DIC (Disseminated Intravascular Coagulation): Given John's recent trauma and surgery (knee replacement), DIC is a plausible diagnosis. The significant drop in platelet count (thrombocytopenia) to 15,000, despite normal anticoagulation labs, could be indicative of DIC, especially in the context of a recent surgical procedure and trauma, which can trigger DIC.

ITP (Immune Thrombocytopenic Purpura): Although less likely given the acute presentation post-surgery, ITP could be considered if there were pre-existing symptoms or signs suggestive of immune-mediated thrombocytopenia. However, the timing and context suggest a more acute, surgery-related cause.
TTP (Thrombotic Thrombocytopenic Purpura): TTP is characterized by thrombocytopenia, microangiopathic hemolytic anemia, renal failure, neurological symptoms, and fever. While thrombocytopenia is present, other classic symptoms of TTP are not mentioned, making it less likely but still a consideration.
Cancer: Although cancer can cause thrombocytopenia through various mechanisms (bone marrow infiltration, splenic sequestration, etc.), there's no direct evidence provided in the scenario to strongly support cancer as a primary diagnosis for John's acute presentation.

Heparin-Induced Thrombocytopenia (HIT): This is a critical diagnosis to consider in any patient who has recently undergone surgery and has been exposed to heparin, as it can lead to severe thrombotic complications. The significant drop in platelet count post-surgery raises suspicion for HIT, and it is crucial to investigate this possibility promptly.
Sepsis: Sepsis can cause DIC and thrombocytopenia. Given John's recent surgery, any sign of infection or sepsis must be promptly identified and treated.

Thrombotic Microangiopathy (TMA) related to other conditions: Besides TTP, other conditions like hemolytic-uremic syndrome (HUS) or atypical HUS could present with thrombocytopenia, though they are less common and typically associated with additional symptoms such as renal failure and microangiopathic hemolytic anemia.
Drug-Induced Thrombocytopenia: Certain drugs can induce immune-mediated thrombocytopenia. While less common, this should be considered if John has been exposed to any new medications recently.