What is the role of mixing studies in the diagnosis of pediatric coagulopathy (coagulation disorders)?

From the Guidelines

Mixing studies are a crucial diagnostic tool in evaluating pediatric coagulopathy, allowing for the distinction between factor deficiencies and inhibitors, and should be performed when a child presents with abnormal coagulation tests. When interpreting the results of mixing studies, it is essential to consider the patient's clinical history, medication use, and other laboratory findings, as well as physiologic differences in hemostasis that occur in pediatric patients, such as naturally lower levels of vitamin K-dependent factors in newborns 1. The process of performing a mixing study involves combining the patient's plasma with normal pooled plasma in a 1:1 ratio and incubating at 37°C, with immediate correction of clotting times suggesting a factor deficiency, and persistent prolongation indicating an inhibitor 1. Key considerations for accurate results include collecting blood samples in citrated tubes, avoiding heparin contamination, and processing within 4 hours, as well as consulting with a pediatric hematologist for further testing and interpretation, especially if specific, expanded testing is necessary or if preliminary testing suggests the presence of a bleeding disorder 1. Some essential points to consider when evaluating pediatric coagulopathy include:

• The prevalence of mild platelet disorders is unknown, and testing for these disorders can be challenging, requiring a relatively large volume of blood and specialist interpretation 1
• The PFA-100 can screen for many platelet function disorders but is not effective for some types of von Willebrand disease and milder platelet abnormalities, and its results can be affected by individual patient characteristics such as hematocrit, platelet count, and medications 1
• Accurate diagnosis often requires additional platelet testing, such as specific von Willebrand testing or platelet aggregation, and consultation with a pediatric hematologist is recommended for interpretation and further testing 1.

From the Research

Role of Mixing Studies in Diagnosing Pediatric Coagulopathy

• Mixing studies, such as the activated partial thromboplastin time (APTT) cross-mixing test, play a crucial role in diagnosing pediatric coagulopathy, including acquired hemophilia A 2.
• The APTT cross-mixing test can detect an inhibitor pattern and inhibitory antibodies against coagulation factors, allowing for early diagnosis and treatment of bleeding disorders 2.
• In pediatric patients, mixing studies can help distinguish between coagulation factor deficiencies and inhibitors, which is essential for guiding treatment decisions 2.

Laboratory Investigations and Diagnostic Tools

• Laboratory investigations, including bleeding scores, platelet count, prothrombin time, and fibrinogen concentration, are essential for diagnosing bleeding disorders in children 3, 4, 5.
• The use of bleeding assessment tools, such as the Pediatric Bleeding Questionnaire (PBQ) and the ISTH Bleeding Assessment Tool (ISTH BAT), can help standardize the diagnosis of bleeding disorders in children 3, 5.
• Mobile applications, such as the mBAT, can facilitate self-screening for pediatric bleeding disorders and enhance diagnosis 6.

Importance of Early Diagnosis and Treatment

• Early diagnosis and treatment of bleeding disorders are critical in pediatric patients to prevent life-threatening bleeding complications 2, 4.
• A thorough understanding of the unique characteristics of pediatric hemostasis and the natural course of bleeding disorders in children is essential for effective management 4.
• The use of mixing studies and other diagnostic tools can help guide treatment decisions and improve outcomes for pediatric patients with bleeding disorders 2, 4.