The international normalized ratio overestimates coagulopathy in patients after major hepatectomy

Abstract BACKGROUND: The International Normalized Ratio (INR) is commonly used to guide therapy after hepatectomy. We hypothesized that the use of thrombelastography (TEG) would demonstrate a decreased incidence of hypocoagulability in this patient population. METHODS: Seventy-eight patients were prospectively enrolled before undergoing hepatectomy. INR, TEG, and coagulation factors were drawn before incision, postoperatively, and on postoperative days 1, 3, and 5. RESULTS: Patients demonstrated an elevated INR at all postoperative time points. However, TEG demonstrated a decreased R value postoperatively, with subsequent normalization. Other TEG measurements were equivalent to preoperative values. All procoagulant factors save factor VIII decreased postoperatively, with a simultaneous decrease in protein C. CONCLUSIONS: TEG demonstrated a brief hypercoagulable state after major hepatectomy, with coagulation subsequently normalizing. The INR significantly overestimates hypocoagulability after hepatectomy and these data call into question current practices using the INR to guide therapy in this patient population. Ó 2014 Elsevier Inc. All rights reserved. Partial hepatectomy remains the treatment of choice for a wide range of both benign and malignant diseases of the liver. Following major hepatectomy, derangement of hepatic synthetic function has been well characterized, including impaired synthesis of serum clotting factors and regulatory proteins

Hypercoagulability is most prevalent early after injury and in female patients

Hypercoagulability after injury is a major source of morbidity and mortality. Recent studies indicate that there is a gender-specific risk in trauma patients. This study was performed to determine the course of coagulation after injury and to determine whether there is a gender difference. We hypothesized that hypercoagulability would occur early after injury and that there would be no difference between men and women. This was a prospective cohort study. Inclusion criteria were admission to the intensive care unit, Injury Severity Score > 4, and the ability to obtain consent from the patient or a relative. A Thrombelastograph (TEG) analysis was performed and routine coagulation parameters and thrombin-antithrombin complexes were measured within 24 hours of injury and then daily for 4 days. Sixty-five patients met criteria for entry into the study. Their mean age was 42 +/- 17 years and their mean Injury Severity Score was 23 +/- 12. Forty patients (62%) were men. The prevalence of a hypercoagulable state by TEG was 62% on day 1 and 26% on day 4 (p < 0.01). Women were significantly more hypercoagulable on day 1 than men as measured by the time to onset of clotting (women, 2.9 +/- 0.7 minutes; men, 3.9 +/- 1.5 minutes; p < 0.01; normal, 3.7-8.3 minutes). Mean platelet counts, international normalized ratios, and partial thromboplastin times were within normal limits throughout the study. Thrombin activation as measured by thrombin-antithrombin complexes decreased from 34 +/- 15 microg/L on day 1 to 18 +/- 8 microg/L (p < 0.01) on day 4, consistent with the prevalence of hypercoagulability by TEG. Hypercoagulability after injury is most prevalent during the first 24 hours. Women are more hypercoagulable than men early after injury. The TEG is more sensitive than routine coagulation assays for the detection of a hypercoagulable state

Thromboelastogram-guided enoxaparin dosing does not confer protection from deep venous thrombosis: a randomized controlled pilot trial

The incidence of deep venous thrombosis (DVT) remains high in general surgery and trauma patients despite widespread prophylaxis with enoxaparin. A recent study demonstrated decreased incidence of DVT if patients on enoxaparin had a change in R time (ΔR) of greater than 1 minute when heparinase-activated thromboelastography (TEG) was compared with normal TEG. We hypothesized that using ΔR-guided dosing would result in decreased DVT rates. A prospective, randomized controlled trial was performed at a Level 1 trauma center. Both trauma and general surgery patients were included. Upon enrollment, demographic data including age, sex, body mass index, and Acute Physiology and Chronic Health Evaluation II score were obtained. Enrolled patients were randomized to standard (30 mg twice a day) or TEG-guided dosing. Dose-adjusted patients underwent daily enoxaparin titration to achieve an ΔR of 1 minute to 2 minutes. Venous thromboembolism screening was performed per institutional protocol. Antithrombin III (AT-III) and anti-Xa levels were drawn at peak enoxaparin concentrations. A total of 87 patients were enrolled. There was no difference in demographic data between the groups. No pulmonary emboli were identified. The control group had a DVT rate of 16%, while the experimental group had a rate of 14% (p = nonsignificant). The experimental group's median enoxaparin dosage, 50 mg twice a day, was significantly higher than that of the control (p < 0.01). TEG ΔR was not different between the control and experimental groups. Beginning at Day 3, anti-Xa levels were higher in the experimental group (p < 0.05). There was no difference in AT-III activity between the two groups; 67% of the patients demonstrated AT-III deficiency. TEG adjusted enoxaparin dosing led to significant increases in anti-Xa activity, which did not correlate with a decreased DVT rate. Failure to reduce the DVT rate and increase ΔR despite increased dosing and increased anti-Xa activity is consistent with the high rate of AT-III deficiency detected in this study cohort. These data suggest that the future of DVT prevention may not lie in the optimization of low molecular weight heparin therapy but rather in compounds that increase antithrombin directly or operate independently of the AT-III pathway. Therapeutic study, level III