Coagulacion Intravascular Diseminada

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  • DIC may cause tissue ischemia from occlusive microthrombi as well as bleeding from both the consumption of platelets and coagulation factors and the anticoagulant effect of products of secondary fibrinolysis.
  • Not all patients who had unequivocal clinical and laboratory signs of DIC had all these postmortem findings,15,25,27,30 and conversely, some patients in whom clinical and laboratory signs were not consistent with DIC did have the typical autopsy findings.15,26,27 and 28 This occasional lack of correlation between the clinical, laboratory, and pathologic findings still remains unexplained. Imagen: Rembrandt. Lección de anatomia. 1632.
  • The intravascular generation of substantial amounts of thrombin via the tissue factor pathway, combined with the failure of the natural blood coagulation inhibitory mechanisms, initiates DIC in most instances.
  • The intravascular generation of substantial amounts of thrombin via the tissue factor pathway, combined with the failure of the natural blood coagulation inhibitory mechanisms, initiates DIC in most instances.
  • The intravascular generation of substantial amounts of thrombin via the tissue factor pathway, combined with the failure of the natural blood coagulation inhibitory mechanisms, initiates DIC in most instances. The major clinical conditions causing DIC and the presumptive initiating pathways are shown in Fig. 126-1. Tissue factor is constitutively present in cell membranes of most tissues , including the media and adventitia of blood vessels. Under normal circumstances blood is not exposed to tissue factor. When, however, blood becomes exposed to tissues (e.g., with trauma, burns, or abruptio placentae) or cells foreign to blood enter the circulation (e.g., metastasis, leukemic cells, amniotic fluid embolism), the coagulation system is ignited. Tissue factor can also be generated and expressed on membranes of monocytes and endothelial cells during the systemic inflammatory response syndrome (SIRS). SIRS designates a series of inflammatory events arising from a variety of infections or other insults like burns, trauma, or autoimmune disorders.36,37 When bacteria are the cause of SIRS the severity of the syndrome can be graded as sepsis, severe sepsis, and septic shock,36 with stepwise increases in the rates of DIC, multiorgan dysfunction, and mortality. The complex events that occur during SIRS involve monocytes, endothelial cells, neutrophils, and platelets; interactions among these cells; cytokines and other mediators; and activation of the complement system.37 During these events, tissue factor can be generated and expressed by monocytes and by endothelial cells throughout the vasculature. In vitro studies and investigations of primates injected with live Escherichia coli and of humans injected with low doses of endotoxin have provided evidence that endotoxin can cause tissue factor exposure to blood by acting directly on monocytes and endothelial cells or by acting indirectly through monocyte secretion of tissue necrosis factor (TNF)-a, interleukin (IL)-1b, and IL-6.41,42 Platelets can also be activated by endotoxin,43 and activated platelets exhibiting P-selectin enhance tissue factor generation by monocytes.44 Additional effects of endotoxin and the cytokines released in response to endotoxin include (1) down-regulation of the two major physiological inhibitory mechanisms of coagulation, endothelial cell thrombomodulin,45 and glycosaminoglycans46; (2) brief enhancement of fibrinolysis by tissue plasminogen activator (t-PA) secretion from endothelial cells; and (3) longer-term profound inhibition of fibrinolysis caused by increased plasma concentrations of plasminogen activator inhibitor (PAI)-1.42 Initiation of DIC by activation of the contact system of coagulation during SIRS is probably unimportant. Thus, blockade of the contact system by a monoclonal antibody against factor XII does not prevent endotoxin-induced DIC,47 and only a modest increase in factor XIIaa is observed in patients with septic shock.48 In contrast, neutrophils become activated during SIRS and release elastase, which both injures the vessel wall49 and inactivates antithrombin.50 Less common initiators of DIC are: a cancer procoagulant that activates factor X, snake venoms that activate factor X or factor II, and activated coagulation factors that are variably contained in concentrates of coagulation factor IX and factor XI (see Infusion of Factor IX and Factor XI Concentrates, below). The widespread generation of thrombin induces deposition of fibrin, which leads to vessel obstruction and consumption of substantial amounts of hemostatic factors, i.e., platelets; fibrinogen; factors V, VIII, and others; protein C (PC); and antithrombin-III (AT-III). These events result in tissue ischemia, mild microangiopathic hemolytic anemia, bleeding, and further impairment of the control mechanism of coagulation. The intravascular thrombi and thrombin itself51 trigger secretion of t-PA from endothelial cells, which sets off compensatory thrombolysis; this, if successful, leads to reopening of the occluded blood vessels. The by-products of thrombolysis, fibrin/fibrinogen degradation products, may, however, further enhance bleeding by interfering with platelet aggregation, fibrin polymerization, and thrombin activity (see Fig. 126-1).
  • In vitro studies and investigations of primates injected with live Escherichia coli and of humans injected with low doses of endotoxin have provided evidence that endotoxin can cause tissue factor exposure to blood by acting directly on monocytes and endothelial cells or by acting indirectly through monocyte secretion of tissue necrosis factor (TNF)-a, interleukin (IL)-1b, and IL-6.41,42 Platelets can also be activated by endotoxin,43 and activated platelets exhibiting P-selectin enhance tissue factor generation by monocytes.44 Additional effects of endotoxin and the cytokines released in response to endotoxin include (1) down-regulation of the two major physiological inhibitory mechanisms of coagulation, endothelial cell thrombomodulin,45 and glycosaminoglycans46; (2) brief enhancement of fibrinolysis by tissue plasminogen activator (t-PA) secretion from endothelial cells; and (3) longer-term profound inhibition of fibrinolysis caused by increased plasma concentrations of plasminogen activator inhibitor (PAI)-1.42 Initiation of DIC by activation of the contact system of coagulation during SIRS is probably unimportant. Thus, blockade of the contact system by a monoclonal antibody against factor XII does not prevent endotoxin-induced DIC,47 and only a modest increase in factor XIIaa is observed in patients with septic shock.48 In contrast, neutrophils become activated during SIRS and release elastase, which both injures the vessel wall49 and inactivates antithrombin.50 Less common initiators of DIC are: a cancer procoagulant that activates factor X, snake venoms that activate factor X or factor II, and activated coagulation factors that are variably contained in concentrates of coagulation factor IX and factor XI (see Infusion of Factor IX and Factor XI Concentrates, below). The widespread generation of thrombin induces deposition of fibrin, which leads to vessel obstruction and consumption of substantial amounts of hemostatic factors, i.e., platelets; fibrinogen; factors V, VIII, and others; protein C (PC); and antithrombin-III (AT-III). These events result in tissue ischemia, mild microangiopathic hemolytic anemia, bleeding, and further impairment of the control mechanism of coagulation. The intravascular thrombi and thrombin itself51 trigger secretion of t-PA from endothelial cells, which sets off compensatory thrombolysis; this, if successful, leads to reopening of the occluded blood vessels. The by-products of thrombolysis, fibrin/fibrinogen degradation products, may, however, further enhance bleeding by interfering with platelet aggregation, fibrin polymerization, and thrombin activity (see Fig. 126-1).
  • In vitro studies and investigations of primates injected with live Escherichia coli and of humans injected with low doses of endotoxin have provided evidence that endotoxin can cause tissue factor exposure to blood by acting directly on monocytes and endothelial cells or by acting indirectly through monocyte secretion of tissue necrosis factor (TNF)-a, interleukin (IL)-1b, and IL-6.41,42 Platelets can also be activated by endotoxin,43 and activated platelets exhibiting P-selectin enhance tissue factor generation by monocytes.44 Additional effects of endotoxin and the cytokines released in response to endotoxin include (1) down-regulation of the two major physiological inhibitory mechanisms of coagulation, endothelial cell thrombomodulin,45 and glycosaminoglycans46; (2) brief enhancement of fibrinolysis by tissue plasminogen activator (t-PA) secretion from endothelial cells; and (3) longer-term profound inhibition of fibrinolysis caused by increased plasma concentrations of plasminogen activator inhibitor (PAI)-1.42 Initiation of DIC by activation of the contact system of coagulation during SIRS is probably unimportant. Thus, blockade of the contact system by a monoclonal antibody against factor XII does not prevent endotoxin-induced DIC,47 and only a modest increase in factor XIIaa is observed in patients with septic shock.48 In contrast, neutrophils become activated during SIRS and release elastase, which both injures the vessel wall49 and inactivates antithrombin.50 Less common initiators of DIC are: a cancer procoagulant that activates factor X, snake venoms that activate factor X or factor II, and activated coagulation factors that are variably contained in concentrates of coagulation factor IX and factor XI (see Infusion of Factor IX and Factor XI Concentrates, below). The widespread generation of thrombin induces deposition of fibrin, which leads to vessel obstruction and consumption of substantial amounts of hemostatic factors, i.e., platelets; fibrinogen; factors V, VIII, and others; protein C (PC); and antithrombin-III (AT-III). These events result in tissue ischemia, mild microangiopathic hemolytic anemia, bleeding, and further impairment of the control mechanism of coagulation. The intravascular thrombi and thrombin itself51 trigger secretion of t-PA from endothelial cells, which sets off compensatory thrombolysis; this, if successful, leads to reopening of the occluded blood vessels. The by-products of thrombolysis, fibrin/fibrinogen degradation products, may, however, further enhance bleeding by interfering with platelet aggregation, fibrin polymerization, and thrombin activity (see Fig. 126-1).
  • Less common initiators of DIC are: a cancer procoagulant that activates factor X, snake venoms that activate factor X or factor II, and activated coagulation factors that are variably contained in concentrates of coagulation factor IX and factor XI (see Infusion of Factor IX and Factor XI Concentrates, below).
  • The widespread generation of thrombin induces deposition of fibrin, which leads to vessel obstruction and consumption of substantial amounts of hemostatic factors, i.e., platelets; fibrinogen; factors V, VIII, and others; protein C (PC); and antithrombin-III (AT-III). These events result in tissue ischemia, mild microangiopathic hemolytic anemia, bleeding, and further impairment of the control mechanism of coagulation. The intravascular thrombi and thrombin itself51 trigger secretion of t-PA from endothelial cells, which sets off compensatory thrombolysis; this, if successful, leads to reopening of the occluded blood vessels. The by-products of thrombolysis, fibrin/fibrinogen degradation products, may, however, further enhance bleeding by interfering with platelet aggregation, fibrin polymerization, and thrombin activity (see Fig. 126-1).
  • The widespread generation of thrombin induces deposition of fibrin, which leads to vessel obstruction and consumption of substantial amounts of hemostatic factors, i.e., platelets; fibrinogen; factors V, VIII, and others; protein C (PC); and antithrombin-III (AT-III). These events result in tissue ischemia, mild microangiopathic hemolytic anemia, bleeding, and further impairment of the control mechanism of coagulation. The intravascular thrombi and thrombin itself51 trigger secretion of t-PA from endothelial cells, which sets off compensatory thrombolysis; this, if successful, leads to reopening of the occluded blood vessels. The by-products of thrombolysis, fibrin/fibrinogen degradation products, may, however, further enhance bleeding by interfering with platelet aggregation, fibrin polymerization, and thrombin activity (see Fig. 126-1).
  • The widespread generation of thrombin induces deposition of fibrin, which leads to vessel obstruction and consumption of substantial amounts of hemostatic factors, i.e., platelets; fibrinogen; factors V, VIII, and others; protein C (PC); and antithrombin-III (AT-III). These events result in tissue ischemia, mild microangiopathic hemolytic anemia, bleeding, and further impairment of the control mechanism of coagulation. The intravascular thrombi and thrombin itself51 trigger secretion of t-PA from endothelial cells, which sets off compensatory thrombolysis; this, if successful, leads to reopening of the occluded blood vessels. The by-products of thrombolysis, fibrin/fibrinogen degradation products, may, however, further enhance bleeding by interfering with platelet aggregation, fibrin polymerization, and thrombin activity (see Fig. 126-1).
  • The intravascular thrombi and thrombin itself51 trigger secretion of t-PA from endothelial cells, which sets off compensatory thrombolysis; this, if successful, leads to reopening of the occluded blood vessels. The by-products of thrombolysis, fibrin/fibrinogen degradation products, may, however, further enhance bleeding by interfering with platelet aggregation, fibrin polymerization, and thrombin activity (see Fig. 126-1).
  • Several protective mechanisms either neutralize components that initiate DIC or correct its deleterious consequences. Thrombin generated in DIC can be effectively removed by the enormous endothelial cell surface area of the microcirculation by means of forming a complex with AT-III, which is bound to endothelial heparan sulfate,52 and by binding to thrombomodulin on the endothelial surface. The latter interaction abolishes thrombin's procoagulant effects on fibrinogen, factor XIII, and platelets, while enhancing activation of the anticoagulant protein PC. Activated PC, in turn, inactivates factors Va and VIIIa in the presence of protein S (PS) and exerts a profibrinolytic effect by inhibiting activation of thrombin activatable fibrinolysis inhibitor (TAFI).53 Tissue factor pathway inhibitor (TFPI) is another line of defense at the vessel wall, although its effect is only exerted when relatively small amounts of tissue factor gain access to the circulation.54 Thrombin binding to endothelial cells also stimulates the release of t-PA, thereby enhancing fibrinolysis.51 Thus, as long as blood flow through the microcirculation is maintained, there is effective neutralization of procoagulant material, unless overwhelming amounts have entered the circulation. The control mechanisms may be seriously compromised by the underlying disease that initiated the DIC. For example, leukemias may deplete or suppress the megakaryocyte pool, hepatic disease may impair both the synthetic and clearance functions of the liver, or shock may decrease neutralization of thrombin by decreasing blood flow through the microcirculation.
  • The manifestations of DIC depend on the magnitude and rate of exposure of blood to the DIC trigger. For example, the dramatic cases of “acute” DIC, characterized by severe bleeding due to excessive consumption of hemostatic components, may develop when blood is exposed to large amounts of tissue factor over a brief period of time. Such a trigger overwhelms the control mechanisms before any compensatory mechanisms have had enough time to respond. Alternatively, “chronic” DIC develops when blood is continuously or intermittently exposed to small amounts of tissue factor.
  • Numerous disorders can provoke DIC (see Fig. 126-1), but only a few constitute major causes, as can be inferred from retrospective clinical studies.4,7,10,12,14,15 and 16 Infectious diseases and malignant disorders together account for about two-thirds of the DIC cases in the major series, except for one study7 that included a disproportionately large number of obstetric cases
  • Acute DIC is frequently heralded by hemorrhage into the skin at multiple sites.4,10 Petechiae, ecchymoses, and oozing from venipunctures, arterial lines, catheters, and injured tissues are common. Bleeding may also occur on mucosal surfaces. Hemorrhage may be life threatening, with massive bleeding into the gastrointestinal tract,10 lungs,4 central nervous system, or orbit.7 Patients with chronic DIC usually exhibit only minor skin and mucosal bleeding.
  • Knowledge of the potential underlying disorders can lead to early detection of acute and chronic DIC. Laboratory tests confirm or exclude a presumptive diagnosis of DIC, discriminate acute from chronic DIC, and distinguish between DIC associated with secondary fibrinolysis and primary fibrinogenolysis. They may also provide guidelines for treatment, help monitor therapy, and provide predictive information with regard to mortality.10,18 The underlying diseases themselves, however, may affect the laboratory findings. For example, impairment of hemostasis, and/or thrombocytopenia unrelated to DIC, can arise from hepatic disease and from marrow involvement by leukemia; impaired hemostasis may also occur normally in the neonatal period. Conversely, the elevated levels of some hemostatic components that are normally observed during pregnancy may obscure the presence of DIC. These limitations in laboratory diagnosis of DIC can be overcome by repeating the tests every 6 to 8 h and observing the dynamics of the process. Patients with acute DIC are critically ill, and therefore rapid diagnosis is essential. The following tests are adequate: platelet count, prothrombin time (PT), activated partial thromboplastin time (aPTT), D-dimer, thrombin time (TT), fibrinogen level, fibrinogen degradation products (FDP), and a blood film to check for fragmented red cells. These parameters will reflect the extent of consumption of hemostatic components, the presence of by-products of in vivo thrombin generation, and the extent of secondary fibrinolysis. In most instances, changes in three or more parameters in addition to a decreased platelet count are consistent with DIC, and no further tests are necessary. A normal fibrinogen level may, however, be present relatively early in DIC since many of the underlying disorders are associated with increased fibrinogen levels, and thus the increased fibrinogen consumption may not have had sufficient time to decrease the fibrinogen below normal levels. Since the normal fibrinogen half-life time is approximately 4 days, a 50 percent or greater decrease in fibrinogen level over a 1-day period is compelling evidence supporting DIC or fibrinolysis, regardless of whether the final value is within the normal range.
  • Knowledge of the potential underlying disorders can lead to early detection of acute and chronic DIC. Laboratory tests confirm or exclude a presumptive diagnosis of DIC, discriminate acute from chronic DIC, and distinguish between DIC associated with secondary fibrinolysis and primary fibrinogenolysis. They may also provide guidelines for treatment, help monitor therapy, and provide predictive information with regard to mortality.10,18 The underlying diseases themselves, however, may affect the laboratory findings. For example, impairment of hemostasis, and/or thrombocytopenia unrelated to DIC, can arise from hepatic disease and from marrow involvement by leukemia; impaired hemostasis may also occur normally in the neonatal period. Conversely, the elevated levels of some hemostatic components that are normally observed during pregnancy may obscure the presence of DIC. These limitations in laboratory diagnosis of DIC can be overcome by repeating the tests every 6 to 8 h and observing the dynamics of the process. Patients with acute DIC are critically ill, and therefore rapid diagnosis is essential. The following tests are adequate: platelet count, prothrombin time (PT), activated partial thromboplastin time (aPTT), D-dimer, thrombin time (TT), fibrinogen level, fibrinogen degradation products (FDP), and a blood film to check for fragmented red cells. These parameters will reflect the extent of consumption of hemostatic components, the presence of by-products of in vivo thrombin generation, and the extent of secondary fibrinolysis. In most instances, changes in three or more parameters in addition to a decreased platelet count are consistent with DIC, and no further tests are necessary. A normal fibrinogen level may, however, be present relatively early in DIC since many of the underlying disorders are associated with increased fibrinogen levels, and thus the increased fibrinogen consumption may not have had sufficient time to decrease the fibrinogen below normal levels. Since the normal fibrinogen half-life time is approximately 4 days, a 50 percent or greater decrease in fibrinogen level over a 1-day period is compelling evidence supporting DIC or fibrinolysis, regardless of whether the final value is within the normal range.
  • Knowledge of the potential underlying disorders can lead to early detection of acute and chronic DIC. Laboratory tests confirm or exclude a presumptive diagnosis of DIC, discriminate acute from chronic DIC, and distinguish between DIC associated with secondary fibrinolysis and primary fibrinogenolysis. They may also provide guidelines for treatment, help monitor therapy, and provide predictive information with regard to mortality.10,18 The underlying diseases themselves, however, may affect the laboratory findings. For example, impairment of hemostasis, and/or thrombocytopenia unrelated to DIC, can arise from hepatic disease and from marrow involvement by leukemia; impaired hemostasis may also occur normally in the neonatal period. Conversely, the elevated levels of some hemostatic components that are normally observed during pregnancy may obscure the presence of DIC. These limitations in laboratory diagnosis of DIC can be overcome by repeating the tests every 6 to 8 h and observing the dynamics of the process. Patients with acute DIC are critically ill, and therefore rapid diagnosis is essential. The following tests are adequate: platelet count, prothrombin time (PT), activated partial thromboplastin time (aPTT), D-dimer, thrombin time (TT), fibrinogen level, fibrinogen degradation products (FDP), and a blood film to check for fragmented red cells. These parameters will reflect the extent of consumption of hemostatic components, the presence of by-products of in vivo thrombin generation, and the extent of secondary fibrinolysis. In most instances, changes in three or more parameters in addition to a decreased platelet count are consistent with DIC, and no further tests are necessary. A normal fibrinogen level may, however, be present relatively early in DIC since many of the underlying disorders are associated with increased fibrinogen levels, and thus the increased fibrinogen consumption may not have had sufficient time to decrease the fibrinogen below normal levels. Since the normal fibrinogen half-life time is approximately 4 days, a 50 percent or greater decrease in fibrinogen level over a 1-day period is compelling evidence supporting DIC or fibrinolysis, regardless of whether the final value is within the normal range.
  • Knowledge of the potential underlying disorders can lead to early detection of acute and chronic DIC. Laboratory tests confirm or exclude a presumptive diagnosis of DIC, discriminate acute from chronic DIC, and distinguish between DIC associated with secondary fibrinolysis and primary fibrinogenolysis. They may also provide guidelines for treatment, help monitor therapy, and provide predictive information with regard to mortality.10,18 The underlying diseases themselves, however, may affect the laboratory findings. For example, impairment of hemostasis, and/or thrombocytopenia unrelated to DIC, can arise from hepatic disease and from marrow involvement by leukemia; impaired hemostasis may also occur normally in the neonatal period. Conversely, the elevated levels of some hemostatic components that are normally observed during pregnancy may obscure the presence of DIC. These limitations in laboratory diagnosis of DIC can be overcome by repeating the tests every 6 to 8 h and observing the dynamics of the process. Patients with acute DIC are critically ill, and therefore rapid diagnosis is essential. The following tests are adequate: platelet count, prothrombin time (PT), activated partial thromboplastin time (aPTT), D-dimer, thrombin time (TT), fibrinogen level, fibrinogen degradation products (FDP), and a blood film to check for fragmented red cells. These parameters will reflect the extent of consumption of hemostatic components, the presence of by-products of in vivo thrombin generation, and the extent of secondary fibrinolysis. In most instances, changes in three or more parameters in addition to a decreased platelet count are consistent with DIC, and no further tests are necessary. A normal fibrinogen level may, however, be present relatively early in DIC since many of the underlying disorders are associated with increased fibrinogen levels, and thus the increased fibrinogen consumption may not have had sufficient time to decrease the fibrinogen below normal levels. Since the normal fibrinogen half-life time is approximately 4 days, a 50 percent or greater decrease in fibrinogen level over a 1-day period is compelling evidence supporting DIC or fibrinolysis, regardless of whether the final value is within the normal range.
  • Knowledge of the potential underlying disorders can lead to early detection of acute and chronic DIC. Laboratory tests confirm or exclude a presumptive diagnosis of DIC, discriminate acute from chronic DIC, and distinguish between DIC associated with secondary fibrinolysis and primary fibrinogenolysis. They may also provide guidelines for treatment, help monitor therapy, and provide predictive information with regard to mortality.10,18 The underlying diseases themselves, however, may affect the laboratory findings. For example, impairment of hemostasis, and/or thrombocytopenia unrelated to DIC, can arise from hepatic disease and from marrow involvement by leukemia; impaired hemostasis may also occur normally in the neonatal period. Conversely, the elevated levels of some hemostatic components that are normally observed during pregnancy may obscure the presence of DIC. These limitations in laboratory diagnosis of DIC can be overcome by repeating the tests every 6 to 8 h and observing the dynamics of the process. Patients with acute DIC are critically ill, and therefore rapid diagnosis is essential. The following tests are adequate: platelet count, prothrombin time (PT), activated partial thromboplastin time (aPTT), D-dimer, thrombin time (TT), fibrinogen level, fibrinogen degradation products (FDP), and a blood film to check for fragmented red cells. These parameters will reflect the extent of consumption of hemostatic components, the presence of by-products of in vivo thrombin generation, and the extent of secondary fibrinolysis. In most instances, changes in three or more parameters in addition to a decreased platelet count are consistent with DIC, and no further tests are necessary. A normal fibrinogen level may, however, be present relatively early in DIC since many of the underlying disorders are associated with increased fibrinogen levels, and thus the increased fibrinogen consumption may not have had sufficient time to decrease the fibrinogen below normal levels. Since the normal fibrinogen half-life time is approximately 4 days, a 50 percent or greater decrease in fibrinogen level over a 1-day period is compelling evidence supporting DIC or fibrinolysis, regardless of whether the final value is within the normal range.
  • No controlled studies of patients with DIC have been performed. Such studies are difficult to carry out in view of the variabilities in DIC triggers, clinical presentations, and grades of severity. Fig. 126-2 shows general guidelines for management of patients with DIC, but decisions regarding treatment must be individualized after all clinically important aspects have been carefully considered. The success of management is related to taking rapid, vigorous measures against the underlying disease; close clinical observation; thoughtful consideration in each individual patient; availability of 24-h coagulation laboratory services; and an adequate supply of platelet concentrates, cryoprecipitate, fresh-frozen plasma, and packed red cells for replacement therapy. Heparin, when indicated, should be administered by continuous infusion
  • No controlled studies of patients with DIC have been performed. Such studies are difficult to carry out in view of the variabilities in DIC triggers, clinical presentations, and grades of severity. Fig. 126-2 shows general guidelines for management of patients with DIC, but decisions regarding treatment must be individualized after all clinically important aspects have been carefully considered. The success of management is related to taking rapid, vigorous measures against the underlying disease; close clinical observation; thoughtful consideration in each individual patient; availability of 24-h coagulation laboratory services; and an adequate supply of platelet concentrates, cryoprecipitate, fresh-frozen plasma, and packed red cells for replacement therapy. Heparin, when indicated, should be administered by continuous infusion.
  • No controlled studies of patients with DIC have been performed. Such studies are difficult to carry out in view of the variabilities in DIC triggers, clinical presentations, and grades of severity. Fig. 126-2 shows general guidelines for management of patients with DIC, but decisions regarding treatment must be individualized after all clinically important aspects have been carefully considered. The success of management is related to taking rapid, vigorous measures against the underlying disease; close clinical observation; thoughtful consideration in each individual patient; availability of 24-h coagulation laboratory services; and an adequate supply of platelet concentrates, cryoprecipitate, fresh-frozen plasma, and packed red cells for replacement therapy. Heparin, when indicated, should be administered by continuous infusion
  • In most clinical circumstances, patients with DIC are seen when the process is already well established. None of the clinical reports has shown a reduction in mortality in patients with DIC treated with heparin; heparin has, at best, improved the levels of hemostatic factors in the treated patients.68 In contrast, heparin administration can seriously aggravate bleeding in such patients,9,11 especially when the patients have severe hemostatic failure due to consumption and when there is hepatic or renal dysfunction. Moreover, heparin can exacerbate bleeding from sites of traumatic injury. Heparin may, in fact, have reduced anticoagulant effect in DIC, since AT-III is commonly depleted and fibrin monomers, which are produced during DIC, protect thrombin from inactivation by heparin-AT-III complex.69 Notwithstanding these considerations, administration of heparin is beneficial in some categories of chronic DIC, e.g., metastatic carcinomas, purpura fulminans, dead fetus syndrome (at time of removal), and aortic aneurysm (prior to resection). Heparin is also indicated for treating thromboembolic complications in large vessels and before surgery in patients with chronic DIC (see Fig. 126-2). Heparin administration may also be helpful in patients with acute DIC when intensive blood component replacement fails to improve excessive bleeding, or when thrombosis threatens to cause irreversible tissue injury (e.g., acute cortical necrosis of the kidney or digital gangrene). Heparin should be used cautiously in all the above conditions. In chronic DIC a continuous infusion of heparin, 500 to 750 U/h without a bolus injection, may be sufficient. If no response is obtained within 24 h, escalating dosages can be used. In hyperacute DIC cases, such as mismatched transfusion, amniotic fluid embolism, septic abortion, and purpura fulminans, an intravenous bolus injection of 5000 to 10,000 units of heparin may be given simultaneously with replacement therapy with blood products; some experts would not give a bolus dose of heparin even under these circumstances. A continuous infusion of 500 to 1000 U/h of heparin may be necessary to maintain the benefit until the underlying disease responds to treatment.
  • AT-III concentrate infusion has been used in the treatment of patients with DIC, either alone or in combination with heparin,70,71 but only small numbers of patients have been studied. In one double-blind controlled study of patients with DIC and septic shock, large doses of AT-III concentrate caused a shortening of the duration of DIC and lowered the mortality by 44 percent, but this decline did not reach statistical significance.72 Two additional trials that await completion show similar trends.73 Thus, no definitive recommendations regarding the clinical use of AT-III concentrate can be made at present.
  • Patients with DIC should not be treated with antifibrinolytic agents like e-aminocaproic acid or tranexamic acid since these drugs block the secondary fibrinolysis that accompanies DIC and presumably helps to preserve tissue perfusion. Indeed, the use of these agents in patients with DIC has been complicated by severe thrombosis.74,75 A different situation prevails in patients with DIC accompanied by primary fibrino(geno)lysis, as in some cases of acute promyelocytic leukemia, giant hemangioma, heat stroke, amniotic fluid embolism, some forms of liver disease, and metastatic carcinoma of the prostate. In these conditions the use of fibrinolytic inhibitors can be considered, provided that (1) the patient is bleeding profusely and has not responded to replacement therapy; and (2) excessive fibrino(geno)lysis is observed, i.e., rapid whole blood clot lysis or a very short euglobulin lysis time. In such circumstances the use of antifibrinolytic agents should be preceded by replacement of depleted blood components and continuous heparin infusion.
  • Coagulacion Intravascular Diseminada

    1. 1. Dr. Héctor U. Cuevas Castillejos
    2. 2. <ul><li>Síndrome clinicopatológico en el cual ocurre coagulación masiva inducida por procoagulantes introducidos o producidos en la circulación sanguínea y sobrepasan los mecanismos anticoagulantes naturales. </li></ul>Coagulación intravascular diseminada Williams Hematology 6th edition (November 28, 2000). Beutler , Lichtman, Coller. McGraw-Hill
    3. 3. <ul><li>Síndrome clinicopatológico en el cual ocurre coagulación masiva inducida por procoagulantes introducidos o producidos en la circulación sanguínea y sobrepasan los mecanismos anticoagulantes naturales. </li></ul>Coagulación intravascular diseminada Williams Hematology 6th edition (November 28, 2000). Beutler , Lichtman, Coller. McGraw-Hill
    4. 4. <ul><li>Puede producir </li></ul><ul><ul><li>Isquemia </li></ul></ul><ul><ul><li>Hemorragia </li></ul></ul>Coagulación intravascular diseminada Furie B, Mechanisms of Thrombus Formation. N Engl J Med 359:938, August 28, 2008 Review Article — Mechanisms of Disease
    5. 5. <ul><li>Patología </li></ul><ul><ul><li>Sangrado multiorgánico difuso </li></ul></ul><ul><ul><li>Necrosis hemorrágica </li></ul></ul><ul><ul><li>Microtrombos en vasos sanguíneos de pequeño calibre </li></ul></ul><ul><ul><li>Trombos en vasos sanguíneos de mediano y gran calibre </li></ul></ul>Coagulación intravascular diseminada Williams Hematology 6th edition (November 28, 2000). Beutler , Lichtman, Coller. McGraw-Hill
    6. 6. <ul><li>Los órganos más frecuentemente afectados por microtrombos difusos: </li></ul>Coagulación intravascular diseminada Moake JL. Thrombotic Microangiopathies N Engl J Med 347:589, August 22, 2002 Review Article <ul><ul><li>Bazo </li></ul></ul><ul><ul><li>Suprarrenales </li></ul></ul><ul><ul><li>Páncreas </li></ul></ul><ul><ul><li>Intestino </li></ul></ul><ul><ul><li>Pulmones </li></ul></ul><ul><ul><li>Riñones </li></ul></ul><ul><ul><li>Cerebro </li></ul></ul><ul><ul><li>Corazón </li></ul></ul><ul><ul><li>Hígado </li></ul></ul>
    7. 7. Coagulación intravascular diseminada <ul><ul><li>Bazo </li></ul></ul><ul><ul><li>Suprarrenales </li></ul></ul><ul><ul><li>Páncreas </li></ul></ul><ul><ul><li>Intestino </li></ul></ul><ul><ul><li>Pulmones </li></ul></ul><ul><ul><li>Riñones </li></ul></ul><ul><ul><li>Cerebro </li></ul></ul><ul><ul><li>Corazón </li></ul></ul><ul><ul><li>Hígado </li></ul></ul><ul><li>Los órganos más frecuentemente afectados por microtrombos difusos: </li></ul>Moake JL. Thrombotic Microangiopathies N Engl J Med 347:589, August 22, 2002 Review Article
    8. 8. <ul><li>Patogénesis </li></ul><ul><ul><li>Trombina – Vía del Factor Tisular </li></ul></ul><ul><ul><li>Falla de los mecanismos inhibitorios de coagulación </li></ul></ul>Coagulación intravascular diseminada Williams Hematology 6th edition (November 28, 2000). Beutler , Lichtman, Coller. McGraw-Hill
    9. 9. <ul><li>Patogénesis </li></ul><ul><ul><li>Trombina – Vía del Factor Tisular </li></ul></ul><ul><ul><li>Falla de los mecanismos inhibitorios de coagulación </li></ul></ul>Coagulación intravascular diseminada Williams Hematology 6th edition (November 28, 2000). Beutler , Lichtman, Coller. McGraw-Hill
    10. 11. <ul><li>Activación del Factor Tisular: </li></ul><ul><ul><li>Antígenos internos </li></ul></ul><ul><ul><ul><li>Trauma, quemaduras, abruptio placentae </li></ul></ul></ul><ul><ul><li>Antígenos externos </li></ul></ul><ul><ul><ul><li>Metástasis, células leucémicas, embolismo de líquido amniótico </li></ul></ul></ul><ul><ul><li>SRIS </li></ul></ul><ul><ul><ul><li>Monocitos, células endoteliales </li></ul></ul></ul><ul><ul><li>Sepsis </li></ul></ul>Coagulación intravascular diseminada Rutherford CJ. Consultative Hemostasis and Thrombosis N Engl J Med 348:1072, March 13, 2003 Book Review
    11. 12. <ul><li>Efectos de Endotoxinas: </li></ul><ul><ul><li>Activación de FNT-alfa, IL 1-b, IL-6 </li></ul></ul><ul><ul><li>Regulación a la baja de los dos principales mecanismos inhibitorios de la coagulación </li></ul></ul><ul><ul><ul><li>Trombomodulina de células endoteliales </li></ul></ul></ul><ul><ul><ul><li>Glucosaminoglicanos </li></ul></ul></ul>Coagulación intravascular diseminada Rutherford CJ. Consultative Hemostasis and Thrombosis N Engl J Med 348:1072, March 13, 2003 Book Review
    12. 13. <ul><li>Efectos de Endotoxinas: </li></ul><ul><ul><li>Incremento transitorio de la fibrinolisis mediante activador del plasminógeno tisular (t-PA) </li></ul></ul><ul><ul><li>Inhibición persistente de la fibrinolisis por concentraciones elevadas del inhibidor del activador del plasminógeno </li></ul></ul>Coagulación intravascular diseminada Rutherford CJ. Consultative Hemostasis and Thrombosis N Engl J Med 348:1072, March 13, 2003 Book Review
    13. 14. <ul><li>Activadores menos frecuentes de la CID: </li></ul><ul><ul><li>Procoagulante neoplásico (activa el factor X) </li></ul></ul><ul><ul><li>Veneno de serpientes (activan el factor X o el II) </li></ul></ul><ul><ul><li>Factores de coagulación activados presentes en cantidades variables en los concentrados de factor IX y XI </li></ul></ul>Coagulación intravascular diseminada Williams Hematology 6th edition (November 28, 2000). Beutler , Lichtman, Coller. McGraw-Hill
    14. 15. Coagulación intravascular diseminada
    15. 16. Coagulación intravascular diseminada <ul><ul><li>Obstrucción vascular </li></ul></ul><ul><ul><li>Consumo de factores de la coagulación, fibrinógeno, factores V, VIII, Proteína C y Antitrombina III. </li></ul></ul>
    16. 17. Coagulación intravascular diseminada <ul><li>Isquemia tisular </li></ul><ul><li>Anemia hemolítica microangiopática leve </li></ul><ul><li>Sangrado </li></ul><ul><ul><li>Obstrucción vascular </li></ul></ul><ul><ul><li>Consumo de factores de la coagulación, fibrinógeno, factores V, VIII, Proteína C y Antitrombina III. </li></ul></ul>
    17. 18. Coagulación intravascular diseminada Williams Hematology 6th edition (November 28, 2000). Beutler , Lichtman, Coller. McGraw-Hill
    18. 19. <ul><li>Mecanismos de Control </li></ul><ul><ul><li>Área de superficie endotelial </li></ul></ul><ul><ul><li>Unión con AT-III </li></ul></ul><ul><ul><ul><li>Heparan sulfato </li></ul></ul></ul><ul><ul><ul><li>Trombomodulina </li></ul></ul></ul><ul><ul><li>Inhibidor del factor tisular </li></ul></ul>Coagulación intravascular diseminada Rutherford CJ. Consultative Hemostasis and Thrombosis N Engl J Med 348:1072, March 13, 2003 Book Review
    19. 20. <ul><li>Manifestaciones clínicas dependen de: </li></ul><ul><ul><li>Magnitud </li></ul></ul><ul><ul><li>Tiempo de exposición con el estímulo desencadenante </li></ul></ul>Coagulación intravascular diseminada Williams Hematology 6th edition (November 28, 2000). Beutler , Lichtman, Coller. McGraw-Hill
    20. 21. Williams Hematology 6th edition (November 28, 2000). Beutler , Lichtman, Coller. McGraw-Hill Infecciones Neoplasias Patologías Obstétricas
    21. 22. <ul><li>Manifestaciones clínicas </li></ul><ul><ul><li>Sangrado </li></ul></ul><ul><ul><li>Trombosis / Tromboembolismo </li></ul></ul><ul><ul><li>Shock </li></ul></ul><ul><ul><li>Insuficiencia Renal </li></ul></ul><ul><ul><li>Insuficiencia Hepática </li></ul></ul><ul><ul><li>Insuficiencia Pulmonar </li></ul></ul>Coagulación intravascular diseminada Williams Hematology 6th edition (November 28, 2000). Beutler , Lichtman, Coller. McGraw-Hill
    22. 23. <ul><li>Laboratorio </li></ul><ul><ul><li>Recuento plaquetario </li></ul></ul><ul><ul><li>TP </li></ul></ul><ul><ul><li>TPT </li></ul></ul><ul><ul><li>Dimero D </li></ul></ul><ul><ul><li>TT </li></ul></ul><ul><ul><li>Fibrinógeno </li></ul></ul><ul><ul><li>Productos degradación del fibrinógeno </li></ul></ul><ul><ul><li>Frotis </li></ul></ul>Coagulación intravascular diseminada Williams Hematology 6th edition (November 28, 2000). Beutler , Lichtman, Coller. McGraw-Hill
    23. 24. Coagulación intravascular diseminada Williams Hematology 6th edition (November 28, 2000). Beutler , Lichtman, Coller. McGraw-Hill Cambios en tres o más parámetros + trombocitopenia = CID <ul><li>Laboratorio </li></ul><ul><ul><li>Recuento plaquetario </li></ul></ul><ul><ul><li>TP </li></ul></ul><ul><ul><li>TPT </li></ul></ul><ul><ul><li>Dimero D </li></ul></ul><ul><ul><li>TT </li></ul></ul><ul><ul><li>Fibrinógeno </li></ul></ul><ul><ul><li>Productos degradación del fibrinógeno </li></ul></ul><ul><ul><li>Frotis </li></ul></ul>
    24. 25. <ul><li>Laboratorio </li></ul><ul><ul><li>Confirma o excluye el diagnóstico </li></ul></ul><ul><ul><li>CID aguda o crónica </li></ul></ul><ul><ul><li>CID con fibrinolisis primaria o secundaria </li></ul></ul>Coagulación intravascular diseminada Williams Hematology 6th edition (November 28, 2000). Beutler , Lichtman, Coller. McGraw-Hill
    25. 26. <ul><li>Alteraciones de la hemostasia y/o trombocitopenia no relacionadas a CID: </li></ul><ul><ul><li>Enfermedad hepática, infiltración a médula ósea </li></ul></ul><ul><ul><li>Neonatos </li></ul></ul><ul><ul><li>Embarazo </li></ul></ul>Coagulación intravascular diseminada Williams Hematology 6th edition (November 28, 2000). Beutler , Lichtman, Coller. McGraw-Hill
    26. 27. <ul><li>Alteraciones de la hemostasia y/o trombocitopenia no relacionadas a CID: </li></ul><ul><ul><li>Enfermedad hepática, infiltración a médula ósea </li></ul></ul><ul><ul><li>Neonatos </li></ul></ul><ul><ul><li>Embarazo </li></ul></ul>Coagulación intravascular diseminada Williams Hematology 6th edition (November 28, 2000). Beutler , Lichtman, Coller. McGraw-Hill ¡¡Repetir laboratorios cada 6 a 8 horas!!
    27. 28. <ul><li>Tratamiento </li></ul><ul><ul><li>Patología de base </li></ul></ul><ul><ul><li>Terapia de reemplazo sanguíneo </li></ul></ul><ul><ul><li>Administración de Heparina </li></ul></ul><ul><ul><li>Administración de antitrombina III </li></ul></ul><ul><ul><li>Inhibidores de la fibrinolisis </li></ul></ul>Coagulación intravascular diseminada Williams Hematology 6th edition (November 28, 2000). Beutler , Lichtman, Coller. McGraw-Hill
    28. 29. <ul><li>Tratamiento </li></ul><ul><ul><li>Patología de base </li></ul></ul><ul><ul><li>Terapia de reemplazo sanguíneo </li></ul></ul><ul><ul><li>Administración de Heparina </li></ul></ul><ul><ul><li>Administración de antitrombina III </li></ul></ul><ul><ul><li>Inhibidores de la fibrinolisis </li></ul></ul>Coagulación intravascular diseminada Williams Hematology 6th edition (November 28, 2000). Beutler , Lichtman, Coller. McGraw-Hill
    29. 30. <ul><li>Tratamiento </li></ul><ul><ul><li>Patología de base </li></ul></ul><ul><ul><li>Terapia de reemplazo sanguíneo </li></ul></ul><ul><ul><li>Administración de Heparina </li></ul></ul><ul><ul><li>Administración de antitrombina III </li></ul></ul><ul><ul><li>Inhibidores de la fibrinolisis </li></ul></ul>Coagulación intravascular diseminada Sharathkumar, AA. Pipe SW. Bleeding Disorders Pediatr. Rev., Apr 2008; 29: 121 - 130.
    30. 31. <ul><li>Tratamiento </li></ul><ul><ul><li>Patología de base </li></ul></ul><ul><ul><li>Terapia de reemplazo sanguíneo </li></ul></ul><ul><ul><li>Administración de Heparina </li></ul></ul><ul><ul><li>Administración de antitrombina III </li></ul></ul><ul><ul><li>Inhibidores de la fibrinolisis </li></ul></ul>Coagulación intravascular diseminada Schmugge M, Risch L, Heparin-Induced Thrombocytopenia-Associated Thrombosis in Pediatric Intensive Care Patients Pediatrics, Jan 2002; 109:e10.
    31. 32. <ul><li>Tratamiento </li></ul><ul><ul><li>Patología de base </li></ul></ul><ul><ul><li>Terapia de reemplazo sanguíneo </li></ul></ul><ul><ul><li>Administración de Heparina </li></ul></ul><ul><ul><li>Administración de antitrombina III </li></ul></ul><ul><ul><li>Inhibidores de la fibrinolisis </li></ul></ul>Coagulación intravascular diseminada Williams Hematology 6th edition (November 28, 2000). Beutler , Lichtman, Coller. McGraw-Hill
    32. 33. <ul><li>Tratamiento </li></ul><ul><ul><li>Patología de base </li></ul></ul><ul><ul><li>Terapia de reemplazo sanguíneo </li></ul></ul><ul><ul><li>Administración de Heparina </li></ul></ul><ul><ul><li>Administración de antitrombina III </li></ul></ul><ul><ul><li>Inhibidores de la fibrinolisis </li></ul></ul>Coagulación intravascular diseminada Williams Hematology 6th edition (November 28, 2000). Beutler , Lichtman, Coller. McGraw-Hill
    33. 34. Bibliografía <ul><li>Williams Hematology 6th edition (November 28, 2000). Beutler , Lichtman, Coller. McGraw-Hill </li></ul><ul><li>Furie B, Mechanisms of Thrombus Formation. N Engl J Med 359:938, August 28, 2008 Review Article — Mechanisms of Disease </li></ul><ul><li>Moake JL. Thrombotic Microangiopathies N Engl J Med 347:589, August 22, 2002 Review Article </li></ul><ul><li>Rutherford CJ. Consultative Hemostasis and Thrombosis N Engl J Med 348:1072, March 13, 2003 Book Review </li></ul><ul><li>Sharathkumar, AA. Pipe SW. Bleeding Disorders Pediatr. Rev., Apr 2008; 29: 121 - 130. </li></ul><ul><li>Schmugge M, Risch L, Heparin-Induced Thrombocytopenia-Associated Thrombosis in Pediatric Intensive Care Patients Pediatrics, Jan 2002; 109:e10. </li></ul>
    34. 35. <ul><li>¡Gracias! </li></ul>[email_address]

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