Disseminated Intravascular Coagulation (DIC)

DIC, consumptive coagulopathy

Usually there is a balance between the clotting and lysis systems but in this condition the coagulation mechanism is activated inappropriately and in a diffuse way. This may lead to thrombosis in the subacute or chronic form but more often haemorrhage occurs as the clotting factors are exhausted. DIC is characterised by evidence of both thrombin and plasmin. Understanding the role of thrombin and plasmin in DIC permits comprehension of the manifestations of the disease.

An explanation of the mechanisms involved is found in the e-medicine link listed at the end.

The condition occurs in response to other pathology rather than as a primary event. There are no predisposing factors in terms of age, sex or race.

Conditions that may be complicated by DIC include:

• Infections, especially septicaemia, typhoid fever, Rocky Mountain spotted fever and parasites. The rash of meningococcal septicaemia is classical
• Malignancy, especially leukaemias
• Major trauma including crush syndrome and occasionally burns
• Some connective tissue disorders including antiphospholipid syndrome¹
• Complications of pregnancy including the placental problem of abruptio placentae, amniotic fluid embolism and severe hypertension of pregnancy with fulminating pre-eclampsia. There is a condition called HELLP, (Haemolysis, Elevated Liver enzymes, Low Platelets). A retained dead fetus tends to produce a thrombotic rather than a haemorrhagic state.
• Incompatible blood transfusion
• Heat stroke
• Dissecting aortic aneurysm
• Some snake bites

The immediately obvious features are usually those of the underlying condition that has caused DIC, especially if it is acute. In addition there may be large bruises or spontaneous bleeding at venepuncture sites, on the soft palate, legs and the site of trauma.

In subacute or chronic DIC the features may be thrombotic instead with signs of venous thrombosis.

In the acute situation there are many presenting features that may be found:

• Bleeding from at least 3 unrelated sites is typical and likely sites include
  • Ears, nose and throat
  • Gastrointestinal tract
  • Respiratory tract
  • Site of venepuncture or IV infusion
• Confusion or disorientation
• Fever
• Signs of haemorrhage
• Signs of adult respiratory distress syndrome (ARDS)
• Skin may show various signs including:
  • Petechiae
  • Purpura
  • Haemorrhagic bullae
  • Acral cyanosis
  • Skin necrosis of lower limbs (purpura fulminans)
  • Signs of thrombosis
  • Localised infarction and gangrene

If DIC is suspected then clotting screen tests are followed by confirmation:

• Prothrombin time elevated
• Activated partial thromboplastin time (aPTT) elevated
• Platelet count reduced
• Fibrinogen level low

If 2 results are positive, diagnosis is possible, if 3 are positive it is likely, if all 4 are positive it is extremely likely.

Confirmatory tests look for evidence of the simultaneous formation of thrombin and plasmin.

• The D-dimer test gives strong evidence of DIC
• Fibrin degradation products (FDP) are helpful but can occur in other conditions such as deep vein thrombosis and in severe disease they may be negative
• In acute disseminated intravascular coagulation PT and aPTT are prolonged, and the platelet count and fibrinogen decrease. D-dimer, FDP, and fibrin monomer levels are elevated.

In subacute or chronic disseminated intravascular coagulation PT and aPTT may be prolonged or normal. The fibrinogen level is decreased modestly and, in some cases, may be within the reference range or increased. Platelets may be slightly low or normal. D-dimer and FDP are slightly elevated.

Other tests may be useful but do not confirm the diagnosis.

• Thrombin time can be prolonged because of fibrinogen consumption
• Thrombin-antithrombin complexes in plasma suggests prior thrombin formation
• Antithrombin levels seem more promising than fibrinogen levels²

A scoring system has been developed to aid diagnosis and it correlates with 28 days mortality.³ It is based on the wave form of aPTT. Such as system may also help assess the response to treatment.⁴

Strategies will depend upon the underlying condition and an understanding of the mechanisms involved.⁵ The first step, if possible, is to treat the underlying condition.⁶ Thus infection will need antibiotics and obstetric complications may need intervention.

The next step is to correct coagulation deficiencies. This may involve transfusing platelets or cryoprecipitate to enhance fibrinogen. Other factors may need to be replaced with fresh frozen plasma. Some people argue that replacing these factors will add "fuel to the fire" of DIC but this approach is controversial and it is strongly argued that normal plasma protease inhibitors should keep the process in check.

The third step is to give heparin. Heparin potentiates the naturally occurring plasma protease inhibitor, antithrombin, to inhibit thrombin, factor Xa, and other coagulation enzymes. The use of heparin is also slightly controversial and too much will aggravate bleeding. It is probably best where there is evidence of digital ischaemia, migratory thrombophlebitis, purpura fulminans, retained dead fetus or leukaemia. The dose required is lower than for treating DVT. There is evidence of benefit from low molecular weight heparin.⁷

Antifibrinolytics such as aminocaproic acid are also of value.⁸ Therapy to stop the coagulation cascade requires an understanding of the mechanisms involved and is promising.⁹

Concentrated antithrombin III appears to have potential in infection but the quality of RCTs is often poor.¹⁰

• The condition can be fatal.
• Organs can be destroyed by infarction and limb ischaemia can lead to loss of digits or more.
• The prognosis depends mostly upon the underlying condition.

DIC has a wide variety of causes and associated pathology and a variety of laboratory findings. This heterogenicity makes it very difficult to produce adequately controlled randomised trials. Hence, much work is based on reproducible animal models. As always with evidence based medicine, the doctor has to ask, "How applicable is the available evidence to the patient in front of me?"