Definition, Etiology, PathogenesisTop
Disseminated intravascular coagulation (DIC) is a syndrome that may develop in the course of various clinical conditions. DIC is a result of generalized activation of coagulation with a concomitant activation or inhibition of fibrinolysis.
1) Acute DIC: Sepsis, severe infection, trauma (particularly extensive, multiorgan trauma or trauma causing fat embolism), internal organ injury (eg, acute pancreatitis, acute liver failure), obstetric complications (premature placental abruption, amniotic fluid embolism, preeclampsia), posttransfusion reactions, transplant rejection, snake bites, and sometimes cancer (acute promyelocytic leukemia [APL]).
2) Chronic DIC: Cancer (solid tumors), giant hemangiomas (Kasabach-Merritt syndrome), and large aortic aneurysms.
2. Pathogenesis: The generalized activation of coagulation may develop due to the following:
1) General effects of proinflammatory cytokines, for instance, in sepsis or major trauma, which lead to impairment of the anticoagulant effects of protein C, activation of platelets, and inhibition of fibrinolysis.
2) Circulating procoagulants, for instance, in the case of obstetric complications or cancer (in patients with APL or prostate cancer, activation of coagulation may be offset by a very severe activation of fibrinolysis).
1) Multiple thrombi in the microcirculation and (less frequently) in major vessels, which cause ischemic multiorgan injury.
2) Consumption of platelets, fibrinogen, and other coagulation factors, which leads to their deficiency and bleeding.
Clinical Features and Natural HistoryTop
Acute DIC has a rapid clinical course associated with severe bleeding (from surgical wounds, nasal and oral mucosa, genitourinary tract, and sites of vascular access), ischemic organ injury (renal failure, liver failure, respiratory insufficiency), and in some cases with shock and stroke (either hemorrhagic or ischemic).
Chronic DIC is associated with a spectrum of bleeding complications and may be clinically innocuous.
Diagnosis is based on serial measurements of parameters of hemostasis in a patient with a condition that may cause DIC. There is no single diagnostic laboratory test. Diagnosis of the cause of DIC (underlying condition) is essential.
1. Acute DIC: Unexplained thrombocytopenia (generally 50,000-100,000/microL); prolonged prothrombin time (PT)/international normalized ratio (INR), activated partial thromboplastin time (aPTT), and thrombin time; low serum levels of fibrinogen (in patients with sepsis this feature may be absent or develop late, because fibrinogen is an acute-phase protein and its levels may be transiently elevated) and other coagulation factors; elevated D-dimer levels.
2. Chronic DIC: Usually suspected due to a mild to moderate platelet count reduction. Other laboratory measures are similar to acute DIC, although findings may be less marked.
Immune thrombocytopenia, thrombotic thrombocytopenic purpura, and hemolytic-uremic syndrome (these are differentiated by severe thrombocytopenia with normal coagulation times), primary or secondary hyperfibrinogenolysis, catastrophic antiphospholipid syndrome.
1. Treatment of the underlying condition (eg, sepsis) is crucial.
2. Transfusions of blood products when indicated:
1) In patients with significant blood loss, transfuse packed red blood cells.
2) In patients with active bleeding (or those requiring an invasive procedure) and a prolonged aPTT or PT/INR (>1.5 × normal), administer fresh-frozen plasma.
3) In patients with a plasma fibrinogen level <1 g/L and bleeding, administer cryoprecipitate 1 IU/10 kg every 24 hours or fibrinogen concentrate (2-3 g); administration can be titrated against the fibrinogen level.
4) In patients with platelet counts <50,000/microL and severe bleeding, administer platelet concentrate 1 to 2 U/10 kg. Prophylactic transfusion is not indicated except in cases of very severe thrombocytopenia (<10,000/microL), as the transfused platelets will be rapidly consumed. A poor response to platelets should be expected.
3. Drugs that may be considered:
1) The role of heparin in the treatment of DIC is controversial. Heparin is indicated in chronic, compensated DIC with predominant thrombosis. It may be effective in pregnant patients with fetal death syndrome and hypofibrinogenemia before induction of delivery, or in patients with severe hemorrhage from a giant hemangioma or an aortic aneurysm before planned resection. Consider using therapeutic doses of heparin in patients with DIC with predominant arterial or venous thrombosis or with severe fulminant purpura with symptomatic occlusion of cutaneous vessels. In patients with thrombosis, low-molecular-weight heparin (LMWH) is preferred, but in patients at high risk of hemorrhage, the use of unfractionated heparin (UFH) may be beneficial due to its short half-life after discontinuation. UFH is administered IV (without an initial bolus) at a dose of 500 IU/h (or 10 IU/kg/h). Subcutaneous injections of prophylactic doses of UFH or LMWH reduce the severity of bleeding in patients with chronic DIC and are indicated in the prevention of venous thromboembolism in severely ill patients with acute DIC without active bleeding.
Contraindications: Features of central nervous system bleeding, severe thrombocytopenia and active bleeding, and acute liver failure.
2) Tranexamic acid (a fibrinolysis inhibitor) 10 to 15 mg/kg IV is indicated only in very rare cases of DIC with severe fibrinolysis (in patients with APL, prostate cancer, and in some patients with Kasabach-Merritt syndrome). Absolute contraindications include hematuria, renal failure, features of ischemic organ injury, and chronic DIC.