Anticoagulation therapy after recent bleeding: is it ever safe?
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Acute Disease↗
Biomedical subjects
R H White
Publications and source records attributed to R H White.
Assessment of manure phosphorus export through turfgrass sod production in Erath County, Texas.
A best management practice (BMP) for exporting manure phosphorus (P) in turfgrass sod from the North Bosque River (NBR) watershed in central Texas was assessed using a geographic information system (GIS). The NBR watershed has a mandate to reduce the total annual P load to the NBR by 50% as a result of total maximum daily load regulation. Since dairy waste applications to fields are identified as the major nonpoint source of P to the river, innovative BMPs, such as export of manure P in turfgrass, will be needed to achieve the 50% reduction. However, methods are needed to evaluate the feasibility of these innovative management practices prior to their implementation. A geospatial database of suitable turfgrass production sites was developed for Erath County using GIS. Erath County largely encompasses the upper portion of the NBR watershed. Information from field experiments, production practices, and ground-truthing was used to search, analyze, and verify a geospatial database developed from national and regional sources. The integration and analyses of large databases supports the search by turf producers for sites suitable for turfgrass sod production in Erath County. In addition, GIS enables researchers and regulators to estimate manure P exports and reduced P loading due to implementation of the manure export BMP on a county scale. Under optimal conditions 198,000 kg manure P yr(-1) could be used and 114,840 kg manure P yr(-1) exported from the NBR watershed through implementation of a system using dairy manure to produce turfgrass sod. This is the equivalent of the manure P applied from 10,032 dairy cows yr(-1) and exported from 5808 dairy cows yr(-1). Application of GIS to large-scale planning and decision-making transcends traditional field-scale applications in precision agriculture.
Agriculture↗
Effect of age on the incidence of venous thromboembolism after major surgery.
BACKGROUND: Most guidelines for administration of thromboprophylaxis after major surgery use age as a major predictor of postoperative venous thromboembolism (VTE). We sought to quantify the effect of age on the risk of symptomatic VTE after a spectrum of surgical procedures. METHODS: Using the California Patient Discharge Data Set and specific ICD-9-CM surgical procedure codes, we retrospectively determined the incidence of VTE diagnosed within 91 days after 40 different urgent or elective surgeries performed in the hospital between 1992 and 1996. Logistic regression was used to quantify the effect of age on the incidence of postoperative VTE and to adjust for other risk factors. RESULTS: 1,464,452 cases underwent one of 40 different procedures (mean cases per procedure = 35,718, range 4500-145 500). There was a significant interaction between age and the type of surgery performed (P<0.0001). Qualitative analysis of the effect of age on the incidence of VTE stratified by the presence or absence of malignancy revealed three general patterns: a steady increase in the incidence of VTE with age, exemplified by appendectomy or cholecystectomy; an increase in VTE up to approximately age 65 with no increase thereafter, exemplified by total hip arthroplasty; and no effect of age on the incidence of VTE, exemplified by vascular surgery. CONCLUSIONS: The relationship between age and the risk of VTE after surgery is complex and depends on the nature of the surgery and the underlying pathologic process. Advancing age was a significant predictor for VTE following surgeries performed for conditions not inherently associated with significant comorbidity. Conversely, advancing age was not associated with a higher incidence of VTE after surgeries performed for conditions strongly associated with serious underlying comorbidity, such as a malignancy or severe peripheral vascular disease.
Adult↗
Urban air pollution, health, and equity.
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Air Pollutants↗
Biosynthesis of the phosphodiester bond in coenzyme F(420) in the methanoarchaea.
The biochemical route for the formation of the phosphodiester bond in coenzyme F(420), one of the methanogenic coenzymes, has been established in the methanoarchaea Methanosarcina thermophila and Methanococcus jannaschii. The first step in the formation of this portion of the F(420) structure is the GTP-dependent phosphorylation of L-lactate to 2-phospho-L-lactate and GDP. The 2-phospho-L-lactate represents a new natural product that was chemically identified in Methanobacterium thermoautotrophicum, M. thermophila, and Mc. jannaschii. Incubation of cell extracts of both M. thermophila and Mc. jannaschii with [hydroxy-(18)O, carboxyl-(18)O(2)]lactate and GTP produced 2-phospho-L-lactate with the same (18)O distribution as found in both the starting lactate and the lactate recovered from the incubation. These results indicate that the carboxyl oxygens are not involved in the phosphorylation reaction. Incubation of Sephadex G-25 purified cell extracts of M. thermophila or Mc. jannaschii with 7,8-didemethyl-8-hydroxy-5-deazariboflavin (Fo), 2-phospho-L-lactate, and GTP or ATP lead to the formation of F(420)-0 (F(420) with no glutamic acids). This transformation was shown to involve two steps: (i) the GTP- or ATP-dependent activation of 2-phospho-L-lactate to either lactyl(2)diphospho-(5')guanosine (LPPG) or lactyl(2)diphospho-(5')adenosine (LPPA) and (ii) the reaction of the resulting LPPG or LPPA with Fo to form F(420)-0 with release of GMP or AMP. Attempts to identify LPPG or LPPA intermediates by incubation of cell extracts with L-[U-(14)C]lactate, [U-(14)C]2-phospho-L-lactate, or [8-(3)H]GTP were not successful owing to the instability of these compounds toward hydrolysis. Synthetically prepared LPPG and LPPA had half-lives of 10 min at 50 degrees C (at pH 7.0) and decomposed into GMP or AMP and 2-phospho-L-lactate via cyclic 2-phospho-L-lactate. No evidence for the functioning of the cyclic 2-phospho-L-lactate in the in vitro biosynthesis could be demonstrated. Incubation of cell extracts of M. thermophila or Mc. jannaschii with either LPPG or LPPA and Fo generated F(420)-0. In summary, this study demonstrates that the formation of the phosphodiester bond in coenzyme F(420) follows a reaction scheme like that found in one of the steps of the DNA ligase reaction and in the biosynthesis of coenzyme B(12) and phospholipids.
Adenosine Triphosphate↗
The first examples of (S)-2-hydroxyacid dehydrogenases catalyzing the transfer of the pro-4S hydrogen of NADH are found in the archaea.
Reduction of 2-oxoacids to the corresponding (S)-2-hydroxyacids is an important transformation in biochemistry. To date all (S)-2-hydroxyacid dehydrogenases belonging to the L-lactate/L-malate dehydrogenase family have been found to transfer the pro-4R hydrogen of either NADH or NADPH to C-2 of the 2-oxoacid substrates during their reduction. Here, we report that recombinantly generated (S)-2-hydroxyacid dehydrogenases present in the methanoarchaea Methanococcus jannaschii and Methanothermus fervidus use the pro-4S hydrogen of NADH to reduce a series of 2-oxoacids to the corresponding (S)-2-hydroxyacids. This information as well as the low sequence identity between these archaeal enzymes and the L-lactate/L-malate family of enzymes indicate that these enzymes are not evolutionary related and therefore constitute a new class of (S)-2-hydroxyacid dehydrogenases.
Alcohol Oxidoreductases↗
Warfarin therapy for an octogenarian who has atrial fibrillation.
In North America, atrial fibrillation is associated with at least 75 000 ischemic strokes each year. Most of these strokes occur in patients older than 75 years of age. The high incidence of stroke in very elderly persons reflects the increasing prevalence of atrial fibrillation that occurs with advanced age, the high incidence of stroke in elderly patients, and the failure of physicians to prescribe antithrombotic therapy in most of these patients. This failure is related to the increased risk for major hemorrhage with advanced age, obfuscating the decision to institute stroke prophylaxis with antithrombotic therapy. This case-based review describes the risk and benefits of prescribing antithrombotic therapy for a hypothetical 80-year-old man who has atrial fibrillation and hypertension, and it offers practical advice on managing warfarin therapy. After concluding that the benefits of warfarin outweigh its risks in this patient, we describe how to initiate warfarin therapy cautiously and how to monitor and dose the drug. We then review five recent randomized, controlled trials that document the increased risk for stroke when an international normalized ratio (INR) of less than 2.0 is targeted among patients with atrial fibrillation. Next, we make the case that cardioversion is not needed for this asymptomatic patient with chronic atrial fibrillation. Instead, we choose to leave the patient in atrial fibrillation and to control his ventricular rate with atenolol. Later, when the INR increases to 4.9, we advocate withholding one dose of warfarin and repeating the INR test. Finally, when the patient develops dental pain, we review the analgesic agents that are safe to take with warfarin and explain why warfarin therapy does not have to be interrupted during a subsequent dental extraction.
Aged↗
Treatment of venous thromboembolism using only low-molecular-weight heparin?
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Administration, Oral↗
Seasonal control of warfarin therapy.
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Anticoagulants↗
Biosynthesis of the methanogenic cofactors.
Our current knowledge of the pathways and genes involved in the biosynthesis of the methanogenic coenzymes methanopterin, coenzyme B, methanofuran, coenzyme F420, and coenzyme M is presented. Proposed reaction mechanisms for several of the novel reactions involved in the pathways are presented.
Coenzymes↗
Identification of coenzyme M biosynthetic 2-phosphosulfolactate phosphatase. A member of a new class of Mg(2+)-dependent acid phosphatases.
Coenzyme M (CoM; 2-mercaptoethanesulfonic acid) is the terminal methyl carrier in methanogenesis. Methanogenic archaea begin the production of this essential cofactor by sulfonating phosphoenolpyruvate to form 2-phospho-3-sulfolactate. After dephosphorylation, this precursor is oxidized, decarboxylated and then reductively thiolated to form CoM. A thermostable phosphosulfolactate phosphohydrolase (EC 3.1.3.-) catalyzing the second step in CoM biosynthesis, was identified in the hyperthermophilic euryarchaeon Methanococcus jannaschii. The predicted ORF MJ1140 in the genome of M. jannaschii encodes ComB, a Mg2+-dependent acid phosphatase that is specific for 2-hydroxycarboxylic acid phosphate esters. Recombinantly expressed purified ComB efficiently hydrolyzes rac-2-phosphosulfolactate, (S)-2-phospholactate, phosphoglycolate and both enantiomers of 2-phosphomalate. In contrast to previously studied phosphoglycolate phosphatases, ComB has a low pH optimum for activity, a narrow substrate specificity and an amino acid sequence dissimilar to any biochemically characterized protein. Like other phosphatases that function via covalent phosphoenzyme intermediates, ComB can catalyze a transphosphorylation reaction. Homologs of comB are identified in all available cyanobacterial genome sequences and in genomes from phylogenetically diverse bacteria and archaea; most of these organisms lack homologs of other CoM biosynthetic genes. The broad and disparate distribution of comB homologs suggests that the gene has been recruited frequently into new metabolic pathways.
Acid Phosphatase↗
Anticoagulation in the elderly.
Oral anticoagulation therapy has demonstrated benefit in the treatment and prevention of a variety of thromboembolic disorders. Most individuals who receive oral anticoagulant therapy are elderly patients with nonvalvular atrial fibrillation and acute or recurrent venous thromboembolism. Anticoagulation in elderly patients poses unique challenges for the practicing clinician because they are simultaneously at higher risk for recurrent thromboembolism and major bleeding, including catastrophic intracranial hemorrhage. The pharmacology of warfarin in the elderly is reviewed, including important drug interactions and current dosing recommendations for elderly patients. Evidence of the benefits and risks of oral anticoagulation therapy are reviewed for patients with atrial fibrillation and venous thromboembolism. This information should enable practitioners to better assess the relative risks and benefit of oral anticoagulation therapy to guide treatment decisions in the elderly.
Age Factors↗
Methanococcus jannaschii generates L-proline by cyclization of L-ornithine.
Cell extracts of Methanococcus jannaschii have been shown to readily convert L-ornithine to L-proline. This cyclization reaction proceeds with the loss of only the C-2 nitrogen, as has been documented for ornithine cyclodeaminase (EC 4.3.1.12). Since no gene homologous to that coding for ornithine cyclodeaminase is present in the genome of M. jannaschii, these results indicate that proline biosynthesis in M. jannaschii is accomplished by a previously unrecognized enzyme.
Ammonia-Lyases↗
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↗
Predictors of rehospitalization for symptomatic venous thromboembolism after total hip arthroplasty.
BACKGROUND: Recent studies have shown that symptomatic venous thromboembolism after total hip arthroplasty most commonly develops after the patient is discharged from the hospital. Risk factors associated with these symptomatic thromboembolic events are not well defined. METHODS: Using administrative data from the California Medicare records for 1993 through 1996, we identified 297 patients 65 years of age or older who were rehospitalized for thromboembolism within three months after total hip arthroplasty. We compared demographic, surgical, and medical variables potentially associated with the development of thromboembolism in these patients and 592 unmatched controls. RESULTS: A total of 89.6 percent of patients with thromboembolism and 93.8 percent of control patients were treated with pneumatic compression, warfarin, enoxaparin, or unfractionated heparin, alone or in combination. In addition, 22.2 percent and 29.7 percent, respectively, received warfarin after discharge. A body-mass index (the weight in kilograms divided by the square of the height in meters) of 25 or greater was associated with rehospitalization for thromboembolism, with an odds ratio of 2.5 (95 percent confidence interval, 1.8 to 3.4). In a multivariate model, the only prophylactic regimens associated with a reduced risk of thromboembolism were pneumatic compression in patients with body-mass indexes of less than 25 (odds ratio, 0.3; 95 percent confidence interval, 0.2 to 0.6) and warfarin treatment after discharge (odds ratio, 0.6; 95 percent confidence interval, 0.4 to 1.0). CONCLUSIONS: In patients who underwent total hip arthroplasty, a body-mass index of 25 or greater was associated with subsequent hospitalization for thromboembolism. Pneumatic compression in patients with a body-mass index of less than 25 and prophylaxis with warfarin after discharge were independently protective against thromboembolism.
Aged↗
Management and dosing of warfarin therapy.
When initiating warfarin therapy, clinicians should avoid loading doses that can raise the International Normalized Ratio (INR) excessively; instead, warfarin should be initiated with a 5-mg dose (or 2 to 4 mg in the very elderly). With a 5-mg initial dose, the INR will not rise appreciably in the first 24 hours, except in rare patients who will ultimately require a very small daily dose (0.5 to 2.0 mg). Adjusting a steady-state warfarin dose depends on the measured INR values and clinical factors: the dose does not need to be adjusted for a single INR that is slightly out of range, and most changes should alter the total weekly dose by 5% to 20%. The INR should be monitored frequently (eg, 2 to 4 times per week) immediately after initiation of warfarin; subsequently, the interval between INR tests can be lengthened gradually (up to a maximum of 4 to 6 weeks) in patients with stable INR values. Patients who have an elevated INR will need more frequent testing and may also require vitamin K1. For example, a nonbleeding patient with an INR of 9 can be given low-dose vitamin K1 (eg, 2.5 mg phytonadione, by mouth). Patients who have an excessive INR with clinically important bleeding require clotting factors (eg, fresh-frozen plasma) as well as vitamin K1.
Administration, Oral↗
A population-based study of the effectiveness of inferior vena cava filter use among patients with venous thromboembolism.
BACKGROUND: There are few population-based data regarding the effectiveness of inferior vena cava filter use in the prevention of symptomatic pulmonary embolism. OBJECTIVE: To determine the 1-year cumulative incidence of rehospitalization for venous thrombosis or pulmonary embolism among patients with thromboembolism treated with a vena cava filter compared with the incidence in a control population with thromboembolism. PATIENTS AND METHODS: Population-based retrospective analysis of linked hospital discharge abstracts in California. From January 1, 1991, through December 30, 1995, 3632 patients were treated with a filter and 64,333 controls were admitted with a principal diagnosis of venous thromboembolism. RESULTS: Filter-treated patients had significantly greater comorbidity, with a higher frequency of previous pulmonary embolism, recent major bleeding, malignant neoplasm, and stroke. Patients who initially manifested pulmonary embolism were significantly more likely to be rehospitalized for pulmonary embolism than patients with an initial diagnosis of venous thrombosis alone, among filter-treated patients (relative risk, 6.72; 95% confidence interval, 3.61-12.49) and controls (relative risk, 5.30; 95% confidence interval, 4.61-6.10). Risk-adjusted proportional hazards modeling showed no significant difference between filter-treated patients and controls in the relative hazard of rehospitalization for pulmonary embolism. However, filter placement was associated with a significantly higher relative hazard of rehospitalization for venous thrombosis among patients who initially manifested pulmonary embolism (relative hazard, 2.62; 95% confidence interval, 2.09-3.29), but not among those who presented with venous thrombosis (relative hazard, 1.14; 95% confidence interval, 0.92-1.43). CONCLUSIONS: Insertion of a vena cava filter was not associated with a significant reduction in the 1-year incidence of rehospitalization for pulmonary embolism. Use of a filter was associated with a higher incidence of rehospitalization for venous thrombosis, but only among patients who initially manifested pulmonary embolism. A prospective clinical study is needed to determine the efficacy of filter use among patients with pulmonary embolism who do not meet strict guidelines for insertion of a vena cava filter.
Adult↗
Temporary reversal of anticoagulation using oral vitamin K.
Brief reversal of oral anticoagulant therapy is frequently necessary prior to minor surgery or invasive procedures. We sought to determine the effect of an oral dose of 2.0 mg of vitamin K(1) on the international normalized ratio (INR) among patients with a stable therapeutic INR who were maintained on their daily dose of warfarin. We prospectively studied a convenience cohort of patients attending an anticoagulation clinic who had either just completed treatment for venous thromboembolism or were receiving prophylaxis for atrial fibrillation, cardiomyopathy, or peripheral vascular disease. Each patient received an oral dose of 2.0 mg of aqueous vitamin K(1). Serial INR measurements were taken over 1 week. There was wide variation in the INR response between patients, from no change to complete reversal of anticoagulation. The effect also varied widely over time. There was a significant inverse correlation between the fall in logarithm of the INR and the daily warfarin dose required to achieve an INR value of 2.5 (r=-0.52, p=0.011). Use of a 2.0 mg oral dose of vitamin K(1) does not reliably reverse (correct) a therapeutic INR in patients maintained on their daily dose of warfarin.
Administration, Oral↗