Semin Thromb Hemost 2012; 38(06): 586-592
DOI: 10.1055/s-0032-1319769
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Problems and Solutions for Testing Hemostasis Assays while Patients Are on Anticoagulants

Armando Tripodi
1   Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Internal Medicine, IRCCS Cà Granda Maggiore Hospital Foundation and Università degli Studi di Milano, Milano, Italy
› Author Affiliations
Further Information

Publication History

Publication Date:
20 June 2012 (online)

Abstract

Anticoagulant drugs affect directly or indirectly several coagulation parameters. This article is aimed at reviewing the problems encountered while testing patients on treatment and presents potential solutions. In general, it is recommended to postpone the performance of laboratory investigation upon discontinuation of the drug, preferably 2 days or more depending on the drug's half-life. If this strategy is unfeasible and patients remain on treatment, results of testing will likely be affected and result interpretation then requires great caution and knowledge of the peculiar and differential mechanism of action of the relevant anticoagulant drug being used.

 
  • References

  • 1 Kearon C, Kahn SR, Agnelli G , et al; American College of Chest Physicians. Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133 (Suppl. 06) 454S-545S
  • 2 Basu D, Gallus A, Hirsh J, Cade J. A prospective study of the value of monitoring heparin treatment with the activated partial thromboplastin time. N Engl J Med 1972; 287 (7) 324-327
  • 3 Konopad E, Grace M, Johnston R, Noseworthy T, Shustack A. Comparison of PT and aPTT values drawn by venipuncture and arterial line using three discard volumes. Am J Crit Care 1992; 1 (3) 94-101
  • 4 Haynes SR, Allardyce W, Cowan B, Tansey P. Accuracy of coagulation studies performed on blood samples obtained from arterial cannulae. Br J Anaesth 1992; 69 (6) 599-601
  • 5 Richiuso N. Accuracy of aPTT values drawn from heparinized arterial lines in children. Dimens Crit Care Nurs 1998; 17 (1) 14-19
  • 6 Lippi G, Salvagno GL, Montagnana M, Lima-Oliveira G, Guidi GC, Favaloro EJ. Quality standards for sample collection in coagulation testing. Semin Thromb Hemost 2012; 38 (6) 565-575
  • 7 Pengo V, Tripodi A, Reber G , et al; Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardisation Committee of the International Society on Thrombosis and Haemostasis. Update of the guidelines for lupus anticoagulant detection. J Thromb Haemost 2009; 7 (10) 1737-1740
  • 8 Tripodi A, Biasiolo A, Chantarangkul V, Pengo V. Lupus anticoagulant (LA) testing: performance of clinical laboratories assessed by a national survey using lyophilized affinity-purified immunoglobulin with LA activity. Clin Chem 2003; 49 (10) 1608-1614
  • 9 Clauss A. [Rapid physiological coagulation method in determination of fibrinogen]. Acta Haematol 1957; 17 (4) 237-246
  • 10 Mannucci PM, Tripodi A. Factor VIII clotting activity. In: Jespersen J, Bertina RM, Haverkate F, eds. Laboratory Techniques in Thrombosis. A Manual. Dordrecht, The Netherlands: Kluwer Academic Publishers; 1999: 107-113
  • 11 Preda L, Tripodi A, Valsecchi C, Lombardi A, Finotto E, Mannucci PM. A prothrombin time-based functional assay of protein S. Thromb Res 1990; 60 (1) 19-32
  • 12 Marciniak E, Gockerman JP. Heparin-induced decrease in circulating antithrombin-III. Lancet 1977; 2 (8038) 581-584
  • 13 Gray E, Mulloy B, Barrowcliffe TW. Heparin and low-molecular-weight heparin. Thromb Haemost 2008; 99 (5) 807-818
  • 14 Ip BK, Thomson AR, Moriarty HT. A comparison of the sensitivity of APTT reagents to the effects of enoxaparin, a low-molecular weight heparin. Pathology 2001; 33 (3) 347-352
  • 15 Wittkowsky AK. Warfarin and other coumarin derivatives: pharmacokinetics, pharmacodynamics, and drug interactions. Semin Vasc Med 2003; 3 (3) 221-230
  • 16 Paul B, Oxley A, Brigham K, Cox T, Hamilton PJ. Factor II, VII, IX and X concentrations in patients receiving long term warfarin. J Clin Pathol 1987; 40 (1) 94-98
  • 17 Dahlbäck B, Carlsson M, Svensson PJ. Familial thrombophilia due to a previously unrecognized mechanism characterized by poor anticoagulant response to activated protein C: prediction of a cofactor to activated protein C. Proc Natl Acad Sci U S A 1993; 90 (3) 1004-1008
  • 18 Tripodi A, Negri B, Bertina RM, Mannucci PM. Screening for the FV:Q506 mutation—evaluation of thirteen plasma-based methods for their diagnostic efficacy in comparison with DNA analysis. Thromb Haemost 1997; 77 (3) 436-439
  • 19 Jorquera JI, Montoro JM, Fernández MA, Aznar JA, Aznar J. Modified test for activated protein C resistance. Lancet 1994; 344 (8930) 1162-1163
  • 20 Ansell J, Hirsh J, Hylek E , et al; American College of Chest Physicians. Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133 (Suppl. 06) 160S-198S
  • 21 Tripodi A. To mix or not to mix in lupus anticoagulant testing? That is the Question. Semin Thromb Hemost 2012; 38 (4) 385-389
  • 22 Tripodi A, Chantarangkul V, Clerici M, Mannucci PM. Laboratory diagnosis of lupus anticoagulants for patients on oral anticoagulant treatment. Performance of dilute Russell viper venom test and silica clotting time in comparison with Staclot LA. Thromb Haemost 2002; 88 (4) 583-586
  • 23 Triplett DA, Barna LK, Unger GA. A hexagonal (II) phase phospholipid neutralization assay for lupus anticoagulant identification. Thromb Haemost 1993; 70 (5) 787-793
  • 24 Triplett DA, Stocker KF, Unger GA, Barna LK. The Textarin/Ecarin ratio: a confirmatory test for lupus anticoagulants. Thromb Haemost 1993; 70 (6) 925-931
  • 25 Bounameaux H, Cirafici P, de Moerloose P , et al. Measurement of D-dimer in plasma as diagnostic aid in suspected pulmonary embolism. Lancet 1991; 337 (8735) 196-200
  • 26 Tripodi A. D-dimer testing in laboratory practice. Clin Chem 2011; 57 (9) 1256-1262
  • 27 Palareti G, Legnani C, Cosmi B, Guazzaloca G, Pancani C, Coccheri S. Risk of venous thromboembolism recurrence: high negative predictive value of D-dimer performed after oral anticoagulation is stopped. Thromb Haemost 2002; 87 (1) 7-12
  • 28 Palareti G, Cosmi B, Legnani C , et al; PROLONG Investigators. D-dimer testing to determine the duration of anticoagulation therapy. N Engl J Med 2006; 355 (17) 1780-1789
  • 29 Tripodi A, Chantarangkul V, Martinelli I, Bucciarelli P, Mannucci PM. A shortened activated partial thromboplastin time is associated with the risk of venous thromboembolism. Blood 2004; 104 (12) 3631-3634
  • 30 Tripodi A. Levels of coagulation factors and venous thromboembolism. Haematologica 2003; 88 (6) 705-711
  • 31 Passamonti SM, Bucciarelli P, Bader R, Martinelli I. Influence of anticoagulant therapy with vitamin K antagonists on plasma levels of coagulation factor VIII. Thromb Res 2010; 126 (3) 243-245
  • 32 Ansell J, Askin D. New targets for anticoagulation and future perspectives. Curr Drug Discov Technol 2012; 9 (2) 150-155
  • 33 Stangier J, Rathgen K, Stähle H, Gansser D, Roth W. The pharmacokinetics, pharmacodynamics and tolerability of dabigatran etexilate, a new oral direct thrombin inhibitor, in healthy male subjects. Br J Clin Pharmacol 2007; 64 (3) 292-303
  • 34 Warkentin TE, Margetts P, Connolly SJ, Lamy A, Ricci C, Eikelboom JW. Recombinant factor VIIa (rFVIIa) and hemodialysis to manage massive dabigatran-associated postcardiac surgery bleeding. Blood 2012; 119 (9) 2172-2174
  • 35 Lindahl TL, Baghaei F, Blixter IF , et al; Expert Group on Coagulation of the External Quality Assurance in Laboratory Medicine in Sweden. Effects of the oral, direct thrombin inhibitor dabigatran on five common coagulation assays. Thromb Haemost 2011; 105 (2) 371-378
  • 36 Mani H, Hesse C, Stratmann G, Lindhoff-Last E. Rivaroxaban differentially influences ex vivo global coagulation assays based on the administration time. Thromb Haemost 2011; 106 (1) 156-164
  • 37 Samama MM, Martinoli JL, LeFlem L , et al. Assessment of laboratory assays to measure rivaroxaban—an oral, direct factor Xa inhibitor. Thromb Haemost 2010; 103 (4) 815-825
  • 38 Tripodi A, Chantarangkul V, Guinet C, Samama MM. The International Normalized Ratio calibrated for rivaroxaban has the potential to normalize prothrombin time results for rivaroxaban-treated patients: results of an in vitro study. J Thromb Haemost 2011; 9 (1) 226-228