23.1). DIC is characterized by great variation both between patients and within the same patient over time. It is a dynamic condition that will progress if untreated but can rapidly improve with appropriate treatment of the underlying cause. Recognition and treatment of the underlying cause are more important in treating DIC than support with haemostatic factors and platelets – giving more coagulation factors, fibrinogen, and platelets without treating the cause results in more substrate for uncontrolled coagulation and more microvascular thrombosis and end organ damage. Due to its severity and dynamic nature, it has been difficult to perform adequate randomized controlled trials in the management and treatment of DIC, although there have been several recent advances in its early diagnosis and treatment.3
The primary triggers of DIC in the elderly are bacterial sepsis and malignancy, particularly disseminated malignancy. Other causes include massive trauma and major surgery. ABO‐incompatible blood transfusions, pancreatitis, and snake bites are rarer but recognized causes. DIC may be precipitated by activation of the coagulation cascade following tissue factor exposure, for example, as in massive trauma and major surgery; activation of the fibrinolytic cascade, e.g. the liberation of plasminogen activators by leukaemic blasts in acute promyelocytic leukaemia or carcinoma of the prostrate; or intravascular platelet activation, e.g. heparin‐induced thrombocytopenia, haemolytic uraemic syndrome, by endotoxins and endothelial cell activation in Gram‐negative sepsis and meningococcal septicaemia or by direct proteolytic cleavage of circulating haemostatic proteins, as occurs in pancreatitis and with some snake venoms (Table 23.1). In addition to uncontrolled activation of and consumption of platelets and the coagulation cascade, there is depletion of the proteins of the natural anticoagulant pathway. Depletion of these further enhances the microvascular thrombosis and also leads to activation of the complement system, resulting in an inflammatory response and generation of vasoactive peptides, such as bradykinin. DIC also provokes a poorly characterized neuroendocrine response involving elevated catecholamines and glucocorticoids.4
Clinically, DIC manifests as simultaneous bleeding and microvascular thrombosis leading to multiple organ dysfunction, including acute kidney injury (AKI), adult respiratory distress syndrome (ARDS), and hepatic and neurological dysfunction, and is often associated with fever, hypotension, lactic acidosis, hypoxia, and proteinuria. While bleeding is the most obvious and commonly recognized manifestation, death by bleeding is rare due to the use of blood and platelet transfusions in the treatment of hypovolaemia. The usual cause of death in DIC is multiorgan failure as a consequence of microvascular thrombosis, which is not immediately clinically apparent. Treatment of multiorgan failure, which is a consequence of anoxia and ischaemic necrosis of vital organs, is far more difficult to treat satisfactorily.5
Figure 23.1 Mechanism of microvascular thrombosis and bleeding in DIC. Broken lines indicate inhibition.
Table 23.1 Mechanisms and precipitating factors in DIC.
| Mechanism | Example |
|---|---|
| Coagulation cascade activation | Tissue factor exposure in trauma and extensive surgery |
| Fibrinolytic cascade activation | Plasminogen activators liberated in acute promyelocytic leukaemia or disseminated prostatic cancer |
| Intravascular platelet aggregation | Haemolytic uraemic syndrome, thrombotic thrombocytopenic purpura, heparin‐induced thrombocytopenia |
| Endothelial cell activation | Gram‐negative sepsis, disseminated malignancy |
| Direct proteolytic cleavage of haemostatic proteins | Pancreatitis, snake venoms |
The bleeding in DIC is multifactorial in origin as a result of depletion of fibrinogen, all coagulation factors, and platelets as a consequence of consumption due to uncontrolled and excessive activation of the coagulation cascade, diminished platelet number due to consumption, and an additional or acquired platelet defect consequent to proteolytic degradation of platelet surface glycoproteins and partial degranulation of α and dense platelet granules. Hyperfibrinolysis leads to elevated levels of fibrinogen and fibrin degradation products (measured as highly increased D‐dimers), which act as competitive inhibitors of fibrin polymerization. The uncontrolled generation of free thrombin and plasmin degrades fibrin, fibrinogen, and coagulation factors, particularly factors V and VIII. Consequently, there is a systemic bleeding diathesis resulting in not only bleeding from local surgical incisions or traumatic wounds but also generalized bruising, petechiae, and purpura, together with bleeding from sites of venepuncture, arterial lines, drains, catheters, and endotracheal tubes. There is also frequent gastrointestinal bleeding, haemoptysis, haematuria, and even intramuscular or intracerebral bleeding. Clinically, the widespread occurrence of abnormal and excessive bleeding is the hallmark of DIC. Excessive bleeding from a single site, particularly following surgery, is usually more indicative of a specific failure of local haemostasis than DIC and requires specific local measures. The microvascular thrombosis results in anoxic damage and ischaemic infarction of vital organs, including lungs, kidneys, brain, pituitary, liver, adrenal, heart, and skin.6
Diagnosis
The diagnosis of DIC is made in the presence of a predisposing cause, the clinical manifestations of systemic bleeding and multiorgan dysfunction, and appropriate laboratory investigations (Table 23.2). The haemoglobin is usually reduced owing to intravascular red cell fragmentation, resulting in a microangiopathic haemolytic anaemia (MAHA), and there is profound thrombocytopenia. Coagulation times are abnormal, with a prolongation of the activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT) and depletion of fibrinogen, all due to consumption. In addition, there is evidence of fibrinolytic activation and fibrin degradation with elevations of serum FDPs or plasma D‐dimers. As well as these rapid and readily available tests, recent studies have shown that waveform analysis of the coagulation profile on automated machines can have both diagnostic and prognostic significance, and laboratory abnormalities can be included in a validated scoring system for DIC. In addition to consumption of the coagulation factors and prolongation of the clotting times, levels of natural anticoagulant pathway proteins – antithrombin, protein C, and protein S – are also significantly reduced, contributing to microvascular thrombosis.7
Table 23.2 Laboratory diagnosis of DIC.
| Test | Result |
|---|---|
| APTT | Prolonged >10 seconds beyond normal |
| PT | Prolonged > 5 seconds beyond normal |
| TT | Prolonged > 10 seconds beyond normal |
| Fibrinogen | Low, usually <1 g l−1 |
| Platelets | Low, usually <50 × 109 l−1 |
| D‐dimer | Raised > 1000 ng/ml |
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