(See also Overview of Coagulation Disorders Overview of Coagulation Disorders Abnormal bleeding can result from disorders of the coagulation system, of platelets, or of blood vessels. Disorders of coagulation can be acquired or hereditary. The major causes of acquired... read more .)
Etiology of DIC
Disseminated intravascular coagulation usually results from exposure of tissue factor to blood, initiating the extrinsic coagulation cascade. In addition, the fibrinolytic pathway is activated in DIC (see figure Fibrinolytic pathway Fibrinolytic pathway ). Stimulation of endothelial cells by cytokines and perturbed microvascular blood flow causes the release of tissue plasminogen activator (tPA) from endothelial cells. Both tPA and plasminogen attach to fibrin polymers, and plasmin (generated by tPA cleavage of plasminogen) cleaves fibrin into D-dimers and other fibrin degradation products. DIC can, therefore, cause both thrombosis and bleeding (if the consumption of platelets and/or coagulation factors is excessive).
DIC occurs most often in the following clinical circumstances:
Complications of obstetrics (eg, abruptio placentae Abruptio Placentae Abruptio placentae is premature separation of a normally implanted placenta from the uterus, usually after 20 weeks gestation. It can be an obstetric emergency. Manifestations may include vaginal... read more , saline-induced therapeutic abortion, retained dead fetus or products of conception, amniotic fluid embolism Amniotic Fluid Embolism Amniotic fluid embolism is a clinical syndrome of hypoxia, hypotension, and coagulopathy that results from entry of fetal antigens into the maternal circulation. Amniotic fluid embolism is a... read more ): Placental tissue with tissue factor activity enters or is exposed to the maternal circulation.
Infection, particularly with gram-negative organisms: Gram-negative endotoxin causes generation or exposure of tissue factor activity in phagocytic, endothelial, and tissue cells.
Cancer, particularly mucin-secreting adenocarcinomas of the pancreas Pancreatic Cancer Pancreatic cancer, primarily ductal adenocarcinoma, accounts for an estimated 57,600 cases and 47,050 deaths in the US annually (1). Symptoms include weight loss, abdominal pain, and jaundice... read more , adenocarcinomas of the prostate Prostate Cancer Prostate cancer is usually adenocarcinoma. Symptoms are typically absent until tumor growth causes hematuria and/or obstruction with pain. Diagnosis is suggested by digital rectal examination... read more , and acute promyelocytic leukemia Acute Myeloid Leukemia (AML) In acute myeloid leukemia (AML), malignant transformation and uncontrolled proliferation of an abnormally differentiated, long-lived myeloid progenitor cell results in high circulating numbers... read more : Tumor cells express and expose (or release) tissue factor.
Shock Shock Shock is a state of organ hypoperfusion with resultant cellular dysfunction and death. Mechanisms may involve decreased circulating volume, decreased cardiac output, and vasodilation, sometimes... read more due to any condition that causes ischemic tissue injury and exposure or release of tissue factor.
Less common causes of DIC include
Severe tissue damage due to head trauma, burns, frostbite, or gunshot wounds
Complications of prostate surgery that allow prostatic material with tissue factor activity (along with plasminogen activators) to enter the circulation
Enzymes in certain snake venoms Pathophysiology Of about 3000 snake species throughout the world, only about 15% worldwide and 20% in the US are dangerous to humans because of venom or toxic salivary secretions (see table ). At least one... read more that enter the circulation, activate one or several coagulation factors, and either generate thrombin or directly convert fibrinogen to fibrin
Profound intravascular hemolysis
Aortic aneurysms Overview of Aortic Aneurysms Aneurysms are abnormal dilations of arteries caused by weakening of the arterial wall. Common causes include hypertension, atherosclerosis, infection, trauma, and hereditary or acquired connective... read more or cavernous hemangiomas (Kasabach-Merritt syndrome) associated with vessel wall damage and areas of blood stasis
Slowly-evolving disseminated intravascular coagulation typically results mainly from cancer, aneurysms, or cavernous hemangiomas.
Pathophysiology of DIC
Slowly evolving DIC primarily causes venous thromboembolic manifestations (eg, deep venous thrombosis Deep Venous Thrombosis (DVT) Deep venous thrombosis (DVT) is clotting of blood in a deep vein of an extremity (usually calf or thigh) or the pelvis. DVT is the primary cause of pulmonary embolism. DVT results from conditions... read more , pulmonary embolism Pulmonary Embolism (PE) Pulmonary embolism (PE) is the occlusion of pulmonary arteries by thrombi that originate elsewhere, typically in the large veins of the legs or pelvis. Risk factors for pulmonary embolism are... read more ), although occasionally cardiac valve vegetations occur; abnormal bleeding is uncommon.
Severe, rapidly evolving DIC, in contrast, causes thrombocytopenia, depletion of plasma coagulation factors and fibrinogen, and bleeding. Bleeding into organs, along with microvascular thromboses, may cause dysfunction and failure in multiple organs. Delayed dissolution of fibrin polymers by fibrinolysis may result in the mechanical disruption of red blood cells, producing schistocytes and mild intravascular hemolysis.
Symptoms and Signs of DIC
In slowly evolving disseminated intravascular coagulation, symptoms of venous thrombosis Symptoms and Signs Deep venous thrombosis (DVT) is clotting of blood in a deep vein of an extremity (usually calf or thigh) or the pelvis. DVT is the primary cause of pulmonary embolism. DVT results from conditions... read more and/or symptoms of pulmonary embolism Symptoms and Signs Pulmonary embolism (PE) is the occlusion of pulmonary arteries by thrombi that originate elsewhere, typically in the large veins of the legs or pelvis. Risk factors for pulmonary embolism are... read more may be present.
In severe, rapidly evolving DIC, skin puncture sites (eg, IV or arterial punctures) bleed persistently, ecchymoses form at sites of parenteral injections, and serious gastrointestinal bleeding may occur.
Diagnosis of DIC
Platelet count, prothrombin time (PT), partial thromboplastin time (PTT), plasma fibrinogen, plasma D-dimer
Disseminated intravascular coagulation is suspected in patients with unexplained bleeding or venous thromboembolism, especially if a predisposing condition exists. If DIC is suspected, platelet count, PT, PTT, plasma fibrinogen level, and plasma D-dimer levels (an indication of in vivo fibrin polymer generation and degradation) are obtained.
Slowly evolving DIC
Slowly evolving DIC produces
Normal to minimally prolonged PT (results are typically reported as international normalized ratio [INR]) and PTT
Normal or moderately reduced fibrinogen level
Increased plasma D-dimer level
Because various disorders stimulate increased synthesis of fibrinogen as an acute-phase reactant, a declining fibrinogen level on 2 consecutive measurements can help make the diagnosis of DIC. Initial PTT values in slowly evolving DIC may actually be shorter than normal, probably because of the presence of activated coagulation factors in the plasma.
Rapidly evolving DIC
Rapidly evolving DIC results in
More severe thrombocytopenia
More prolonged PT and PTT
Rapidly declining plasma fibrinogen level
High plasma D-dimer level
A factor VIII level can sometimes be helpful if severe, acute DIC must be differentiated from massive hepatic necrosis, which can cause similar abnormalities in coagulation studies. The factor VIII level is elevated in hepatic necrosis because factor VIII is made in hepatic sinusoidal endothelial cells, and released as they are destroyed; factor VIII may be reduced in DIC because of the thrombin-induced generation of activated protein C, which proteolyses the activated form of factor VIII.
Treatment of DIC
Treatment of cause
Possibly replacement therapy (eg, platelets, cryoprecipitate, fresh frozen plasma))
Immediate correction of the cause is the priority (eg, broad-spectrum antibiotic treatment of suspected gram-negative sepsis, evacuation of the uterus in abruptio placentae, blood volume repletion). If treatment is effective, disseminated intravascular coagulation should subside quickly.
If bleeding is severe or involves a critical location (eg, brain, gastrointestinal tract), or if there is an urgent need for surgery, then adjunctive replacement therapy is indicated. Replacement may consist of
Platelet concentrates to correct thrombocytopenia (in case of rapidly declining platelet count or platelets < 10,000 to 20,000/microL [< 10 to 20 ×109/L])
Cryoprecipitate to replace fibrinogen (and factor VIII) if the fibrinogen level is declining rapidly or is < 100 mg/dL (< 2.9 micromol/L).
Fresh frozen plasma to increase levels of other clotting factors and natural anticoagulants (antithrombin, proteins C, S, and Z)
The effectiveness of infusion of concentrates of antithrombin in severe, rapidly evolving DIC is unresolved. Blood volume replacement Intravenous Fluid Resuscitation Almost all circulatory shock states require large-volume IV fluid replacement, as does severe intravascular volume depletion (eg, due to diarrhea or heatstroke). Intravascular volume deficiency... read more when hypotension is present is essential to arrest the DIC.
Slowly evolving DIC
Heparin is useful in the treatment of slowly evolving disseminated intravascular coagulation with venous thrombosis or pulmonary embolism. Heparin usually is not indicated in rapidly evolving DIC with bleeding or bleeding risk. An exception is in women with a retained dead fetus and evolving DIC with a progressive decrease in platelets, fibrinogen, and coagulation factors. In these latter patients, heparin is given for several days to control DIC, increase fibrinogen and platelet levels, and decrease excessive coagulation factor consumption. Heparin is then stopped and the uterus evacuated.
In disseminated intravascular coagulation (DIC), coagulation is usually activated when blood is exposed to tissue factor. In association with coagulation, the fibrinolytic pathway is also activated.
DIC usually begins rapidly and causes bleeding and microvascular occlusion, leading to organ failure.
DIC sometimes begins slowly and causes thromboembolic phenomena rather than bleeding.
Severe, rapid-onset DIC causes severe thrombocytopenia, prolonged prothrombin time and partial thromboplastin time, a rapidly declining plasma fibrinogen level, and a high plasma D-dimer level.
Immediate correction of the cause is the priority; severe bleeding may also require replacement therapy with platelets, cryoprecipitate (containing fibrinogen), and fresh frozen plasma (containing other coagulation factors).
Heparin is useful in slow-onset DIC, but rarely in DIC of rapid onset (except in women with a retained dead fetus).