| Disseminated intravascular coagulation | |
|---|---|
| Other names | Disseminated intravascular coagulopathy, consumptive coagulopathy, defibrination syndrome[1] |
 | |
| Micrograph showing acutethrombotic microangiopathy due to DIC in akidney biopsy. Aclot is present in thehilum of theglomerulus (center of image). | |
| Specialty | Hematology |
| Symptoms | Chest pain,shortness of breath, leg pain, problems speaking, problems moving part of the body, bleeding[1] |
| Complications | Organ failure[2] |
| Types | Acute, chronic[1] |
| Causes | Sepsis,surgery,major trauma,cancer,complications of pregnancy,snake bites,frostbite,burns[1] |
| Diagnostic method | Blood tests[2] |
| Differential diagnosis | Thrombotic thrombocytopenic purpura,hemolytic-uremic syndrome[1] |
| Treatment | Directed at the underlying condition[3] |
| Medication | Platelets,cryoprecipitate,fresh frozen plasma,heparin[2] |
| Prognosis | 20–50% risk of death[4] |
| Frequency | 1% of people admitted to hospital[4] |
Disseminated intravascular coagulation (DIC) is a condition in whichblood clots form throughout the body, blockingsmall blood vessels.[1] Symptoms may includechest pain,shortness of breath, leg pain, problems speaking, or problems moving parts of the body.[1] Asclotting factors andplatelets are used up,bleeding may occur.[1] This may includeblood in the urine,blood in the stool, or bleeding into the skin.[1] Complications may includeorgan failure.[2]
Relatively common causes includesepsis,surgery,major trauma,cancer, andcomplications of pregnancy.[1] Less common causes includesnake bites,frostbite, andburns.[1] There are two main types: acute (rapid onset) and chronic (slow onset).[1] Diagnosis is typically based onblood tests.[2] Findings may includelow platelets, lowfibrinogen, highINR, or highD-dimer.[2]
Treatment is mainly directed towards the underlying condition.[2][3] Other measures may include givingplatelets,cryoprecipitate, orfresh frozen plasma.[2] Evidence to support these treatments, however, is poor.[2]Heparin may be useful in the slowly developing form.[2] About 1% of people admitted to hospital are affected by the condition.[4] In those with sepsis, rates are between 20% and 50%.[4] The risk of death among those affected varies from 20% to 50%.[4]
In DIC, the underlying cause usually leads to symptoms and signs, and DIC is discovered on laboratory testing. The onset of DIC can be sudden, as in endotoxic shock oramniotic fluid embolism, or it may be insidious and chronic, as in cancer. DIC can lead to multiorgan failure and widespread bleeding.[5]
DIC can occur in the following conditions:[5][6][7][8]
Liver disease,HELLP syndrome,thrombotic thrombocytopenic purpura,hemolytic uremic syndrome, andmalignant hypertension may mimic DIC but originate via other pathways.[9] It is not the same as conditions where the blood vessels leak, such ascapillary leak syndrome.[10]
Under homeostatic conditions, the body is maintained in a finely tuned balance of coagulation andfibrinolysis. The activation of the coagulation cascade yieldsthrombin that convertsfibrinogen tofibrin; the stable fibrin clot being the final product ofhemostasis. The fibrinolytic system then functions to break down fibrinogen and fibrin. Activation of the fibrinolytic system generatesplasmin (in the presence of thrombin), which is responsible for the lysis of fibrin clots. The breakdown of fibrinogen and fibrin results in polypeptides calledfibrin degradation products (FDPs) or fibrin split products (FSPs). In a state of homeostasis between clot formation and clot dissolution, the presence of plasmin is critical, as it is the central proteolytic enzyme of coagulation and is necessary for the breakdown of fibrin clots, or fibrinolysis.[11]
In DIC, the processes of coagulation and fibrinolysis are dysregulated, and the result is widespread clotting with resultant bleeding. Regardless of the triggering event of DIC, once initiated, the pathophysiology of DIC is similar in all conditions. One critical mediator of DIC is the release of a transmembrane glycoprotein calledtissue factor (TF). TF is present on the surface of many cell types (including endothelial cells, macrophages, and monocytes) and is not normally in contact with the general circulation, but is exposed to the circulation after vascular damage. For example, TF is released in response to exposure to cytokines (particularlyinterleukin 1),tumor necrosis factor, andendotoxin.[12] This plays a major role in the development of DIC in septic conditions. TF is also abundant in tissues of the lungs, brain, and placenta. This helps to explain why DIC readily develops in patients with extensive trauma. Upon exposure to blood and platelets, TF binds with activated factor VIIa (normally present in trace amounts in the blood), forming the extrinsic tenase complex. This complex further activates factor IX and X to IXa and Xa, respectively, leading to the common coagulation pathway and the subsequent formation of thrombin and fibrin.[7]
The release of endotoxin is the mechanism by whichGram-negative sepsis provokes DIC. Inacute promyelocytic leukemia, treatment causes the destruction of leukemic granulocyte precursors, resulting in the release of large amounts of proteolytic enzymes from their storage granules, causing microvascular damage. Other malignancies may enhance the expression of various oncogenes that result in the release of TF andplasminogen activator inhibitor-1 (PAI-1), which prevents fibrinolysis.[13]
Excess circulating thrombin results from the excess activation of the coagulation cascade. The excess thrombin cleaves fibrinogen, which ultimately leaves behind multiple fibrin clots in the circulation. These excess clots trap platelets to become larger clots, which leads to microvascular and macrovascular thrombosis. This lodging of clots in the microcirculation, in the large vessels, and in the organs is what leads to the ischemia, impaired organ perfusion, and end-organ damage that occurs with DIC.[14][15]
Coagulation inhibitors are also consumed in this process. Decreased inhibitor levels will permit more clotting so that apositive feedback loop develops in which increased clotting leads to more clotting. At the same time, thrombocytopenia occurs and this has been attributed to the entrapment and consumption of platelets. Clotting factors are consumed in the development of multiple clots, which contributes to the bleeding seen with DIC.[14][15]
Simultaneously, excess circulating thrombin assists in the conversion of plasminogen to plasmin, resulting in fibrinolysis. The breakdown of clots results in an excess of FDPs, which have powerful anticoagulant properties, contributing to hemorrhage. The excess plasmin also activates the complement and kinin systems. Activation of these systems leads to many of the clinical symptoms that patients experiencing DIC exhibits, such as shock, hypotension, and increased vascular permeability. The acute form of DIC is considered an extreme expression of the intravascular coagulation process with a complete breakdown of the normal homeostatic boundaries. DIC is associated with a poor prognosis and a high mortality rate.[14][15]
There has been a recent challenge however to the basic assumptions and interpretations of the pathophysiology of DIC. A study ofsepsis and DIC in animal models has shown that a highly expressed receptor on the surface of hepatocytes, termed theAshwell-Morell receptor, is responsible for thrombocytopenia in bacteremia and sepsis due toStreptococcus pneumoniae (SPN) and possibly other pathogens. Thethrombocytopenia observed in SPN sepsis was not due to increased consumption of coagulation factors such as platelets, but instead was the result of this receptor's activity, enabling hepatocytes to ingest and rapidly clear platelets from circulation.[16] By removing prothrombotic components before they participate in the coagulopathy of DIC, the Ashwell-Morell receptor lessens the severity of DIC, reducing thrombosis and tissue necrosis, and promoting survival. The hemorrhage observed in DIC and among some tissues lacking this receptor may therefore be secondary to increased thrombosis with loss of the mechanical vascular barrier.[14][15]
Activation of theintrinsic andextrinsic coagulation pathways causes excess thrombus formation in the blood vessels. Consumption of coagulation factors due to extensive coagulation in turn causes bleeding.[14][15]
The diagnosis of DIC is not made on a single laboratory value, but rather the constellation of laboratory markers and a consistent history of an illness known to cause DIC. Laboratory markers consistent with DIC include:[3][7][17]
A diagnostic algorithm has been proposed by the International Society of Thrombosis and Haemostasis. This algorithm appears to be 91% sensitive and 97% specific for the diagnosis of overt DIC. A score of 5 or higher is compatible with DIC and it is recommended that the score is repeated daily, while a score below 5 is suggestive but not affirmative for DIC and it is recommended that it is repeated only occasionally:[17][18] It has been recommended that a scoring system be used in the diagnosis and management of DIC in terms of improving outcome.[19]
Treatment of DIC is centered on treating the underlying condition. Transfusions ofplatelets orfresh frozen plasma can be considered in cases of significant bleeding, or those with a planned invasive procedure. The target goal of such transfusion depends on the clinical situation.Cryoprecipitate can be considered in those with a lowfibrinogen level. Treatment of thrombosis with anticoagulants such as heparin is rarely used due to the risk of bleeding.[citation needed]
Recombinant human activatedprotein C was previously recommended in those with severe sepsis and DIC, butdrotrecogin alfa has been shown to confer no benefit and was withdrawn from the market in 2011.[21]
Recombinant factor VII has been proposed as a "last resort" in those with severe hemorrhage due to obstetric or other causes, but conclusions about its use are still insufficient.[22]
Prognosis varies depending on the underlying disorder, and the extent of the intravascularthrombosis (clotting). The prognosis for those with DIC, regardless of cause, is often grim: between 20% and 50% of patients will die.[23] DIC withsepsis (infection) has a significantly higher rate of death than DIC associated with trauma.[23]
DIC is observed in approximately 1% of academic hospital admissions.[24] DIC occurs at higher rates in people with bacterial sepsis (83%),[25] severe trauma (31%),[26] and cancer (6.8%).[27]
