Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Approach to the adult patient with a bleeding diathesis

Reed E Drews, MD
Section Editor
Lawrence LK Leung, MD
Deputy Editor
Jennifer S Tirnauer, MD


Bleeding that is spontaneous, excessive, or delayed in onset following tissue injury results from a localized pathologic process or a disorder of the hemostatic process, involving a complex interplay among vascular integrity, platelet number and function, coagulation factors, and fibrinolysis. This topic review will discuss the diagnostic approach to the patient with abnormal bleeding.

Congenital and acquired disorders of platelet function, as well as the hemostatic process and associated disorders, are discussed separately.

(See "Overview of hemostasis".)

(See "Approach to the adult with unexplained thrombocytopenia".)

(See "Congenital and acquired disorders of platelet function".)

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Sep 2017. | This topic last updated: Jan 11, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Wahlberg T, Blombäck M, Hall P, Axelsson G. Application of indicators, predictors and diagnostic indices in coagulation disorders. I. Evaluation of a self-administered questionnaire with binary questions. Methods Inf Med 1980; 19:194.
  2. Wahlberg T, Blombäck M, Brodin U. Carriers and noncarriers of haemophilia A: I. Multivariate analysis of pedigree data, screening blood coagulation tests and factor VIII variables. Thromb Res 1982; 25:401.
  3. Koreth R, Weinert C, Weisdorf DJ, Key NS. Measurement of bleeding severity: a critical review. Transfusion 2004; 44:605.
  4. Rodeghiero F, Tosetto A, Abshire T, et al. ISTH/SSC bleeding assessment tool: a standardized questionnaire and a proposal for a new bleeding score for inherited bleeding disorders. J Thromb Haemost 2010; 8:2063.
  5. Tosetto A, Castaman G, Plug I, et al. Prospective evaluation of the clinical utility of quantitative bleeding severity assessment in patients referred for hemostatic evaluation. J Thromb Haemost 2011; 9:1143.
  6. Buresly K, Eisenberg MJ, Zhang X, Pilote L. Bleeding complications associated with combinations of aspirin, thienopyridine derivatives, and warfarin in elderly patients following acute myocardial infarction. Arch Intern Med 2005; 165:784.
  7. Labos C, Dasgupta K, Nedjar H, et al. Risk of bleeding associated with combined use of selective serotonin reuptake inhibitors and antiplatelet therapy following acute myocardial infarction. CMAJ 2011; 183:1835.
  8. Kadir RA, Economides DL, Sabin CA, et al. Frequency of inherited bleeding disorders in women with menorrhagia. Lancet 1998; 351:485.
  9. Kouides PA, Byams VR, Philipp CS, et al. Multisite management study of menorrhagia with abnormal laboratory haemostasis: a prospective crossover study of intranasal desmopressin and oral tranexamic acid. Br J Haematol 2009; 145:212.
  10. Achneck HE, Sileshi B, Parikh A, et al. Pathophysiology of bleeding and clotting in the cardiac surgery patient: from vascular endothelium to circulatory assist device surface. Circulation 2010; 122:2068.
  11. Burns ER, Lawrence C. Bleeding time. A guide to its diagnostic and clinical utility. Arch Pathol Lab Med 1989; 113:1219.
  12. The bleeding time. Lancet 1991; 337:1447.
  13. Gralnick HR, Rick ME, McKeown LP, et al. Platelet von Willebrand factor: an important determinant of the bleeding time in type I von Willebrand's disease. Blood 1986; 68:58.
  14. Mannucci PM, Lombardi R, Bader R, et al. Heterogeneity of type I von Willebrand disease: evidence for a subgroup with an abnormal von Willebrand factor. Blood 1985; 66:796.
  15. Posan E, McBane RD, Grill DE, et al. Comparison of PFA-100 testing and bleeding time for detecting platelet hypofunction and von Willebrand disease in clinical practice. Thromb Haemost 2003; 90:483.
  16. Favaloro EJ, Facey D, Henniker A. Use of a novel platelet function analyzer (PFA-100) with high sensitivity to disturbances in von Willebrand factor to screen for von Willebrand's disease and other disorders. Am J Hematol 1999; 62:165.
  17. Francis J, Francis D, Larson L, et al. Can the Platelet Function Analyzer (PFA)-100 test substitute for the template bleeding time in routine clinical practice? Platelets 1999; 10:132.
  18. Suchman AL, Griner PF. Diagnostic uses of the activated partial thromboplastin time and prothrombin time. Ann Intern Med 1986; 104:810.
  19. Ockelford PA, Carter CJ. Disseminated intravascular coagulation: the application and utility of diagnostic tests. Semin Thromb Hemost 1982; 8:198.
  20. Exner T, Triplett DA, Taberner D, Machin SJ. Guidelines for testing and revised criteria for lupus anticoagulants. SSC Subcommittee for the Standardization of Lupus Anticoagulants. Thromb Haemost 1991; 65:320.
  21. Greenberg CS, Devine DV, McCrae KM. Measurement of plasma fibrin D-dimer levels with the use of a monoclonal antibody coupled to latex beads. Am J Clin Pathol 1987; 87:94.
  22. Wells PS, Anderson DR, Rodger M, et al. Evaluation of D-dimer in the diagnosis of suspected deep-vein thrombosis. N Engl J Med 2003; 349:1227.
  23. Kojima Y, Urano T, Kojima K, et al. The significant enhancement of fibrinolysis by calcium ion in a cell free system: the shortening of euglobulin clot lysis time by calcium ion. Thromb Haemost 1994; 72:113.
  24. Urano T, Sakakibara K, Rydzewski A, et al. Relationships between euglobulin clot lysis time and the plasma levels of tissue plasminogen activator and plasminogen activator inhibitor 1. Thromb Haemost 1990; 63:82.
  25. Takada A, Takada Y, Urano T, et al. Fluctuations of euglobulin lysis time, tissue plasminogen activator, and free and total plasminogen activator inhibitor levels in plasma in daytime. Thromb Res 1990; 57:13.
  26. Kaufman RJ, Dorner AJ, Fass DN. von Willebrand factor elevates plasma factor VIII without induction of factor VIII messenger RNA in the liver. Blood 1999; 93:193.
  27. Abildgaard CF, Suzuki Z, Harrison J, et al. Serial studies in von Willebrand's disease: variability versus "variants". Blood 1980; 56:712.
  28. Girolami A, Sartori MT, Simioni P. An updated classification of factor XIII defect. Br J Haematol 1991; 77:565.
  29. Langdown J, Luddington RJ, Huntington JA, Baglin TP. A hereditary bleeding disorder resulting from a premature stop codon in thrombomodulin (p.Cys537Stop). Blood 2014; 124:1951.
  30. Lentaigne C, Freson K, Laffan MA, et al. Inherited platelet disorders: toward DNA-based diagnosis. Blood 2016; 127:2814.
  31. Soucie JM, Evatt B, Jackson D. Occurrence of hemophilia in the United States. The Hemophilia Surveillance System Project Investigators. Am J Hematol 1998; 59:288.
  32. Asakai R, Chung DW, Davie EW, Seligsohn U. Factor XI deficiency in Ashkenazi Jews in Israel. N Engl J Med 1991; 325:153.
  33. Bolton-Maggs PH, Young Wan-Yin B, McCraw AH, et al. Inheritance and bleeding in factor XI deficiency. Br J Haematol 1988; 69:521.
  34. Lämmle B, Wuillemin WA, Huber I, et al. Thromboembolism and bleeding tendency in congenital factor XII deficiency--a study on 74 subjects from 14 Swiss families. Thromb Haemost 1991; 65:117.
  35. Mariani G, Lo Coco L, Bernardi F, Pinotti M. Molecular and clinical aspects of factor VII deficiency. Blood Coagul Fibrinolysis 1998; 9 Suppl 1:S83.
  36. Pinotti M, Toso R, Redaelli R, et al. Molecular mechanisms of FVII deficiency: expression of mutations clustered in the IVS7 donor splice site of factor VII gene. Blood 1998; 92:1646.
  37. Perry DJ. Factor VII Deficiency. Br J Haematol 2002; 118:689.
  38. Castoldi E, Govers-Riemslag JW, Pinotti M, et al. Coinheritance of Factor V (FV) Leiden enhances thrombin formation and is associated with a mild bleeding phenotype in patients homozygous for the FVII 9726+5G>A (FVII Lazio) mutation. Blood 2003; 102:4014.
  39. Mathijssen NC, Masereeuw R, Verbeek K, et al. Prophylactic effect of recombinant factor VIIa in factor VII deficient patients. Br J Haematol 2004; 125:494.
  40. Giansily-Blaizot M, Biron-Andreani C, Aguilar-Martinez P, et al. Inherited factor VII deficiency and surgery: clinical data are the best criteria to predict the risk of bleeding. Br J Haematol 2002; 117:172.
  41. Mannucci PM, Duga S, Peyvandi F. Recessively inherited coagulation disorders. Blood 2004; 104:1243.