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You could face a question in any of the USMLE steps (specially CK) that requires you to know what are these two tests and what are the differences between them.

Both of Apt test and Kleihaur-Betke test are used to detect the presence of fetal blood within a sample.

In Apt Test, it's used to detect the presence or absence of fetal blood (qualitative) in a vaginal discharge to rule out vasa previa late in pregnancy or to detect the origin of a neonatal bloody vomiting whether it's a genuine upper GI hemorrhage/hemoptysis or simply a swallowed maternal blood during delivery or from cracked nipple.

In Kleihauer-Betke Test, the sample is maternal peripheral smear and is used to see how much of fetal blood (quantitative) has been transfused into the maternal serum in order to assess the risk of isoimmunization and thence the risk of hemolytic disease of the newborn.

Both of them relies on the fact that HbF is resistant to alkali (Apt) and acids (Kleihauer) and so the HbA containing RBCs (maternal) will be hemolyzed but not the fetal RBCs as they contain the HbF.

Beware of two tricks:

First; the mother herself may have HbF if for example she's a sickle cell trait or disease. This will render both tests showing false positive results.

Second; if Kleihauer is performed late after delivery then there's a chance of false negative result since the fetal blood RBCs might have been hemolyzed and disappeared from the maternal circulation at the time of the test. This is specially true if there was ABO incompatibility as well. Because in this situation the fetal RBCs will be quickly "neutralized" by the naturally-occurring maternal Anti-A or Anti-B antibodies and no chance for fetal RBCs to be detected.

Here's a table that summarizes the differences;

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