Search

Abstract 4351 INTRODUCTION: While recombinant activated Factor VII (rFVIIa) is increasingly used for management of uncontrolled hemorrhage in a variety of clinical settings, its efficacy appears mixed. Few studies have examined the association between coagulation studies and rFVIIa efficacy in cardiac surgery. DESIGN/METHODS: We performed a retrospective study of all patients at Brigham and Women’s Hospital (BWH) from February 2005 through March 2011 who received rFVIIa for uncontrolled hemorrhage during or after cardiac surgery. rFVIIa-mediated hemostasis was determined based on clinical descriptions in the medical record. Laboratory studies, clinical parameters, blood product transfusions, and chest tube output were compiled from the medical record. RESULTS AND DISCUSSION: Forty-seven patients were identified for this study. The median age was 65 years (range, 16–85). Thirty-one patients were male. Eleven had a perioperative left ventricular ejection fraction < 35%. Of 47 surgeries performed, 30 were emergent or urgent and 16 elective (data was missing in 1 case). Twelve required an intraaortic balloon pump, and 12 placement or removal of a ventricular assist device. Median cardiopulmonary bypass (CPB) time was 281.5 min (range, 104–744; n = 45). Over a median follow-up period of 52 days (range, 0–1673), 22 patients (46.8%) died, 10 within one day of receiving rFVIIa. Median survival was 443 days (90% confidence interval (CI) [30, not-yet-reached]). The median dose of rFVIIa was 40.2 mcg/Kg. rFVIIa-mediated hemostasis was achieved in 23 patients (48.9%), while continued bleeding was observed in 24 (51.1%). Thromboembolic complications attributed to rFVIIa developed in 9 patients (arterial, 5; venous, 4). Median transfusion requirements decreased after rFVIIa administration for the entire population, although the differences were not statistically significant. Survival status could not be reliably incorporated into models of transfusion requirements in this retrospective study, prohibiting further analysis. Mean coagulation studies before vs after rFVIIa were: PT, 24.9 sec +/− 18.3 (n = 44) vs 15.4 sec +/− 4.9 (n = 47); INR, 2.3 +/− 2.5 (n = 44) vs 1.2 +/− 0.5 (n = 47); and PTT, 57.3 sec +/− 27.2 (n = 40) vs 48.4 sec +/− 17.8 (n = 44), respectively. Plasma fibrinogen was excluded from the analysis, as levels were not measured in over one-third of cases. Univariate analyses identified several clinical or laboratory variables associated with rFVIIa-mediated hemostasis: PT after rFVIIa administration (p = 0.02 by Fisher’s exact test), INR before rFVIIa (p = 0.05), INR after rFVIIa (p = 0.05), PTT after rFVIIa (p = 0.008), pH after rFVIIa (p = 0.04), and survival status (p = 0.008). In stepwise multivariable logistic regression analyses, only normalization of PTT after rFVIIa was significantly associated with rFVIIa-mediated hemostasis (odds ratio (OR) = 0.169, 95% CI [0.041,0.694], p = 0.01). Stepwise multivariable regression models of PT, INR, and PTT after rFVIIa showed a strong association of PTT and only a marginal association of PT with rFVIIa-mediated hemostasis (PTT: OR = 0.181, 95% CI [0.047,0.722], p = 0.02; PT: OR = 0.10, 95% CI [0.01,0.98], p = 0.05). Chest tube output was recorded for 14 patients who received rFVIIa in the CSICU rather than in an operating room. Of these, 8 (57.1%) had a reduction in chest tube output of ≥ 25% and 5 (21.4%) a reduction of ≥ 50%. While none of the variables examined showed a significant association with reduced chest tube output, concordance with rFVIIa-mediated hemostasis among this small subset of patients was poor (for ≥ 25% reduction: concordance 64.3%, 90% CI [39,84.7], p = 1.0 by McNemar’s test; for ≥ 50% reduction: concordance 57.1%, 90% CI [32.5,79.4]), p = 0.2). CONCLUSION: In cardiac surgery patients who receive rFVIIa for uncontrolled hemorrhage, normalization of PTT after rFVIIa appears to be strongly correlated with rFVIIa-mediated hemostasis. This suggests that optimal hemostasis with rFVIIa occurs following concomitant repletion of other coagulation factors in both extrinsic and intrinsic pathways, although the possibility that normalization of coagulation studies in both pathways is a marker of rFVIIa-mediated hemostasis has not been ruled out. Prospective trials may help to determine whether correction of PTT and other coagulation parameters can improve rFVIIa efficacy in cardiac surgery. Disclosures: No relevant conflicts of interest to declare.

Abstract 2062 INTRODUCTION: Diagnosis of heparin-induced thrombocytopenia (HIT) is challenging in cardiac surgery patients, as nearly all develop postoperative thrombocytopenia, and 10–50% have platelet factor 4 (PF4) IgG antibodies after surgery. Pre-test probability scores for HIT have not been widely used by cardiac surgeons at our institution due to concerns regarding thromboembolic complications in untreated HIT, leading to overuse of direct thrombin inhibitors (DTIs) as empiric therapy for postoperative thrombocytopenia. DESIGN/METHODS: From August through September 2010, we incorporated a hematologist into work rounds in the Brigham and Women's Hospital (BWH) Cardiac Surgery Intensive Care Unit (CSICU). The hematologist collaborated with cardiac surgeons to create literature-based, multidisciplinary guidelines on hematology topics in CSICU patients. For postoperative thrombocytopenia, the guidelines (1) discouraged empiric use of DTIs on postoperative days (POD) 0–3, except in suspected catastrophic HIT; (2) allowed for empiric DTI use on POD ≥ 4 while awaiting PF4 antibody test results; and (3) suggested discontinuation of DTIs after two negative PF4 antibody tests drawn on POD ≥ 4. We performed a retrospective analysis of projected DTI use in BWH cardiac surgery patients based on the guidelines. RESULTS AND DISCUSSION: From February 2010 through February 2011, 80 cardiac surgery patients received DTIs for suspicion of HIT. The median age was 72 years (range, 30–90). Forty-two patients were male. The most common procedures were aortic valve replacement (n = 36), mitral valve replacement (n = 32), and coronary artery bypass grafting (n = 31). Six required an intraaortic balloon pump. Nine were reoperations. PF4 antibody tests, performed using polytypic (Diagnostica Stago) or IgG-specific (Gen-Probe GTI Diagnostics) PF4 antibody ELISA assays, were positive in 19/80 cases (23.75%). Among a subset of 20 patients for whom pre-test probability scores were calculated, correlation between 4 T's and Lillo-Le Louet scores was poor (high probability score, 45% and 15%, respectively; concordance, 50%; p = 0.109 (McNemar's test)). Initiation of DTIs was in disagreement with the guidelines in 17/80 cases (21.25%), of which PF4 antibody tests were negative in 15 and positive in 2. Of the 15 PF4 antibody-negative cases, 12 had no evidence of thrombosis; two developed superficial or deep venous thromboses but tolerated heparin reexposure, and one with multiple negative PF4 antibody tests developed a radial artery thrombosis on POD 9 and was treated with heparin and thrombectomy. Both of the PF4 antibody positive cases were unusual presentations of HIT; in one case, the guidelines would have supported delaying initiation of DTIs by one day, which would not have changed overall clinical course for this patient. Patients in whom DTIs were started on POD ≥ 4 were more likely to test positive for PF4 antibodies than patients in the POD 0–3 group (50% vs 11.1%, respectively; p = 0.0004 (Fisher's exact test)). Almost all cases in which initiation of DTIs disagreed with the guidelines occurred in the POD 0–3 group rather than the POD ≥ 4 group (16 vs 1, respectively; p = 0.008). Overall, the guidelines would have delayed DTI initiation by approximately 1–2 days in 20% of patients and shortened duration of DTI therapy in roughly 15%, leading to a 163-day reduction in total bivalirudin use, a 7-day reduction in argatroban use, and a projected yearly cost savings of $81,414.29–83,055.82 in DTI usage, with minimal impact on patient outcomes. Since launching of these guidelines and other coordinated hospital-wide efforts, overall DTI use at BWH has decreased markedly and stabilized. CONCLUSION: Our analysis suggests a potential role for multidisciplinary clinical care models incorporating hematologists into surgical and critical care units. Disclosures: Fanikos: Baxter: ran a symposium at American Society of Health-System Pharmacists.