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Biomedical subjects

M A Crowther

Publications and source records attributed to M A Crowther.

At least 19 recordsLinked to original sources
PubMed2002

Vitamin K deficiency and D-dimer levels in the intensive care unit: a prospective cohort study.

Patients in the intensive care unit (ICU) are at risk for the development of vitamin K deficiency. We sought to determine the frequency of this deficiency by performing a prospective cohort study in which patients were screened for vitamin K deficiency on ICU admission and every other day thereafter. Vitamin K deficiency was diagnosed by a functional coagulation factor II to Echis factor II ratio < 0.70. Activity of the coagulation cascade was measured by D-dimer. In total, 40 patients were enrolled into the study. Seven of the patients had ratios < 0.70 on the day of admission to the ICU, and three patients developed ratios < 0.70. Thus, 10 of 40 patients (25%; 95% confidence interval, 12-38%) had vitamin K deficiency. Two patients developed coagulopathy, as indicated by an International Normalized Ratio of more than 1.4. D-dimer levels were elevated in 86 of 111 samples. We conclude that vitamin K deficiency is common among critically ill patients, particularly on admission to the ICU. Our findings suggest that additional clinical research is warranted to determine whether vitamin K supplementation on admission to the ICU reduces the risk of ICU-acquired vitamin K deficiency and its attendant complications over the course of the ICU stay.

Aged↗
PubMed2001

Does the location of thrombosis determine the risk of disease recurrence in patients with proximal deep vein thrombosis?

PURPOSE: To determine if the location of deep vein thrombosis is a predictor of recurrent venous thromboembolism during the initial 3 months of anticoagulant therapy. METHODS: The study population consisted of 1,149 consecutive patients with symptomatic proximal deep vein thrombosis. In all patients, deep vein thrombosis was confirmed by Duplex ultrasound or venography and was classified as popliteal, femoral, or iliofemoral. Patients received initial treatment with unfractionated heparin, enoxaparin, or reviparin for least 4 days, as well as a coumarin derivative, with a target international normalized ratio of 2.0 to 3.0, starting on the 1st or 2nd day of treatment. All patients were followed for 3 months, and all episodes of recurrent venous thromboembolism were confirmed with objective diagnostic tests. RESULTS: The overall rate of recurrent venous thromboembolism during the initial 3 months of anticoagulant therapy was 5.5% (63/1,149). The rate of recurrence in patients with popliteal vein thrombosis was 5.1% (23/453); in patients with femoral vein thrombosis, it was 5.3% (34/645); and in patients with iliofemoral vein thrombosis, it was 11.8% (6/51). Two clinical risk factors were associated with an increased risk of recurrent venous thromboembolism: iliofemoral vein thrombosis (odds ratio [OR] = 2.4; 95% confidence interval [CI]: 0.95, 5.9), and cancer (OR = 2.6; 95% CI: 1.5, 4.4). CONCLUSIONS: Patients with extensive iliofemoral vein thrombosis who receive conventional anticoagulant therapy have a greater than twofold higher risk of developing recurrent venous thromboembolism than patients without iliac vein involvement (i.e., 11.8% vs. 5.2%). Prospective studies are needed to determine whether alternative antithrombotic strategies are warranted in such patients.

Anticoagulants↗
PubMed2001

Thrombolysis for restoration of patency to haemodialysis central venous catheters: a systematic review.

Urokinase, previously used to restore patency to thrombosed haemodialysis catheters, is now unavailable in North America. We performed systematic reviews of four questions related to the safety and efficacy of alternative agents for catheter thrombolysis, searching Medline and the Cochrane Controlled Clinical Trials Register. In dialysis patients, large case series have documented that urokinase is safe and effective (>70 % efficacy for catheter instillation, and >80 % for systemic lysis). Experience with streptokinase is limited and allergic complications develop with repeated use. Studies of catheter instillation with 1--2 mg of tPA per lumen reported short-term success in 83--98 % of uses. One non-peer-reviewed study described 44--59 % success using systemic tissue plasminogen activator (tPA), 2.5 mg through each of 2 lumens, over 1 h. Meta-analysis of randomized comparisons of urokinase and tPA as full-dose thrombolytic agents suggested that 1 mg tPA was likely equivalent in thrombolytic potency to 36,000 units urokinase. In nondialysis populations, four case series suggested that catheter instillation with 0.5--2 mg tPA was effective and safe in reestablishing patency, and a randomized controlled trial found 2--4 mg tPA more effective than 5,000--10,000 units urokinase. No complications have been reported in any patient treated with systemic or local tPA for catheter thrombolysis. In studies of fistula thrombolysis with 5--50 mg tPA major complications occurred in one episode in 130 patients treated. This review suggests that 1--2 mg/lumen tPA is a suitable dose for catheter instillation and likely to be more effective than 5000 units/lumen urokinase. Systemic lysis with 5--10 mg tPA is likely to be safe and effective in suitably selected patients. Further studies are needed.

Catheterization, Central Venous↗
PubMed2001

Anticoagulation therapy.

Despite refinements and standardization in the use of anticoagulants, many problems remain for clinicians. Dr. Crowther describes appropriate starting and maintenance doses of warfarin, factors accounting for inter- and intra-observer variability and importantly, the management of the over-anticoagulated patients and bleeding patients. Dr. White compares unfractionated heparin (UFH) and low molecular weight heparin (LMWH) and addresses whether there truly are differences in the efficacy and safety of different LMWH's for both arterial and venous indications. Dr. Ortel discusses the management of the problem patient who requires anticoagulants, the management of heparin-induced thrombocytopenia, the pregnant patient, the obese patient, patients who have renal insufficiency and/or liver disease, patients with malignant disease, and other challenging patient populations.

Anticoagulants↗
PubMed2001

Treatment of warfarin-associated coagulopathy: a physician survey.

STUDY OBJECTIVES: (1) To determine physician preferences in the management of warfarin-induced excessive anticoagulation (AC); and (2) to assess compliance with the American College of Chest Physicians (ACCP) guidelines for the reversal of excessive AC. DESIGN: Cross-sectional physician survey. PARTICIPANTS: Members of the Canadian Society of Internal Medicine practicing in Ontario, Canada. MEASUREMENTS AND RESULTS: Physicians were asked to provide management preferences in six clinical scenarios describing warfarin-induced excessive AC. The scenarios represent various combinations of international normalized ratio (INR) value, treatment setting, and presence and severity of bleeding. In scenarios with INRs < 5.2 without bleeding, conservative approaches complying with the ACCP guidelines, such as withholding warfarin or reducing its dose, were most common. In scenarios with high INRs (ie, > 7.1) and/or bleeding, the selection of vitamin K in any form ranged between 71% and 82%. However, compliance with the ACCP-recommended doses and the routes of vitamin K administration ranged from 1 to 10%. In five of the six scenarios, subcutaneous injection, a route not recommended by the ACCP, was the most common method of vitamin K delivery. CONCLUSIONS: Physician preferences for the reversal of warfarin-induced excessive AC were highly variable and, in most cases, did not follow the recommendations of the ACCP consensus guidelines. Furthermore, the widespread reported use of subcutaneous vitamin K is concerning because this route of vitamin K administration has been demonstrated to be less effective than IV administration of vitamin K. These findings highlight the need for randomized controlled trials to compare the efficacy of different routes of administration of vitamin K for warfarin-associated coagulopathy.

Adult↗
PubMed2001

Fibrinolytic variables in patients with recurrent venous thrombosis: a prospective cohort study.

To determine whether fibrinolytic testing predicts recurrent venous thrombosis, we have performed a prospective cohort study in which 303 patients with a first episode of venous thromboembolism underwent comprehensive fibrinolytic testing while receiving oral anticoagulants, and after anticoagulants had been discontinued. They were then followed for up to 3 years for recurrent venous thrombosis. No systematic differences in the levels or activity of type 1 plasminogen activator inhibitor (PAI-1), tissue plasminogen activator (tPA) or euglobulin clot lysis times were detected between patients who did, or did not, suffer recurrent thrombosis. There were also no differences in these variables when patients whose initial thrombosis was idiopathic were compared to patients whose thrombosis occurred in the setting of a known thrombotic risk factor. Based on these results, neither measuring fibrinolytic parameters in patients with venous thromboembolism, nor modification of treatment based on the results of such testing, are justified. Our study also confirms that patients with idiopathic venous thromboembolism have a high risk of recurrence.

Anticoagulants↗
PubMed2000

Treatment of warfarin-associated coagulopathy with oral vitamin K: a randomised controlled trial.

BACKGROUND: Warfarin-associated coagulopathy is a frequent clinical complication. We aimed to assess whether treatment with vitamin K is safe and more effective than placebo in rapidly lowering the international normalised ratio (INR) into the therapeutic range in over anticoagulated patients receiving warfarin. METHODS: We did a multicentre, double-blind, placebo-controlled, randomised trial in five tertiary care hospitals. In this study, patients receiving warfarin who had an INR value between 4.5 and 10.0, and who did not have an indication for the immediate normalisation of their INR, had their warfarin withheld, and were randomly allocated to receive either 1 mg of vitamin K or placebo orally. The primary outcome measure was the INR value on the day after treatment. Secondary outcome measures included INR values on subsequent days, and the risk of haemorrhage and recurrent thrombosis over a 3 month follow-up period. FINDINGS: Patients given vitamin K had a more rapid decrease in the INR than those given placebo (25 of 45 (56%] vs nine of 44 [20%] patients with INR values of 1.8-3.2 on the day after treatment, respectively, p=0.001; odds ratio [OR] 0.21, 95% CI 0.07-0.57). Fewer patients given vitamin K had bleeding episodes during the follow-up period than those given placebo (two [4%] vs eight [17%] patients, respectively, p=0.050; OR 0.87, 95% CI 0.019-0.999). INTERPRETATION: Low dose oral vitamin K is more effective than placebo for the rapid lowering of raised INR values in patients taking warfarin.

Administration, Oral↗
PubMed2000

Pharmacokinetic profile of a low-molecular weight heparin (reviparin) in pregnant patients. A prospective cohort study.

Anticoagulant therapy during pregnancy is problematic. Patients are frequently treated with long-term low-molecular weight heparin despite a lack of evidence for its effectiveness, and in the absence of validated dosing recommendations. The objectives of this investigation were to characterize the safety and pharmacokinetic behavior of a low-molecular weight heparin (reviparin) administered throughout pregnancy. Forty-two patients followed in a tertiary-care rheumatology clinic who received prophylactic doses of reviparin (4900 anti-Xa units subcutaneously once daily) were enrolled in this investigation. Anti-Xa heparin levels, weights, and gestational ages of the patients were obtained on up to four occasions distributed throughout their pregnancy. The achieved anti-Xa heparin levels were highly correlated with the patient's weight, irrespective of the gestational age. No toxicity other than injection site hematomas was observed. The achieved intensity of anticoagulation with reviparin varies during pregnancy in direct proportion to the patient's weight. This variability may mandate dose adjustment in response to changes in a patient's weight during pregnancy, particularly if low-molecular weight heparin is administered at therapeutic doses.

Abortion, Habitual↗
PubMed2000

A reliable screening test to identify adult carriers of the (--SEA) alpha zero-thalassemia deletion. Detection of embryonic zeta-globin chains by enzyme-linked immunosorbent assay.

Homozygous (--SEA) alpha zero-thalassemia deletion, the cause of up to 80% of fetal hydrops in Southeast Asia, is encountered in many other countries. Heterozygous carrier rates of the deletion in Southeast Asian populations range from 4% to 14%. The laboratory screening for adult carriers of (--SEA) and other alpha zero-thalassemia deletions currently rests primarily with microscopic detection of hemoglobin H inclusion bodies within erythrocytes (Hb H screen). This test is laborious and observer dependent and has poor sensitivity. We assessed a colorimetric enzyme-linked immunosorbent assay (ELISA) to detect embryonic zeta-globin chains in adult hemolysates as an alternative to detect (--SEA) alpha zero-thalassemia deletion carriers. Blood samples from 221 adults with a mean corpuscular volume less than 80 micron 3 (80 fL) were studied prospectively by currently accepted hemoglobin screening tests and ELISA. Suspected cases of alpha-thalassemia were confirmed by DNA-based diagnostics. ELISA was highly sensitive (1.0) and specific (0.94) for the detection of adult carriers of (--SEA) alpha zero-thalassemia deletion. The hemoglobin H screen had a sensitivity of 0.47 and specificity of 0.99. The zeta-globin ELISA proved simple to perform, rapid, and applicable to high volume or population-based screening programs.

Adult↗
PubMed2000

Perioperative anticoagulation in patients with chronic atrial fibrillation who are undergoing elective surgery: results of a physician survey.

OBJECTIVE: To survey physicians' anticoagulation preferences in patients with chronic atrial fibrillation who are undergoing elective surgery. MATERIALS AND METHODS: A survey was performed that asked physicians to provide pre- and postoperative anticoagulation preferences for two clinical scenarios of patients with chronic atrial fibrillation (high stroke risk, low stroke risk) undergoing elective surgery. In addition to the interruption of warfarin therapy, perioperative anticoagulation options were as follows: a) in-hospital full dose intravenous heparin; b) outpatient full dose subcutaneous unfractionated heparin or low molecular weight heparin (LMWH); c) low dose unfractionated heparin or LMWH (postoperative only); d) nothing other than stopping warfarin preoperatively and restarting it postoperatively; or e) another anticoagulant strategy. RESULTS: In the high stroke risk scenario, the proportions of respondents preferring anticoagulation options a, b, d and e in the preoperative period were 24%, 20%, 54% and 2%, respectively; the proportions preferring options a, b, c, d and e in the postoperative period were 35%, 13%, 15%, 35% and 1%, respectively. In the low stroke risk scenario, the proportions of respondents preferring options a, b, d and e in the preoperative period were 7%, 10%, 80% and 3%, respectively; the proportions preferring options a, b, c, d and e in the postoperative period were 11%, 9%, 10%, 68% and 2%, respectively. CONCLUSIONS: In patients with chronic atrial fibrillation who underwent elective surgery, perioperative anticoagulant management preferences varied widely in patients at high risk for stroke, but were more uniform and less aggressive in patients at low risk for stroke.

Anticoagulants↗
PubMed1999

A randomized trial comparing 5-mg and 10-mg warfarin loading doses.

BACKGROUND: Warfarin sodium therapy is usually initiated with a loading dose to reduce the time required to elevate the international normalized ratio (INR). Warfarin loading doses are associated with early overanticoagulation and the development of a potential hypercoagulable state; they also may not hasten achieving an INR value between 2.0 and 3.0. This study was designed to prospectively confirm our observation that a 5-mg warfarin sodium loading dose is as effective as a 10-mg loading dose in achieving a therapeutic INR for 2 consecutive days on days 3 and 4 or 4 and 5 of therapy. METHODS: Fifty-three patients initiating warfarin therapy with a target INR of 2.0 to 3.0 were randomly allocated to receive an initial dose of 5 or 10 mg of warfarin. Subsequent doses were based on dosing algorithms. The INR was measured daily for 5 days. The primary end point of the study was the proportion of patients whose INR values were between 2.0 and 3.0 on 2 consecutive daily determinations on days 3, 4, or 5 of the study and whose INR did not exceed 3.0 at any point during the study. RESULTS: Five (24%) of 21 patients in the 10-mg group and 21 (66%) of 32 patients in the 5-mg group achieved the primary end point (relative risk 2.22, 95% confidence interval 1.30-3.70 [P < .003]). A trend toward less overanticoagulation was seen in the 5-mg warfarin group. CONCLUSION: A 10-mg loading dose of warfarin is unlikely to be more effective than a 5-mg loading dose in achieving an INR of 2.0 to 3.0 by day 4 or 5 of therapy.

Aged↗
PubMed1999

Physician preferences for perioperative anticoagulation in patients with a mechanical heart valve who are undergoing elective noncardiac surgery.

STUDY OBJECTIVE: To determine physicians' anticoagulation preferences in patients with a mechanical heart valve who are undergoing elective surgery, and to determine the effect of different risks of thromboembolism (TE) and postoperative bleeding on anticoagulation preferences. DESIGN: Mail survey of physicians who prescribe anticoagulant therapy. METHODS AND RESULTS: Physicians were asked to provide anticoagulation preferences in four clinical scenarios of patients with a mechanical heart valve who are undergoing elective surgery. Physicians were asked to select from three preoperative anticoagulation options (two aggressive, one less aggressive) and four postoperative anticoagulation options (two aggressive, two less aggressive). IV heparin was the most frequently selected anticoagulation option. Depending on the scenario, it was preferred by 39 to 79% of respondents for preoperative anticoagulation therapy, and by 44 to 84% of respondents for postoperative anticoagulant therapy. The risk of TE had a strong influence on anticoagulation preferences: more respondents preferred aggressive anticoagulant management in high-risk compared with low-risk TE scenarios (p < 0.001). Anticoagulation preferences were not influenced by the risk of bleeding: the proportion of respondents who preferred aggressive anticoagulant management did not differ in high-risk and low-risk bleeding scenarios (p > 0.05). Of respondents who preferred IV heparin for postoperative anticoagulation therapy, the risk of bleeding influenced the timing of heparin initiation: fewer respondents preferred early heparin initiation (within 12 h after surgery) in high-risk compared with low-risk bleeding scenarios (p < 0.01). CONCLUSIONS: (1) Preoperative and postoperative IV heparin were the most frequently selected anticoagulation options. (2) The risk of TE, but not the risk of bleeding, influenced the aggressiveness of anticoagulant management. (3) If IV heparin was selected, the risk of bleeding influenced the timing of heparin initiation.

Aged↗
PubMed1999

The effects of low-intensity warfarin on coagulation activation in patients with antiphospholipid antibodies and systemic lupus erythematosus.

The optimal intensity of oral anticoagulant therapy for the prevention of thromboembolism in patients with antiphospholipid antibodies (APLA) and systemic lupus erythematosus is controversial. Retrospective studies have suggested that patients with APLA are resistant to oral anticoagulant therapy, with a targeted International Normalization Ratio (INR) of 2.0 to 3.0, and that a higher intensity of anticoagulation (INR: 2.6 to 4.5) is required to prevent recurrent thromboembolism. To investigate if patients with APLA are resistant to the anticoagulant effect of low intensities of warfarin therapy, we performed a randomized trial in which 21 patients with APLA and systemic lupus erythematosus were allocated to receive one of three intensities of warfarin (INR: 1.1 to 1.4, 1.5 to 1.9 or 2.0 to 2.5) or placebo for four months. The main outcome was the effect of each intensity of warfarin therapy on prothrombin fragment 1+2 level (F1+2), that was used as a marker of coagulation activation. When F1+2 levels in patients allocated to the three warfarin intensities were compared to F1+2 levels in the placebo group, there was a statistically significant decrease (p<0.05) in the patient group receiving warfarin with a targeted INR of 2.0 to 2.5 at two, three and four months, and in the patient group with a targeted of INR 1.5 to 1.9 at three months. We conclude that in patients with APLA and systemic lupus erythematosus, warfarin therapy, with a targeted INR of 2.0 to 2.5, is effective in suppressing coagulation activation, and therefore, might be effective in preventing thromboembolism.

Adolescent↗
PubMed1998

Relation of factor V Leiden genotype to risk for acute deep venous thrombosis after joint replacement surgery.

BACKGROUND: A point mutation in coagulation factor V (A1691G) is associated with increased risk for venous thrombosis. However, limited information is available about the prospective risk for deep venous thrombosis in specific high-risk clinical settings. OBJECTIVE: To determine whether the factor V Leiden mutation is associated with an increased occurrence of deep venous thrombosis in patients undergoing hip or knee replacement surgery. DESIGN: Retrospective analysis of plasma samples obtained during six prospective clinical trials that compared different antithrombotic prophylaxis regimens in patients undergoing hip or knee replacement surgery. SETTING: Inpatients at the University of Rochester Medical Center, McMaster University Medical Center, Hamilton Civic Hospitals, and the Genesee Hospital. PATIENTS: 825 patients hospitalized for hip or knee replacement surgery. MEASUREMENTS: Venographically diagnosed postoperative deep venous thrombosis was correlated with factor V genotype. RESULTS: The factor V Leiden mutation was not associated with a significantly increased risk for venographically detected deep venous thrombosis. The absolute incidence of deep venous thrombosis was 31% (95% CI, 15% to 47%) in patients with the mutation and 26% (CI, 22% to 29%) in patients without the mutation (relative risk, 1.2 [CI, 0.6 to 2.9]). The factor V Leiden mutation was not significantly associated with deep venous thrombosis in subgroups of patients receiving warfarin or heparin. The incidence of clinical hemorrhage was similar in patients with (10%) and without (8%) the mutation. CONCLUSIONS: The factor V Leiden mutation is not a significant risk factor for acute deep venous thrombosis in this group of patients. Current data do not justify routine preoperative screening for this mutation or intensified perioperative prophylaxis in patients with the factor V Leiden mutation who are undergoing hip or knee joint replacement surgery and are receiving effective antithrombotic prophylaxis.

Aged↗
PubMed1998

Low-dose oral vitamin K reliably reverses over-anticoagulation due to warfarin.

BACKGROUND: Patients receiving long-term warfarin frequently develop asymptomatic excessive prolongation of their international normalized ratio (INR) results. The most appropriate management strategy in these patients is unknown. This prospective cohort study was designed to address whether 1 mg of oral vitamin K effectively reduces the INR value of such patients. METHODS: A prospective cohort study was performed in two tertiary care teaching hospitals, in which 62 patients receiving warfarin who had INR values between 4.5 and 10.0 received 1 mg of oral vitamin K. All patients had daily INR values and clinical assessments performed. RESULTS: The mean INR value at presentation was 5.79 (95% confidence interval (CI) 5.48 to 6.09, range 4.5 to 9.5). Sixteen hours after receiving the 1 mg of oral vitamin K, the mean INR was 2.86 (95% CI 2.50 to 3.23). On the second and third days after vitamin K, the mean INR values were 2.20 (1.93 to 2.47) and 2.14 (1.85 to 2.44), respectively. No adverse events or bleeding complications were observed. In three patients (6%) the INR value rose between the time of vitamin K administration and the next INR determination; two patients received a further 2 mg dose of subcutaneous vitamin K. CONCLUSIONS: In patients receiving warfarin who have asymptomatic excessive prolongations in their INR results, 1 mg of oral vitamin K reliably reduces the INR to the therapeutic range within 24 h. This therapy is more convenient, less expensive, and might be safer than parenteral vitamin K. Thus, it should be considered in all non-bleeding patients receiving warfarin, who present with INR results of 4.5 to 9.5.

Administration, Oral↗
PubMed1996

Splenectomy done during hematologic remission to prevent relapse in patients with thrombotic thrombocytopenic purpura.

OBJECTIVE: To assess whether splenectomy done during hematologic remission reduces the relapse rate in patients with relapsing thrombotic thrombocytopenic purpura. DESIGN: Consecutive case series. SETTING: Tertiary care teaching hospital. PATIENTS: 6 consecutive patients seen during a 10-year period who had had one or more relapses of thrombotic thrombocytopenic purpura. INTERVENTIONS: All patients had elective splenectomy while in hematologic remission and were followed after surgery for as long as 8.0 years. MEASUREMENTS: Attack rates (events per year) were calculated for each patient from time of presentation to time of splenectomy and from time of splenectomy to January 1996. RESULTS: A total of 26 episodes of thrombotic thrombocytopenic purpura occurred over 22.3 patient-years before splenectomy. After splenectomy, 3 acute episodes occurred over 22.7 patient-years. The attack rate (+/-1 SD) decreased from 2.3 +/- 2.0 events per year to 0.1 +/- 0.1 events per year. CONCLUSION: In patients who have had one or more relapses of thrombotic thrombocytopenic purpura, splenectomy done during hematologic remission reduces the frequency of acute relapse and the resulting need for medical therapy.

Humans↗
PubMed1996

Thrombocytopenia in pregnancy: diagnosis, pathogenesis and management.

Maternal thrombocytopenia is a common find during pregnancy. The rapid determination of its cause can often be difficult, with the diagnosis only being made in retrospect once the course of the platelet count is known. The majority of patients with thrombocytopenia in pregnancy will have incidental thrombocytopenia of pregnancy which is of no clinical significance.

Female↗