DOCSLIB.ORG

Aspirin Versus Anticoagulation for Prevention of Venous Thromboembolism Major Lower Extremity Orthopedic Surgery: a Systematic Review and Meta-Analysis

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Aspirin Versus Anticoagulation for Prevention of Venous Thromboembolism Major Lower Extremity Orthopedic Surgery: a Systematic Review and Meta-Analysis ORIGINAL RESEARCH Aspirin Versus Anticoagulation for Prevention of Venous Thromboembolism Major Lower Extremity Orthopedic Surgery: A Systematic Review and Meta-Analysis Frank S. Drescher, MD1*, Brenda E. Sirovich, MD, MS2, Alexandra Lee, MS3, Daniel H. Morrison, MD, MS4, Wesley H. Chiang, MS2, Robin J. Larson, MD, MPH2 1Geisel School of Medicine at Dartmouth, Pulmonary and Critical Care Medicine, Veterans Affairs Medical Center, White River Junction, Vermont; 2Geisel School of Medicine at Dartmouth, and the Dartmouth Institute for Health Policy and Clinical Practice, Center for Education, Lebanon, New Hampshire; 3Herbert Wertheim College of Medicine at Florida International University, Miami, Florida; 4Geisel School of Medicine at Dartmouth, Sec- tion of Otolaryngology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire. BACKGROUND: Hip fracture surgery and lower extremity screened participants for deep venous thrombosis (DVT). arthroplasty are associated with increased risk of both Overall rates of DVT did not differ statistically between aspi- venous thromboembolism and bleeding. The best pharma- rin and anticoagulants (relative risk [RR]: 1.15 [95% confi- cologic strategy for reducing these opposing risks is dence interval {CI}: 0.68–1.96]). Subgrouped by type of uncertain. surgery, there was a nonsignificant trend favoring anticoa- gulation following hip fracture repair but not knee or hip PURPOSE: To compare venous thromboembolism (VTE) arthroplasty (hip fracture RR: 1.60 [95% CI: 0.80–3.20], 2 tri- and bleeding rates in adult patients receiving aspirin versus als; arthroplasty RR: 1.00 [95% CI: 0.49–2.05], 5 trials). The anticoagulants after major lower extremity orthopedic risk of bleeding was lower with aspirin than anticoagulants surgery. following hip fracture repair (RR: 0.32 [95% CI: 0.13–0.77], 2 DATA SOURCES: Medline, Cumulative Index to Nursing trials), with a nonsignificant trend favoring aspirin after and Allied Health Literature, and the Cochrane Library arthroplasty (RR: 0.63 [95% CI: 0.33–1.21], 5 trials). Rates through June 2013; reference lists, ClinicalTrials.gov, and of pulmonary embolism were too low to provide reliable scientific meeting abstracts. estimates. STUDY SELECTION: Randomized trials comparing aspirin CONCLUSION: Compared with anticoagulation, aspirin to anticoagulants for prevention of VTE following major may be associated with higher risk of DVT following hip lower extremity orthopedic surgery. fracture repair, although bleeding rates were substantially DATA EXTRACTION: Two reviewers independently lower. Aspirin was similarly effective after lower extremity extracted data on rates of VTE, bleeding, and mortality. arthroplasty and may be associated with lower bleeding risk. Journal of Hospital Medicine 2014;9:579–585. VC 2014 DATA SYNTHESIS: Of 298 studies screened, 8 trials includ- Society of Hospital Medicine ing 1408 participants met inclusion criteria; all trials Each year in the United States, over 1 million adults ity and mortality for patients, as well as substantial undergo hip fracture surgery or elective total knee or costs to the healthcare system.6 Although VTE is con- hip arthroplasty.1 Although highly effective for sidered to be a preventable cause of hospital admis- improving functional status and quality of life,2,3 each sion and death,7,8 the postoperative setting presents a of these procedures is associated with a substantial particular challenge, as efforts to reduce clotting must risk of developing a deep vein thrombosis (DVT) or be balanced against the risk of bleeding. pulmonary embolism (PE).4,5 Collectively referred to Despite how common this scenario is, there is no as venous thromboembolism (VTE), these clots in the consensus regarding the best pharmacologic strategy. venous system are associated with significant morbid- National guidelines recommend “pharmacologic thromboprophylaxis,” leaving the clinician to select the specific agent.4,5 Explicitly endorsed options include aspirin, vitamin K antagonists (VKA), unfrac- *Address for correspondence and reprint requests: Frank Drescher, tionated heparin, fondaparinux, low-molecular-weight MD, Assistant Professor of Medicine, Geisel School of Medicine at Dart- heparin (LMWH) and IIa/Xa factor inhibitors. Among mouth, Pulmonary and Critical Care Medicine, Veterans Affairs Medical these, aspirin, the only nonanticoagulant, has been the Center,(111) 215 North Main Street, White River Junction, VT 05009; 4,9,10 Telephone: 802-295-9363; Fax: 802-291-6257; E-mail: source of greatest controversy. [email protected] Two previous systematic reviews comparing aspirin Additional Supporting Information may be found in the online version of to anticoagulation for VTE prevention found conflict- this article. ing results.11,12 In addition, both used indirect com- Received: February 12, 2014; Revised: May 9, 2014; Accepted: May 20, parisons, a method in which the intervention and 2014 2014 Society of Hospital Medicine DOI 10.1002/jhm.2224 comparison data come from different studies, and sus- 13,14 Published online in Wiley Online Library (Wileyonlinelibrary.com). ceptibility to confounding is high. We aimed to An Official Publication of the Society of Hospital Medicine Journal of Hospital Medicine Vol 9 | No 9 | September 2014 579 Drescher et al | VTE Prevention After Orthopedic Surgery overcome the limitations of prior efforts to address our inclusion criteria. We used exploded Medical Sub- this commonly encountered clinical question by con- ject Headings terms and key words to generate sets ducting a systematic review and meta-analysis of for “aspirin” and “major orthopedic surgery” themes, randomized controlled trials that directly compared then used the Boolean term, “AND,” to find their the efficacy and safety of aspirin to anticoagulants for intersection. VTE prevention in adults undergoing common high- risk major orthopedic surgeries of the lower Additional Search Methods extremities. We manually reviewed references of relevant articles and searched ClinicalTrials.gov to identify any MATERIAL AND METHODS ongoing studies or unpublished data. We further Review Protocol searched the following sources: American College of Prior to conducting the review, we outlined an Chest Physicians (ACCP) Evidence-Based Clinical 4,17 approach to identifying and selecting eligible studies, Practice Guidelines, American Academy of Ortho- 5 prespecified outcomes of interest, and planned sub- paedic Surgeons guidelines (AAOS), and annual group analyses. The meta-analysis was performed meeting abstracts of the American Academy of Ortho- 18 according to the Preferred Reporting Items for System- paedic Surgery, the American Society of Hematol- 19 20 atic Reviews and Meta-Analyses and Cochrane ogy, and the ACCP. guidelines.15,16 Study Selection Study Eligibility Criteria Two pairs of 2 reviewers independently scanned the We prespecified the following inclusion criteria: (1) titles and abstracts of identified studies, excluding only the design was a randomized controlled trial; (2) the those that were clearly not relevant. The same reviewers population consisted of patients undergoing major independently reviewed the full text of each remaining orthopedic surgery including hip fracture surgery or study to make final decisions about eligibility. total knee or hip arthroplasty; (3) the study compared Data Extraction and Quality Assessment aspirin to 1 or more anticoagulants: VKA, unfractio- Two reviewers independently extracted data from nated heparin, LMWH, thrombin inhibitors, pentasac- each included study and rendered judgments regarding charides (eg, fondaparinux), factor Xa/IIa inhibitors the methodological quality using the Cochrane Risk dosed for VTE prevention; (4) subjects were followed of Bias Tool.21 for at least 7 days; and (5) the study reported at least 1 prespecified outcome of interest. We allowed the use Data Synthesis of pneumatic compression devices, as long as devices We used Review Manager (RevMan 5.1) to calculate were used in both arms of the study. pooled risk ratios using the Mantel-Haenszel method and random-effects models, which take into account Outcome Measures the presence of variability among included stud- We designated the rate of proximal DVT (occurring ies.16,22 We also manually pooled absolute event rates in the popliteal vein and above) as the primary out- for each study arm using the study weights assigned in come of interest. Additional efficacy outcomes the pooled risk ratio models. included rates of PE, PE-related mortality, and all- cause mortality. We required that DVT and PE were Assessment of Heterogeneity and Reporting Biases diagnosed by venography, computed tomography We assessed statistical variability among the studies (CT) angiography of the chest, pulmonary angiogra- contributing to each summary estimate and considered phy, ultrasound Doppler of the legs, or ventilation/ studies unacceptably heterogeneous if the test for het- perfusion scan. We allowed studies that screened par- erogeneity P value was <0.10 or the I2 exceeded ticipants for VTE (including the use of fibrinogen leg 50%.14,16 We constructed funnel plots to assess for scanning). publication bias but had too few studies for reliable A bleeding event was defined as any need for post- interpretation. operative blood transfusion or otherwise clinically sig- nificant bleeding (eg, prolonged postoperative wound Subgroup Analyses bleeding). We further defined major bleeding as the We prespecified subgroup analyses based on the indica- requirement
Load more

Recommended publications
  • Surfen, a Small Molecule Antagonist of Heparan Sulfate
    Surfen, a small molecule antagonist of heparan sulfate Manuela Schuksz*†, Mark M. Fuster‡, Jillian R. Brown§, Brett E. Crawford§, David P. Ditto¶, Roger Lawrence*, Charles A. Glass§, Lianchun Wang*, Yitzhak Torʈ, and Jeffrey D. Esko*,** *Department of Cellular and Molecular Medicine, Glycobiology Research and Training Center, †Biomedical Sciences Graduate Program, ‡Department of Medicine, Division of Pulmonary and Critical Care Medicine and Veteran’s Administration San Diego Medical Center, ¶Moores Cancer Center, and ʈDepartment of Chemistry and Biochemistry, University of California at San Diego, La Jolla, CA 92093; and §Zacharon Pharmaceuticals, Inc, 505 Coast Blvd, South, La Jolla, CA 92037 Communicated by Carolyn R. Bertozzi, University of California, Berkeley, CA, June 18, 2008 (received for review May 26, 2007) In a search for small molecule antagonists of heparan sulfate, Surfen (bis-2-methyl-4-amino-quinolyl-6-carbamide) was first we examined the activity of bis-2-methyl-4-amino-quinolyl-6- described in 1938 as an excipient for the production of depot carbamide, also known as surfen. Fluorescence-based titrations insulin (16). Subsequent studies have shown that surfen can indicated that surfen bound to glycosaminoglycans, and the extent block C5a receptor binding (17) and lethal factor (LF) produced of binding increased according to charge density in the order by anthrax (18). It was also reported to have modest heparin- heparin > dermatan sulfate > heparan sulfate > chondroitin neutralizing effects in an oral feeding experiments in rats (19), sulfate. All charged groups in heparin (N-sulfates, O-sulfates, and but to our knowledge, no further studies involving heparin have carboxyl groups) contributed to binding, consistent with the idea been conducted, and its effects on HS are completely unknown.
    [Show full text]
  • A 74-Year-Old Woman with Abdominal Pain and Fever
    A SELF-TEST IM BOARD REVIEW DAVID L. LONGWORTH, MO, JAMES K. STOLLER, MD, EDITORS OF CLINICAL PETER MAZZONE, MD CRAIG NIELSEN, MD RECOGNITION Department of Pulmonary and Critical Department of General Internal Care Medicine, Cleveland Clinic Medicine, Cleveland Clinic A 74-year-old woman with abdominal pain and fever 74-YEAR-OLD WOMAN was transferred pulmonary embolism, and a subsequent pul- from a local hospital for further evalua- monary angiogram was read as normal. A tion and management of abdominal pain with chest CT scan did not reveal anything other fever. than the small bilateral pleural effusions seen The patient had presented to the local on the chest radiograph. A thoracentesis hospital 11 days before with a 1-day history of revealed transudative fluid only. Intravenous bilateral upper-quadrant abdominal pain. She heparin was discontinued. described the pain as a constant ache with Past history. The patient had had essen- intermittent sharper pains accompanied by tial thrombocythemia for 5 years, for which nausea, but she could not identify any precip- she took hydroxyurea until 2 months before itants of the pain. She was also constipated. admission. Hydroxyurea was restarted at the A few days after being admitted to the local hospital because her platelet count was local hospital, the patient had developed a high at 750 x 109/L (normal 150-400 x fever and mild shortness of breath. She was 109/L), but it was stopped 3 days later because treated empirically for a possible pulmonary of mucositis. More than 30 years ago, the infection with a variety of antibiotics (ceftri- patient had been diagnosed with "pernicious Her platelet axone, ticarcillin-clavulanate, erythromycin, anemia.
    [Show full text]
  • Treatment of 51 Pregnancies with Danaparoid Because of Heparin
    ©2005 Schattauer GmbH,Stuttgart Blood Coagulation, Fibrinolysis and CellularHaemostasis Treatment of 51 pregnancies withdanaparoidbecause of heparin intolerance EdelgardLindhoff-Last1 ,Hans-Joachim Kreutzenbeck2 ,Harry N. Magnani3 1 Division ofVascular Medicine,Department of Internal Medicine,University Hospital Frankfurt, Germany 2 MedicalDepartment, Celltech, Essen, Germany 3 Clinical Consultant Marketing, OrganonBV, Oss,The Netherlands Summary Pregnant patients withacute venous thrombosis or ahistoryof required (3/14) or an adverse eventled to atreatment discon- thrombosis mayneed alternative anticoagulation, when heparin tinuation (11/14).Four maternal bleeding events were recorded intolerance occurs. Onlylimited dataonthe useofthe hepari- during pregnancy, deliveryorpostpartum, twoofthemwere noiddanaparoid areavailable in literature.We reviewedthe use fatal duetoplacental problems.Three fetal deathswererec- of danaparoid in 51 pregnancies of 49 patients identified in litera- orded,all associated with maternal complications antedating da- turebetween 1981 and 2004.All patients had developed hepa- naparoiduse.Danaparoid cross-reactivity was suspectedin4 rin intolerance (32 duetoheparin-induced thrombocytopenia, HITpatientsand 5non-HITpatientswith skin reactions and was 19 mainlydue to heparin-induced skin rashes)and had acurrent confirmedserologicallyinone of the twoHIT patients tested.In and/or pasthistoryofthromboembolic complications.The initial none of fivefetal cordblood- andthree maternal breast milk- danaparoid doseregimens ranged
    [Show full text]
  • Avoiding Intelligence Failures in the Cardiac Catheterization Laboratory
    Review Avoiding Intelligence Failures in the Cardiac Catheterization Laboratory: Strategies for the Safe and Rational Use of Dalteparin or Enoxaparin during Percutaneous Coronary Intervention Jonathan D. Marmur, MD, Renee P. Bullock-Palmer, MD, Shyam Poludasu, MD, Erdal Cavusoglu, MD ABSTRACT: Low-molecular-weight heparin (LMWH) has been a of unstable angina (UA) and non-ST-segment elevation myocardial mainstay for the management of acute coronary syndromes (ACS) for infarction (NSTEMI). The ESSENCE and TIMI 11B trials support almost a decade. However, several recent developments have seriously the use of LMWH over unfractionated heparin (UFH) in acute coro - threatened the prominence of this drug class: (i) the adoption of an nary syndromes managed with a predominantly medical approach early invasive strategy, frequently leading to percutaneous coronary in - 1,2 tervention (PCI) where the dosing and monitoring of LMWH is un - as opposed to an invasive initial strategy. familiar to most operators, (ii) the results of the SYNERGY trial, which Since the publication of the ESSENCE and TIMI 11B trials, not only failed to establish the superiority of enoxaparin over unfrac - the management of acute coronary syndromes (ACS) has tionated heparin with respect to efficacy, but also demonstrated more evolved to favor an early invasive strategy. This evolution is sup - bleeding with LMWH, and (iii) the results of the REPLACE-2 and ported by a number of studies, including the FRISC II and the ACUITY trials, which have demonstrated the advantages of an ACS TACTICS TIMI-18 trials. 3,4 The Superior Yield of the New and PCI treatment strategy based on direct thrombin inhibition with bivalirudin.
    [Show full text]
  • Heparin-Induced Thrombocytopenia (Hit)
    HEPARIN‐INDUCED THROMBOCYTOPENIA (HIT) OBJECTIVE: To assist clinicians with the diagnosis and initial management of heparin‐induced thrombocytopenia (HIT) and suspected HIT. BACKGROUND: HIT is a transient, immune‐mediated adverse drug reaction in patients recently exposed to heparin that generally produces thrombocytopenia and often results in venous and/or arterial thrombosis. HIT occurs in up to 5% of patients receiving unfractionated heparin (UFH) and in <1% who receive low molecular weight heparin (LMWH). HIT is characterised by immunoglobulin G (IgG) antibodies that recognize an antigen complex of platelet factor 4 (PF4) bound to heparin. These antibodies trigger a highly prothrombotic state by causing intravascular platelet aggregation, intense platelet, monocyte and endothelial cell activation and excessive thrombin generation. CLINICAL FEATURES: HIT typically presents with a fall in platelet count with or without venous and/or arterial thrombosis. Thrombocytopenia: A platelet count fall >30% beginning 5‐10 days after heparin exposure, in the absence of other causes of thrombocytopenia, should be considered to be HIT, unless proven otherwise. A more rapid onset of platelet count fall (often within 24 hours of heparin exposure) can occur when there is a history of heparin exposure within the preceding 3 months. Bleeding is very infrequent. Thrombosis: HIT is associated with a high risk (30‐50%) of new venous or arterial thromboembolism. Thrombosis may be the presenting clinical manifestation of HIT or can occur during or shortly after the thrombocytopenia. Other clinical manifestations of HIT: Less frequent manifestations include heparin‐induced skin lesions, adrenal hemorrhagic infarction, transient global amnesia, and acute systemic reactions (e.g. chills, dyspnea, cardiac or respiratory arrest following IV heparin bolus).
    [Show full text]
  • Low Molecular Weight Heparins and Heparinoids
    NEW DRUGS, OLD DRUGS NEW DRUGS, OLD DRUGS Low molecular weight heparins and heparinoids John W Eikelboom and Graeme J Hankey UNFRACTIONATED HEPARIN has been used in clinical ABSTRACT practice for more than 50 years and is established as an effective parenteral anticoagulant for the prevention and ■ Several low molecular weight (LMW) heparin treatment of various thrombotic disorders. However, low preparations, including dalteparin, enoxaparin and molecularThe Medical weight Journal (LMW) of heparinsAustralia haveISSN: recently 0025-729X emerged 7 October as nadroparin, as well as the heparinoid danaparoid sodium, more2002 convenient, 177 6 379-383 safe and effective alternatives to unfrac- are approved for use in Australia. 1 tionated©The heparin Medical (BoxJournal 1). of AustraliaIn Australia, 2002 wwwLMW.mja.com.au heparins are ■ LMW heparins are replacing unfractionated heparin for replacingNew Drugs,unfractionated Old Drugs heparin for preventing and treating the prevention and treatment of venous thromboembolism venous thromboembolism and for the initial treatment of and the treatment of non-ST-segment-elevation acute unstable acute coronary syndromes. The LMW heparinoid coronary syndromes. danaparoid sodium is widely used to treat immune heparin- ■ induced thrombocytopenia. The advantages of LMW heparins over unfractionated heparin include a longer half-life (allowing once-daily or twice-daily subcutaneous dosing), high bioavailability and Limitations of unfractionated heparin predictable anticoagulant response (avoiding the need
    [Show full text]
  • Low Molecular Weight Heparinoid, ORG 10172 (Danaparoid), and Outcome After Acute Ischemic Stroke a Randomized Controlled Trial
    Original Contributions Low Molecular Weight Heparinoid, ORG 10172 (Danaparoid), and Outcome After Acute Ischemic Stroke A Randomized Controlled Trial The Publications Committee for the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) Investigators Context.—Anticoagulation with unfractionated heparin is used commonly for ANTICOAGULATION with unfrac- treatment of acute ischemic stroke, but its use remains controversial because it has tionated heparin commonly is used to not been shown to be effective or safe. Low molecular weight heparins and hepa- treat persons with acute ischemic 1 rinoids have been shown to be effective in preventing deep vein thrombosis in per- stroke. However, the use of heparin re- mains controversial because it is not es- sons with stroke, and they might be effective in reducing unfavorable outcomes fol- 2-6 lowing ischemic stroke. tablished as safe or effective. A recent open trial demonstrated a modest effect Objective.—To test whether an intravenously administered low molecular from subcutaneously administered hep- weight heparinoid, ORG 10172 (danaparoid sodium), increases the likelihood of a arin in preventing recurrent stroke favorable outcome at 3 months after acute ischemic stroke. within 14 days but no improvement in Design.—Randomized, double-blind, placebo-controlled, multicenter trial. outcomes.7 Thus, whether an intrave- Setting and Participants.—Between December 22, 1990, and December 6, nously administered anticoagulant that 1997, 1281 persons with acute stroke were enrolled at 36 centers across the United would act more rapidly would be effec- States. tiveremainsunanswered.Thesearchfor Intervention.—A 7-day course of ORG 10172 or placebo was given initially as alternative medications that possess the a bolus within 24 hours of stroke, followed by continuous infusion in addition to the antithrombotic characteristics of hepa- best medical care.
    [Show full text]
  • Guidelines for Administration of Anticoagulation for Patients Receiving Haemodialysis Lead Clinician
    Guidelines for administration of Anticoagulation for patients receiving haemodialysis Lead Clinician: Dr. Diwaker Implementation date: January 2014 Last updated: April 2017 Last review date: May 2017 Planned review date: May 2019 Department: Renal Services SaTH Directorate: Medicine Hospital Site: SaTH Keywords: Tinzaparin, Heparin, anti-coagulant, HIT Comments: 1.0 INTRODUCTION The anticoagulant regime should be tailored to the needs of the individual patient, this includes the appropriate anticoagulant drug for the patients clinical condition. When blood comes into contact with the extra corporeal circuit, platelet adherence and activation of the intrinsic clotting cascade occurs, leading to thrombosis. Clots in the dialyser reduce the effective surface area of the dialyser and in extreme situations clots in the circuit may prevent treatment from continuing and result in loss of blood in the circuit. The aim is to anticoagulate the circuit without putting the patient at risk of bleeding. Fractionated heparin (Tinzaparin) is the recommended choice for stable patients on haemodialysis. Heparin is widely used for anticoagulation as the dose can be adjusted. It’s half-life is dramatically less than Tinzaparin. (30mins-2 hours rather than 4-5 hours) Indications for use of heparin would be the unwell CHD, AKI, uraemic patient. Heparin is the anti-coagulant of choice for those patients on Warfarin. We audit the loss of Haemodialysis circuits (ie when the dialysis lines are clotted and blood is lost to the patient). This audit trail shows that the majority of “Lost Circuits” occur when the patient is being dialysed “Heparin Free” or when the ACT guidelines have been misinterpreted.
    [Show full text]
  • Treatment of Acute Ischemic Stroke
    The New England Journal of Medicine Drug Therapy The molecular events initiated by acute focal ische- mia can be summarized as a time-dependent cascade, characterized by decreased energy production; over- A LASTAIR J.J. WOOD, M.D., Editor stimulation of neuronal glutamate receptors (excito- toxicity); excessive intraneuronal accumulation of sodium, chloride, and calcium ions; mitochondrial in- TREATMENT OF ACUTE ISCHEMIC jury; and eventual cell death (Fig. 1).7, 1 4 -1 6 The funda- STROKE mental goals of intervention are to restore normal cer- ebral blood flow as soon as possible and to protect THOMAS BROTT, M.D., AND JULIEN BOGOUSSLAVSKY, M.D. neurons by interrupting or slowing the ischemic cas- cade.7, 1 4 , 1 5 Studies using magnetic resonance imaging (MRI) and positron-emission tomography suggest that critical ischemia rapidly produces a core of in- SCHEMIC stroke exacts a heavy toll in death and farcted brain tissue surrounded by hypoxic but po- disability worldwide. In the United States, where tentially salvageable tissue.8,17,18 Iit is the third leading cause of death and the lead- ing cause of serious long-term disability, approxi- EARLY EVALUATION AND SUPPORTIVE mately 750,000 strokes occur annually, with an an- TREATMENT nual mortality rate exceeding 150,000.1-4 Only about one third of patients who are having a In June 1996, the Food and Drug Administration stroke are aware of its symptoms, and most bystand- (FDA) approved tissue plasminogen activator (t-PA) ers are not knowledgeable about the signs of stroke. as a safe and effective treatment for stroke if it is giv- When symptoms or signs are recognized, emergency en within three hours after the onset of symptoms of medical services should be notified.19,20 Assessment stroke.5 Subsequently, results of large clinical trials should begin with evaluation of the patient’s airway, testing the efficacy of antiplatelet, antithrombotic, breathing, and circulation — the “ABCs” of resusci- and neuroprotective treatments appeared.
    [Show full text]
  • Danaparoid Sodium Lowers Proteinuria in Diabetic Nephropathy
    Danaparoid Sodium Lowers Proteinuria in Diabetic Nephropathy JOHAN W. VAN DER PIJL,* FOKKO J. VAN DER WOUDE,* PETRONELLA H. L. M. GEELHOEDDUIJVESTIJN,t MARIJKE FROLICH, FELIX J. M. VAN DER MEER, HERMAN H. P.J. LEMKES,” and LEENDERT A. VAN ES,* *Department of Nephrology, Leiden University Hospital, P0 Box 9600, 2300 RC Leiden, The Netherlands; tDepartment of Internal Medicine, Den Haag, The Netherlands; *Department of Clinical Chemistry, Leiden University Hospital, Leiden, The Netherlands; Department of Hematology, Leiden University Hospital, Leiden, The Netherlands; ‘Department of Endocrinology, Leiden University Hospital, Leiden, The Netherlands. Abstract. Diabetic nephropathy is a progressive renal disease sodium, the albumin excretion ratio standardized for urinary with thickening of the gbomerular basement membrane and creatinine reduced with 17% in comparison with an increase of mesangial expansion and proliferation as histological hall- 23% after placebo (95% confidence interval of the difference, marks. The presence of the glycosaminoglycan side chains of -75.9-3.9%; P = 0.03). The percentage change of the urinary heparan sulfate proteoglycan, an important constituent of the protein excretion corrected for urinary creatinine differed at 8 glomerular basement membrane, is decreased in diabetic ne- wk significantly between both treatment arms (P 0.001). phropathy proportionally to the degree of proteinuria. Danap- Additional parameters for safety as hematobogical, hemostasis, aroid sodium is a mixture of sulfated glycosaminoglycans biochemical parameters, and fundusphotography did not show consisting mainly of heparan sulfate. The study presented here any clinically significant difference for both groups. Only two involved performing a randomized placebo-controlled cross- patients had minor skin hematomas at the injection site while over study with danaparoid sodium in diabetic patients with using danaparoid sodium.
    [Show full text]
  • Is Danaparoid Anticoagulation Suitable for Patients with HIT and ARF Requiring CVVRT? an Analysis of Case Reports
    Magnani and Wester, 1:9 http://dx.doi.org/10.4172/scientificreports.423 Open Access Open Access Scientific Reports Scientific Reports Case Report OpenOpen Access Access Is Danaparoid Anticoagulation Suitable for Patients with HIT and ARF Requiring CVVRT? An Analysis of Case Reports Magnani HN1* and Wester JPJ2 1Clinical consultant, Oss, The Netherlands 2Department of Intensive Care Medicine, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands Abstract Purpose: To assess the efficacy and safety outcomes of case reports of danaparoid anticoagulation in critically ill ICU patients suffering from HIT who require CRRT. Method: A retrospective analysis of 103 cases. Results: Based on clinical signs, pre-treatment 4T scores and serological testing, HIT was reasonably ‘confirmed’ in 67.0% of the cases and ‘suspected’ in the remainder. The patients, with HIT and ARF received the danaparoid treatment regimen for CRRT for 1–39 (median 7) days. Dose adaptation was necessary in 40.2% of the patients to overcome thrombosis or bleeding (risk). Satisfactory CRRT anticoagulation was provided for 93.6% of 94 cases with information, 53.9% of the patients survived. The hospital mortality of 46.1% was mainly attributed to concomitant morbidity, but 5 deaths were related to thrombosis (n=2) or bleeding (n=3). Maintenance plasma anti-Xa activity correlated poorly with bleeding or thrombotic complications but positively with the minor bleeding frequency, hence advice to restrict the upper limit to 0.8 U/mL or preferably to use evidence of bleeding and systemic thrombosis/ circuit clotting to judge the need for dose adaptation. The benefit (no thrombosis)/harm (bleeding induction) ratio and combined inefficacy and major haemorrhagic frequency were 10.5 and 16.6% respectively, showing a generally favourable response to danaparoid.
    [Show full text]
  • Non-Interventional (Ni) Study Protocol
    Apixaban B0661069 NON-INTERVENTIONAL STUDY PROTOCOL Update 1, 08 January 2016 NON-INTERVENTIONAL (NI) STUDY PROTOCOL Post Author isation Safet y St udi es (PA SS) infor mation Title CARBOS – Comparative risk of major bleeding with new oral anticoagulants (NOACs) and Phenprocoumon in patients with atrial fibrillation: a retrospective claims database study in Germany Protocol number B0661069 Protocol version identifier Update 1.0 Date of last version of protocol 08 January 2016 EU Post Authorisation Study (PAS) ENCEPP/SDPP/11313 register number Active substance Apixaban (B01AF02) Phenprocoumon (B01AA04) Rivaroxaban (B01AX06; B01AF01) Dabigatran (B01AX06) Product reference EU/1/11/691/006 EU/1/11/691/007 EU/1/11/691/008 EU/1/11/691/009 EU/1/11/691/010 EU/1/11/691/011 Pfizer Confidential Page 1 of 112 Apixaban B0661069 NON-INTERVENTIONAL STUDY PROTOCOL Update 1, 08 January 2016 EU/1/11/691/012 EU/1/11/691/014 Procedure number Not Available Marketing Authorisation Holder (MAH) Pfizer Pharma GmbH Joint PASS No Research question and objectives The aim of this study is to investigate whether there are differences in the occurrence of major bleeding events in patients with NVAF and prescribed oral anticoagulation therapies in a real-world setting. It will be investigated whether the occurrence of major bleeding events in NVAF patients under anticoagulant therapy differs between patients treated with VKA (e.g. Phenprocoumon) and patients treated with Apixaban, Dabigatran or Rivaroxaban respectively. Country of study Germany Author Fabian Volz Pfizer
    [Show full text]