Diffuse intravascular coagulation is an acquired clinical syndrome characterized by systemic hemorrhage and microcirculatory failure due to activation of coagulation factors, microthrombosis, massive depletion of coagulation factors and secondary fibrinolysis caused by different pathogenic factors.
Etiology
1. Infectious diseases. Bacterial sepsis is a common cause of acute DIC, Gram-negative bacterial infections such as meningococcal, Escherichia coli, Pseudomonas aeruginosa infections, etc.. Gram-positive bacterial infections such as Staphylococcus aureus infections, etc. Viral severe hepatitis, epidemic hemorrhagic fever, measles, viral myocarditis, rickettsial infection, typhus, etc. are also likely to cause DIC.
2, malignant tumor. It accounts for 24-34% of DIC patients. Acute promyelocytic leukemia is common, accounting for 20% to 28.3% of the total incidence of DIC.
3. Pathological obstetrics. It accounts for 4-12% of DIC patients. Commonly seen in amniotic fluid embolism, stillbirth retention, severe gestational hypertensive syndrome, uterine rupture, and placental abruption.
4.Surgery and extensive tissue injury accounts for 1-5% of patients with DIC. The brain, prostate, pancreas, uterus and other tissues are rich in tissue factor (TF), and surgery and trauma to these organs can cause TF release and induce DIC. large burns, severe crush injuries, fractures, snake bites are also prone to DIC.
5, systemic diseases. Systemic diseases such as malignant hypertension, pulmonary heart disease combined with severe infection, giant hemangioma, ARDS, acute pancreatitis, liver failure, hemolytic anemia, blood group incompatibility transfusion, diabetic ketoacidosis, systemic lupus erythematosus, heat stroke, fat embolism, graft-versus-host disease (GVHD), malaria, etc.
In addition, certain factors during the disease process can also trigger the coagulation system and promote the development of DIC, such as elevated body temperature, acidosis, shock, hypoxia-induced vascular endothelial cell damage, which can trigger or aggravate DIC; some snake bites can occur DIC.
Pathogenesis
1.Tissue injury. Severe infection and trauma, major surgery, tumor lysis during tumor treatment, tissue destruction or decomposition and vascular damage and release of tissue factor (TF) substances into the blood, so that the exogenous coagulation pathway is activated, of which TF release is the most important factor promoting DIC. Snake venom and other toxins can also activate the exogenous coagulation pathway or directly cross the sea FX and thrombin.
2, vascular endothelial injury. Bacteria, viruses, endotoxins, antigen-antibody complexes, persistent hypoxia, acidosis, particles or colloidal substances into the body can damage the endothelium, especially the microvascular endothelium. Damaged endothelium can induce the development of DIC by
(i) expression and release of large amounts of TF and activation of the coagulation system;
(ii) Exposed subendothelial collagen and other tissues can directly activate factor Ⅻ or factor Ⅺ to initiate the endogenous coagulation system;
(iii) triggering platelet activation, platelet adhesion, aggregation and release and formation of microthrombi. In addition, various inflammatory cells release TNF, IL-1, IL-6, IFN, platelet-activating factor (PAF), complement components C3a, C5a and oxygen radicals, and other humoral factors that aggravate endothelial damage and stimulate TF expression, further promoting and accelerating the coagulation process.
3. Hemolysis and platelet damage. When hemolysis occurs, a large number of granulocytes are destroyed and a large number of highly active pro-coagulant substances such as TF, lysosomal enzymes and trypsin are released. Heterotypic transfusion, falciparum malaria, and importation of large amounts of stock blood can cause massive destruction of erythrocytes and massive release of ADP for platelet activation. Inflammation, drugs, hypoxia and other factors can cause platelet damage, platelet membrane inner acidic phospholipid exposure, activation of platelet membrane glycoprotein GP IIb/IIIa to promote platelet aggregation and structural changes, its surface phosphatidylserine or inositol phospholipids and other negatively charged, so that coagulation factors in the platelet phospholipid surface is concentrated, confined, and promote the activation of thrombinogen, the formation of fibrin network and blood cells to form clots. Platelets act on the blood clot retraction to form a thrombus.
4. Activation of fibrinolytic system. After bacterial infection, vascular endothelial cell damage and release TF and promote coagulation. Complement is also closely related to the activation of coagulation, fibrinolysis and kinin system. Endotoxin causes tissue factor activity in monocyte membranes during Gram-negative bacterial infections. The levels of Peptidogyciw (a DIC-inducing peptide glycan) and technoic acid in the cell wall of Gram-positive bacteria are also associated with the development of DIC. Mucin, TF, and proteolytic enzymes secreted by tumor cells can promote coagulation and induce DIC, and snake bites can cause DIC, except for snake venom, which can convert fibrinogen to fibrin, and TF release after tissue damage.
In addition, the monocyte-macrophage system can remove a certain amount of procoagulant substances in blood; severe liver dysfunction, reduced synthesis of protein C (PC), antithrombin III (AT-III) and other anticoagulant substances, inactivation of F Ⅸa, F Ⅺa, F Ⅹa function is reduced; other diseases such as nephrotic syndrome, malignant tumor, leukemia, pregnancy poisoning and other causes of blood hypercoagulation; acidosis, shock leading to severe Microcirculatory disorders are also a contributing factor to DIC.
Abnormal coagulation function and microthrombosis are the key to the occurrence of DIC. The pathogenic process goes through three stages: hypercoagulable phase, consumptive hypocoagulable phase, and secondary fibrinolytic phase. The hypercoagulable phase at the beginning of the disease is the early change of DIC, and the related pathogenic factors cause the activation of coagulation factors and the occurrence of clotting and microthrombosis. After the coagulation process occurs due to depletion of coagulation factors, the patient enters the depleted hypocoagulation phase. Microthrombosis can lead to fibrinogen activation and fibrinolysis after formation of microthrombi, and the patient undergoes secondary fibrinolysis. However, the coexistence of coagulation and fibrinolysis during the pathogenesis of DIC results in microthrombosis and consequent microcirculatory failure, which can be life-threatening in severe cases.
Clinical manifestations
The main clinical symptoms of DIC are: bleeding, microcirculatory disorders, multi-organ dysfunction and anemia. The first three symptoms are common in acute DIC.
1. Bleeding. Hemorrhage is caused by the anticoagulant effect of FDP formed by fibrinolysis secondary to the massive depletion of coagulation factors and platelets in patients during DIC, and the reduced coagulation ability of patients. The incidence of extensive bleeding from their tissues and organs is about 84-95%, with multiple, spontaneous bleeding predominating. In mild cases, it is manifested as a few bleeding spots on the skin and mucous membrane, while in severe cases, extensive skin and mucous membrane sheet petechiae or hematomas can be seen.
2.Microcirculatory disorders and shock. The incidence of DIC is about 30~80%, during which the microvessels of tissues and organs are embolized by fibrin and/or platelet thrombosis and microcirculatory disorders occur. Skin microvascular embolism is most common, manifesting as cyanosis of the skin of the fingertips, toe tips, nasal tips, auricles, and in severe cases, patchy hemorrhagic or dry necrosis of the skin.
As a result of microcirculatory thrombosis, the amount of blood returned to the heart is reduced, the original disease can cause the conversion of kinin-releasing enzyme into kinin-releasing enzyme, and the level of bradykinin is increased and leads to reduced small vessel tone, increased plasma leakage, and reduced circulating blood volume, thus contributing to the development of shock and aggravating DIC.
DIC-induced shock often has the following characteristics.
(1) The presence of circulatory disturbances in the course of the underlying disease that are incompatible with the condition;
②Severe extensive bleeding and terminal cyanosis of the extremities;
(3) The presence of multi-organ insufficiency syndrome.
Hemolysis is seen in about 25% of patients and is microangiopathic hemolysis. It is characterized by some contracted red blood cells with spines and lysosomal cells such as crescentic and armor-shaped red blood cell fragments in peripheral blood smear. Due to the high brittleness of the lysosomal cells, the red blood cells suffer mechanical damage when passing through, deformation and rupture and hemolysis occurs. The patient develops xanthogranuloma, anemia, and hemoglobinuria. hemolysis is mild and not easily detected in the early stages of DIC, but is extremely likely to occur in the later stages. The proportion of peripheral blood broken red blood cells greater than 2% has auxiliary diagnostic significance for DIC.
4. Symptoms of the primary disease. Depending on the primary disease, the clinical manifestations are not exactly the same, see the relevant sections of the relevant content.
Treatment
The treatment of DIC mainly includes the following aspects: removing the cause and controlling the underlying disease that triggers DIC, blocking the intravascular coagulation process, maintaining PLT and plasma coagulation factors at normal levels, antifibrinolytic therapy, thrombolytic therapy, symptomatic and supportive treatment. Among them, early removal of the causative factors and blocking the coagulation link are the key to treatment and the basis for successful patient rescue.
1. Treatment of underlying diseases and removal of causative factors. Eliminating the cause and treating the primary disease is the fundamental measure for treating DIC. It is important to control the triggering factors of DIC caused by the primary disease, such as actively controlling the infection, removing the dead fetus in utero and anti-tumor treatment. Other measures such as replenishing blood volume, preventing and treating shock, improving hypoxia and correcting water and electrolyte disorders and acid-base imbalance have positive effects on improving blood circulation and preventing or stopping the occurrence of DIC. After the cause of DIC is removed, the patient’s condition can be relieved and the occurrence and development of DIC can be prevented.
2.Anticoagulation therapy. Anticoagulation therapy is an important measure to block the pathological process of DIC, reduce organ function damage, and promote the restoration of coagulation-anticoagulation and coagulation-fibrinolysis balance of the body. In general, anticoagulation therapy for DIC must be carried out simultaneously with the management of the underlying disease. On the basis of anticoagulation therapy, the simultaneous supplementation of coagulation factors and antifibrinolytic therapy will be determined according to the patient’s specific situation.
Anticoagulation therapy includes the following.
1.Heparin therapy
2.Other anticoagulation and antiplatelet drugs
3.Supplementation of coagulation factors and platelets
4.Fibrinolytic inhibition drugs are usually applied simultaneously with anticoagulant drugs
5.Thrombolytic therapy
6.Chinese herbal medicine is commonly used to activate blood circulation and remove blood stasis, such as compound Danshin injection, Chuanxiongzin, Danshinone injection and Acanthopanax acidic mucopolysaccharide, etc., which have certain efficacy in the treatment of DIC.
7.Other domestic cases in the treatment of DIC complicated by shock, it has been reported that scopolamine, scopolamine or phenibut can release vasospasm. Low molecular dextran has good effect on unblocking blood vessels. Various different therapies such as urokinase, blood exchange, plasma removal, and hemodialysis have also been proposed, but the efficacy is still difficult to be confirmed and needs further study.