A patient with a markedly prolonged aPTT and normal PT suggests dysfunction of which coagulation pathway, with kallikrein as a key activator?

• A. Intrinsic pathway
• B. Extrinsic pathway
• C. Common pathway
• D. Anticoagulant pathway

Answer: (A)

The test is distinguishing intrinsic versus extrinsic activation of coagulation. A markedly prolonged aPTT with a normal PT indicates a problem in the intrinsic pathway (and/or its initiation by contact activation) rather than the extrinsic pathway. Kallikrein serves as a key activator of the intrinsic pathway by activating factor XII (the Hageman factor) on negatively charged surfaces, which then sets off the cascade through factors XI, IX, and VIII before the common pathway. Because the aPTT is prolonged while the PT is not, the defect points to the intrinsic pathway. If the issue were in the extrinsic pathway, the PT would also be prolonged; a defect in the common pathway would typically prolong both tests. The anticoagulant pathway isn’t the pattern tested by these assays.