Regional Anesthesia in the Patient Receiving Antithrombotic or Thrombolytic Therapy: American Society of Regional Anesthesia and Pain Medicine Evidence-Based Guidelines (Third Edition)

The actual incidence of neurologic dysfunction resulting from hemorrhagic complications associated with neuraxial blockade is unknown. Although the incidence cited in the literature is estimated to be less than 1 in 150,000 epidural and less than 1 in 220,000 spinal anesthetics, recent epidemiologic surveys suggest that the frequency is increasing and may be as high as 1 in 3000 in some patient populations. Overall, the risk of clinically significant bleeding increase with age, associated abnormalities of the spinal cord or vertebral column, the presence of an underlying coagulopathy, difficulty during needle placement, and an indwelling neuraxial catheter during sustained anticoagulation (particularly with standard heparin or low-molecular weight heparin). The need for prompt diagnosis and intervention to optimize is also consistently reported. In response to these patient safety issues, the American Society of Regional Anesthesia and Pain Medicine (ASRA) convened its Third Consensus Conference on Regional Anesthesia and Anticoagulation. Practice guidelines or recommendations summarize evidence-based reviews. However, the rarity of spinal hematoma defies a prospective randomized study, and there is no current laboratory model. As a result, the ASRA consensus statements represent the collective experience of recognized experts in the field of neuraxial anesthesia and anticoagulation. These are based on case reports, clinical series, pharmacology, hematology, and risk factors for surgical bleeding. An understanding of the complexity of this issue is essential to patient management.

[1]  C. Yuan,et al.  Ginseng pharmacology: multiple constituents and multiple actions. , 1999, Biochemical pharmacology.

[2]  B. Eriksson,et al.  A Once-Daily, Oral, Direct Factor Xa Inhibitor, Rivaroxaban (BAY 59-7939), for Thromboprophylaxis After Total Hip Replacement , 2006, Circulation.

[3]  J. Heit,et al.  Efficacy and safety of intravenous phytonadione (vitamin K1) in patients on long-term oral anticoagulant therapy. , 2001, Mayo Clinic proceedings.

[4]  K. Chung,et al.  EFFECT OF A GINKGOLIDE MIXTURE (BN 52063) IN ANTAGONISING SKIN AND PLATELET RESPONSES TO PLATELET ACTIVATING FACTOR IN MAN , 1987, The Lancet.

[5]  R. Beavis,et al.  Spontaneous Spinal Epidural Hematoma During Pregnancy , 2005, Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques.

[6]  D. Hsu,et al.  Delayed retroperitoneal haematoma after failed lumbar plexus block. , 2005, British journal of anaesthesia.

[7]  J. Durbridge,et al.  Epidural haematoma after dural puncture in a parturient with neurofibromatosis. , 2001, British journal of anaesthesia.

[8]  Christopher L. Wu,et al.  Oral Anticoagulant Prophylaxis and Epidural Catheter Removal , 1996, Regional Anesthesia & Pain Medicine.

[9]  C. Dumont,et al.  An evaluation of the infraclavicular block via a modified approach of the Raj technique. , 2001, Anesthesia and analgesia.

[10]  G. Raskob,et al.  Oral thrombin inhibitor dabigatran etexilate vs North American enoxaparin regimen for prevention of venous thromboembolism after knee arthroplasty surgery. , 2009, The Journal of arthroplasty.

[11]  S. Yusuf,et al.  Benefits and Risks of the Combination of Clopidogrel and Aspirin in Patients Undergoing Surgical Revascularization for Non–ST-Elevation Acute Coronary Syndrome: The Clopidogrel in Unstable angina to prevent Recurrent ischemic Events (CURE) Trial , 2004, Circulation.

[12]  B. Newman Postnatal paraparesis following epidural analgesia and forceps delivery. , 1984, Anaesthesia.

[13]  W. Yoo,et al.  Epidural hematoma mimicking transverse myelitis in a patient with primary antiphospholipid syndrome , 2008, Rheumatology International.

[14]  R. Cotton,et al.  VARIANT FORMS OF PHENYLKETONURIA , 1976, The Lancet.

[15]  Thomas Yk Chan,et al.  Adverse Interactions Between Warfarin and Nonsteroidal Antiinflammatory Drugs: Mechanisms, Clinical Significance, and Avoidance , 1995, The Annals of pharmacotherapy.

[16]  I. Wijesurendra Spinal haematoma following epidural anaesthesia in a patient with eclampsia , 1999, Anaesthesia.

[17]  H. Ostermann Low molecular weight heparins , 1998, Der Internist.

[18]  H. Harke,et al.  A combined technique of local thrombolysis and regional neural blockade in severe venous occlusions , 2004, Intensive Care Medicine.

[19]  F. Millar,et al.  Hemostasis-altering Drugs and Central Neural Block: A Survey of Anesthetic Practice in Scotland and the United Kingdom , 1996, Regional Anesthesia & Pain Medicine.

[20]  A. Le Querrec [Venous thromboembolism in pregnancy]. , 2003, La Revue du praticien.

[21]  L. Bertini,et al.  [Technical difficulties in epidural blocks and spinal bleeding complications]. , 2001, Minerva anestesiologica.

[22]  L. Brancazio,et al.  Pharmacokinetics and pharmacodynamics of subcutaneous heparin during the early third trimester of pregnancy. , 1995, American journal of obstetrics and gynecology.

[23]  D. Eisenberg,et al.  Advising Patients Who Seek Alternative Medical Therapies , 1997, Annals of Internal Medicine.

[24]  A. Schatzberg,et al.  A placebo-controlled, double-blind, randomized trial of an extract of Ginkgo biloba for dementia. North American EGb Study Group. , 1997, JAMA.

[25]  H. Bruck,et al.  Effects of renal impairment on the pharmacokinetics, pharmacodynamics and safety of rivaroxaban, an oral, direct Factor Xa inhibitor. , 2010, British journal of clinical pharmacology.

[26]  L. Landow A synthetic pentasaccharide for the prevention of deep-vein thrombosis. , 2001, The New England journal of medicine.

[27]  P. Kamphuisen,et al.  Bleeding risk and reversal strategies for old and new anticoagulants and antiplatelet agents , 2011, Journal of thrombosis and haemostasis : JTH.

[28]  W. Ageno,et al.  Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. , 2008, The New England journal of medicine.

[29]  E. Hylek,et al.  Warfarin maintenance dosing patterns in clinical practice: implications for safer anticoagulation in the elderly population. , 2005, Chest.

[30]  M. Bailey,et al.  Noncompliance in the inpatient administration of enoxaparin in conjunction with epidural or spinal anesthesia. , 2000, The Journal of arthroplasty.

[31]  S. Halpern,et al.  Spinal subdural haematoma in a parturient after attempted epidural anaesthesia , 1993, Canadian journal of anaesthesia = Journal canadien d'anesthesie.

[32]  N. Dowling,et al.  The U.S. Thrombosis and Hemostasis Centers pilot sites program , 2007, Journal of Thrombosis and Thrombolysis.

[33]  M. Gent,et al.  Rivaroxaban for thromboprophylaxis after orthopaedic surgery: Pooled analysis of two studies , 2007, Thrombosis and Haemostasis.

[34]  T. Horlocker,et al.  Neurologic Complications of 405 Consecutive Continuous Axillary Catheters , 2003, Anesthesia and analgesia.

[35]  Jeffrey S. Ginsberg,et al.  Use of antithrombotic agents during pregnancy. , 1992, Chest.

[36]  D. Doblar,et al.  Spontaneous acute thoracic epidural hematoma causing paraplegia in a patient with severe preeclampsia in early labor. , 2005, International journal of obstetric anesthesia.

[37]  C. Kessler,et al.  Monitoring the anticoagulant effects of a low molecular weight heparin preparation. Correlation of assays in orthopedic surgery patients receiving ardeparin sodium for prophylaxis of deep venous thrombosis. , 1995, American journal of clinical pathology.

[38]  W. Gogarten The influence of new antithrombotic drugs on regional anesthesia , 2006, Current opinion in anaesthesiology.

[39]  J. Ahn,et al.  Paraplegia Subsequent to Administration of Tissue Plasminogen Activator and Intravenous Heparin Following Myocardial Infarction-A Case Report , 2000, The journal of spinal cord medicine.

[40]  K. W. Turnbull Neuraxial anesthesia is contraindicated in patients undergoing heparinization for surgery. Con: neuraxial block is useful in patients undergoing heparinization for surgery. , 1996, Journal of cardiothoracic and vascular anesthesia.

[41]  S. Dohi,et al.  Spinal subarachnoid hematoma after lumbar puncture in a patient receiving antiplatelet therapy. , 1983, Anesthesia and analgesia.

[42]  J. Neilson,et al.  Saving Mothers’ Lives: Reviewing maternal deaths to make motherhood safer: 2006–2008 , 2011, BJOG : an international journal of obstetrics and gynaecology.

[43]  D. Schroeder,et al.  Risk Assessment of Hemorrhagic Complications Associated with Nonsteroidal Antiinflammatory Medications in Ambulatory Pain Clinic Patients Undergoing Epidural Steroid Injection , 2002, Anesthesia and analgesia.

[44]  L. Rasmussen,et al.  Lumbar regional anaesthesia and prophylactic anticoagulant therapy , 1991, Anaesthesia.

[45]  J. Hirsh,et al.  Parenteral anticoagulants: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). , 2008, Chest.

[46]  Christopher L. Wu,et al.  Does Continuous Peripheral Nerve Block Provide Superior Pain Control to Opioids? A Meta-Analysis , 2006, Anesthesia and analgesia.

[47]  R. Vogelzang,et al.  Spontaneous Spinal Epidural Hematoma in Pregnancy Associated With Using Low Molecular Weight Heparin , 2009, Obstetrics and gynecology.

[48]  W. Young,et al.  Spinal epidural hematoma associated with tissue plasminogen activator treatment of acute myocardial infarction , 1999, Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions.

[49]  N. Paradis,et al.  Spinal epidural hematoma complicating thrombolytic therapy with tissue plasminogen activator--a case report. , 2002, The Journal of emergency medicine.

[50]  Y. Han,et al.  Spinal Epidural Hematoma After Thrombolysis for Deep Vein Thrombosis with Subsequent Pulmonary Thromboembolism: A Case Report , 2006, CardioVascular and Interventional Radiology.

[51]  M. Gent,et al.  BAY 59‐7939: an oral, direct Factor Xa inhibitor for the prevention of venous thromboembolism in patients after total knee replacement. A phase II dose‐ranging study , 2005, Journal of thrombosis and haemostasis : JTH.

[52]  V. Chan,et al.  A Comparative Study of Low-Dose Hyperbaric Spinal Lidocaine 0.5% Versus 5% for Continuous Spinal Anesthesia , 1997, Regional Anesthesia & Pain Medicine.

[53]  G. Plosker,et al.  Bivalirudin: a review of its potential place in the management of acute coronary syndromes. , 2002, Drugs.

[54]  M. Matthews Association of Ginkgo biloba with intracerebral hemorrhage , 1998, Neurology.

[55]  P. Guigui,et al.  Acute spontaneous spinal epidural hematoma: an important differential diagnosis in patients under clopidogrel therapy. , 2008, The spine journal : official journal of the North American Spine Society.

[56]  E. Nylander,et al.  Vascular injury following cardiac catheterization, coronary angiography, and coronary angioplasty. , 1994, European heart journal.

[57]  K. Rathgen,et al.  The pharmacokinetics, pharmacodynamics and tolerability of dabigatran etexilate, a new oral direct thrombin inhibitor, in healthy male subjects. , 2007, British journal of clinical pharmacology.

[58]  T. Stan,et al.  The Incidence of Neurovascular Complications Following Axillary Brachial Plexus Block Using a Transarterial Approach: A Prospective Study of 1,000 Consecutive Patients , 1993, Regional Anesthesia & Pain Medicine.

[59]  J. Hirsh,et al.  Heparin: mechanism of action, pharmacokinetics, dosing considerations, monitoring, efficacy, and safety. , 1992, Chest.

[60]  H. Aken,et al.  Regional anaesthesia and thromboembolism prophylaxis/anticoagulation , 1997 .

[61]  R. Sánchez,et al.  Epidural anesthesia in cardiac surgery: is there an increased risk? , 1998, Journal of cardiothoracic and vascular anesthesia.

[62]  C. Lockwood Inherited thrombophilias in pregnant patients: detection and treatment paradigm. , 2002, Obstetrics and gynecology.

[63]  T. Fuji,et al.  A dose‐ranging study evaluating the oral factor Xa inhibitor edoxaban for the prevention of venous thromboembolism in patients undergoing total knee arthroplasty , 2010, Journal of thrombosis and haemostasis : JTH.

[64]  C. Dyke Safety of glycoprotein IIb-IIIa inhibitors: A heart surgeon's perspective. , 1999, American heart journal.

[65]  E. Pogatzki-Zahn,et al.  Effectiveness and safety of postoperative pain management: a survey of 18 925 consecutive patients between 1998 and 2006 (2nd revision): a database analysis of prospectively raised data. , 2008, British journal of anaesthesia.

[66]  W. Hammonds,et al.  Page kidney resulting from massive subcapsular hematoma. Complication of lumbar sympathetic nerve block. , 1984, Urology.

[67]  J. Rowin,et al.  Spontaneous bilateral subdural hematomas associated with chronic Ginkgo biloba ingestion , 1996, Neurology.

[68]  A. Shetter,et al.  Spinal epidural hematoma associated with epidural anesthesia: complications of systemic heparinization in patients receiving peripheral vascular thrombolytic therapy. , 1990, Anesthesiology.

[69]  R. J. Ain,et al.  Epidural hematoma after epidural steroid injection in a patient withholding enoxaparin per guidelines. , 2005, Anesthesiology.

[70]  H. Büller,et al.  A new oral direct thrombin inhibitor, dabigatran etexilate, compared with enoxaparin for prevention of thromboembolic events following total hip or knee replacement: the BISTRO II randomized trial , 2005, Journal of thrombosis and haemostasis : JTH.

[71]  Lorri A. Lee,et al.  Injuries Associated with Regional Anesthesia in the 1980s and 1990s: A Closed Claims Analysis , 2004, Anesthesiology.

[72]  G. Y. Wong,et al.  Preoperative Antiplatelet Therapy Does Not Increase the Risk of Spinal Hematoma Associated with Regional Anesthesia , 1995, Anesthesia and analgesia.

[73]  J. Gerancher,et al.  Transient paraparesis after postdural puncture spinal hematoma in a patient receiving ketorolac. , 1997, Anesthesiology.

[74]  Kenichi A. Tanaka,et al.  Warfarin reversal with prothrombin complex concentrate confers better antifibrinolytic activity compared with recombinant activated factor VII. , 2008, Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis.

[75]  J. Nunnelee Low-molecular-weight heparin. , 1997, Journal of vascular nursing : official publication of the Society for Peripheral Vascular Nursing.

[76]  N. Rosencher,et al.  Selected new antithrombotic agents and neuraxial anaesthesia for major orthopaedic surgery: management strategies , 2007, Anaesthesia.

[77]  J. Bouma,et al.  CERVICAL CARCINOMA IN YOUNGER PATIENTS , 1983, The Lancet.

[78]  Y. Kimura,et al.  Effects of Various Ginseng Saponins on 5‐Hydroxytryptamine Release and Aggregation in Human Platelets , 1988, The Journal of pharmacy and pharmacology.

[79]  A. Morreale,et al.  Probable interaction between warfarin and ginseng. , 1997, American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists.

[80]  N. Elder,et al.  Use of alternative health care by family practice patients. , 1997, Archives of family medicine.

[81]  P. Isakson,et al.  Effects of Celecoxib, a Novel Cyclooxygenase‐2 Inhibitor, on Platelet Function in Healthy Adults: A Randomized, Controlled Trial , 2000, Journal of clinical pharmacology.

[82]  B. Lindblad,et al.  Risk of combining low molecular weight heparin for thromboprophylaxis and epidural or spinal anesthesia. , 1993, Seminars in thrombosis and hemostasis.

[83]  J. Katz,et al.  Low-dose warfarin coupled with lower leg compression is effective prophylaxis against thromboembolic disease after hip arthroplasty. , 2007, The Journal of arthroplasty.

[84]  N. Dahlgren,et al.  Severe Neurological Complications after Central Neuraxial Blockades in Sweden 1990–1999 , 2004, Anesthesiology.

[85]  K. C. Srivastava Evidence for the mechanism by which garlic inhibits platelet aggregation. , 1986, Prostaglandins, leukotrienes, and medicine.

[86]  Anna Lee,et al.  Incidence and Risk of Adverse Perioperative Events among Surgical Patients Taking Traditional Chinese Herbal Medicines , 2006, Anesthesiology.

[87]  J. Crowhurst Paraplegia following epidural analgesia , 1982, Anaesthesia.

[88]  C. Roberts,et al.  Regional block versus general anaesthesia for caesarean section and neonatal outcomes: a population-based study , 2009, BMC medicine.

[89]  A. García López,et al.  Spinal epidural hematoma following thrombolytic therapy for acute myocardial infarction. , 1999, Orthopedics.

[90]  Ming-cheng Lin,et al.  Spinal epidural hematoma following tissue plasminogen activator and heparinization for acute myocardial infarction. , 2002, Japanese heart journal.

[91]  Jeffrey R. Wilson,et al.  CLASP: a randomised trial of low-dose aspirin for the prevention and treatment of pre-eclampsia among 9364 pregnant women , 1994, The Lancet.

[92]  A. Mushlin,et al.  How well does the activated partial thromboplastin time predict postoperative hemorrhage? , 1986, JAMA.

[93]  B. Bouma,et al.  Thrombin activatable fibrinolysis inhibitor (TAFI)--how does thrombin regulate fibrinolysis? , 2006, Annals of medicine.

[94]  E. Cooke,et al.  Letter: Monitoring during low-dose heparin prophylaxis. , 1976, The New England journal of medicine.

[95]  P. Thürmann,et al.  Clinically Important Drug Interactions with Anticoagulants , 1996, Clinical pharmacokinetics.

[96]  J. Neal,et al.  Epidural Anesthesia and Analgesia: Their Role in Postoperative Outcome , 1995, Anesthesiology.

[97]  I. I. Brekhman,et al.  New substances of plant origin which increase nonspecific resistance. , 1969, Annual review of pharmacology.

[98]  R. Berrisford,et al.  Pulmonary haemorrhage after percutaneous paravertebral block. , 1999, British journal of anaesthesia.

[99]  T. Fuji,et al.  Dabigatran etexilate prevents venous thromboembolism after total knee arthroplasty in Japanese patients with a safety profile comparable to placebo. , 2010, The Journal of arthroplasty.

[100]  Sheng-Chih Chen,et al.  Antiplatelet components in Panax ginseng. , 1990, Planta Medica.

[101]  K. Toyoda,et al.  [Acute cervical spinal epidural hematoma during antithrombotic therapy: dual warnings against antithrombotic therapy]. , 2003, Rinshō shinkeigaku Clinical neurology.

[102]  M. Jain,et al.  Ajoene, the antiplatelet principle of garlic, synergistically potentiates the antiaggregatory action of prostacyclin, forskolin, indomethacin and dypiridamole on human platelets. , 1986, Thrombosis research.

[103]  Spencer S. Liu,et al.  Neuraxial anesthesia and analgesia in the presence of standard heparin. , 1998, Regional anesthesia and pain medicine.

[104]  C. Nielsen Bleeding after intercostal nerve block in a patient anticoagulated with heparin. , 1989, Anesthesiology.

[105]  R. Fragen,et al.  Clopidogrel and Neuraxial Block: The Role of the PFA II and P2Y12 Assays , 2009, Regional Anesthesia & Pain Medicine.

[106]  A. Gray Patient with eclampsia. , 1966, Nursing mirror and midwives journal.

[107]  Mark Crowther,et al.  Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). , 2008, Chest.

[108]  I. Greer Prevention of venous thromboembolism in pregnancy. , 2003, European journal of medical research.

[109]  W. Stigelman,et al.  Goodman and Gilman's the Pharmacological Basis of Therapeutics , 1986 .

[110]  J. Hirsh Oral anticoagulant drugs. , 1991, The New England journal of medicine.

[111]  W. Osta,et al.  Epidural analgesia in vascular surgery patients actively taking clopidogrel. , 2010, British journal of anaesthesia.

[112]  A. James Thromboembolism in pregnancy: recurrence risks, prevention and management , 2008, Current opinion in obstetrics & gynecology.

[113]  B. Riu,et al.  [Epidural hematoma after hemorrhagic shock in a parturient]. , 2006, Canadian journal of anaesthesia = Journal canadien d'anesthesie.

[114]  J. Stothard,et al.  Thromboprophylaxis and death after total hip replacement. , 1997, The Journal of bone and joint surgery. British volume.

[115]  A. Ho,et al.  Neuraxial blockade and hematoma in cardiac surgery: estimating the risk of a rare adverse event that has not (yet) occurred. , 2000, Chest.

[116]  B. Eriksson,et al.  Comparative Pharmacodynamics and Pharmacokinetics of Oral Direct Thrombin and Factor Xa Inhibitors in Development , 2009, Clinical pharmacokinetics.

[117]  A. Clemens,et al.  Pharmacology, Pharmacokinetics, and Pharmacodynamics of Dabigatran Etexilate, an Oral Direct Thrombin Inhibitor , 2009, Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis.

[118]  T. Rao,et al.  Anticoagulation Following Placement of Epidural and Subarachnoid Catheters:: An Evaluation of Neurologic Sequelae , 1981, Anesthesiology.

[119]  D. Schroeder,et al.  Frequency of Myocardial Infarction, Pulmonary Embolism, Deep Venous Thrombosis, and Death following Primary Hip or Knee Arthroplasty , 2002, Anesthesiology.

[120]  A. Winnie,et al.  Intrathecal bleeding after the intraoperative use of heparin and urokinase during continuous spinal anesthesia. , 1996, Anesthesia and analgesia.

[121]  J. Brichant,et al.  Belgian guidelines concerning central neural blockade in patients with drug-induced alteration of coagulation: an update. , 2005, Acta anaesthesiologica Belgica.

[122]  D. Hall,et al.  Inherited and acquired thrombophilias and poor pregnancy outcome: should we be treating with heparin? , 2003, Current opinion in obstetrics & gynecology.

[123]  J. Hirsh,et al.  Use of antithrombotic agents during pregnancy: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. , 2004, Chest.

[124]  F. Enneking,et al.  Oral anticoagulants and regional anesthesia: a perspective. , 1998, Regional anesthesia and pain medicine.

[125]  B M Hibbard,et al.  Serious non-fatal complications associated with extradural block in obstetric practice. , 1990, British journal of anaesthesia.

[126]  D. Rosen,et al.  An epidural hematoma in an adolescent patient after cardiac surgery. , 2004, Anesthesia and analgesia.

[127]  S. Ondra,et al.  Caution in performing epidural injections in patients on several antiplatelet drugs. , 1999, Anesthesiology.

[128]  F. Plaat,et al.  The natural caesarean: a woman-centred technique , 2008, BJOG: an International Journal of Obstetrics and Gynaecology.

[129]  K. Samii,et al.  Hématome péridural chez une parturiente au décours ďun choc hémorragique , 2006 .

[130]  H. J. Park,et al.  Effects of dietary supplementation of lipophilic fraction from Panax ginseng on cGMP and cAMP in rat platelets and on blood coagulation. , 1996, Biological & pharmaceutical bulletin.

[131]  J. Heit Perioperative Management of the Chronically Anticoagulated Patient , 2001, Journal of Thrombosis and Thrombolysis.

[132]  S. Vale Subarachnoid haemorrhage associated with Ginkgo biloba , 1998, The Lancet.

[133]  R. D. Wang,et al.  Case report: continuous interscalene block associated with neck hematoma and postoperative sepsis. , 2010, Anesthesia and analgesia.

[134]  A. Kaye,et al.  Bleeding risk in interventional pain practice: assessment, management, and review of the literature. , 2004, Pain physician.

[135]  R. Rosenquist,et al.  Neuraxial bleeding: fibrinolytics/thrombolytics. , 1998, Regional anesthesia and pain medicine.

[136]  D. Warner,et al.  Enoxaparin associated with psoas hematoma and lumbar plexopathy after lumbar plexus block. , 1997, Anesthesiology.

[137]  G. Raskob,et al.  Hemorrhagic complications of anticoagulant treatment. , 1992, Chest.

[138]  J. Hirsh,et al.  New antithrombotic drugs: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). , 2008, Chest.

[139]  J. Kaye,et al.  The efficacy of Ginkgo biloba on cognitive function in Alzheimer disease. , 1998, Archives of neurology.

[140]  S. Steinhubl,et al.  Pharmacokinetics and Pharmacodynamics of a Bolus and Infusion of Cangrelor: A Direct, Parenteral P2Y12 Receptor Antagonist , 2010, Journal of clinical pharmacology.

[141]  R. Dyer,et al.  Prospective, Randomized Trial Comparing General with Spinal Anesthesia for Cesarean Delivery in Preeclamptic Patients with a Nonreassuring Fetal Heart Trace , 2003, Anesthesiology.

[142]  S. Ozgoçmen,et al.  Spinal epidural hematoma associated with streptokinase treatment for myocardial infarction , 2004, Spinal Cord.

[143]  T. Salerno,et al.  Thoracic epidural anesthesia for coronary bypass via left anterior thoracotomy in the conscious patient. , 2001, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.

[144]  E. Wallmark,et al.  Effect on platelet aggregation of oral administration of 10 non-steroidal analgesics to humans. , 2009, Scandinavian journal of haematology.

[145]  Spencer S. Liu,et al.  Uncomplicated Removal of Epidural Catheters in 4365 Patients With International Normalized Ratio Greater Than 1.4 During Initiation of Warfarin Therapy , 2010, Regional Anesthesia & Pain Medicine.

[146]  A. Turpie,et al.  A synthetic pentasaccharide for the prevention of deep-vein thrombosis after total hip replacement. , 2001, The New England journal of medicine.

[147]  P. Morley-Forster,et al.  Epidural Hematoma Following Epidural Analgesia in a Patient Receiving Unfractionated Heparin for Thromboprophylaxis , 1999, Regional Anesthesia & Pain Medicine.

[148]  John M Fessenden,et al.  Gingko Biloba: A Case Report of Herbal Medicine and Bleeding Postoperatively from a Laparoscopic Cholecystectomy , 2001, The American surgeon.

[149]  E. Ernst,et al.  Garlic for treating hypercholesterolemia. A meta-analysis of randomized clinical trials. , 2000, Annals of internal medicine.

[150]  Vivian Gu,et al.  Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke. , 2008, The New England journal of medicine.

[151]  H. Wulf,et al.  Epidural anaesthesia and spinal haematoma , 1996, Canadian journal of anaesthesia = Journal canadien d'anesthesie.

[152]  S. W. Helperin,et al.  Hematoma following epidural anesthesia: report of a case. , 1971, Anesthesiology.

[153]  J. Weiler,et al.  Heparin detection by the activated coagulation time: a comparison of the sensitivity of coagulation tests and heparin assays. , 1997, Journal of cardiothoracic and vascular anesthesia.

[154]  S. A. Rooholamini,et al.  Retroperitoneal hematoma as a complication of pudendal block. Diagnosis made by computed tomography. , 1996, The Western journal of medicine.

[155]  P. Widimsky,et al.  Thoracic epidural anesthesia for off-pump coronary artery bypass without intubation. , 2001, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.

[156]  L. Jørgensen,et al.  Lumbar Regional Anaesthesia and Prophylactic Anticoagulant Therapy: Is the Combination Safe? , 1992 .

[157]  H. Hemker,et al.  The Relative Importance of the Factors II, VII, IX and X for the Prothrombinase Activity in Plasma of Orally Anticoagulated Patients , 1989, Thrombosis and Haemostasis.

[158]  J. Chelly,et al.  International normalized ratio and prothrombin time values before the removal of a lumbar plexus catheter in patients receiving warfarin after total hip replacement. , 2008, British journal of anaesthesia.

[159]  R. Rosenquist,et al.  Regional Anesthesia in the Anticoagulated Patient: Defining the Risks (The Second ASRA Consensus Conference on Neuraxial Anesthesia and Anticoagulation) , 2003, Regional Anesthesia & Pain Medicine.

[160]  J. L. Swisher,et al.  Practice Advisory for the Prevention, Diagnosis, and Management of Infectious Complications Associated with Neuraxial Techniques: A Report by the American Society of Anesthesiologists Task Force on Infectious Complications Associated with Neuraxial Techniques* , 2010, Anesthesiology.

[161]  A. Shorr,et al.  Twice vs three times daily heparin dosing for thromboembolism prophylaxis in the general medical population: A metaanalysis. , 2007, Chest.

[162]  M. Keegan,et al.  Epidural catheter removal before unanticipated anticoagulation: the pharmacy fail-safe. , 1999, Anesthesiology.

[163]  T. Horlocker,et al.  Postoperative epidural analgesia and oral anticoagulant therapy. , 1994, Anesthesia and analgesia.

[164]  C. Verheyen,et al.  The Safety and Efficacy of Extended Thromboprophylaxis With Fondaparinux After Major Orthopedic Surgery of the Lower Limb With or Without a Neuraxial or Deep Peripheral Nerve Catheter: The EXPERT Study , 2007, Anesthesia and analgesia.

[165]  A. Borgeat,et al.  Prolonged Horner syndrome due to neck hematoma after continuous interscalene block. , 2001, Anesthesiology.

[166]  C. Samama,et al.  Regional anaesthesia and antithrombotic agents: recommendations of the European Society of Anaesthesiology , 2010, European journal of anaesthesiology.

[167]  P. Klineberg,et al.  Thoracic Epidural Anesthesia for Cardiac Surgery: The Effects on Tracheal Intubation Time and Length of Hospital Stay , 2002, Anesthesia and analgesia.

[168]  D. Hoppensteadt,et al.  Evaluation of hemostatic and fibrinolytic alterations associated with daily administration of low-molecular-weight heparin for a 12-week period. , 1995, Seminars in thrombosis and hemostasis.

[169]  M. Zenz,et al.  Severe bleeding following lumbar sympathetic blockade in two patients under medication with irreversible platelet aggregation inhibitors. , 2002, Anesthesiology.

[170]  J. Hirsh,et al.  American College of Chest Physicians and the National Heart, Lung, and Blood Institute National Conference on Antithrombotic Therapy , 1986 .

[171]  J. Douketis,et al.  Anticoagulant Effect at the Time of Epidural Catheter Removal in Patients Receiving Twice-daily or Once-daily Low-molecular-weight Heparin and Continuous Epidural Analgesia after Orthopedic Surgery , 2002, Thrombosis and Haemostasis.

[172]  R. Collins,et al.  Reduction in Fatal Pulmonary Embolism and Venous Thrombosis by Perioperative Administration of Subcutaneous Heparin , 1989 .

[173]  Jeffrey S. Ginsberg,et al.  The APTT Response of Pregnant Plasma to Unfractionated Heparin , 2002, Thrombosis and Haemostasis.

[174]  S. Mehta Anticoagulant drugs and central nerve blockade , 1992, Anaesthesia.

[175]  Anthony Rodgers,et al.  Reduction of postoperative mortality and morbidity with epidural or spinal anaesthesia: results from overview of randomised trials , 2000, BMJ : British Medical Journal.

[176]  A. Macario,et al.  A Retrospective Examination of Regional Plus General Anesthesia in Children Undergoing Open Heart Surgery , 2000, Anesthesia and Analgesia.

[177]  Small subcutaneous doses of heparin in prevention of venous thrombosis. , 1973, The New England journal of medicine.

[178]  G. Guyatt,et al.  Grades of recommendation for antithrombotic agents. , 1998, Chest.

[179]  A. Rodgers,et al.  Attitudes and Practices of New Zealand Anaesthetists with Regard to Epidural and Subarachnoid Anaesthesia , 1996, Anaesthesia and intensive care.

[180]  B. Jeanneret,et al.  Spontaneous spinal epidural haematoma during Factor Xa inhibitor treatment (Rivaroxaban) , 2012, European Spine Journal.

[181]  J. Weitz,et al.  New Antithrombotic Drugs , 2009, Clinical pharmacology and therapeutics.

[182]  M. Mulroy,et al.  Epidural hematoma after outpatient epidural anesthesia. , 2002, Anesthesia and analgesia.

[183]  X. Capdevila,et al.  Effects of perioperative analgesic technique on the surgical outcome and duration of rehabilitation after major knee surgery. , 1999, Anesthesiology.

[184]  F. Ralley,et al.  Neuraxial anesthesia is contraindicated in patients undergoing heparinization for surgery. Pro: neuraxial anesthesia should not be used in patients undergoing heparinization for surgery. , 1996, Journal of cardiothoracic and vascular anesthesia.

[185]  A. Smaranda,et al.  [Neuraxial hematoma after combined regional anesthesia: conservative resolution]. , 2005, Revista espanola de anestesiologia y reanimacion.

[186]  Janis Km Epidurai Hematoma Foliowing Postoperative Epidural Analgesia: A Case Report , 1972 .

[187]  Turan M. Itil,et al.  A Placebo-Controlled, Double-blind, Randomized Trial of an Extract of Ginkgo Biloba for Dementia , 1997 .

[188]  S. Scheitel,et al.  Underreporting the use of dietary supplements and nonprescription medications among patients undergoing a periodic health examination. , 1999, Mayo Clinic proceedings.

[189]  J. Levin,et al.  A Critical Reappraisal of the Bleeding Time* , 1990, Seminars in thrombosis and hemostasis.

[190]  T. Horlocker,et al.  Neuraxial block and low-molecular-weight heparin: balancing perioperative analgesia and thromboprophylaxis. , 1998, Regional anesthesia and pain medicine.

[191]  B. Reitz,et al.  A Report of Two Hundred Twenty Cases of Regional Anesthesia in Pediatric Cardiac Surgery , 2000, Anesthesia and analgesia.

[192]  R. Weller,et al.  Extensive retroperitoneal hematoma without neurologic deficit in two patients who underwent lumbar plexus block and were later anticoagulated. , 2003, Anesthesiology.

[193]  R. Califf,et al.  Scientific evidence underlying the ACC/AHA clinical practice guidelines. , 2009, JAMA.

[194]  V. Volpini,et al.  Machado‐Joseph disease, spinopontine atrophy, and SCA3 , 1997, Neurology.

[195]  R. Ruff,et al.  Complications of lumbar puncture followed by anticoagulation. , 1981, Stroke.

[196]  C. Lockwood Heritable coagulopathies in pregnancy. , 1999, Obstetrical & gynecological survey.

[197]  D. Foo Operative treatment of spontaneous spinal epidural hematomas: a study of the factors determining postoperative outcome. , 1997, Neurosurgery.

[198]  R. Tuncer,et al.  Lumbar epidural hematoma following lumbar puncture: the role of high dose LMWH and late surgery. A case report. , 2007, Neurocirugia.

[199]  B. Lindblad,et al.  Protamine neutralization of intravenous and subcutaneous low-molecular-weight heparin (tinzaparin, Logiparin™). An experimental investigation in healthy volunteers , 1994, Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis.

[200]  M. Chaney Intrathecal and Epidural Anesthesia and Analgesia for Cardiac Surgery , 1997, Anesthesia and analgesia.

[201]  B. Newman Postnatal paraparesis following epidural analgesia and forceps delivery , 1983 .

[202]  R. Caplan,et al.  Nerve injury associated with anesthesia. , 1990, Anesthesiology.

[203]  T. Barrington,et al.  Acute Spinal Subdural Hematoma: A Case Report and Review of Literature , 1984, Spine.

[204]  Herng‐Ching Lin,et al.  Anesthetic management as a risk factor for postpartum hemorrhage after cesarean deliveries. , 2011, American journal of obstetrics and gynecology.

[205]  J. Vaisman Pelvic hematoma after an ilioinguinal nerve block for orchialgia. , 2001, Anesthesia and analgesia.

[206]  Toshiyasu Suzuki,et al.  Spinal epidural hematoma following epidural catheter removal during antiplatelet therapy with cilostazol , 2008, Journal of Anesthesia.

[207]  C. Amory,et al.  Is ilioinguinal/iliohypogastric nerve block always totally safe in children? , 2003, Paediatric anaesthesia.

[208]  Shoko Kawaguchi,et al.  [A case of epidural hematoma associated with epidural catheterization which occurred on 12th days after the last medication of ticlopidine hydrochloride]. , 2002, Masui. The Japanese journal of anesthesiology.

[209]  H. Hyderally Epidural Hematoma Unrelated to Combined Spinal-Epidural Anesthesia in a Patient with Ankylosing Spondylitis Receiving Aspirin After Total Hip Replacement , 2005, Anesthesia and analgesia.

[210]  G. Ryan,et al.  Maternal-perinatal outcome associated with the syndrome of hemolysis, elevated liver enzymes, and low platelets in severe preeclampsia-eclampsia. , 1986, American journal of obstetrics and gynecology.

[211]  J. Vermylen,et al.  Anticoagulants and Spinal‐Epidural Anesthesia , 1994, Anesthesia and analgesia.

[212]  C. Carlsson,et al.  Epidural hematoma associated with epidural anesthesia: complications of anticoagulant therapy. , 1992, Anesthesiology.

[213]  J. Hirsh,et al.  The Relationship between Anti-Factor Xa Level and Clinical Outcome in Patients Receiving Enoxaparine Low Molecular Weight Heparin to Prevent Deep Vein Thrombosis after Hip Replacement , 1989, Thrombosis and Haemostasis.

[214]  J. Rowlingson,et al.  Do Antiplatelet Agents Contribute to the Development of Perioperative Spinal Hematoma? , 1998, Regional Anesthesia & Pain Medicine.

[215]  L. Fleisher,et al.  Practice Alert for the Perioperative Management of Patients with Coronary Artery Stents: A Report by the American Society of Anesthesiologists Committee on Standards and Practice Parameters , 2009, Anesthesiology.

[216]  J. Hirsh,et al.  Antiplatelet drugs: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). , 2008, Chest.

[217]  K. H. Kimbel,et al.  Ginkgo biloba , 1992, The Lancet.

[218]  D. Schroeder,et al.  Statistics: detecting a rare adverse drug reaction using spontaneous reports. , 1998, Regional anesthesia and pain medicine.

[219]  M. Tryba [Hemostatic requirements for the performance of regional anesthesia. Workshop on hemostatic problems in regional anesthesia]. , 1989, Regional-Anaesthesie.

[220]  S. Frostick,et al.  Oral dabigatran etexilate vs. subcutaneous enoxaparin for the prevention of venous thromboembolism after total knee replacement: the RE‐MODEL randomized trial , 2007, Journal of thrombosis and haemostasis : JTH.

[221]  J. Parvizi,et al.  Can Epidural Anesthesia and Warfarin be Coadministered? , 2007, Clinical orthopaedics and related research.

[222]  J. Kujovich Hormones and pregnancy: thromboembolic risks for women , 2004, British journal of haematology.

[223]  M. Tryba [Epidural regional anesthesia and low molecular heparin: Pro]. , 1993, Anasthesiologie, Intensivmedizin, Notfallmedizin, Schmerztherapie : AINS.

[224]  A. Paganini-Hill,et al.  Association of low protein Z levels with ischemic stroke in young women , 2007, Thrombosis and Haemostasis.

[225]  A. Jackson,et al.  Magnetic resonance imaging of extradural blood patches: appearances from 30 min to 18 h. , 1993, British journal of anaesthesia.

[226]  V. Laux,et al.  Preclinical and clinical characteristics of rivaroxaban: a novel, oral, direct factor Xa inhibitor. , 2007, Seminars in thrombosis and hemostasis.

[227]  M. Leider Goodman & Gilman's The Pharmacological Basis of Therapeutics , 1985 .

[228]  L. Chan,et al.  Spinal epidural hematoma following central neuraxial blockade and subcutaneous enoxaparin: a case report. , 2004, Journal of clinical anesthesia.

[229]  C. Badenhorst Epidural Hematoma After Epidural Pain Control and Concomitant Postoperative Anticoagulation , 1995, Regional Anesthesia & Pain Medicine.

[230]  T. Horlocker,et al.  Anticoagulation and neuraxial block: historical perspective, anesthetic implications, and risk management. , 1998, Regional anesthesia and pain medicine.

[231]  R. McCarthy,et al.  Determination of residual antiplatelet activity of clopidogrel before neuraxial injections. , 2011, British journal of anaesthesia.

[232]  R. Pizov,et al.  Platelet function recovery after cessation of aspirin: preliminary study of volunteers and surgical patients , 2010, European journal of anaesthesiology.

[233]  R. Beyth,et al.  Hemorrhagic complications of anticoagulant and thrombolytic treatment: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). , 2008, Chest.

[234]  K. Bozic,et al.  Bleeding complications from femoral and sciatic nerve catheters in patients receiving low molecular weight heparin. , 2006, Anesthesia and analgesia.

[235]  A. Quick Aspirin and bleeding time. , 1970, JAMA.

[236]  K. Rathgen,et al.  Influence of Renal Impairment on the Pharmacokinetics and Pharmacodynamics of Oral Dabigatran Etexilate , 2010, Clinical pharmacokinetics.

[237]  W. Humphreys,et al.  Comparative Metabolism of 14C-Labeled Apixaban in Mice, Rats, Rabbits, Dogs, and Humans , 2009, Drug Metabolism and Disposition.

[238]  A. Gori,et al.  Different methodologies for evaluating the effect of clopidogrel on platelet function in high‐risk coronary artery disease patients , 2007, Journal of thrombosis and haemostasis : JTH.

[239]  R. Centor,et al.  Reassessment of clinical practice guidelines: go gently into that good night. , 2009, JAMA.

[240]  J. Finsterer,et al.  Recovery from acute paraplegia due to spontaneous spinal, epidural hematoma under minimal-dose acetyl-salicylic acid , 2008, Neurological Sciences.

[241]  E. Connolly,et al.  Management of Spinal Epidural Hematoma After Tissue Plasminogen Activator: A Case Report , 1996, Spine.

[242]  J. Modig The role of lumbar epidural anaesthesia as antithrombotic prophylaxis in total hip replacement. , 1985, Acta chirurgica Scandinavica.

[243]  W. Maloney,et al.  Deep venous thrombosis prophylaxis for knee replacement: warfarin and pneumatic compression. , 1998, American journal of orthopedics.

[244]  L. Hillis,et al.  Antiplatelet therapy for ischemic heart disease. , 2004, The New England journal of medicine.

[245]  G. Guyatt,et al.  Grades of recommendation for antithrombotic agents: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). , 2008, Chest.

[246]  K. D. Rose,et al.  Spontaneous spinal epidural hematoma with associated platelet dysfunction from excessive garlic ingestion: a case report. , 1990, Neurosurgery.

[247]  S. Kopp,et al.  Anticoagulation in pregnancy and neuraxial blocks. , 2008, Anesthesiology clinics.

[248]  E. Antman,et al.  Evaluation of the novel factor Xa inhibitor edoxaban compared with warfarin in patients with atrial fibrillation: design and rationale for the Effective aNticoaGulation with factor xA next GEneration in Atrial Fibrillation-Thrombolysis In Myocardial Infarction study 48 (ENGAGE AF-TIMI 48). , 2010, American heart journal.

[249]  H. Kehlet,et al.  Chronic pain following Caesarean section , 2004, Acta anaesthesiologica Scandinavica.

[250]  S. Stehr,et al.  Spinal epidural hematoma after spinal anesthesia in a patient treated with clopidogrel and enoxaparin. , 2004, Anesthesiology.

[251]  S. Frostick,et al.  Dabigatran etexilate versus enoxaparin for prevention of venous thromboembolism after total hip replacement: a randomised, double-blind, non-inferiority trial , 2007, The Lancet.

[252]  M. Avram,et al.  Factor VII Levels and International Normalized Ratios in the Early Phase of Warfarin Therapy , 2010, Anesthesiology.

[253]  J. Hirsh,et al.  The pharmacology and management of the vitamin K antagonists: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. , 2004, Chest.

[254]  H. Wulf,et al.  Rückenmarksnahe Regionalanästhesien und Thrombo - embolie prophylaxe/antithrombotische Medikation* 2. überarbeitete Empfehlung der Deutschen Gesellschaft für Anästhesiologie und Intensivmedizin Regional anaesthesia and thromboembolism prophylaxis/anticoagulation - Revised recommendations of the Germ , 2007 .

[255]  B. Lindblad,et al.  Low molecular weight heparin for thromboprophylaxis and epidural/spinal anaesthesia – is there a risk? , 1992, Acta anaesthesiologica Scandinavica.

[256]  N. Rainov,et al.  Nontraumatic spinal epidural hematoma associated with clopidogrel. , 2006, Zentralblatt für Neurochirurgie.

[257]  J. Langhoff‐Roos,et al.  Inherited thrombophilias and adverse pregnancy outcome: screening and management. , 2005, Seminars in perinatology.

[258]  R. Collins,et al.  Reduction in fatal pulmonary embolism and venous thrombosis by perioperative administration of subcutaneous heparin. Overview of results of randomized trials in general, orthopedic, and urologic surgery. , 1988, The New England journal of medicine.

[259]  R V Patel,et al.  Effects of epidural anesthesia and analgesia on coagulation and outcome after major vascular surgery. , 1991, Anesthesia and analgesia.

[260]  D. Greenblatt Elimination half-life of drugs: value and limitations. , 1985, Annual review of medicine.

[261]  R. Yarnell,et al.  Epidural hematoma complicating cholestasis of pregnancy. , 1996, Current opinion in obstetrics & gynecology.

[262]  M. Stafford-Smith Impaired haemostasisd and regional anaesthesia , 1996, Canadian journal of anaesthesia = Journal canadien d'anesthesie.

[263]  R. Venkataramanan,et al.  Changes in the pharmacokinetics of the low-molecular-weight heparin enoxaparin sodium during pregnancy. , 1999, American journal of obstetrics and gynecology.

[264]  J. Heit,et al.  Prevention of venous thromboembolism. , 2001, Clinics in geriatric medicine.

[265]  S. Alahuhta,et al.  Nordic guidelines for neuraxial blocks in disturbed haemostasis from the Scandinavian Society of Anaesthesiology and Intensive Care Medicine , 2010, Acta anaesthesiologica Scandinavica.

[266]  M. Gent,et al.  A randomized evaluation of betrixaban, an oral factor Xa inhibitor, for prevention of thromboembolic events after total knee replacement (EXPERT) , 2008, Thrombosis and Haemostasis.

[267]  R. Shlansky-Goldberg Platelet aggregation inhibitors for use in peripheral vascular interventions: what can we learn from the experience in the coronary arteries? , 2002, Journal of vascular and interventional radiology : JVIR.

[268]  C. Ko,et al.  The rate of bleeding complications after pharmacologic deep venous thrombosis prophylaxis: a systematic review of 33 randomized controlled trials. , 2006, Archives of surgery.

[269]  K. Follett,et al.  Spinal epidural hematoma following coronary thrombolysis with tissue plasminogen activator. Report of two cases. , 1995, Journal of neurosurgery.

[270]  J. de Andrés,et al.  Anticlotting drugs and regional anaesthetic and analgesic techniques: comparative update of the safety recommendations , 2007, European journal of anaesthesiology.

[271]  K. McGoldrick,et al.  Severe Neurological Complications After Central Neuraxial Blockades in Sweden 1990-1999 , 2005 .

[272]  Clifford W Colwell,et al.  Prevention of Venous Thromboembolism* American College of Chest Physicians Evidence- Based Clinical Practice Guidelines (8th Edition) , 2008 .

[273]  F. Ventura,et al.  Spinal epidural hematoma following coronary thrombolysis. A case report. , 2004, Journal of neurosurgical sciences.

[274]  P. Tsai,et al.  General anaesthesia is associated with increased risk of surgical site infection after Caesarean delivery compared with neuraxial anaesthesia: a population-based study. , 2011, British journal of anaesthesia.

[275]  J. Douketis,et al.  The perioperative management of antithrombotic therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). , 2008, Chest.

[276]  W. Humphreys,et al.  Apixaban Metabolism and Pharmacokinetics after Oral Administration to Humans , 2009, Drug Metabolism and Disposition.

[277]  M. Tryba European practice guidelines: thromboembolism prophylaxis and regional anesthesia. , 1998, Regional anesthesia and pain medicine.

[278]  Z. Amoura,et al.  Changes in Enoxaparin Pharmacokinetics During Pregnancy and Implications for Antithrombotic Therapeutic Strategy , 2008, Clinical pharmacology and therapeutics.

[279]  M. Feuring,et al.  Dabigatran etexilate – a novel, reversible, oral direct thrombin inhibitor: Interpretation of coagulation assays and reversal of anticoagulant activity , 2010, Thrombosis and Haemostasis.

[280]  H. Masumoto,et al.  Clinical Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the Novel Factor Xa Inhibitor Edoxaban in Healthy Volunteers , 2010, Journal of clinical pharmacology.

[281]  S. Monteith,et al.  Spontaneous spinal hematomas and low-molecular-weight heparin. Report of four cases and review of the literature. , 2004, Journal of neurosurgery. Spine.

[282]  A. Greinacher,et al.  Recombinant Hirudin in Clinical Practice: Focus on Lepirudin , 2001, Circulation.

[283]  J. D. Greaves,et al.  Serious spinal cord injury due to haematomyelia caused by spinal anaesthesia in a patient treated with low‐dose heparin , 1997, Anaesthesia.

[284]  C. Frigon,et al.  Bowel hematoma following an iliohypogastric‐ilioinguinal nerve block , 2006, Paediatric anaesthesia.

[285]  J. Salmon,et al.  Prolonged paradoxical effect of aspirin on platelet behaviour and bleeding time in man. , 1979, Thrombosis research.

[286]  J. M. Nicoletti,et al.  Acute spinal subdural hematoma. Case report. , 1974, Journal of neurosurgery.

[287]  M. Taboada,et al.  Intraneural hematoma after nerve stimulation-guided femoral block in a patient with factor XI deficiency: case report. , 2011, Journal of clinical anesthesia.

[288]  A. James Practice bulletin no. 123: thromboembolism in pregnancy. , 2011, Obstetrics and gynecology.

[289]  S. Mackinnon,et al.  Intrafascicular Injection of Ammonium Sulfate and Bupivacaine in Peripheral Nerves of Neonatal and Juvenile Rats , 1997, Regional Anesthesia & Pain Medicine.

[290]  J. Stangier Clinical Pharmacokinetics and Pharmacodynamics of the Oral Direct Thrombin Inhibitor Dabigatran Etexilate , 2008, Clinical pharmacokinetics.

[291]  K. Shimoji,et al.  Renal subcapsular hematoma after lumbar plexus block. , 1996, Anesthesiology.

[292]  M. Paech,et al.  Complications of obstetric epidural analgesia and anaesthesia: a prospective analysis of 10,995 cases. , 1998, International journal of obstetric anesthesia.

[293]  T. Kitajima,et al.  Delayed Severe Airway Obstruction Due to Hematoma Following Stellate Ganglion Block , 1998, Regional Anesthesia & Pain Medicine.

[294]  P. Wille-Jørgensen,et al.  A comparison of recombinant hirudin with a low-molecular-weight heparin to prevent thromboembolic complications after total hip replacement. , 1997, The New England journal of medicine.