Heparin Sensitivity Index Research Articles

The association between heparin sensitivity index and postoperative blood loss in Chinese patients undergoing elective off-pump coronary artery bypass grafting: a single center retrospective study

BackgroundThe heparin sensitivity index (HSI) is closely associated with perioperative ischemic events and increased blood loss in cardiac surgery. Previous studies have produced conflicting results. Therefore, this study aimed to investigate the relationship between HSI and postoperative blood loss specifically in Chinese patients undergoing elective off-pump coronary artery bypass grafting (OPCAB).MethodsPatients underwent OPCAB between March 2021 and July 2022 were retrospectively included. Enrolled patients were classified into Low-HSI (HSILOW; HSI < 1.3) and Normal-HSI (HSINORM; HSI ≥ 1.3) groups. HSI = [(activated clotting time (ACT) after heparin) – (baseline ACT)] / [loading dose of heparin (IU/kg)]. Primary outcome included postoperative blood loss at 24 h. Secondary outcomes were total postoperative blood loss, transfusion requirement of red blood cell (RBC), fresh frozen plasma (FFP), platelet concentrates (PC), and other complications.ResultsWe retrospectively analyzed 303 Chinese OPCAB patients. HSILOW group had higher preoperative platelet (PLT) count (221 × 109/L vs. 202 × 109/L; P = 0.041) and platelet crit (PCT) value (0.23% vs. 0.22%; P = 0.040) compared to HSINORM group. Two groups showed no significant differences in postoperative blood loss at 24 h (460 mL vs. 470 mL; P = 0.252), total blood loss (920 mL vs. 980 mL; P = 0.063), RBC transfusion requirement (3.4% vs. 3.1%; P = 1.000), FFP transfusion requirement (3.4% vs. 6.2%; P = 0.380), and other complications. Preoperative high PLT count was associated with low intraoperative HSI value (odds ratio: 1.006; 95% confidence interval: 1.002, 1.011; P = 0.008).ConclusionsIntraoperative HSI value was not associated with postoperative blood loss in Chinese patients undergoing OPCAB. Preoperative high PLT count was an independent predictor of low intraoperative HSI value.

Relationship between estimated and observed heparin sensitivity indices in cardiac and thoracic aortic surgery

BackgroundLittle evidence exists on the relationship between the estimated heparin sensitivity index (HSI) based on commonly available clinical and laboratory data and observed HSI in the adult population. This retrospective study assessed the relationship between the observed and estimated HSIs.MethodsThis study was conducted in an academic, single-institution setting. Patients aged ≥ 20 years who underwent cardiac and thoracic aortic surgery and requiring cardiopulmonary bypass were included. Clinical and laboratory data, including age, sex, and platelet count, were collected. The fibrinogen-albumin ratio index was calculated by dividing the fibrinogen value by the albumin value, multiplied by 10.The HSI was calculated using the formula: (activated clotting time after initial heparin administration—baseline activated clotting time)/initial heparin dose (IU/kg). The estimated HSI was based on the results of multiple regression analysis that included clinically relevant factors. The intraclass correlation coefficient between the observed and estimated HSIs was used to assess.ResultsIn total, 560 patients with valid activated clotting time (ACT) values after initial heparin administration were included in the final analysis to explore associated factors using the estimated HSI. Multiple regression analysis revealed that hemodialysis, platelet count, fibrinogen-to-albumin ratio index, baseline activated clotting time, and initial heparin dose were significantly associated with the HSI. The mean (standard deviation) observed and estimated HSIs were 1.38 (0.43) and 1.55 (0.13), respectively, with an intra-class correlation coefficient of 0.10.ConclusionsThe correlation between the observed and estimated HSIs was low, and a formula with high accuracy for estimating the HSI is needed.

Patients with infective endocarditis undergoing cardiac surgery have distinct ROTEM profiles and more bleeding complications compared to patients without infective endocarditis.

The coagulation system is crucial in the pathogenesis of infective endocarditis and undergoes significant changes during course of the disease. However, little is known about the implications of those changes in the perioperative period. Aim of the present study was to delineate the specific coagulation patterns and their clinical consequence in patients undergoing cardiac surgery due to infective endocarditis. In this single-centre, exploratory, prospective observational study, we investigated the incidence and degree of coagulopathy in patients with (n = 31) and without infective endocarditis (n = 39) undergoing cardiac valve surgery. The primary outcome was the differences between these two groups in rotational thromboelastometry (ROTEM) results before, during and after surgery. The secondary outcomes were the differences between the groups in heparin sensitivity, bleeding complications, and transfusion requirements. Most ROTEM parameters in EXTEM, INTEM and FIBTEM assays were significantly altered in patients with infective endocarditis. Clotting time in the EXTEM assay was significantly prolonged in the endocarditis group at all time-points, while all clot firmness parameters (A5, A10 and MCF) were significantly increased. The heparin sensitivity index was significantly lower in the endocarditis group (median index 0.99 vs 1.17s. IU-1.kg-1, p = .008), indicating increased heparin resistance. Patients with infective endocarditis had more bleeding complications as assessed by the universal definition of perioperative bleeding score (OR 3.0, p = .018), and more patients with endocarditis underwent early re-exploration (p = .018). The findings of this exploratory investigation show significantly altered coagulation profiles in patients with infective endocarditis, with concomitant hyper- and hypocoagulability. Furthermore, the incidence of bleeding complications and transfusion requirements were increased in patients with endocarditis. These results show the potential of ROTEM to detect coagulation abnormalities in patients with infective endocarditis. Existing point-of-care coagulation testing guided algorithms for optimizing perioperative coagulation management possibly need to be adjusted for these high-risk patients undergoing cardiac surgery.

Infective Endocarditis Is a Risk Factor for Heparin Resistance in Adult Cardiovascular Surgical Procedures: A Retrospective Study

Heparin resistance (HR), defined as a decrease in heparin responsiveness, can result in adverse events with prolonged duration of surgery. Although some clinical risk factors have been suggested, the relationship with the surgical diagnosis is unclear. The aim of present study was to elucidate the clinical predictors of HR including the surgical diagnosis. This retrospective cohort study determined the incidence of HR (defined as activated clotting time [ACT] <400 seconds after 250-350 IU/kg of heparin administration) and heparin sensitivity index (HSI) was calculated from the rate of change in ACT per heparin dose. Preoperative demographic data, medication history, and laboratory data also were analyzed. Single institution, tertiary care hospital. Adult patients who underwent cardiovascular surgery with cardiopulmonary bypass between January 2012 and September 2018. None. Of 287 patients, 88 (30.7%) were classified as HR. In univariate analysis, infective endocarditis (IE), platelet count, and serum fibrinogen and albumin levels were associated with HR. After adjustment for baseline ACT and initial heparin dose, IE (odds ratio 4.57, [95% CI: 1.10-19.1]; p=0.037) and albumin ≤3.5 g/dL (3.17, [1.46-6.93]; p=0.004) were associated independently with HR. Patients with IE had significantly lower HSI than those with other diseases. All HR patients were treated with additional heparin, and 17 of them received human antithrombin-III concentrate. Infective endocarditis and preoperative hypoalbuminemia were associated independently with HR. The optimal anticoagulation strategy for patients with these risk factors requires further investigations based on the authors' findings.

Application of goal-directed therapy for the use of concentrated antithrombin for heparin resistance during cardiac surgery.

The maintenance of anticoagulation in adult patients undergoing cardiopulmonary bypass is dependent upon a number of factors, including heparin concentration and adequate antithrombin activity. Inadequate anticoagulation increases the risk of thrombosis and jeopardizes both vascular and extracorporeal circuit integrity. The purpose of this study was to evaluate a goal-directed approach for the use of antithrombin in patients who were resistant to heparin. Following institutional review board approval, data were obtained from quality improvement records. A goal-directed protocol for antithrombin was established based upon heparin dosing (400 IU kg-1 body weight) and achieving an activated clotting time of ⩾500 seconds prior to cardiopulmonary bypass. Two groups of patients were identified as those receiving antithrombin and those not receiving antithrombin. Outcome measures included activated clotting time values and transfusion rates. Consecutive patients (n = 140) were included in the study with 10 (7.1%) in the antithrombin group. The average antithrombin dose was 1,029.0 ± 164.5 IU and all patients had restoration to the activated clotting time levels. Patients in the antithrombin group were on preoperative heparin therapy (80.0% vs. 24.6%, p = 0.001). Prior to cardiopulmonary bypass the activated clotting time values were lower in the antithrombin group (417.7 ± 56.1 seconds vs. 581.1 ± 169.8 seconds, p = 0.003). Antithrombin patients had a lower heparin sensitivity index (0.55 ± 0.17 vs. 1.05 ± 0.44 seconds heparin-1 IU kg-1, p = 0.001), received more total heparin (961.3 ± 158.5 IU kg-1 vs. 677.5 ± 199.0 IU kg-1, p = 0.001), more cardiopulmonary bypass heparin (22,500 ± 10,300 IU vs. 12,100 ± 13,200 IU, p = 0.016), and more protamine (5.4 ± 1.2 vs. 4.1 ± 1.1 mg kg-1, p = 0.003). The intraoperative transfusion rate was higher in the antithrombin group (70.0% vs. 35.4%, p = 0.035), but no differences were seen postoperatively. Utilization of a goal-directed algorithm for the administration of antithrombin for the treatment of heparin resistance is effective in patients undergoing cardiac surgery.

Heparin sensitivity and postoperative blood loss in patients undergoing cardiac surgery with cardiopulmonary bypass.

Heparin-associated coagulation disorder is an important factor related to postoperative bleeding in patients undergoing cardiac surgery with cardiopulmonary bypass. Currently, the relationship between heparin sensitivity and postoperative bleeding is unknown. To investigate the relationship between individual heparin sensitivity and postoperative blood loss in patients undergoing cardiac surgery. Prospective controlled study. Tertiary teaching hospital, Urumqi, Xinjiang, PR China. The study was conducted from January 2016 to August 2018. A total of 195 adult patients undergoing cardiac valve replacement surgery were included. After initial heparin dosing (2.5 mg kg), patients were divided into three groups according to the whole blood activated clotting time (ACT): group A, insensitive group (ACT < 480 s); group B, sensitive group (480 s < ACT < 750 s); group C, hypersensitive group (ACT > 750 s). First, intra-operative and 24-h postoperative blood loss. Second, antithrombin (AT) and factor X mRNA levels. Third, the plasma levels of AT-III and factor X. Fourth, heparin sensitivity index. Blood loss was approximately 20 to 25% lower in group B than in groups A and C, which was statistically significant (P < 0.01). The AT-III mRNA levels increased from groups A to C and was positively associated with heparin sensitivity; the factor X mRNA levels changed in the opposite direction; a significant difference was observed between groups A and C (P < 0.05). The factor X plasma level showed the same trend as its mRNA. The AT-III plasma level was significantly lower in group B than in groups A and C (P < 0.05). Postoperative blood loss is related to heparin sensitivity in patients undergoing cardiac surgery, and the moderately sensitive patients have the least postoperative bleeding. Individual variation in heparin sensitivity is related to the mRNA and plasma levels of AT-III and factor X. Registration number ChiCTR-RPC-17012259.

Preoperative Low-Molecular-Weight Heparin Prophylaxis Associated with Increased Heparin Resistance Frequency in On-Pump Coronary Artery Bypass Graft Surgery.

Background Unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) are being used for preoperative management of critical coronary artery disease. However, preoperative UFH therapy may cause a reduction in antithrombin concentrations, leading to various degrees of heparin resistance (HR). The main purpose of this study is to investigate the effects of preoperative LMWH on HR during cardiopulmonary bypass (CPB). Methods Data were retrospectively reviewed from adult patients that underwent on-pump coronary artery bypass graft (CABG) surgery. Four hundred fifty-seven patients underwent CABG, and 139 of them, who had isolated on-pump CABG, were included in the study. The heparin sensitivity index was calculated if activated clotting time levels were discovered below 400 seconds. Values less than 1.3 were accepted as HR. Results Of 139 patients who underwent on-pump CABG, preoperative LMWH was administered in 59 patients (56.8%). Intraoperative HR occurred in 29 patients (20.9%). Patients who received preoperative LMWH had an increased risk of developing HR compared with patients who did not receive LMWH (odds ratio 4.8 and 95% confidence interval 1.7–13.5). CPB duration and aortic clamp duration were significantly longer in patients who developed intraoperative HR when compared to those in patients who did not develop HR. Conclusion Preoperative treatment with LMWH may cause intraoperative HR. Corrective and preventive arrangements with close follow-up should be performed in this group of patients.

Predicting Heparin Responsiveness in Children Before Cardiopulmonary Bypass: A Retrospective Cohort Study.

Inadequate or excess administration of unfractionated heparin for cardiopulmonary bypass (CPB) can cause significant harm. Age-dependent differences in the pharmacodynamics and pharmacokinetics of heparin contribute to increased variability of heparin responsiveness in children. The aims of the current study were to (1) examine the correlation between predicted and observed heparin responsiveness in children before CPB measured using the Hemostasis Management System (HMS) Plus (Medtronic, Minneapolis, MN), (2) describe age-specific reference intervals for heparin sensitivity index (HSI) observed in children, and (3) test predictive models of HSI using preoperative clinical and laboratory data. In this retrospective cohort study, children (ages ≤17 years) who required therapeutic heparinization for CPB in a 40-month period between September 2010 and December 2013 were investigated. Children weighing ≥45 kg or with a height ≥142 cm were excluded. HSI was defined as the difference between activated clotting time after heparin administration and the baseline activated clotting time divided by the heparin-loading dose (IU) per kilogram. Lin's concordance correlation coefficient was used for the primary analysis of the relationship between predicted and observed HSI. Reference intervals were calculated for HSI using medians and 2.5% and 97.5% percentiles according to established guidelines for clinical and laboratory standards. Nonparametric regression analyses were used to model the relationship between HSI (dependent variable) and preoperative covariates (independent variables). A total of 1281 eligible children were included in the final analysis. Overall, there was a moderate correlation between predicted and observed HSI measured using HMS Plus System (rho_c = 0.46; 95% confidence interval, 0.41-0.50; P < .001). Sixty-five percent (829 of 1281) of predicted HSI values were less than observed. From adjusted regression models, HSI was best predicted by preoperative international normalized ratio, platelet count, and weight, but this model accounted for only 25% of the variance in HSI. In a large cohort of children, heparin responsiveness before CPB was not reliably predicted by either in vitro measurement using the HMS Plus System or commonly available preoperative clinical and laboratory data. We describe age-specific reference intervals for HSI in children, and we anticipate that these data will aid the identification of heparin resistance in this population.

Antithrombin activity and heparin response in neonates and infants undergoing congenital cardiac surgery: a retrospective cohort study.

The immature coagulation system during infancy has age-related physiological differences in proteins that contribute to significant variation in heparin responsiveness through alterations in heparin-enhanced thrombin inhibition. The primary aim of this study was to evaluate the relationship between preoperative antithrombin (AT) activity and heparin responsiveness in neonates and infants undergoing congenital cardiac surgery. In this retrospective cohort study, neonates (aged 0-28 days) and infants (aged 29-365 days) undergoing congenital cardiac surgery in the 12-month period from October 2013 to 2014 were studied. The two age groups were compared for the primary endpoint of heparin response measured by the heparin sensitivity index (HSI), with heparin loading doses and heparin resistance being secondary endpoints. Multivariable linear regression analyses were used to explore the relationship between AT activity and heparin response measured by HSI. There were 122 infants and 19 neonates included in the study. After adjusting for low-molecular-weight heparin, unfractionated heparin, and platelet count, there was a significant relationship between AT activity and HSI (r = 0.44; P = 0.009). The median [interquartile range] HSI did not differ between neonates and infants (0.76 [0.69- 0.98] vs 0.89 [0.70-1.10] sec·unit(-1)·kg(-1), respectively; median difference, 0.08; 95% confidence interval [CI], -0.01 to 0.17; P = 0.182), despite the mean (standard deviation) AT activity differing between age groups [60 (16)% vs 84 (18)%, respectively; mean difference, 24; 95% CI, 15 to 32; P < 0.001]. There was a moderate relationship between AT activity and heparin response measured by HSI. Comparing neonates and infants, there was similar heparin responsiveness measured by HSI despite differing AT activity levels. These findings should help guide the perioperative administration of exogenous AT to neonates and infants and suggest that, outside the neonatal period, preoperative AT activity may be used to identify children at risk of decreased heparin responsiveness.

Heparin Dose and Postoperative Bleeding in Patients Undergoing Cardiopulmonary Bypass

Heparin is the most widely used anticoagulant for cardiopulmonary bypass (CPB). Several authors suggest that lower doses of heparin during CPB would produce lower postoperative chest tube losses and fewer transfusion events. In the present study, a heparin dose–response (HDR) test was used to determine the heparin dose for each patient. We hypothesize that higher doses of heparin do not cause increased postoperative bleeding and transfusion events in postoperative patients undergoing CPB when the heparin dose is determined by a HDR test. This prospective observational study followed 66 patients undergoing CPB-supported primary coronary artery bypass grafting. Patients were placed in one of two groups, sensitive (n = 37) or resistant (n = 29) based on the result of a HDR test slope. Data on patient characteristics, secondary outcomes, transfusion, and the primary outcome, chest tube losses, were collected. Patient characteristics differed in the baseline activated coagulation time (ACT) and thromboelastograph G parameter as well as number of patients with hypercholesterolemia. The resistant group had lower postheparin and postprotamine ACTs and heparin sensitivity index. Initial heparin dose, total heparin dose, heparin dose per kilogram, HDR, and protamine dose were higher in the heparin-resistant group. The primary outcome, postoperative chest tube loss volume, was collected at four time points and the two groups were then compared. The heparin-resistant group was noninferior to the sensitive group and had clinically fewer transfused patients and transfusion events. The resistant group was noninferior to the sensitive group with respect to chest tube losses at all measured time points. Higher doses of heparin determined by a HDR test do not cause increased postoperative chest tube losses or increased transfusion events.

An Evaluation of Factors Affecting Activated Coagulation Time

Although failure to achieve an adequate activated coagulation time (ACT) after full heparinization before cardiopulmonary bypass often is attributed to antithrombin (AT) deficiency, it remains unclear if this is a causative mechanism of decreased heparin responsiveness. Therefore, the authors determined the relationship between AT and other coagulation-related factors that affect the ACT measurement and heparin sensitivity index before the establishment of cardiopulmonary bypass. Observational study. University medical center. Adult elective cardiac surgical patients. Preoperative data collection included demographics, type of preoperative medical therapy, hemoglobin, platelet count, and AT. Intraoperative measurements included ACT and anti-Xa activity. Of the 203 patients enrolled in this study, 10% (n = 21) did not achieve an adequate ACT (≥400 seconds) after full heparinization. Subnormal AT activity (55%-79%) was not related to a low ACT and a low heparin sensitivity index. Preoperative low-molecular-weight heparin therapy did not cause a decreased ACT response. However, preoperative low hemoglobin levels and high platelet counts were associated with a decreased ACT. All these observations suggest that failure to achieve an adequate ACT is, in general, not an indicator of AT deficiency but could be affected by high platelet counts and low hemoglobin levels.

The influence of heparin resistance on postoperative complications in patients undergoing coronary surgery

SummaryBackgroundHeparin resistance is relatively frequent in patients undergoing coronary surgery. We aimed to assess the impact of heparin resistance on the outcome of patients undergoing coronary surgery with cardiopulmonary bypass (CABG). Three definitions of heparin resistance were adopted.Material/MethodsWe performed a retrospective review of 756 consecutive patients undergoing isolated CABG. All anaesthesia records were reviewed manually. Heparin resistance was recognized if: ACT was less than 400 seconds after 300 U/kg heparin (local criteria), ACT was less than 480 seconds after 400 U/kg or more heparin (stringent criteria), or if heparin sensitivity index was lower than 1.3. Postoperative assessment included perioperative morbidity and mortality. A multiple logistic regression model was used to investigate the influence of all demographic, preoperative and surgical variables, as well as heparin resistance (variably defined) on hospital mortality and postoperative complications.ResultsHeparin sensitivity index, local criteria and stringent criteria identified 64.8%, 12.0% and 4.3% heparin resistant patients, respectively. Heparin-resistant patients more frequently had preoperative heparin administration, unstable course of coronary artery disease, and higher coronary symptoms scoring. Severe form of heparin resistance (expressed by the ACT less than 480 seconds after 400 U/kg heparin) was an independent predictor of death (OR 4.92; CI 1.11–21.89).ConclusionsMild forms of heparin resistance are relatively frequent and are not associated with increased morbidity and mortality. The isolation of severe heparin resistance as an independent predictor of death in our large cohort of coronary patients suggests that this phenomenon should be given more attention in future studies.

Heparin responsiveness during off-pump coronary artery bypass graft surgery: predictors and clinical implications

To evaluate the clinical impact of reduced heparin responsiveness (HR(reduced)) on the incidence of myocardial infarction (MI) following off-pump coronary artery bypass graft surgery (OPCAB), and to identify the predictors of HR(reduced). A total of 199 patients scheduled for elective OPCAB were prospectively enrolled. During anastomosis, 150 U/kg of heparin was injected to achieve an activated clotting time (ACT) of ≥ 300 s, and the heparin sensitivity index (HSI) was calculated. HSIs below 1.0 were considered reduced (HR(reduced)). The relationships between the HSI and postoperative MI, cardiac enzyme levels and preoperative risk factors of HR(reduced) were investigated. There was no significant relationship between the HSI and cardiac enzyme levels after OPCAB. The incidence of MI after OPCAB was not higher in HR(reduced) patients. HR(reduced) occurred more frequently in patients with low plasma albumin concentrations and high platelet counts. HR(reduced) was not associated with adverse ischemic outcomes during the perioperative period in OPCAB patients, which seemed to be attributable to a tight prospective protocol for obtaining a target ACT regardless of the presence of HR(reduced).

Activated Clotting Times, Heparin Responses, and Antithrombin

Activated Clotting Times, Heparin Responses, and Antithrombin

Heparin Dose Response Is Independent of Preoperative Antithrombin Activity in Patients Undergoing Coronary Artery Bypass Graft Surgery Using Low Heparin Concentrations

Unfractionated heparin's primary mechanism of action is to enhance the enzymatic activity of antithrombin (AT). We hypothesized that there would be a direct association between preoperative AT activity and both heparin dose response (HDR) and heparin sensitivity index (HSI) in patients undergoing coronary artery bypass graft surgery. Demographic and perioperative data were collected from 304 patients undergoing primary coronary artery bypass graft surgery. AT activity was measured after induction of general anesthesia using a colorimetric method (Siemens Healthcare Diagnostics, Tarrytown, NY). Activated coagulation time (ACT), HDR, and HSI were measured using the Hepcon HMS Plus system (Medtronic, Minneapolis, MN). Heparin dose was calculated for a target ACT using measured HDR by the same system. Multivariate linear regression was performed to identify independent predictors of HDR. Subgroup analysis of patients with low AT activity (<80% normal; <0.813 U/mL) who may be at risk for heparin resistance was also performed. Mean baseline ACT was 135 ± 18 seconds. Mean calculated HDR was 98 ± 21 s/U/mL. Mean baseline AT activity was 0.93 ± 0.13 U/mL. Baseline AT activity was not significantly associated with baseline or postheparin ACT, HDR, or HSI. Addition of AT activity to multivariable linear regression models of both HDR and HSI did not significantly improve model performance. Subgroup analysis of 49 patients with baseline AT <80% of normal levels did not reveal a relationship between low AT activity and HDR or HSI. Preoperative AT activity, HDR, and HSI were not associated with cardiac troponin I levels on the first postoperative day, intensive care unit duration, or hospital length of stay. Although enhancing AT activity is the primary mechanism by which heparin facilitates cardiopulmonary bypass anticoagulation, low preoperative AT activity is not associated with impaired response to heparin or to clinical outcomes when using target ACTs of 300 to 350 seconds.

Stabilized Infective Endocarditis and Altered Heparin Responsiveness During Cardiopulmonary Bypass

Although active infective endocarditis (IE) is known as a risk factor for decreased heparin responsiveness during cardiopulmonary bypass (CPB), evidence is lacking in patients with stabilized IE. We investigated whether heparin responsiveness was still altered in stabilized IE patients undergoing cardiac surgery in a prospective, controlled trial. A total of 16 patients with stabilized IE without signs of active inflammation (IE group) and 48 patients without systemic infection (control group) undergoing valve surgery were included. Heparin responsiveness was assessed using the heparin sensitivity index (HSI), whereas heparin resistance was defined as an activated clotting time (ACT) occurring less than 400 s after the initial heparinization. Preoperative antithrombin III activity was lower and fibrinogen level was higher in the IE group. ACT after initial heparinization was shorter in the IE group. The HSI was lower and the number of patients with HSI <1.0 was greater in the IE group. Heparin resistance occurred more frequently in the IE group. Heparin responsiveness during CPB was significantly reduced in the IE group, and it seems to be associated with preoperative hypercoagulability and reduced antithrombin III activity. Therapeutic measures such as the administration of antithrombin III concentrate should be considered in these patients even when they are in a stabilized condition without active inflammation.

Preoperative low molecular weight heparin reduces heparin responsiveness during cardiac surgery

Cardiac surgery with cardiopulmonary bypass requires systemic anticoagulation, defined by an activated clotting time (ACT) of 400-480 sec. Patients with altered heparin responsiveness require disproportionately higher doses of heparin to achieve this target ACT. A common risk factor for heparin resistance is preoperative heparin therapy. Recently, therapy with low molecular weight heparin (LMWH) has become an acceptable substitute for prolonged heparin therapy. The current study examines the effect of preoperative LMWH therapy on subsequent heparin responsiveness during cardiac surgery. Records of patients undergoing cardiac surgery with cardiopulmonary bypass over a period of four months were reviewed. We identified patients who, during the week preceding surgery, had received prolonged (>24 hr) therapy with either sc LMWH (LMWH group) or continuous iv unfractionated heparin (Heparin group). A Control group consisted of patients who received neither heparin nor LMWH preoperatively. The heparin sensitivity index (calculated as the first change in ACT from baseline divided by the first intraoperative heparin dose, normalized to body weight), was compared among groups using ANOVA. One hundred and thirty-nine patients were included in the analysis. The heparin sensitivity index was 33-45% higher in the Control group (1.6+/-0.7 sec.IU-1.kg-1; P<0.0001) compared to the LMWH (1.2+/-0.4 sec.IU-1.kg-1) and Heparin (1.1+/-0.5 sec.IU-1.kg-1) groups. In a multivariable model, the use of preoperative LMWH remained a significant predictor of reduced intraoperative heparin responsiveness (P=0.002). Prolonged preoperative LMWH therapy, similar to the known effect of prolonged unfractionated heparin infusion, reduces subsequent intraoperative response to heparin.

Risk factors for fatal myocardial infarction after coronary bypass graft surgery

Background and objective The incidence and clinical impact of perioperative myocardial infarction during coronary artery bypass graft surgery vary greatly depending upon the diagnostic criteria applied. Fatal perioperative myocardial infarction has a less arguable diagnosis and clinical impact. The aim of this paper is to find out the risk factors for fatal myocardial infarction after coronary surgery. Methods Data from 1561 consecutive patients, who underwent coronary revascularization during a 10-month period, have been retrospectively analysed. After an univariate analysis for pre- and intraoperative risk factors, a multivariate model (logistic regression analysis) was settled. Results Preoperative use of subcutaneous/intravenous heparin, a heparin sensitivity index < 1.3 and need for a thromboendarterectomy of the left anterior descending coronary artery are independent risk factors for fatal myocardial infarction. The relative risk for fatal myocardial infarction was about 2 in the case of preoperative heparin use or heparin sensitivity index < 1.3 and 5.5 in the case of thromboendarterectomy of the left anterior descending coronary artery. Conclusions In patients undergoing coronary artery bypass surgery, preoperative anticoagulation management with heparin may represent a risk factor for fatal myocardial infarction. Patterns of heparin resistance, whether or not due to heparin pretreatment, seem to be closely related to fatal myocardial infarction.

Risk factors for fatal myocardial infarction after coronary bypass graft surgery.

The incidence and clinical impact of perioperative myocardial infarction during coronary artery bypass graft surgery vary greatly depending upon the diagnostic criteria applied. Fatal perioperative myocardial infarction has a less arguable diagnosis and clinical impact. The aim of this paper is to find out the risk factors for fatal myocardial infarction after coronary surgery. Data from 1561 consecutive patients, who underwent coronary revascularization during a 10-month period, have been retrospectively analysed. After an univariate analysis for pre- and intraoperative risk factors, a multivariate model (logistic regression analysis) was settled. Preoperative use of subcutaneous/intravenous heparin, a heparin sensitivity index < 1.3 and need for a thromboendarterectomy of the left anterior descending coronary artery are independent risk factors for fatal myocardial infarction. The relative risk for fatal myocardial infarction was about 2 in the case of preoperative heparin use or heparin sensitivity index < 1.3 and 5.5 in the case of thromboendarterectomy of the left anterior descending coronary artery. In patients undergoing coronary artery bypass surgery, preoperative anticoagulation management with heparin may represent a risk factor for fatal myocardial infarction. Patterns of heparin resistance, whether or not due to heparin pretreatment, seem to be closely related to fatal myocardial infarction.