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Biomedical subjects

Mark A Crowther

Publications and source records attributed to Mark A Crowther.

At least 37 records · Page 2Linked to original sources
PubMed2005

Are brand-name and generic warfarin interchangeable? Multiple n-of-1 randomized, crossover trials.

BACKGROUND: Warfarin is a commonly used anticoagulant in North America. Several generic formulations have been approved, raising concern over the safety and efficacy of these products compared with brand-name Coumadin. OBJECTIVE: To ensure that generic warfarin products can be safely interchanged with Coumadin. METHODS: Multiple n-of-1 randomized, double-blind, crossover trials switched outpatients (N = 7) between a generic warfarin formulation (Apo-warfarin) and Coumadin over 30 weeks. Study patients took each drug for five 3-week periods, with international normalized ratio (INR) measurements taken twice per period. Inter- and intrapatient differences between generic warfarin and Coumadin were compared, and overall study patient results were compared with those of a Coumadin control group. RESULTS: There were no differences between warfarin products in terms of mean INR results or number of dosage adjustments required. There also was no difference in INR variation based on warfarin formulation (p > 0.69), nor was a patient and warfarin interaction found (p > 0.81). The INR results were not influenced by whether patients were maintained on Coumadin only (control group) or interchanged between Coumadin and generic warfarin (p = 0.98). CONCLUSIONS: It appears that patients can safely and effectively switch between generic warfarin and Coumadin.

Aged↗
PubMed2005

A randomized trial of diagnostic strategies after normal proximal vein ultrasonography for suspected deep venous thrombosis: D-dimer testing compared with repeated ultrasonography.

BACKGROUND: With suspected deep venous thrombosis and normal results on proximal vein ultrasonography, a negative d-dimer result may exclude thrombosis and a positive D-dimer result may be an indication for venography. OBJECTIVE: To evaluate and compare the safety of 2 diagnostic strategies for deep venous thrombosis. DESIGN: Randomized, multicenter trial. SETTING: Four university hospitals. PATIENTS: 810 outpatients with suspected deep venous thrombosis and negative results on proximal vein ultrasonography. INTERVENTIONS: Erythrocyte agglutination D-dimer testing followed by no further testing if the result was negative and venography if the result was positive (experimental) or ultrasonography repeated after 1 week in all patients (control). MEASUREMENTS: Symptomatic deep venous thrombosis diagnosed initially and symptomatic venous thromboembolism during 6 months of follow-up. RESULTS: Nineteen of 408 patients (4.7%) in the D-dimer group and 3 of 402 patients (0.7%) in the repeated ultrasonography group initially received a diagnosis of deep venous thrombosis (P < 0.001). During follow-up of patients without a diagnosis of deep venous thrombosis on initial testing, 8 patients (2.1% [95% CI, 0.9% to 4.0%]) in the D-dimer group and 5 patients (1.3% [CI, 0.4% to 2.9%]) in the repeated ultrasonography group developed symptomatic venous thromboembolism (difference, 0.8 percentage point [CI, -1.1 to 2.9 percentage points]; P > 0.2). Venous thromboembolism occurred in 1.0% (CI, 0.2% to 2.8%) of those with a negative D-dimer result. LIMITATIONS: Seventy patients (8.6%) deviated from the diagnostic protocols, and 9 patients (1.1%) had inadequate follow-up. CONCLUSION: In outpatients with suspected deep venous thrombosis who initially had normal results on ultrasonography of the proximal veins, a strategy based on D-dimer testing followed by no further testing if the result was negative and venography if the result was positive had acceptable safety and did not differ from the safety of a strategy based on withholding anticoagulant therapy and routinely repeating ultrasonography after 1 week.

Female↗
PubMed2005

Perioperative anticoagulation in patients with mechanical heart valves undergoing elective surgery: results of a survey conducted among Korean physicians.

The optimal perioperative anticoagulation management in patients on warfarin therapy is poorly defined due to the lack of randomized trials. Because guidelines are heterogeneous, it was hypothesized that "treatment strategies are not uniform in clinical practice". Between February 2003 and May 2003, a questionnaire with 4 different clinical scenarios was distributed to physicians by e-mail, or direct contact was made by a survey monitor. Two scenarios described the cases of patients with a mechanical heart valve (MHV) in the mitral position, with additional risk factors for a systemic embolism; one undergoing major (scenario 1) and the other minor surgery (scenario 3). Two scenarios described patients with an aortic MHV; one undergoing major (scenario 2) and the other minor (scenario 4) surgery. Different preoperative and postoperative management options were offered. The treatment options for all scenarios were the same. Of the 90 questionnaires distributed, 52 (57.8%) were returned. Hospitalization for full-dose intravenous unfractionated heparin (IV UH) was the most commonly selected strategy in the preoperative phase for scenarios 1 (59%), 2 (42%) and 3 (44%). In scenario 4, 34% chose IV UH. Outpatient, full- dose, subcutaneous UH or low-molecular-weight heparin (LMWH) was the most selected option in the postoperative phase for all scenarios, with the exception of number 4 (52.9% in scenario 1, 34% in scenario 2, 32%, in scenario 3 and 28% in scenario 4). Even among expert clinicians, the management of perioperative anticoagulation is heterogeneous. In particular, the definition of risk categories and the optimal intensity of antithrombotic drugs need to be defined by well-designed prospective studies.

Anticoagulants↗
PubMed2005

Bleeding in cardiac surgery: its prevention and treatment--an evidence-based review.

Expected and unexpected bleeding occur frequently in patients undergoing cardiac surgery. Bleeding after cardiac surgery can be broadly divided into two groups: surgical (unrecognized bleeding vessel, anastomosis, or other suture line) or nonsurgical bleeding (caused by coagulopathy). Factors influencing both surgical and nonsurgical bleeding can be further broken down into those occurring preoperatively and those that occur intraoperatively and postoperatively. A thorough understanding of these factors is necessary to reduce bleeding. This is a desirable clinical goal, because excessive bleeding is associated with adverse outcomes.

Algorithms↗
PubMed2005

Anticoagulant prophylaxis in special populations with an indwelling epidural catheter or renal insufficiency.

The prevention of deep venous thrombosis in postoperative patients who have an indwelling epidural catheter and patients with impaired renal function is a frequently encountered and challenging clinical management problem. Such patients make up a considerable proportion of patients in a medical-surgical intensive care unit. The management of such patients is problematic because low-molecular-weight heparins, the anticoagulant of choice as thromboprophylaxis for many clinical indications, are generally avoided in such patients. This review focuses on anticoagulant prophylaxis in such patients, including reasonable approaches for using low-molecular-weight heparins as thromboprophylaxis.

Analgesia, Epidural↗
PubMed2005

Thrombocytopenia in medical-surgical critically ill patients: prevalence, incidence, and risk factors.

OBJECTIVE: The purpose of this study is to describe the prevalence, to analyze the incidence and independent risk factors for thrombocytopenia, and to examine the impact of thrombocytopenia developing in the intensive care unit (ICU) on patient outcome in a well-defined cohort of critically ill patients in a medical-surgical ICU. MATERIALS AND METHODS: As part of a prospective cohort study examining the frequency and clinical importance of venous thromboembolism in the ICU, we enrolled consecutive patients older than 18 years expected to be in the ICU for more than 72 hours. Exclusion criteria were an admitting diagnosis of trauma, orthopedic surgery or cardiac surgery, pregnancy, and life support withdrawal. Patients had platelet counts performed as directed by clinical need. We defined thrombocytopenia as a platelet count of less than 150 x 10(9)/L and severe thrombocytopenia as a platelet count of less than 50 x 10(9)/L. Protocol-directed care included routine thromboprophylaxis and twice weekly screening ultrasonography of the legs. Patients were followed to hospital discharge. RESULTS: Of the 261 enrolled patients, 121 (46%, 95% confidence interval [CI], 40%-53%) had thrombocytopenia (62 on ICU admission and 59 acquired during their ICU stay). Patients who developed a platelet count less than 150 x 10(9)/L during their ICU stay had higher ICU and hospital mortality (P = .03 and .005, respectively), required longer mechanical ventilation (P = .05), and were more likely to receive platelets (P < .001), fresh frozen plasma (P = .005), and red blood cell transfusions (P = .004) than patients who did not develop thrombocytopenia. The only independent risk factors for thrombocytopenia developing during the ICU stay were administration of nonsteroidal anti-inflammatory drugs before ICU admission (hazard ratio, 2.8; 95% CI, 1.3-6.0) and dialysis during the ICU stay (hazard ratio, 3.1; 95% CI, 1.2-7.8). Of the 33 patients who underwent 36 tests for heparin-induced thrombocytopenia, none tested positive. CONCLUSIONS: We found that about 50% of the patients admitted to the ICU had at least one platelet count of less than 150 x 10(9)/L during their ICU stay. Patients who developed thrombocytopenia were more likely to die, required longer duration of mechanical ventilation, and were more likely to require blood product transfusion. Heparin-induced thrombocytopenia was frequently suspected but did not develop in these critically ill patients.

Aged↗
PubMed2005

Dalteparin thromboprophylaxis for critically ill medical-surgical patients with renal insufficiency.

PURPOSE: Thromboprophylaxis with low-molecular-weight heparin (LMWH) may be more effective than unfractionated heparin but also more likely to bioaccumulate and potentially cause bleeding in patients with renal insufficiency. The objectives of this study were to assess, among medical-surgical patients in the intensive care unit receiving dalteparin 5,000 IU daily for thromboprophylaxis, (1) the relationship between renal dysfunction and LMWH bioaccumulation as measured by trough anti-Xa levels, (2) the relationship between renal dysfunction and risk of bleeding as measured by a surrogate marker (peak anti-Xa levels), and (3) the relationship between anti-Xa levels, bleeding events, and thrombotic events. MATERIALS AND METHODS: In this prospective single-center cohort study, we enrolled patients 18 years or older, expected to stay 72 hours or longer, and with a creatinine clearance 30 mL/min or higher at intensive care unit admission. We administered 5,000 IU dalteparin subcutaneously each day. The main phase 1 objective was to detect bioaccumulation of dalteparin by measuring trough anti-Xa levels (22-23 hours post dalteparin). The main phase 2 objective was to examine the relationship between renal dysfunction and peak anti-Xa levels (4 hours post dalteparin). We recorded creatinine clearance daily and bleeding and thrombotic events, blinded to anti-Xa levels. RESULTS: We enrolled 19 patients aged 62.7 (13.2) years with an APACHE II score of 23.5 (9.4). We measured trough anti-Xa levels on 185 occasions in 19 patients; we measured peak anti-Xa levels on 113 occasions in 11 patients. We identified no bioaccumulation of LMWH in this study, as detected by trough anti-Xa levels. Most peak anti-Xa levels were in the conventional prophylactic range. CONCLUSIONS: When administered in prophylactic doses to critically ill patients with a wide range of calculated creatinine clearances, we found no evidence of bioaccumulation of dalteparin. If dalteparin does not bioaccumulate, it may be an attractive alternative agent for thromboprophylaxis.

Anticoagulants↗
PubMed2005

Deep venous thrombosis: clinically silent in the intensive care unit.

PURPOSE: The reliability of clinical signs and the physical examination in the evaluation of deep venous thrombosis (DVT) in the critically ill is unknown. The purpose of this study was to determine the diagnostic properties of clinical examination for signs of DVT in a cohort of medical-surgical intensive care unit (ICU) patients using screening compression ultrasonography as a reference standard. MATERIALS AND METHODS: We prospectively included patients older than 18 years with an expected length of ICU stay of more than 72 hours. Patients underwent bilateral lower limb screening compression ultrasound twice weekly and structured physical examination twice weekly by 2 independent trained research coordinators blinded to the ultrasonography results. We classified patients according to 2 methods: method 1, a DVT Risk Stratification System of 3 categories and method 2, a DVT Risk Score, both of which use the history and physical examination to stratify patients for their risk of DVT. RESULTS: We included 239 patients in our study, 32 of whom had DVT based on the results of their compression ultrasound. We excluded 7 patients with DVT on ICU admission and 2 who did not undergo any structured examinations. We matched controls with cases (9:1) based on duration of ICU stay. Cases and controls were then allocated to low, moderate, and high risk strata for DVT. Using method 1, the area under the receiver operating characteristic curve (AUC) was 0.57 (95% CI, 0.33-0.78, P = .01). Using method 2, the AUC was 0.59 (95% CI, 0.42-0.75, P = .02). An AUC of 1.0 indicates an ideal test, and AUC of 0.50 indicates a test with no diagnostic utility. CONCLUSIONS: The history and physical examination for DVT are not useful in detecting lower limb DVT in the ICU.

Aged↗
PubMed2005

Evidence based treatment of the antiphospholipid syndrome II. Optimal anticoagulant therapy for thrombosis.

INTRODUCTION: Current consensus recommendations suggest that patients with antiphospholipid antibodies (APLA) are at high risk of recurrent arterial or venous thromboembolism (VTE) despite warfarin administered to achieve an international normalized ratio (INR) of 2.0 to 3.0. These recommendations have been called into question by three recently reported studies. METHODS: We sought to determine the current "best practice" for the prevention of recurrent TE in patients with APLA and TE. Data was derived from a MEDLINE search and review of recent conference abstracts. The literature search was confined to studies of treatment to prevent recurrent thrombosis in patients with APLA. RESULTS: The overall proportion of patients suffering recurrent TE when allocated to moderated-intensity warfarin (target INR of 2.0 to 3.0) was 5/113 (4.4%), and it was 11/110 (10.0%) when such patients were randomized to high-intensity warfarin (target INR of 3.0 to 4.0). APLA-positive patients with noncardioembolic/nonatheroembolic stroke appear to have similar risks of recurrent TE whether they are treated with warfarin or aspirin. DISCUSSION: Patients with APLA and TE have an acceptable rate of recurrent TE if they are treated with usual-intensity warfarin. Patients with APLA and stroke are probably best treated with aspirin, while those with other forms of arterial TE are likely best treated with moderate-intensity warfarin plus aspirin.

Anticoagulants↗
PubMed2005

Anticoagulation therapy in the antiphospholipid syndrome: recent advances.

PURPOSE OF REVIEW: The antiphospholipid syndrome is currently best treated with anticoagulation. This review discusses the recent literature addressing the duration, intensity, and appropriateness of anticoagulation or antiplatelet therapy in various clinical subcategories of this syndrome. RECENT FINDINGS: Several recent articles reaffirm the benefits of long-term anticoagulation in patients with venous thromboembolism or undergoing renal transplantation and support recommendations for usual International Normalized Ratio targets. Aspirin seems to confer benefits similar to those of anticoagulation in arterial stroke. Appropriate anticoagulation strategies for pregnancy are controversial. SUMMARY: Anticoagulation will remain the mainstay of treatment for most patients with antiphospholipid syndrome. The optimal therapy for specific subgroups of patients will, however, require further good-quality studies.

Anticoagulants↗
PubMed2005

Bridging anticoagulation with low-molecular-weight heparin after interruption of warfarin therapy is associated with a residual anticoagulant effect prior to surgery.

Bridging anticoagulation with low-molecular-weight heparin (LMWH) is common in patients who require temporary interruption of warfarin before surgery or a procedure, but whether such patients have a residual anticoagulant effect just before a procedure is not known. Consecutive patients who received bridging anticoagulation with LMWH had anti-Xa levels measured just before a procedure. The proportion of patients with a residual anticoagulant effect, defined as an anti-Xa level > or = 0.10 IU/ml, was determined. Multivariable regression analysis identified predictors of a residual anticoagulant effect, expressed as an odds ratio (OR) and corresponding 95% confidence interval (CI). A pre-procedure residual anticoagulant effect was detected in 12 of 73 (16%) patients overall, in 11 of 37 (30%) patients who received therapeutic-dose LMWH, and in 1 of 36 patients (3%) who received low-dose LMWH. Receiving therapeutic-dose LMWH (OR = 118.8; 95% CI: 5.8, 999.9), and increasing age (OR = 4.0; 95% CI: 1.3, 12.5) were predictors of a residual pre-procedure anticoagulant effect. In patients who require bridging anticoagulation with LMWH, a residual anticoagulant effect from LMWH is detected in 1 of 6 patients, and receiving therapeutic-dose LMWH is the strongest predictor of such an effect.

Age Factors↗
PubMed2005

Pathogenesis of atherosclerosis.

Atherosclerosis is no longer considered a disorder due to abnormalities in lipid metabolism. In fact, the inciting event of atherosclerosis is likely an inflammatory insult that occurs decades before the disease becomes clinically apparent. Rapidly evolving knowledge of the pathogenesis of atherosclerosis, coupled with novel, target-specific therapies, is revolutionizing the treatment of atherosclerosis. As a result, a variety of treatments are now undergoing evaluation for their ability to ameliorate the inflammatory pathways likely to cause the atherosclerotic process to initiate and propagate. Once initiated, atherosclerosis progresses as a result of a well-studied series of changes in the constituent cellular make-up of the vessel wall. Specific cytokine-mediated events in this cycle are required for lesional growth. The clinical manifestations of atherosclerosis occur so late in this process that interventions such as percutaneous coronary interventions can deal with isolated areas of disease; however, they do not influence the underlying disease process.

Adipose Tissue↗