Subscribe to RSS
DOI: 10.1055/s-0032-1326780
Laboratory Investigations for Bleeding Disorders
Publication History
Publication Date:
25 September 2012 (online)
Abstract
Bleeding disorder panels often include the prothrombin time (PT)/international normalized ratio (INR), activated partial thromboplastin time (APTT), fibrinogen level, and thrombin time (TT). We explored the detection of abnormalities from bleeding disorders by these tests among subjects referred for bleeding disorder assessments, using data from a bleeding disorder study to determine sensitivities and specificities. Among subjects referred to hematologists for bleeding disorder assessment, coagulation defects were uncommon and the APTT and TT detected many nonsignificant abnormalities. While all test and panel specificities were acceptable (88 to 100%), coagulation screening tests were less sensitive to clinically significant abnormalities (1.0 to 2.1%) than von Willebrand disease (VWD) screens (6.7%), and light transmission platelet aggregometry (LTA) (26%). Accordingly, panels comprising PT/INR, APTT, fibrinogen, and TT had lower sensitivity to bleeding disorders (3.7%) than panels expanded to include VWD screens (8.5%), or VWD screens and LTA (30%). These findings have important implications for bleeding disorder diagnosis.
-
References
- 1 Watson HG, Greaves M. Can we predict bleeding?. Semin Thromb Hemost 2008; 34 (1) 97-103
- 2 Chee YL, Greaves M. Role of coagulation testing in predicting bleeding risk. Hematol J 2003; 4 (6) 373-378
- 3 Hayward CP, Moffat KA, Plumhoff E, Van Cott EM. Approaches to investigating common bleeding disorders: an evaluation of North American coagulation laboratory practices. Am J Hematol 2012; 87 (Suppl. 01) S45-S50
- 4 Hayward CP. Diagnosis and management of mild bleeding disorders. Hematology (Am Soc Hematol Educ Program) 2005; 2005 (1) 423-428
- 5 Puetz J. Thrombin time and fibrinogen as initial screening tests for people with inherited bleeding disorders. Haemophilia 2010; 16 (4) 700-701
- 6 Verhovsek M, Moffat KA, Hayward CP. Laboratory testing for fibrinogen abnormalities. Am J Hematol 2008; 83 (12) 928-931
- 7 Dzik WH. Predicting hemorrhage using preoperative coagulation screening assays. Curr Hematol Rep 2004; 3 (5) 324-330
- 8 Hayward CP, Harrison P, Cattaneo M, Ortel TL, Rao AK ; Platelet Physiology Subcommittee of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Platelet function analyzer (PFA)-100 closure time in the evaluation of platelet disorders and platelet function. J Thromb Haemost 2006; 4 (2) 312-319
- 9 Harrison P, Mackie I, Mumford A , et al.; British Committee for Standards in Haematology. Guidelines for the laboratory investigation of heritable disorders of platelet function. Br J Haematol 2011; 155 (1) 30-44
- 10 Hayward CP, Pai M, Liu Y , et al. Diagnostic utility of light transmission platelet aggregometry: results from a prospective study of individuals referred for bleeding disorder assessments. J Thromb Haemost 2009; 7 (4) 676-684
- 11 Hayward CP, Moffat KA, Raby A , et al. Development of North American consensus guidelines for medical laboratories that perform and interpret platelet function testing using light transmission aggregometry. Am J Clin Pathol 2010; 134 (6) 955-963
- 12 Hayward CP. Diagnostic evaluation of platelet function disorders. Blood Rev 2011; 25 (4) 169-173
- 13 Morris WH, Kumar A. What is the significance of an isolated elevated activated partial thromboplastin time in the preoperative setting?. Cleve Clin J Med 2007; 74 (Suppl. 01) S13-S15
- 14 Carling MS, Jeppsson A, Wessberg P, Henriksson A, Baghaei F, Brisby H. Preoperative fibrinogen plasma concentration is associated with perioperative bleeding and transfusion requirements in scoliosis surgery. Spine 2011; 36 (7) 549-555
- 15 Abbasi S, Khan FA. Effect of pre-operative coagulation testing on intra-operative transfusion requirements in surgical patients. J Coll Physicians Surg Pak 2005; 15 (6) 319-322
- 16 Ng KF, Lai KW, Tsang SF. Value of preoperative coagulation tests: reappraisal of major noncardiac surgery. World J Surg 2002; 26 (5) 515-520
- 17 Schramm B, Leslie K, Myles PS, Hogan CJ. Coagulation studies in preoperative neurosurgical patients. Anaesth Intensive Care 2001; 29 (4) 388-392
- 18 Howells II RC, Wax MK, Ramadan HH. Value of preoperative prothrombin time/partial thromboplastin time as a predictor of postoperative hemorrhage in pediatric patients undergoing tonsillectomy. Otolaryngol Head Neck Surg 1997; 117 (6) 628-632
- 19 Zwack GC, Derkay CS. The utility of preoperative hemostatic assessment in adenotonsillectomy. Int J Pediatr Otorhinolaryngol 1997; 39 (1) 67-76
- 20 Houry S, Georgeac C, Hay JM, Fingerhut A, Boudet MJ ; The French Associations for Surgical Research. A prospective multicenter evaluation of preoperative hemostatic screening tests. Am J Surg 1995; 170 (1) 19-23
- 21 Borhany M, Pahore Z, Ul Qadr Z , et al. Bleeding disorders in the tribe: result of consanguineous in breeding. Orphanet J Rare Dis 2010; 5: 23
- 22 Macpherson CR, Jacobs P, Dent DM. Abnormal peri-operative haemorrhage in asymptomatic patients is not predicted by laboratory testing. S Afr Med J 1993; 83 (2) 106-108
- 23 Burk CD, Miller L, Handler SD, Cohen AR. Preoperative history and coagulation screening in children undergoing tonsillectomy. Pediatrics 1992; 89 (4 Pt 2) 691-695
- 24 Schmidt JL, Yaremchuk KL, Mickelson SA. Abnormal coagulation profiles in tonsillectomy and adenoidectomy patients. Henry Ford Hosp Med J 1990; 38 (1) 33-35
- 25 Bushick JB, Eisenberg JM, Kinman J, Cebul RD, Schwartz JS. Pursuit of abnormal coagulation screening tests generates modest hidden preoperative costs. J Gen Intern Med 1989; 4 (6) 493-497
- 26 Manning SC, Beste D, McBride T, Goldberg A. An assessment of preoperative coagulation screening for tonsillectomy and adenoidectomy. Int J Pediatr Otorhinolaryngol 1987; 13 (3) 237-244
- 27 Suchman AL, Mushlin AI. How well does the activated partial thromboplastin time predict postoperative hemorrhage?. JAMA 1986; 256 (6) 750-753
- 28 Close HL, Kryzer TC, Nowlin JH, Alving BM. Hemostatic assessment of patients before tonsillectomy: a prospective study. Otolaryngol Head Neck Surg 1994; 111 (6) 733-738
- 29 Suchman AL, Griner PF. Diagnostic uses of the activated partial thromboplastin time and prothrombin time. Ann Intern Med 1986; 104 (6) 810-816
- 30 Watel A, Jude B, Caron C, Vandeputte H, Gaeremynck E, Cosson A. Successes and failures of the activated partial thromboplastin time in the preoperative evaluation. Ann Fr Anesth Reanim 1986; 5 (1) 35-39
- 31 Eisenberg JM, Clarke JR, Sussman SA. Prothrombin and partial thromboplastin times as preoperative screening tests. Arch Surg 1982; 117 (1) 48-51
- 32 Peterson P, Hayes TE, Arkin CF , et al. The preoperative bleeding time test lacks clinical benefit: College of American Pathologists' and American Society of Clinical Pathologists' position article. Arch Surg 1998; 133 (2) 134-139
- 33 Biron C, Mahieu B, Rochette A , et al. Preoperative screening for von Willebrand disease type 1: low yield and limited ability to predict bleeding. J Lab Clin Med 1999; 134 (6) 605-609
- 34 Xu J, Yu Z, Zhang L, Ruan C, Yang R. Diagnosis and management of von Willebrand disease in China. Semin Thromb Hemost 2011; 37 (5) 607-614
- 35 Woods AI, Sánchez-Luceros A, Meschengieser SS, Kempfer AC, Blanco AN, Lazzari MA. Diagnosis and management of von Willebrand disease in a single institution of Argentina. Semin Thromb Hemost 2011; 37 (5) 568-575
- 36 Favaloro EJ, Bonar R, Favaloro J, Koutts J. Diagnosis and management of von Willebrand disease in Australia. Semin Thromb Hemost 2011; 37 (5) 542-554
- 37 Flood VH, Gill JC, Friedman KD, Bellissimo DB, Haberichter SL, Montgomery RR. Von Willebrand disease in the United States: a perspective from Wisconsin. Semin Thromb Hemost 2011; 37 (5) 528-534
- 38 Federici AB, Bucciarelli P, Castaman G , et al. Management of inherited von Willebrand disease in Italy: results from the retrospective study on 1234 patients. Semin Thromb Hemost 2011; 37 (5) 511-521
- 39 Lassila R, Holme PA, Landorph A, Petrini P, Onundarson PT, Hillarp A. Nordic Haemophilia Council's practical guidelines on diagnosis and management of von Willebrand disease. Semin Thromb Hemost 2011; 37 (5) 495-502
- 40 Keeney S, Collins P, Cumming A, Goodeve A, Pasi J. Diagnosis and management of von Willebrand disease in the United Kingdom. Semin Thromb Hemost 2011; 37 (5) 488-494
- 41 de Wee EM, Leebeek FW, Eikenboom JC. Diagnosis and management of von Willebrand disease in The Netherlands. Semin Thromb Hemost 2011; 37 (5) 480-487
- 42 Favaloro EJ. Von Willebrand disease: local diagnosis and management of a globally distributed bleeding disorder. Semin Thromb Hemost 2011; 37 (5) 440-455
- 43 Favaloro EJ. Diagnosis and classification of von Willebrand disease: a review of the differential utility of various functional von Willebrand factor assays. Blood Coagul Fibrinolysis 2011; 22 (7) 553-564
- 44 Dutt T, Burns S, Mackett N, Benfield C, Lwin R, Keenan R. Application of UKHCDO 2004 guidelines in type 1 von Willebrand Disease—a single centre paediatric experience of the implications of altered or removed diagnosis. Haemophilia 2011; 17 (3) 522-526
- 45 Nichols WL, Hultin MB, James AH , et al. von Willebrand disease (VWD): evidence-based diagnosis and management guidelines, the National Heart, Lung, and Blood Institute (NHLBI) Expert Panel report (USA). Haemophilia 2008; 14 (2) 171-232
- 46 Castilloux JF, Moffat KA, Liu Y, Seecharan J, Pai M, Hayward CP. A prospective cohort study of light transmission platelet aggregometry for bleeding disorders: is testing native platelet-rich plasma non-inferior to testing platelet count adjusted samples?. Thromb Haemost 2011; 106 (4) 675-682
- 47 Pai M, Wang G, Moffat KA , et al. Diagnostic usefulness of a lumi-aggregometer adenosine triphosphate release assay for the assessment of platelet function disorders. Am J Clin Pathol 2011; 136 (3) 350-358
- 48 Quiroga T, Goycoolea M, Matus V , et al. Diagnosis of mild platelet function disorders. Reliability and usefulness of light transmission platelet aggregation and serotonin secretion assays. Br J Haematol 2009; 147 (5) 729-736
- 49 Mezzano D, Quiroga T, Pereira J. The level of laboratory testing required for diagnosis or exclusion of a platelet function disorder using platelet aggregation and secretion assays. Semin Thromb Hemost 2009; 35 (2) 242-254
- 50 Remaley AT, Kennedy JM, Laposata M. Evaluation of the clinical utility of platelet aggregation studies. Am J Hematol 1989; 31 (3) 188-193
- 51 Nair SC, Dargaud Y, Chitlur M, Srivastava A. Tests of global haemostasis and their applications in bleeding disorders. Haemophilia 2010; 16 (Suppl. 05) 85-92
- 52 Clauss A. Rapid physiological coagulation method in determination of fibrinogen. Acta Haematol 1957; 17 (4) 237-246
- 53 Hayward CP, Moffat KA, Pai M , et al. An evaluation of methods for determining reference intervals for light transmission platelet aggregation tests on samples with normal or reduced platelet counts. Thromb Haemost 2008; 100 (1) 134-145
- 54 Zeller JA, Schlesinger S, Runge U, Kessler C. Influence of valproate monotherapy on platelet activation and hematologic values. Epilepsia 1999; 40 (2) 186-189
- 55 Hauser E, Seidl R, Freilinger M, Male C, Herkner K. Hematologic manifestations and impaired liver synthetic function during valproate monotherapy. Brain Dev 1996; 18 (2) 105-109
- 56 Lawrie ASKS, Kitchen S, Purdy G, Mackie IJ, Preston FE, Machin SJ. Assessment of actin FS and actin FSL sensitivity to specific clotting factor deficiencies. Clin Lab Haematol 1998; 20 (3) 179-186
- 57 Peyvandi F, Palla R, Menegatti M , et al; European Network of Rare Bleeding Disorders Group. Coagulation factor activity and clinical bleeding severity in rare bleeding disorders: results from the European Network of Rare Bleeding Disorders. J Thromb Haemost 2012; 10 (4) 615-621
- 58 Peyvandi F, Palla R, Menegatti M, Mannucci PM. Introduction. Rare bleeding disorders: general aspects of clinical features, diagnosis, and management. Semin Thromb Hemost 2009; 35 (4) 349-355
- 59 Acharya SS, Coughlin A, Dimichele DM ; North American Rare Bleeding Disorder Study Group. Rare Bleeding Disorder Registry: deficiencies of factors II, V, VII, X, XIII, fibrinogen and dysfibrinogenemias. J Thromb Haemost 2004; 2 (2) 248-256