DISSEMINATED INTRAVASCULAR COAGULATION
Introduction
Disseminated intravascular coagulation, (DIC) has a number of pseudonyms including:
● Consumption coagulopathy
● Defibrination syndrome
It is a systemic pathological process that results in both thrombosis and hemorrhage initiated by a number of defined disorders.
Both acute and chronic forms exist. These guidelines relate predominantly to the acute form.
Management of acute DIC involves supportive measures, treating the underlying cause and replacing platelet and clotting factors. In certain selected circumstances careful use of heparin may be warranted.
Overall prognosis will be closely related to the underlying pathology
Pathophysiology
In DIC there is a dynamic massive and generalized activation of the clotting system, followed by a generalized activation of the fibrinolytic system. (See appendix 1 below for a summary of the coagulation and fibrinolytic systems).
The coagulation pathways are activated by various procoagulant mediators of either the intrinsic or the extrinsic systems.
Acute versus chronic DIC:
If the activation process occurs slowly, an excess of procoagulants is produced, predisposing to thrombosis. As long as the liver can compensate for the consumption of clotting factors, and the bone marrow is able to maintain an adequate platelet count, the bleeding diathesis will not be clinically apparent. This is the picture of chronic compensated DIC; its clinical presentation consists of primarily thrombotic manifestations, which can be venous or arterial. Trousseau’s syndrome, is a hypercoagulable state associated with malignancy, and is an example of a chronic DIC.
If the reaction is rapid, the clinical picture is acute decompensated DIC and is dominated by intravascular coagulation; depletion of platelets, fibrinogen, prothrombin, and factors V and VIII; and the production, via the action of plasmin, of fibrin degradation products, which further interfere with hemostasis. The clinical picture here is a systemic bleeding diathesis. The intravascular fibrin strands cause mechanical shearing of circulating red cells producing the picture of microangiopathic hemolytic anemia
In summary therefore chronic DIC tends to produce thrombotic episodes, whilst acute DIC tends to produce bleeding episodes.
Activation of the coagulation cascade:
With activation of the coagulation system in acute DIC, fibrin binds to microvascular endothelium and platelets and coagulation factors are consumed.
Clinically multi-site bleeding occurs. A secondary fibrinolysis may then further accentuate bleeding.
Generalized activation of the clotting system can be due to:
1. Extrinsic system
(F3) widespread tissue damage:
● Trauma, including major surgery.
● Burns
● Shock states in general
2. Intrinsic system
(F12) Foreign substances:
● Infection/sepsis
● Disseminated malignancy
● Obstetric conditions, including:
FDIU/ Abruptions/ Amniotic fluid embolism/ Severe PET/Eclampsia.
● Venoms
● Severe pancreatitis
● Fat embolism
Commonest causes:
The three commonest causes of acute DIC are:
1. Infection.
2. Trauma.
● This also includes major surgery.
3. Malignancy
● Malignancy more commonly results in a chronic DIC, however acute DIC is also possible.
Complications
Clinical complications will manifest as the multiorgan dysfunction syndrome, (MODS).
The following may be seen, (in decreasing order of frequency) 1
1. Bleeding.
2. Renal dysfunction.
3. Hepatic dysfunction.
4. Respiratory dysfunction.
5. Shock.
6. Thromboembolism.
7. Central nervous system involvement.
Clinical Features
Diagnosis is based on the triad of:
- The correct clinical setting.
● The patient is suffering from one of the recognized causes of DIC.
2. Evidence of MODS:
In varying combinations of:
● Multi-site bleeding, (The usual clinical manifestation is bleeding and not thrombosis).
● Renal failure
● Hypotension.
● Hepatic failure
● ARDS
● Altered conscious state
3. Laboratory evidence, (see below).
Investigations
Evidence of characteristic DIC coagulopathy:
- Evidence of excessive conversion of fibrinogen to fibrin and its subsequent lysis.
● Decreased fibrinogen levels.
● Increased FDPs.
● Increased Thrombin time (reflects ongoing fibrinoysis, due to the increased FDPs).
- Low platelet levels.
- Disordered coagulation cascade.
● Increased INR.
● Increased APPT.
Further investigations should include:
- FBE:
● In addition to the platelet count the blood film should also be examined.
Note that DIC is a thrombotic micro-angiopathy, (resulting in destruction of RBCs and morphological fragmentation), as is TTP-HUS. The pathologies however are different. The pathology in DIC is due to activation of the coagulation cascades, whereas in TTP-HUS it is due to a defect in platelet function, possible secondary to a deficiency in the enzyme ADAMTS 13.
5. U&Es/ glucose.
● Look for renal impairment
6. LFTs:
● Look for hepatic impairment.
Differentiation of DIC from TTP-HUS:
Patients with TTP-HUS present with thrombocytopenia and a microangiopathic blood smear, but usually have normal levels of the coagulation components and little or no prolongation of the PT or APTT. The fibrinogen levels and FDP levels in TTP-HUS are also normal.
In addition to the different laboratory findings, TTP-HUS is usually not seen in the typical clinical settings that are associated with DIC (eg, sepsis, trauma, malignancy, and obstetrical complications).
Establishing the correct diagnosis is important clinically, because TTP-HUS in adults is initially treated with plasma exchange, which may be life-saving; this is not the modality used to treat DIC
Management
Principles of management of DIC include:
1. Supportive.
- Treatment of the underlying cause.
- Blood components in selected cases.
Supportive
Patients are at risk of MODS to varying degrees, and treatment accordingly is supportive in an ICU environment.
Ventilation, dialysis and inotropic support may all be required.
Treatment of the underlying cause.
This is an essential aspect in determining the eventual outcome for any given case.
Blood components in selected cases:
Many patients do not require specific therapy for the coagulopathy associated with DIC, either because it is of short duration or because it is not severe enough to present a major risk of bleeding or thrombosis
There is no current evidence to support the routine administration of platelets and coagulation factors in patients who are not bleeding or who are not at high risk of bleeding.
In general terms:
Treatment with platelets and coagulation factors (FFP) is justified in patients who have:
● Serious bleeding.
Actively bleeding patients with a significantly elevated prothrombin time (INR) and/or a fibrinogen concentration <50 mg/dL, should receive fresh frozen plasma (or cryoprecipitate) in order to keep the fibrinogen level >100 mg/dL.
● Are at high risk for bleeding (eg, after surgery).
● Require invasive procedures.
● Patients with marked or moderate thrombocytopenia (<50,000/micro/L) and serious bleeding should be given platelet transfusions.
RBC transfusion may be given as clinically indicated.
The administration of heparin is generally limited to the subset of patients with chronic, compensated DIC who have predominantly thrombotic manifestations.
Appendix 1
The coagulation cascade and fibrinolytic system:
Extrinsic clotting pathway Intrinsic clotting pathway, (F12)
(F3, tissue thromboplastin)
F7 F8, 9, 10
X Xa F5
Prothrombin (F2) Thrombin
Plasminogen Fibrinogen (F1) Fibrin
(Stable clot)
tPA
(from
endothelium)
Plasmin
FDPs
(including
D-Dimers)