Disseminated intravascular coagulation

Introduction to disseminated intravascular coagulation Disseminated intravascular coagulation (DIC) is a condition that occurs on many serious diseases or under certain special conditions to activate the human coagulation system by pathogenic factors, resulting in microcirculation diffuse microthrombus formation and secondary fibrinolysis. Hyperthyroidism syndrome. basic knowledge The proportion of illness: 0.001% Susceptible people: no specific people Mode of infection: non-infectious Complications: pulmonary embolism, acute respiratory distress syndrome

Disseminated intravascular coagulopathy

(1) Causes of the disease

DIC can be caused by various diseases in various clinical departments, such as infection, tumor, pathology, surgery and trauma.

1. Infectious diseases The DIC induced by infection accounts for 31% to 43% of the total number of cases.

(1) bacterial infection: Gram-negative bacterial infection is the most common cause of DIC, such as meningococcal, Escherichia coli, Pseudomonas aeruginosa, etc.; some serious Gram-positive bacterial infections, such as Staphylococcus aureus sepsis Etc. can also lead to DIC, occasional reports of diffuse tuberculosis complicated with DIC.

(2) Viral infection: epidemic hemorrhagic fever, severe hepatitis and other viral diseases, a variety of multiple rash viruses, such as rubella virus, measles virus.

(3) Rickettsia infection: such as typhus, ginger worm disease.

(4) Protozoal infections: such as cerebral malaria.

(5) spirochete infection: such as leptospirosis.

(6) Fungal infections: such as histoplasmosis.

2. The incidence of malignant tumors accounts for 24% to 34% of DIC patients, such as various types of acute leukemia, malignant lymphoma, prostate cancer, pancreatic cancer, liver cancer, kidney cancer, lung cancer, brain tumor, malignant hemangioendothelioma, Neuroblastoma, leiomyosarcoma, etc.

3. Pathological obstetrics accounted for 4% to 12% of DIC patients, such as amniotic fluid embolism, infectious abortion, stillbirth retention, severe pregnancy-induced hypertension syndrome, uterine rupture, placental abruption, placenta previa and so on.

4. The incidence of surgery and trauma accounts for 1% to 5% of DIC. It has also been reported that up to 15% of organs with rich tissue factors such as brain, prostate, pancreas, uterus and placenta can be released due to surgery and trauma. Induction of DIC, extensive burns, severe crush injuries, fractures and snake bites also lead to DIC.

5. The incidence of iatrogenic diseases accounts for 4% to 8% of DIC, and its increasing incidence has attracted the attention of scholars at home and abroad. The occurrence of iatrogenic DIC is often related to the following factors:

(1) Drugs: a variety of antipyretic analgesics, certain biological and enzyme preparations, fibrinolytic inhibitors, corticosteroids and a small number of antibiotics.

(2) Surgery and other medical operations: Some large-scale surgery and medical operations can cause extensive tissue ischemia, hypoxia and injury, leading to the release of tissue clotting factors and induction of DIC.

(3) Tumor treatment: a variety of tumor cells are rich in tissue clotting factor substances. In the process of surgery, radiation and chemotherapy, with the destruction of tumor cells, such substances can be released in large quantities, causing blood clotting through exogenous pathways. The reaction causes the occurrence of DIC.

(4) Abnormal medical procedures:

1 hemolytic transfusion reaction.

2 Gram-negative bacteria and other polluting inputs.

3 Some Chinese medicines and a large number of non-isotonic liquids caused by severe hemolysis reactions.

6. The incidence of various systemic diseases accounts for about 15% of DIC.

(1) Cardiovascular system: malignant hypertension, pulmonary heart disease, myocardial infarction, aortic aneurysm, giant hemangioma, non-infectious thrombotic endocarditis, cyanotic congenital heart disease and hyperlipidemia Among them, pulmonary heart disease complicated with DIC is the most common.

(2) Respiratory system: Krebs pneumonia, respiratory distress syndrome, pulmonary infarction and severe pulmonary insufficiency.

(3) Digestive system: biliary infection, bacterial peritonitis, acute necrotizing pancreatitis, acute hemorrhagic necrotic enteritis, acute hepatic insufficiency, severe cirrhosis and pseudomembranous colitis.

(4) Hematopoietic system: acute leukemia, hemolytic anemia, fulminant purpura, massive or old blood transfusion, blood type incompatibility and high-viscosity syndrome caused by various causes.

(5) urinary system: acute nephritis, acute tubular and cortical necrosis, hemolytic uremic syndrome.

(6) Endocrine system: diabetic ketoacidosis and some endocrine crisis.

(7) Immune diseases: systemic lupus erythematosus, polyarteritis, acute vasculitis, and panniculitis.

(8) Others: carbon monoxide poisoning, heat stroke, fat embolism, neonatal scleredema, giant cavernous hemangioma, graft-versus-host disease (GVHD) after organ transplantation, status epilepticus and severe infusion reaction.

7. Inducing factors can induce or promote the occurrence of DIC. The main factors for development are: 1 The function of mononuclear macrophage system is suppressed, it is found in severe hepatitis, splenectomy, continuous use of corticosteroids in large doses, and the activity of 2 fibrinolysis system is reduced. Mainly seen in the use of anti-fibrinolytic drugs improper or excessive, 3 pregnancy and other high-coagulation state, 4 factors that can reduce the DIC "starting threshold", such as: hypoxia, acidosis, blood stasis, dehydration, shock and so on.

(two) pathogenesis

The pathogenesis of DIC is very complex and can vary from underlying disease. It is summarized as follows:

1. Exogenous coagulation system activation In the pathogenesis of DIC, factor III (tissue factor) is released into the bloodstream, triggering the coagulation reaction through the exogenous coagulation system, leading to microthrombus formation, which plays an extremely important role.

In addition to tissue factor, many tissues of the human body can release tissue factor substances when they are damaged or destroyed. After entering the bloodstream, they have the same activity and effect of tissue factor: 1 kinds of tumor cells, 2 red blood cells, mainly red blood cells Membrane phospholipids, ie "erythropoietin", 3 white blood cells, are primarily their granular contents.

Some exogenous substances that enter the bloodstream, such as certain snake venom, insect toxins, amniotic fluid, fetal or stillbirth, necrosis and metabolites, also have a tissue factor-like effect. Under certain conditions, they are also the "starting" factors of DIC. .

2. The endogenous coagulation pathway initiates various pathogenic factors to activate the factor XII to activate the endogenous coagulation system, which is also an important link in the pathogenesis of DIC.

Factors that can cause factor XII activation are:

1 vascular endothelial injury, such as severe infection, ischemia, hypoxia, acidosis, certain drugs and extensive vascular disease, etc.

2 Certain bacteria, endotoxins, viruses, thrombin and certain drugs have direct activation factor XII.

3 Recent studies have shown that activated platelets have direct activation of factor XII and XI in the presence of high molecular weight kininogen and kallikrein, 4 plasma free saturated fatty acids, certain antigen-antibody complexes and medical treatment. The inner surface of the device in operation, etc., can also directly activate Factor XII.

3. Platelet activation, procoagulant response A variety of DIC pathogenic factors can cause platelet damage, which causes adhesion, aggregation and release of a series of contents and metabolites in the vascular endothelium. These substances play an important role in the pathogenesis of DIC:

1 As described above, activated platelets can directly activate factor XII and initiate the internal coagulation system.

2 Platelet factor III released after platelet activation is an indispensable substance in the first and second phases of coagulation, and its appearance accelerates the blood coagulation process.

3 Activated platelets release metabolites such as adenosine diphosphate, serotonin, thromboxane A2, etc., have the effect of inducing platelet aggregation and strong contraction of blood vessels, which will further accelerate the pathological process of DIC, leading to platelet activation during DIC The factors are: extensive vascular endothelial damage; some microorganisms and their metabolites, such as viruses, endotoxins, etc. directly damage platelets; exogenous or DIC early formation of endogenous thrombin has the effect of activating platelets.

The above pathological changes will lead to the formation of thrombin in the body. Thrombin is a key factor in the pathogenesis of DIC. On the one hand, it directly converts fibrinogen into fibrin to form a thrombus, and at the same time, through strong positive feedback on coagulation factors and platelets. Function, further accelerate the blood coagulation process, can also directly activate the fibrinolytic system, aggravate the coagulation disorder, the main role of thrombin in the pathogenesis of DIC is shown in Figure 1.

4. Plasmin activation-induced coagulation-anticoagulant disorder further aggravates the pathogenesis of DIC. In addition to thrombin, another key factor is plasmin. In recent years, scholars have listed both as DIC. The key factors of the mechanism.

The activation factors of plasmin in the DIC process are as follows:

1 Activated Factor XII converts plasminogen to plasmin by activating plasminogen activator,

2 The thrombin formed in the early stage has a strong plasmin-promoting effect.

3 many exogenous and endogenous substances, such as certain bacteria, viruses, endotoxins, urokinase, pleural effusion, ascites, etc., can directly promote the conversion of plasminogen to plasmin,

4 Vascular endothelial cells are rich in tissue plasminogen activator (t-PA), which can be released into the bloodstream to activate plasminogen under injury or fibrin stimulation.

The role of plasmin in DIC is as follows:

1 Degradation of fibrin, clearing blood clots, but at the same time can cause delayed bleeding,

2 kinds of fibrin degradation products can affect vascular permeability and platelet function, and increase bleeding,

As a proteolytic enzyme, 3 plasmin can degrade various coagulation factors. In recent years, studies have shown that various clotting factors in DIC patients are reduced. In addition to the consumption during thrombus formation, the degradation of plasmin may be an important factor. the reason.

5. Microthrombus formation Microthrombus formation is the basic pathological change of DIC, and it is also a characteristic change of DIC. The detection rate of microthrombus is very different. It has been found that infectious diseases can cause up to 50% of DIC. There are also reports of a positive rate of up to 90%. The presence of microthrombus in DIC is extremely extensive, and is more common in the lung, kidney, brain, liver, heart, adrenal gland, gastrointestinal tract, skin and mucous membranes.

The shape of DIC microthrombus is related to its formation site. It can be round, elliptical, columnar, strip-like, polygonal, etc. In glomerular capillaries, it can be irregular mass or honeycomb and curved strip. Ordinary hematoxylin-eosin staining is a homogeneous unstructured red body, often filled with microvessels. When the thrombus is large, there may be vacuoles formed by lipid dissolution around or in the center. Neutrophils and the like are present in them, and platelets are often seen in the periphery of the thrombus. If the thrombus is specially stained with cellulose, it is a dark blue homogeneous or misty body, and the morphology is similar to that of hematoxylin-eosin staining. Electron microscopy studies have shown that the ultrastructure of microthrombus in different parts can be different. The microthrombus is a clear mass under the electron microscope, but there is no clear boundary film. When the magnification is high, the microthrombus can be seen (50-60) nm× 10nm microparticles, or a 22nm striated fibrin bundle bound or covered on the surface of the thrombus, DIC glomerular ultrastructure shows swelling and proliferation of capillary endothelial cells, intraluminal Platelets, The retinoic protein or fibrin-like mass is blocked, and there are white blood cells scattered between them. The DIC caused by amniotic fluid embolism, in addition to micro-thrombus, amniotic fluid plug, amniotic fluid crystal and amniotic fluid can be found in the pulmonary capillaries. Exfoliated cells and other ingredients.

DIC microthrombus can be divided into different types according to its composition:

1 fibrin thrombosis, which is the most important component of DIC microthrombus. Recently, fibrin thrombosis has been divided into intraluminal cell-free reaction type, intraluminal with cell-reactive type, extra-endothelium-free fibroblast-reactive type and endothelium-external fiber. Cell type, etc.

2 platelet thrombosis, early thrombosis of DIC, mainly caused by platelet aggregation, because platelets can be depolymerized and unstable, so less found in active tissue examination or autopsy,

3 platelet-fibrin thrombosis, with fibrin as the core, or peripheral platelet deposition, such thrombosis is also more common in DIC,

4 platelet-fibrin-erythrocyte thrombosis, also known as mixed thrombus, is more common in larger blood vessels, in addition to platelet deposition and fibrin clot formation, can be mixed with red blood cells, red blood cells are mostly surrounded by fibrin and scattered, may have Dissolved and caused hemosiderosis, this thrombus is rare in DIC, secondary pathological changes accompanied by microvascular embolism: thrombus distal vasospasm, interstitial edema, focal hemorrhage and ischemic necrosis Therefore, in organs with microthrombus formation, corresponding transient functional damage or even irreversible functional failure may occur.

6. Coagulation abnormalities Coagulation abnormalities are the most common pathophysiological changes of DIC, and the detection rate can be as high as 90% to 100%. The coagulation evolution process is as follows:

(1) Initial hypercoagulable phase: This is an early change of DIC. The laboratory examination of clotting time can be significantly shortened, prothrombin time is shortened, and other clotting factor levels and activities are normal or increased.

(2) Consumable hypocoagulation period: At the same time of hypercoagulable phase, due to the consumption of hypercoagulable period and the degradation of clotting factor by plasmin, the blood coagulability is reduced, and the laboratory examination can find that the clotting time is significantly prolonged. And a variety of clotting factors are low or even undetectable, this period lasts longer in DIC, often constitutes the main clinical features of DIC and laboratory abnormalities.

(3) Secondary fibrinolysis: With the formation of intravascular thrombosis, the consumption of a large number of platelets and coagulation factors and compensatory anticoagulation are enhanced, the coagulation process is gradually weakened, the fibrinolysis process is gradually strengthened, and it becomes DIC pathology. The main contradiction in the process, prolonged clotting time, clot lysis, euglobulin lysis and plasminogen determination showed fibrinolysis.

(4) Microcirculatory disorders: Microcirculatory disorders are one of the most common pathophysiological changes in DIC. The direct cause of this is the extensive capillary microthrombus formation, but may also be related to the following factors:

1DIC extensive bleeding leads to a decrease in blood volume,

2 extensive embolism of the lungs, liver, and intestines causes pulmonary and portal pressure to rise, and blood flow to the heart is reduced.

3 kinin system activation, causing systemic vasodilation, blood pressure,

4 fibrin degradation products cause increased vascular permeability, extravasation of plasma, and further decline in blood volume.

5 fibrinolytic activity is enhanced, fibrin peptide A, peptide B is increased, the blood vessels are contracted, and tissue perfusion is further reduced.

6 extensive thrombosis in the myocardium, myocardial cell swelling and degeneration, and even necrosis, rupture, cardiac insufficiency, resulting in reduced stroke volume, 7 primary disease on the circulatory system damage.

DIC microcirculatory disorders can lead to the following adverse consequences:

1 aggravation of tissue ischemia, hypoxia, causing metabolic acidosis and other metabolites,

2 The capillary sphincter begins to reflect sputum, followed by relaxation and expansion, more capillaries open, blood flow becomes slower and stagnant,

3 tissue, organ due to embolism, microcirculatory disorders and other reasons, blood perfusion is further reduced, and toxic damage, resulting in transient or persistent dysfunction,

4 due to capillary vasospasm, intravascular thrombosis and hypoxia caused by increased erythrocyte fragility, leading to microvascular hemolysis, this phenomenon has been confirmed in capillary fluoroscopy, especially under scanning electron microscopy.

Disseminated intravascular coagulation prevention

Actively treat the primary disease and avoid the occurrence of predisposing factors.

Disseminated intravascular coagulation complications Complications pulmonary embolism acute respiratory distress syndrome

Pulmonary embolism can cause acute respiratory distress syndrome; renal embolism can cause acute renal failure; cerebral embolism can cause brain edema or cerebral palsy; liver embolism can cause liver failure.

Disseminated intravascular coagulation symptoms Common symptoms Intravascular coagulation coma bleeding tendency hematuria microinflammation state coagulopathy blood hypoxemia sepsis convulsion hypotension

The clinical manifestations of DIC are closely related to the primary disease, clinical type, and stage of development. Because DIC is a clinical syndrome that occurs on the basis of certain serious diseases, and only exists at a certain stage of complex pathological processes. Therefore, its clinical manifestations can have the following characteristics:

1 Because of the many primary diseases of DIC, the clinical manifestations of DIC are often concealed by the symptoms and signs of the primary disease.

2 DIC pathological development process can have a leaping change, so the clinical manifestations also have great variability,

3 Some patients with DIC (13.5% to 20%) have no significant DIC-specific manifestations except for the primary symptoms and signs. The four most common symptoms of DIC in the clinic are bleeding tendency, shock, embolism and microvessels. Pathological hemolysis.

Disseminated intravascular coagulation

There are three basic requirements for DIC laboratory testing:

1 Due to the rapid onset of DIC, the rapid development of the DIC, in addition to research, laboratory tests strive to be simple and fast, generally should be issued within 2h test results report,

2 At present, most DIC experimental projects do not have diagnostic specificity, so the significance of experimental testing should be closely combined with clinical and comprehensive analysis.

3 multiple blood coagulation tests have normal values, and the physiological fluctuation range is large. The experimental results of different stages of DIC are also different. Therefore, the dynamic detection has a greater diagnostic value for DIC.

1. Platelet volume and quality

(1) Decrease in platelet count: Thrombocytopenia is the most common and most important laboratory abnormality in DIC. Danus et al believe that in patients with non-platelet-proliferative diseases, if the number of platelets exceeds 150×109/L, DIC diagnosis can be basically ruled out. The incidence of DIC thrombocytopenia is generally around 90%, and most of them are severely reduced.

(2) The average platelet volume increased: the normal volume of platelets in the circulation was (10.46±2.80) fl. In DIC, the proportion of young platelets increased due to the massive destruction of platelets, so the average volume increased (12.8±3.6). ) fl, and volume increase is one of the evidences of accelerated platelet destruction.

(3) Platelet dysfunction: Acquired platelet function defects are also one of the common experimental abnormalities of DIC. In acute and chronic DIC, the abnormal rate can reach 50% and 90%, mainly as follows:

1 aggregation function is abnormal, early aggregation is enhanced, and then decreased, the formation of fibrin degradation products during DIC, especially the early fibrin degradation product fragments X, Y can inhibit platelet aggregation,

2 anti-fibrinolytic activity is significantly reduced,

3 Adhesive abnormalities, early adhesion of DIC increased, middle and late can be reduced.

(4) Release and increase of metabolites: During the pathogenesis of DIC, due to the primary disease, extensive vascular endothelial injury and thrombin, platelets are activated in large amounts, and their release and metabolites are significantly increased in plasma, some of which are platelet-specific. The detection of molecular markers has great significance for the diagnosis of DIC, especially chronic DIC.

1 platelet factor IV (PF4): PF4 is one of the platelet-specific proteins. Animals such as Fuster found that the PF4 content and activity of chronic DIC dogs increased by 2 times. Our clinical test also confirmed this change, abnormal rate. About 70%.

2 Thromboxane B2 (TXB2): TXB2 is one of the final metabolites of platelet arachidonic acid. When DIC is used, plasma TXB2 is significantly increased, and the abnormal rate can reach about 90%.

3 platelet alpha granule membrane protein 140 (GMP-140): GMP-140 is a platelet alpha granule membrane, a glycoprotein specific to dense granules and lysosomes. It has recently been found in vascular endothelial cells, DIC, With the activation and destruction of platelets, GMP-140 can release human blood flow or chelate on the surface of platelets, so the number of molecules in plasma and on the surface of platelets can be increased.

2. Coagulation factors related experiments In the previous DIC test, traditional coagulation experiments such as fibrinogen, prothrombin time, APIT, factor V, VII, etc., have important value, in recent years due to many high sensitivity and specific detection In addition to fibrinogen, the importance of other projects has been decreasing.

(1) Fibrinogen: The decrease of fibrinogen in blood of patients with DIC is very common, and its incidence rate is about 70%, but it can be elevated in the early stage of DIC. Currently, it is less than 1.5g/L or higher in China. 4.0 g/L is the standard for reduction or elevation.

(2) prothrombin time (PT): prothrombin, factor V, VII, X and the reduction or lack of any factor in fibrinogen, can cause abnormal PT results, DIC due to the aforementioned various coagulation factors A large amount of consumption and degradation, the incidence of PT prolongation can be as high as 85% to 100%, usually with a normal control value (12 ~ 13s) extended more than 3s as an abnormality, early DIC, because the blood is in a hypercoagulable state, so PT shortening also Certain diagnostic significance.

(3) Thrombin coagulation time (TT): There are three main factors affecting TT results:

1 plasma fibrinogen content is reduced;

2 Heparin-like substances in the blood increase,

3 The content of fibrin degradation products in blood increased, because the above factors may be abnormal due to DIC, so TT prolongation is extremely common, the positive rate can reach 62% to 85%, generally considered to be longer than the normal control value (17 ~ 22s) 3s, help DIC diagnosis.

(4) Activated partial thromboplastin time (APIT): Due to the consumptive reduction and degradation of various clotting factors in DIC, the APTT test is more prolonged, the positive rate can reach 60% to 70%, and the normal value of APIT is experimental. The room is slightly different, at 40 to 50 s, it is generally considered that the prolongation of more than 10 s than the normal control value may have diagnostic significance.

(5) Determination of other coagulation factors: such as factor VIII: C, V, VII, X, XII, and protein C, protein S determination, for the diagnosis of DIC, VIII: C determination in the diagnosis of liver disease combined with DIC There is important value.

3. Determination of fibrin monomer (FM) and its complexes According to the current understanding, fibrin formation and its degradation products are produced, which is an important basis for patients with high thrombinemia. DIC has both the acceleration of fibrin formation. There is also secondary fibrinolysis, so FM and fibrin (original) degradation products (FDP) are increased, and the soluble complex formed by FM and FDP is also increased.

(1) Protamine co-coagulation (3P) test: Protamine can bind to FDP, and FM is separated from soluble FM-FDP complex, and then polymerized to form fibrin. The positive rate of this test is higher in DIC. 36.8%78.3%, because the 3P test is simple, the positive rate is high, and has certain specificity, it is regarded as an important experimental index in the diagnosis of DIC.

(2) Ethanol gel (EGF) test: The principle and significance of this test are the same as those of the 3P test. The positive rate of DIC is lower, about 50%, but the specificity is higher.

(3) Determination of soluble fibrin monomer complex (SFMC): SFMC increased in DIC patients, fibrinogen decreased, and SFMC/fibrinogen ratio increased significantly, but in surgery or other diseases, despite increased SFMC However, since fibrinogen tends to increase in stress, its ratio is only mild and moderately elevated, thus contributing to the identification of DIC and certain similar diseases.

4. Fibrinolytic assay for secondary fibrinolysis is one of the important pathological changes in DIC, so the detection of corresponding indicators is of great significance in the diagnosis of DIC, especially in the middle and later stages.

(1) Euglobulin lysis test (ELT): Since the euglobulin precipitated in an acidic environment contains a plasminogen activator, the relative content of the plasminogen activator can be determined from the euglobulin lysis rate. When fibrinolysis is carried out, the dissolution time of euglobulin is often shortened (normal >120min), and the positive rate of DIC in this test is low, 28% to 38%.

(2) Determination of plasminogen (PLG): In DIC, in the late stage, due to the activation of the fibrinolytic system, a large amount of plasminogen was converted to plasmin, so the level of plasminogen in the blood decreased, and the normal value (Congo red) Color development method) 3.5KU / L ± 0.7KU / L, DIC positive rate of 50% ~ 70%.

(3) Determination of fibrin/fibrinogen degradation products (FDP): Because of the high incidence of fibrinolysis in the late stage of DIC, FDP measurement is also one of the important indicators of DIC, in addition to the staphylococcal collection test. Certain value.

5. Peripheral blood broken red blood cells observation Some scholars in China and Japan pay much attention to this test. It is considered to be one of the important methods for diagnosing DIC in the case of emergency or experimental conditions. Microvascular embolism, sputum and microvessels due to DIC Pathological hemolysis, so red blood cells destroy and cause a lot of broken red blood cells and fragments in the blood, and there are a variety of deformed red blood cells, such as helmet-shaped, triangular, spinous red blood cells, etc., peripheral blood broken red blood cells more than 10%, is important for DIC One of the signs.

6. Anti-thrombin III (AT-III) determination AT-III is one of the most important physiological anticoagulant substances in human body, with antithrombin, inhibitory factor IXa, Xa, XIIa and plasmin, DIC Due to the activation of coagulation factors, the consumption of AT-III is so large that the blood concentration is reduced (normal value is 0.2-0.4 g/L), the activity is decreased (normal value is 80% to 120%), and the abnormal rate is about 80%. -III activity is reduced, and it also affects the efficacy of anticoagulant therapy such as heparin. Therefore, the measurement of AT-III is not only diagnostic for DIC, but also has the value of guiding treatment. In recent years, it has been found that after effective treatment of DIC, AT-III activity can be Rapid recovery, it is a good indicator of efficacy monitoring of DIC.

7. Protein C (PC) determination According to Cao Zhongxin of Northwestern University School of Medicine, the antigen level of DIC was significantly decreased (normal 5 mg / L), the positive rate was above 86%, and patients with thrombotic thrombocytopenic purpura (TTP) The PC level is normal, so this test may be considered to help identify DIC and TTP.

8. Fibrin production and conversion rate determination Some so-called non-clinical DIC patients have neither clinical symptoms nor routine experimental abnormalities, only fibrin production and conversion rate are accelerated. This test is still in the exploration stage, from theory It is speculated that it may be a sensitive indicator for diagnosing DIC.

9. Determination of molecular markers related to coagulation In the process of endothelial injury, platelet activation and coagulation activation, vascular endothelium, platelets and coagulation factors can secrete, release or degrade a variety of substances with specific labeling meaning, called molecules Mark.

In addition to the aforementioned platelet activation and metabolites, the more mature detection projects currently include:

(1) Thrombin-antithrombin complex (TAT): This test mainly measures the activation state of thrombin and its plasma level.

(2) Prothrombin fragment 1+2 (Fl 2): Fl 2 is a degradation product of prothrombin to thrombin, so its level directly reflects the activation level of thrombin.

(3) D-dimer: D-dimer is a degradation product of cross-linked fibrin, which is one of the specific molecular markers for fibrin formation and degradation in human body.

(4) Fibrinopeptide A (FPA): FPA is the first peptide fragment released during the conversion of fibrinogen to fibrin by thrombin, which is elevated in blood (urine). Indirectly reflects increased thrombin activity and initiation of the coagulation activation process.

(5) Endothelin (ET): ET is mainly a bioactive substance with strong vasoconstriction and regulation of coagulation and fibrinolysis, which is released by vascular endothelial cells. It can sensitively and specifically reflect the ability of endothelial cells to synthesize ET and the degree of endothelial damage.

(6) Thrombomodulin (TM): TM is synthesized by endothelial cells and is a thrombin receptor. The complex formed by TM and thrombin has a strong function of activating protein C. Plasma TM levels mainly reflect endothelial synthesis. The ability of TM and the extent of endothelial damage.

Diagnostic differential diagnosis of disseminated intravascular coagulation

Diagnostic criteria

1. Bleeding tendency bleeding is one of the most common symptoms of DIC, and sometimes even the only clinical basis for DIC diagnosis.

(1) Incidence: The incidence of DIC bleeding is between 84% and 95.4%. Even if it is considered to be up to 100%, the difference in the incidence of DIC bleeding may be different from the underlying disease, the clinical type is different, and the disease is diagnosed. The difference is related.

(2) Features and parts: DIC bleeding is mostly spontaneous, continuous oozing, bleeding parts can be spread throughout the body, more common in the skin, mucous membranes, gums, wounds and puncture sites, followed by a larger amount of internal bleeding, can be expressed For hemoptysis, hematemesis, hematuria, melena and intracranial hemorrhage.

(3) Clinical features: In addition to a very small number of cases, the bleeding tendency of DIC has the following clinical features:

1 Hemorrhagic sudden occurrence, often difficult to explain with the symptoms of the primary disease or the primary disease, and the patient has no history of previous bleeding.

2 The bleeding site is extensive and multiple, that is, there are often more than 2 sites with bleeding symptoms. According to 256 cases of DIC of Union Hospital of Tongji Medical University, there are 79 cases with simultaneous bleeding in 2 sites, accounting for 30.9%; There were 22 cases of bleeding at the same site, accounting for 8.6%, while the proportion of single site bleeding was very small.

3 more bleeding with other clinical manifestations of DIC, such as shock, skin embolism and necrosis and organ dysfunction.

4 conventional hemostasis treatment measures such as fibrinolysis inhibitors and simple blood transfusion or coagulation factor supplementation, etc., the effect is not significant, and sometimes can aggravate the condition, and anti-coagulation treatment and other comprehensive measures often have a certain effect.

2. Shock or microcirculatory failure shock or microcirculatory failure is one of the most important and common clinical manifestations of DIC, the incidence rate is between 30% and 80%, Matsuda 136 patients with DIC, 33% have shock; Among the 256 cases of Union Hospital affiliated to the Medical University, 46.5% of them had shock performance.

Clinical features: Shock or microcirculatory failure caused by DIC, in addition to the performance of general shock, clinically have the following characteristics:

1 shock suddenly occurs, the clinical can not find the most common causes of shock, such as blood loss, poisoning, allergies and severe pain, etc.

2 shock often occurs with other DIC manifestations such as bleeding tendency and embolism, but the severity of shock and bleeding is inconsistent.

3 In the early stage of shock, a variety of organs can appear, especially the symptoms and signs of vital organs insufficiency, such as kidney, lung and cerebral cortical insufficiency, etc., which is quite different from the general shock only in the end stage.

4 shock is mostly refractory, clinically serious, the conventional treatment effect is not obvious or may even aggravate the condition.

3. Microvascular embolism

(1) Incidence: Due to the difference in DIC conditions, the difference in specimens and examination methods, the incidence of DIC thromboembolic disease is very different.

(2) Clinical features:

1DIC embolization is microvascular embolism: widespread and diffuse, and there are few localized localized symptoms and signs of thrombosis or embolism. Therefore, clinical and imaging evidence of DIC embolism cannot be found by traditional concepts and methods.

2 Many patients with DIC embolization are superficial embolism: mainly manifested as skin and mucous membrane blemishes, and then developed into extensive thromboembolic necrosis. At this time, spotted or plaque-like plaques are visible on the skin, and the center of the lesion is high. The dark red small blood clot on the surface is surrounded by a hemorrhagic lesion with a slightly flaky color of different sizes. With the development of the disease, the bleeding spots around the thrombus may be necrotic due to ischemia, hypoxia, and may have epidermis. Shedding, necrotic foci are often scattered, more common in the eyelids, limbs, chest and back and perineum and other subcutaneous fat, tissue soft parts, mucosal damage similar to the skin, prone to oral, digestive, anal and other parts It can be diffuse focal necrosis and ulcer formation, or it can be a large piece of plaque necrosis, shedding, and can cause symptoms such as upper gastrointestinal bleeding.

3 Some embolizations of DIC patients occur in the deep part of the body cavity: especially vital organs. At this time, except for a few cases, the evidence of embolism can be detected directly by biopsy. Most of the symptoms are related to organ failure. According to the former Tongji Medical Department Case statistics of the University affiliated Union Hospital and other hospitals, the highest incidence of organ embolism in DIC is kidney, accounting for 54%; followed by lung, mainly respiratory distress syndrome and respiratory insufficiency, accounting for 44.6%; Disseminated embolism of the cerebral cortex again, manifested as varying degrees of disturbance of consciousness and unexplained intracranial hypertension syndrome, accounting for about 24%; a few may have symptoms and signs of cerebral thrombosis, and other myocardial and liver microvascular embolism, Adrenal cortex, pituitary or mesenteric embolism, etc., at this time can produce transient or permanent dysfunction of the corresponding organs.

The incidence of thromboembolism and dysfunction in various tissues caused by DIC is shown in Table 1.

4. Hemolysis found in microvascular hemolytic DIC is found in about 25% of patients, and the red blood cell destruction caused by it is of great value in the diagnosis of DIC.

The occurrence of DIC hemolysis is mainly caused by the following factors:

In 1DIC, there is extensive thrombosis in the capillaries and reflex vasospasm. Therefore, the lumen is highly narrow. When the red blood cells pass through such narrow capillaries, they are deformed and destroyed by mechanical action. This is the main cause of DIC hemolysis. Microvascular hemolysis),

2 fibrin thrombus in capillaries, the surface is not very smooth, there are many attachments such as fibrin, which can cause mechanical damage to the red blood cells in the circulation, such as shackles, extrusion, and increase the destruction of red blood cells.

3 patients' red blood cells due to ischemia, hypoxia, metabolic toxicity products, resulting in increased mechanical fragility.

DIC hemolysis is clinically characterized by microvascular disease intravascular hemolysis, often with the following characteristics:

1 Most lack the symptoms and characteristics of typical acute intravascular hemolysis, such as chills, fever, low back pain, jaundice, etc., which may be related to the lesser degree of hemolysis.

In 2 cases, unexplained progressive anemia, or decreased hemoglobin during routine blood tests, may be the only evidence suggesting DIC hemolysis.

3 Because microvascular disease is the main cause of DIC hemolysis, the evidence of red blood cell destruction is obvious. For example, a large number of red blood cell fragments and broken red blood cells can be seen in the blood, as well as triangular, helmet-shaped, spinous-shaped and other shaped red blood cells.

5. Clinical manifestations of primary disease In addition to the above-mentioned main clinical manifestations, there are corresponding symptoms and signs of underlying diseases causing DIC, such as infection, tumor, pathology, surgery, trauma and so on, each with its corresponding clinical manifestations.

6. Other clinical manifestations of other DICs are still found in the literature:

1 neonatal DIC mainly manifests as edema of the extremities, wilting, pale gray or pale, nose flapping, irregular breathing, not crying or snoring, skin swelling, convulsions, etc.

In addition to bleeding spots and plaque necrosis in 2DIC, there may be fulminant purpura, fingertips and necrosis, and a few may be nasal necrosis.

1. Domestic Standards The diagnostic criteria established by the Fifth National Conference on Thrombosis and Hemostasis (Wuhan) in 1995 are as follows:

(1) Clinical manifestations:

1 There are basic diseases that cause DIC,

2 have the following two or more clinical manifestations: A. multiple bleeding tendency; B. microcirculatory failure or shock that is difficult to explain with primary disease; C. symptoms and signs of multiple microvascular embolism, such as skin, subcutaneous, mucosal embolism Necrosis, as well as early lung, kidney, brain and other organ dysfunction; D. anticoagulant therapy is effective.

(2) Laboratory indicators: There are at least three exceptions at the same time:

1 platelet <100×109/L or progressive decline (liver disease, leukemia, platelet <50×109/L); or more than 2 plasma platelet activation products: -TG, PF4, TXB2, GMP-140 ,

2 plasma fibrinogen content <1.5g / L or progressive decline or > 4g / L (leukemia and other malignant tumors <1.8g / L, liver disease <1.0g / L),

Positive 33P test or plasma FDP>20mg/L (liver disease: FDP>60mg/L), or elevated D-dimer (positive),

4 prothrombin time is shortened or prolonged by more than 3s or dynamically (hepatic disease: prothrombin time extended by more than 5s),

5 plasminogen content and activity decreased,

6AT-III content and activity decreased (not suitable for liver disease),

7 plasma factor VIII: C activity <50% (necessary for liver disease).

Difficult cases should have the following one or more abnormalities:

1 factor VIII: C decreases, vWF: Ag increases, VIII: C/vWF: Ag ratio decreases,

2 plasma TAT concentration increases, or F1 2 levels increase,

3 plasma plasmin-plasmin inhibitor complex (PIC) concentration increased, 4 blood (urine) fibrin peptide A level increased.

2. Foreign common standards

(1) Colman criteria: The first DIC (experimental) diagnostic indicator proposed by Colman in 1971,

1 thrombocytopenia (<100×109/L),

2 prothrombin time is prolonged,

3 fibrinogen decreased (<1.5g / L), if only 2 of the above 3 abnormalities, then one or more of the following 3 items are required:

1 thrombin clotting time is prolonged,

2 serum FDP increased 4 times than normal (or 3P test positive),

3 euglobulin dissolution time is shortened.

(2) The Japanese scoring diagnostic criteria were proposed by Japanese scholars in recent years (Table 3).

3. Diagnostic evaluation

(1) The lack of specificity of DIC microthrombotic embolism: the duration of acute DIC is also short, often ignored by clinicians, or not found, or attributed to the primary disease, in fact, a wide range of microthrombus Formation, not hemorrhage, is the most common cause of hypoxia and organ dysfunction. If you can diagnose and treat DIC during hypercoagulable period, it will significantly improve the prognosis. DIC hemorrhage is the manifestation of body coagulation and hematopoietic decompensation. The main feature is systemic multi-site hemorrhage, often unable to explain the primary disease, understand the clinical features of DIC, improve the vigilance of DIC, routine monitoring of DIC in patients with basic diseases prone to DIC, is the key to early diagnosis of DIC .

(2) DIC's laboratory tests lack specificity: DIC cannot be diagnosed by one or several tests, which is the main reason why the internationally consistent diagnosis standards have not been established. The diagnostic standards developed in China are comprehensive. However, through the use of these years, some scholars believe that there are still many problems, for example, too cumbersome, some projects are time-consuming, laborious, costly, and operability is poor, some foreign scholars believe that, in fact, if PT, APTT, Both fibrinogen quantification and platelet count were abnormal, and the primary etiology and typical clinical manifestations of DIC were established. The diagnosis was basically established.

The following points should also be noted in the analysis of the test results:

1 fibrinogen can not easily rule out the diagnosis of acute DIC, because fibrinogen is an acute phase-reactive protein, which can be increased due to the primary disease of DIC. When DIC is suspected, if fibrinogen is suddenly reduced from very high level to normal lowDIC

DIC

3PDIC3P

FDP()FDPFDP

D-FDPD-

(3)DIC33DIC()FDP

(4)DICDICDIC1+2(F1+2)-(TAT)

Differential diagnosis

1.DICDIC

2.(TTP) DIC

3.DIC

D-

FPATATF1 2AT-

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