ABSTRACT
The diagnosis of inhibitors of blood coagulation is often the most challenging problem
in the clinical laboratory. Immediate attention must be given to the following patient
groups whose principal laboratory abnormality is the prolonged activated partial thromboplastin
time (aPTT): the patient with (1) hemophilia who previously responded to an adequate
dose of clotting factor product and now fails to show effective clinical response
to the same replacement concentrate; (2) previously benign clinical history who now
presents with soft tissue bleeding or emergent internal hemorrhaging; (3) sudden onset
of generalized ecchymoses who was previously well; (4) postpartum state; (5) malignancy,
lymphoma, rheumatoid arthritis, or other autoimmune disorders; and (6) drug reactions.
Immediate attention must be given to the prolonged prothrombin time (PT), aPTT, and
thrombin time (TT) in order to respond to urgent queries from a perplexed internist,
hematologist, intensivist, or surgeon caring for a patient with unexpected bleeding.
Sometimes the problem of a prolonged ``clotting time'' arises preoperatively, causing
unanticipated delay in operative procedures. For this reason, the laboratory support,
usually in the coagulation section of a clinical laboratory or reference laboratory,
must be quick, unequivocal and precise.
The most common finding is an isolated mild, moderate, or severe prolongation of the
aPTT with a normal PT, TT, and platelet count. The aPTT mixing study (The Mix), usually
modified for time and temperature, along with appropriate controls, is the seminal
test. This is the basis for all further testing. It may be supported by direct factor
assays, and, therefore, the laboratory must know the reagent responsiveness and sensitivity
for each clotting factor. By definition, complete correction of the aPTT in a 1:1
mix of patient and reference plasma is a factor deficiency. In this article, incomplete
or minimal correction of The Mix will be characterized with particular attention to
the various inhibitor assays, in other words, Oxford, Bethesda, and Nijmegen assays
and the enzyme-linked immunosorbent assay (ELISA). An investigative approach to final
characterization of the intensity (quantification) of the inhibitor and the exclusion
of a lupus anticoagulant (LA) will be discussed.
KEYWORD
Inhibitors - hemophilia - lupus anticoagulant - antibodies factor VIII - Bethesda
assay - Oxford assay - Nijmegen assay
