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

• some case reports suggest that COVID-19 vaccines could increase blood clotting in some predisposed subjects, as can be seen from the alteration of the D-dimer level ^12,13

• potential marker of clotting in Long COVID-19 patients ¹⁴

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