New Clinical Application Of Coagulation Reagent D-Dimer

With the deepening of people's understanding of thrombus, D-dimer has been used as the most commonly used test item for thrombus exclusion in coagulation clinical laboratories. However, this is only a primary interpretation of D-Dimer. Now many scholars have given D-Dimer a richer meaning in the research on D-Dimer itself and its relationship with diseases. The content of this issue will lead you to appreciate its new application direction.

The basis of clinical application of D-dimer

01. The increase of D-Dimer represents the activation of the coagulation system and fibrinolysis system in the body, and this process shows a high transformation state. Negative D-Dimer can be used for thrombus exclusion (the most core clinical value); while D-Dimer positive cannot prove the formation of thromboembolism. Whether or not thromboembolism is formed depends on the balance of these two systems.

02. The half-life of D-Dimer is 7-8h, and it can be detected 2h after thrombosis. This feature can be well matched with clinical practice, and it will not be difficult to monitor because the half-life is too short, and it will not lose the significance of monitoring because the half-life is too long.

03. D-Dimer can be stable in blood samples after in vitro for at least 24-48 hours, so that the D-Dimer content detected in vitro can accurately reflect the D-Dimer level in vivo.

04. The methodology of D-Dimer is all based on antigen-antibody reaction, but the specific methodology is many but not uniform. The antibodies in the reagent are diversified, and the detected antigen fragments are inconsistent. When choosing a brand in the laboratory, it needs to be screened.

Traditional coagulation clinical application of D-dimer

1. VTE exclusion diagnosis:

The D-Dimer test combined with clinical risk assessment tools can be efficiently used to exclude deep vein thrombosis (DVT) and pulmonary embolism (PE).

When used for thrombus exclusion, there are certain requirements for D-Dimer reagent and methodology. According to the D-Dimer industry standard, the combined pre-test probability requires a negative predictive rate of ≥97% and a sensitivity of ≥95%.

2. Auxiliary diagnosis of disseminated intravascular coagulation (DIC):

The typical manifestation of DIC is hyperfibrinolysis system, and the detection that can reflect hyperfibrinolysis plays an important role in the DIC scoring system. It has been clinically shown that D-Dimer will be significantly increased (more than 10 times) in DIC patients. In the domestic and foreign DIC diagnostic guidelines or consensus, D-Dimer is used as one of the laboratory indicators for diagnosing DIC, and it is recommended to carry out FDP jointly. Effectively improve the efficiency of DIC diagnosis. The diagnosis of DIC cannot be made only by relying on a single laboratory index and the results of a single examination. It needs to be comprehensively analyzed and dynamically monitored in combination with the clinical manifestations of the patient and other laboratory indicators.

New clinical applications of D-Dimer

1. The application of D-Dimer in patients with COVID-19: In a sense, COVID-19 is a thrombotic disease induced by immune disorders, with diffuse inflammatory response and microthrombosis in the lungs. It is reported that more than 20% of patients with VTE in hospitalized cases of COVID-19.

• D-Dimer levels on admission independently predicted in-hospital mortality and screened out potentially high-risk patients. At present, D-dimer has become one of the key screening items for patients with COVID-19 when they are admitted to the hospital.

• D-Dimer can be used to guide whether to initiate heparin anticoagulation in patients with COVID-19. It has been reported that in patients with D-Dimer ≥ 6-7 times the upper limit of the reference range, initiation of heparin anticoagulation can significantly improve patient outcomes.

• Dynamic monitoring of D-Dimer can be used to assess the occurrence of VTE in patients with COVID-19.

• D-Dimer surveillance, which can be used to assess the outcome of COVID-19.

• D-Dimer monitoring, when the disease treatment is faced with a decision, can D-Dimer provide some reference information? There are many clinical trials abroad being observed.

2. D-Dimer dynamic monitoring predicts VTE formation:

As mentioned above, the half-life of D-Dimer is 7-8h. It is precisely because of this feature that D-Dimer can dynamically monitor and predict the formation of VTE. For transient hypercoagulable state or microthrombosis, D-Dimer will increase slightly and then decrease rapidly. When there is persistent fresh thrombus formation in the body, the D-Dimer in the body will continue to rise, showing a peak-like rising curve. For people with a high incidence of thrombosis, such as acute and severe cases, postoperative patients, etc., if the D-Dimer level rapidly increases, be alert to the possibility of thrombosis. In the "Expert Consensus on the Screening and Treatment of Deep Vein Thrombosis in Trauma Orthopedic Patients", it is recommended that patients with medium and high risk after orthopedic surgery should dynamically observe the changes of D-Dimer every 48 hours. Imaging examinations should be performed in a timely manner to check for DVT.

3. D-Dimer as a prognostic indicator for various diseases:

Due to the close relationship between the coagulation system and inflammation, endothelial injury, etc., the elevation of D-Dimer is also often observed in some non-thrombotic diseases such as infection, surgery or trauma, heart failure, and malignant tumors. Studies have found that the most common poor prognosis of these diseases is thrombosis, DIC, etc. Most of these complications are the most common related diseases or states that cause D-Dimer elevation. Therefore, D-Dimer can be used as a broad and sensitive evaluation index for diseases.

• For tumor patients, several studies have found that the 1-3-year survival rate of malignant tumor patients with elevated D-Dimer is significantly lower than that of normal D-Dimer patients. D-Dimer can be used as an indicator for evaluating the prognosis of malignant tumor patients.

• For VTE patients, multiple studies have confirmed that D-Dimer-positive patients with VTE have a 2-3 times higher risk of subsequent thrombus recurrence during anticoagulation than negative patients. Another meta-analysis including 7 studies with a total of 1818 subjects showed that, Abnormal D-Dimer is one of the main predictors of thrombus recurrence in VTE patients, and D-Dimer has been included in multiple VTE recurrence risk prediction models.

• For mechanical valve replacement (MHVR) patients, a long-term follow-up study of 618 subjects showed that the risk of adverse events in patients with abnormal D-Dimer levels during warfarin after MHVR was about 5 times that of normal patients. Multivariate correlation analysis confirmed that D-Dimer level was an independent predictor of thrombotic or cardiovascular events during anticoagulation.

• For patients with atrial fibrillation (AF), D-Dimer can predict thrombotic events and cardiovascular events in oral anticoagulation. A prospective study of 269 patients with atrial fibrillation followed for about 2 years showed that during oral anticoagulation, about 23% of patients with INR reached the target showed abnormal D-Dimer levels, while patients with abnormal D-Dimer levels developed The risks of thrombotic events and comorbid cardiovascular events were 15.8 and 7.64 times, respectively, of patients with normal D-Dimer levels.

• For these specific diseases or specific patients, elevated or persistently positive D-Dimer often indicates poor prognosis or worsening of the disease.

4. Application of D-Dimer in oral anticoagulation therapy:

• D-Dimer determines the duration of oral anticoagulation: The optimal duration of anticoagulation for patients with VTE or other thrombus remains inconclusive. Regardless of whether it is NOAC or VKA, relevant international guidelines recommend that prolonged anticoagulation should be decided according to the bleeding risk in the third month of anticoagulation therapy, and D-Dimer can provide individualized information for this.

• D-Dimer guides the adjustment of oral anticoagulant intensity: Warfarin and new oral anticoagulants are the most commonly used oral anticoagulants in clinical practice, both of which can reduce the level of D-Dimer. and activation of the fibrinolytic system, thereby indirectly reducing the level of D-Dimer. Experimental results show that D-Dimer-guided anticoagulation in patients effectively reduces the incidence of adverse events.

In conclusion, D-Dimer test is no longer limited to traditional applications such as VTE exclusion diagnosis and DIC detection. D-Dimer plays an important role in disease prediction, prognosis, use of oral anticoagulants, and COVID-19. With the continuous deepening of research, the application of D-Dimer will become more and more extensive.