene therapy targeting the hypoxia inducible factor pathway may be an attractive alternative to traditional blood doping techniques. Hypoxia activates a large number of genes with essential roles in cell and tissue adaptation to low oxygen. Cobalt chloride is a well established chemical inducer of hypoxia-like responses such as erythropoiesis. Cobalt supplementation is not banned and therefore would not be detected by current anti-doping testing. Although there is as yet no direct or anecdotal evidence of cobalt chloride administration to athletes, its use should be warned against as being not only unfair but potentially dangerous.

Cell Hypoxia↗

[Preoperative laboratory testing].

The preoperative laboratory screening is commonplace in clinical practice and is traditionally defined as the practice of prescribing laboratory testing before surgery on patients undergoing a given procedure. The wide heterogeneity of the solutions prospected over the past decades emphasizes the objective difficulty at issuing definitive guidelines and recommendations. Despite its widespread use, a systematic evaluation of the clinical and cost-effectiveness of routine laboratory testing demonstrates that several approaches are as yet unsuitable, as inappropriate investigations may lead to evaluation of borderline or false-positive laboratory abnormalities. Three major difficulties can be identified when issuing reliable recommendations: articulation and appropriateness of diagnostic protocols, contestualization, in terms of surgical procedures and suitable clinical contests that might achieve the greatest advantages from results of laboratory testing, and impact of these tests on clinical management and outcome. This article aims to provide a comprehensive review of the current literature on this topic, attempting to suggest a suitable approach to the puzzling issue of preoperative laboratory testing.

Clinical Laboratory Techniques↗

Peripheral neuropathy with hypomyelinating features in adult-onset Krabbe's disease.

We describe three brothers suffering from Krabbe's disease with onset in the fifth decade. The proband showed a complete deficiency of leukocyte enzyme galactocerebrosidase and was found to be heterozygous for two previously described mutations: G > A809 and 502T/del consisting of a 30 kb deletion. In all three brothers the neurological examination showed features of asymmetrical peripheral neuropathy associated with pyramidal signs and the electrophysiological examination showed a generalized slowing of nerve conduction velocities. Two patients died at 59 and 61 years of age due to respiratory failure. Both the proband and his brother underwent a sural nerve biopsy. In the former the most striking finding was the presence of uniformly thin myelin sheaths without evidence of demyelination; a complete absence of fibers was found in the latter. Our findings confirm that peripheral neuropathy may be the presenting feature of late-onset Krabbe's disease. Hypomyelination rather than demyelination may represent the distinguishing pathological finding of this condition.

Adult↗

Efficacy of desmopressin as surgical prophylaxis in patients with acquired von Willebrand disease undergoing thyroid surgery.

Coagulation abnormalities may occur in patients with thyroid diseases. We report on 14 patients undergoing thyroid surgery for a thyroid disease with an alteration of coagulation parameters resembling von Willebrand disease. Subcutaneous desmopressin was first tested and then used successfully in these patients as surgical prophylaxis, with no side-effects or bleeding complications during or after surgery. This study highlights the need for coagulation studies in patients with thyroid diseases undergoing thyroid surgery. Subcutaneous desmopressin may be used in these patients in order to prevent a surgically related bleeding risk.

Adult↗

Prothrombotic effects and clinical implications of third-generation oral contraceptives use.

Although the use of oral contraceptives has been frequently associated with an increased risk of thromboembolic events, definitive prothrombotic mechanisms have not so far been fully elucidated. The aim of our investigation was the evaluation of the activities of antithrombin, protein C, protein S and the resistance to activated protein C in 137 healthy users of third-generation oral contraceptives and in 170 healthy women who were not consuming oral contraceptives. Women on oral contraceptives showed a marked prothrombotic pattern, characterized by reduced activities of antithrombin and protein S, and increased resistance to activated protein C. Nearby 50% of oral contraceptive users displayed activities of protein S below the lower value of the reference range (controls, 10%; P < 0.001). No significant differences were observed between two progestagens (desogestrel or gestodene) on the coagulation parameters tested. We believe that, due to the adverse effect on haemostasis, the administration of third-generation oral contraceptives should be carefully considered in women carrying prothrombotic abnormalities.

Adult↗