What is not associated with DIC -
Plasma fibrinogen levels are reduced due to consumption in microvascular coagulation by which intravascular clotting occurs. Reference to earlier comments on normal blood coagulation (Chapter 3) may be helpful at this point. It suffices here to recall that clotting can be initiated by either the extrinsic pathway, which is triggered by the release of tissue factor (tissue thromboplastin); or the intrinsic pathway, which involves the activation of factor XII by surface contact, collagen, or other negatively charged substances. Both pathways lead to the generation of throm- bin. Clotting normally is limited by the rapid clearance of activated clotting factors by the macrophages and the liver, endogenous anticoagulants (e.g., protein C), and the con- comitant activation of fibrinolysis. DIC usually is triggered by either (1) the release of tissue factor or thromboplastic substances into the circulation or (2) widespread endothelial cell damage (Fig. 11-28). Throm- boplastic substances can be released into the circulation from a variety of sources--for example, the placenta in obstetric complications or ceain types of cancer cells, paicularly those of acute promyelocytic leukemia and adenocarcino- mas. Cancer cells can also provoke coagulation in other ways, such as by releasing proteolytic enzymes and by expressing tissue factor. In gram-negative and gram-positive sepsis (impoant causes of DIC), endotoxins or exotoxins stimu- late the release of tissue factor from monocytes. Activated monocytes also release IL-1 and tumor necrosis factor, both of which stimulate the expression of tissue factor on endo- thelial cells and simultaneously decrease the expression of thrombomodulin. The latter, you may recall, activates protein C, an anticoagulant (Chapter 3). The net result of these alterations is the enhanced generation of thrombin and the blunting of inhibitory pathways that limit coagulation. Severe endothelial cell injury can initiate DIC by causing the release of tissue factor and by exposing subendothelial col- lagen and von Willebrand factor (vWF). However, even subtle forms of endothelial damage can unleash procoagulant activity by stimulating the increased expression of tissue factor on endothelial cell surfaces. Widespread endothelial injury can be produced by the deposition of antigen-antibody complexes (e.g., in systemic lupus erythematosus), by tem- perature extremes (e.g., after heat stroke or burn injury), or by infections (e.g., due to meningococci or rickettsiae). As discussed in Chapter 3, endothelial injury is an impoant consequence of endotoxemia, and, not surprisingly, DIC is a frequent complication of gram-negative sepsis. Disorders associated with DIC are listed in Table 11-12. Of these, DIC is most often associated with sepsis, obstetric complications, malignancy, and major trauma (especially trauma to the brain). The initiating events in these conditions are multiple and often interrelated. For example, in obstetric conditions, tissue factor derived from the placenta, retained dead fetus, or amniotic fluid enters the circulation; however, shock, hypoxia, and acidosis often coexist and can lead to widespread endothelial injury. Trauma to the brain releases fat and phospholipids, which act as contact factors and thereby activate the intrinsic arm of the coagulation cascade. Whatever the pathogenetic mechanism, DIC has two con- sequences. First, there is widespread fibrin deposition within the microcirculation. The associated obstruction leads to ischemia in the more severely affected or vulnerable organs and hemolysis as red cells are traumatized while passing through vessels narrowed by fibrin thrombi (micro- angiopathic hemolytic anemia). Second, a bleeding diathesis results from the depletion of platelets and clotting factors and the secondary release of plasminogen activators. Plasmin cleaves not only fibrin (fibrinolysis) but also factors V and VIII, thereby reducing their concentration fuher. In addition, fibrinolysis creates fibrin degradation products. These inhibit platelet aggregation, have antithrombin activity, and impair fibrin polymerization, all of which contribute to the hemostatic failure (Fig. 11-28). Reference: textbook of Pathology, 7th edition, Author :Harsha Mohan, page number 317 Ref Robbins 9/e pg 450
Thrombocytopenia
Increased PT
Hyperfibrinogenemia
Increased FDP
Haematology