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Chapter 11 - Role of global assays in thrombosis and thrombophilia

from Section 2 - Special considerations in pediatric patients

Published online by Cambridge University Press:  18 December 2014

By
Meera Chitlur  and
Mindy L. Simpson
Edited by
Neil A. Goldenberg  and
Marilyn J. Manco-Johnson
Meera Chitlur
Affiliation:
Wayne State University
Mindy L. Simpson
Affiliation:
Rush University Medical Center, Chicago
Neil A. Goldenberg
Affiliation:
The Johns Hopkins University School of Medicine
Marilyn J. Manco-Johnson
Affiliation:
Hemophilia and Thrombosis Center, University of Colorado, Denver
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Summary

Introduction

Hemostasis is a complex process and is difficult to monitor in its entirety. Many laboratory tests have been developed to discern specific parts of the coagulation process in an attempt to diagnose disorders such as a tendency toward bleeding or clotting abnormally, and/or to predict clinical outcomes in these disorders. Because an in vitro test is simply a model of an in vivo process, it is important to understand what each test is measuring and its limitations. Traditional clotting assays such as the prothrombin time (PT) and activated partial thromboplastin time (APTT) measure the time for initiation of clot formation when, following initiation of coagulation in plasma via differing activators (PT: “thromboplastin,” comprised of tissue factor and phospholipid; APTT: “partial thromboplastin,” comprised of phospholipid without tissue factor), thrombin mediates the conversion of fibrinogen to fibrin. The endpoint of the PT and APTT occurs when only approximately 5% of thrombin has been produced [1]. PT and APTT also do not provide information regarding the rate and extent of clot formation, nor lytic function. As for other global tests, they are non-specific assays and, for abnormal test results, further testing is generally warranted to evaluate causality. Specific testing may include factor assays to evaluate for a factor deficiency or antibody testing to assess for inhibitory antibodies. The need for improved testing of hemostasis has been long recognized but an accepted standardized test is not yet widely available.

Thrombophilic states and the propensity toward thrombosis are difficult to diagnose/predict with laboratory assays. Testing for thrombophilia can be cumbersome, generally requiring testing for individual abnormalities, and may be difficult with smaller patients due to the amount of blood required for comprehensive testing. There is a need for improved thrombophilia/thrombosis testing and monitoring. Global assays attempt to better define the complete course of clot formation and breakdown through avenues such as the measurement of thrombin generation, fibrin formation, plasmin generation, and clot dissolution. Through a more complete picture of the hemostatic process, global assays may fill the gaps in knowledge regarding hemostatic abnormalities.

Type
Chapter
Information
Pediatric Thrombotic Disorders , pp. 142 - 157
Publisher: Cambridge University Press
Print publication year: 2015

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