diabetes

D-Dimer

Generality

D-dimer is a degradation product of fibrin, a protein responsible for the formation of clots (thrombi) in blood vessels.

In the clinical setting, the determination of D-dimer in the blood is part of the diagnostic procedure of deep vein thrombosis and pulmonary embolism . This examination is therefore particularly useful in the study of diseases related to excessive or inappropriate coagulation.

What's this

D-dimer, fibrin and blood coagulation

D-dimer is the most known and characteristic degradative product of stabilized fibrin polymers. Following a hemorrhage these fibrin polymers intersect to form a sort of cork ( clot ), which stops bleeding in synergy with platelets and other cells trapped inside it.

After buffering the bleeding, the fibrin clot must necessarily be removed. From the dissolution process of this cap ( fibrinolysis ), by various substances, first of all plasmin, originate the so-called degradation products of fibrin and fibrinogen (FDPs), to which also the D-dimer belongs. These elements are formed whenever the stabilized fibrin is cut by the appropriate enzymes; since fibrin is not normally present in the blood as such, but in the form of a precursor (fibrinogen) activated by the lesion of blood vessels, the presence in the circulation of D-dimers and other activated fibrin degradation products implies a previous activation of the coagulation cascade . Not only that, since for the formation of the clot the fibrin deriving from fibrinogen must be "stabilized" by the so-called XIIIa factor (activated by thrombin), the degradation products of fibrinogen and of non-stabilized fibrin express a primitive activation of fibrinolysis.

D-dimers and FDPs are present and measurable, even in very low concentration, even in perfectly healthy subjects, since the various pro-coagulant and anti-coagulant factors are in a condition of perfect homeostatic balance .

On the two plates of this scale we find on one side the activation of the coagulation mechanisms, with consequent fibrin formation, and on the other the stabilized fibrin lysis and the inhibition of the circulating thrombin (necessary for the activation of fibrinogen in fibrin) .

Unfortunately, in various conditions, pathological or not, this balance is lost and - depending on whether the scale hangs on the side of the first or second plate - you can have thrombotic diseases (excessive coagulation of the blood) or hemorrhagic (insufficient blood coagulation). In the first case the body tries to compensate for the problem by increasing the fibrinolytic phenomena (fibrin degradation), with a consequent increase in the D-dimers present in the blood.

In summary, the presence of D-dimer in the blood is the consequence of a triple mechanism:

  1. Activation of coagulation with fibrin formation;

  2. Stabilization by action of factor XIII (activated by thrombin);
  3. Successive proteolysis by the fibrinolytic system (plasmin).

Why do you measure

D-dimer represents a laboratory marker of hypercoagulability . The evaluation of this parameter can be used for the diagnosis of pathologies that can lead to an excessive coagulation or to the tendency to inappropriate formation of clots .

The determination of D-dimer measures its plasma concentration.

When is the exam indicated?

The test is indicated - in an emergency situation - when serious pathologies related to thrombus formation are suspected, such as:

  • Deep venous thrombosis ;
  • Pulmonary thrombo-embolism .

That is to say that the evaluation of D-dimer is indicated when the patient presents serious symptoms attributable to a thrombotic event, such as:

  • Pain in one leg, in a context that makes one suspect a deep vein thrombosis (recent orthopedic intervention, neoplasms, lodging etc.);
  • Swelling and / or discoloration in the lower limbs;
  • Acute dyspnea (sudden breathlessness, often in the absence of underlying heart and lung disease).
  • Cough, hemoptysis (presence of blood in the sputum) and chest pain.

For this application, the doctor is not interested to know if a value is normal or pathological referring to a healthy population (as happens for other tests), but considers whether it can be excluded that the patient has a thrombotic disease. The test is particularly useful, therefore, in the exclusion of pathologies related to excessive or inappropriate coagulation.

D-dimer levels can also be used to support the diagnosis of disseminated intravascular coagulation (CID) and to monitor therapeutic treatment at regular intervals.

The test can be requested, together with PT, aPTT, fibrinogen and platelet count, to support the diagnosis.

The D-Dimer examination limit is related to its low specificity : high parameter values ​​can also be found in the event of pregnancy, tumors, recent surgery, trauma or infection. This test is indicative, in fact, of the presence of high amounts of fibrin degradation products.

To remember

The test result may indicate a significant increase in the formation of clots (thrombi) and their degradation, without indicating the cause. Therefore, a positive result is suggestive, but not diagnostic for a thrombotic pathology.

Normal values

The D-dimer is detectable in low concentration in the blood of healthy subjects, to indicate the existence of a state of equilibrium between the formation of fibrin and its lysis, even in physiological conditions.

The reference interval (normal range) is 0-500 ng / ml

Note : the diagnostic threshold can change according to age, sex and instrumentation in use. Furthermore, the different methods used in hospital laboratories to quantitatively measure D-dimer make the results not comparable. For this reason, it is preferable to consult the ranges listed directly on the report.

D-dimer High - Causes

The concentration of D-dimer increases in all circumstances, specific or non-specific, associated with or characterized by fibrin formation and fibrinolysis.

Physiological and pathological conditions associated with increased D-dimer include:

  • Old age;
  • Neonatal period;
  • Physiological and pathological pregnancy (including the puerperium);
  • Patients hospitalized and / or with functional disabilities;
  • Infections (in particular, Gram negative sepsis);
  • Neoplasms;
  • Surgical interventions;
  • Trauma;
  • Burns;
  • Disseminated intravascular coagulation (CID);
  • Venous thrombo-embolism;
  • Ischemic heart disease;
  • Peripheral arteriopathy of the lower limbs;
  • Aneurysms;
  • Congestive heart failure;
  • Acute respiratory distress syndrome (ARDS);
  • Subarachnoid hemorrhages and subdural hematomas;
  • Liver disease and nephropathy;
  • Inflammatory bowel diseases;
  • Chronic inflammatory diseases (eg SLE, rheumatoid arthritis etc.)
  • Thrombolytic therapy.

D-dimer Low - Causes

Normally, low or normal values ​​of the D-dimer do not indicate the presence of a problem.

How to measure it

The D-dimer test is performed by taking a blood sample from a vein in the arm.

Preparation

No specific preparation by the patient is required.

However, some conditions influence the specificity of the test, making D-dimer a less useful indicator for diagnostic purposes.

These factors include:

  • Age of the patient (increase in D-dimer values ​​in elderly patients);
  • Intercurrent acute inflammation;
  • Neoplasms;
  • Recent traumas;
  • Post-surgical state.

Therefore, in such situations, clinical data should be interpreted with greater caution.

Interpretation of Results

The dosage of fibrin dissolution products, in particular D-dimer, is carried out to investigate the organism's fibrinolytic activity in the presence of doubts about diseases such as disseminated intravascular coagulation, deep vein thrombosis and pulmonary embolism.

Because of the numerous conditions that can increase the blood levels of D-dimer (see table), it is a test with low specificity, but which in the presence of negative results excludes the diagnosis of venous thromboembolism with an almost absolute certainty.

Due to this high sensitivity / specificity ratio, the diagnostic role of D-dimer is precisely to exclude deep venous thrombosis and pulmonary embolism (generally called "venous thromboembolism - VTE") in the presence of low values.

Conditions associated with an increase in D-dimers (DD)

Physiological conditions
  • Neonatal period
  • Physiological pregnancy (and puerperium)
  • Cigarette smoke
  • Black race
  • D-dimer is often elevated in elderly subjects, presumably in relation to lower mobility and atherosclerosis
Pathological conditions
  • tumors

  • Post-surgery

  • Traumas and fixed assets

  • CID (disseminated intravascular coagulation)

  • Venous thromboembolism (deep vein thrombosis and pulmonary embolism)

  • Ischemic heart disease

  • Stroke

  • Infections

  • Peripheral arterial disease

  • Congestive heart failure

  • Hemolytic crises in sickle cell anemia

  • Subarachnoid hemorrhages and subdural hematomas

  • Extensive burns

  • ARDS

  • Liver disease

  • Kidney diseases

  • therapies

  • Thrombolytic therapy
  • If D-dimer values ​​are normal, deep vein thrombosis or pulmonary embolism can be ruled out as a cause of the disorders.
  • If the D-Dimer values ​​are high and there is a well-founded suspicion of deep vein thrombosis or pulmonary embolism, it is necessary to proceed with confirmation with further diagnostic investigations:
    • In the suspicion of deep vein thrombosis, an echocolordoppler of the lower limbs will be required.
    • If pulmonary embolism is likely, however, a scintigraphy or a pulmonary CT scan with contrast medium will be performed.