D-dimers: What are they?

Since butD-dimers are so-called fibrin cleavage products. These are formed in fibrinolysis (dissolution of blood clots) from cross-linked fibrin. They have a half-life of about eight hours.D-dimer can be used as a reliable test in cases of suspected thrombosis or pulmonary embolism, but precise localization of the event is not possible with this method. Other fibrin cleavage products are fragment D and E, which are formed from fibrinogen by the action of plasmin. The physiologic half-life of D-dimers is approximately 8 hours.

The procedure

Material needed

  • 1 ml citrated blood, frozen (preferred); 1 ml citrated plasma (maximum transport time: 4 hours).

Preparation of the patient

  • Not known

Disruptive factors

  • None known

Standard values

Male or female (not pregnant)* . <500 µg/l
Pregnancy
1st trimester (third trimester of pregnancy) <701 µg/l
2nd trimester <1.205 µg/l
28TH-32ND SSW <1.672 µg/l
32nd SSW – end <2,584 µg/l

* According to a meta-analysis, age-adjusted cutoff values (age × 10 μg/l D-dimer concentration in patients >50 years) increased diagnostic specificity from 34 to 46% without compromising sensitivity.

Indications

  • Suspected hyperfibrinolysis – excessive dissolution of fibrin (blood clots).
  • Suspicion of thrombosis or pulmonary embolism

Interpretation

Interpretation of increased values

  • Acute aortic syndrome (AAS): clinical pictures that can lead to rupture (“tear”) directly or indirectly via aortic dissection (splitting (dissection) of the wall layers of the aorta); differential diagnoses include dissections of the aorta (s. Below), intramural hematomas of the aortic wall (hemorrhage into the aortic wall), and aortic ulcers penetrating by plaque rupture (PAU; ulcerating defect of the inner wall of the aorta).
  • Aortic dissection – (synonym: aneurysm dissecans aortae) – splitting of the wall layers of the aorta (aorta), usually caused by a tear in the intima (inner vessel wall) with subsequent hemorrhage between the layers.
  • Disseminated intravascular coagulation – acute coagulation disorder caused by excessive activation of coagulation (DIC).
  • Hemolytic uremic syndrome (HUS) – triad of microangiopathic hemolytic anemia (MAHA; form of anemia in which erythrocytes (red blood cells) are destroyed), thrombocytopenia (abnormal reduction in platelets/platelets), and acute kidney impairment (AKI); Mostly occurring in children in the context of infections; most common cause of acute renal failure requiring dialysis in childhood.
  • Hyperfibrinolysis – overflowing dissolution of blood clots, which can have various causes such as dysfibrinogenemia or fibrinogen deficiency.
  • Liver cirrhosis – connective tissue remodeling of the liver leading to functional impairment.
  • Pulmonary embolismocclusion of a pulmonary vessel, resulting in a reduced supply to the affected section of the lung.
  • Myocardial infarction (heart attack)
  • Pregnancy
  • Sepsis (blood poisoning)
  • Thrombosisocclusion of a vein, usually in the lower extremities, which leads to congestion of the blood.
  • Transplant rejection
  • Tumors
    • Breast, ovarian, and pancreatic adenocarcinoma; solid lung and colon tumors.
    • Malignant melanoma: here, elevated D-dimer levels correlated positively and significantly with tumor thickness (≥ 2 mm), lymph node involvement, and metastasis (formation of daughter tumors).
  • Condition after surgical intervention.

Note: False-high levels of D-dimer are also measured in inflammation, hemorrhage, trauma, necrosis, and pregnancy (see above). Furthermore, a higher frequency of false-positive findings was observed in patients older than 65 years. Interpretation of Decreased Values

  • Not relevant to disease

Further notes

  • A decision criterion for or against a D-dimer determination is the Wells score (see below Thrombosis/physical examination).
  • A threshold of 500 µg/l is specified for most D-dimer tests.This does not take into account that D-dimer levels increase with age, potentially leading to too many unnecessary further diagnostic procedures. The formula age x 10 may give a good age-adjusted threshold.
  • Negative D-dimers exclude thrombosis or pulmonary embolism with greater than 99%. Probability.
  • D-dimers are not diagnostic when the following factors are present:
    • Disseminated intravascular coagulation (DIC).
    • Malignant tumors (malignant neoplasms).
    • Renal insufficiency/renal impairment (renally insufficient patients have elevated D-dimer levels regardless of the presence of pulmonary embolism, and the more severe the renal insufficiency, the more so; here, an appropriate D-dimer threshold must be determined in the future).
    • Sepsis (blood poisoning)
    • Therapy with anticoagulants (blood clotting inhibitors).
    • Condition after surgery or major trauma (injury) within the last four weeks.
  • Notice:
    • The specificity of a positive D-dimer test decreases with age and is as low as 10% in patients older than 80 years.
    • The D-dimer test alone is not suitable for identifying those elderly patients with unprovoked venous thromboembolism (VTE) who have a low risk of recurrence and in whom anticoagulation can be safely discontinued; this is also indicated by results of a Swiss study.
  • According to a meta-analysis, age-adjusted cutoff values (age × 10 μg/l D-dimer concentration in patients > 50 years) increased diagnostic specificity from 34 to 46% without compromising sensitivity.
  • In patients with stable coronary artery disease (CAD), elevated D-dimer levels (> 273 ng/mL) predict the following about patients’ long-term prognosis:
    • Risk for patients to have a serious coronary or cardiovascular event within the next six years was 45% higher than in patients with low D-dimer concentration (≤ 112 ng/ml).
    • Risk of venous thromboembolism (VTE) increased more than 4-fold.
    • All-cause mortality (all-cause death rate) was increased by 65%.
  • Patients’ D-dimer levels after terminated anticoagulation appear to be useful for predicting recurrence risk (risk of recurrence) of venous thromboembolism (VTE): in patients with thrombosis after major trigger, 5.7 recurrences occurred per 100 patient-years if the D-dimer level was elevated. In patients with major risk factors, the recurrence rate was: 5.74 (95% CI: 3.19-9.57) events per 100 patient-years in patients with elevated D-dimer levels and 2.68 (95% CI: 1.45-4.56) in patients with normal levels. In patients with low risk factors, the rates were: 7.79 (95% CI: 5.71-10.4) and 3.34 (95% CI: 2.39-4.53), respectively.