• cyclooxygenase 1;
  • gene expression;
  • glycoprotein IIb/IIIa receptor;
  • inflammation;
  • platelets;
  • thrombosis


  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Disclosure of Conflicts of Interest
  9. References

Summary.  Background:  During and shortly after coronary artery bypass graft (CABG) surgery, there is an increase in thromboembolic events. CABG, a strong inflammatory stimulus, is associated with a hypercoaguable state. Platelets might contribute to this hypercoaguable state because they have a pivotal role in thrombosis. In the days following surgery there is augmented platelet regeneration in response to the inflammatory stimulus.

Objectives:  The aim of this study was to investigate any changes in platelet mRNA profiles to test the hypothesis that post-CABG surgery platelets are associated with a prothrombotic state.

Methods:  Blood was sampled and platelets purified from 11 patients before and 3–6 days after CABG. Gene expression profiling was performed using low density array (LDA) plates for seven of the patients.

Results:  Forty-five genes were examined and those significantly up-regulated were glycoprotein (GP)IIb, GPIIIa and cyclooxygenase-1 (COX-1). These findings were confirmed in four more patients, including flow cytometry analysis of the GPIIb/IIIa receptor.

Conclusions:  CABG surgery up-regulates mRNA and protein levels of proteins that are key players in platelet aggregation. Marked elevation of GPIIb/IIIa mRNA levels results in significantly increased GPIIb/IIIa expression in platelets post-CABG surgery, which may be a reason for increased thrombus formation and myocardial infarction after CABG.


  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Disclosure of Conflicts of Interest
  9. References

During and shortly after coronary artery bypass graft (CABG) surgery, there is an increase in myocardial infarction (MI) risk. The incidence varies from 3 to 30%, depending on methods of diagnosis and the patient cohort [1]. Also, after major non-cardiac surgery there is an increased risk of MI, with an incidence of up to 5% [2–4]. The majority of these events occur within 3 days of surgery [5,6]. Arterial thrombosis occurring on an atherosclerotic plaque rupture is the major cause of non-operative MI [7]. The mechanisms behind postoperative MI risk have not been identified and studies provide conflicting evidence on whether thrombosis is the cause. One thing that all surgery patients have in common is that surgery is associated with acute systemic inflammatory and hypercoaguable states that might increase the risk of arterial thrombosis [8,9].

Platelets play a pivotal role in coronary thrombosis and inflammation after plaque rupture, either spontaneously or after coronary intervention [10]. They are also major players in blood coagulation, and may contribute to the hypercoaguable state seen after surgery. It has been shown that there is an increase in platelet activation and reactivity after surgery, and also platelet-leukocyte aggregate formation [11,12]. To combat the adverse effects of surgery, patients undergo antiplatelet treatment. The two most commonly used therapies are the cyclooxygenase 1 (COX-1) inhibitor, aspirin, and the adenosine diphosphate (ADP) receptor P2Y12 antagonist, clopidogrel [13,14]. However both of these treatments have limitations; it has been shown that aspirin does not sufficiently inhibit platelet aggregation in the early postoperative period [15], and there is evidence of inter- and intra-variability in individual responses to clopidogrel [16].

Major surgeries consume significant amounts of platelets, and this leads to augmented platelet regeneration in the days following surgery. Even though they are anuclear cells, platelets still contain a considerable amount of mRNAs [17–20]. In newly released platelets mRNA levels are higher [21], which allows for de novo protein synthesis even after they are released from the megakaryocytes [22]. However, it is not known if inflammatory stimuli such as CABG surgery alter the mRNA profile of these newly released platelets. Therefore, the aim of this study was to study changes in platelet mRNA to see if these changes can suggest a plausible mechanism behind the increased risk of MI in the days following CABG surgery.

Materials and methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Disclosure of Conflicts of Interest
  9. References


Patients were eligible if they were planned for elective coronary by-pass surgery ± aortic valve replacement (n = 2) according to standard surgical procedures at the Department of Thoracic Surgery at Karolinska University Hospital, Solna, Sweden. In total, 11 patients undergoing open heart surgery were enrolled in the study. All subjects provided written consent to participate, and the study protocol was approved by the Ethics Committee of the Karolinska Institute.

Blood samples were collected before and 3–6 days (average 4.5) after CABG surgery, which was performed on-pump for all patients. Basic characteristics of all subjects are shown in Table 1 and biological measurements are listed in Table 2. None of the patients received a platelet infusion before or after surgery, however four did receive blood transfusions.

Table 1.   Demographic data and basic characteristics
Characteristicsn = 11
  1. ACEi, angiotensin converting enzyme inhibitors; ARB, angiotensin receptor blockers.

 Age, years, mean (range)67 (57–83)
 Sex, male/female11/0
 Smoking, yes/previous/no1/5/5
 Diabetes, yes/no1/10
 Hypertension treated, yes/no8/3
 Hyperlipidemia treated, yes/no8/3
 Betablocker therapy, yes/no11/0
 ACEi or ARBs therapy, yes/no7/4
Warfarin, yes/no
 Before surgery0/11
 After surgery1/10
Aspirin, yes/no 
 Before surgery11/0
 After surgery10/1
 Before surgery2/9
 After surgery0/11
Table 2.   Blood chemistry measurements before and after surgery
VariableBefore surgeryAfter surgeryP-value
  1. Values are mean ± SD. CRP, C-reactive protein; WBC, white blood cell count.

  2. *Measured in four patients.

Hemoglobin (g/l)139 ± 8103 ± 13< 0.0001
CRP (mg/l)3 ± 3123 ± 49< 0.0001
WBC (×109/l)6.3 ± 1.68.2 ± 1.4< 0.001
Platelets (×109/l)211 ± 48220 ± 700.6
Median platelet volume (fl)*7.8 ± 0.28.5 ± 0.30.03


Adenosine diphosphate (ADP) was purchased from Sigma (St Louis, MO, USA). Surface expression of platelet glycoprotein (GP) IIb/IIIa (CD41/CD61) and platelet-endothelial cell adhesion molecule-1 (PECAM-1, CD31) were measured using a phycoerythrin (PE)-conjugated CD41 monoclonal antibody (MAb) (clone HIP8; BD Biosciences Pharmingen, San Diego, CA, USA) and a fluorescein isothiocyanate (FITC)-conjugated CD31 MAb (clone 5.6E; Immunotech, Marseille, France), respectively. The corresponding FITC- or PE-conjugated isotypic control antibodies were also from BD Biosciences Pharmingen and Immunotech.

Preparation of platelets for RNA isolation

Human platelets were purified using a centrifugation, filtration and leukocyte depletion protocol [23]. Sixty milliliters of blood was collected from 11 patients in Vacutainer® EDTA-tubes (BD Biosciences, Franklin Lakes, NJ, USA). Platelet-rich plasma (PRP) was obtained through centrifugation (20 min, 200 × g at room temperature (RT)). The top two-thirds of PRP were removed and centrifuged again (10 min, 200 × g, RT). The PRP was then passed through a Pall AutoStop™ Leukocyte removal filter (Pall Corporation, Port Washington, NY, USA). Further leukocyte depletion was then performed on each individual platelet filtrate using 50 μL anti-CD45 Dynabeads® (Invitrogen, Carlsbad, CA, USA) according to the manufacturer’s instructions. After cell depletion, the platelets were collected by centrifugation (20 min, 800 × g, RT), and stored in RLT buffer (Qiagen, Valencia, CA, USA) or RNA later buffer (Ambion, Austin, TX, USA) at −85 °C until RNA isolation.

Total RNA isolation and cDNA synthesis

RNA was isolated following the protocol in the mirVana miRNA Isolation Kit (Ambion). For samples stored in RLT a modified isolation protocol was used. To these samples 400 μL of the lysis buffer from the mirVana kit was added and the manufacturer’s protocol was then followed. RNA concentration and quality were analyzed using the Nanodrop 1000 Spectrophotometer (NanoDrop Technologies, Wilmington, DE, USA) and Agilent 2100 Bioanalyzer (Agilent Technologies Inc., Santa Clara, CA, USA), respectively.

Gene expression studies

To investigate which housekeeping genes to use for gene expression studies, cDNA from platelets before and after CABG from four patients were analyzed using TaqMan Human Endogenous Control Plate (Applied Biosystems, Foster City, CA, USA). cDNA was synthesized using the high capacity cDNA reverse transcription kit (Applied Biosystems). Three housekeeping genes were chosen; eukaryotic 18s (Hs99999901_s1), β2-microglobulin (B2M) (Hs99999907_m1) and 50S ribosomal protein (RPLPO) (Hs99999902_m1).

Low density assay (LDA) plates were designed for analysis of platelet gene expression (Applied Biosystems). Housekeeping genes used are as above and an additional 45 genes were chosen for analysis based on an in-depth literature search of genes that were identified in platelet transcriptome studies [17–19]. Genes identified in these studies that have roles in platelet functionality, the immune response and inflammation were chosen (gene expression assays for these are shown in Table 3). To analyze platelet gene expression, cDNA was mixed with 2× Taqman Universal PCR mix (Applied Biosystems) in a volume of 100 μL and all samples were run in quadruple. The samples were loaded onto a low density assay plate and run according to the manufacturer’s instructions (Applied Biosystems). Relative quantification (RQ) of gene expression was calculated using the 2-ΔΔct method [24]. The pre-operation platelet sample in every paired sample was used as a reference, and B2M was used as the housekeeping gene because it was stable in each individual studied. This was performed for the first seven patients recruited to the study. For the remaining four patients, quantitative polymerase (Q-PCR) was performed for the following genes, GPIIb (ITGA2B), GPIIIa (ITGB3) and COX-1 (PTGS1), and B2M was used as the housekeeping gene.

Table 3.   Gene expression analysis of platelets after CABG
Gene symbolGene nameTaqman® GEAP-valueFold regulation
  1. ND, not detected.

  2. *Indicates genes with a fold change of ≥ 2; P = 0.05 or less.

  3. Genes studied in 11 individuals. The remaining genes were studied in seven individuals.

  4. mRNA gene expression levels after CABG surgery are shown as fold change. Relative quantification levels of each gene were examined in relation to the housekeeping gene β2-microglobulin, using the before surgery samples as a reference.

 CCL3Chemokine (C-C motif) ligand 3Hs00234142_m10.21−0.35
 CCL5 (RANTES)Chemokine (C-C motif) ligand 5Hs00174575_m10.08−0.54
 CCL7Chemokine (C-C motif) ligand 7Hs00171147_m1NDND
 CXCL2Chemokine (C-X-C motif) ligand 2Hs00601975_m1NDND
 CXCL3Chemokine (C-X-C motif) ligand 3Hs00171061_m10.08−0.93
 CXCL5Chemokine (C-X-C motif) ligand 5Hs00171085_m10.08−0.71
 CXCL12 (SDF1)Chemokine (C-X-C motif) ligand 12Hs00171022_m1NDND
 IL10Interleukin 10Hs00961622_m1NDND
 IL1BInterleukin 1βHs01555410_m10.5−20.91
 IL6Interleukin 6Hs00985639_m1NDND
 PDGFCPlatelet-derived growth factor CHs00211916_m10.021.91
 PF4Platelet factor 4Hs00236998_m10.940.55
 PPBPPro-platelet basic proteinHs00234077_m10.580.31
 RELT(TNFRSF19L)RELT tumor necrosis factor receptorHs00262701_m1NDND
 VEGFB*Vascular endothelial growth factor BHs00173634_m10.32.18
 CXCR3Chemokine (C-X-C motif) receptor 3Hs00171041_m1NDND
 ITGA2B (GPIIb)*Integrin, alpha 2b (platelet glycoprotein IIb)Hs01116228_m10.0015.9
 ITGB3 (GPIIIa)*Integrin, beta 3 (platelet glycoprotein IIIa)Hs01001469_m10.0014.9
 IL10RAInterleukin 10 receptor, alphaHs00155485_m10.03−12.59
 ITGAMIntegrin, alpha MHs00355885_m10.69−0.97
 ITGB2Integrin, beta 2Hs00164957_m10.81−4.17
 F11R*F11 receptorHs00375889_m10.022.03
 P2RY12Purinergic receptor P2Y, 12Hs00224470_m10.03−0.89
 F2RCoagulation factor II receptorHs00169258_m10.021.43
 F2RL1Coagulation factor II receptor-like 1Hs00173741_m1NDND
PG synthesis
 COX-1 (PTGS1)*Cyclooxygenase 1Hs00377726_m10.0013.8
 COX-2 (PTGS2)Cyclooxygenase 2Hs00153133_m1NDND
 PTGER4Prostaglandin E receptor 4Hs00168761_m1NDND
 TBXAS1Thromboxane A synthase 1Hs01022706_m10.691.13
Acute phase protein
 CRPC-reactive proteinHs00265044_m1NDND
 PTX3Pentraxin 3Hs00173615_m1NDND
 F5Coagulation factor VHs00914120_m1NDND
 SERPINE1 (PAI-1)Serpin peptidase inhibitorHs01126604_m10.580.35
 PLAUPlasminogen activator, urokinaseHs01547054_m1NDND
 F3Coagulation factor IIIHs01076032_m1NDND
Membrane molecule
 GP5Glycoprotein VHs03027242_s10.810.67
 GP6*Glycoprotein VIHs00212574_m10.022.4
 ICAM2*Intercellular adhesion molecule 2Hs00609563_m10.022.07
 PECAM1*Platelet/endothelial cell adhesion moleculeHs00169777_m10.022.26
 SELPSelectin PHs00174583_m10.02−1.06
 THBS1Thrombospondin 1Hs00962908_m10.31.45
 MMP9Matrix metallopeptidase 9Hs00234579_m1NDND
 MMP17Matrix metallopeptidase 17Hs01108847_m1NDND
 PTPRCProtein tyrosine phosphatase, receptor type CHs00365634_g1NDND

Flow cytometry analysis

Venous blood was obtained from four patients and collected in Vacutainer® sodium citrate tubes (BD, Franklin Lakes, NJ, USA). Aliquots of 5 μL blood were added to 45 μL of Hepes-buffered saline (150 mm NaCl, 5 mm KCl, 1 mm MgSO4, 10 mm Hepes, pH 7.4) containing appropriately diluted fluorescent antibodies for the detection of GPIIb/IIIa or PECAM-1 expression in the absence or presence of ADP (1 μm final concentration). The samples were incubated at room temperature for 20 min, and then fixed with 0.5% (v/v) formaldehyde saline. Whole blood flow cytometric platelet analyses were carried out using a FC500 flow cytometer (Beckman-Coulter Corp., Hialeah, FL, USA) as previously described [12]. Standardization of platelet fluorescent signals was performed using SPHERO rainbow calibration particles (BD Pharmingen, San Diego, CA, USA). Platelet expression of GPIIb/IIIa and PECAM-1 are reported as fluorescence intensity arbitrary units.

Statistical analysis

Data are presented as absolute numbers, mean ± SD or range. Differences between before and after surgery samples were analyzed using the non-parametric Wilcoxon matched-pairs signed rank test.


  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Disclosure of Conflicts of Interest
  9. References

Biological measurements of patients post-CABG

Post-surgery CRP levels and white blood cell numbers increased, while hemoglobin levels decreased (Table 2). There was no change in platelet counts between blood samples. There was also a small but significant increase in the platelet volume in the four patients who were used in the FACs analysis.

Effect of CABG on platelet gene expression

An in-depth literature search was performed to identify genes that were of interest for this study (Table 3). We examined 45 genes that are associated with platelet function and inflammation. Genes that were up- or down-regulated by a factor of two were considered to be relevant. Using this cut-off point, only seven of the 45 genes analyzed were significantly up-regulated in response to CABG surgery (Table 3).

The most markedly elevated genes according to our selection criteria were: GPIIb, GPIIIa and COX-1 (Fig. 1). GPIIb and GPIIIa were up-regulated by a factor of approximately five and four, respectively, while COX-1 mRNA levels were approximately three times higher than pre-surgery values. Other genes with a fold change more than two were F11 receptor (F11R), GPVI, intercellular adhesion molecule 2 (ICAM2) and platelet/endothelial cell adhesion molecule (PECAM1), while there was a strong trend towards an increased expression of vascular endothelial growth factor B (VEGFB) (Table 3).


Figure 1.  CABG surgery increases platelet GPIIb, GPIIIa and COX-1 mRNA levels. Relative platelet mRNA gene expression of GPIIb, GPIIIa and COX-1. Levels are expressed in relation to the housekeeping gene, B2M, using pre-surgery platelets in every paired sample as a reference. n = 11; *P = 0.001.

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To check for leukocyte contamination we examined the levels of protein tyrosine phosphatase, receptor type C (PTPRC), also known as CD45. In four out of the seven patients we tested there were no detectable levels of PTPRC, in the remaining three we could detect some PTPRC but at very low levels.

Effects of CBAG surgery on platelet reactivity and adhesion molecule expression

GPIIb/IIIa is the principal fibrinogen receptor on platelets and was assessed using a PE-CD41 MAb. Basal levels of the constitutively expressed receptor were elevated in the 3–6 days after CABG surgery, when compared with those from before surgery (1.5 times higher). ADP stimulation markedly enhanced GPIIb/IIIa expression on the platelet surface, and this was even more pronounced in platelets after CABG (Fig. 2). Another constitutively expressed gene with increased expression was the adhesion molecule PECAM-1 (CD31); its levels remained unchanged before and after the surgery, and also regardless of ADP stimulation (Fig. 2).


Figure 2.  CABG surgery enhances platelet expression of CD41/CD61 but not CD31. Venous blood samples were obtained before and 3–6 days after CABG surgery. Platelet surface expression of GPIIb/IIIa (CD41) and PECAM1 (CD31) in the absence (unstimulated; white bars) or presence of in vitro stimulation (1 μm ADP; grey bars) was analyzed using whole blood flow cytometry. n = 4; *P < 0.05 as compared with unstimulated samples; †P < 0.05 as compared with corresponding samples before CABG surgery.

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  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Disclosure of Conflicts of Interest
  9. References

CABG surgery represents one of the strongest models of inflammation in humans and results in extensive acute inflammation. After CABG there is a huge increase in gene expression and plasma protein levels of inflammatory mediators such as tumor necrosis factor, interleukin (IL) 6 and IL1 [25–27]. This extreme inflammatory response might contribute to a number of post-surgery complications, including thrombus formation and MI [9]. The aim of this study was to study changes in gene expression of platelets after CABG surgery with the hypothesis that the findings might offer possible mechanisms behind the increased risk of MI seen in the days following CABG and other surgery. To the best of our knowledge this is the first study of gene expression in platelets influenced by the strong inflammatory stimulus of CABG. Studying platelet gene expression in this context offers the advantage that it is not influenced by drugs of hemodilution when compared with platelet function studies. Briefly, we noted an increase in mRNA and protein levels of GPIIb/IIIa receptor and mRNA levels of COX-1 in platelets after CABG.

GPIIb/IIIa is the most abundant platelet membrane glycoprotein, a heterodimer that is formed by the association of two subunits, GPIIb and GPIIIa. The heterodimer binds fibrinogen, and mediates the final common pathway of platelet activation/aggregation and thus thrombus formation [28]. After CABG we noted an increase in the mRNA levels of both GPIIb and GPIIIa. It has been recently established that circulating platelets, albeit as anucleated cells, are capable of synthesizing proteins. It has also been shown that young platelets have a significantly greater rate of protein synthesis than older platelets [29], and that platelets stored in blood banks have been shown to be able to synthesize GPIIb/IIIa [30]. Therefore, we used flow cytometric analysis to confirm increased GPIIb/IIIa on platelets. After CABG there was an increase in the basal levels of surface expressed GPIIb/IIIa, and stimulation with ADP resulted in further recruitment of more complexes to the surface. Elevated platelet GPIIb/IIIa expression is likely to facilitate fibrinogen binding on platelets, and subsequently enhance platelet aggregability. A limitation with the present study is that platelet aggregability was not assessed in parallel with the gene expression analysis, which could have possibly elucidated the functional consequence of elevated GPIIb/IIIa expression.

It should be noted that an increase in mRNA levels does not always result in an increase in protein levels. In the present study, we showed a marked increase of platelet PECAM-1 mRNA expression after the surgery. However, we did not find any increases of PECAM-1 expression in circulating platelets or upon platelet activation. Our findings also imply that there are multiple regulatory mechanisms in platelet protein synthesis, not only at transcription but also at translation levels.

Inflammatory mediators from surgery trauma, such as IL6, are associated with thrombocytosis [31], and work performed by our group and others has shown that after CABG there is a systemic increase in plasma IL6 [25,27]. Our results showed an increase in CRP levels and numbers of circulating leukocytes, both of which confirm a strong inflammatory reaction. Platelet consumption during CABG surgery leads to a marked reduction of blood platelet counts immediately after the surgery [32,33]. CABG surgery-evoked inflammatory stress, however, provokes swift platelet turnover [34], and results in a quick recovery of circulating platelet levels within a few days, which are similar to or even higher than pre-surgery levels. An enhanced platelet turnover was suggested by the increase we saw in median platelet volume after CABG surgery (n = 4), which is an indicator of enhanced platelet turnover [35]. Therefore, the reason for an increase in GPIIb/IIIa receptors after CABG is most likely due to the regenerated pool of platelets that contains ‘newer’ platelets with increased mRNA levels and an increased ability to synthesize proteins.

Our finding that CABG surgery and the resulting inflammation give rise to an increase of platelet GPIIb/IIIa receptors brings GPIIb/IIIa inhibitors back into clinical focus. Oral GPIIb/IIIa receptor blockers have not been successful in reducing the incidence of re-infarction after a primary MI and surgery [36,37]. However, a role for the intravenous administration of these drugs cannot be excluded, especially regarding MI after surgery, where the most likely mechanism behind this risk is increased platelet aggregation stimulated by inflammation.

An important enzyme in platelet activation is COX-1, which is the key enzyme in thromboxane A2 production [38]. In this study there was an increase in gene expression of COX-1 mRNA after CABG. Aspirin is one of the most widely used antiplatelet therapies used in the postoperative period, and works by irreversibly inhibiting COX-1. It has been shown that the low dose of aspirin used in clinical practise does not result in sufficient platelet inhibition in the majority of CABG patients within 10 days after surgery [32,39,40]. This phenomenon has been called aspirin resistance and the mechanism behind it is largely unknown. Several mechanisms have been proposed for the inadequate aspirin response, including increased platelet number.

There are two isoforms of COX, COX-1 and COX-2. COX-1 is responsible for the majority of platelet thromboxane synthesis, but it was also shown that there is a small amount of COX-2 present in platelets [41]. It was hypothesized that an increase in COX-2 could be responsible for aspirin resistance post-CABG. In the seven patients we analyzed using the LDA arrays we did not see any detectable levels of COX-2 before or after surgery (Table 3). What we did see in the newly released platelets is that in the 3–6 days after CABG surgery there was an increase in the amount of COX-1 mRNA. If the increase in mRNA levels results in an increase of COX-1 protein levels, then current standard aspirin treatments may not be able to fully inhibit the increased amount of COX-1 produced after surgery. This could mean that these newer platelets are producing more COX-1 and that the current aspirin dosages prescribed are insufficient to inhibit the higher COX-1 levels. We did not investigate COX-1 protein levels but Zimmermann and co-workers did not see an increase in its levels after CABG, which suggests that insufficient COX-1 inhibition is not a problem. However, Brambilla et al. have recently shown that a higher dose of aspirin might overcome aspirin resistance after CABG [42], speaking in favor of a role for COX-1.

One other interesting change we noted was an increase in Glycoprotein VI (GPVI) levels. GPVI is one of three platelet membrane receptors for collagen, and is critical for collagen-induced platelet activation. The interaction of platelets with collagen and extracellular matrix is an initial event in arterial thrombosis [43]. Other genes that were up-regulated are F11R, ICAM2, PDGFC and PECAM1. All of these, including GPVI, were only just up-regulated by a factor of 2; however, as they were only examined in seven patients, they will need to be studied in further detail.

In conclusion, the expression of a number of genes that code for proteins involved in platelet aggregation, namely COX-1, GPIIb and GPIIIa, are enhanced after CABG surgery. Of course there are some limitations regarding the work performed, especially regarding the number of patients used for the FACS analysis (n = 4). However, our data support the idea that platelets can react quickly to physiological and/or pathophysiological stimuli and carry out active de novo synthesis of certain proteins, which are critical for their functions. This, together with the enhanced regeneration of the platelet pool, may be a reason for increased thrombus formation and MI after CABG and other major surgery. Our findings suggest a need for reinforced antiplatelet therapy to reduce this increased risk of MI.


  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Disclosure of Conflicts of Interest
  9. References

We are grateful to E. Wallgren at the Cardiology Unit, R. Stålesen, and M. Daleskog at the Clinical Pharmacology Unit, Department of Medicine, Karolinska University Hospital, Solna, for their excellent technical support. This research was supported by Stockholm City Council (SLL), the Swedish Heart-Lung Foundation, the Swedish Research Council and Karolinska Institutet.

Disclosure of Conflicts of Interest

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Disclosure of Conflicts of Interest
  9. References

The authors state that they have no conflict of interest.


  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Disclosure of Conflicts of Interest
  9. References
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