D-Dimer test, Fragment D-dimer, Diagnosis of Disseminated Intravascular Coagulopathy (DIC)

Sample

1. Citrated plasma is needed.
2. It is stable for 8 hours at room temp. It can be kept at -20 °C for 6 months.

Indications

1. This test is done to diagnose DIC (disseminated intravascular coagulopathy).
2. It can diagnose other thromboembolic disorders (venous thrombosis).
3. It can diagnose Pulmonary embolism.
4. For the diagnosis of acute myocardial infarction.
   1. D-Dimer may be increased in atrial fibrillation, congestive heart failure, and cirrhosis.

Pathophysiology

1. Definition:
   1. D-Dimers are produced by the action of plasmin on cross-linked fibrin.
   2. The presence of D-Dimer confirms that both thrombin generation and plasmin generation have occurred.
   3. Factor XIII generates D-dimer, by covalently linking the D regions of fibrin molecule.
   4. D-dimer assesses both thrombin and plasmin activity.
2. Damaged blood vessels and exposure to collagen activates both intrinsic and extrinsic cascade of blood coagulation.

3. Disseminated intravascular coagulopathy (DIC):
   1. This is a widespread inappropriate intravascular deposition of fibrin with consumption of coagulation factors and platelets which occurs due to many diseases with the release of procoagulants into circulation or this may cause widespread endothelial damage of platelets aggregation.
4. Causes of DIC are:
   1. Infections.
   2. Malignancy.
   3. Hypersensitivity reactions.
   4. Vascular abnormalities.
   5. Widespread tissue damage.
   6. Other causes like liver failure, pancreatitis, snake venoms, heatstroke, and acute hypoxia.
      

      DIC pathogenesis

      

      Disseminated intravascular coagulopathy (DIC)  mechanism

   7. S/S of DIC are:
      1. The main feature is the bleeding, especially from the site of venipuncture or a recent injury.
      2. There may be bleeding in the gastrointestinal tract. oropharynx, into the lungs, and in the urogenital tract.
      3. During delivery, vaginal bleeding may be very severe.
      4. microthrombi may cause skin lesions.
      5. There may be gangrene of the finger or toes.
      6. Patients may develop renal failure.
      7. Patients may have cerebral ischemia.
      8. Some patients with mucin-producing adenocarcinoma may develop subacute or chronic DIC.
   8. Diagnosis of DIC:
      1. 1. Fibrinogen concentration is low.
         2. Platelets are low.
         3. Thrombin time is prolonged.
         4. Fibrinogen degradation products (FDP) like D-imer is increased and found in the urine and serum.
         5. PT and APTT are prolonged in the acute phase.
   9. FDP and d-Dimer form as a complication of the disseminated intravascular coagulopathy (DIC).
   10. There is a trigger for the increased clot formation, then fibrinolysis leads to the formation of FDP and d-Dimer.
       

       DIC mechanism

4. The D-Dimer test detects the cross-linked fibrin degradation products.
5. The fragment D-dimer assesses both thrombin and plasmin activity.
   1. Plasmin acts on Fibrin polymer clot and gives rise to FDP and D-dimer.
6. FDPs and Plasmin act on the fibrin clot and gives rise to D-dimer products.

7. The D-dimer assay is more specific than the FDP assay.
8. D-dimer is a highly specific measurement of fibrin degradation products that occurs.
9. Combining the positive test of FDP and D-dimer is highly specific and sensitive for the diagnosis of DIC.
10. A positive D-dimer result is an evidence for DIC or other causes of intravascular thrombosis.

11. Thrombotic problems such as deep vein thrombosis, sickle cell anemia, pulmonary embolism, and thrombosis of malignancy are associated with raised levels of D-dimer.
12. This can be used as a screening test for deep vein thrombosis (DVT).
    1. The concentration of the fibrin breakdown products will increase when there is fresh venous thrombosis.
    2. A negative result is useful in the emergency department for excluding the DVT in the clinically suspected patients.
13. Advantage of D-dimer:
    1. There is no interference of the fibrinogen, so the test can be done on the plasma without any need to collect it in the special tube.
14. The disadvantage is that it has limited usefulness because of its use in fibrinolysis and it will not detect breakdown products from the fibrinogen.
    11. D-dimer elevated level has limited value in cancers, inflammation after the surgery, or trauma, this will limit its usefulness.

Normal D-dimer

Source 1

• Negative
• <0.25 mg/L

Source 2

• Normal = negative ( no D-dimer fragments are seen).
• <250 ng/mL (<250 µg/L).

Source 4

• Normally plasma is negative for D-dimer.
• Qualitative: It is negative
• Quantitative : < 250 ng/mL or < 250  µg/L ( SI unit)
• Critical value >40 mg/L (40 µg/mL).

Source 6

• <0.4 mcg/mL

False-positive test:

1. This is seen in heparin therapy.
2. The Rheumatoid factor can give false high values of FDP.
3. This test is positive in patients after surgery or trauma.
4. The false-positive test is seen in estrogen therapy and pregnancy.

Increased Level is seen in:

1. Primary and secondary fibrinolysis.
   1. DIC
   2. Thrombolytic therapy.
   3. Deep vein thrombosis.
   4. Pulmonary embolism.
   5. Arterial thromboembolism.
   6. Vaso-occlusive crises of sickle cell anemia.
   7. pregnancy ( Especially postpartum period).
   8. Malignancy.
   9. Surgery.

• Please see more details in the fibrinogen degradation products FDP.

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