PATIENTS REFERRED FOR BLEEDING SYMPTOMS OF UNKNOWN CAUSE: DOES EVALUATION OF THROMBIN GENERATION CONTRIBUTE TO DIAGNOSIS?

Main Article Content

Elena Holm *
Eva Zetterberg
Susanna Lövdahl
Erik Berntorp
(*) Corresponding Author:
Elena Holm | elena.holm@med.lu.se

Abstract

Introduction

Patients with mild to moderate bleeding symptoms referred for coagulation investigation sometimes never receive a definitive diagnosis. Bleed assessment tools have been developed and validated to assess the severity of symptoms. Global coagulation assays, e.g., the thrombin generation test (thrombogram) have a potential to identify hemostatic defects that are not detected in specific assays.

Material and Methods

One hundred and eighty-five patients referred to our centre because of bleeding symptoms were evaluated using  the bleeding assessment tool (BAT) described by Tosetto and colleagues in 2006.  Blood samples were investigated for thrombin generation (TG) capacity (Technoclone) , in platelet poor (PPP)  plasma , and specific clotting factors, i.e, von Willebrand factor, factor VIII and IX, as well as INR, APTT, platelet count, and platelet adhesion.

Results

Of the 185 patients, five women were diagnosed with mild von Willebrand disease and one male with mild hemophilia A. The remaining 179 subjects (76% females and 24% males with average ages of 33 and 28 years, respectively) were evaluated further. In the total cohort and among women, peak TG, and lag time   correlated with bleeding score (p=0.01 and p=0.04, respectively with correlation coefficients).  No such correlations were found among males.

 

Discussion and conclusion

 

Although our study showed some correlation between TG and bleeding score, results are generally consistent with a previous report which failed to demonstrate the value of TG measurement in a similar setting. In conclusion, the complexity of the mechanisms underlying clinical bleeding complicates the ability to use TG tests as reliable predictors of bleeding. Mild congenital bleeding disorders, especially VWD, should be specifically screened for in patients with mild/moderate symtoms.



Downloads month by month

Downloads

Download data is not yet available.

Article Details

Author Biographies

Elena Holm, Malmö Centre for Thrombosis and Haemostasis, Lund University Sweden

MD

Eva Zetterberg, Malmö Centre for Thrombosis and Haemostasis, Lund university

MD, PhD

Susanna Lövdahl, Malmö Centre for Thrombosis and Haemostasis, Lund university

PhD

Erik Berntorp, Malmö Centre for Thrombosis and Haemostasis, Lund university

MD, PhD

References

[1] Tosetto A, Rodeghiero F, Castaman G, Goodeve A, Federici AB, Batlle J, Meyer D, Fressinaud E, Mazurier C, Goudemand J, Eikenboom J, Schneppenheim R, Budde U, Ingerslev J, Vorlova Z, Habart D, Holmberg L, Lethagen S, Pasi J, Hill F, Peake I. A quantitative analysis of bleeding symptoms in type 1 von Willebrand disease: results from a multicenter European study (MCMDM-1 VWD). Journal of thrombosis and haemostasis : JTH. 2006;4:766-73.

[2] Ay C, Haselbock J, Laczkovics C, Koder S, Pabinger I. Thrombin generation in patients with a bleeding tendency of unknown origin. Annals of hematology. 2011;90:1099-104.

[3] Hemker HC, Wielders S, Kessels H, Beguin S. Continuous registration of thrombin generation in plasma, its use for the determination of the thrombin potential. Thrombosis and haemostasis. 1993;70:617-24.

[4] Ten Cate H. Thrombin generation in clinical conditions. Thrombosis research. 2012;129:367-70.

[5] Dargaud Y, Beguin S, Lienhart A, Al Dieri R, Trzeciak C, Bordet JC, Hemker HC, Negrier C. Evaluation of thrombin generating capacity in plasma from patients with haemophilia A and B. Thrombosis and haemostasis. 2005;93:475-80.

[6] Bowman M, Mundell G, Grabell J, Hopman WM, Rapson D, Lillicrap D, James P. Generation and validation of the Condensed MCMDM-1VWD Bleeding Questionnaire for von Willebrand disease. Journal of thrombosis and haemostasis : JTH. 2008;6:2062-6.

[7] Strandberg K, Lethagen S, Andersson K, Carlson M, Hillarp A. Evaluation of a rapid automated assay for analysis of von Willebrand ristocetin cofactor activity. Clin Appl Thromb Hemost. 2006;12:61-7.

[8] Veyradier A, Fressinaud E, Sigaud M, Wolf M, Meyer D. A new automated method for von Willebrand factor antigen measurement using latex particles. Thrombosis and haemostasis. 1999;81:320-1.

[9] Hellem AJ. Platelet adhesiveness in von Willebrand's disease. A study with a new modification of the glass bead filter method. Scandinavian journal of haematology. 1970;7:374-82.

[10] Varadi K, Negrier C, Berntorp E, Astermark J, Bordet JC, Morfini M, Linari S, Schwarz HP, Turecek PL. Monitoring the bioavailability of FEIBA with a thrombin generation assay. Journal of thrombosis and haemostasis : JTH. 2003;1:2374-80.

[11] Rodeghiero F, Tosetto A, Abshire T, Arnold DM, Coller B, James P, Neunert C, Lillicrap D, VWF ISj, Perinatal/Pediatric Hemostasis Subcommittees Working G. ISTH/SSC bleeding assessment tool: a standardized questionnaire and a proposal for a new bleeding score for inherited bleeding disorders. Journal of thrombosis and haemostasis : JTH. 2010;8:2063-5.