D-dimer

Exam Cram

• D-dimers are produced by clot breakdown in the systemic venous system & pulmonary arterial tree

• Indications

  • • Rule out PE

    • Rule out DVT

• Highly sensitive: can rule out VTE (95%)

• Poorly specific: cannot diagnose VTE, requires follow up USS/ CTPA, (50%)

Indications

There are only two concrete indications for a d-dimer:

1. Rule out a DVT

2. Rule out a PE

Aortic Dissection: A negative d-dimer reduces the probability of aortic dissection and is present in the ADD-RS score. As of 2024, I have not seen this used. 

Interpretation

Sensitivity: 95%

Specificity: 50%

D-dimers are a very sensitive test and a useful screening test, good at ruling out the disease.

They have a poor specificity however and cannot be used to make a diagnosis, hence all patients with a raised d-dimer should have a lower limb USS ?DVT or CTPA ?PE. 

Click the link to read more about sensitivity and specificity. 

• Sensitivity = % true positive out of all the individuals with a disease. 

• Specificity = % true negatives within all without the disease. 

This is not the same as positive & negative predictive values. 

Age Adjusted cut off

Historically a cut off of 0.5 was used (unsure the units). 

However, a cut off 0.01 / yr is used (70yr old = 0.7) which can safely avoid CTPA/ USS scans. 

Ultrahigh D-dimers

Ultra high d-dimer results are informally labelled x10 upper limit, e.g. 5,000.

Ultra high d-dimers are associated with increased mortality and serious underlying conditions:

• Recent trauma or operation

• Venous thromboembolism (VTE)

• Systemic inflammation: e.g. SLE, RA

• Chronic infections e.g. HCV

• Cancer, particularly haematological 

Therefore if an individual presents with right calf pain and there d-dimer is > 5000 but USS is negative for a right DVT- further history & examination with consideraion for a left USS or CTPA. 

Deeper Dive

None of these indications I have seen used in clinical practice. D-dimer levels reflect thrombosis levels and the conditions dicussed involve blood clotting. 

1. Aortic dissection

2. Cerebral sinus thrombosis

3. Myocardial infarction

4. Stroke

Aortic dissection risk stratification

Clinical practice I have observed is that a d-dimer cannot rule out an aortic dissection. The only investigation of choice for aortic dissection is CT-Angiogram. However the ADD-RS (Aortic dissection detection- risk score), not externally validated, uses a d-dimer to help rule out aortic dissection in low risk groups. 

Cerebral sinus thrombosis

One could hypothesise using it to rule out a cerebral sinus thrombosis. Research is conflicting. It is reasonable to state your risk is lower with a normal d-dimer. It has not been my clinical practice to use a d-dimer to exclude cerebral sinus thrombosis. 

 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4517419/

https://emj.bmj.com/content/35/6/396.2 

Myocardial infarction

Common clinical practice does not use d-dimer in the diagnosis or management of myocardial infarction. However PE (pulmonary embolus) are an important differential and a -ve d-dimer is often used to rule out a PE. Research suggests d-dimer levels correlate with worse outcomes however I have not seen this used in practice

https://pubmed.ncbi.nlm.nih.gov/10966534/ suggests d-dimer adds to the evaluation

https://thrombosisjournal.biomedcentral.com/articles/10.1186/s12959-021-00354-y 

Stroke

D-dimers are not routinely used in stroke diagnosis or management. PE and DVT are common serious complications, likely from immobility and the coagulopathy involved with the arterial stroke. A d-dimer is commonly used to rule this out.  The evidence suggests d-dimer is not specific or sensitive enough to provide decision making information on stroke diagnosis or management.

https://onlinelibrary.wiley.com/doi/10.1002/jcla.24271#:~:text=The%20findings%20suggest%20that%20D,associations%20to%20the%20laboratory%20indicator.