neonatal disseminated intravascular coagulation
Introduction
Introduction to disseminated intravascular coagulation in neonates Disseminated intravascular coagulation (DIC) is not an independent disease, but a complication of many serious stages of the disease. It is characterized by the activation of the coagulation system by the body under certain pathogenic factors, and the coagulation process is accelerated. Fibrin deposition and platelet aggregation occur within the circulation, resulting in extensive microthrombus formation in the blood vessels, and extensive bleeding occurs due to the consumption of coagulation factors. Due to the extensive formation of microthrombus in the microcirculation, tissue ischemia, hypoxia, affect important organ function, and even the qualitative changes of the generator. Due to the prevalence of serious diseases, the incidence of DIC is high. The main clinical manifestations are extensive skin, mucous membrane and visceral hemorrhage, blood pressure drop, shock and embolism. basic knowledge The proportion of the disease: the proportion of the disease in a specific group is 0.01% - 0.02% Susceptible population: newborn Mode of infection: non-infectious complication:
Cause
Neonatal disseminated intravascular coagulopathy
(1) Causes of the disease
Neonatal DIC is more common, which is related to certain physiological characteristics of newborns:
1. Low immunity is susceptible to severe infection.
2. The clotting factor decreases the physiological decline of various coagulation factors, such as fibrinogen and factor VII cannot pass through the placenta; due to the immature liver synthesis function, the general level of vitamin K-dependent factors is low, especially prothrombin.
3. Low reactivity, poor regulation, low body temperature, respiratory and circulatory failure, hypoxia, acidosis, etc., the mononuclear macrophage system has low clearance ability.
4. The blood is thick and hypercoagulable. The blood is thick and coagulated, and the fibrinolytic activity is strong.
5. The impact of certain obstetric factors
(1) Infection: Severe infection is the main cause of neonatal DIC.
(2) Hypoxia: Acid deficiency leads to acidosis and increased blood viscosity.
(3) Cold damage: due to cold and subcutaneous fat hardening, microcirculation perfusion is insufficient, capillary damage.
(4) Hemolysis: Due to the destruction of red blood cells, a large amount of phospholipid thromboplastin substances are released, which promotes DIC.
(5) Others: Premature infants are prone to various diseases and impaired coagulation mechanism, and the incidence of DIC is high.
Some obstetric factors, such as early exfoliation of the placenta, placenta previa, severe pregnancy-induced hypertension, etc., due to placental damage release tissue thromboplastin into the fetal circulation, triggering DIC.
(two) pathogenesis
DIC is a pathological process complicated by many diseases. The occurrence of DIC is essentially the pathological activation of the coagulation system and the fibrinolysis system.
1. The coagulation system is activated by pathogenic factors such as endotoxin, antigen-antibody complex, etc., which can cause extensive vascular endothelial cell damage and platelet membrane defects, platelet factor (PF3) and TXA2 are released, and blood contacts collagen tissue of exposed vessel wall. The XII factor is immediately activated and forms a blood-active thromboplastin through a series of waterfall reactions, which activates the blood (internal coagulation) system, causing pathogenic factors such as hypoxia, acidosis, obstetric factors, etc., damage to the tissue or vessel wall. Releases tissue thromboplastin, and after a series of activation processes, finally forms tissue active thromboplastin, which activates the tissue (exocoagulation) system, the formation of active thromboplastin, accelerates the formation of thrombin, and makes fibrin The original decomposition into fibrin monomer, thrombin can activate the XII factor, so that the fibrin monomer synthesizes fibrin clots, complete intravascular coagulation, in addition, the pathogenic factors can activate the coagulation system through the following two ways, one is Platelets and/or red blood cells are destroyed in large quantities, releasing coagulation substances and accelerating the blood coagulation process; second, mononuclear-macrophage system dysfunction (such as severe liver disease) ), You can not clear the blood of excess procoagulant substances, can lead to the occurrence of DIC.
2. The fibrinolytic system (referred to as fibrinolytic system) is activated during the activation of the coagulation system, and the fibrinolytic system is activated at the same time, mainly in the following four ways:
(1) The formed thrombin directly activates plasminogen to become plasmin, so that fibrin is dissolved.
(2) The activated factor XII converts vasopressin to a kallikrein, which converts plasminogen to plasmin.
(3) Some organs such as lung, spleen, kidney, uterus and other plasminogen activators, DIC, these organs are often involved, plasminogen activator is released into the blood circulation, making plasminogen into fiber Lysozyme.
(4) hypoxia, acidosis, blood loss, trauma, surgery, etc. can activate fibrinolytic activity.
After fibrinolytic enzyme formation, it acts on fibrin and fibrinogen to decompose it into fibrin degradation products (FDP). FDP has a strong anticoagulant effect and aggravates bleeding.
Prevention
Neonatal disseminated intravascular coagulation prevention
Disseminated intravascular coagulation (DIC) is a pathological process and clinical hemorrhagic syndrome caused by a variety of causes. In pediatrics, various system diseases are involved, most commonly serious infections, including bacteria and viral infections, followed by shock, lack of Oxygen, hemolysis, cell and tissue damage can be caused. Therefore, early diagnosis, early treatment, active treatment of primary diseases, removal of the cause is the key to prevent the prevention of DIC. Children such as severe pneumonia, sepsis, acute hemolysis, newborn Children with severe asphyxia, etc., should control the development of the disease as early as possible, so as not to aggravate the disease and produce DIC.
Complication
Neonatal disseminated intravascular coagulation complications Complication
The disease is a complication of the development of many diseases to severe stages.
Symptom
Neonatal disseminated intravascular coagulation symptoms common symptoms shock skin ecchymosis thrombocytopenia hemoglobin urinary jaundice
1. Bleeding is caused by a large amount of clotting factors, thrombocytopenia and secondary fibrinolysis, bleeding, common skin defects, ecchymosis, umbilical oozing, puncture point oozing, severe digestive tract, urinary tract, lung Bleeding and other generalized bleeding.
2. Shock due to extensive thrombosis in the microcirculation, the pathway is blocked, circulatory disorders occur, and shock occurs.
3. Embolism due to extensive thrombosis in the microcirculation, hypoxic-ischemic injury occurred in the affected organs, and multiple organ failure occurred.
4. Hemolysis is damaged by red blood cell deformation, microvascular hemolysis occurs, hemoglobinuria, jaundice, fever.
Examine
Neonatal disseminated intravascular coagulation examination
Blood routine
(1) Blood test: visible red blood cells are helmet-shaped, triangular, twisted and red blood cell debris, and increased reticulocytes.
(2) Platelet count: about 93% of thrombocytopenia, progressive decline, less than 100 × 109 / L (100,000 / mm3), less than 50 × 109 / L (50,000 / mm3), often compared Early appearance, the surrounding blood can be seen more newborn, larger platelets, platelets 30 × 109 / L, there may be intracranial hemorrhage.
2. Coagulation test
(1) clotting time (test tube method): normal is 7 to 12 minutes, shortened during DIC hypercoagulable period ( 6 points), but the hypercoagulable period is short, and the period of consumption and low coagulation is significantly prolonged.
(2) Prothrombin time (PT): 90% of DIC can be prolonged, the normal value of neonatal PT is related to age, some people think that it is 12-20s (average 16s) within 4 days after birth, DIC diagnostic criteria: age 4 Within days, 20s, and those older than 5 days 15s.
(3) Partial thromboplastin time (KPTT) of white clay: The results of domestic normal newborn cord blood test are basically similar to those of older children (37~45s). It is generally considered that >45s can be used as the diagnostic standard for DIC.
(4) Determination of fibrinogen: normal neonatal value of 1.17 ~ 2.25g / L (117 ~ 225mg / dl) 2 ~ 2.5g / L (200 ~ 250mg / dl), fibrinogen <160mg, It has a reference value [using semi-quantitative method, less than 1:32 is equivalent to less than 1.6 g/L (160 mg/dl)], less than 1.17 g/L (117 mg/dl) is the diagnostic standard, and fibrinogen is extremely low in DIC. Prompt prognosis.
3. Fibrinolytic examination
(1) Plasma thrombin time (TT): The normal value of neonates is 19-44 s ( 16.3 s for older children), FDP has antithrombin effect, and FDP increases when fibrinolysis is hyperactive, which prolongs TT and exceeds that of the control group. 3s has diagnostic significance, but it should be noted that fibrinogen can also cause TT prolongation when it is extremely reduced.
(2) Plasma protamine paracoagulation test (3P test): In DIC, due to secondary fibrinolysis, the complex formed by FDP and fibrin monomer increased, this experiment is positive, it should be noted that about 65% Infants with increased fibrinolytic activity within 24 hours after birth can have FDP, but if the 3P test is still positive after 24h, it has pathological significance. In addition, in the late stage of DIC, due to the consumption of coagulation factors and the antithrombin effect of FDP, or due to FDP It has been cleared by the mononuclear-macrophage system, and the 3P test can be turned negative, so the negative 3P test cannot exclude D1C.
(3) euglobulin dissolution time: it is an index reflecting the fibrinolytic activity. Due to secondary fibrinolysis, plasmin activity is enhanced in DIC, so the dissolution time of euglobulin is shortened, and normal neonatal 3~ Within 7 days, the physiological fibrinolytic activity increased, the euglobulin dissolution time was 84 min, then turned to normal, 120 min, and DIC was often <90 min. This test is not very sensitive, and this test is generally not performed.
In addition, several new experimental indicators such as antithrombin II (AT-II), VII and V factors, and platelet B-thromboxin (B-TG) have been used in recent years.
Comprehensive of the above laboratory tests, can be divided into two categories: 1 DIC screening test: thrombocytopenia; PT prolongation; KPTT prolongation; plasma fibrinogen reduction, 2 test for DIC diagnosis: increased FDP; VII and V factor Reduced, prolonged thrombin time (not corrected for protamine).
According to the primary etiology and condition, B-ultrasound, CT, X-ray and other imaging examinations were selected to confirm the diagnosis and differential diagnosis, and to guide the treatment and judge the prognosis.
Diagnosis
Diagnostic diagnosis of neonatal disseminated intravascular coagulation
Diagnostic criteria
1. History to observe the development of primary disease, observe changes in bleeding tendency.
2. The main indicators of DIC monitor the dynamic changes of D-dimer, platelets, clotting time, prothrombin time, 3P test and other items.
3. The primary disease has diseases related to DIC.
4. Bleeding tends to be clinically multiple bleeding tendency.
5. Microcirculatory failure or shock is not easy to explain microcirculation failure or shock with the primary disease.
6. Symptoms and signs of multiple microvascular embolism such as skin, subcutaneous, mucosal embolization and necrosis and early renal, brain, lung and other organ dysfunction.
7. Platelet decline
8. Fibrinogen fibrinogen <1.5 g/L or progressively reduced or higher than 4 g/L (<1 g/L in liver disease).
The 9.3P test was positive for the 3P test or 0.2 g/L for FDP (0.6 g/L for liver disease).
10. The plasma prothrombin time is shortened or prolonged by 3s or dynamically; or the time of partial thromboplastin in kaolin is shortened or prolonged by >10s.
11. The euglobulin dissolution time euglobulin dissolution time is shortened by <70 min or plasminogen is reduced.
12. Other VIII: C reduction, increased VWF: Ag, decreased VIII: C/VW: Ag, decreased antithrombin III (ATIII) content and activity; plasma B-platelet globulin (B-TG) or thromboxane A2 (TX A2) increased; plasma fibrin peptide A (FPA) increased or fibrin turnover rate increased; positive thrombus test.
In 1987, the first Chinese Society of Hematology National Conference on Thrombosis and Hemostasis, the diagnostic criteria (amendments) for DIC are as follows: 1 there are basic diseases that are prone to cause DIC, 2 have the following two or more clinical manifestations: A. multiple hemorrhagic tendencies, B. Microcirculatory failure or shock that is not easy to explain by primary disease, C. Symptoms and signs of multiple microvessels, such as skin, subcutaneous mucosal embolism, necrosis and early appearance of kidney, gallbladder, liver and other organ dysfunction, D. Anticoagulant therapy is effective, 3 laboratory tests have the following three or more abnormalities: A. platelets are less than 100 × 109 / L (100,000 / mm3) or progressive decline [hepatic disease DIC is less than 50 × 109 / L (50,000) /mm3)], B. fibrinogen is less than 1.5g / L or progressive decline, or higher than 4.0g / L (liver disease DIC is less than 1.0g / L), C.3P test positive or FDP higher than 20mg / L (hepatic disease DIC higher than 60mg / L), D. prothrombin time shortened or prolonged more than 3s or dynamic changes, or APTT shortened or prolonged more than 10s, E. euglobulin dissolution time shortened, or plasminogen Reduction, F. Difficulties, special should have the following one or more experimental abnormalities: factor VIII: C decreased, vwF: Ag increased, VIII: C / vwF: Ag ratio decreased; AT-III contained And reduce the activity, or B-TG plasma TXB2 increased plasma fibrinopeptide A (FPA) or increase the growth rate of the conversion of fibrinogen, thrombosis test positive.
Differential diagnosis
1. Neonatal hemorrhagic disease should first be differentiated from neonatal hemorrhagic disease caused by vitamin K deficiency. The baby is generally in good condition, platelet count, PT, PTT, fibrinogen is normal, blood FDP is normal, and vitamin K treatment is effective.
2. Severe liver disease, severe liver disease often occurs, abnormal blood coagulation test, due to multiple bleeding, jaundice, disturbance of consciousness, renal failure, decreased platelet and fibrinogen, prolonged prothrombin time, easy to be confused with DIC, should be combined with clinical Analysis, liver disease without thrombosis, 3P test negative, FDP and euglobulin lysis time is normal, heparin treatment has no effect.
3. Thrombotic thrombocytopenic purpura This disease is a microthrombus that is widely formed in the capillaries: microvascular hemolysis, thrombocytopenic purpura, kidney and nervous system damage, very similar to DIC, but this disease has characteristic transparent thrombus, thrombosis There is no red, white blood cells, no consumption of coagulation, so prothrombin time and fibrinogen are generally normal, and sometimes abnormal, pathological biopsy can confirm the diagnosis.
4. In addition, hemophilia, congenital fibrinogen deficiency, etc. should also be excluded, primary fibrinolysis is extremely rare, streptokinase and urokinase treatment are typical examples, this disease and DIC are extremely difficult to identify because two Can be induced by the same cause at the same time, both have fibrinolysis characteristics, such as hemorrhage, FDP increased, the difference between the two is mainly fibrinolytic sites, DIC secondary fibrinolysis is a physiological response to thrombosis, typical sites are limited to microcirculation The primary fibrinolysis is in the large blood vessels, and the endothelial cells release the active factor.
