Peripheral versus central venous blood sampling does not influence the assessment of platelet activation in cirrhosis.

Cirrhotic patients have an increased risk of bleeding and thromboembolic events, with platelets being involved as key players in both situations. The impact of peripheral versus central blood sampling on platelet activation remains unclear. In 33 cirrhotic patients, we thus analyzed platelet function in peripheral (P) and central (C) blood samples. Platelet surface expression of P-selectin, activated glycoprotein (GP) IIb/IIIa, and leukocyte-platelet aggregate formation were measured by flow cytometry in response to different agonists: thrombin receptor-activating peptide-6, adenosine diphosphate, collagen-related peptide (CrP), epinephrine, AYPGKF, Pam3CSK4, and lipopolysaccharide. Unstimulated platelet surface expression of P-selectin (p = .850) and activated GPIIb/IIIa (p = .625) were similar in peripheral and central blood samples. Stimulation with various agonists yielded similar results of platelet surface expression of P-selectin and activated GPIIb/IIIa in peripheral and central samples, except for CrP-inducible expression of activated GPIIb/IIIa (median fluorescence intensity, MFI in P: 7.61 [0.00-24.66] vs. C: 4.12 [0.00-19.04], p < .001). The formation of leukocyte-platelet aggregate was similar in central and peripheral blood samples, both unstimulated and after stimulation with all above-mentioned agonists. In conclusion, peripheral vs. central venous blood sampling does not influence the assessment of platelet activation by flow cytometry in cirrhosis.Abbreviations: ACLD: advanced chronic liver disease; ADP: adenosine diphosphate; ALD: alcoholic liver disease; AYPGKF: PAR-4 agonist AYPGKF; CrP: collagen related protein; EPI: epinephrine; FACS: fluorescence-activated cell sorting; GP: glycoprotein; HVPG: hepatic venous pressure gradient; IQR: interquartile range; LPS: lipopolysaccharide; LSM: liver stiffness measurement; MFI: median fluorescence intensity; NAFLD: nonalcoholic fatty liver disease; PAM: lipopeptide Pam3CSK4; PAR: protease-activated receptor; PBS: phosphate-buffered saline; PH: portal hypertension; TIPS: transjugular intrahepatic portosystemic stent shunt; TLR: toll-like receptor; TRAP-6: thrombin receptor-activator peptide-6; vWF: von Willebrand factor.

Exercise based assessment of cardiac autonomic function in type 1 versus type 2 diabetes mellitus.

BACKGROUND: Cardiac autonomic neuropathy (CAN) is a complication of diabetes mellitus (DM) that is associated with increased mortality. Exercise-based assessment of autonomic function has identified diminished parasympathetic reactivation after exercise in type 2 DM. It is postulated herein, that this would be more prominent among those with type 1 DM. METHODS: Sixteen subjects with type 1 DM (age 32.9 ± 10.1 years), 18 subjects with type 2 DM (55.4 ± 8.0 years) and 30 controls (44.0 ± 11.6 years) underwent exercise-based assessment of autonomic function. Two 16-min submaximal bicycle tests were performed followed by 45 min of recovery. On the second test, atropine (0.04 mg/kg) was administered near end-exercise so that all of the recovery occurred under parasympathetic blockade. Plasma epinephrine and norepinephrine levels were measured at rest, during exercise, and during recovery. RESULTS: There were no differences in resting or end-exercise heart rates in the three groups. Parasympathetic effect on RR-intervals during recovery (p < 0.03) and heart rate recovery (p = 0.02) were blunted in type 2 DM. Type 1 DM had higher baseline epinephrine and norepinephrine levels (p < 0.03), and exhibited persistent sympathoexcitation during recovery. CONCLUSIONS: Despite a longer duration of DM in the study patients with type 1 versus type 2 DM, diminished parasympathetic reactivation was not noted in type 1 DM. Instead, elevation in resting plasma catecholamines was noted compared to type 2 DM and controls. The variable pathophysiology for exercise-induced autonomic abnormalities in type 1 versus type 2 DM may impact prognosis.

High-Dose Epinephrine Enhances Platelet Aggregation at the Expense of Procoagulant Activity.

Platelet activation is characterized by shape change, granule secretion, activation of fibrinogen receptor (glycoprotein IIb/IIIa) sustaining platelet aggregation, and externalization of negatively charged aminophospholipids contributing to platelet procoagulant activity. Epinephrine (EPI) alone is a weak platelet activator. However, it is able to potentiate platelet activation initiated by other agonists. In this work, we investigated the role of EPI in the generation of procoagulant platelets. Human platelets were activated with convulxin (CVX), thrombin (THR) or protease-activated receptor (PAR) agonists, EPI, and combination thereof. Platelet aggregation was assessed by light transmission aggregometry or with PAC-1 binding by flow cytometry. Procoagulant collagen-and-THR (COAT) platelets, induced by combined activation with CVX-and-THR, were visualized by flow cytometry as Annexin-V-positive and PAC-1-negative platelets. Cytosolic calcium fluxes were monitored by flow cytometry using Fluo-3 indicator. EPI increased platelet aggregation induced by all agonist combinations tested. On the other hand, EPI dose-dependently reduced the formation of procoagulant COAT platelets generated by combined CVX-and-THR activation. We observed a decreased Annexin-V-positivity and increased binding of PAC-1 with the triple activation (CVX + THR + EPI) compared with CVX + THR. Calcium mobilization with triple activation was decreased with the higher EPI dose (1,000 µM) compared with CVX + THR calcium kinetics. In conclusion, when platelets are activated with CVX-and-THR, the addition of increasing concentrations of EPI (triple stimulation) modulates platelet response reducing cytosolic calcium mobilization, decreasing procoagulant activity, and enhancing platelet aggregation.

Modulation of Platelet Functions Assessment during Menstruation and Ovulatory Phases.

During menstruation, endometrial hemostasis is achieved by platelet aggregation, fibrin deposition, and thrombus formation that interact with local endocrine and immunological factors which cause termination of menstrual bleeding. Interactions between steroidal sex hormones and platelet functions are not well understood. The aim of this study was to evaluate the effect of platelet function during the menstrual cycle and luteal phase in women of reproductive age. The cross-sectional study on women of reproductive age included 44 healthy women. Platelet function was assessed by PFA-100TM analyzer with collagen/epinephrine and collagen/ADP cartridges during the menstrual cycle and luteal phase. There were no significant differences in platelet function between menstruation and ovulatory phase. Platelet activity in Arab collagen/epinephrine cartridge increased during menstruation compared to non-Arab ethnic subjects and no significant differences in platelet function were found when using collagen/ADP cartridge. This study suggested modulation in platelet functions during menstruation and luteal phase in women of reproductive age. Further studies, including a large number of subjects, platelet genetic and progesterone factors change in platelet clotting associated to menstrual cycle should be conducted.

Systematic errors in detecting biased agonism: Analysis of current methods and development of a new model-free approach.

Discovering biased agonists requires a method that can reliably distinguish the bias in signalling due to unbalanced activation of diverse transduction proteins from that of differential amplification inherent to the system being studied, which invariably results from the non-linear nature of biological signalling networks and their measurement. We have systematically compared the performance of seven methods of bias diagnostics, all of which are based on the analysis of concentration-response curves of ligands according to classical receptor theory. We computed bias factors for a number of ß-adrenergic agonists by comparing BRET assays of receptor-transducer interactions with Gs, Gi and arrestin. Using the same ligands, we also compared responses at signalling steps originated from the same receptor-transducer interaction, among which no biased efficacy is theoretically possible. In either case, we found a high level of false positive results and a general lack of correlation among methods. Altogether this analysis shows that all tested methods, including some of the most widely used in the literature, fail to distinguish true ligand bias from "system bias" with confidence. We also propose two novel semi quantitative methods of bias diagnostics that appear to be more robust and reliable than currently available strategies.

Holter ECG assessment of the effects of three different local anesthetic solutions on cardiovascular system in the sedated dental patients with coronary artery disease.

OBJECTIVE: The purpose of the study is to compare the effects of lidocaine alone, epinephrine-combined lidocaine and prilocaine with octapressin on the cardiovascular system during minor oral surgery of sedated cardiac dental patients under local anesthesia. METHODS: Connected to a Holter electrocardiogram (ECG) monitor for a total of 5 hours starting 1 hour before the procedure, twenty patients with high risk of coronary artery disease were included in the prospective cohort study. All the patients had three operations at 3 different appointments with at least one-week intervals and each operation was performed under local anesthesia achieved by 3.6 mL of 3% prilocaine with octapressin, 3.6 mL of 2% lidocaine with 1:80.000 epinephrine and 3.6 mL of 2% lidocaine without a vasoconstrictor. Data of the Holter ECG device assessed at the end of every hour and evaluated statistically. Repeated measures ANOVA, Friedman test, and Wilcoxon signed ranks test were used to perform statistical analysis. RESULTS: Heart-rate showed significant differences between lidocaine with epinephrine and pure lidocaine in an hour following the injection (p<0.05 for all). Cardiac rhythm showed significant differences between prilocaine with octapressin and pure lidocaine at the second hour after its administration (p<0.05 for all). There were no significant differences between 3 local anesthetics in terms of ST segment deviation. CONCLUSION: In minor oral operation on the sedated patients with cardiac disease, the use of 3.6 mL or a less amount of local anesthetic injection containing epinephrine appears to be a predictable and safe method.

Quantitative assessment of brain microvascular and tissue oxygenation during cardiac arrest and resuscitation in pigs.

Cardiac arrest is associated with a very high rate of mortality, in part due to inadequate tissue perfusion during attempts at resuscitation. Parameters such as mean arterial pressure and end-tidal carbon dioxide may not accurately reflect adequacy of tissue perfusion during cardiac resuscitation. We hypothesised that quantitative measurements of tissue oxygen tension would more accurately reflect adequacy of tissue perfusion during experimental cardiac arrest. Using oxygen-dependent quenching of phosphorescence, we made measurements of oxygen in the microcirculation and in the interstitial space of the brain and muscle in a porcine model of ventricular fibrillation and cardiopulmonary resuscitation. Measurements were performed at baseline, during untreated ventricular fibrillation, during resuscitation and after return of spontaneous circulation. After achieving stable baseline brain tissue oxygen tension, as measured using an Oxyphor G4-based phosphorescent microsensor, ventricular fibrillation resulted in an immediate reduction in all measured parameters. During cardiopulmonary resuscitation, brain oxygen tension remained unchanged. After the return of spontaneous circulation, all measured parameters including brain oxygen tension recovered to baseline levels. Muscle tissue oxygen tension followed a similar trend as the brain, but with slower response times. We conclude that measurements of brain tissue oxygen tension, which more accurately reflect adequacy of tissue perfusion during cardiac arrest and resuscitation, may contribute to the development of new strategies to optimise perfusion during cardiac resuscitation and improve patient outcomes after cardiac arrest.

PGE2 suppresses NK activity in vivo directly and through adrenal hormones: effects that cannot be reflected by ex vivo assessment of NK cytotoxicity.

Surgery can suppress in vivo levels of NK cell cytotoxicity (NKCC) through various mechanisms, including catecholamine-, glucocorticoid (CORT)-, and prostaglandin (PG)-mediated responses. However, PGs are synthesized locally following tissue damage, driving proinflammatory and CORT responses, while their systemic levels are often unaffected. Thus, we herein studied the role of adrenal factors in mediating in vivo effects of PGs on NKCC, using adrenalectomized and sham-operated F344 rats subjected to surgery or PGE(2) administration. In vivo and ex vivo approaches were employed, based on intravenous administration of the NK-sensitive MADB106 tumor line, and based on ex vivo assessment of YAC-1 and MADB106 target-line lysis. Additionally, in vitro studies assessed the kinetics of the impact of epinephrine, CORT, and PGE(2) on NKCC. The results indicated that suppression of NKCC by epinephrine and PGE(2) are short lasting, and cannot be evident when these compounds are removed from the in vitro assay milieu, or in the context of ex vivo assessment of NKCC. In contrast, the effects of CORT are long-lasting and are reflected in both conditions even after its removal. Marginating-pulmonary NKCC was less susceptible to suppression than circulating NKCC, when tested against the xenogeneic YAC-1 target line, but not against the syngeneic MADB106 line, which seems to involve different cytotoxicity mechanisms. Overall, these findings indicate that elevated systemic PG levels can directly suppress NKCC in vivo, but following laparotomy adrenal hormones mediate most of the effects of endogenously-released PGs. Additionally, the ex vivo approach seems limited in reflecting the short-lasting NK-suppressive effects of catecholamines and PGs.

The assessment of PFA-100 test for the estimation of blood loss in renal transplantation operation.

BACKGROUND: Platelet dysfunction is well known factor that may play a role in bleeding diathesis in uremia. In recent years, Platelet Function Assay 100 (PFA-100) was introduced to measure platelet function. The purpose of this study was to determine whether an abnormal PFA-100 is an accurate predictor of bleeding in dialysis patients undergoing renal transplantation (RTx). MATERIAL/METHODS: We included 98 dialysis patients undergoing RTx operation. PFA-100 test measuring collagen/epinephrine (Col/EPI) and collagen/adenosine 5'-diphosphate (Col/ADP) closure was performed in each patients after induction of anesthesia. We compared intraoperative blood loss measured by gravimetric method during RTx operation method between patients with normal Col/EPI and Col/ADP closure times (group 1, n= 51) and with prolonged Col/EPI and Col/ADP closure times (group 2, n=47). RESULTS: Intraoperative blood loss calculated by gravimetric method was 273+/-50 ml in the group 1 and 303+/-109 ml in the group 2 (p>0.05). Blood loss in gross formula was 356+/-87 ml in the group 1 and 450+/-99 ml in group 2 (p>0.05). CONCLUSIONS: Assessment of platelet function with preoperative measurement of PFA-100 in RTx patients is not an effective method for estimating the risk of blood loss in the intraoperative and postoperative periods.

The risk of false results in the assessment of platelet function in the absence of antiplatelet medication: comparison of the PFA-100, multiplate electrical impedance aggregometry and verify now assays.

OBJECTIVES: Evaluation of aspirin (ASA) responsiveness with platelet function tests varies by the choice of blood mixture and functional test and cut off values for defining the the treatment used. Addition to that we also aimed to determine agreement between three tests and to research whether there is any necessity to measure baseline platelet activity. METHODS: The study group comprised of 52 patients with multiple risk factors receiving primary prophylaxis of ASA (100 mg/day). For each patient inhibition of platelet aggregation with aspirin was determined using three different whole blood tests: Multiplate electrical impedance aggregometry, Verify Now Aspirin, and collagen-epinephrine closure time PFA-100. Platelet aggregation was assessed with multiplate electrical impedance aggregometry,and was defined as the area under curve (AUC,AUxmin). Maximal 6,4 microM collagen-induced AUC were used to quantify platelet aggregation due to ASA. The ASA response was defined as >30 % reduction in basal platelet aggregation with multiplate electrical impedance aggregometry. Collagen induced platelet aggregation at the Verify Now Aspirin assay quantitated the ASA-induced platelet inhibition as aspirin reaction units (ARU). According to manufacturer insert ARU>550 indicates aspirin resistance. ASA platelet function studies were assessed twice at baseline (pre-aspirin), and after 7 day(post-aspirin) were performed. RESULTS: After ASA intake none of the patients was found aspirin resistant with PFA-100. (CEPI-CT (129+/-36 vs 289+/-18 ). None of the patients was found aspirin resistant with PFA-100. As>30 % reduction in basal platelet aggregation with multiplate electrical impedance aggregometry is selected all of the patients have been stratified as responders.(COL TEST 688+/-230 vs 169+/-131 AU) None of the patients with Verify Now Aspirin found resistance to ASA(594+/-62 vs 446+/-43).Prior to ASA intake 15 of all patients with VN(501+/-16) and 2 of all patients with multiplate electrical impedance aggregometry (223+/-40 AUC )aggregation levels below the cut off label before ingestion of ASA.None of the patients was above the cut off label with PFA -100 (129+/-36). CONCLUSIONS: Verify Now ASA assay, multiplate electrical impedance aggregometry and PFA-100 seem to be reliable tests in reflecting ASA effect on platelets. Cut off labels for the defining the responsiveness given by manufacturer may show significant interindividual variability with Verify Now ASA assay and multiplate electrical impedance aggregometry, and these test may show platelet inhibition despite the absence of ASA intake. Consideration of the pretreatment values may eliminate the risk of overestimation in the assessment of platelet inhibition by ASA.

An in vitro beating heart model for long-term assessment of experimental therapeutics.

AIMS: Within the framework of studies aiming at regenerative medicine for cardiovascular disease, we have developed an in vitro model to analyse human embryonic stem (ES) cell engraftment into the myocardium. METHODS AND RESULTS: This model is based on organotypic rat ventricular slices maintained in culture at the air-medium interface on semi-porous membranes. Survival and differentiation of human cardiomyocytes derived from ES cells were then assessed for several months. In addition, we observed that ventricular tissue slices not only exhibited normal histology, but also rhythmic contractions till the end of the experiments (up to 3 months). Similar results were obtained using ventricular slices obtained from two human foetuses at 8 and 9.5 weeks of age. Calcium transients were associated with the beating frequency, and the pattern was modulated in a dose-dependent manner by epinephrine. CONCLUSION: Our data suggest that the organotypic heart slice culture on semi-porous membranes is a relevant in vitro heart model for long-term histological and physiological studies.

[The assessment of platelet function in patients with essential thrombocythemia]. / Ocena czynnosci plytek krwi u chorych na nadplytkowosc samoistna.

UNLABELLED: Essential thrombocythemia (ET) is associated with an increased risk of both thromboembolic and bleeding complications. Changes in platelet count and function are crucial but leukocyte activation is also suspected. The aim of the study. The study was designed to assess platelet function by optical and impedance platelet aggregometry and also PFA-100 analyser in ET patients at the time of diagnosis MATERIAL AND METHODS: The tests were performed in 32 ET patients. In each patient platelet aggregation tests by optical (in platelet rich plasma) and impedance methods (in whole blood) after stimulation with ADP, collagen, epinephrine were done. The platelet function was also assessed by PFA-100 method. The control group consisted of 20 healthy volunteers. RESULTS: In optical platelet aggregometry different platelet function abnormalities were seen in 31 patients (97%). The most frequent was decreased aggregation (19/32) with all used agonists but especially with epinephrine. Spontaneous aggregation was observed in 10 cases and in one we observed hyperaggregation. In whole blood platelet aggregometry abnormal results concerned 23 patients (72%). The most typical (14/32) was hyperactivity of platelets (especially after ADP). In this method we noted spontaneous aggregation in patients and in 4 patients' diminished aggregation. Mixed aggregation disturbances were observed in 6 patients. The closure time in the cohort of patients was significantly prolonged with both cartridges in comparison to control group and was outside reference ranges in 25/32 patient. No significant correlation between values of platelet aggregation in platelet rich plasma and in whole blood was found. No significant differences were observed between ET patients with and without clinical symptoms of bleeding/thrombosis although closure time with both cartridges was longer in patients with bleeding. CONCLUSIONS: In majority of ET patients different platelet function abnormalities are present. The platelet aggregation results depend on environment in which tests are performed. The PFA-100 seems to be a good method for detection of platelet defects in ET.

Effects of milrinone versus epinephrine on left ventricular relaxation after cardiopulmonary bypass following myocardial revascularization: assessment by color m-mode and tissue Doppler.

OBJECTIVE: The purpose of this study was to evaluate the left ventricular lusitropic effects of epinephrine versus milrinone after cardiopulmonary bypass. DESIGN: Prospective randomized study. SETTING: Single institution, university teaching hospital. PARTICIPANTS: Adult patients undergoing coronary artery bypass grafting under cardiopulmonary bypass. INTERVENTIONS: After separation from cardiopulmonary bypass, patients were randomized to receive intravenous epinephrine by continuous infusion (0.03 microg/kg/min) or milrinone (50 microg/kg followed by 0.5 microg/kg/min). Transesophageal echocardiographic evaluation of left ventricular diastolic function, with emphasis on relaxation, was performed before and after bypass and after the administration of either epinephrine or milrinone. MEASUREMENTS AND MAIN RESULTS: Measurements included pulse-wave Doppler analysis of mitral inflow and pulmonary vein and left ventricular outflow tract velocities. Left ventricular inflow velocity of propagation measured with color M-mode and tissue Doppler assessment of early mitral annulus velocity were used to evaluate left ventricular relaxation. Values of velocity of propagation and mitral annulus velocity improved significantly after bypass, suggesting improved relaxation. The administration of either epinephrine or milrinone did not result in further improvement in left ventricular relaxation. CONCLUSIONS: After cardiopulmonary bypass, left ventricular relaxation was significantly improved. Neither epinephrine nor milrinone exhibited favorable lusitropic effects after bypass.

Assessment of the antiplatelet effects of low to medium dose aspirin in the early and late phases after ischaemic stroke and TIA.

Vascular events commonly recur in stroke patients on aspirin, and may reflect incomplete inhibition of platelet function with aspirin therapy. The platelet function analyser (PFA-100) activates platelets by aspirating a blood sample at a moderately high shear rate through a capillary to a biologically active membrane with a central aperture. The membrane is coated with collagen, and either ADP (C-ADP) or epinephrine (C-EPI). The time taken for activated platelets to adhere, aggregate, and occlude the aperture is called the closure time. Previous studies have shown that aspirin prolongs the C-EPI closure time, without prolongation of the C-ADP closure time, in the majority of control subjects. We hypothesised that the PFA-100 would provide a sensitive assay for the detection of early and convalescent phase cerebrovascular disease (CVD) patients who had incomplete inhibition of platelet function with aspirin. We investigated potential cyclooxygenase-dependent and -independent mechanisms that might influence the responsiveness to aspirin using the PFA-100. Patients were studied during the early (< or = 4 weeks, n=57) and convalescent phases ((< or = 3 months, n=46) after ischaemic stroke or TIA. To investigate potential mechanisms that could contribute to aspirin responsiveness on the PFA-100, we measured von Willebrand factor antigen levels, and carried out platelet aggregometry experiments in platelet-rich plasma in response to sodium arachidonate (1 mM) and ADP (5 microM). Sixty percent of patients in the early phase and 43% of patients in the convalescent phase did not have prolonged C-EPI closure times on 75-300 mg of aspirin daily, and were defined as aspirin non-responders. Median C-ADP closure times were significantly shorter in aspirin non-responders than aspirin-responders in both the early and convalescent phases after symptom onset (P=0.008), suggesting platelet hyper-reactivity to collagen or ADP in the aspirin non-responder subgroup. There was a significant inverse relationship between plasma von Willebrand factor antigen levels and C-EPI closure times in both early and convalescent phase CVD patients (P=0.008). Mean von Willebrand factor antigen levels were significantly higher in aspirin non-responders than aspirin responsive patients in the early (P=0.001), but not convalescent phase (P=0.2) after stroke and TIA. None of the patients studied were defined as being aspirin-resistant using sodium arachidonate- or ADP-induced platelet aggregometry. A large proportion of ischaemic CVD patients have incomplete inhibition of platelet function with low to medium dose aspirin using the PFA-100. The results suggest that cyclooxygenase-independent mechanisms, including elevated von Willebrand factor antigen levels, play an important role in mediating aspirin non-responsiveness on the PFA-100.

Comparative efficacy and costs of various topical anesthetics for repair of dermal lacerations: a systematic review of randomized, controlled trials.

STUDY OBJECTIVES: To compare the efficacy of infiltrated local anesthesia with topical anesthesia for repair of dermal laceration, to analyze the efficacy of single or multicomponent topical anesthetics, and to identify topical formulations that are potentially less costly and equally efficacious as cocaine-containing topical anesthetics. DESIGN: Systematic review of randomized controlled trials. SETTING: University-affiliated hospital. PATIENTS: Pediatric and adult subjects. MEASUREMENTS AND MAIN RESULTS: Twenty-two trials that randomized more than 3000 patients were identified. The majority of studies demonstrated equivalent or superior analgesic efficacy for topical formulations compared with conventional intradermal infiltration. We found that cocaine is not a mandatory component of topical anesthesia. The literature discloses no significant difference in anesthetic efficacy between topical tetracaine-epinephrine-cocaine and each of the following 6 cocaine-free formulations: lidocaine-epinephrine-tetracaine, lidocaine-epinephrine, tetracaine-phenylephrine, tetracaine-lidocaine-phenylephrine, bupivicaine-norepinephrine, or prilocaine-phenylephrine. CONCLUSION: Topical anesthetics are an efficacious, noninvasive means of providing analgesia before suturing of dermal lacerations. The use of cocaine-containing topical anesthetics can no longer be justified in light of its high cost and potential adverse effects. We have summarized the evidence, mostly favorable, supporting the use of various non-cocaine-containing topical anesthetics.

The PFA-100: a potential rapid screening tool for the assessment of platelet dysfunction.

The PFA-100 is a device that simulates high shear dependent platelet function in vitro and thus is particularly useful for screening for von Willebrand's disease (VWD). The aim of this study was to assess the overall potential of the PFA-100 as a primary clinical screening tool using the wide spectrum of clinical samples assessed for platelet function within our institution. The PFA-100 test was performed using both collagen/ADP (CADP) and collagen/epinephrine (CEPI) cartridges on samples from 337 patients with a wide variety of haemostatic defects. One hundred and eighty-two patients were defined as having normal platelet function based on classical laboratory tests and von Willebrand factor levels. The overall clinical sensitivity of the PFA-100 for platelet abnormalities (including VWD) was 81% for CADP and 86% for CEPI. The overall specificity was found to be 82% for CADP and 80% for CEPI. When utilizing both cartridges in combination (with both results either higher or lower than the upper cutoff of the normal ranges), the overall false positive and false negative rates were 12% and 6%, respectively. The PFA-100 proved to be sensitive in detecting classical defects by giving prolonged closure times in samples from patients with major platelet function defects (e.g. von Willebrand's disease, Glanzmann's thrombasthenia and Bernard Soulier syndrome). However, there were a small number of false negative results (6%) obtained with various milder platelet defects (e.g. Hermansky Pudlak syndrome, storage pool and release defects, type I VWD and macrothrombocytopenia). The PFA-100 test provides a useful rapid screening tool and should increase the efficiency and reduce the cost of the routine diagnosis of platelet dysfunction.

[Assessment of the protective effect of vitamin E during development of experimental myocardial damage]. / Otsinka zakhysnoï diï vitaminu E za rozvytku eksperymental'noho dribnovohnyshchevoho urazhennia miokarda.

It was shown that creatinphosphokinase activity of blood serum might be used as a criterion for evaluating the level of sparsely distributed damage in myocardium as a result of adrenaline administration. The protective effect of vitamin E under adrenaline-induced myocarditis was studied. The best effect was obtained after triple intramuscular injection of vitamin E before administration of pathological agent. Intravenous injection of the preparation has no benefits over that of intramuscular way of administration. Preventive action of vitamin E shows functioning itself in an increase of the quantity and activity of ubiquinone--the component of electron transport chain in mitochondria.