D-Dimer test

What Sample for the D-Dimer test is needed?

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 for D-Dimer test

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 by atrial fibrillation, congestive heart failure, and cirrhosis.

What is the definition of D-dimer?

1. D-dimers are produced by the action of plasmin on cross-linked fibrin clots.
2. The presence of D-Dimer confirms that both thrombin generation and plasmin generation have occurred.
3. Factor XIII generates a D-dimer by covalently linking the D regions of the fibrin molecule.
4. D-dimer assesses both thrombin and plasmin activity.
5. Damaged blood vessels and exposure to collagen activate both intrinsic and extrinsic cascade of blood coagulation.
   1. SO D-dimer is a fibrin degradation product (fragment).
   2. It is found in the blood as a small protein fragment after the degradation of the fibrin clot (fibrinolysis).
   3. It consists of 2 D-fragments of fibrin protein joined by a cross-link, so-called protein dimer.

D-Dimer test: DIC mechanism

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.

S/S of DIC are:

1. The patient may have weakness and malaise.
2. The main feature is bleeding, especially from the site of venipuncture or a recent injury.
   1. There may be bleeding in the gastrointestinal tract. Oropharynx, into the lungs, and in the urogenital tract.
   2. During delivery, vaginal bleeding may be very severe.
   3. Acrocyanosis is irregular-shaped cyanotic patches.
3. Microthrombi may cause skin lesions.
   1. There may be gangrene of the finger or toes.
4. There may be occult bleeding to massive GIT bleeding.
   1. There is abdominal distension.
5. Patients may develop renal failure.
   1. There may be hematuria.
   2. There is oliguria.
6. Patients may have cerebral ischemia.
   1. There may be subarachnoid hemorrhage.
   2. There is a slight confusion about convulsions and coma.
7. These patients have respiratory symptoms like:
   1. Cyanosis.
   2. Hypoxemia.
   3. Adult respiratory distress syndrome (ARDS).
   4. Tachypnea.
   5. Pulmonary infarction.
8. Some patients with mucin-producing adenocarcinoma may develop subacute or chronic DIC.

Complications of Disseminated Intravascular Coagulopathy (DIC):

1. Thrombotic problems such as deep vein thrombosis, sickle cell anemia, pulmonary embolism, and thrombosis of malignancy are associated with raised levels of D-dimer.
2. FDP and d-Dimer form as a complication of disseminated intravascular coagulopathy (DIC).

How do you determine the Diagnosis of Disseminated Intravascular Coagulopathy (DIC)?

1. Fibrinogen concentration is low.
2. Platelets are low.
3. Thrombin time is prolonged.
4. Fibrinogen degradation products (FDP) like D-dimer are increased and found in the urine and serum.
5. PT and APTT are prolonged in the acute phase.
6. The D-Dimer test detects the cross-linked fibrin degradation 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 diagnosing DIC.
10. A positive D-dimer result is evidence of DIC or other causes of intravascular thrombosis.
11. D-dimer can be used as a screening test for deep vein thrombosis (DVT).
    1. The fibrin breakdown product concentration will increase when fresh venous thrombosis occurs.
    2. A negative result is useful in the emergency department for excluding DVT in clinically suspected patients.

Advantages of D-dimer:

1. There is no interference from the fibrinogen, so the test can be done on the plasma without any need to collect it in the special tube.

The disadvantage of D-dimer:

1. It has limited usefulness because of its use in fibrinolysis and will not detect breakdown products from the fibrinogen.
2. D-dimer elevated level has limited value in cancers, inflammation after surgery, or trauma, limiting its usefulness.

The main features of Disseminated Intravascular Coagulopathy (DIC) are due to different factors:

What are the Normal values of 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

What factors will lead to a 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 of D-dimer is seen in the following:

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 the postpartum period).
   8. Malignancy.
   9. Surgery.

Questions and answers:

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