BACKGROUND: The Etablissement Français du Sang Alsace (EFS Alsace) successively implemented universal use of platelet additive solutions (PASs) and pathogen inactivation (PI) for platelet components ...(PCs). To assess the impact of these changes, EFS Alsace evaluated PC use, red blood cell (RBC) component use, and transfusion‐related adverse events after implementation of these new technologies.
STUDY DESIGN AND METHODS: EFS Alsace prospectively collects data on production, distribution, and response to transfusion of all blood components with greater than 99.5% data acquisition. Adverse events attributed to platelet (PLT) transfusions were collected through a mandatory, active hemovigilance program. A retrospective review of prospectively collected data was conducted covering three periods: 1) apheresis and whole blood–derived PCs in plasma, 2) apheresis and whole blood–derived PCs with PAS, and 3) PCs prepared with PI and PAS. Data on component utilization were analyzed for all patients receiving PCs in each period and for the subset of hematology‐oncology patients to evaluate PC use in an intensely transfused population. Values for all continuous variables were summarized as mean and standard deviation, median, and range.
RESULTS: Approximately 2000 patients received PCs in each period. PLT and RBC use per patient was not increased after PI (analysis of variance, F = 1.9 and 2.9, respectively) and the incidence of acute transfusion reactions was significantly reduced (p < 0.001).
CONCLUSIONS: Universal use of PI was implemented without impacting component use, as indicated by total dose of PLTs per patient, and outcomes to transfusion were improved.
BACKGROUND
The INTERCEPT Blood System (IBS) using amotosalen‐HCl and ultraviolet (UV)A inactivates a large spectrum of microbial pathogens and white blood cells in therapeutic plasma. Our aim was to ...evaluate to what extent IBS modifies the capacity of plasma to generate thrombin and induces qualitative or quantitative modifications of plasma proteins.
STUDY DESIGN AND METHODS
Plasma units from four donors were collected by apheresis. Samples were taken before (control CTRL) and after IBS treatment and stored at −80°C until use. The activities of plasma coagulation factors and inhibitors and the thrombin generation potential were determined using assays measuring clotting times and the calibrated automated thrombogram (CAT), respectively. The proteomic profile of plasma proteins was examined using a two‐dimensional differential in‐gel electrophoresis (2D‐DIGE) method.
RESULTS
Nearly all of the procoagulant and antithrombotic factors tested retained at least 78% of their initial pre‐IBS activity. Only FVII and FVIII displayed a lower level of conservation (67%), which nevertheless remained within the reference range for conventional plasma coagulation factors. The thrombin generation profile of plasma was conserved after IBS treatment. Among the 1331 protein spots revealed by 2D‐DIGE analysis, only four were differentially expressed in IBS plasma compared to CTRL plasma and two were identified by mass spectrometric analysis as transthyretin and apolipoprotein A1.
CONCLUSION
The IBS technique for plasma moderately decreases the activities of plasma coagulation factors and antithrombotic proteins, with no impact on the thrombin generation potential of plasma and very limited modifications of the proteomic profile.
BACKGROUND: A photochemical treatment (PCT) process has been developed to inactivate pathogens and white blood cells (WBCs) in therapeutic plasma. Process validation studies were performed in three ...European blood centers under routine operating conditions.
STUDY DESIGN AND METHODS: Each center prepared 30 apheresis and 30 to 36 whole blood–derived plasma units for PCT. Each whole blood–derived plasma unit contained a mixture of two to three matched donations. After removal of pretreatment control samples (control fresh‐frozen plasma C‐FFP), 546 to 635 mL of plasma was treated with 15 mL of 6 mmol per L amotosalen, 3 J per cm2 UVA treatment, and removal of residual amotosalen with a compound adsorption device. After processing, plasma samples (PCT‐FFP) were withdrawn, frozen at −60°C within 8 hours of collection, and assayed for coagulation factors and residual amotosalen.
RESULTS: A total of 186 units of plasma were processed. The mean prothrombin time (12.2 ± 0.6 sec) and activated partial thromboplastin time (32.1 ± 3.2 sec) of PCT‐FFP were slightly prolonged compared to C‐FFP. Fibrinogen and Factor (F)VIII were most sensitive to PCT (26% mean reduction). PCT‐FFP, however, retained sufficient levels of fibrinogen (217 ± 43 mg/dL) and FVIII (97 ± 29 IU/dL) for therapeutic plasma. Mean levels of FII, FV, FVII, F IX, FX, FXI, and FXIII in PCT‐FFP were comparable to C‐FFP (81%‐97% retention of activity). Antithrombotic proteins were not significantly affected by PCT with retention ranging between 83 and 97 percent. Mean residual amotosalen levels were 0.6 ± 0.1 μmol per L.
CONCLUSION: Process validation studies in three European centers demonstrated retention of coagulation factors in PCT‐FFP within the required European and respective national standards for therapeutic plasma.
The aim of this study was to determine whether low platelet response to the P2Y(12) receptor antagonist clopidogrel as assessed by Vasodilator-stimulated phosphoprotein flow cytometry test (VASP- ...FCT) predicts cardiovascular events in a high-risk population undergoing percutaneous coronary intervention (PCI).
Impaired platelet responsiveness to clopidogrel is thought to be a determinant of cardiovascular events after PCI. The platelet VASP-FCT is a new assay specific to the P2Y(12) adenosine diphosphate receptor-pathway. In this test, platelet activation is expressed as platelet reactivity index (PRI).
Four-hundred sixty-one unselected patients undergoing urgent (n = 346) or planned (n = 115) PCI were prospectively enrolled. Patients were classified as low-response (LR) and response (R) to clopidogrel, depending on their PRI. Optimal PRI cutoff was determined by receiver-operator characteristic curve analysis to 61% (LR: PRI > or =61% and R: PRI <61%). Follow-up was obtained at a mean of 9 +/- 2 months in 453 patients (98.3%).
At follow-up, total cardiac mortality rates and possible and total stent thrombosis were higher in LR patients. Multivariate analysis identified creatinine clearance (hazard ratio HR: 0.95; 95% confidence interval CI: 0.93 to 0.98, p < 0.001), drug-eluting stent (HR: 5.73; 95% CI: 1.40 to 23.43, p = 0.015), C-reactive protein (HR: 1.01; 95% CI: 1.001 to 1.019, p = 0.024), and LR to clopidogrel (HR: 4.00; 95% CI: 1.08 to 14.80, p = 0.037) as independent predictors of cardiac death. The deleterious impact of LR to clopidogrel on cardiovascular death was significantly higher in patients implanted with drug-eluting stent.
In patients undergoing PCI, LR to clopidogrel assessed by VASP-FCT is an independent predictor of cardiovascular death at the PRI cutoff value of > or =61%. The LR clinical impact seems to be dependent on the type of stent implanted.
It was the study objective to determine whether glycaemic control affects the extent of platelet inhibition by thienopyridines as assessed by vasodilator-stimulated phosphoprotein flow cytometry ...(VASP-FCT) in patients with diabetes mellitus (DM) undergoing percutaneous coronary intervention (PCI) during acute coronary syndrome (ACS). Although the proportion of high on-treatment residual platelet reactivity is higher in DM, the contributions of glycaemic control and other factors associated with DM, such as excess body weight and inflammation, to this impaired platelet inhibition by thienopyridines have not yet been fully characterised. In this study, the extent of P2Y12 ADP receptor pathway inhibition was evaluated by the VASP-FCT. Platelet activation was expressed as the platelet reactivity index (PRI). Low response to clopidogrel (LR) was defined as a PRI of >61%. Four hundred forty-five consecutive ACS patients (DM = 160, NDM = 285) were enrolled. The proportion of LR was higher in DM patients (50 vs. 37.5%). In DM, PRI was not correlated with glycosylated haemoglobin (HbA1c) or glycaemia. In a univariate analysis, LR was associated with age, male sex, overweight, and white blood cell count (WBC). In a multivariate analysis, WBC >10,000 and body weight >80 kg were the sole independent predictors of LR to clopidogrel (hazard ratio (HR) 3.02 1.36-6.68, p=0.006 and HR 2.47 1.14-5.35, p = 0.021, respectively). Conversely, in non-DM patients, ST-elevation myocardial infarction was the sole independent predictor of LR. In conclusion, in ACS DM patients undergoing PCI, the extent of P2Y12 inhibition by clopidogrel is not related to glycaemic control but is related to body weight and inflammatory status as assessed by the WBC.
Objectives We sought to determine whether low platelet response to the P2Y12 receptor antagonist clopidogrel as assessed by vasodilator-stimulated phosphoprotein flow cytometry test (VASP-FCT) ...differentially affects outcomes in patients with or without chronic kidney disease (CKD) undergoing percutaneous coronary intervention (PCI). Background Although both CKD and impaired platelet responsiveness to clopidogrel are strong predictors of unfavorable outcome after PCI, the impact of their association is unknown. The platelet VASP-FCT assay is specific for the P2Y12 ADP receptor pathway. In this test, platelet activation is expressed as the platelet reactivity index (PRI). Methods Four-hundred forty unselected patients (CKD: 126, estimated glomerular filtration rate eGFR <60 ml/min/1.73 m2 ), no-CKD: 314 eGFR >60 ml/min/1.73 m2 ) undergoing urgent (n = 336) or planned (n = 104) PCI were prospectively enrolled. In each subgroup, patients were classified as low-responders (LR: PRI ≥61%) or responders (R: PRI <61%) to clopidogrel. Results At a mean follow-up of 9 ± 2 months, all-cause mortality, cardiac death, and possible stent thrombosis were higher in CKD than in no-CKD patients. Within the CKD group, the LR status was associated with higher rates of all-cause mortality (25.5% vs. 2.8%, p < 0.001), cardiac death (23.5% vs. 2.8%, p < 0.001), all stent thrombosis (19.6% vs. 2.7%, p = 0.003), and MACE (33.3% vs. 12.3%, p = 0.007). Conversely, in no-CKD patients, the LR status did not affect outcomes. Multivariate analysis identified Killip class ≥3, drug-eluting stent implantation, and the interaction between LR and CKD (hazard ratio: 11.96, 95% confidence interval: 1.22 to 116.82; p = 0.033) as independent predictors of cardiac death. Conclusions In CKD patients, the presence of low platelet response to clopidogrel is associated with worse outcomes after PCI.
Soluble glycoprotein V (sGPV) is a new plasma marker of thrombosis released from the platelet surface by thrombin. sGPV levels are increased in patients with atherothrombotic diseases, but the ...determinants of sGPV levels are unknown in the general population. Identification of these potential confounding factors is needed for correct design and analysis of clinical studies on cardiovascular diseases. The aim of this study was to determine the normal range of plasma values and the factors controlling sGPV levels in a population of normal individuals. Three hundred blood donors were recruited at the Etablissement Français du Sang-Alsace for the measurement of plasma levels of sGPV, platelet factor 4 (PF4), thrombin-antithrombin complexes (TAT) and D-dimers. The plasma level of sGPV was (median interquartile range) 27.5 23.5-34.4 microg/l and displayed a Gaussian distribution. sGPV had a lower interindividual coefficient of variation (33%) than PF4 (176%), TAT (87%) or D-dimers (82%). sGPV levels were independent of age and sex but sensitive to red cell (r = 0.412; p < 0.0001) and platelet counts (r = 0.267; p = 0.001), total cholesterol (r = -0.313; p < 0.0001), food intake (r = 0.184; p = 0.0014) and smoking (r = -0.154; p = 0.039). Contrary to PF4 and TAT, sGPV did not differ between venous and arterial blood samples of 12 healthy individuals. Red cell and platelet counts, total cholesterol, current smoking and recent food intake are important determinants of sGPV levels and must be taken into account in clinical studies using sGPV as a thrombosis marker. Normal distribution of sGPV levels in the general population supports its use in clinical applications.
Background. Haemodialysis patients exhibit an excessive burden of atherothrombotic disease, which is not explained adequately by traditional risk factors. Hyperhomocyst(e)inaemia, a consistent ...finding in uraemic patients, is now widely recognized as an independent risk factor for vascular disease. The aim of this study was to examine the hypothesis that hyperhomocyst(e)inaemia is associated with cardiovascular complications in dialysed patients. Methods. In a cohort of 63 stable chronic haemodialysis patients, we examined the causal relationship between hyperhomocyst(e)inaemia and vascular endothelial and haemostatic function. All their markers were determined before and after an 8-week course of a 10 mg per day oral folate supplementation, a manoeuvre known to decrease hyperhomocyst(e)inaemia in uraemic patients. Results. History of at least one cardiovascular atherothrombotic event was present in 47.6% of the haemodialysed patients, and radiographic evidence of vascular calcifications in 70%. Hyperhomocyst(e)inaemia was found in all patients, averaging 3.5-fold the upper limit of normal values (P<0.001), despite the lack of clinical and biological evidence of malnutrition. Fibrinogen, von Willebrand factor and plasminogen activator inhibitor type 1, but not endothelin 1, were significantly higher in haemodialysis patients than in controls. After adjustment for all variables, past history of cardiovascular events was independently associated with higher levels of homocyst(e)inaemia only (odds ratio (OR) 1.06; 95% confidence interval (CI) 1.01–1.12; P<0.026). The presence of aortic calcifications was independently and significantly associated with age (OR 1.37; 95% CI 1.07–1.75; P<0.025), homocyst(e)inaemia (OR 1.14; 95% CI 1.02–1.27; P<0.05) and fibrinogen concentration only (OR 9.74; 95% CI 1.25–75.2; P<0.05). None of the endothelial–haemostatic factors was, however, related to homocyst(e)ine levels. Mid-term folate supplementation decreased plasma homocyst(e)ine levels significantly without achieving normal values. No significant change of endothelial–haemostatic markers was observed, however, despite the drop in plasma homocyst(e)ine. Conclusions. Hyperhomocyst(e)inaemia is associated with increased cardiovascular risk in haemodialysis patients. Folate supplementation was partially effective in lowering hyperhomocyst(e)inaemia, but its usefulness in terms of reduction in cardiovascular morbidity and mortality remains to be determined in prospective trials.
To assess the association between the occurrence first of preeclampsia and antiphospholipid antibodies.
We conducted a prospective case-control study of 180 pregnant women with their first incidents ...of preeclampsia and no histories of thrombosis or systemic autoimmune diseases. Preeclampsia (n = 180) was defined as blood pressure (BP) at least 140/90 mmHg after 20 weeks' gestation and proteinuria at least 0.3 g per 24 hours. Two control subjects were matched to each case (n = 360). They were pregnant women without hypertension or proteinuria and without histories of thrombosis or systemic autoimmune disease. Lupus anticoagulant (activated partial thromboplastin time, diluted thromboplastin time, platelet neutralization procedure) and anticardiolipin antibodies (immunoenzymatic assays) were assessed in both groups, and the coagulation state (levels of thrombin-antithrombin III complexes, fragments 1 + 2 of prothrombin) was also evaluated. The analysis design was a sequential plan with 5% type I error and 95% power.
There was no association between antiphospholipid antibodies and preeclampsia. The odds ratio for the association was 0.95 (95% confidence interval 0.45, 2.61). Antiphospholipid antibodies were detected in eight of 180 preeclamptic women and in 19 of 360 controls. In contrast, there was a clear, confirmed activation of coagulation during preeclampsia.
Despite evidence of a prothrombotic state during preeclampsia, it is unlikely that antiphospholipid antibodies (lupus anticoagulant and anticardiolipin antibodies) represent risk factors for preeclampsia among women with no previous preeclampsia and no histories of thrombosis or systemic autoimmune disease.
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