D-dimer

D-dimer is a commonly tested biological marker which is produced by the enzymatic breakdown of cross-linked fibrin which forms the fibrous mesh of a blood clot. The measurement of D-dimer in the circulation acts as a marker of coagulation and fibrinolysis, which can be useful in the diagnosis of multiple diseases.

Validated uses of D-dimer

• excluding the diagnosis of pulmonary embolism or venous thromboembolism using various clinical decision tools:
  • Wells criteria for pulmonary embolism
  • Wells criteria for DVT
  • Geneva score
  • pulmonary embolism rule out criteria (PERC)
• determining the optimal duration of anticoagulation therapy in patients with venous thromboembolic disease
• D-dimer in addition to platelet count, prothrombin time and fibrinogen can be used to diagnose and monitor disseminated intravascular coagulation (DIC)
• determining patients at high risk for thrombosis who have cancer or are hospitalized for other reasons

Unvalidated uses of D-dimer

• predicting the risk of stroke in patients with atrial fibrillation
• ruling out aortic dissection in low-risk patients (ADD-RS plus D-dimer)
• helping predict cardiovascular risk in HIV infected patients

Conditions associated with a raised D-dimer

• stroke, venous thromboembolic disease, atrial fibrillation, aortic dissection and disseminated intravascular coagulation
• ­­normal pregnancy
• increasing age (age-related adjustments should be made)
• pre-eclampsia and eclampsia
• severe liver disease
• malignancy
• congestive cardiac failure
• renal disease
• sickle cell disease
• any surgery or trauma
• sepsis
• fibrinolytic therapy
• venous malformations
• acute allergic reactions ^5,6
  • ​including anaphylaxis, urticaria, mild allergic reactions
• pulmonary sarcoidosis: D-dimer level correlated to activity/stage of disease ⁷, not currently used as a disease marker ⁸

Conditions associated with an extremely high D-Dimer

In a large study in 2016 an extreme elevated level was arbitrarily defined as >5,000 µg/L FEU ⁴. An older study from 2011, defined an extreme elevated D-dimer as >50,000 µg/L FEU ⁹. A study series of adult-onset Still disease only, found very high D-dimers in four of 22 patients, defined in this case as >5,000 µg/L FEU ¹¹.

The vast majority of cases were associated with severe disease:

• malignancy
• sepsis
• venous thromboembolism
• others
  • trauma
  • surgery
  • aortic dissection/aneurysm
  • massive GI bleeding (and other sites)
  • HELLP syndrome
  • cardiac arrest: samples taken post successful CPR
  • adult-onset Still disease ^10,11