bubble_chart Overview

Disseminated intravascular coagulation (DIC) is caused by the formation of diffuse microthrombi in the microcirculation under the influence of certain disease factors, leading to secondary consumption of coagulation factors and hyperfibrinolysis, which results in microcirculatory dysfunction. Clinically, it manifests as a series of severe symptoms including bleeding, shock, embolism, and hemolysis. DIC is not an independent disease but rather a secondary hemorrhagic clinical syndrome. Delayed diagnosis and treatment can often be life-threatening.

bubble_chart Etiology

disease cause and pathogenesis of disease

There are many diseases that can cause DIC, with infections being the most common clinically: bacteria, viruses, Chinese Taxillus Herb, parasites, and fungi, etc.; followed by malignant tumors, tissue injury, pathological obstetrics, severe liver diseases, immune diseases, and hemolytic diseases, etc.

Due to different disease causes, the pathogenesis of DIC also varies. In most cases, it is often the result of a combination of several factors.

1. Tissue injury releases tissue thromboplastin, activating the extrinsic coagulation pathway, seen in various traumas, burns, pathological obstetric diseases, leukemia, metastatic cancer, and poisonous snake bites, etc.
2. Vascular endothelial injury exposes collagen tissue, activating the intrinsic coagulation pathway. Commonly seen in infections, shock, hypoxemia, acidosis, nephritis, and severe summerheat stroke, etc.
3. The destruction of red blood cells and platelets releases phospholipid substances, activating the intrinsic coagulation pathway. Commonly seen in diseases involving intravascular hemolysis and massive platelet destruction due to various causes.
4. Injury to the mononuclear-phagocyte system weakens the clearance of fibrin and activated coagulation factors, inducing DIC. Seen in fulminant hepatitis, severe liver diseases, and post-splenectomy.

In addition, under conditions such as blood stasis, hemoconcentration, and vascular spasms, slowed blood flow and increased blood viscosity can also induce DIC.

Based on the progression of coagulation mechanism abnormalities, DIC can be divided into late stage [third stage]: namely, the hypercoagulable phase, consumptive hypocoagulable phase, and secondary hyperfibrinolysis phase.

bubble_chart Clinical Manifestations

In addition to the manifestations of the primary disease, when complicated by DIC, abnormalities in the coagulation mechanism can lead to bleeding, microcirculatory failure resulting in shock, organ dysfunction due to injury-induced lesions, and mechanical injury to red blood cells causing microvascular nature of disease hemolysis. The severity of these clinical manifestations varies, and vigilance should be heightened to detect them promptly for early diagnosis.

1. Bleeding, typically presenting as widespread spontaneous hemorrhage, is one of the most common early symptoms of DIC. The most frequent occurrences are purpura, ecchymosis, or hematomas on the skin and mucous membranes, followed by oozing or persistent bleeding at wound or injection sites. In severe cases, internal bleeding may occur, with gastrointestinal bleeding being the most common, along with hemoptysis, hematuria, vaginal bleeding, or even intracranial bleeding.
2. Shock manifests as cold extremities, cyanosis, oliguria, hypotension, and respiratory or circulatory failure, often seen in acute DIC caused by vascular endothelial injury. Once shock occurs, it often exacerbates the progression of DIC, creating a vicious cycle. Conventional anti-shock measures are usually ineffective, leading to irreversible shock.
3. Embolism results from widespread microthrombosis in the microcirculation, causing hemodynamic disturbances. If prolonged, the affected organs may suffer hypoxia, functional failure, or even tissue necrosis. The incidence of visceral embolism, in descending order, includes the lungs, kidneys, gastrointestinal tract, brain, and liver. Pulmonary embolism may present with sudden chest pain, chest tightness, shortness of breath, cyanosis, and hemoptysis; renal embolism may cause oliguria, proteinuria, azotemia, or even renal failure; gastrointestinal embolism may lead to hematemesis, hematochezia, abdominal pain, and diarrhea; cerebral embolism may result in headache, spasms, unconsciousness, and abnormal pupillary changes. In severe cases, advanced-stage patients may exhibit multi-organ embolism.
4. Hemolysis occurs when red blood cells are mechanically injured and ruptured by fibrin strands as they pass through narrowed microvessels, leading to microvascular nature of disease hemolysis. Patients may exhibit anemia, jaundice, and hemoglobinuria.

Clinically, based on the onset and severity of the condition, DIC is classified into three types: (1) Acute type, with a sudden onset, typically within hours to 1–2 days, characterized by severe bleeding, often accompanied by shock and a high mortality rate; (2) Subacute type, with a slower onset, usually over days to weeks, generally without shock; (3) Chronic type, with a gradual onset, lasting months or even years, where bleeding symptoms are mild or insignificant, often overlapping with the clinical manifestations of the primary disease, making diagnosis difficult.

bubble_chart Auxiliary Examination

Laboratory tests are an important basis for diagnosing DIC, primarily including two categories: consumptive coagulation disorders and secondary hyperfibrinolysis. Due to the inconspicuous clinical manifestations during the hypercoagulable phase, it is easily overlooked. The main changes include increased blood coagulability, shortened clotting time, recalcification time, prothrombin time, and kaolin partial thromboplastin time, as well as elevated fibrinogen levels.

1. Tests for platelet abnormalities: (1) Platelet count, progressively decreasing; (2) Platelet lifespan measurement, significantly shortened; (3) Platelet aggregation test, reduced aggregation in the advanced stage; (4) Platelet release reaction test, increased release.
2. Tests for consumption of coagulation factors: (1) Prolonged prothrombin time; (2) Prolonged kaolin partial thromboplastin time; (3) Decreased fibrinogen levels and increased conversion rate; (4) Reduced factor VIII coagulant activity (VIII:C), increased factor VIII-related antigen (VWF:Ag); decreased VIII:C/VWF:Ag ratio; (5) Reduced ATⅢ levels and activity.
3. Tests for hyperfibrinolysis: (1) Shortened euglobulin lysis time; (2) Prolonged thrombin time; (3) Increased FDP levels in blood; (4) Positive 3P test or ethanol gel test.
4. Peripheral blood smear examination often reveals triangular, polygonal, helmet-shaped red blood cells and red cell fragments.

bubble_chart Diagnosis

During the development of DIC, the hypercoagulable phase in the acute type is relatively brief, and the consumptive hypocoagulable phase and secondary hyperfibrinolysis phase are not strictly separate independent stages but often overlap. Therefore, the diagnosis of DIC must be based on a comprehensive analysis of clinical manifestations and laboratory test results. The diagnostic criteria are as follows: (1) Clinically, there is an underlying disease prone to cause DIC, along with two or more of the following clinical manifestations: multiple bleeding tendencies, microcirculatory failure or shock not easily explained by the primary disease, symptoms and signs of multiple microvascular thrombosis, and effectiveness of early anticoagulation therapy; (2) Laboratory tests show three or more of the following abnormalities: progressive decrease in platelet count, plasma fibrinogen content below 1500 mg/L or progressive decline, positive 3P test or serum FDP content exceeding 20 mg/L, prothrombin time shortened or prolonged by more than 3 seconds compared to normal controls or activated partial thromboplastin time shortened or prolonged by more than 10 seconds, shortened euglobulin lysis time or decreased plasminogen. The presence of fragmented and deformed red blood cells exceeding 2% in peripheral blood smears also has certain diagnostic significance.

bubble_chart Treatment Measures

1. Clearing the disease cause and predisposing factors are important measures in preventing and treating DIC. Appropriate antibiotics should be selected to control infections, timely removal of uterine cavity contents in pathological obstetrics, and counteracting shock can halt intravascular coagulation. Additionally, implementing robust supportive therapies, particularly correcting hypovolemia and hypoxemia, reducing blood viscosity, addressing acidosis, and relieving microvascular spasms, is also crucial.
2. Anti-platelet aggregation drugs are suitable for milder cases, uncertain diagnoses, or when heparin use is contraindicated or raises concerns. Commonly used drugs include: (1) Low molecular weight dextran 500ml, intravenous drip, 1-2 times daily; (2) Dipyridamole 100-200mg, intravenous drip, every 4-6 hours; (3) Compound Salvia injection 20-30ml added to 5% glucose solution for intravenous drip, 2-3 times daily; other options such as aspirin, prostaglandin E, and Maitong can also be used.
3. Heparin
   1. Indications: The hypercoagulable phase and consumptive hypocoagulable phase of DIC, with symptoms such as bleeding, shock, and progressive thrombocytopenia. Particularly when skin shows ecchymosis, necrosis, cyanosis of extremities, ischemia, or venous thrombosis, indicating fibrin deposition in blood vessels, which is the primary indication for heparin use. Additionally, DIC occurring in cases of malignant tumors, acute promyelocytic leukemia, giant hemangioma, and retained dead fetus also falls under the indications.
   2. Contraindications: The hyperfibrinolytic phase of DIC, fulminant hepatic failure, bleeding in enclosed spaces (intracranial, mediastinal, pericardial, or spinal), fresh wounds, or recent surgery.
   3. Dosage and administration: The principle is early use with sufficient dosage and duration. Specific application should be flexibly adjusted based on the underlying disease, severity, disease phase, patient condition, and drug response. Heparin therapy includes the following methods: micro-dose: 20-50mg/day, subcutaneous injection, for DIC prevention; small dose: 50-100mg/day; medium dose: 100-200mg/day; large dose: 200-400mg/day, generally less commonly used. During heparin use, monitoring tests should be conducted, with frequent measurement of coagulation time via the tube method, aiming to maintain it at 20-30 minutes, ideally twice the control value, or with partial thromboplastin time prolonged by 2-3 times. Efficacy of heparin therapy is judged by clinical improvement, cessation or reduction of bleeding, stable blood pressure recovery, increased urine output, and improvement or normalization of DIC laboratory indicators. Treatment can typically continue for 5-7 days, with discontinuation considered after the condition stabilizes.
4. Supplementation of coagulation factors: On the basis of heparin anticoagulation therapy, fresh whole blood, plasma, or fibrinogen concentrate can be transfused. If the DIC pathological process persists, washed red blood cell suspensions, platelet suspensions, or antithrombin III concentrates can be supplemented.
5. Antifibrinolytic therapy: Fibrinolysis aids in dissolving thrombi during DIC but may lead to rebleeding; antifibrinolytic drugs can reduce fibrinolytic activity, promote coagulation, and aid hemostasis. However, they must be appropriately selected based on heparin therapy. Otherwise, they may exacerbate DIC progression, so antifibrinolytic drugs should not be the first-line hemostatic agents. Commonly used clinical options include:
   1. 6-Aminocaproic acid (EACA) 4-20g/day, intravenous drip;
   2. Para-aminomethylbenzoic acid (PAMBA), 0.2-0.4g per dose, intravenous injection or drip;
   3. Tranexamic acid (AMCHA) 0.4-1.0g per dose, intravenous drip;
   4. Aprotinin, 80,000-100,000 U/day, divided into 2-3 intravenous drips.

bubble_chart Differentiation

In terms of differential diagnosis, acute DIC should be distinguished from coagulation disorders caused by severe liver disease and primary hyperfibrinolysis. If DIC occurs in liver disease, the platelet count should be below 50×10⁹/L, fibrinogen below 1000 mg/L, and FDP above 60 mg/L.