D-Dimer has been put on the map in the last year for its sensitivity in indicating microscopic blood clotting - seen in both COVID-19 and the COVID-19 vaccine. Find out more about this effective marker and why it is essential to check this as part of your blood panel screening if you do suspect cardiovascular impairment.
What is D-Dimer?
D-Dimer is a product of fibrin blood clot degradation called fibrinolysis. It is present in minimal amounts in healthy human plasma (100-200 ng/mL). Once the coagulation cascade has been activated D-Dimer raises.
D-Dimer is reliably used to detect clotting, typically in deep vein thrombosis (DVT) and Pulmonary Embolism (PE), where a clot travels to the lungs. A clot dislodging from a vein and traveling to an artery causes venous thromboembolism (VTE). A clot traveling to the heart can cause arterial fibrillation and one embolising in the brain will initiate a stroke. If a blood clot blocks blood flow to an organ, such as the kidney, heart or brain, it may cause irreversible damage (infarction) leading to organ failure.
Within allopathic medicine D-Dimer testing is combined with other laboratory testing and scans to identify correct disease diagnosis and monitor progression, typically used to help exclude DVT and PE.
Where might I see raised levels of D-Dimer?
- The presence of a blood clot that is less than 14 days old.
- Disseminated intravascular coagulation
- Pregnancy and postpartum state
- Surgery or physical trauma
- Malignancy – it may be used to predict metastasis and progression in various cancers (Hong Dai et al. 2018)
- Autoimmune disease – RA, SLE, and others (Xue Li et al. 2021)
- Infection/sepsis (Rodelo J R et al. 2012)
- Endothelial dysfunction/Diabetes mellitis (Hileman C O et al. 2012)(Pereira Domingueti et al 2016)
- Acute Respiratory Distress Syndrome (ARDS) (Wang Deng et al. 2012)
- COVID-19 – poor prognosis if levels are greater than 4 x the cut-off level in hospitalised patients. (Xiaokang He et al. 2021)
- COVID-19 vaccine-induced immune thrombotic thrombocytopenia (VITT) (Fanni C et al. 2021; Perry et al. 2021)
- Autoimmune vasculitis – D-Dimer was positively associated with disease progression and inflammation, rather than clotting risk (Borowiec A et al. 2020).
- Increased risk of stroke and CHD with increasing baseline levels of D-Dimer (Zakai N A et al. 2017)
- Increased risk of further cardiac events in patients who have undergone balloon angioplasty, artherectomy or angioplasty with stent (Chen et al, 2021)
- Presence of atrial thrombus in atrial fibrillation (Danese et al 2014)
- Sickle Cell Disease (Naik R P et al. 2016)
- Hypertension (Lip G Y et al 1997)
- Liver disease (Yun Li et al. 2016)
- Renal impairment (Robert-Ebadi H et al. 2014)
What do I need to know about testing and D-Dimer levels?
- D-Dimer levels tend to increase with age.
- Levels may also be progressively increased during pregnancy and so use of D-Dimer is not recommended as a marker during pregnancy.
- Levels are higher in women vs men and black populations vs Caucasians. It is lowest in Asian populations (Zakai N A et al. 2017)
The effect of pregnancy on levels of D-Dimer
The NHS uses cut-off reference ranges according to age:
Age (Years) D-dimer (ng/ml)
Are false results a possibility with D-Dimer?
- Anti-coagulant therapy can cause false negative D-Dimer.
- False negative or falsely low results can occur with hyper lipaemia.
- Rheumatoid factor seen in those with Rheumatoid Arthritis may cause high levels (Kyung Soon Song et al. 1999). (although evidence is conflicting)
- Raised Bilirubin can cause false positives.
- Haemolysis (rupturing of red blood cells) caused by improper collection and handling.
What other markers do I need to consider in relation to D-Dimer?
- D-Dimer and CRP are both independent but additive risk markers for ischaemic heart disease (Lowe G D O et al. 2014).
- D-Dimer has been shown to increase the release of inflammatory cytokines IL-6 and IL-1ß from in vitro monocytes. Plasminogen activator inhibitor bioactivity and Plasminogen activator inhibitor Antigen type 2 levels were also increased. (Robson S C et al. 1994).
- In severely ill hospital patients, there is a link between increased inflammatory cytokines and increased D-Dimer levels. These are positively correlated with the severity of illness (Shorr et al. 2002).
- Patients who are hospitalised with COVID and have raised inflammatory cytokines appear to be at increased risk of going on to develop raised D-Dimer and coagulopathy related to increased mortality (Poudel et al. 2021).