Differential Diagnosis for Elevated D-Dimers without DVT or PE

Elevated D-dimers can be caused by various conditions beyond deep vein thrombosis (DVT) and pulmonary embolism (PE). Here's a categorized differential diagnosis:

• Single Most Likely Diagnosis
  • Recent surgery or trauma: Elevated D-dimers can occur after recent surgery or trauma due to the body's fibrinolytic response to tissue injury.
• Other Likely Diagnoses
  • Malignancy: Certain types of cancer, such as pancreatic, ovarian, and lung cancer, can increase D-dimer levels due to tumor-related coagulation activation.
  • Infection: Severe infections like sepsis can lead to elevated D-dimers due to the activation of coagulation and fibrinolysis pathways.
  • Cardiovascular disease: Conditions like myocardial infarction, atrial fibrillation, and heart failure can also elevate D-dimer levels.
• Do Not Miss Diagnoses
  • Aortic dissection: Although less common, aortic dissection is a life-threatening condition that can cause elevated D-dimers and must not be missed.
  • Pulmonary embolism in unusual locations (e.g., subsegmental PE): While the question specifies "without PE," it's crucial to consider the possibility of a PE in an unusual location that might not be immediately apparent.
• Rare Diagnoses
  • Thrombotic thrombocytopenic purpura (TTP): A rare blood disorder characterized by clotting in small blood vessels throughout the body, which can elevate D-dimer levels.
  • Hematologic malignancies (e.g., leukemia, lymphoma): Certain hematologic malignancies can increase D-dimer levels due to coagulation activation or fibrinolysis.
  • Inflammatory conditions (e.g., rheumatoid arthritis, lupus): Chronic inflammatory diseases can occasionally lead to elevated D-dimers, although this is less common.

Each of these conditions has a different pathophysiological basis for elevating D-dimer levels, ranging from direct coagulation activation to secondary effects of inflammation or malignancy. A thorough clinical evaluation, including history, physical examination, and additional diagnostic tests, is essential to determine the underlying cause of elevated D-dimers in the absence of DVT or PE.