Disseminated Intravascular Coagulation (DIC): What the Physician Should Know?

Perspective

Disseminated Intravascular Coagulation (DIC) can be defined as a widespread hypercoagulable state that can lead to both microvascular and macrovascular clotting compromising blood flow resulting in multiple organ dysfunction syndrome. The consumption coagulopathy and thrombocytopenia will precipitate haemorrhage which may be the presenting symptom. It typically occurs as an acute complication in patients with underlying life-threatening illnesses such as severe sepsis, haematological malignancies, severe trauma, or placental abruption [1]. While disease states that may cause many of the signs and symptoms consistent with DIC such as acute or chronic liver failure can obscure a patient’s prognosis, mortality rates have been shown to double in septic patients or those with severe trauma if they are also suffering from DIC [2]. Multiple medical conditions can lead to the development of DIC either through a systemic inflammatory response or the release of pro-coagulants into the bloodstream [3-5]. The most common cause of DIC is severe sepsis occurring in up to 30 -50% cases, classically with gram-negative bacteria sepsis but the prevalence may be similar in sepsis due to gram-positive organisms. It occurs in 20% of patients with metastasized adenocarcinoma or lymphoproliferative disease, 1-5% of patients with chronic diseases such as solid tumours and aortic aneurysms. Obstetric complications such as placenta abruption, haemolysis, elevated liver enzymes, and low platelet count (HELLP syndrome), and amniotic fluid embolism have also been known to lead to DIC. About 15% of cases of DIC have also been linked to complications occurring after surgery. Other causes of DIC include trauma, pancreatitis, malignancy, snake bites, liver disease, transplant rejection, and blood transfusion reactions [6-10]. Perhaps the manifestation of the ‘macrophage activation-like syndrome’ may be the entity leading to early death in sepsis [11]. As the. pathophysiology of DIC is rarely straightforward, the classification is largely arbitrary (Table 1). The differential diagnosis would include dysfibrinogenemia, haemolytic uraemic syndrome, heparin-induced thrombocytopenia, Immune Thrombocytopenia (ITC), thrombotic Thrombocytopenic Purpura (TTP) [1]. As DIC can be a complication of many medical conditions, the reported prevalence will remain greater in higher than lower acuity settings because of the higher level of clinical suspicion [1,2,6]. It is now believed that most cases result from activation of coagulation factors from both intrinsic and extrinsic pathways, i.e. consumption coagulopathy, and activation of fibrinolysis is secondary to the process. [1,2,6,12,13]. Rarely, the condition may result from a primary activation of the fibrinolytic system. The intrinsic system of coagulation is triggered from the stimulation of platelets by exposure to bacteria, immune complexes, or to endothelial damage by bacteria endotoxin. Contact activation may result from exposure to particulate matter, amniotic fluid globules, or damaged vessel wall. The extrinsic system is triggered by tissue thromboplastin liberated by trauma and disseminated malignant disease. This activation generates thrombin which aggregates platelets, leading to platelet consumption and thrombocytopenia. Intravascular thrombin generates fibrin, thus depleting fibrinogen, prothrombin and other coagulation factors. In addition, fibrinolysis is stimulated producing Fibrin Degradation Products (FDPs), which further inhibit platelet function and fibrin polymerization. If the vascular endothelium is extensively damaged, surface contact stimulates platelet and tissue factors which then activate both coagulation and fibrinolysis. In DIC there is failure of inhibition of coagulation and fibrinolysis follows. The main problem is what causes the inappropriate activation of the haemostatic mechanism which results in widespread formation of fibrin and secondary depletion of platelets and clotting factors. [1,12,13]. The clinical presentation varies from no bleeding to complete haemostatic failure with widespread haemorrhage. This can occur from the mouth, nose or venepuncture sites, and skin shows widespread ecchymosis. The patient is often acutely ill and shocked, but the clinical severity will vary according to the initiating factors. In less severe forms of DIC a patient may show prolonged bleeding after venepuncture, or scattered ecchymosis with no other specific clinical signs. The second clinical feature is reflected by a variable degree of tissue and organ damage due to laying down of fibrin. The most serious manifestation is renal involvement, which vary in severity from reversible tubular necrosis to complete irreversible bilateral renal cortical necrosis. The skin is also vulnerable and large areas of gangrene is associated with fulminant septicaemias (purpura fulminans or gangrenosa). Adult respiratory distress syndrome (shock-lung) is associated with the diffuse fibrin deposition in the small vessels of the lung, and similarly acute liver or adrenal failure may complicate the syndrome. Microangiopathic haemolytic anaemia is common in patients with disseminated malignant disease [1,6,14].

  

    
Infections 
    
Exposure to thromboplastins 
    
Neoplasia 
    
Obstetric 
    
Hypovolaemia 
  
  

    
Sepsis with Gram-negative    or Gram- positive organisms

      Rickettsial diseases

      Certain virus infections, e.g. cytomegalovirus 
    
Some snake bites, e.g.    Echis carinatus

      Excessive tissue trauma

      Burns

      Fat embolism

      Incompatible blood transfusions

      Heart-Lung bypass 
    
Leukaemia (especially    promyelocytic)

      Cancer: lung, breast, prostate, gastrointestinal tract 
    
Septic abortion

      Retained dead fetus

      Amniotic fluid embolism

      Eclampsia

      Premature separation of the placenta 
    
Heat stroke

      Hypovolaemic shock

      Diabetic keto-acidosis

      Liver failure 
  

Table 1: Some disorders contributing to DIC.