Platelet Function Analyzer Research Articles

Anticoagulant action of low, physiologic, and high albumin levels in whole blood.

Albumin is the most abundant plasma protein. Critical illness is often associated with altered, predominately decreased, serum albumin levels. This hypoalbuminaemia is usually corrected by administration of exogenous albumin. This study aimed to track the concentration-dependent influence of albumin on blood coagulation in vitro. Whole blood (WB) samples from 25 volunteers were prepared to contain low (19.3 ± 7.7 g/L), physiological (45.2 ± 7.8 g/L), and high (67.5 ± 18.1 g/L) levels of albumin. Haemostatic profiling was performed using a platelet function analyzer (PFA) 200, impedance aggregometry, a Cone and Platelet analyzer (CPA), calibrated automated thrombogram, and thrombelastometry (TEM). Platelet aggregation-associated ATP release was assessed via HPLC analysis. In the low albumin group, when compared to the physiological albumin group, we found: i) shortened PFA 200-derived closure times indicating increased primary haemostasis; ii) increased impedance aggregometry-derived amplitudes, slopes, ATP release, as well as CPA-derived average size indicating improved platelet aggregation; iii) increased TEM-derived maximum clot firmness and alpha angles indicating enhanced clot formation. TEM measurements indicated impaired clot formation in the high albumin group compared with the physiological albumin group. Thus, albumin exerted significant anticoagulant action. Therefore, low albumin levels, often present in cancer or critically ill patients, might contribute to the frequently occurring venous thromboembolism.

In vitro analysis of platelet function in acute aneurysmal subarachnoid haemorrhage.

Platelet function might play an essential role in the pathogenesis of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid haemorrhage (SAH). Thus, impaired platelet function and disturbed primary haemostasis induced by intake of acetylsalicylic acid (ASA) might influence the rate of DCI. Primary haemostasis and platelet function can be measured with in vitro diagnosis (platelet function analyser test, PFA 100). The aim of this study is to evaluate the rate of DCI, haemorrhagic complications and the neurological outcome. Two groups were compared (patients with regular platelet function versus patients with impaired platelet function). This is a retrospective observational study. An initial cohort of 787 patients with SAH has been treated from January 2005 to September 2012. Seventy-nine patients (10%) with aneurysmal SAH, a history of ASA medication and PFA testing within the first 24h after aneurysm rupture have been included. The overall rate of DCI in the present study was 43%. In vitro platelet function testing showed pathological primary haemostasis in 69.6%. The DCI rate was higher in patients with regular tested primary haemostasis (p=0.02, OR=3.16, 95%CI=[1.19; 8.83]). However, outcome assessment by mGOS did not show a significant difference between the groups. Patients with impaired primary haemostasis did not display a higher rate of haemorrhagic complications. Impairment of primary haemostasis resulting from an impairment of platelet function at an early stage after SAH might lead to a lower rate of DCI. In vitro testing of platelet function might be useful to predict the occurrence of DCI in the course.

Effects of aspirin dose escalation on platelet function and urinary thromboxane and prostacyclin levels in normal dogs.

Established "low" aspirin dosages inconsistently inhibit platelet function in dogs. Higher aspirin dosages consistently inhibit platelet function, but are associated with adverse effects. The objectives of this study were to use an escalation in dosage to determine the lowest aspirin dosage that consistently inhibited platelet function without inhibiting prostacyclin synthesis. Eight dogs were treated with five aspirin dosages: 0.5mg/kg q24h, 1mg/kg q24h, 2mg/kg q24h, 4mg/kg q24h and 10mg/kg q12h for 7days. Utilizing aggregometry and a whole-blood platelet function analyzer (PFA-100), platelet function was evaluated before and after treatment. Urine 11-dehydro-thromboxane-B2 (11-dTXB2 ) and 6-keto-prostaglandin-F1α (6-keto-PGF1α ), were measured. Compared to pretreatment, there were significant post-treatment decreases in the maximum aggregometry amplitude and increases in the PFA-100 closure times for all dosages expect 0.5mg/kg q24h. There was no difference in amplitude or closure time among the 2mg/kg q24h, 4mg/kg q24h, and 10mg/kg q12h dosages. Compared to pretreatment values, there was a significant decrease in urinary 11-dTXB2 -to-creatinine and 6-keto-PGF1α -to-creatinine ratios, but there was no dose-dependent decrease for either metabolite. An aspirin dosage of 2mg/kg q24h consistently inhibits platelet function without decreasing prostacyclin synthesis significantly more than lower aspirin dosages.

Comparison of the effects of 7.2% hypertonic saline and 20% mannitol on whole blood coagulation and platelet function in dogs with suspected intracranial hypertension - a pilot study

BackgroundHyperosmolar therapy with either mannitol or hypertonic saline (HTS) is commonly used in the treatment of intracranial hypertension (ICH). In vitro data indicate that both mannitol and HTS affect coagulation and platelet function in dogs. The aim of this study was to compare the effects of 20% mannitol and 7.2% HTS on whole blood coagulation using rotational thromboelastometry (ROTEM®) and platelet function using a platelet function analyzer (PFA®) in dogs with suspected ICH. Thirty client-owned dogs with suspected ICH needing osmotherapy were randomized to receive either 20% mannitol (5 ml/kg IV over 15 min) or 7.2% HTS (4 ml/kg IV over 5 min). ROTEM® (EXTEM® and FIBTEM® assays) and PFA® analyses (collagen/ADP cartridges) were performed before (T0), as well as 5 (T5), 60 (T60) and 120 (T120) minutes after administration of HTS or mannitol. Data at T5, T60 and T120 were analyzed as a percentage of values at T0 for comparison between groups, and as absolute values for comparison between time points, respectively.ResultsNo significant difference was found between the groups for the percentage change of any parameter at any time point except for FIBTEM® clotting time. Within each group, no significant difference was found between time points for any parameter except for FIBTEM® clotting time in the HTS group, and EXTEM® and FIBTEM® maximum clot firmness in the mannitol group. Median ROTEM® values lay within institutional reference intervals in both groups at all time points, whereas median PFA® values were above the reference intervals at T5 (both groups) and T60 (HTS group).ConclusionsUsing currently recommended doses, mannitol and HTS do not differ in their effects on whole blood coagulation and platelet function in dogs with suspected ICH. Moreover, no relevant impairment of whole blood coagulation was found following treatment with either solution, whereas a short-lived impairment of platelet function was found after both solutions.

Serum Concentration of Growth Differentiation Factor-15 Is Independently Associated with Global Platelet Function and Higher Fibrinogen Values in Adult Healthy Subjects.

AbstractGrowth differentiation factor-15 (GDF-15) has recently emerged as a strong and independent predictor of cardiovascular events and mortality. However, the pathophysiological mechanisms underlying this important association remain speculative. This study was aimed to investigate the potential associations between the serum concentration of GDF-15 and clinical or laboratory parameters in a population of ostensibly healthy subjects. The study population consisted of 44 healthy volunteers enrolled from the laboratory staff (14 males and 30 females; mean age, 47 ± 11 years), who had their blood collected for assessing complete blood cell count, GDF-15, serum creatinine, albumin, cardiac troponin T, galectin-3, routine coagulation tests, D-dimer, von Willebrand factor, and platelet function testing using platelet function analyzer-100. In univariate analysis, serum GDF-15 was found to be positively associated with age and plasma fibrinogen, and negatively associated with renal function and collagen-epinephrine (CEPI). In multiple linear regression analysis, serum GDF-15 remained significantly associated with renal function, CEPI, and plasma fibrinogen. Healthy subjects with GDF-15 above the median value had a twofold probability of displaying shorter CEPI closure times. Taken together, these results suggest that higher serum values of GDF-15 may be associated with overall global platelet hyperactivity and increased plasma fibrinogen, so providing another plausible explanation for the association between GDF-15, cardiovascular events, and mortality.

Intraoperative Anesthetic Management of Lung Transplantation: Center-Specific Practices and Geographic and Centers Size Differences

Although increasing evidence in lung transplantation (LTx) suggests that intraoperative management could influence outcomes, there are no guidelines available regarding intraoperative management of LTx. The overall goal of the study was to assess geographic and center volume-specific clinical practices in perioperative management. Prospective data analysis. Online survey from a single-center university hospital. European and non-European LTx centers. An online survey was sent to 176 centers currently performing LTx procedures. It covered organizational data, general anesthesia considerations, fluid therapy and coagulation, antioxidant and anti-inflammatory therapies, and ventilation strategies. The response rates were 57.5% (n = 42) from European and 32% (n = 33) from non-European countries. Significant differences between European and non-European countries were use of volatile hypnotics (p = 0.016), use of sufentanil (p < 0.001), inotropic agents (p = 0.001) and colloid infusion (p < 0.001), use of calibrated pulse contour analysis (p = 0.004), use of intraoperative traditional laboratory-based coagulation tests (p = 0.001) and platelet function analysis (p = 0.005), and use of higher peak inspiratory pressure (p = 0.009). Center volume-specific differences were use of fentanyl (p = 0.03) and the use of higher peak inspiratory pressure (p = 0.005) for ventilation. Induction of anesthesia and use of advanced hemodynamic monitoring, therapy for pulmonary hypertension, antioxidant and anti-inflammatory therapies, and ventilation strategies were not different among the centers. This survey demonstrated for the first time statistically significant differences among European and non-European centers and among low- versus high-volume centers regarding intraoperative management during LTx. These observations will be of some guidance for the LTx community and may trigger more extensive studies.

Acute effects of 30 minutes of exposure to a smartphone call on in vitro platelet function.

Significant concerns are now regularly raised about the safety of excessive mobile phone use. This study was aimed to assess the acute effects of radiofrequency waves emitted by a commercial smartphone on platelet function. Two sequential citrated blood samples were collected from 16 healthy volunteers recruited from laboratory staff. The first sample was placed in a plastic rack, 1 cm distant from a commercial smartphone receiving a 30-min call and emitting 900 MHz radiofrequency waves. The second sample was placed in another plastic rack, isolated from radiofrequency wave sources, for the same period. The platelet count and the mean platelet volume were then assessed in all blood samples, whereas platelet function was evaluated using the platelet function analyser-100 (PFA-100). A 30-min exposure of citrated blood to smartphone radiofrequency waves induced significant prolongation of collagen-epinephrine aggregation (median increase, 10%) and a considerable increase of mean platelet volume (median increase, 5%), whereas collagen-adenosine diphosphate aggregation and platelet count remained unchanged. This study demonstrates that smartphone radiofrequency waves induce significant perturbation of platelet structure and function, thus providing further support to concerns regarding excessive use of mobile phones. Caution should also be taken with regards to blood products containing platelets, which should be kept far away from mobile phones and smartphones throughout the production pipeline and storage period.

Abstract 143: Bridging the Gender Gap: Sex Differences in Von Willebrand Factor Aptamer Inhibition Across Species

Introduction: A gender gap exists in stroke, with increased morbidity and mortality in women. The underlying mechanisms remain unknown, although differences in platelet biology may play a role. Inhibition of the interaction between VWF and GP 1B-IX-V has demonstrated thrombolytic efficacy. Hypothesis: We hypothesized that sex differences in reperfusion after stroke were attributable to the VWF-GP IB-IX-V axis, and inhibition of this interaction would yield clear discrepancies. Methods: Adult wild-type (C57BL/6J) mice were anesthetized, the right carotid artery exposed and baseline carotid flow obtained by Doppler. Thrombosis was induced with a FeCl 3 patch. After 20-minute stabilization, mice were intravenously administered vehicle (n, male=12, female=8) or VWF aptamer. Aptamer (0.5 mg/kg) administration was assessed using a bolus (5 min; n, male=5, female=8) method. Given the minimal observed thrombolytic effect in females, a continuous infusion (45 min; n, female=5) was also attempted. Next, blood from male (n=8) and female (n=8) adult wild-type beagles was mixed with VWF aptamer (control, 6.25 nM, 12.5 nM, 25 nM, and 100 nM), and platelet reactivity was assessed (Platelet Function Analyser-100). Statistical analysis was performed using a two-way ANOVA with multiple comparisons. Results: Bolus VWF aptamer restored carotid blood flow in male mice (Figure 1), compared to females (p&lt;0.001) and vehicle (p&lt;0.01). With continuous infusion, reperfusion in female mice was significantly higher than vehicle (p&lt;0.01). Male canines (264.3 ± 70.3 s) demonstrated significantly more platelet inhibition (p&lt;0.01) than females (175.3 ± 83.2 s) at the 12.5 nM VWF aptamer concentration. Conclusions: Following VWF inhibition, in vivo thrombolytic efficacy in mice is gender dependent, while ex vivo platelet activity varies in canines. The mechanisms underlying these differences in platelet biology are unclear, but this indicates that the VWF-GP IB-IX-V axis plays a role.

Variables That Affect Results of PFA-100 in a Group of Healthy Blood Donors in the Slovak Population

Abstract Background: The platelet function analyzer (PFA-100) is a system analyzing platelet function determined for detection of the functional inherited and acquired platelet disorders, screening of von Willebrand disease (vWD) and recently also considered as useful for monitoring of antiplatelet treatment. The PFA-100 test uses a high shear flow system to simulate in vitro the conditions to which platelets are subjected at the site of a damaged blood vessel wall. Aim of study: We decided to establish the reference intervals of PFA closure time (CT) in the Slovak population of healthy blood donors. Patients and methods: Fifty age and gender matched healthy blood donors were enrolled in the study. We investigated the relationships between PFA-100 CT, gender and ABO blood groups. Results: The reference intervals for CT measured on CEPI (collagen/epinephrine) and CADP (collagen/adenosine diphosphate) cartridge in 3.2% citrated blood were 86 - 199 sec. and 42 - 119 sec., respectively. Blood group O was associated with significantly longer CEPI CT (p&lt;0.05) compared to non - O groups. The prolongation of CADP CT in blood donors with blood group O was without significance. The influence of gender as another variable analyzed with CT has not been evaluated as statistically significant. Conclusion: PFA-100 CT should be interpreted carefully with consideration of both the patient’s clinical presentation and laboratory variables such as ABO blood group.

Evaluation of platelet function in thrombocytopenia

Whole blood aggregometry is a functional assay for determination of platelet function. Until now, whole blood aggregometry has not been considered feasible at low platelet counts. Hence, the objectives of the present study were to explore platelet function in thrombocytopenia using a novel index of impedance aggregometry adjusted for platelet count and evaluate the association to platelet function assessed by flow cytometry. Hirudin anticoagulated blood was collected from 20 healthy volunteers, 20 patients with primary immune thrombocytopenia (ITP), and 17 hematological cancer patients. Platelet function was analyzed by impedance aggregometry and by flow cytometry. Collagen, adenosine diphosphate, thrombin receptor agonist peptide-6, and ristocetin were used as agonists for both analyses. Thrombocytopenia in healthy whole blood was induced in vitro employing a recently published method. Platelet aggregation of thrombocytopenic patients was evaluated relative to the aggregation of healthy volunteers at the same platelet count. In flow cytometry, platelet function was described as expression of the platelet surface glycoproteins: bound fibrinogen, CD63, and P-selectin. Similar platelet counts were obtained in the patient groups (p = 0.69) (range: 13–129 × 109/l). Aggregation adjusted for platelet count was significantly increased in ITP patients compared to healthy platelets across all agonists. The platelet aggregation was high in the 95% prediction interval, with 18 ITP patients above the prediction interval in at least two agonists. In contrast, the platelet aggregation was low in the prediction interval in cancer patients, and three cancer patients with platelet aggregation below the prediction interval in at least one agonist. ITP patients displayed increased expression of bound fibrinogen and CD63 following activation, compared with particularly cancer patients, but also compared with healthy platelets. This study demonstrated the feasibility of a novel approach to perform platelet function analyses in thrombocytopenia using impedance aggregometry adjusted for platelet count.

Hypercoagulability after distal pancreatectomy: Just meaningless alterations?

BackgroundPerioperative and short-term postoperative parameters are similar comparing spleen-preserving distal pancreatectomy (SPDP) and distal pancreatectomy with splenectomy (DPS). But there are no sound data evaluating the long term risk of postoperative thromboses and infectious complications after splenectomy. The present study evaluated whether the coagulation status differs in patients after SPDP and DPS, and whether that matters clinically. MethodsA total of 41 patients after DP (SPDP = 20; DPS = 21) were followed up, focusing on alterations of patient coagulation and immune status. To assess kinetics of the coagulation process, qualitative tests (multiple platelet function analyzer, rotational thrombelastography) were used in addition to global coagulation tests. ResultsCoagulation tests revealed a significant enhanced tendency for blood-platelet aggregation and coagulation activation in patients after DPS compared to patients after SPDP. No septic or thromboembolic events were observed in any patient. ConclusionHypercoagulability in splenectomized patients persists over years. Thus, a correlation of this finding with thromboembolic events and mortality years after splenectomy should to be performed in a large cohort.

Clinical utility of closure times using the platelet function analyzer-100/200.

The "platelet function analyzer" (PFA)-100 was first introduced to us in 1995. Since then, the instrument has appeared in over 50 reviews and almost 1000 publications. Recently, the PFA-100 has been "upgraded" to the PFA-200, which has transformed the user interface and electronic management, but retained the fundamental mechanics, and essentially provides the same results. The PFA-100/200 has conceivable clinical utility to screen for von Willebrand Disease (VWD) and platelet disorders, and in monitoring desmopressin (DDAVP) therapy in both, and possibly anti-platelet therapy. Its great strengths are its usage simplicity and sensitivity to conditions affecting primary hemostasis. However, as a "global" test, its limitation is that closure time (CT) test results are neither predictive of, nor specific for, any individual disorder. However, utilized properly, the PFA-100/200 reflects a valuable addition to hemostasis laboratories involved in identification or therapeutic-monitoring of disorders of primary hemostasis.

The use of regression analysis in determining reference intervals for low hematocrit and thrombocyte count in multiple electrode aggregometry and platelet function analyzer 100 testing of platelet function

Low platelet counts and hematocrit levels hinder whole blood point-of-care testing of platelet function. Thus far, no reference ranges for MEA (multiple electrode aggregometry) and PFA-100 (platelet function analyzer 100) devices exist for low ranges. Through dilution methods of volunteer whole blood, platelet function at low ranges of platelet count and hematocrit levels was assessed on MEA for four agonists and for PFA-100 in two cartridges. Using (multiple) regression analysis, 95% reference intervals were computed for these low ranges. Low platelet counts affected MEA in a positive correlation (all agonists showed r2 ≥ 0.75) and PFA-100 in an inverse correlation (closure times were prolonged with lower platelet counts). Lowered hematocrit did not affect MEA testing, except for arachidonic acid activation (ASPI), which showed a weak positive correlation (r2 = 0.14). Closure time on PFA-100 testing was inversely correlated with hematocrit for both cartridges. Regression analysis revealed different 95% reference intervals in comparison with originally established intervals for both MEA and PFA-100 in low platelet or hematocrit conditions. Multiple regression analysis of ASPI and both tests on the PFA-100 for combined low platelet and hematocrit conditions revealed that only PFA-100 testing should be adjusted for both thrombocytopenia and anemia. 95% reference intervals were calculated using multiple regression analysis. However, coefficients of determination of PFA-100 were poor, and some variance remained unexplained. Thus, in this pilot study using (multiple) regression analysis, we could establish reference intervals of platelet function in anemia and thrombocytopenia conditions on PFA-100 and in thrombocytopenia conditions on MEA.

Evaluating platelet function disorders in children with bleeding tendency – A single center study

Platelet function disorders (PFDs) are a common cause of mild bleeding tendency. However, they cannot be recognized by standard screening studies. The gold standard test for PFD is platelet aggregation, performed by light transmission aggregometry (LTA). A newer and less validated method is the closure time (CT), performed by the platelet function Analyzer 100 (PFA-100). Data regarding the validity of these tests in children are limited. The aim of this study was to evaluate the usefulness of LTA and PFA-100 for the diagnosis of pediatric patients with bleeding tendency.This retrospective study included patients one month–18 year old that had LTA tests performed at the coagulation laboratory of Rabin Medical Center between the years 2006–2015. Bleeding severity was assessed using a pediatric bleeding score. Patients were excluded from analysis if they had thrombocytopenia, thrombocytosis or coagulation factors deficiencies. One hundred and thirty-seven (137) patients were included in the analysis. The median age was 7.5 years (range one month–18 years). Most patients (93%) had a bleeding score of 2 or more. Abnormal LTA was found in 40% and prolonged CT in 23% of the patients. Abnormal LTA was significantly more common in patients with a bleeding score of 2 or more compared to patients with a lower bleeding scores (P = 0.04). No significant correlation was found between the bleeding severity and the number of agonists which induced abnormal responses (p = 0.52) or the CT (p = 0.35). Furthermore, no correlation was found between abnormal LTA and prolonged CT.To conclude, we were able to diagnose 40% of children who presented with bleeding tendency with platelet aggregation defects by LTA. Abnormal LTA was significantly more prevalent in patients with a bleeding score of 2 and above. In contrast, CT was not found to be sensitive as a screening tool for PFD. Therefore, our data extend the validity of the use of LTA for the evaluation of pediatric patients with bleeding tendency.

Honokiol as a specific collagen receptor glycoprotein VI antagonist on human platelets: Functional ex vivo and in vivo studies

Honokiol, derived from Magnolia officinalis, has various pharmacological properties. Platelet activation plays a critical role in cardiovascular diseases. Honokiol has been reported to inhibit collagen-stimulated rabbit platelet aggregation. However, detailed further studies on the characteristics and functional activity of honokiol in platelet activation are relatively lacking. In the present study, honokiol specifically inhibited platelet aggregation and Ca+2 ion mobilization stimulated with collagen or convulxin, an agonist of glycoprotein (GP) VI, but not with aggretin, an agonist of integrin α2β1. Honokiol also attenuated the phosphorylation of Lyn, PLCγ2, PKC, MAPKs, and Akt after convulxin stimulation. Honokiol have no cytotoxicity in zebrafish embryos. Honokiol diminished the binding of anti-GP VI (FITC-JAQ1) mAb to human platelets, and it also reduced the coimmunoprecipitation of GP VI-bound Lyn after convulxin stimulation. The surface plasmon resonance results revealed that honokiol binds directly to GP VI, with a KD of 289 μM. Platelet function analysis revealed that honokiol substantially prolonged the closure time in human whole blood and increased the occlusion time of thrombotic platelet plug formation in mice. In conclusion, honokiol acts as a potent antagonist of collagen GP VI in human platelets, and it has therapeutic potential in the prevention of the pathological thrombosis.

Open heart surgery: Management of nonsurgical bleeding in the peri-operative period; 31/2-years institutional experience

BACKGROUND:Excessive perioperative bleeding remains a major complication following open heart surgery, resulting in increased morbidity and mortality of some patients in our institution.A study of the principal causes of excessive nonsurgical haemostatic perioperative bleeding,clinical evaluation,treatment and preventive strategies is justified.OBJECTIVE/AIM: To identify the causes of bleeding in patients with haemorrhage that did not require reexploration and assess the impact on the patient outcomes from different causes of nonsurgical bleeding perioperatively.MATERIALS AND METHOD: For a period of 31/2 years (March 2013 – February 2016), the National Cardiothoracic Center of Excellence,UNTH,Ituku/Ozalla,Enugu,Nigeria, partnered with different foreign cardiac missions (USA,UK and India) for the performance of open heart surgery.The case files of the patients managed in the envisaged period were retrieved and analyzed using SPSS, version 2.0(Chicago). The data analyzed were patients' demographics, the total number of open heart surgery cases, the number that had perioperative nonsurgical bleeding,clinical detection strategies,treatment and preventive modalities as well as the outcome.RESULTS: During the period,a total number of 78 cases of open heart surgery (OHS) were done.There were 43 males and 35 females, with a ratio of approximately 1.3:1.The youngest age was 5 months and the oldest was 74 years, with a mean of 11.1 +/-SD 0.05. Out of these 78 cases, a total of 7 patients had perioperative nonsurgical bleeding, giving a percentage of 9%.3 patients were noticed intraoperatively in the operating room (OR) while 4 were noticed postoperatively in the intensive care unit (ICU). Treatment included the use of tranexemic acid or aprotinin, fresh frozen plasma (FFP) or fresh whole blood, platelet concentrate and additional doses of protamine, when incomplete reversal of heparin was the cause.CONCLUSION: Detection of the cause(s) of nonsurgical bleeding without thromboelastography or platelet function analyzer can be quite challenging in our environment.Applying appropriate pharmacologic agents among other interventions can reduce allogenic blood requirements with their attendant complications.KEY WORDS:Perioperative,Open heart surgery (OHS),thromboelastography,platelet function analyzer.

Serum omentin and vaspin levels in cirrhotic patients with and without portal vein thrombosis.

AIMTo investigate serum omentin and vaspin levels in cirrhotic patients; and to assess the relationship of these levels with hemostatic parameters, metabolic abnormalities, cirrhosis severity and etiology.METHODSFifty-one cirrhotic patients (17 with portal vein thrombosis) were analyzed. Serum omentin and vaspin levels were measured with commercially available direct enzyme-linked immunosorbent assays (ELISAs). To assess platelet activity, the following tests were performed using a MULTIPLATE®PLATELET FUNCTION ANALYZER: (1) an ADP-induced platelet activation test; (2) a cyclooxygenase dependent aggregation test (ASPI test); (3) a von Willebrand factor and glycoprotein Ib-dependent aggregation (using ristocetin) test (RISTO test); and (4) a test for thrombin receptor-activating peptide-6 induced activation of the thrombin receptor, which is sensitive to IIb/IIIa receptor antagonists.RESULTSOmentin, but not vaspin, serum concentrations were significantly decreased in patients with portal vein thrombosis (PVT) (P = 0.01). Prothrombin levels were significantly increased in patients with PVT (P = 0.01). The thrombin receptor activating peptide (TRAP) test results were significantly lower in the PVT group (P = 0.03). No significant differences in adipokines serum levels were found regarding the etiology or severity of liver cirrhosis assessed according to the Child-Pugh or Model of End-Stage Liver Disease (MELD) scores. There was a significant increase in the TRAP (P = 0.03), ASPI (P = 0.001) and RISTO high-test (P = 0.02) results in patients with lower MELD scores. Serum omentin and vaspin levels were significantly down-regulated in patients without insulin resistance (P = 0.03, P = 0.02, respectively). A positive relationship between omentin and vaspin levels were found both when all of the patients were analyzed (r = 0.41, P = 0.01) and among those with PVT (r = 0.94, P < 0.001).CONCLUSIONSerum omentin levels are increased in patients without PVT. Cirrhosis origin and grade do not affect omentin and vaspin levels. The analyzed adipokines do not influence platelet activity.

The Role of Platelet Function Analyzer Testing in Cardiac Surgery Transfusion Management

Background: Identifying high-risk patients for transfusion after cardiac operations would alter postoperative management. The aim of this study was to investigate closure time (CT) measured by platelet function analyzer (PFA) for prediction of bleeding and transfusions. Methods: 66 patients were scheduled for coronary artery bypass graft (CABG) surgery and 30 patients for valve repair and replacement (non-CABG). Measurements of PFA-100® CT for collagen and adenosine diphosphate (cADP) and collagen and epinephrine (cEPI) were performed 15 min after protamine administration. Blood loss was measured, and the amount of transfusion products was recorded postoperatively. Results: The study demonstrated significant differences between CABG patients with cADP-CT ≥ 118 s and those with cADP-CT < 118 s with regard to blood loss for 24 h (p = 0.001) and blood loss for 25-48 h (p = 0.003) as well as fresh frozen plasma (p = 0.015), platelet (p > 0.001) and red blood cell (p = 0.002) units given in 48 postoperative h. There were no differences cardiopulmonary bypass when was applied. In non-CABG patients, there were no differences in blood loss and transfusion requirements with respect to cADP-CT and cEPI-CT. Conclusion: Postoperative platelet dysfunction measured by a prolonged cADP-CT was significant predictor of blood loss and transfusion in CABG patients.

Adequate Platelet Function Inhibition Confirmed by Two Inductive Agents Predicts Lower Recurrence of Ischemic Stroke/Transient Ischemic Attack.

Background The correlation between platelet function and recurrent ischemic stroke or TIA remains uncertain. Objective To investigate two inductive agents to detect platelet functions and assess associations with recurrent ischemic stroke/TIA. Method The study included 738 ischemic stroke/TIA patients. On days 0, 3, and 9 after antiplatelet therapy, platelet function tests were determined by maximum aggregation rate (MAR) using a PL-11 platelet function analyzer and phase matching reagents. Two induction agents were used: arachidonic acid (AA) and adenosine diphosphate (ADP). At 3-month follow-up, recurrence of stroke/TIA was recorded. Result Cut-off values of adequate platelet function inhibition were MARADP < 35% and MARAA < 35%. Data showed that antiplatelet therapy could reduce the maximum aggregation rate. More importantly, adequate platelet function inhibition of either MARADP or MARAA was not associated with the recurrence of stroke/TIA, but adequate platelet function inhibition of not only MARADP but also MARAA predicts lower recurrence (0/121 (0.00%) versus 18/459 (3.92%), P = 0.0188). Conclusion The platelet function tested by PL-11 demonstrated that adequate inhibition of both MARADP and MARAA could predict lower risk of ischemic stroke/TIA recurrence.

Impact of high-dose statins on vitamin D levels and platelet function in patients with coronary artery disease

BackgroundStatins represent a pivotal treatment in coronary artery disease, offering a reduction in cardiovascular risk even beyond their lipid-lowering action. However, the mechanism of these “pleiotropic” benefits of statins is poorly understood. Vitamin D has been suggested as a potential mediator of the anti-inflammatory, anti-thrombotic and vascular protecting effects of statins. Aim of present study was to assess the impact of a high-intensity statin therapy on vitamin D levels and platelet function in patients with coronary artery disease. MethodsPatients discharged on dual antiplatelet therapy and high-intensity statins after an ACS or elective PCI were scheduled for main chemistry and vitamin D levels assessment at 30–90days post-discharge. Vitamin D (25-OHD) dosing was performed by chemiluminescence method through the LIAISON® Vitamin D assay (Diasorin Inc). Platelet function was assessed by Multiplate® (multiple platelet function analyser; Roche Diagnostics AG). ResultsAmong 246 patients included, 142 were discharged on a new statin therapy or with an increase in previous dose (Inc-S), while 104 were already receiving a high-dose statin at admission, that remained unchanged (Eq-S). Median follow-up was 75.5days. Patients in the Inc-S group were younger (p=0.01), smokers (p<0.001), with a less frequent history of hypercholesterolemia (p=0.05), diabetes (p=0.03), hypertension (p=0.02), or previous cardiovascular events (p<0.001). They were more often admitted for an acute coronary syndrome (p<0.001) and used less anti-hypertensive drugs or nitrates. Higher total circulating calcium was observed in the Inc-S group (p=0.004), while baseline vitamin D levels were similar in the 2 groups (p=0.30). A significant reduction in the circulating low-density lipoprotein (LDL) cholesterol was observed in the Inc-S group. Vitamin D levels increased in the Inc-S patients but not in the Eq-S group (delta-25OHD: 23.2±20.5% vs 3.1±4.7%, p=0.003), with a linear relationship between the magnitude of vitamin D elevation and the reduction of LDL cholesterol (r=−0.17, p=0.01). Platelet reactivity was significantly lower in the Inc-S patients, when evaluating aggregation with different platelet activating stimuli (arachidonic acid, p=0.02, collagen, p=0.004, thrombin-activating peptide, p=0.07, ADP, p=0.002). ConclusionsIn patients with coronary artery disease, the addition of a high-intensity statin treatment, besides the lipid-lowering effects, is associated to a significant increase in vitamin D levels and lower platelet reactivity, potentially providing explanation of the “pleiotropic” benefits of statins therapy in cardiovascular disease.