Sermin Tetik

Thromboelastography-Based Transfusion Algorithm Reduces Blood Product Use after Elective CABG: A Prospective Randomized Study

Abstract  Objective: Bleeding and allogeneic transfusion remain constant problems in cardiac surgical procedures. In this study, we aimed to test the role of a routine thromboelastography (TEG)‐based algorithm on bleeding and transfusions in patients undergoing elective coronary artery bypass grafting (CABG). Methods: Patients (n = 224) undergoing elective CABG with cardiopulmonary bypass were prospectively randomized into two groups according to transfusion strategy: in group 1 (clinician‐directed transfusion, n = 110) need for blood transfusion was based on clinicians discretion and standard coagulation tests and in group 2 (TEG algorithm group, n = 114) kaolin‐activated (k) TEG‐based algorithm‐guided perioperative transfusion management. Transfusion, blood loss, and outcome data were recorded. Results: There were no differences in consumption of packed cell units, blood loss, re‐exploration for bleeding, and early clinical outcome between the groups. Patients in the TEG group had significantly lower median units of fresh frozen plasma and platelets compared with the other group (p = 0.001). The median number of total allogeneic units transfused (packed cells and blood products) was significantly reduced in the TEG group compared with the other group (median 2, range 1–3 units vs. median 3, range 2–4 units, respectively, p = 0.001). The need for tranexamic acid was significantly diminished in the TEG group compared with the other group (10.3% vs. 19%, respectively, p = 0.007). Conclusion: Our results show that routine use of a kTEG‐guided algorithm reduces the consumption of blood products in patients undergoing elective CABG. Adopting such an algorithm into routine management of these patients may help to improve clinical outcome and reduce the potential risks of transfusion‐related complications and total costs after CABG.

The impact of platelet functions and inflammatory status on the severity of preeclampsia

Abstract Objective: To find out whether there is a correlation between the extent of platelet activation and inflammation and the severity of preeclampsia (PE) in the third trimester of pregnancy. Methods: Forty-one women with PE (n = 23 severe, n = 18 mild) and 80 normotensive pregnant (NP) women were included in the study. Their blood samples were obtained and interleukin (IL)-8 and IL-10 levels measured by an enzyme-linked immunosorbent assay. Basal CD61 and CD62P expressions on CD41-positive platelets were analyzed with the use of flow-cytometry. Platelet aggregation was induced by adenosine diphosphate and determined by aggregometry. Results: CD62P expression was increased in severely preeclamptic women, and the platelet aggregation was decreased in both mildly and severely preeclamptic women in comparison with NP women. However, CD61 expression was similar among the groups. An enhanced inflammatory response was seen in severely preeclamptic women demonstrated by increased levels of IL-8 and decreased levels of IL-10. However, the intensity of platelet activation did not correlate directly with the change in plasma levels of IL-8 and IL-10 in preeclamptic women. Conclusions: Platelets may have a role in the inflammatory response in PE. However, the severity of inflammation is found to be independent from the intensity of platelet activation in preeclamptic women. This seems to be related to mechanisms causing alterations of cytokine levels such as IL-8 and IL-10, rather than platelet activation.

Postoperative Statin Therapy Attenuates the Intensity of Systemic Inflammation and Increases Fibrinolysis After Coronary Artery Bypass Grafting

A total of 25 patients undergoing coronary artery bypass grafting (CABG) were included in the study. Patients received statin (20 mg daily) postoperatively for 2 weeks. All analyses were performed at 2 different time points: preoperatively (group 1) and 2 weeks after operation (group 2). Interleukin (IL)-6, IL-8, plasminogen activator inhibitor 1 (PAI-1), tumor necrosis factor α (TNF-α), tissue plasminogen activator (t-PA) levels, and tissue factor pathway inhibitor (TFPI) were evaluated. Statin treatment caused a significant reduction in the plasma level of PAI-1 (preop: 15.04 ± 0.13 ng/mL vs postop: 13.89 ± 2.14 ng/mL; P < .05) and increased t-PA levels (preop: 109.74 ± 0.13 vs postop: 231.40 ± 1.22 ng/mL; P < .001). Plasma TNF-α and IL-6 levels did not change with treatment. Statin treatment caused a significant reduction in plasma IL-8 level (279.70 ± 3.42 ng/mL vs postop: 207.18 ± 3.63 ng/mL, P < .05), and TFPI (4.87 ± 2.05 ng/mL vs postop: 6.27 ± 1.25 ng/mL; P < .05). The results demonstrate that atorvastatin attenuates systemic inflammatory reaction after cardiac surgery.

Oxidative Modification of Fibrinogen Affects Its Binding Activity to Glycoprotein (GP) IIb/IIIa

Aim: Proteins are sensitive biomarkers of human diease condition associated with oxidative stress. Alteration of protein structures by oxidants may result in partial or complete loss of protein functions. We have investigated the effect of structural modifications induced by metal ion catalyzed oxidation of fibrinogen on its binding capacity to glycoprotein IIb/IIIa (GpIIb/IIIa) and human platelets. Methods: We identified and quantified of binding capacity of native and oxidized fibrinogen to its receptor in vitro by flow cytometer. Dityrosine formation on oxidized fibrinogen were detected spectrophotometrically. Elevated degradation products of fibrinogen after oxidation were revealed in the HPLC analysis. The native and oxidized fibrinogen were analyzed on mass spectrum upon digestion with tyripsin. Results: Oxidatively modified fibrinogen showed less binding activity than native fibrinogen to GpIIb/IIIa coated micro beads and human platelets whereas slightly higher binding capaticity to ADP induced stimulated platelets. Formation of dityrosines in the amino acid side chains of fibrinogen were observed upon oxidation. Decreased binding capacity of oxidized fibrinogen correlated with intensities of dityrosine formation. Oxidized fibrinogen had more ion-mass intensities at higher than native fibrinogen. Clinical implications: Important point is decreased of binding capacity of the oxidized fibrinogen to own receptor. The decreased rate of binding, leading to effect in the diseases of clot formation may acount for the association between oxidation of fibrinogen and the incidence of effect in human diseases.

Low-Density Lipoprotein Specifically Binds Glycoprotein IIb/IIIa: A Flow Cytometric Method for Ligand-Receptor Interaction

Primary platelet aggregation requires agonist-mediated activation of membrane receptor glycoprotein (GP) IIb/IIIa, binding of fibrinogen to GpIIb/IIIa, and cellular events after fibrinogen binding. This study investigated whether fibrinogen receptor GpIIb/IIIa is also the binding site for low-density lipoprotein (LDL) in platelets by using GpIIb/IIIa-coated polystyrene microbeads incubated with various concentrations of fluorescein isothiocyanate (FITC)-labeled ligands. Binding was assayed by flow cytometry. Binding of fibrinogen (Fg)-FITC and LDL-FITC to GpIIb/IIIa coated microbeads was concentration dependent, reaching saturation. Binding of LDL-FITC to GpIIb/IIIa coated microbeads was inhibited by fibrinogen. Binding of LDL-FITC or Fg-FITC to freshly isolated platelets gave similar results as those of GpIIb/IIIa coated microbeads. Glycoprotein IIb/IIIa, the fibrinogen receptor on platelets is also one of the binding sites of LDL on platelets. This rapid and reliable flow cytometric technique using coated microbeads may be used as a first step for the study of all ligand receptor interactions.

The protective effects of tacrolimus on rat uteri exposed to ischemia-reperfusion injury: a biochemical and histopathologic evaluation

OBJECTIVE To evaluate the effects of the immunosuppressant tacrolimus as an antioxidant and analyze the histopathologic changes in rat uteri exposed to experimental ischemia-reperfusion (I/R) injury. DESIGN Experimental study. SETTING Experimental surgery laboratory in a university. ANIMAL(S) Twenty-eight female rats exposed to experimentally induced uterine I/R injury. INTERVENTION(S) Group I: control group; group II: uterine I/R injury-induced group; group III: pre-ischemia tacrolimus group; group IV: post-ischemia tacrolimus group. MAIN OUTCOME MEASURE(S) Uterine tissue malondialdehyde (MDA) level as a marker of lipid peroxidation and glutathione (GSH) level and superoxide dismutase (SOD) and catalase (CAT) activities as markers of tissue antioxidant capacity; histopathologic examination of all uterine rat tissue. RESULT(S) Following aortic I/R injury, MDA levels were significantly increased whereas GSH levels and CAT and SOD activities were found to be decreased compared with control animals. MDA levels were found to recover prominently after the administration of tacrolimus in both groups III and IV. Administration of tacrolimus improved uterine GSH levels and CAT activity in the tacrolimus-treated groups. CONCLUSION(S) Our results indicate that tacrolimus reduces oxidative damage in rat uteri exposed to I/R injury induced by distal abdominal aortic occlusion. Histologic evaluation reveals that tacrolimus attenuates the inflammatory response and protects the tissue damage induced by I/R injury.

Composition of the Essential Oil of Cistus parviflorus L. from Turkey

Abstract Water distilled essential oil of Cistus parviflorus L. from Turkey was analyzed by GC/MS. Seventy-six representing 89.4% of the oil were identified. 8-α-13-oxy-14-ene-epilabdane (18.2%), manoyl oxide (9.1%) and δ-cadinene (6%) were characterized as major constituents.

Effect of Oxidized Fibrinogen on Hemostatic System: In Vitro Study

Standard coagulation assays were performed with control and oxidized fibrinogen (Fg), using prothrombin time (PT; 12.5 ± 0.4 vs 25 ± 0.8 seconds, P < .001) and activated partial thromboplastin time (aPTT; 33 ± 2.5 vs 63 ± 4.7 seconds, P < .001). Fibrin clot (MA), clot formation initiation (r), and rate of clot lysis (LY30) were measured, a reflection exposure of Fg to Fe3+/ ascorbate oxidative system by thrombelastograph (TEG) analysis (0, 6, 12, 24, and 48 hours, 6.2 ± 1.3 vs 5.5 ± 1.2, 4.3 ± 1.0 [P < .01], 3.9 ± 1.6, 3.2 ± 0.8, [P < .001]). Maximum amplitude level was found to be lower than control (69.1 ± 7.2 vs 67.9 ± 12.4, 64.0 ± 11.4, 60.2 ± 21.2, 42.2 ± 15.2, P < .001). The lysis rate was changed according to oxidation time between Fg exposed to Fe3+/ascorbate and control exposed to Fe 3+/ascorbate for the same treatment time (1.9 ± 0.71 vs 7 ± 0.5, 1.6 ± 0.1, 1.2 ± 0.5, 0.9 ± 1.3, P < .001). We revealed dysregulation of hemostatic system with contribution of oxidized Fg, which was in direct proportion to the intensity of Fg oxidation.

Clopidogrel Provides Significantly Greater Inhibition of Platelet Activity Than Aspirin When Combined With Atorvastatin After Coronary Artery Bypass Grafting: A Prospective Randomized Study:

Objective: We aimed to compare the effects of 2 different antiplatelet agents on platelet activity in patients receiv- ing atorvastatin after coronary artery bypass grafting (CABG). Methods: We prospectively randomized 50 patients undergoing CABG into 2 groups; group 1 started to receive atorvastatin (10 mg) plus clopidogrel (75 mg; C + A, n = 25) and group 2 atorvastatin (10 mg) and acetylsalicylic acid (ASA; 300 mg, ASA + A, n = 25) daily on postoperative day 1 and continued for 6 months after operation. Adenosine diphosphate (ADP)–induced pla- telet aggregation and the expressions of glycoprotein (Gp) IIb, GpIIIa, P-selectin, and fibrinogen (Fg) and low-density lipoprotein (LDL) binding to platelets were assessed preoperatively and at postoperative days 7, 90, and 180. Results: The mean age of the patients was 59.6 ± 7.6 years, and 82% of the patients were males. The combination of C + A markedly inhibited ADP-induced platelet aggregation compared with ASA + A at postoperative days 90 and 180 (52% ± 6.0% vs 56% ± 7.25% and 19.6% ± 3.2% vs 37% ± 4.1%, P = .039 and P = .0001, respectively). The therapy of C + A significantly suppressed the expressions of GpIIIa at postoperative days 7, 90, and 180 (P = .0001, P = .0001, and P = .0001, respectively) and P-selectin at postoperative days 90 and 180 (P = .035 and P = .002, respectively) when compared to ASA + A. The expression of GpIIb was also significantly depressed at postoperative day 180 in group 1 when compared to group 2 (P = .0001). Low-density lipoprotein binding was significantly increased at day 180 postoperatively in both the groups (basal: 42.9% ± 5.6% vs 45.3% ± 4.4% and day 180: 60.3% ± 4.6% vs 61.8% ± 5.7%, P = .0001). Conclusions: Our results demonstrate that the combination of C + A is more effective than that of ASA + A in inhibiting ADP-mediated platelet aggregation and expression of major platelet receptors after CABG.

Composition of the Essential Oil of Cistus laurifolius L. from Turkey

Abstract The water distilled essential oil of Cistus laurifolius L. from Turkey was analyzed by GC/MS. Sixty four compounds representing 67% of the oil were identified. Borneol (6.1%) and nonacosane (2.8%) were the major constituents.