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Patients Referred for Bleeding Symptoms of Unknown Cause : Does Evaluation of Thrombin Generation Contribute to Diagnosis?

Holm, Elena LU ; Zetterberg, Eva LU ; Lövdahl, Susanna LU and Berntorp, Erik LU (2016) In Mediterranean Journal of Hematology and Infectious Diseases 8(1). p.2016014-2016014
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... (More)

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 symptoms.

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Contribution to journal
publication status
published
subject
in
Mediterranean Journal of Hematology and Infectious Diseases
volume
8
issue
1
pages
2016014 - 2016014
publisher
Universita Cattolica del Sacro Cuore
external identifiers
  • Scopus:84958162701
  • WOS:000370730200001
ISSN
2035-3006
DOI
10.4084/MJHID.2016.014
language
English
LU publication?
yes
id
c7a41a81-ae1b-4709-844d-be29601ecd8d
date added to LUP
2016-04-12 11:46:38
date last changed
2017-01-01 08:22:36
@article{c7a41a81-ae1b-4709-844d-be29601ecd8d,
  abstract     = {<p>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.</p><p>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.</p><p>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.</p><p>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 symptoms.</p>},
  author       = {Holm, Elena and Zetterberg, Eva and Lövdahl, Susanna and Berntorp, Erik},
  issn         = {2035-3006},
  language     = {eng},
  number       = {1},
  pages        = {2016014--2016014},
  publisher    = {Universita Cattolica del Sacro Cuore},
  series       = {Mediterranean Journal of Hematology and Infectious Diseases},
  title        = {Patients Referred for Bleeding Symptoms of Unknown Cause : Does Evaluation of Thrombin Generation Contribute to Diagnosis?},
  url          = {http://dx.doi.org/10.4084/MJHID.2016.014},
  volume       = {8},
  year         = {2016},
}