• Pre-operative levels of cell-derived microparticles as a risk factor for post-operative coagulopathy in patients undergoing valve heart surgery
  • Mehrnaz Abdolalian,1 Elham Khalaf Adeli,2,* Fatemeh Yari,3
    1. Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Iranian Blood Transfusion Organization (IBTO), Tehran, Iran
    2. Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran
    3. Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran


  • Introduction: Valvular heart disease (VHD) is one of the most common heart problems worldwide. Most VHD patients require heart surgery to repair or replace a defective valve under cardiopulmonary bypass (CPB). Post-operative coagulopathy and bleeding is an important complication of cardiac surgery that increases mortality. Multiple surgical factors such as CPB induce coagulopathy. Cell-derived microparticles (MPs) are membrane vesicles with a size ranges from 0.1 to 1 µm. MPs levels are higher in valve heart disease in comparison to healthy subjects. MPs are procoagulant because they accelerate coagulation cascade and thrombin generation. There are evidences that low levels of MPs are associated with bleeding episodes. Recently, MPs have been used as biomarkers to predict complication of diseases. In this present study, the role of pre-operative MPs as a risk factor for post-operative coagulopathy in patients undergoing heart valve surgery will be investigated.
  • Methods: This cohort case saries study was performed from January to march 2021 on forty (n=40) adult patients undergoing heart valve surgery with CPB at shaheed rajaie cardiovascular medical and research Center. Plavix was discontinued 5 days prior to surgery and warfarin was discontinued 72 hours before surgery. Patients with anemia, known bleeding disorders, emergency surgery and re-exploration were excluded. Informed written consent was obtained from all subjects. Clinical and laboratory data of patients were collected. Before induction of anesthesia, Venous blood samples were drawn into a plastic vacuum tubes containing 3.2% sodium citrate. MPs were isolated with centrifugation. Total pre-operative concentration of MPs was determined using Bradford method. Flow cytometry analysis was performed to determine MPs count and phenotype using the following monoclonal antibodies: CD41-FITC for platelet-derived microparticles (PMPs) ,and CD14-PE for monocyte-derived microparticles (MMPs).To determine the MPs size and their quantification was used Yellow-green microbeads with 1.0 μm in diameter. Data were analyzed with IBM SPSS 25.0 statistical software. Post-operative coagulopathy was defined aPTT>48s or INR>1.5. Comparison of concentration and MPs count between coagulopathic and non-coagulopathic patients was performed using Mann-whitney U test. The relationship between pre-operative concentration and MPs count whit post-operative routine coagulation test (INR, aPTT) and ICU(24h) bleeding were assessed using Spearman rank correlation analysis. The role of MPs level as a risk factor for post-operative coagulopathy was performed using univariate and multivariate logistic regression analysis. Statistical significance was considered as P< 0.05.
  • Results: In post-operative stage, 32.5% of patients were coagulopathic and 67.5% of patients were non-coagulopathic. ICU-bleeding was significantly higher in coagulopathic patients compared to non-coagulopathic patients (P=0.02). The pre-operative MPs concentration was significantly lower in coagulopathic patients compared to non-coagulopathic patients (P=0.006). Comparison of PMPs and MMPs count were not significant between two groups. After correlation analysis, The pre-operative MPs concentration was correlated negatively to post-operative aPTT and INR (Respectively, P= 0.003 ρ=-0.45, P=0.02 ρ=-0.35 ). The univariate logistic regression analysis for post-operative coagoulopathy indicated that pre-operative MPs concentration led to the elevated risk of coagulopathy (OR 0.988; 95%CI 0.978-0.999; P=0.02). Through further multivariate logistic analysis and considering confounding variables such as CPB time, cross clamp time and operation time, pre-operative MPs concentration was found to be risk factor for occurrence of post-operative coagulopathy (OR 0.989; 95%CI 0.978-0.999; P=0.04).
  • Conclusion: Considering the role of MPs in hemostasis and accelerating coagulation cascade; in this present study, patients with low MPs concentration in pre-operative stage, had longer routine coagulation tests in post-operative stage. Therefore presurgical MPs concentration was considered as main risk factors for post-operative coagulopathy in patients undergoing heart valve surgery.
  • Keywords: Cell derived microparticles, Coagulopathy, Cardiac surgery