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Effect of anti-platelet factor-4/heparin antibody induction on early saphenous vein graft occlusion after coronary artery bypass surgery.

ABSTRACT: Antibodies to complexes of heparin and platelet factor 4 (PF4) are capable of causing heparin-induced thrombocytopenia (HIT). Recent evidence suggests that anti-PF4/heparin antibodies may be prothrombogenic even in the absence of thrombocytopenia and clinically-recognized HIT.To determine if induction of anti-PF4/heparin antibodies is an independent risk factor for early saphenous vein graft (SVG) occlusion or adverse clinical outcome after coronary artery bypass graft (CABG) surgery.Anti-PF4/heparin antibody titers were measured in 368 patients prior to and then 4 days, 6 weeks and 6 months after CABG surgery. Serotonin release assay (SRA) and antibody isotype analysis were also performed on 6-week samples. SVG patency was determined in 297 patients 6 months after surgery by multidetector computed tomography coronary angiography.Six weeks after surgery, 52% of patients were anti-PF4/heparin seropositive and 9% were SRA positive. Six months after surgery, neither the percentage of occluded SVG (19% vs. 20%, P = NS), the percentage of patients with an occluded SVG (33% vs. 33%, P = NS) nor the incidence of adverse clinical events (21% vs. 24%, P = NS) differed between seropositive and seronegative groups. Neither IgG isotype nor SRA positivity was additionally predictive of SVG occlusion or adverse clinical outcome.Induction of anti-PF4/heparin antibodies, even those capable of heparin-dependent platelet activation, is not independently associated with early SVG occlusion or adverse clinical outcomes after CABG surgery.

SUBMITTER: Gluckman TJ

PROVIDER: S-EPMC3004149 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature

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Effect of anti-platelet factor-4/heparin antibody induction on early saphenous vein graft occlusion after coronary artery bypass surgery.

Gluckman T J TJ Segal J B JB Schulman S P SP Shapiro E P EP Kickler T S TS Prechel M M MM Conte J V JV Walenga J M JM Shafique I I Rade J J JJ

Journal of thrombosis and haemostasis : JTH 20090623 9

<h4>Background</h4>Antibodies to complexes of heparin and platelet factor 4 (PF4) are capable of causing heparin-induced thrombocytopenia (HIT). Recent evidence suggests that anti-PF4/heparin antibodies may be prothrombogenic even in the absence of thrombocytopenia and clinically-recognized HIT.<h4>Objectives</h4>To determine if induction of anti-PF4/heparin antibodies is an independent risk factor for early saphenous vein graft (SVG) occlusion or adverse clinical outcome after coronary artery b ...[more]

PMID: 19552638

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Project description:Objectives: Coronary artery bypass grafting (CABG) success is reduced by graft occlusion. Understanding factors associated with graft occlusion may improve patient outcomes. The aim of this study was to develop a predictive risk score for saphenous vein graft (SVG) occlusion after CABG. Methods: This retrospective cohort study enrolled 3,716 CABG patients from January 2012 to March 2013. The development cohort included 2,477 patients and the validation cohort included 1,239 patients. The baseline clinical data at index CABG was analyzed for their independent impact on graft occlusion in our study using Cox proportional hazards regression. The predictive risk scoring tool was weighted by beta coefficients from the final model. Concordance (c)-statistics and comparison of the predicted and observed probabilities of predicted risk were used for discrimination and calibration. Results: A total of 959 (25.8%) out of 3,716 patients developed at least one late SVG occlusion. Significant risk factors for occlusion were female sex [beta coefficients (β) = 0.52], diabetes (β = 0.21), smoking (currently) (β = 0.32), hyperuricemia (β = 0.22), dyslipidemia (β = 0.52), prior percutaneous coronary intervention (PCI) (β = 0.21), a rising number of SVG (β = 0.12) and lesion vessels (β = 0.45). On-pump surgery (β = -0.46) and the use of angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB) (β = -0.59) and calcium channel blockers (CCB) (β = -0.23) were protective factors. The risk scoring tool with 11 variables was developed from the derivation cohort, which delineated each patient into risk quartiles. The c-statistic for this model was 0.71 in the validation cohort. Conclusions: An easy-to-use risk scoring tool which included female sex, diabetes, smoking, hyperuricemia, dyslipidemia, prior PCI, a rising number of SVG and lesion vessels, on-pump surgery, the use of ACEI/ ARB and CCB was developed and validated. The scoring tool accurately estimated the risk of late SVG occlusion after CABG (c-statistic = 0.71).

Project description:The purpose of this study was to determine if an incomplete response to or inadequate antiplatelet effect of aspirin, or both, contribute to saphenous vein graft (SVG) occlusion after coronary artery bypass graft (CABG) surgery.Thrombosis is the predominant cause of early SVG occlusion. Aspirin, which inhibits cyclooxygenase-1 activity and thromboxane generation in platelets, reduces early SVG occlusion by one-half.Aspirin responsiveness and platelet reactivity were characterized 3 days and 6 months after coronary artery bypass graft surgery in 229 subjects receiving aspirin monotherapy by platelet aggregation to arachidonic acid, adenosine diphosphate, collagen and epinephrine, Platelet Function Analyzer-100 (Siemens Healthcare Diagnostics, Newark, Delaware) closure time (CT) using collagen/epinephrine agonist cartridge and collagen/adenosine diphosphate (CADP) agonist cartridge, VerifyNow Aspirin assay (Accumetrics, Inc., San Diego, California), and urine levels of 11-dehydro-thromboxane B(2) (UTXB(2)). SVG patency was determined 6 months after surgery by computed tomography coronary angiography.Inhibited arachidonic acid-induced platelet aggregation, indicative of aspirin-mediated cyclooxygenase-1 suppression, occurred in 95% and >99% of subjects 3 days and 6 months after surgery, respectively. Despite this, 73% and 31% of subjects at these times had elevated UTXB(2). Among tested parameters, only UTXB(2) and CADP CT measured 6 months after surgery correlated with outcome. By multivariate analysis, CADP CT of ?88 s (odds ratio: 2.85, p = 0.006), target vessel diameter of ?1.5 mm (odds ratio: 2.38, p = 0.01), and UTXB(2) of ?450 pg/mg creatinine (odds ratio: 2.59, p = 0.015) correlated with SVG occlusion. CADP CT and UTXB(2) in combination further identified subjects at particularly high and low risk for SVG occlusion.Aspirin-insensitive thromboxane generation measured by UTXB(2) and shear-dependent platelet hyper-reactivity measured by Platelet Function Analyzer-100 CADP CT are novel independent risk factors for early SVG thrombosis after coronary artery bypass graft surgery.

Project description:ImportanceObservational studies have suggested that the use of radial artery grafts for coronary artery bypass grafting may improve clinical outcomes compared with the use of saphenous vein grafts, but this has not been confirmed in randomized trials.ObjectiveTo compare clinical outcomes between patients receiving radial artery vs saphenous vein grafts for coronary artery bypass grafting after long-term follow-up.Design, setting, and participantsPatient-level pooled analysis comparing radial artery vs saphenous vein graft in adult patients undergoing isolated coronary artery bypass grafting from 5 countries (Australia, Italy, Serbia, South Korea, and the United Kingdom), with enrollment from 1997 to 2009 and follow-up completed in 2019.InterventionsPatients were randomized to undergo either radial artery (n?=?534) or saphenous vein (n?=?502) grafts for coronary artery bypass grafting.Main outcomes and measuresThe primary outcome was a composite of death, myocardial infarction, or repeat revascularization and the secondary outcome was a composite of death or myocardial infarction.ResultsA total of 1036 patients were randomized (mean age, 66.6 years in the radial artery group vs 67.1 years in the saphenous vein group; 376 [70.4%] men in the radial artery group vs 351 [69.9%] in the saphenous vein group); 942 (90.9%) of the originally randomized patients completed 10 years of follow-up (510 in the radial artery group). At a median (interquartile range) follow-up of 10 (10-11) years, the use of the radial artery, compared with the saphenous vein, in coronary artery bypass grafting was associated with a statistically significant reduction in the incidence of the composite outcome of death, myocardial infarction, or repeat revascularization (220 vs 237 total events; 41 vs 47 events per 1000 patient-years; hazard ratio, 0.73 [95% CI, 0.61-0.88]; P?<?.001) and of the composite of death or myocardial infarction (188 vs 193 total events; 35 vs 38 events per 1000 patient-years; hazard ratio, 0.77 [95% CI, 0.63-0.94]; P?=?.01).Conclusions and relevanceIn this individual participant data meta-analysis with a median follow-up of 10 years, among patients undergoing coronary artery bypass grafting, the use of the radial artery compared with the saphenous vein was associated with a lower risk of a composite of cardiovascular outcomes.

Project description:Background Perivascular adipose tissue (PVAT) is associated with metabolically driven chronic inflammation called metaflammation, which contributes to vascular function and the pathogenesis of vascular disease. The saphenous vein (SV) is commonly used as an essential conduit in coronary artery bypass grafting, but the long-term patency of SV grafts is a crucial issue. The use of the novel "no-touch" technique of SV harvesting together with its surrounding tissue has been reported to result in good long‑term graft patency of SV grafts. Herein, we investigated whether PVAT surrounding the SV (SV-PVAT) has distinct phenotypes compared with other PVATs of vessels. Methods and Results Fat pads were sampled from 48 patients (male/female, 32/16; age, 72±8 years) with coronary artery disease who underwent elective coronary artery bypass grafting. Adipocyte size in SV-PVAT was significantly larger than the sizes in PVATs surrounding the internal thoracic artery, coronary artery, and aorta. SV-PVAT and PVAT surrounding the internal thoracic artery had smaller extents of fibrosis, decreased gene expression levels of fibrosis-related markers, and less metaflammation, as indicated by a significantly smaller extent of cluster of differentiation 11c-positive M1 macrophage infiltration, higher gene expression level of adiponectin, and lower gene expression levels of inflammatory cytokines, than did PVATs surrounding the coronary artery and aorta. Expression patterns of adipocyte developmental and pattern-forming genes were totally different among the PVATs of the vessels. Conclusions The phenotype of SV-PVAT, which may result from inherent differences in adipocytes, is closer to that of PVAT surrounding the internal thoracic artery than that of PVAT surrounding the coronary artery or that of PVAT surrounding the aorta. SV-PVAT has less metaflammation and consecutive adipose tissue remodeling, which may contribute to high long-term patency of grafting when the no-touch technique of SV harvesting is used.

Dataset Information

Effect of anti-platelet factor-4/heparin antibody induction on early saphenous vein graft occlusion after coronary artery bypass surgery.

Publications

Effect of anti-platelet factor-4/heparin antibody induction on early saphenous vein graft occlusion after coronary artery bypass surgery.

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