Synonyms: DIC, consumptive coagulopathy

Description

Usually there is a balance between the clotting and lysis systems; however, in disseminated intravascular coagulation (DIC), the coagulation mechanism (especially thrombin) 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 activation.

Epidemiology

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.

Risk factors

Conditions that may be complicated by disseminated intravascular coagulation (DIC) include:

• Infections, especially septicaemia, E. coli O157, 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 with symptoms of Haemolysis, Elevated Liver enzymes, Low Platelets: HELLP syndrome. 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

Presentation

The immediately obvious features are usually those of the underlying condition that has caused disseminated intravascular coagulation (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 three 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

Investigation

If disseminated intravascular coagulation (DIC) is suspected then clotting screen tests are followed by confirmation:

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

If two results are positive, diagnosis is possible; if three are positive, it is likely; if all four 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 (FDPs) are helpful but can occur in other conditions such as deep vein thrombosis (DVT) 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 DIC, 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 a system may also help assess the response to treatment.⁴

Management

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.^7,8

• Correct coagulation deficiencies - this may involve transfusing platelets, fresh frozen plasma or cryoprecipitate to enhance fibrinogen. Some people argue that replacing these factors will add "fuel to the fire" of disseminated intravascular coagulation (DIC) but this approach is controversial and it is strongly argued that normal plasma protease inhibitors should keep the process in check. They should only be given if there is associated haemorrhage with prolonged PT and aPTT.
• Heparin - this 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 studies are balanced in regards effectiveness. It is probably best where there is evidence of digital ischaemia, migratory thrombophlebitis, purpura fulminans, retained dead fetus, leukaemia or thrombosis (warfarin is usually ineffective in these patients). The dose required is lower than for treating DVT and there is evidence of benefit from both low molecular weight heparin⁹ and unfractionated heparin.
• Antifibrinolytics such as aminocaproic acid are also of value.¹⁰ Therapy to stop the coagulation cascade requires an understanding of the mechanisms involved and is promising.¹¹
• Concentrated antithrombin III - appears to have potential in infection but the quality of randomised controlled trials is often poor.¹²
• Activated protein C - this inactivates factors Va and VIIIa and has been shown to be effective in sepsis-induced DIC.^7,8

Complications and prognosis

• 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?"

Document references

1. Asherson RA, Espinosa G, Cervera R, et al; Disseminated intravascular coagulation in catastrophic antiphospholipid syndrome: clinical and haematological characteristics of 23 patients. Ann Rheum Dis. 2005 Jun;64(6):943-6. [abstract]
2. Sivula M, Tallgren M, Pettila V; Modified score for disseminated intravascular coagulation in the critically ill. Intensive Care Med. 2005 Sep;31(9):1209-14. Epub 2005 Jun 15. [abstract]
3. Bakhtiari K, Meijers JC, de Jonge E, et al; Prospective validation of the International Society of Thrombosis and Haemostasis scoring system for disseminated intravascular coagulation. Crit Care Med. 2004 Dec;32(12):2416-21. [abstract]
4. Bick RL; Disseminated intravascular coagulation: objective clinical and laboratory diagnosis, treatment, and assessment of therapeutic response. Semin Thromb Hemost. 1996;22(1):69-88. [abstract]
5. Levi M, Opal SM; Coagulation abnormalities in critically ill patients. Crit Care. 2006;10(4):222. [abstract]
6. Labelle CA, Kitchens CS; Disseminated intravascular coagulation: treat the cause, not the lab values. Cleve Clin J Med. 2005 May;72(5):377-8, 383-5, 390 passim. [abstract]
7. DeLoughery TG; Thrombocytopenia and other hot topics. Am J Clin Oncol. 2009 Aug;32(4 Suppl):S13-7. [abstract]
8. Thachil J, Toh CH; Disseminated intravascular coagulation in obstetric disorders and its acute Blood Rev. 2009 Jul;23(4):167-76. Epub 2009 May 12. [abstract]
9. Slofstra SH, van 't Veer C, Buurman WA, et al; Low molecular weight heparin attenuates multiple organ failure in a murine model of disseminated intravascular coagulation. Crit Care Med. 2005 Jun;33(6):1365-70. [abstract]
10. Riewald M, Riess H; Treatment options for clinically recognized disseminated intravascular coagulation. Semin Thromb Hemost. 1998;24(1):53-9. [abstract]
11. Betrosian AP, Berlet T, Agarwal B; Purpura fulminans in sepsis. Am J Med Sci. 2006 Dec;332(6):339-45. [abstract]
12. Wiedermann CJ, Kaneider NC; A systematic review of antithrombin concentrate use in patients with disseminated intravascular coagulation of severe sepsis. Blood Coagul Fibrinolysis. 2006 Oct;17(7):521-6. [abstract]

Internet and further reading

• Becker JU, Wira CR; Disseminated Intravascular Coagulation; eMedicine. Sep 2009.
• Messmore HL, Wehrmacher WH; Disseminated intravascular coagulation, from Postgradute Medicine online
• Toh CK, Dennis M; Disseminated intravascular coagulation: old disease, new hope. Clinical Review; BMJ 2003;327:974-977 (25 October)

Acknowledgements