The Association between Glycosylated Hemoglobin Level and Platelets Reactivity in Patients with Diabetes Mellitus Undergoing Elective Coronary Artery Bypass Grafting.

BACKGROUND: Diabetic patients tend to have increased platelet reactivity after coronary artery bypass grafting (CABG). The aim of this study was to determine the association between hemoglobin A1c (HbA1c) values and platelet reactivity and to evaluate the consequent impact on clinical outcomes in patients undergoing CABG. METHODS: This prospective observational trial consecutively enrolled 225 diabetic patients undergoing CABG, between February 2014 and October 2018. HbA1c levels and platelet function (multiple electrode aggregometry [MEA]) were analyzed the day before surgery and on postoperative day 4 (POD 4). Patients were divided into two groups according to the HbA1c value: HBA1c < 7% and HbA1c ≥ 7%. RESULTS: Significantly higher postoperative ASPI (platelet function test based on arachidonic acid) and ADP (platelet function test based on adenosine diphosphate) test values were observed at POD 4 compared with preoperative values (ASPI test: p < 0.001; ADP test: p < 0.001). The prevalence of preoperative aspirin resistance (AR) was 46.4% relative to 57.2% after surgery showing consistent increase in postoperative AR by approximately 10%. In addition, the prevalence of AR in the HbA1c < 7% group was higher by 10% compared with the HbA1c ≥ 7% group, both before and after surgery. We did not demonstrate differences in clinical outcomes between the HbA1c groups. CONCLUSION: Perioperative assessment of platelet reactivity in diabetic patients detects those with AR who may be at increased risk of adverse ischemic events. A personalized approach guided by MEA and administration of early and more potent antiaggregation therapy after CABG can be beneficial in this group of patients.

Starting Pediatric VAD Program: Transforming Challenges into Opportunities; A Case Series of a Single Center.

BACKGROUND: The prevalence of heart failure is constantly increasing in both children and adults. End-stage heart failure in children unresponsive to medical therapy has limited treatment options. Surgical options include heart transplantation or implantation of durable ventricular assist devices (VADs). To start the VAD program, it was necessary to train core team members, invite experienced proctors and adjust the organizational approach. METHODS: We present our first seven pediatric patients who underwent a VAD implantation with primary indication end-stage dilated cardiomyopathy. RESULTS: The median age on implant was four and a half years and the median duration of VAD support was 39 days with long term survival achieved in three patients. The causes of death were multiorgan failure, thromboembolic events, sepsis, and low cardiac output syndrome. Ischemic stroke was the reason for successful neurointervention during VAD support in two patients. CONCLUSIONS: To establish a VAD program, numerous specialties must be included with adequate training and learning for all team members.

Successful separation of xypho-omphalopagus conjoined twins with extrauterine twin-twin transfusion syndrome: a case report.

Conjoined twining is a rare medical phenomenon, with an overall prevalence of 1.47 per 100 000 births. This report describes a successful separation of xypho-omphalopagus conjoined twins complicated by unbalanced blood shunting through the porto-systemic anastomoses within the shared liver parenchyma. Significant extrauterine twin-twin transfusion syndrome caused by unbalanced shunting is an extremely rare, and probably under-recognized, hemodynamic complication in conjoined twins necessitating urgent separation. Progressive deterioration with a poor outcome can be prevented if the condition is recognized in a timely manner.

Preoperative Anaesthesiologic Evaluation of Patient with Known Allergy.

Anaphylaxis is an unanticipated systemic hypersensitivity reaction which can produce deleterious effects, even death, if not treated promptly. Preventive approach implies taking a thorough anamnesis with the emphasis on previously diagnosed allergies. If an allergic reaction occurred during previous surgery, a detailed documentation of administered anaesthetic agents and drugs would be crucial for the following anaesthesiologic management. Preoperative planning and avoiding cross-reactivity with drugs commonly used during anaesthesia are the key points to prevent an anaphylaxis. In case of emergency surgery when the exact identification of allergens is not possible, premedication prophylaxis should be considered. General measures for prevention of anaphylaxis could be undertaken as well, such as the choice of anaesthesiologic drugs and techniques in the operating theatre adequately equipped for the management of predictable anaphylaxis.

Results of extracorporeal life support implementation in routine clinical practice: single center experience.

AIM: To describe our experience in the clinical application of extracorporeal life support (ECLS) and analyze whether ECLS leads to acceptable clinical outcomes in patients with cardiac failure. METHODS: Data from clinical database of University Hospital Center Zagreb, Croatia, on 75 patients undergoing ECLS support from 2009 to 2014 due to cardiac failure were retrospectively analyzed. Outcomes were defined as procedural and clinical outcomes. ECLS as a primary procedure and ECLS as a postcardiotomy procedure due to inability to wean from cardiopulmonary bypass were analyzed. RESULTS: ECLS was used in 75 adult patients, and in 24 (32%) of those procedural success was noted. ECLS was implemented as a primary procedure in 36 patients and as a postcardiotomy procedure in 39 patients. Nine out of 39 (23.08%) patients had postcardiotomy ECLS after heart transplantation. Bleeding complications occurred in 30 (40%) patients, both in primary (11/36 patients) and postcardiotomy group (19/39 patients). ECLS was established by peripheral approach in 46 patients and by central cannulation in 27 patients. In 2 patients, combined cannulation was performed, with an inflow cannula placed into the right atrium and an outflow cannula placed into the femoral artery. Eleven patients treated with peripheral approach had ischemic complications. CONCLUSION: ECLS is a useful tool in the treatment of patients with refractory cardiac failure and its results are encouraging in patients who otherwise have an unfavorable prognosis. Patient outcomes may be further improved by technological advances, more clinical experience in application of the technique, careful patient selection, and multidisciplinary approach in patient management.

Bleeding risk assessment using multiple electrode aggregometry in patients following coronary artery bypass surgery.

Individual variability in the response to antiplatelet therapy (APT), frequently administered preoperatively, has been established by various platelet function assays and could reflect bleeding tendency after coronary artery bypass surgery (CABG). Our hypothesis is that multiple electrode whole-blood aggregometry (MEA) can identify patients at risk for excessive bleeding. We enrolled 211 patients (155 male and 56 female) undergoing isolated CABG in a prospective observational study. Patients were divided into four groups with respect to their preoperative APT management. MEA, using the ASPI and the ADP test, was performed prior to surgery. The primary endpoint was chest tube output (CTO) and the secondary endpoint was perioperative packed red blood cell concentrate (PRBC) administration. Patients were characterized as bleeders if their 24 h CTO exceeded the 75th percentile of distribution. 24 h CTO value of 11.33 ml/kg presented 75th percentile of distribution, thus cut-off value for "bleeder category". The proportion of patients characterized as bleeders was significantly different among the groups in regard to preoperative APT (p = 0.039). Significant differences in both ASPI (p < 0.001) and ADP (p = 0.038) tests were observed between different preoperative APT groups. Significant correlations between the ASPI test (r = -0.170, p = 0.014) and ADP test (r = -0.206, p = 0.003) with 24 h CTO were found. The receiver operating curve revealed an ASPI test value of <20 area under curve (AUC) units (AUC 0.603, p = 0.023) and an ADP test <73 AUC (AUC 0.611, p = 0.009) as a "bleeder" determinant. The proportion of patients transfused with PRBC did not significantly differ among the groups in regard to preoperative APT (p = 0.636). Comparison of the ASPI test values between patients with respect to PRBC administration revealed lower values in the ASPI test in a group of patients transfused with PRBC (mean, 27.88 vs. 40.32 AUC, p = 0.002). Our study showed that MEA is a useful method of predicting CABG patients with excessive postoperative bleeding.

Bleeding risk assessment using whole blood impedance aggregometry and rotational thromboelastometry in patients following cardiac surgery.

Excessive bleeding after cardiopulmonary bypass (CPB) is risk factor for adverse outcomes after elective cardiac surgery (ECS). Differentiating between patients who bleed due to surgical issues and those whose excessive chest tube output (CTO) is due to coagulopathy, remains challenging. Bedside suitable tests to identify hemostatic disturbances and predict excessive bleeding are desirable. The study sought to evaluate prediction of excessive bleeding after ECS using two bedside suitable devices for platelet function and viscoelastic blood clot properties assessment. We enrolled 148 patients (105 male and 43 female) undergoing ECS in a prospective observational study. Patients were characterized as bleeders if their 24 h CTO exceeded the 75th percentile of distribution. Multiple electrode aggregometry (MEA, with ASPI, ADP and the TRAP test) and rotational thromboelastometry (TEM, with ExTEM, HepTEM and FibTEM test), were performed at three time points: preoperatively (T1), during CPB (T2), and after protamine administration (T3). The primary endpoint was CTO and the secondary endpoint was administration of blood products, 30-day and 1 year mortality. The best predictors of increased bleeding tendency were the tests performed after protamine administration (T3). At T3, patients characterized as bleeders had significantly lower MEA ASPI (median, 14 vs. 27 AUC, p = 0.004) and ADP test values (median, 22 vs. 41 AUC, p = 0.002) as well as TEM values expressed in maximum clot firmness after 30 min (MCF 30) for ExTEM (53 vs. 56 mm, p = 0.005), HepTEM (48 vs. 52 mm, p = 0.003) and FibTEM (8 vs. 11 mm, p < 0.001) test. 24 h CTO inversely correlated with both the MEA (ASPI test: r = -0.236, p = 0.004; ADP test: r = -0.299, p < 0.001), and TEM MCF 30 (ExTEM: r = -0.295, p < 0.001; HepTEM: -0.329, p < 0.001; FibTEM: -0.377, p < 0.001) test values. Our study showed that MEA and TEM are useful methods for prediction of excessive bleeding after ECS. In order to prevent excessive postoperative CTO, hemostatic interventions with timely and targeted blood component therapy according to MEA and TEM results should be considered.

Assessment of platelet function by whole blood impedance aggregometry in coronary artery bypass grafting patients on acetylsalicylic acid treatment may prompt a switch to dual antiplatelet therapy.

Residual platelet reactivity (RPR) following coronary artery bypass grafting (CABG) might be related to thrombotic complications and major ischemic cardiac events. The aim of this study was to evaluate the changes in platelet reactivity monitored pre- and postoperatively using multiple-electrode aggregometry (MEA) and to propose an alternative therapeutic approach in a subgroup of patients with postoperative RPR. Ninety-nine patients undergoing elective CABG were enrolled in the study, of whom 41 (41.4%) were diabetic. Preoperatively, all patients received 100 mg acetylsalicylic acid (ASA), with 47 of 99 (47.4%) patients receiving an additional 75 mg clopidogrel (CLO). The blood samples were drawn the day before surgery, and on the first and 4th postoperative day. Platelet count and fibrinogen level were documented, as well as type and daily dose of antiplatelet therapy (APT) received pre- and postoperatively. Multiple-electrode aggregometry using tests based on arachidonic acid (ASPI test) and adenosine diphosphate (ADP test) was performed on the day before and 4 days after surgery. Preoperatively, we detected 31 of 99 (31.3%) patients with RPR (ASPI > 30 AUC). Platelet count correlated with both the ASPI (P = 0.03) and ADP (0.002) tests. Fibrinogen correlated with ADP test values (P < 0.001) and was found to have a higher level in the diabetic subgroup (P = 0.01). In comparison with preoperative results, we detected higher values of ASPI test postoperatively (P = 0.04), with 46 of 99 (46.5%) patients having RPR despite a higher dose of 300 mg ASA being administered. Postoperatively, diabetic patients had higher ASPI test values (P = 0.01), and a higher proportion of patients with RPR compared with the nondiabetic subgroup (58.5 vs 38%, P = 0.04). The subgroup of patients with detected ASPI >30 AUC at the 4th postoperative day consequently received as a part of our clinical routine an additional 75 mg CLO per day, in terms of platelet inhibition optimization. Multiple-electrode aggregometry can recognize patients with RPR during both the pre- and post-CABG period. Postoperatively administered ASA (300 mg) did not sufficiently inhibit platelet aggregation in 46.5% of post-CABG patients. In this group of patients a switch to dual APT should be considered.

Definition of acetylsalicylic acid resistance using whole blood impedance aggregometry in patients undergoing coronary artery surgery.

A beneficial effect of acetylsalicylic acid (ASA) on vein graft patency has been described, but some patients experience adverse cardiac events despite appropriate ASA treatment. Study aim was to define ASA resistance using Multiple electrode aggregometry (MEA) preoperatively in group of patients undergoing coronary artery bypass grafting (CABG). Prospective observational trial at University Hospital Center Zagreb enrolled 131 patients scheduled for CABG, and divided them into 4 groups with respect to preoperative antiplatelet therapy (APT). Group 1 received 100 mg ASA per day, Group 2 100 mg ASA + 75 mg clopidogrel per day, Group 3 75 mg clopidogrel per day, and Group 4 did not receive any APT. MEA with ASPI test (sensitive to ASA) and ADP test (sensitive to clopidogrel) was performed prior to surgery. In Group 1, patients were characterized as ASA resistant if their ASPI test value exceeded the 75th percentile distribution. Study enrolled 131 patients. Significant differences both in the ASPI (p < 0.001) and the ADP test (p = 0.038) were observed between patients in different APT groups. In Group (1) ASPI test value of 30 AUC presented 75th percentile of distribution, thus indicating ASA resistance. Group 2 patients had slightly lower ADP test values, but no significant difference occurred (mean 60.05 vs. 63.32 AUC, p = 0.469). In Group 1 and 2, significant correlations between the ADP test and both, platelet count (r = 0.347, p < 0.001) and fibrinogen level (r = 0.364, p < 0.001) were observed. Association between low response to ASA and post-CABG major adverse ischemic events risk increase has been described thus indicating need for ASA resistant patients detection. In patients with preoperative ASPI test exceeding 30 AUC postoperative, ASA dose adjustment or clopidogrel addition according to MEA results should be considered.

[Disorders of hemostasis in chronic renal failure and renal transplantation]. / Poremecaj hemostaze u bolesnika s kronicnim bubreznim zatajenjem i nakon transplantacije bubrega.

The presence of end-stage renal disease (ESRD) has been associated with profound clinical effects on hemostasis ranging from thrombosis to bleeding complications. The pathogenesis of uremic bleeding is multifactorial. It has been attributed to platelet dysfunction, the most important feature, particularly platelet-platelet and platelet-vessel wall interactions. Renal replacement therapy has helped reduce bleeding episodes, but the risk of morbidity and mortality due to hemorrhage persists. Abnormalities of blood coagulation and fibrinolysis predispose uremic patients to hypercoagulable state carrying the risk of atherosclerotic cardiovascular disease and thrombotic complications such as thrombosis of the vascular access wall. There are differences in the measurement of various hemostatic parameters in patients with ESRD concerning treatment with either hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD). Hemostatic disturbances are overlapped by changes in the coagulation/fibrinolytic system after renal transplantation (RT). Despite the etiology, renal transplant patients are at an increased risk of thromboembolic events as a consequence of prothrombotic clotting and fibrinolytic abnormalities. This hypercoagulable state is to a large extent associated with immunosuppressive drugs. This review will give a summary of views on hemostasis in patients with ESRD and after RT.

Intragastric Application of Aspirin, Clopidogrel, Cilostazol, and BPC 157 in Rats: Platelet Aggregation and Blood Clot.

We suggest that the stable gastric pentadecapeptide BPC 157 may rescue thrombocyte function. We focused on the antithrombotic agent aspirin, clopidogrel, and cilostazol application in rats; arachidonic acid, ADP, collagen, and arachidonic acid/PGE1 platelet aggregation (aggregometry) and blood clot viscoelastic properties (thromboelastometry); and the pentadecapeptide BPC 157. Rats received intragastrically for three days once daily treatment with antithrombotic agents-aspirin (10 mg/kg) or clopidogrel (10 mg/kg) or cilostazol (10 mg/kg). Medication (BPC 157 (10 µg/kg) or an equal volume of saline (5 ml/kg)) was given intragastrically, immediately after each antithrombotic agent application. For multiple electrode aggregometry and modified rotational thromboelastometry studies, blood sampling was at 2 h after last application. Adenosine diphosphate (ADP test 6.5 µM), arachidonic acid (ASPI test 0.5 mM), a combination of arachidonic acid and prostaglandin E1 (ASPI test 0.5 mM and PGE1-test 30 nM), and collagen (COL test 3.2 µg/ml) were used as aggregation agonists. Given with aspirin, clopidogrel, or cilostazol in rats, BPC 157 counteracted their inhibitory effects on aggregation activated by arachidonic acid, ADP, collagen, and arachidonic acid/PGE1. Specifically, this includes recovery of the aggregation induced by arachidonic acid (vs. aspirin, vs. clopidogrel, and vs. cilostazol), arachidonic acid/PGE1 (vs. cilostazol), ADP (vs. clopidogrel), or collagen (vs. clopidogrel). Contrarily, there is no effect on the used tests (extrinsic/intrinsic hemostasis system, the fibrin part of the clot) EXTEM, INTEM, and FIBTEM; clotting time; clot formation time; alpha-angle; maximum clot firmness; lysis index after 30 minutes; and maximum lysis. In conclusion, we revealed that BPC 157 largely rescues thrombocyte function.

Activated coagulation time vs. intrinsically activated modified rotational thromboelastometry in assessment of hemostatic disturbances and blood loss after protamine administration in elective cardiac surgery: analysis from the clinical trial (NCT01281397).

BACKGROUND: Excessive bleeding after cardiopulmonary bypass (CPB) is risk factor for adverse outcomes after elective cardiac surgery (ECS). Although many different point-of-care devices to diagnose hemostatic disturbances after CPB are available, the best test is still unclear. The study aim was to compare the accuracy of hemostatic disorder detection between two point-of-care devices. METHODS: We enrolled 148 patients (105 male and 43 female) undergoing ECS in a prospective observational study. Rotational thromboelastometry (TEM, with InTEM test), and Activated coagulation time (ACT) measurement were performed 15 min after protamine administration. The cohort group was divided into two subgroups according to occurrence of excessive postoperative bleeding. Endpoints were defined in two ways: as total amount of chest tube output (CTO) and blood product transfusion requirements. RESULTS: Total amount of CTO value of 1507,50 mL presented 75th percentile of distribution, thus cut-off value for bleeder category. InTEM parameters, but not ACT, correlated significantly with CTO. InTEM parameters with the strongest correlation to CTO were tested for accuracy in predicting excessive postoperative bleeding using ROC analysis. InTEM A 10 value of 38 mm, InTEM A 20 value of 49 mm and InTEM A 30 value of 51 mm delineated bleeding tendency. Patients with total amount of CTO exceeding 75th percentile were more frequently transfused with fresh frozen plasma (51.4% vs. 9.9%, p < 0.001), fibrinogen concentrate (21.6% vs. 2.7%, p = 0.001) and platelet concentrate (13.5% vs. 0.9%, p = 0.004). CONCLUSION: Our study showed that InTEM test, but not ACT is useful in prediction of bleeding tendency after protamine administration following weaning from CPB. InTEM test could be used as a first line test in screening of possible hemostatic disorder following protamine administration.