John R. Bartholomew

Rectus sheath hematoma

Abstract Rectus sheath hematoma (RSH) is a known complication of anticoagulation therapy and a source of potential morbidity and mortality. Early diagnosis and appropriate treatment may help to prevent complications including hemodynamic instability, the abdominal compartment syndrome or multiorgan dysfunction. Although the diagnosis can be made clinically, it can be confirmed with computed tomography of the abdomen. Most patients can be managed conservatively; however, it is often necessary to suspend anticoagulation in the acute setting. Rectus sheath hematoma is not a contraindication to resuming anticoagulation once the hematoma has been adequately managed and the patient has returned to a stable clinical baseline.

Combined Effect of Chronic Kidney Disease and Peripheral Arterial Disease on All-Cause Mortality in a High-Risk Population

BACKGROUND AND OBJECTIVES Chronic kidney disease (estimated glomerular filtration rate <60 ml/min per 1.73 m(2)) and peripheral arterial disease (ankle-brachial index <0.9) independently predict mortality. It was hypothesized that the risk for death is higher in patients with both chronic kidney disease and peripheral arterial disease compared with those with chronic kidney disease or peripheral arterial disease alone. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS A total of 1079 patients who had an ankle-brachial index and serum creatinine recorded within 90 d of each other in 1999 were studied retrospectively. Glomerular filtration rate was estimated using the Modification of Diet in Renal Disease equation. Patients were categorized into four groups: Chronic kidney disease and peripheral arterial disease, chronic kidney disease alone, peripheral arterial disease alone, or no chronic kidney disease or peripheral arterial disease. RESULTS The overall 6-yr mortality rate was 28% (n = 284). Patients with both chronic kidney disease and peripheral arterial disease had the highest mortality rate (45%) compared with patients with chronic kidney disease alone (28%), peripheral arterial disease alone (26%), and neither condition (18%). After adjustment for clinical and demographic variables, the chronic kidney disease and peripheral arterial disease group had an increased odds for death when compared with the no chronic kidney disease or peripheral arterial disease group or the single disease groups. CONCLUSIONS These findings indicate that patients with both chronic kidney disease and peripheral arterial disease have a significantly higher risk for death than patients with either disease alone.

Transitioning from argatroban to warfarin in heparin-induced thrombocytopenia: an analysis of outcomes in patients with elevated international normalized ratio (INR).

Background: Heparin-induced thrombocytopenia (HIT) can lead to catastrophic thromboembolic complications and requires treatment with an alternative, rapidly active anticoagulant, such as a direct thrombin inhibitor (DTI), either to prevent or treat these complications. Switching to oral warfarin after initial treatment with a DTI is necessary in most patients. Most references related to warfarin suggest that an increased risk for bleeding will occur with elevated international normalized ratios (INRs) > 4.6. In patients receiving argatroban, it is not uncommon to achieve an INR > 4 during this transition.Because the clinical outcomes in patients achieving an INR > 4 during combined argatroban/warfarin therapies for HIT are not well described, we evaluated the clinical outcomes of 111 patients with this phenomenon.Methods: We identified patients from the prospective studies of argatroban anticoagulation, Argatroban-911 and Argatroban–915. Data collected from these studies included death from all causes, amputation, new thrombosis, major bleeding, INR values, argatroban doses, aPTT values, platelet counts, and duration of therapy.Results: Patients were on argatroban monotherapy for a median of 2.8 (0.1–8.1) days, and on cotherapy for a median of 3.7 (0.9–12.8) days. The median platelet count was 70.9 (18–325) × 109/L at the time of HIT diagnosis and increased to 94 (30–324) × 109/L by the time warfarin was initiated. At a median argatroban dose of 1.4 (0.2–2.0) mcg/kg/min, the maximum INR ranged from 4.1 to 21.2 (median 6.4, n = 111) and the corresponding aPTT ranged from 48.1 to 105 (median 71, n = 93) seconds. After argatroban cessation, the first recorded INR within 4 to 24 hours ranged from 1.5 to 12.5 (median 2.9, n = 58). Adverse clinical outcomes occurred in 9 (8.1%) patients during cotherapy and in 12 (10.8%) patients after argatroban anticoagulation was discontinued. Adverse clinical outcomes included 7 cases of new thrombosis, 3 amputations, 12 deaths and 1 major bleed. Eleven of 12 (91.7%) patients died due to causes other than thrombosis, and most deaths (83%) occurred following cotherapy. Five (4.5%) patients developed new thrombosis during argatroban/warfarin cotherapy despite an INR > 4. In contrast only 1 (0.9%) patient experienced major bleeding.Conclusion: In patients receiving argatroban/warfarin cotherapy and with an elevated INR > 4, the risk for thrombosis exceeds the risk of bleeding. Traditional paradigms concerning elevated INRs and warfarin may need to be redesigned for the patient population on cotherapy with direct thrombin inhibitors.Abbreviated Abstract. The clinical outcomes of 111 patients with INRs > 4 while on combined argatroban (dose ≤ 2 mcg/kg/min) and warfarin were evaluated. Adverse clinical outcomes (7 new thrombosis, 3 amputations, 12 deaths and 1 major bleed) occurred in 21 patients. Eleven deaths were due to causes other than thrombosis. Five patients developed new thrombosis while only 1 had major bleeding. The risk for thrombosis exceeds the risk of bleeding in patients with HIT despite an INR > 4.

Retrievability and Device-Related Complications of the G2 Filter: A Retrospective Study of 139 Filter Retrievals

PURPOSE To evaluate the retrievability and safety of the G2 filter. MATERIALS AND METHODS A retrospective study of all G2 filter retrievals at a single institution was conducted. Hospital records and imaging studies were reviewed for complications, and factors affecting retrieval were analyzed. RESULTS From 2005 to 2009, a total of 139 patients presented for retrieval of their G2 filter, and 131 pairs of pre- and post-placement cavagrams and 39 computed tomography scans were available for analysis. The following findings were recorded: limb penetration (n = 33), tilt greater than 15° (n = 22), local migration greater than 2 cm (n = 17), retained thrombus within the filter (n = 16), deformity (n = 10), inferior vena cava (IVC) occlusion (n = 3), fracture (n = 2), and pulmonary embolism breakthrough (n = 2). A total of 118 filters were removed, with a mean indwelling time of 131.8 days (range, 3-602 d). Indwell time (< 90, 90-180, or > 180 d) did not affect retrieval (P = .4). There were 21 filters (15.1%) left in situ as a result of severe tilt (n = 9), significant thrombus in the filter (n = 5), IVC occlusion (n = 3), filter incorporation into the caval wall (n = 3), or lack of central venous access (n = 1). There was a strong relationship between penetration and caudal migration (P < .0001). Severe tilt was associated with prolonged fluoroscopic times for retrieval (P = .003). CONCLUSIONS The majority of G2 filters can be removed without difficulty. The most common factor affecting retrieval was severe tilting. The indwelling time had no impact on retrieval. G2 filter-related complications were frequent but most, including fractures, were clinically insignificant.

A Direct Comparison of Early and Late Outcomes With Three Approaches to Carotid Revascularization and Open Heart Surgery

OBJECTIVES The aim of this study was a comparison of risk-adjusted outcomes of 3 approaches to carotid revascularization in the open heart surgery (OHS) population. BACKGROUND Without randomized clinical trials, the best approach to managing coexisting severe carotid and coronary disease remains uncertain. Staged carotid endarterectomy (CEA) followed by OHS or combined CEA and OHS are commonly used. A recent alternative is carotid artery stenting (CAS). METHODS From 1997 to 2009, 350 patients underwent carotid revascularization within 90 days before OHS at a tertiary center: 45 staged CEA-OHS, 195 combined CEA-OHS, and 110 staged CAS-OHS. The primary composite endpoint was all-cause death, stroke, and myocardial infarction (MI). Staged CAS-OHS patients had higher prevalence of previous stroke (p = 0.03) and underwent more complex OHS. Therefore, the propensity score adjusted multiphase hazard function models with modulated renewal to account for staging, and competing risks were used. RESULTS Using propensity analysis, staged CAS-OHS and combined CEA-OHS had similar early hazard phase composite outcomes, whereas staged CEA-OHS incurred the highest risk driven by interstage MI. Subsequently, staged CAS-OHS patients experienced significantly fewer late hazard phase events compared with both staged CEA-OHS (adjusted hazard ratio: 0.33; 95% confidence interval: 0.15 to 0.77; p = 0.01) and combined CEA-OHS (adjusted hazard ratio: 0.35; 95% confidence interval: 0.18 to 0.70; p = 0.003). CONCLUSIONS Staged CAS-OHS and combined CEA-OHS are associated with a similar risk of death, stroke, or MI in the short term, with both being better than staged CEA-OHS. However, the outcomes significantly favor staged CAS-OHS after the first year.

A randomized, open-label pilot study comparing desirudin and argatroban in patients with suspected heparin-induced thrombocytopenia with or without thrombosis: PREVENT-HIT Study.

Because of an extreme risk for thromboemboli, patients with suspected heparin-induced thrombocytopenia (HIT) require immediate initiation of an alternative anticoagulant. The only therapies approved by the Food and Drug Administration require intravenous infusion of expensive direct thrombin inhibitors. This prospective, randomized, open-label, exploratory study compared the clinical and economic utility of subcutaneous desirudin vs argatroban, the most frequently used agent for suspected or immunologically confirmed HIT, with or without thrombosis. Sixteen patients were randomized to treatment with fixed-dose desirudin (15 or 30 mg) every 12 hours or activated partial thromboplastin time-adjusted argatroban by intravenous infusion. Arm A included 8 patients naive to direct thrombin inhibitor therapy, whereas Arm B included 8 patients on argatroban for at least 24 hours before randomization. The primary efficacy measure was the composite of new or worsening thrombosis (objectively documented), amputation, or death. Other end points included major and minor bleeding while on drug therapy, time to platelet count recovery, and pharmacoeconomics. No amputations or deaths occurred. One patient randomized to argatroban had worsening of an existing thrombosis. Major bleeding occurred in 2 patients on argatroban and in none during desirudin treatment. There was 1 minor bleed in each treatment group. The average medication cost per course of treatment was

Argatroban Anticoagulation in Intensive Care Patients: Effects of Heart Failure and Multiple Organ System Failure:

1688 for desirudin and

Argatroban Anticoagulation for Heparin-Induced Thrombocytopenia in Elderly Patients.

8250 for argatroban. Desirudin warrants further study as a potentially cost-effective alternative to argatroban in patients with suspected HIT.

An algorithm for managing warfarin resistance.

We retrospectively evaluated argatroban dosing patterns, clinical outcomes, and the effects of heart failure and multiple organ system failure on dosing requirements in 65 adult, intensive care patients administered argatroban anticoagulation for clinically suspected heparin-induced thrombocytopenia (n = 56) or history of heparin-induced thrombocytopenia (n = 9). Argatroban was initiated then titrated to achieve target activated partial thromboplastin times 1.5 to 3 times normal control (ie, 42-84 seconds). Overall, argatroban was initiated at 1.14 ± 0.62 µg/kg/min (mean ± SD) and administered for 11.4 ± 9.5 days, with comparable dosing patterns between patients with suspected, versus previous, heparin-induced thrombocytopenia. Sixty-four (98.5%) patients achieved target activated partial thromboplastin times, typically following no or one dose adjustment. Therapeutic doses were lower in patients with, versus without, heart failure (0.58 ± 0.28 vs 0.97 ± 0.6 µg/kg/min, P = .042) and decreased as the number of failed organ systems increased from 1 to 2 to =3 (1.10 ± 0.67 vs 0.87 ± 0.47 vs 0.58 ± 0.47 µg/kg/min, P = .008). From argatroban initiation until patient discharge or death, 11 (16.9%) patients (3 off argatroban) developed thromboembolic complications; 14 (21.5%) died (11 off argatroban, 7 from multiple organ system failure); and 1 (1.5%) required amputation. Nine patients (13.8%) experienced bleeding, none fatal. This experience suggests that argatroban administered at approximately 1 µg/kg/min provides adequate levels of anticoagulation in many intensive care unit patients with suspected or previous heparin-induced thrombocytopenia. Reduced doses are needed when heart failure or multiple organ system failure is present.

Who Should Get Extended Thromboprophylaxis After Bariatric Surgery?: A Risk Assessment Tool to Guide Indications for Post-discharge Pharmacoprophylaxis.

BackgroundArgatroban, a direct thrombin inhibitor that has reduced clearance in elderly versus younger volunteers, is used for thromboprophylaxis or treatment in heparin-induced thrombocytopenia (HIT).ObjectiveTo evaluate the effect of aging on argatroban therapy, including dosage, anticoagulant responses, clinical outcomes and factors influencing those responses, in elderly patients with HIT or a history of HIT.MethodsThis was a retrospective multicentre database analysis of 118 inpatients treated with argatroban at six medical centres between August 2001 and January 2005. Sixty-two adults aged ≥;65 years were administered argatroban for clinically diagnosed HIT (n = 54) or a history of HIT (n = 8). Argatroban infusion was adjusted to achieve activated partial thromboplastin times (aPTTs) 1.5–3 times baseline. All study measures and analyses were prospectively defined. Argatroban dosage patterns, aPTTs and platelet count responses, and 37-day outcomes (death, amputation, new thrombosis, major bleeding) were summarised for patients stratified by age (65–74 years [n = 31]; 75–84 years [n = 26]; ≥85 years [n = 5]) to identify possible age-related trends. Regression analyses explored relationships between dose and patient age, liver function and renal function. Cox proportional hazards models evaluated the effect of age, dose, gender, aPTT and platelet count on the risk of new thrombosis.ResultsIn each age group, the median argatroban dosage was initially 1.0 µg/kg/min and was generally maintained at or near that dose during therapy (median, 5–7 days). Therapeutic aPTTs occurred within 11.5 hours; the median aPTT during therapy was 54.7 seconds, without obvious trend by age. By regression analysis, the initial and mean argatroban dosages decreased 0.08–0.09 µg/kg/min with each 0.2 mg/dL increase in serum creatinine, but no association was detected between dose and patient age, serum total bilirubin, calculated creatinine clearance or blood urea nitrogen. Platelet counts recovered within 6–7 days of initiating therapy, without apparent trend by age. No patient experienced amputation or major bleeding, and no patient in the oldest group died or had new thrombosis. Overall, 13 (21%) patients died (9 in the 65–74 years group; 1 receiving argatroban) and 5 (8%) had new thrombosis (4 in the 65–74 years group; 2 receiving argatroban), comparing favourably with previously reported rates, irrespective of patient age. By univariate (but not multivariate) analysis, the risk of new thrombosis decreased with increasing argatroban dose (hazard ratio 0.020; 95% CI 0.001, 0.757; p = 0.035). No effect of age or the other covariates considered on thrombotic risk was detected.ConclusionArgatroban at a median initial dosage of 1.0 µg/kg/min, adjusted to achieve median aPTTs of 54.7 seconds during therapy, generally provided safe, adequate anticoagulation across a wide age range in elderly patients with HIT or a history of HIT. In these elderly patients, age was not a significant determinant of argatroban dosage or thrombotic risk. Prospective evaluation of this initial dose of argatroban in the elderly is warranted.