PubMed Health⌕ Search

Biomedical subjects

Mark Crowther

Publications and source records attributed to Mark Crowther.

At least 19 recordsLinked to original sources
PubMed2006

Postpartum management of women at increased risk of thrombosis--results of a Canadian pilot survey.

OBJECTIVE: To determine current practice patterns in the postpartum management of women at increased risk of thrombosis. METHODS: Physicians affiliated with the University of Toronto departments of Obstetrics and Gynecology, Rheumatology, Hematology, and Obstetric Medicine who provide care to pregnant women were mailed a questionnaire that presented 6 clinical scenarios involving postpartum management of a woman at risk for thrombosis, with (1) recurrent pregnancy loss and antiphospholipid antibody syndrome (APS) treated with aspirin (ASA) in the pregnancy; (2) 2 pregnancy losses and a low titer antiphospholipid antibody (aPL) treated with ASA and low molecular weight (LMW) heparin with placental insufficiency; (3) known APS and pregnancy loss treated with LMW heparin and delivered by cesarean section; (4) a previous 17 week fetal death and aPL; (5) a previous deep vein thrombosis while on oral contraception; and (6) systemic lupus erythematosus and secondary APS with a history of a stillbirth. Physicians were asked whether they would recommend postpartum coagulation, and if so to choose from a list of treatment options. RESULTS: Of the 71 questionnaires mailed, 44 were returned (62%). Three physicians replied that their practices do not include patients similar to those presented in the cases and chose not to respond to the clinical scenarios. Percentages of responders recommending treatment in each scenario were 29% for Case 1, 49% for Case 2, 63% for Case 3, 41% for Case 4, 51% for Case 5, and 58% for Case 6. Recommendation for treatment differed among medical specialties, with rheumatologists being less likely to treat in all cases. Prophylactic heparin was selected as the treatment of choice most frequently by those recommending anticoagulation 70% (84/120). CONCLUSION: Postpartum treatment recommendations for women at increased risk of thrombosis are variable across different practitioner specializations demonstrating clinical equipoise regarding therapy. More definitive research is needed and broader study of physicians involved in the care of these patients is planned to more accurately describe and understand the decision to treat these patients.

Antibodies, Antiphospholipid↗
PubMed2006

Does celecoxib potentiate the anticoagulant effect of warfarin? A randomized, double-blind, controlled trial.

BACKGROUND: The management of patients who are receiving warfarin therapy and have musculoskeletal problems that require treatment with a nonsteroidal antiinflammatory drug (NSAID) is problematic because NSAID use may increase the risk for bleeding. Cyclooxygenase-2 selective NSAIDs such as celecoxib may be less likely to promote gastrointestinal bleeding; however, there are concerns that they could potentiate the anticoagulation effect of warfarin. OBJECTIVE: To determine whether celecoxib potentiates the anticoagulant effect of warfarin, as measured by the international normalized ratio (INR). METHODS: We performed a randomized, controlled, crossover trial to assess the effect on INR of celecoxib versus codeine (control treatment) in 15 patients who were receiving warfarin therapy and required analgesic treatment for osteoarthritis. During Phase 1 of the study, patients were randomly allocated to receive celecoxib 200 mg/day or codeine phosphate 7-15 mg 3-4 times daily for 5 weeks. During Phase 2 of the study, patients stopped the first study medication and started the other study medication; there was no drug-free interval between phases. Weekly INR testing was performed during the 10 week study period. Adopting the intent-to-treat principle, we used generalized estimating equations to analyze the data. RESULTS: There was no significant difference in the mean INR values during each 5 week treatment period when patients received either celecoxib or codeine. There was, therefore, insufficient evidence to reject the hypothesis that these 2 treatments had an equal effect on the INR (mean difference [95% CI] 0.10 [-0.04 to 0.24]; p = 0.16) based on mean imputation. This finding was confirmed after we repeated the analysis with multiple imputations (mean difference [95% CI] 0.093 [-0.16 to 0.35]; p = 0.47). CONCLUSIONS: Our results suggest that treatment with celecoxib does not potentiate the INR when taken with warfarin. Larger randomized trials are warranted to address the effects of coadministered warfarin and celecoxib on clinical outcomes.

Aged↗
PubMed2006

The risk of hemorrhage among patients with warfarin-associated coagulopathy.

OBJECTIVES: Among warfarin-treated patients with international normalized ratio (INR) >5, we sought to determine the risk of major bleeding within 30 days. BACKGROUND: For warfarin-treated patients, the risk of bleeding increases as the INR rises, particularly if the INR exceeds 4. The 30-day risk of hemorrhage among outpatients with excessively prolonged INR values is unknown. METHODS: To assess anticoagulation care in the U.S., a cohort of 6,761 patients taking warfarin was prospectively assembled from 101 participating sites (43% were community-based cardiology practices). From this cohort, 1,104 patients were identified with a first episode of INR >5. RESULTS: A total of 979 met eligibility criteria; complete follow-up information was available for 976 (99.7%). Ninety-six percent (n = 937) of patients had an INR value between 5 and 9; 80% of INR values were <7. Thirteen patients (1.3%) experienced major hemorrhage during the 30-day follow-up period; among patients whose INR was >5 and <9, 0.96% experienced major hemorrhage. None of the bleeding events was fatal. Intervention with vitamin K was uncommon (8.7%). Warfarin doses were withheld for the majority of patients. Fifty percent of patients who were managed conservatively and retested on day 4 or 5 had an INR of 2.0 or less. CONCLUSIONS: For warfarin-treated outpatients presenting with an INR >5 and <9, the 30-day risk of major bleeding is low (0.96%). Intervention with vitamin K among asymptomatic patients presenting with an INR <9 is not routine practice in the U.S.

Aged↗
PubMed2006

Thrombophilic abnormalities, oral contraceptives, and risk of cerebral vein thrombosis: a meta-analysis.

Recent studies suggest that thrombophilic abnormalities and the use of oral contraceptives (OCs) are the leading causes of cerebral vein thrombosis (CVT). The purpose of this study was to assess the association between CVT and thrombophilic states, OCs, and their interaction. For data sources, we used the MEDLINE, EMBASE, and Cochrane Library databases (January 1994 to March 2005), reference lists of retrieved articles, and contact with content experts. We selected studies comparing the prevalence of OC use and the prevalence of prothrombitic abnormalities in patients with CVT compared with healthy controls. Two reviewers independently selected studies and extracted study characteristics, quality, and outcomes. Odds ratios (ORs) were calculated for each trial and pooled using the Mantel-Haenszel method. Seventeen studies were included. There was an increased risk of CVT in patients using OCs (OR 5.59; 95% confidence interval [CI] 3.95 to 7.91; P < .001), and in patients with factor V Leiden (OR 3.38; 95% CI 2.27 to 5.05; P < .001), with mutation G20 210A of prothrombin (OR 9.27; 95% CI 5.85 to 14.67; P < .001) and with hyperhomocysteinemia (OR 4.07; 95% CI 2.54 to 6.52; P < .001). We concluded that OC users, and patients with factor V Leiden, the prothrombin G20 120A mutation, and hyperhomocysteinemia are at a significantly increased risk of CVT.

Adolescent↗
PubMed2006

Acquired thrombophilia during pregnancy.

Acquired thrombophilic states are common causes of thrombosis and other forms of pregnancy-associated complications. A growing body of evidence is available to guide the use of anticoagulants in patients who have antiphospholipid antibodies; unfortunately, the results of these studies are conflicting, and solid, evidence-based treatment recommendations cannot be made. Other forms of acquired thrombophilia are uncommon or of unknown clinical significance. Treatments aimed at mitigating the impacts of these states lack clear evidence to support their use.

Antiphospholipid Syndrome↗
PubMed2006

Measuring the anticoagulant effect of low molecular weight heparins in the critically ill.

Antithrombotic prophylaxis in critically ill patients frequently fails. Venous thromboembolism is associated with adverse clinical outcomes, including a prolonged intensive care unit stay and death. A potential mechanism by which critically ill patients may be predisposed to antithrombotic failure is the inability to achieve 'prophylactic' anticoagulant drug levels as a result of impaired absorption. For example, previous studies have shown that patients on inotropes have reduced serum levels of low molecular weight heparin, presumably on the basis of reduced absorption from the subcutaneous injection site. In the previous issue of the journal, Rommers and colleagues examined whether subcutaneous edema reduces absorption of a low molecular weight heparin; although small, and thus underpowered, the authors failed to find any relationship between the level of low molecular weight heparin and the presence of edema. These findings provide reassurance that subcutaneously administered medications may be used in critically ill patients with edema.

Administration, Cutaneous↗
PubMed2006

Dalteparin versus warfarin for the prevention of recurrent venous thromboembolic events in cancer patients: a pharmacoeconomic analysis.

OBJECTIVE: In a recent randomised trial (CLOT [Comparison of Low molecular weight heparin versus Oral anticoagulant Therapy for long term anticoagulation in cancer patients with venous thromboembolism]), which evaluated secondary prophylaxis of venous thromboembolism (VTE) in cancer patients, dalteparin reduced the relative risk of recurrent VTEs by 52% compared with oral anticoagulation therapy (p = 0.002). A Canadian pharmacoeconomic analysis was conducted to measure the economic value of dalteparin for this indication. DESIGN: The study was conducted from the Canadian healthcare system. The first part of this study utilised the CLOT trial database, from which resource utilisation data were converted into Canadian cost estimates (Can dollars, year 2005 values). Univariate and multivariate regression analyses were conducted to compare the total cost of therapy between patients randomised to treatment with dalteparin or oral therapy. Health state utilities and treatment preferences were then measured in 24 oncology care providers using the time trade-off technique. RESULTS: When all of the cost components were combined for the entire population (n = 676), patients in the dalteparin group had significantly higher overall costs than the control group (Can dollars 4162 vs Can dollars 2003; p < 0.001). The preference assessment revealed that 23 of 24 respondents (96%) selected dalteparin over warfarin, with an associated gain of 0.157 QALYs. When the incremental cost of dalteparin (Can dollars 2159 per patient) was combined with the QALY gain, the findings revealed that dalteparin was associated with a cost of approximately Can dollars 13,800 (95% CI 12,400, 15,100) per QALY gained. CONCLUSIONS: Given the practical advantages of dalteparin in terms of convenience, improved efficacy and the acceptable economic value, this analysis suggests that long-term dalteparin therapy is a sound alternative to warfarin for the prevention of recurrent VTEs in patients with cancer.

Adult↗
PubMed2006

Effect of chronic kidney disease on red blood cell rheology.

BACKGROUND: Anemia of renal failure is primarily a problem of decreased RBC production due to erythropoietin deficiency. RBC survival is also reduced, perhaps due to decreased RBC deformability. This study measured blood viscosity over a range of shear rates in erythropoietin-treated patients on hemodialysis (HD), and compared the findings to matched patients with chronic renal insufficiency (CRI) and healthy controls. METHODS: Four groups (control, CRI, non-diabetic HD, and diabetic HD) of 9 matched subjects were recruited. Blood viscosity was measured using a cone-plate viscometer over a variety of shear rates (11 to 225 s(-1)). RESULTS: Control subjects had lower viscosity values throughout all shear rates when compared to the 3 renal disease groups (P value=0.039). A trend was observed to higher levels of renal function being associated with decreased blood viscosity in patients with CRI. CONCLUSIONS: Patients with kidney disease have increased blood viscosity at all shear rates. This may be related to changes in RBC shape and decreased deformability in patients with kidney disease, independent of HD- or DM-status. This may have implications for strategies to treat anemia in these patients.

Aged↗
PubMed2006

Practice patterns for deep vein thrombosis prophylaxis in minimal-access surgery.

BACKGROUND: There are no comprehensive evidence-based guidelines for deep vein thrombosis (DVT) prophylaxis in patients undergoing minimal-access surgery (MAS). METHODS: We completed a cross-sectional survey of general surgeons practising in Ontario, in order to establish current practice patterns for DVT prophylaxis for MAS procedures. RESULTS: The mean duration of practice of respondents was 15.4 years, with most (67.0%) practising outside an academic centre. For minor MAS, most surgeons do not give DVT prophylaxis (73.8% in laparoscopic cholecystectomy and 63.7% in laparoscopic inguinal hernia repair). For major MAS, a minority of surgeons do not give DVT prophylaxis (4.1% in laparoscopic colorectal surgery and 13.6% in laparoscopic splenectomy). However, there remains considerable variation in the mechanism (pharmacological, mechanical), approach and duration (perioperative, postoperative) of DVT prophylaxis among respondents in all case scenarios evaluated. Academic surgeons and surgeons in practice for 15 years or less are more aggressive with preoperative heparin administration. CONCLUSIONS: There is substantial and important variability in the current practice of general surgeons with respect to DVT prophylaxis for MAS. Considerable benefit will be derived from clinical trials that provide data to establish appropriate DVT prophylaxis guidelines for MAS.

Follow-Up Studies↗
PubMed2005

Are brand-name and generic warfarin interchangeable? A survey of Ontario patients and physicians.

BACKGROUND: The issue of therapeutic equivalence has been a source of controversy in Canada since the approval of generic warfarin products in 2000. OBJECTIVES: We surveyed Ontario patients and physicians on perceptions of generic warfarin and brand substitution. METHODS: Self-administered questionnaires employed 7.0-point Likert scales of agreement. Patient participants were drawn from a thromboembolism clinic in Hamilton, Ontario. Physician participants were from a random sample of 375 Ontario family physicians, internists, cardiologists and hematologists. RESULTS: Eighty-one patients responded: 52% female, mean age 63.4 years and 63% brand-name warfarin users. Overall, 33% of respondents agreed or strongly agreed that they would feel comfortable taking generic warfarin. However, seventeen percent agreed or strongly agreed that generic warfarin was neither as safe nor as effective as brand-name warfarin, with this view more common amongst patients taking brand-name than those taking generic warfarin. One hundred and ten (29.3%) physicians returned the survey--29% females, mean age 45.3 years, 22% family physicians. Forty-four percent agreed or strongly agreed that they would rather prescribe brand-name than generic warfarin for patients starting warfarin therapy, while 40.7% agreed or strongly agreed that they would not feel comfortable switching from brand-name to generic warfarin. However, only 19.4% of physicians who had switched patients from brand-name to generic warfarin actually reported difficulties in managing the switch. CONCLUSION: While most patients and physicians appear to have accepted the principle of therapeutic equivalence of generic and brand-name warfarin, a sizable minority has concerns that could influence prescribing and compliance.

Anticoagulants↗
PubMed2005

Systematic overview of warfarin and its drug and food interactions.

BACKGROUND: Warfarin is a highly efficacious oral anticoagulant, but its use is limited by a well-founded fear of bleeding. Drug and food interactions are frequently cited as causes of adverse events with warfarin. We provide an updated systematic overview of the quality, clinical effect, and importance of these reported interactions. DATA SOURCES: MEDLINE, TOXLINE, IPA, and EMBASE databases from October 1993 to March 2004. Database searches combined the keyword warfarin with drug interactions, herbal medicines, Chinese herbal drugs, and food-drug interactions. STUDY SELECTION: Eligible articles contained original reports of warfarin drug or food interactions in human subjects. Non-English articles were included if sufficient information could be abstracted. DATA EXTRACTION: Reports were rated independently by 2 investigators for interaction direction, clinical severity, and quality of evidence. Quality of evidence was based on previously validated causation criteria and study design. DATA SYNTHESIS: Of 642 citations retrieved, 181 eligible articles contained original reports on 120 drugs or foods. Inter-rater agreement was excellent, with weighted kappa values of 0.84 to 1.00. Of all reports, 72% described a potentiation of warfarin's effect and 84% were of poor quality, 86% of which were single case reports. The 31 incidents of clinically significant bleeding were all single case reports. Newly reported interactions included celecoxib, rofecoxib, and herbal substances, such as green tea and danshen. CONCLUSIONS: The number of drugs reported to interact with warfarin continues to expand. While most reports are of poor quality and present potentially misleading conclusions, the consistency of reports of interactions with azole antibiotics, macrolides, quinolones, nonsteroidal anti-inflammatory drugs, including selective cyclooxygenase-2 inhibitors, selective serotonin reuptake inhibitors, omeprazole, lipid-lowering agents, amiodarone, and fluorouracil, suggests that coadministration with warfarin should be avoided or closely monitored. More systematic study of warfarin drug interactions in patients is urgently needed.

Anticoagulants↗
PubMed2005

Prophylaxis of Thromboembolism in Critical Care (PROTECT) Trial: a pilot study.

PURPOSE: There is no randomized trial comparing low-molecular weight heparin (LMWH) and unfractionated heparin (UFH) for thromboprophylaxis in medical-surgical ICU patients. The primary objective of this randomized pilot study on LMWH vs UFH was to assess the feasibility of conducting a large randomized trial with respect to timely enrollment and blinded study drug administration, practicality of twice-weekly lower limb ultrasounds to screen for deep venous thrombosis, LMWH bioaccumulation and dose adjustment in renal insufficiency, and recruitment rates for a future trial in medical-surgical intensive care unit (ICU) patients. Its additional goals were to evaluate the suitability of the exclusion criteria and to document the range of research activities that precede accrual of patients into a trial to plan multisite management. MATERIALS AND METHODS: By computerized telephone randomization, we allocated 129 medical-surgical ICU patients to treatment with dalteparin 5,000 IU QD SC or that with UFH 5,000 IU BID SC. Within each clinical center, only the study pharmacist was not blinded. We performed bilateral lower limb compression ultrasounds within 48 hours of ICU admission, twice weekly, on suspicion of deep venous thrombosis, and 7 days after ICU discharge. Research coordinators and investigators at 7 centers reported the time they engaged in all research activities before the first patient was randomized. RESULTS: Timely complete study drug administration occurred after enrollment. More than 99% of scheduled doses were administered in a blinded fashion. Scheduled ultrasounds were performed without exception. No bioaccumulation of dalteparin was observed when creatinine clearance decreased to lower than 30 mL/min. Average recruitment was 2 patients/center per month before the study exclusion criteria were modified. Study startup activities required, on average, 65.5 hours of combined investigator and research coordinator time at each center. Careful examination of the accrual in the pilot study led to a reexamination of the Prophylaxis of Thromboembolism in Critical Care Trial (PROTECT) study exclusion criteria. CONCLUSIONS: This pilot study suggests that a multicenter randomized clinical trial comparing LMWH with UFH in critically ill medical-surgical patients is feasible. Pilot studies can improve the design of larger trials and may enhance successful timely completion.

Anticoagulants↗
PubMed2005

Deep venous thrombosis in medical-surgical critically ill patients: prevalence, incidence, and risk factors.

OBJECTIVE: Critically ill patients may be at high risk of venous thromboembolism. The objective was to determine the prevalence, incidence, and risk factors for proximal lower extremity deep venous thrombosis among critically ill medical-surgical patients. DESIGN: Prospective cohort. SETTING: Closed university-affiliated intensive care unit. PATIENTS: We enrolled consecutive patients > or =18 yrs of age expected to be in intensive care unit for > or =72 hrs. Exclusion criteria were an admitting diagnosis of trauma, orthopedic surgery, pregnancy, and life support withdrawal. INTERVENTIONS: Interventions included bilateral lower extremity compression ultrasound within 48 hrs of intensive care unit admission, twice weekly, and if venous thromboembolism was clinically suspected. Thromboprophylaxis was protocol directed and universal. We recorded deep venous thrombosis risk factors at baseline and daily, using multivariate regression analysis to determine independent predictors. Patients were followed to hospital discharge. RESULTS: Among 261 patients with a mean Acute Physiology and Chronic Health Evaluation II score of 25.5 (+/-8.4), the prevalence of deep venous thrombosis was 2.7% (95% confidence interval 1.1-5.5) on intensive care unit admission, and the incidence was 9.6% (95% confidence interval 6.3-13.8) over the intensive care unit stay. We identified four independent risk factors for intensive care unit-acquired deep venous thrombosis: personal or family history of venous thromboembolism (hazard ratio 4.0, 95% confidence interval 1.5-10.3), end-stage renal failure (hazard ratio 3.7, 95% confidence interval 1.2-11.1), platelet transfusion (hazard ratio 3.2, 95% confidence interval 1.2-8.4), and vasopressor use (hazard ratio 2.8, 95% confidence interval 1.1-7.2). Patients with deep venous thrombosis had a longer duration of mechanical ventilation (p = .03), intensive care unit stay (p = .005), and hospitalization (p < .001) than patients without deep venous thrombosis. CONCLUSIONS: Despite universal thromboprophylaxis, medical-surgical critically ill patients remain at risk for lower extremity deep venous thrombosis. Further research is needed to evaluate the risks and benefits of more intense venous thromboembolism prophylaxis.

APACHE↗
PubMed2005

Thromboembolism in children with acute lymphoblastic leukaemia treated on Dana-Farber Cancer Institute protocols: effect of age and risk stratification of disease.

Children with acute lymphoblastic leukaemia (ALL) are at increased risk for thromboembolism (TE). Identification of a susceptible population is crucial for effective thromboprophylaxis. However, the risk factors for ALL-associated TE are unclear. Concomitant asparaginase (ASP) and steroid therapy has been shown to increase the incidence of TE. Dana-Farber Cancer Institute (DFCI)-ALL protocols use a combination of ASP and steroids during the postinduction intensification phase when high-risk (HR) patients receive thrice the steroid-dose given to standard-risk (SR) patients. We studied prospectively assembled cohorts of children treated on two consecutive DFCI-ALL protocols to define the risk factors for symptomatic TE. Ten (11%) of 91 patients developed symptomatic TE; eight (seven HR) during intensification. Seven (44%) of 16 older patients (>/=10 years) compared with three of 75 (4%) younger patients developed TE (P < 0.0001). Nine of 35 (26%) HR and one of 56 (2%) SR patients developed TE (P = 0.0006). Gender, ALL-immunophenotype, steroid-type or ASP dosing schedule did not alter the risk but older age and HR-disease were factors predisposing to TE associated with DFCI-ALL protocols. Age-related risk may partly reflect the effect of ALL-risk stratification. Higher dose steroids combined with ASP may lead to an increased risk of TE in HR patients.

Adolescent↗