Disseminated Intravascular Coagulation (DIC), Introduction Disseminated intravascular coagulation (DIC) is an acquired syndrome. It is a complication of an underlying illness, and involves systemic activation of the coagulation system when blood is exposed to procoagulants such as tissue factor. Thrombin is produced in disproportionate amounts, leading to widespread deposition of excess fibrin. The accumulation of intravascular fibrin impairs circulation via formation of microvascular thrombi. The end results of which are vessel damage and tissue ischemia. The excessive amount of fibrin also causes consumption of platelets and clotting factors. If DIC is left undiagnosed and/or untreated, life-threatening haemorrhage may result. Classification Acute (decompensated) DIC: Occurs in a short amount of time when pro-coagulants are expelled into the blood. Thrombin is produced in vast amounts trigging coagulation and excess deposition of intravascular fibrin, resulting in severe bleeding, tissue injury and/or organ failure. Acute DIC is typically seen in severe infection, obstetric complications and massive tissue injury due to trauma or burns. Chronic (compensated) DIC: Occurs when the blood is exposed to small amounts of pro-coagulant continuously over an extended period of time. It is seen in conditions such as malignancy and less commonly chronic infections such as tuberculosis, osteomyelitis and in inflammatory bowel disease. More rarely, chronic DIC can be seen in cases of aortic aneurysm and dead fetus in utero. Although these patients are generally asymptomatic, they can manifest with signs such as minor skin/ mucosal bleeds and/or thrombosis. Aetiology DIC is not an isolated condition. Most often, it is secondary to a systemic response of an underlying cause, such as the following: The most common condition associated with DIC is septicaemia due to bacterial infection, however, systemic infections by other organisms such as viruses or parasites can also cause DIC. Cancers, obstetric complications, massive tissue injury and systemic diseases follow septicaemia in prevalence. In cases trauma, head trauma with the presence of systemic inflammatory response syndrome (SIRS) is suggested to be most strongly correlated with DIC. Statistics obtained from Leung, L. (2012) Basic sciences In discussing the general mechanisms underlying DIC, it is imperative to understand and review the normal pathway of coagulation and clotting. Coagulation is split up into primary haemostasis and secondary haemostasis. Primary haemostasis occurs when there is damage to tissue or blood vessels. Platelets are aggregated to form primary clots at the injury site. The primary clots are subsequently strengthened by secondary haemostasis, which involves activation of both the extrinsic and intrinsic pathways. The extrinsic pathway is triggered by tissue damage to the outside of the blood vessel. Damage to the tissue stimulates the activation of tissue factor, (also known as tissue thromboplastin), which catalyzes the activation of factor X. Measuring prothrombin time (PT) monitors the extrinsic pathway and the tendency of the blood to clot. The ratio of a patient’s PT to the laboratory mean of normal patients (control sample) ultimately generates the International Normalized Ratio (INR). The intrinsic pathway involves the activation of Hageman factor (factor XII). It is activated on negatively charged sites by a process known as contact activation. Activation of factor XII is followed by a cascade of events resulting in activation of factor X. The intrinsic pathway is monitored by the activated partial thromboplastin time (aPTT). The control of coagulation The final common pathway for the aboves generates thrombin, a potent inducer of connective tissue growth factors that converts fibrinogen into fibrin clots. By mediating thrombin activatable fibrinolysis inhibitor (TAFI), thrombin also regulates fibrinolysis, thus prevents the clots from disintegrating. As thrombin is being swept away from the site of tissue injury, it attaches itself to thrombomodulin to activate protein C, a vitamin-K dependent glycoprotein that inhibits pro-coagulant factors V and VIII. The other potent inhibitor of coagulation also includes antithrombin III. Plasmin and fibrinolysis Eventually, the formed clot is degraded and resorbed by a process known as fibrinolysis. The main enzyme responsible for this process is plasmin. Plasmin degrades the fibrin clot into D-dimers and fibrin degradation product (FDPs), also known as fibrin split products. It also degrades intact fibrinogen and various clotting factors. (Kumar, Robbins & et al. 2007) Pathophysiology The major mechanisms that trigger DIC involve The release of tissue thromboplastin or thromboplastic substances into the circulation; and Injury to the endothelial cells Examples of tissue thromboplastic substances that may trigger DIC are from obstetric complications, trauma and burns, or from the granules of leukemic cells in AML. Bacterial endotoxins in gram-negative sepsis, can cause release of cytokines (e.g. interleukin-1 and tumour necrosis factor (TNF)) from activated monocytes. These cytokines cause activation of tissue thromboplastin on endothelial cell membranes and decrease thrombomodulin expression, thus a shift towards procoagulation. DIC as a consumptive coagulaphy DIC is a combination of two important hallmarks, i.e. the continuous generation of intravascular fibrin; and consumption of clotting factors and platelets. In addition, increased clotting is accompanied by decreased fibrinolysis. Without counteraction from the anticoagulant pathway, increased thrombin continuously intensifies the coagulation cascade through positive feedback. The accumulation of intravascular fibrin then results in widespread deposition of microthrombi, causing ischemic damage of various tissues and impaired organ perfusion. If not treated within a timely manner, multi-organ failure may result. Another consequence of DIC is microangiopathic haemolytic anaemia (MAHA), where red blood cells become fragmented as they try to squeeze through the narrowed vessels. Thrombocytopenia may also result during this process, as the clot traps and consumes platelets. In addition to platelets, coagulation factors and inhibitors become consumed by the same course. As plasminogen is activated, plasmin is stimulated, cleaving the fibrin clot. Degradation of fibrin produces the by-products fibrin degradation products (FDPs) and D-dimers. In DIC, FDPs enhance bleeding by interfering with normal fibrin polymerization. They also interfere with platelet aggregation by binding to the platelet surface glycoprotein IIb/IIIa fibrinogen receptor. Furthermore, bleeding diathesis is exacerbated by plasmin, since plasmin can also degrade fibrinogen and other clotting factors. (Kumar, Robbins & et al, 2007) Diagnosis Diagnosis of DIC can be challenging, as there is no single routine laboratory test available that is sensitive and specific for DIC. However, several laboratory tests often return abnormal giving imperative clues for DIC. In general, combining history (e.g. presence of sepsis, trauma, malignancy), clinical impression and abnormal laboratory results, help to make the diagnosis of DIC. Clinical Presentation DIC may not present with any specific sign or symptom, rather the patient may only present with symptoms of the underlying cause. However, a history of spontaneous blood loss from gingiva, venepuncture sites, post-operative surgical sites or drains may provide diagnostic value. In general, acute DIC, which is associated with sepsis, obstetric complications or major trauma may present with wide spread petechiae and ecchymosis. Blood oozing from wound sites, intravenous lines and catheters is also commonly seen in acute DIC. For those patients that developed DIC after surgical procedures, haemorrhage may develop around surgical sites or drains and tracheostomies. When injury to the pulmonary vasculature has occurred, haemoptysis and dyspnoea may occur. Acute respiratory distress syndrome (ARDS) may result from pulmonary microthrombosis due to DIC. In addition, sepsis, trauma and amniotic fluid embolism can lead to lung injury associated with ARDS. In chronic DIC (which may occur in cancer patients) the patient is usually asymptomatic. The liver and bone marrow are generally able to replenish the depleted coagulation proteins and platelets respectively when the blood is continuously exposed to small amounts of tissue factor. The patient may present with thrombotic complications such as DVTs in the extremities or superficial migratory thrombophlebitis (also known as Trousseau’s syndrome). Minor skin and mucosal bleeding may be presentations Although an accurate history may give clues to a diagnosis of DIC, clinical observation and laboratory studies are necessary for a definite diagnosis. Laboratory Investigations When investigating a patient for DIC, a wide range of abnormalities can be seen. The laboratory findings seen in acute (decompensated) vs. chronic (compensated) DIC are slightly different. The following laboratory studies provide suspicion of DIC. Platelet Count: Moderate to severe thrombocytopenia (
Posted on: Tue, 26 Aug 2014 10:29:34 +0000
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