John M. Koerber

A comparison of lepirudin and argatroban outcomes

Although both argatroban and lepirudin are used for the management of heparin-induced thrombocytopenia (HIT), data comparing these agents are lacking. The objective of this project was to compare the clinical outcomes of lepirudin vs argatroban therapy. Patients who received a direct thrombin inhibitor (DTI) from January 2000 to December 2001 were identified. Medical charts were retrospectively reviewed and relevant data extracted. The primary efficacy outcome was effective anticoagulation and the primary safety outcome was major bleeding. Data were analyzed using the t test and Fisher’s exact test. Sixty-one lepirudin patients and 29 argatroban patients received a DTI during the study period. A new diagnosis of HIT was the indication for DTI therapy in 44.8% of argatroban patients and 57.4% of lepirudin patients. Effective anticoagulation was achieved in 77.8% of argatroban patients and 69.5% of lepirudin patients (p = .61). Major bleeding occurred in 10.3% and 11.5% of argatroban and lepirudin patients, respectively (p = 1.0). Argatroban and lepirudin demonstrated comparable safety and efficacy outcomes.

Correlation of activated clotting time and activated partial thromboplastin time to plasma heparin concentration.

Study Objective. To determine the correlation between activated clotting time (ACT) or activated partial thromboplastin time (aPTT) and plasma heparin concentration.

Use of the Activated Partial Thromboplastin Time for Heparin Monitoring

The objectives of the present study were to evaluate the relationship between heparin concentration and activated partial thromboplastin time (aPTT) results, define a heparin concentration-derived therapeutic range for each aPTT instrument, compare aPTT- and heparin concentration-guided dosage adjustment decisions, and compare laboratory- and bedside aPTT-guided decisions. In phase 1, 102 blood samples were analyzed for bedside and laboratory aPTTs and heparin concentration (used to establish aPTT therapeutic range). In phase 2, 100 samples were analyzed in the same manner. Correlations for aPTT compared with heparin ranged from 0.36 to 0.82. Dosage adjustment decisions guided by the aPTT agreed with those based on heparin concentration 63% to 80% of the time. Laboratory and bedside aPTT dosage adjustment decisions agreed 59% to 68% of the time. The correlation of aPTT with heparin concentration and agreement between aPTT- and heparin-guided decisions vary with the aPTT instrument. Decisions guided by laboratory aPTT results often disagree with decisions guided by bedside aPTT results.

Correlation between Activated Clotting Time and Activated Partial Thromboplastin Times

OBJECTIVE: To evaluate the correlation between clotting time tests and heparin concentration, the correlation between activated clotting time (ACT) and activated partial thromboplastin time (aPTT) results, and to compare the clinical decisions based on ACT results with those based on aPTT results. METHODS: Retrospective evaluation of a large database containing heparin concentrations, ACT results (1 device), and aPTT results (3 different instruments: 2 bedside, 1 laboratory-based). Correlations between heparin concentrations and clotting time tests and between ACT results and aPTT results were determined. Clinical decisions regarding heparin dosage adjustments based on ACT results were compared with those based on aPTT results. RESULTS: Correlations between clotting time tests and heparin concentrations were r = 0.72 for ACT and r = 0.74–0.86 for the aPTT instruments. The laboratory-based aPTT had the highest correlation to heparin concentrations. The correlation between ACT and aPTT results ranged from r = 0.64–0.67. Heparin dosage adjustment decisions based on ACT results agreed with decisions based on aPTT results 59–63% of the time. CONCLUSIONS: The laboratory-based aPTT has a stronger correlation to heparin concentration than the bedside-based aPTT and ACT. The correlation between ACT and aPTT was similar among 3 different aPTT instruments. Decisions to adjust heparin therapy based on ACT results differed from decisions based on aPTT results more than one-third of the time.

Comparing Methods of Establishing the aPTT Therapeutic Range of Heparin

BACKGROUND: The American College of Chest Physicians (ACCP) recommends that the activated partial thromboplastin time (aPTT) therapeutic range for unfractionated heparin be defined as the aPTT corresponding to a heparin concentration of 0.3–0.7 μ/mL by heparin anti-factor Xa assay. This recommendation suggests that a therapeutic range defined in this manner should be superior to traditional empiric therapeutic ranges of 1.5–2.5 times the control. A pilot study was conducted to evaluate the ACCP recommendation for heparin monitoring. OBJECTIVE: To compare heparin dosage adjustments guided by a heparin concentration–derived therapeutic range (HCDTR) with those influenced by traditional empiric therapeutic ranges for the aPTT. METHODS: This study was conducted in 2 phases. In phase 1, the various aPTT therapeutic ranges were established and/or defined. The first empiric therapeutic range (E1) was established by performing an aPTT test on healthy volunteers. This E1 was defined as 1.5–2.5 times the mean normal aPTT. A second empiric therapeutic range (E2) was defined as 1.5–2.5 times the patients baseline aPTT. The aPTT HCDTR had been defined in a previous study as 48–61 seconds. In phase 2, heparin dosage adjustment decisions guided by each empiric range and the HCDTR for the aPTT were compared with heparin dosage adjustment decisions guided by actual heparin concentrations. Decisions were in agreement when both the aPTT result and plasma heparin concentration indicated the same dosage change. Forty patients had a bedside aPTT determined prior to receiving continuous infusion heparin and again within 48 hours of heparin initiation. Plasma heparin concentration by anti-factor Xa assay was performed on the blood samples obtained after heparin initiation. Heparin dosage adjustment decisions were evaluated by determining the agreement of each aPTT test result with the corresponding plasma heparin concentration. An overall level of agreement (defined as the % of decisions that were in agreement) for each aPTT therapeutic range was determined. RESULTS: The level of agreement in dosage adjustment decisions between heparin concentration and E1, E2, and HCDTR was 28/40 (70%), 28/39 (72%), and 23/40 (58%), respectively (p = 0.34). Heparin dosage adjustment decisions based on an aPTT HCDTR did not significantly differ from heparin dosage adjustment decisions guided by traditional empiric therapeutic ranges for a bedside aPTT. CONCLUSIONS: This pilot study showed similar heparin dosage adjustment decisions using an empiric aPTT therapeutic range versus a heparin concentration–derived aPTT therapeutic range.

Major bleeding with apixaban in atrial fibrillation: patient characteristics, management, and outcomes

ABSTRACT Objectives: To identify patient characteristics, bleed management, and bleed outcomes in patients experiencing an apixaban major bleeding event and to identify opportunities to improve the safe use of apixaban. Methods: This retrospective single health-system study identified apixaban patients experiencing a major bleeding event between January 2013 and May 2016 through electronic medical record review. Patient characteristics, bleed management, and outcomes were extracted in those with a confirmed major bleed assessed by the International Society on Thrombosis and Haemostasis criteria. Results: Fifty major bleeding events occurred in 49 patients (79 ± 9.8 years). Patient characteristics included history of hypertension (94%), anemia (68%), and concomitant antiplatelet use (68%). Gastrointestinal bleeding occurred in 72% of patients and intracranial hemorrhage in 14% of patients. Packed red blood cells (PRBCs) were utilized in 82% of patients and reversal agents were administered to 6% of patients. Mortality during the hospital admission for the bleed was 0%. Anticoagulation was held at discharge in 64% of patients and remained held at 30 days in the majority of patients. Of those on concurrent aspirin therapy, an appropriate indication was not found in 64.7% of patients. Conclusions: Patients with major bleeding were elderly and frequently on inappropriate concomitant antiplatelet therapy. The majority of patients were managed with PRBC transfusion. More than half of patients had anticoagulation therapy held at discharge. Concerns with prescribing and patient management were identified leading to recommendations for improving the safe use of apixaban therapy.

905: CHARACTERIZATION OF WARFARIN MAJOR BLEEDING EVENTS IN REAL-WORLD CLINICAL PRACTICE.

Learning Objectives: Warfarin has long been the gold standard for stroke and systemic embolism prevention in atrial fibrillation. Direct oral anticoagulants offer an alternative to warfarin but lack an established reversal agent. With increased attention on anticoagulation safety, there is a need for contemporary data evaluating warfarin major bleeding in the practice setting. Methods: This single center, retrospective, observational study identified patients with a warfarin bleeding event between July 2011 and June 2014. Identification occurred through health-system adverse event reporting or by cross-referencing warfarin with ICD-9 codes for atrial fibrillation, hemorrhage, transfusion, and an INR of >1.8. Charts were reviewed to confirm the presence of a major bleed (International Society on Thrombosis and Haemostasis criteria) and temporal relationship to warfarin. Patient characteristics, bleed management, and outcomes were evaluated. Results: A random sample of 58 patients was included. Gastrointestinal and intracranial bleeds occurred in 65% and 5% of patients, respectively. The mean age was 76.3 yr. Nearly 50% of patients were admitted to the ICU. Drug interactions were present in 81% and concomitant antiplatelet therapy in 67%. Over half of patients had a history of renal dysfunction. Sixteen percent of patients had a procedure within 7 days of bleed, and 21% presented with an INR >5. Median HAS-BLED score was 4 and CHADS2 score was 3. Bleed management strategies included: procedure/surgery in 33%, blood products in 98%, vitamin K in 71%, and recombinant Factor VIIa in one patient. Anticoagulation was held at discharge in over half of patients. In-hospital and 30-day mortality were 7% and 12%, respectively. Conclusions: Patients experiencing a warfarinrelated major bleed in practice were elderly and often on interacting medications or antiplatelet therapy. Majority of bleeding events were gastrointestinal. Bleed management usually included vitamin K and blood products, while hemostatic agents were rarely used. In-hospital mortality was 7% while the 30-day mortality rate was 12%.