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Disseminated intravascular coagulation or Disseminated intravascular coagulopathy
Classification and external resources
ICD-10 D65.
ICD-9 286.6
DiseasesDB 3765
eMedicine med/577  emerg/150
MeSH D004211

Disseminated intravascular coagulation (DIC), also called consumptive coagulopathy, is a pathological process in the body where the blood starts to coagulate throughout the whole body. The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify Diseases The International Statistical Classification of Diseases and Related Health Problems 10th Revision ( ICD -10) is a coding of diseases and signs symptoms abnormal findings The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify Diseases The following is a list of codes for International Statistical Classification of Diseases and Related Health Problems. The Diseases Database is a free Website that provides information about the relationships between medical conditions Symptoms, and Medications. eMedicine is an online clinical medical knowledge base that was founded in 1996 by Scott Plantz and Richard Lavely two medical doctors Medical Subject Headings ( MeSH) is a huge Controlled vocabulary (or metadata system for the purpose of indexing journal articles and books Pathology (from Greek grc πάθος pathos, "fate harm" and grc -λογία -logia) is the study and Blood is a specialized Bodily fluid that delivers necessary substances to the body's cells such as nutrients and oxygen—and transports Waste products Coagulation is a complex process by which Blood forms Clots It is an important part of Hemostasis (the cessation of blood loss from a damaged vessel whereby This depletes the body of its platelets and coagulation factors, resulting in the paradoxic situation in which there is a high risk for simultaneous catastrophic thrombosis as well as massive hemorrhage. Platelets, or Thrombocytes, are small cytoplasmic bodies derived from cells They circulate in the Blood of Mammals and are involved Thrombosis is the formation of a blood Clot ( Thrombus) inside a Blood vessel, obstructing the flow of Blood through the Circulatory Bleeding, technically known as hemorrhaging / haemorrhaging (see American and British spelling differences) is the loss of Blood from It occurs in critically ill patients in fulminant sepsis as well those with malignancy. Sepsis is a serious medical condition characterized by a whole-body inflammatory state (called a Systemic inflammatory response syndrome or SIRS caused Cancer (medical term Malignant Neoplasm) is a class of Diseases in which a group of cells display uncontrolled It is more commonly seen in Gram-negative sepsis (particularly meningococcal sepsis) than in Gram-positive sepsis. Gram-negative bacteria are those Bacteria that do not retain Crystal violet dye in the Gram staining protocol Neisseria meningitidis, also simply known as meningococcus, is a heterotrophic Gram-negative diplococcal Bacterium best known for Gram-positive bacteria are those that are stained dark blue or violet by Gram staining. In the past, it was a common consequence of treatment of acute promyelocytic leukemia, and may occur in other hematogenic malignancies, but can occur in solid tumors as well as a paraneoplastic syndrome. Acute promyelocytic leukemia is a subtype of Acute myelogenous leukemia (AML a Cancer of the Blood and Bone marrow. A paraneoplastic syndrome is a Disease or Symptom that is the consequence of the presence of Cancer in the body but is not due to the local presence

Contents

Etiology

There are a variety of causes of DIC[1], all usually causing the release of chemicals into the blood that instigates the coagulation.

Diagnosis

Although numerous blood tests are often performed on patients prone to DIC, the important measures are: full blood count (especially the platelet count), fibrin degradation products or D-dimer tests (markers of fibrinolysis), bleeding time and fibrinogen levels. A blood test is a laboratory analysis performed on a Blood sample that is usually extracted from a Vein in the arm using a needle, or via A complete blood count ( CBC) also known as full blood count ( FBC) or full blood exam ( FBE) or blood panel, is Platelets, or Thrombocytes, are small cytoplasmic bodies derived from cells They circulate in the Blood of Mammals and are involved Fibrin degradation product (FDPs are components of the blood produced by Clot degeneration D-dimer is a Fibrin degradation product, a small protein fragment present in the blood after a blood clot is degraded by Fibrinolysis. Fibrinolysis is the process wherein a Fibrin clot, the product of Coagulation, is broken down Bleeding time is a Medical test done on someone to assess their Platelet function Fibrin (also called Factor Ia) is a Protein involved in the clotting of blood The protamine paracoagulation phenomenon can also be observed. Decreased platelets, elevated FDPs or D-dimers, prolonged bleeding time and decreased fibrinogen are markers of DIC. On peripheral blood smear, evidence of microangiopathic hemolytic anemia (specifically schistocytes) may be present (as in thrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome (HUS))

Pathophysiology

Under homeostatic conditions, the body is maintained in a finely tuned balance of coagulation and fibrinolysis. A Blood Film or Peripheral Blood Smear is a slide made from a drop of Blood, that allows the cells to be examined microscopically In Medicine ( Hematology) microangiopathic hemolytic anemia (MAHA is a microangiopathic subgroup of Hemolytic anemia ( Anemia, loss Red blood cells are the most common type of Blood cell and the Vertebrate body's principal means of delivering Oxygen to the body tissues via the Blood Thrombotic thrombocytopenic purpura ( TTP or Moschcowitz disease) is a rare disorder of the blood-coagulation system causing extensive microscopic In Medicine, hemolytic-uremic syndrome (or haemolytic-uraemic syndrome, abbreviated HUS is a disease characterized by Microangiopathic hemolytic anemia The activation of the coagulation cascade yields thrombin that converts fibrinogen to fibrin; the stable fibrin clot being the final product of hemostasis. The fibrinolytic system then functions to break down fibrinogen and fibrin. Activation of the fibrinolytic system generates plasmin (in the presence of thrombin), which is responsible for the lysis of fibrin clots. The breakdown of fibrinogen and fibrin results in polypeptides called fibrin degradation products (FDPs) or fibrin split products (FSPs). In a state of homeostasis, the presence of thrombin is critical, as it is the central proteolytic enzyme of coagulation and is also necessary for the breakdown of clots, or fibrinolysis.

In DIC, the processes of coagulation and fibrinolysis lose control, 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 called tissue 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 (particularly interleukin), tumor necrosis factor, and endotoxin. 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 activation, TF binds with coagulation factors that then trigger both the intrinsic and the extrinsic pathways of coagulation.

The release of endotoxin is the mechanism by which Gram-negative sepsis provokes DIC. In acute promyelocytic leukemia, treatment causes the destruction of leukemic granulocyte precusors, 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 and plasminogen activator inhibitor-1 (PAF-1), which prevents fibrinolysis. Plasminogen activator inhibitor-1 is the principal inhibitor of Tissue plasminogen activator (tPA and Urokinase (uPA the activators of Plasminogen [2]

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.

Coagulation inhibitors are also consumed in this process. Decreased inhibitor levels will permit more clotting so that a feedback system develops in which increased clotting leads to more clotting. At the same time, thrombocytopenia occurs because of the entrapment and consumption of platelets. Clotting factors are consumed in the development of multiple clots, which contributes to the bleeding seen with DIC.

Simultaneously, excess circulating thrombin assists in the conversion of plasminogen to plasmin, resulting in fibrinolysis. The breakdown of clots results in excess amounts 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 exhibit, 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.

Treatment

The only effective treatment is the reversal of the underlying cause. Anticoagulants are given exceedingly rarely when thrombus formation is likely to lead to imminent death (such as in coronary artery thrombosis or cerebrovascular thrombosis). Platelets may be transfused if counts are less than 5,000-10,000/mm3 and massive hemorrhage is occurring, and fresh frozen plasma may be administered in an attempt to replenish coagulation factors and anti-thrombotic factors, although these are only temporizing measures and may result in the increased development of thrombosis. Blood transfusion is the process of transferring Blood or blood-based products from one person into the Circulatory system of another Fresh Frozen Plasma ( FFP) is defined as the fluid portion of one unit of Human blood that has been centrifuged separated and frozen solid at -18° C (or colder

DIC results in lower fibrinogen levels (as it has all been converted to fibrin), and this can be tested for in the hospital lab. Fibrin (also called Factor Ia) is a Protein involved in the clotting of blood A medical laboratory or clinical laboratory is a Laboratory where tests are done on clinical specimens in order to get information about the Health A more specific test is for "fibrin split products" (FSPs) or "fibrin degradation products" (FDPs) which are produced when fibrin undergoes degradation when blood clots are dissolved by fibrinolysis. Fibrin degradation product (FDPs are components of the blood produced by Clot degeneration Fibrinolysis is the process wherein a Fibrin clot, the product of Coagulation, is broken down

In some situations, infusion with antithrombin may be necessary. Antithrombin (AT is a small protein molecule that inactivates several enzymes of the Coagulation system A new development is drotrecogin alfa (Xigris), a recombinant activated protein C product. Drotrecogin alfa (activated ( Xigris, marketed by Eli Lilly and Company) is a Recombinant form of human activated Protein C that has Protein C is a major physiological Anticoagulant. It is a Vitamin K -dependent Serine protease Enzyme ( that is activated by Thrombin Activated Protein C (APC) deactivates clotting factors V and VIII, and the presumed mechanism of action of drotrecogin is the cessation of the intravascular coagulation. Factor V is a Protein of the Coagulation system rarely referred to as proaccelerin or labile factor. Factor VIII (FVIII is an essential Clotting factor A deficiency of FVIII causes Hemophilia A, a bleeding disorder Due to its high cost and its severe adverse effects, it is only used strictly on indication in intensive care patients with severe sepsis. Intensive Care Medicine or critical care medicine is a branch of medicine concerned with the provision of Life support or organ support systems in patients [3] The large, multicenter ENHANCE trial provided more evidence that there may be a favorable benefit/risk ratio to administering activated protein C in adults[4], but was unable to make definitive conclusions about efficacy due to the lack of a placebo control, and particularly in children, there is a high risk of hemorrhage (27. 4% in patients aged 0-18 years)[5]

The prognosis for those with DIC, regardless of cause, is often grim, leading the initials to be known colloquially as "death is coming". [6]

References

  1. ^ Ledingham, J; D Warrell (2000). Concise Oxford Textbook of Medicine. Oxford University Press. ISBN 0-19-262870-4,.  
  2. ^ Rak J, Yu JL, Luyendyk J, Mackman N (2006). "Oncogenes, trousseau syndrome, and cancer-related changes in the coagulome of mice and humans". Cancer Res. 66 (22): 10643–6. doi:10.1158/0008-5472.CAN-06-2350. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 17108099.  
  3. ^ Dhainaut J, Yan S, Joyce D, Pettilä V, Basson B, Brandt J, Sundin D, Levi M (2004). "Treatment effects of drotrecogin alfa (activated) in patients with severe sepsis with or without overt disseminated intravascular coagulation. ". J Thromb Haemost 2 (11): 1924-33. doi:10.1111/j.1538-7836.2004.00955.x. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 15550023.  
  4. ^ Vincent JL, Bernard GR, Beale R, et al (2005). "Drotrecogin alfa (activated) treatment in severe sepsis from the global open-label trial ENHANCE: further evidence for survival and safety and implications for early treatment". Crit. Care Med. 33 (10): 2266–77. doi:10.1097/01.CCM.0000181729.46010.83. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 16215381.  
  5. ^ Goldstein B, Nadel S, Peters M, et al (2006). "ENHANCE: results of a global open-label trial of drotrecogin alfa (activated) in children with severe sepsis". Pediatr Crit Care Med 7 (3): 200–11. doi:10.1097/01.PCC.0000217470.68764.36. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 16575354.  
  6. ^ Norman K (2004). "Alternative treatments for disseminated intravascular coagulation. ". Drug News Perspect 17 (4): 243-50. doi:10.1358/dnp.2004.17.4.829051. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 15334173.  

See also

Sepsis is a serious medical condition characterized by a whole-body inflammatory state (called a Systemic inflammatory response syndrome or SIRS caused Septic shock is a very serious medical condition caused by decreased tissue perfusion and oxygen delivery as a result of Infection and Sepsis, though the
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