Beyond the platelet count: heparin antibodies as independent risk predictors.

A major potential side effect of heparin is immunogenicity, eliciting antibody development to a protein complex comprised of platelet factor 4 and heparin. Nevertheless, the clinical implications of heparin antibody positive patients remain broad, ranging from no apparent clinical consequences to life-threatening arterial and venous thromboemboli. The "Iceberg Model" has been proposed to depict this spectrum, with a relatively large population of antibody-positive patients forming the base of the iceberg, a smaller population of thrombocytopenic patients in the middle and a limited number of patients with thrombocytopenia and thrombosis comprising the apex. An underlying assumption of this model is that thrombosis occurs only in settings of relative or absolute thrombocytopenia. However, several recent studies suggest that antibody formation to platelet factor 4/heparin complexes, even in the absence of thrombocytopenia, may be associated with thrombotic events. In this review, we summarize these data, consider potential mechanisms for thrombosis, and suggest recommendations for testing and management of antibody-positive patients.

Hemostasis and glycemic control in the cardiac surgical patient.

The Centers for Disease Control and Prevention estimate that 6% of the US population meets diagnostic criteria for diabetes mellitus, with at least one third of this group being undiagnosed. A majority of adult blindness, renal insufficiency, and limb amputation may be directly attributed to diabetes. Although the incidence of type 1, autoimmune-mediated diabetes remains relatively stable, increasing age, physical inactivity, and obesity have produced explosive growth in insulin resistance and type 2 diabetes. A direct association between diabetes and atherothrombotic disease remains indisputable. However, recent data further suggest that even minor elevations of fasting plasma glucose, in "nondiabetic" subjects, increase cardiovascular risk. Alterations in hemostasis may play an important contributory role. Both hyperglycemia and hyperinsulinemia induce prothrombotic characteristics, including overexpression of vascular endothelial plasminogen activator inhibitor-1 (PAI-1), down-regulation of fibrinolysis, elevation of plasma coagulation proteins (ie, fibrinogen, factor VII, factor X), and enhanced platelet activation. Furthermore, endothelial dysfunction-characterized by an inflammatory phenotype-commonly accompanies diabetes. Given data supporting prothrombotic potential of both acute and chronic hyperglycemia, aggressive perioperative glucose control appears imperative.

Association of leukocyte-depleted blood transfusions with infectious complications after cardiac surgery.

BACKGROUND: To test the hypothesis that leukocyte-mediated immunosuppression may contribute to postoperative infections after blood transfusions, we compared the incidence of postoperative infections in patients undergoing elective coronary artery bypass graft (CABG) surgery who received either leukocyte-depleted (LD-RBCC) or non-LD transfusions of red blood cell concentrates (RBCC) within 48 h of surgery. MATERIALS AND METHODS: Data for all primary elective CABG patients between 1995 and 1998 who received allogeneic RBCC transfusions in the first 48 h after surgery were collected. Patients were divided into two groups (group LD: LD-RBCC transfusions only; group non-LD: non-LD-RBCC transfusions only were excluded). Patients who received a combination of LD and non-LD-RBCC transfusions, or any blood products other than RBCC were excluded. Infectious complications recorded included pneumonia, acute respiratory distress syndrome, mediastinitis, leg wound/sternal wound infection, nosocomial infection, catheter-related infection, urinary tract infection, decubitus ulcers, and bacteremia/fungemia. RESULTS: One hundred forty-two patients received only LD-RBCC transfusions, and 1,765 patients received only non-LD-RBCC transfusions. Power analysis demonstrated that the sample size attained 80% power to detect an odds ratio of 2.1 at a significance level of p < 0.05. Infection rates were not significantly different between the non-LD and LD groups (7.57% vs. 9.52%, p = 0.40). Leukocyte depletion status of RBCC transfusions was not a predictor of infectious complications (p = 0.73). However, total units of RBCC received was highly associated with increased infection (p = 0.0001). CONCLUSIONS: No association between postoperative infections and the use of leukocyte-depleted blood was identified. However, an increased incidence of postoperative infections was observed to be associated with blood transfusions in general.

Effect of a dexmedetomidine substitution during a nationwide propofol shortage in patients undergoing coronary artery bypass graft surgery.

STUDY OBJECTIVE: To assess the effect of substituting dexmedetomidine for propofol during a nationwide propofol shortage on postoperative time to extubation and opioid requirements in patients who underwent coronary artery bypass graft (CABG) surgery. DESIGN: Retrospective case-control study. SETTING: Single-center cardiothoracic intensive care unit (ICU) in a tertiary academic medical center. PATIENTS: Seventy adults undergoing isolated, primary, elective CABG who received dexmedetomidine between April 1 and June 30, 2010, during the propofol shortage (35 patients [cases]) or who received propofol between January 1 and March 31, 2010, or between July 1 and September 30, 2010 (35 patients [controls]) for postoperative sedation were included. Patients in the dexmedetomidine group were matched 1:1 to patients in the propofol group based on age, sex, weight, number of vessels bypassed, preoperative ejection fraction, cardiopulmonary bypass time, and aortic cross-clamp time. MEASUREMENTS AND MAIN RESULTS: The primary outcome consisted of opioid requirements in the first 12 hours after arrival to the ICU in the dexmedetomidine- and propofol-treated patients. Secondary outcomes included the time to extubation (from ICU admission until extubation) and opioid requirements in the first 24 hours. No significant demographic differences were noted between treatment groups. Median opioid requirements in the first 12 hours, as measured by morphine equivalents, were 8.0 mg in the propofol group and 7.0 mg in the dexmedetomidine group (p=0.1). Similarly, at 24 hours, opioid requirements were 16.7 and 17.3 mg in the propofol and dexmedetomidine groups, respectively (p=0.4). The time to extubation demonstrated that patients in the propofol group were extubated at a median of 300 minutes and patients in the dexmedetomidine group were extubated at a median of 318 minutes after ICU arrival (p=0.5). CONCLUSION: No statistically significant differences were noted between the propofol and dexmedetomidine groups when assessing the outcomes of opioid requirements and the time to extubation. A multicenter, prospective, randomized, blinded study is needed to determine the optimal sedative after CABG surgery.

Infectious complications after cardiac surgery: lack of association with fresh frozen plasma or platelet transfusions.

OBJECTIVE: The purpose of this study was to examine the effect of perioperative transfusion of platelets and fresh frozen plasma (FFP) on infection rates after cardiac surgery. DESIGN: Retrospective study comparing infection rates after cardiac surgery among patients receiving combinations of packed red blood cells (PRBCs), platelets, and FFP. SETTING: Tertiary care university teaching hospital. PARTICIPANTS: All elective primary coronary artery bypass (CABG) surgery patients from July 1995 to January 1998 before introduction of leukocyte-reduced blood products. INTERVENTIONS: Multivariate logistic and linear regression models were applied to identify clinical risk factors for postoperative infection and to determine the relationship between perioperative administration of PRBCs, platelets, and FFP with postoperative infection. MEASUREMENTS AND MAIN RESULTS: Transfusion of PRBCs, diabetes, age, preoperative hematocrit, and the duration of cardiopulmonary bypass were significantly associated with postoperative infection; platelet or FFP transfusion added no additional risk to PRBC transfusion alone. CONCLUSIONS: Infectious complications in a population of adult primary CABG surgery patients were not increased by transfusion of platelets or FFP. It is PRBC transfusion that confers an increased risk of postoperative infection in this population.

Preoperative anti-PF4/heparin antibody level predicts adverse outcome after cardiac surgery.

OBJECTIVE: Preexisting serum antibodies to heparin/platelet factor 4 complexes may predispose adult cardiac surgical patients to increased perioperative morbidity and mortality. We sought to determine the association between preoperative serum antibodies directed against platelet factor 4/heparin complexes and major complications (in-hospital death or length of stay >10 days) in adult cardiac surgical patients. METHODS: In a prospective observational study of 466 patients undergoing elective coronary artery bypass grafting, valvular heart surgery, or both, preoperative serum was assayed for anti-platelet factor 4/heparin antibody by using a commercially available enzyme-linked immunosorbent assay (Asserachrom HPIA). Known preoperative risk factors were assessed, and patients were assigned a risk score by using the validated method of Parsonnet and colleagues. RESULTS: Major complications (death or postoperative hospitalization >10 days) occurred in 108 patients (23%). Overall, 59 (13%) patients had a positive preoperative anti-platelet factor 4/heparin antibody screen (upper limit of normal is 0.5 optical density units). A positive assay result independently predicted an increased risk of major complications (P = .0284; odds ratio, 1.98; 95% confidence interval, 1.06-3.62) over and above the effect of the Parsonnet risk score (P < .001; odds ratio, 1.07; 95% confidence interval, 1.05-1.10). The level of preoperative anti-platelet factor 4/heparin antibody was also significantly associated with major complications (P = .036; odds ratio, 1.31; 95% confidence interval, 1.02-1.68) independently of the Parsonnet risk score. No association (P > .75) existed between the Parsonnet risk score and preoperative anti-platelet factor 4/heparin antibody level. CONCLUSIONS: Serum antibodies directed against platelet factor 4/heparin complexes are prevalent in the adult patient population undergoing cardiac surgery. The presence of these antibodies before surgery is an independent predictor for death or prolonged hospitalization after adult cardiac surgery.