Makris, M.

Spahn, D. R.

van Veen, J. J.

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British Journal of Anaesthesia 106 (1): 1–3 (2011)doi:10.1093/bja/aeq357EDITORIAL IRoutine preoperative coagulation tests: an outdatedpractice?J. J. van Veen 1, D. R. Spahn 2 and M. Makris 1*1 Sheffield Haemophilia and Thrombosis Centre, Royal Hallamshire Hospital, Glossop Road, Sheffield S10 2JF, UK2 Anaesthesiology, Intensive Care Medicine and OR-Management, University Hospital Zurich, CH-8091 Zurich, Switzerland* E-mail: m.makris@shef.ac.ukRoutine coagulation tests have been used for many years inthe preoperative setting in the belief that they identifypatients who may have acquired or congenital bleeding dis-orders, and on the assumption that testing will predict peri-operative bleeding allowing treatment to be given andprevent it. Coagulation ‘screens’ typically include the pro-thrombin time (PT) and the activated partial thromboplastintime (APTT). Both tests were originally developed to aid in thediagnosis of inherited bleeding disorders such as haemo-philia and were not intended as screening tests.Activation of coagulation can be achieved through the intrin-sic or the extrinsic pathway leading to activation of the commonpathway and conversion of fibrinogen to fibrin leading to clotformation. Although the cascade model of coagulation is notphysiological, it is useful as a means to understand the mechan-ism by which traditional coagulation tests detect coagulopa-thies. The APTT activates plasma typically with substancessuch as kaolin or silica which cause activation of the contactpathway and, subsequently, the intrinsic and common coagu-lation pathways. A deficiency in any of these pathways willtherefore prolong the APTT. The PT is activated with supraphy-siological concentrations of tissue factor and detects FVIIdeficiency and also deficiencies in the common pathway. Bothtests can also be prolonged by the presence of a lupus anticoa-gulant, inhibitors such as anticoagulants, and acute conditionsassociated with an acquired bleeding state.Inherited coagulation defects are rare. The incidence of hae-mophilia A and B is estimated at 1:50001 2 and 1:30 0003 malebirths, respectively. Severe, clinically relevant, deficiencies of FII,FV, FVII, FX, and fibrinogen are even rarer with an incidencevarying between 1:300 000 and 1:2 000 000,4 although thismay be higher in populations where consanguineous marriagesare more common. FXI deficiency is common in Ashkenazi Jewswith a prevalence of 8%5 but rare in a general population.4 Themajority of patients with these bleeding disorders will be awareof their diagnosis through either a personal or family history ofbleeding and will be registered at specialized haemophiliacentres. Indiscriminate screening by routine coagulationtesting will therefore only very rarely identify previously unde-tected individuals. In contrast, prolongation of the APTT is acommon occurrence with the most common reasons beingmild FXII deficiency and the presence of a lupus anticoagulant,neither of which is associated with a bleeding tendency. Moder-ate and severe FXII deficiency was found in 2.3% of otherwisehealthy Austrian blood donors6 and in 10.3% of patients under-going cardiac surgery.7 Lupus anticoagulant can be found in1.2–3.8% of healthy individuals, but the incidence increaseswith age and chronic disease, and was found in up to 30% ofpatients with systemic lupus erythematosus.8 The ability of alupus anticoagulant to prolong the APTT or PT depends on thecombination of reagents and analysers used and may thereforevary between laboratories. Other causes of a prolonged APTTnot associated with a bleeding tendency include high molecularweight kininogen deficiency and prekallikrein deficiency. Finally,a normal range is calculated by the mean +2 standard devi-ations of measurements in healthy, non-bleeding subjectsand by definition 2.5% of measurements in normal individualswill show a prolonged clotting time. Therefore, if routine coagu-lation testing is done to identify previously undiagnosed bleed-ing disorders, it is much more likely to identify a prolongedroutine coagulation test that is not associated with a bleedingtendency. In practice, this can lead to further unnecessaryVolume 106, Number 1, January 2011& The Author [2011]. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved.For Permissions, please email: journals.permissions@oup.comtesting and postponement or delay of the surgery. To furthercompound the situation, a normal routine test does notexclude the presence of, sometimes severe, bleeding disorders.The most common of these is mild von Willebrand disease.Deficiency of von Willebrand factor can occur in up to 1% ofthe population, but only 1:10 000 are estimated to have a clini-cally significant bleeding disorder.9 Although FVIII may bereduced in patients with von Willebrand disease who thereforewill have a prolonged APTT, in milder forms FVIII may benormal and patients may not be detected by routine testing.Mild haemophilia A or B may also be missed if an insensitivereagent/analyser combination is used, or during an acutephase response where a temporarily high FVIII level maylead to shortening of the APTT. Other conditions that cannotbe detected by routine coagulation testing but may be associ-ated with clinically significant bleeding include the rare inher-ited bleeding disorders such as FXIII and alpha 2 antiplasmindeficiency and platelet function disorders.The British Committee for Standards in Haematology(BCSH) has recently published guidelines on the use of thePT and APTT in the preoperative setting based on a systematicreview of the literature.10 They included studies that enabledthe calculation of predictive values (PV) and likelihood ratios(LR) of the coagulation tests and bleeding history for perio-perative bleeding in paediatric ENT (six studies), generalsurgery (two studies), and one study in adult ENT surgery.Three studies were prospective and in total measurementsof more than 12 000 patients were included. They foundpoor positive PV and low LR for bleeding with an abnormalcoagulation test, whereas the perioperative bleeding rateswere similar in patients with and without abnormal coagu-lation tests. A similar conclusion was reached in a review ofstudies of patients undergoing bronchoscopy, central veincannulation, angiography, liver and kidney biopsy, and para-centesis.11 The BCSH guideline does not recommend the useof routine coagulation tests to predict perioperative bleedingrisk in unselected patients before surgery or other invasiveprocedures.10 The systematic review did not include studiesof intracranial, neurosurgical, or ophthalmic surgery due to apaucity of data, and although testing may be more justifiedin procedures with a higher risk from bleeding, the argumentsregarding poor sensitivity and specificity of these tests remain.A bleeding history is subjective and common symptoms arefound in up to 25% of a healthy population without bleedingdisorders including epistaxis, gum bleeding, and post-partumhaemorrhage.9 The use of a standardized bleeding question-naire has been suggested as being better than indiscriminatecoagulation testing as a screening tool for perioperative bleed-ing,12 and there are suggestions that in patients with congeni-tal bleeding disorders, a structured history is at least asinformative as laboratory testing to predict bleeding.13 14 TheBCSH guideline recommends that a bleeding history, includingfamily history, evidence of excessive post-traumatic or post-surgical bleeding, and use of antithrombotic drugs should betaken in all patients before surgery or invasive procedures.10Therefore, based on the available evidence, a reasonableapproach to assessing the perioperative bleeding risk isthat a structured bleeding history is taken and coagulationtesting is undertaken only if there is concern about a bleed-ing tendency arising from the history. This may then alsoinclude referral to haematology to investigate disordersthat are not detected by routine testing. Testing, however,should be considered in patients with acute conditionspotentially associated with a haemorrhagic tendency suchas liver disease, sepsis, diffuse intravascular coagulation, pre-eclampsia, cholestasis, and poor nutritional states leading tovitamin K deficiency.Coagulation testing is often routinely undertaken in anti-coagulated patients or patients to be started on anticoagu-lants. The APTT is used to monitor unfractionated heparin,lepirudin, bivalirudin, and argatroban whereas the INR isused for the monitoring of coumarin anticoagulants. TheAPTT and PT are insensitive to low molecular weight heparins,fondaparinux and danaparoid. Although prolongation of theAPTT can occur at therapeutic doses of these agents, specificanti-Xa measurements should be used to assess the degreeof anticoagulation, if necessary. Recently, two new oral antic-oagulants, rivaroxaban and dabigatran, were licensed forthromboprophylaxis after total hip and knee replacementand they do not require routine monitoring. Rivaroxaban isa direct anti-Xa inhibitor that can prolong both the PT andAPTT (PT more than APTT). Neither test is suitable tomonitor the degree of anticoagulation, although a specifi-cally calibrated PT assay has been suggested, and alsomore specialized assays that are not generally available.15Dabigatran is a direct thrombin inhibitor that can alsoprolong both the PT and APTT (APTT more than PT). Again,neither of these tests is suitable for monitoring the degreeof anticoagulation, and although a normal APTT may indicatethat no or low plasma concentrations of dabigatran arepresent, this depends on the reagent/analyser combinationused. A normal thrombin time is more likely to indicatethat no dabigatran is present and other more specialized,but not generally available, tests such as the ecarin clottingtime have also been proposed.16Finally, there is increasing interest in the possibility of peri-operative monitoring of the effect of antiplatelet agents suchas aspirin and clopidogrel. Although various point-of-caretests have been developed, there remain significant ques-tions about their sensitivity, specificity, and ability topredict bleeding,17 and none of these tests are therefore cur-rently routinely recommended in the preoperative setting butare the subject of ongoing studies.In conclusion, we feel that indiscriminate use of routinecoagulation testing in the preoperative setting is nothelpful and may cause unnecessary further testing anddelay of surgery. Coagulation testing should be restricted towell-defined circumstances:† Patients with a family history of known inherited bleed-ing disorders.† Patients with a personal history of bleeding identified bystructured history taking or a family history of bleeding.Ideally, these individuals should be investigatedBJA Editorial I2electively by a haematologist before any surgery orinvasive procedure.† Patients with acute illnesses such as sepsis or con-ditions that can be associated with a coagulopathysuch as chronic liver disease.† Patients on some anticoagulants. As anticoagulants,but not necessarily antiplatelet drugs,18 are stoppedbefore operation for elective surgery, coagulationtesting should only be required for emergency surgery.When surgery is performed on anticoagulated patients,appropriate testing can be useful in excluding over-anticoagulation at the time of surgery.Conflict of interestThe authors have declared no conflicts of interest related tothis editorial. Dr D.R. Spahn has provided a full declaration ofinterests that was published in Br J Anaesth 2010; 105: 103–5, doi: 10.1093/bja/aeq166.References1 Fukutake K. Current status of hemophilia patients and recombi-nant coagulation factor concentrates in Japan. Semin ThrombHemost 2000; 26: 29–322 Smit C, Rosendaal FR, Varekamp I, et al. Physical condition, lon-gevity, and social performance of Dutch haemophiliacs, 1972–85.Br Med J 1989; 298: 235–83 Giannelli F, Green PM, Sommer SS, et al. Haemophilia B: databaseof point mutations and short additions and deletions—eighthedition. Nucleic Acids Res 1998; 26: 265–84 Bolton-Maggs PH, Perry DJ, Chalmers EA, et al. The rare coagu-lation disorders—review with guidelines for management fromthe United Kingdom Haemophilia Centre Doctors’ Organisation.Haemophilia 2004; 10: 593–6285 Asakai R, Chung DW, Davie EW, Seligsohn U. Factor XI deficiencyin Ashkenazi Jews in Israel. N Engl J Med 1991; 325: 153–86 Halbmayer WM, Haushofer A, Schon R, et al. The prevalence ofmoderate and severe FXII (Hageman factor) deficiency amongthe normal population: evaluation of the incidence of FXIIdeficiency among 300 healthy blood donors. Thromb Haemost1994; 71: 68–727 Halbmayer WM, Haushofer A, Radek J, Schon R, Deutsch M,Fischer M. Prevalence of factor XII (Hageman factor) deficiencyamong 426 patients with coronary heart disease awaitingcardiac surgery. Coron Artery Dis 1994; 5: 451–48 Petri M. Epidemiology of the antiphospholipid antibody syndrome.J Autoimmun 2000; 15: 145–519 Sadler JE, Mannucci PM, Berntorp E, et al. Impact, diagnosis andtreatment of von Willebrand disease. Thromb Haemost 2000; 84:160–7410 Chee YL, Crawford JC, Watson HG, Greaves M. Guidelines on theassessment of bleeding risk prior to surgery or invasive pro-cedures. British Committee for Standards in Haematology. Br JHaematol 2008; 140: 496–50411 Segal JB, Dzik WH. Paucity of studies to support that abnormalcoagulation test results predict bleeding in the setting of invasiveprocedures: an evidence-based review. Transfusion 2005; 45:1413–2512 Koscielny J, Ziemer S, Radtke H, et al. A practical concept forpreoperative identification for patients with impaired primaryhemostasis. Clin Appl Thromb Hemost 2004; 10: 195–20413 Sramek A, Eikenboom JC, Briet E, Vandenbroucke JP, Rosendaal FR.Usefulness of patient interview in bleeding disorders. Arch InternMed 1995; 155: 1409–1514 Tosetto A, Rodeghiero F, Castaman G, et al. A quantitative analy-sis of bleeding symptoms in type 1 von Willebrand disease:results from a multicenter European study (MCMDM-1 VWD).J Thromb Haemost 2006; 4: 766–7315 Samama MM, Martinoli JL, LeFlem L, et al. Assessment of labora-tory assays to measure rivaroxaban—an oral, direct factor Xainhibitor. Thromb Haemost 2010; 103: 815–2516 van Ryn J, Stangier J, Haertter S, et al. Dabigatran etexilate—anovel, reversible, oral direct thrombin inhibitor: interpretation ofcoagulation assays and reversal of anticoagulant activity.Thromb Haemost 2010; 103: 1116–2717 Lippi G, Favaloro EJ, Salvagno GL, Franchini M. Laboratory assess-ment and perioperative management of patients on antiplatelettherapy: from bench to bedside. Clin Chim Acta 2009; 405: 8–1618 Chassot PG, Delabays A, Spahn DR. Perioperative antiplatelettherapy: the case for continuing therapy in patients at risk formyocardial infarction. Br J Anaesth 2007; 99: 316–28British Journal of Anaesthesia 106 (1): 3–5 (2011)doi:10.1093/bja/aeq358EDITORIAL IINerve location in regional anaesthesia: finding what liesbeneath the skinP. Marhofer 1* and W. Harrop-Griffiths 21 Department of Anaesthesia, Intensive Care Medicine and Pain Therapy, Medical University of Vienna, Waehringer Guertel 18-20, A-1090Vienna, Austria2 Department of Anaesthesia, Imperial College Healthcare NHS Trust, St Mary’s Hospital, Praed Street, London W2 1NY, UK* E-mail: peter.marhofer@meduniwien.ac.atEditorial II BJA3

Routine preoperative coagulation tests: an outdated practice?

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