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Scientific Calendar August 2018

Besides bacterial infections, which of the following are associated with an elevated D-dimer? Deep vein thrombosis (DVT)
Cancer
Sickle cell disease (SCD)
HIV
All of the above

Background information

D-dimer is a fibrin degradation product (FDP), a small protein fragment present in the blood after a blood clot (thrombosis) is degraded by fibrinolysis. It is aptly named as it contains two D domains produced from cross-linked fibrin.

Several clinical scenarios might prompt a practitioner to measure or monitor D-dimer levels. In general, the D-dimer test may be ordered to screen for underlying thromboembolic events such as deep vein thrombosis (DVT) or pulmonary embolism (PE), or to learn whether there is any change during the course of a specific therapy or disease process. In practice, D-dimer measurement has been most comprehensively validated in the exclusion of venous thromboembolism (VTE) in certain patient populations and the diagnosis and monitoring of coagulation activation in disseminated intravascular coagulation (DIC) [2].

The D-dimer test is used for its negative predictive value. Whilst a negative result rules out a thromboembolic event, a positive result can give an indication of thrombosis, but does not rule out other potential common causes such as sickle cell disease (SCD), cancer, HIV, surgery and pregnancy [1], therefore further investigation is required.

Due to the injury to vascular endothelial cells caused by toxins released from fast-growing tumour cells, and the fibrinolytic activator on the surface of tumour cells, cancer patients often exhibit abnormal coagulation and fibrinolytic activities, and their D-dimer levels tend to be higher than those in non-neoplastic populations [3].

Patients with sickle cell disease, one of the most common inherited diseases worldwide [4], experience both large and small vessel occlusions leading to end-organ damage and complications such as avascular necrosis (AVN). These multifactorial vaso-occlusive events result from various processes, such as reduced red cell deformability and a chronically activated coagulation pathway. An important component of the hypercoagulable state is increased thrombin production, supported by findings of an elevated D-dimer [4].

Whilst healthcare provision in the past decade has largely focused on the prevention and management of HIV, the link between HIV infection and thrombosis has gone largely unrecognised. Studies have shown that increased D-dimer levels are strongly associated with increased mortality in HIV-infected individuals as well as being predictors of the immune reconstitution inflammatory syndrome (IRIS) after commencing antiretroviral treatment. IRIS is a condition that is seen in some AIDS patients shortly after starting antiretroviral therapy. Recovery of the immune system is accompanied by an overwhelming response to a previously acquired opportunistic infection that paradoxically makes the symptoms of infection worse. Because elevated D-dimers have been shown to be very good predictors of patients at high risk, there is a strong possibility that testing for D-dimers will become part of the HIV treatment programmes in the near future. This would allow high-risk patients to be identified to possibly receive an alternate drug regimen and almost certainly to be assigned to a much closer follow-up [1].

References

  1. Sysmex Educational Enhancement and Development (2012): The Role of the D-dimer test in clinical diagnostics. SEED Coagulation. July 2012.
  2. Soheir S. Adam et al. (2009): D-dimer antigen: Current concepts and future prospects. Blood. 113(13):2878-2885.
  3. Jing Yu et al. (2016): Tumor-specific D-Dimer Concentration Ranges and Influencing Factors : A Cross-Sectional Study. Plos One. ODI:10.1371/journal.pone.0165390 (November 11 2016):1-12.
  4. Nirmish Shah, MD, et al. (2012): Characterization of the hypercoagulable state in patients with sickle cell disease. Thromb Res. 2012 November. 130(5):e241-e245.

Scientific Calendar 2018

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