obstetric disseminated intravascular coagulation
Introduction
Introduction to obstetric disseminated intravascular coagulation Disseminated intravascular coagulation (DIC) is not an independent disease, but an intermediate disease or complication characterized by extensive intravascular coagulation and hemorrhagic tendencies associated with certain clinically diagnosed diseases. DIC means that under the action of certain pathogenic factors, coagulation factors and platelets are activated, a large amount of blood coagulation substances enter the blood circulation, causing microvascular thrombosis in the blood vessels, or secondary fibrinolysis, resulting in organ dysfunction, hemorrhage, anemia and even The pathological process of shock is characterized by coagulopathy. The clinical characteristics are changeable, and the laboratory diagnosis methods are not uniform. There is no specific treatment plan at present. Some conventional treatment methods, such as the use of heparin, have not undergone rigorous research and demonstration, which was formerly called consumptive coagulation. The components consumed in the DIC process are rare. During the whole pregnancy, DIC can be complicated by different diseases, especially in the third trimester and during childbirth. It is a serious complication that seriously affects maternal life. . basic knowledge Probability ratio: maternal incidence rate 0.2% Susceptible people: women who are pregnant during pregnancy Mode of infection: non-infectious Complications: shock, pulmonary edema, hematuria
Cause
Obstetric disseminated intravascular coagulopathy
Infectious abortion (25%):
In the case of illegal abortion and intrauterine injection of drugs in the second trimester, the infection causes bacterial and bacterial toxins to enter the blood, causing chorioamitis, amnion resulting in sepsis, damage to vascular endothelial cells, platelet aggregation, tissue necrosis and release of thromboplastin.
Expired abortions in the dead (25%):
Pritchard (1959) reported that about 25% of pregnant women had a low-fibrinogenemia in the fetal death for more than 4 weeks, and almost no coagulopathy was found before 4 weeks. The hypoproteinemia occurred because of stillbirth. The retention, release of tissue thrombin and trigger DIC.
Early exfoliation of the placenta (20%):
It is an obstetric emergency that endangers the life of mother and child. The incidence rate in China is 0.46% to 2.1%. The reported rate in the southern United States is 0.46% to 1.3%. The difference is due to different diagnostic criteria. The fetal death rate is 1.2% and 9.2% respectively. The cause of placental abruption is unknown, but most occur in patients with hypertension, due to spastic contraction of spiral arterioles, decidual ischemia, hypoxia injury necrosis, release of thromboplastin, postpartum hematoma, consumption of fibrinogen as low fiber Prokaryemia, fibrinogen <1 ~ 1.5g / L bleeding tendency and organ embolism.
Amniotic fluid embolism (15%):
Amniotic fluid contains epithelial cells, bristles, keratin, fetal fat, meconium, mucus and other particulate matter. Amniotic fluid enters the blood circulation and triggers the internal and external coagulation system, which can destroy platelet aggregation, promote coagulation, and activate coagulation factor VII. The surface of the vascular endothelium forms endogenous thromboplastin, which has a strong procoagulant effect. The amniotic fluid not only contains procoagulant substances, but also contains fibrinolytic enzymes, activates the fibrinolytic system, and converts plasminogen to fibrinolysis. Enzymes, which dissolve fibrin into fibrin degradants (HDP), can also dissolve fibrinogen, consume a lot of coagulation factors, especially platelets and fibrinogen, and fibrin dissolves, making blood high. The condensed state changes sharply to low-coagulation and high-solubility, so amniotic fluid embolism leads to DIC, the condition is dangerous, develops rapidly, falls into deep shock, and even dies within a few minutes.
Shock (5%):
Late shock, microcirculation congestion, slow blood flow, increased blood viscosity, easy accumulation of red blood cells, and severe ischemia, hypoxia and accumulation of a large number of acidic metabolites, can damage vascular endothelial cells, activate endogenous coagulation The system causes DIC, traumatic shock, and the damaged tissue can also activate the exogenous coagulation system.
Severe hypertensive disorder complicating pregnancy (15%):
Pathophysiological changes, severe vasospasm contraction, blood concentration, ischemia, hypoxia, and endothelial cell damage in the body cause loss of epoprostenol (prostacyclin) synthase, thromboxane (TXA2) synthase Increase, PGI2 / TXA2 ratio decreased, collagen increased, thereby activating platelets, triggering platelet adhesion and aggregation, release of adenosine diphosphate (ADP), serotonin (5-HT), catecholamines further platelets, thrombocytopenia, so severe Hypertensive disorder complicating pregnancy has conditions for activating the endogenous coagulation system. Clinical manifestations include hemorrhagic symptoms, hematemesis, and hematuria. However, there is no hypofibrinogenemia in the laboratory and hemolytic anemia and thrombocytopenia, so hemolysis Anemia is not secondary to fibrinolysis, but hypertensive hemolysis in pregnancy with hypertensive disease. Non-consumptive coagulopathy should be differentiated from DIC. Hemolytic anemia, thrombocytopenia and hepatic enzyme increase are collectively referred to as Hellp syndrome. Whether there is a causal relationship between Hellp and DIC needs further observation.
Pathogenesis
The above factors cause DIC to be usually through the following ways.
1. First, a large number of tissue factors enter the blood circulation, initiate exogenous clotting pathways, such as severe trauma during surgery, placental abruption, fetal death, etc. In these cases, there are a large number of tissue factors (ie, factor III, or Tissue thromboplastin (TTP) is released into the bloodstream, forms a complex with Ca2 in plasma, and factor VII, and activates the exogenous coagulation system. It is currently believed that the activation of the coagulation system is mainly mediated by TTP. Mononuclear cells or macrophages, like endothelial cells, have TTP expression on the cell surface when stimulated by a causative agent or medium.
2. Secondly, activate coagulation factor VII, initiate endogenous coagulation pathway. For example, bacterial endotoxin can damage vascular endothelial cells during infective abortion, expose subintimal collagen, and coagulate factor XII with collagen or endotoxin. The thiol configuration on the amino acid is altered, and the active site is exposed to serine residues. In addition, factor XII and activated factor XIIa may also be soluble in kinase, such as kallikrein, fibrinolysis or trypsin. The enzyme XIIf is produced by the action of the enzyme, which is called enzymatic activation. XIIf is a kallikrein activator, which activates plasma kallikrein to kallikrein, which further activates factor XII. Thereby accelerating the response of the endogenous coagulation system, XIIa and XIIf can also activate fibrinolysis, kinin and complement systems in succession to further promote the development of DIC.
3. Infective abortion and amniotic fluid embolism due to bacterial endotoxin and some particulate matter in amniotic fluid into the blood circulation can activate platelets, so that the membrane glycoprotein IIb ~ IIIa complex as a fibrinogen receptor functional expression, combined with fibrinogen Promote platelet aggregation, and pathogenic factors damage vascular endothelial cells, subendothelial collagen and microfiber exposure, and bind platelets by von Willebrand factor (vWF) or directly bind to platelet membrane glycoprotein Ib. Activated platelets release adenosine diphosphate (ADP), serotonin (5-HT), thromboxane A2 (tromboxane, TXA2), which in turn activates platelets, resulting in the formation of micromers. In addition, when platelets are activated , membrane phospholipids change, that is, negatively charged phospholipids from the inner layer of the membrane to the outer layer, through the interaction of Ca2 with factors XI, Xa, X, II, promote the formation of thrombin with the participation of cofactors V and VIII, usually In the pathogenesis of DIC, platelets have multiple secondary effects, but they can also play a primary role.
4. Vascular endothelial cells (VEC) have two-way interaction with vascular tone, coagulation and fibrinolysis. Under the action of pathogenic factors, such as severe infectious abortion (pathogens can be bacteria, viruses, fungi, protozoa, spirochetes). Or rickettsia), often damage vascular endothelial cells, dysregulation of physiological balance, for example, endotoxin can directly act on VEC, or release tumor necrosis factor (TNF) through monocyte macrophages and neutrophils In VEC, VEC can also be mediated by interleukin-1 (IL-1), platelet activating factors (PAF) and complement (C5a). TNF and IL-1 can alter the surface properties of VEC. Myeloblasts, monocytes and T cells adhere to the surface, PAF causes platelet aggregation, release, promotes neutrophil and monocyte chemotaxis and granule secretion, and promotes interaction between endothelial cells and neutrophils, C3a and C5a can release IL-1 from monocytes, and C5a can enhance the production of oxygen free radicals by activated neutrophils, which results in damage to endothelial cells and promotes DIC.
In conclusion, coagulation is activated during DIC, causing thrombin and plasmin to occur in circulating blood. On the one hand, thrombin excises fibrin peptide A, B from fibrinogen, and the remaining fibrin monomer is polymerized in microcirculation. Fibrin, which forms thrombus, interferes with blood flow, peripheral ischemia, damages organs, and thrombocytopenia. On the other hand, plasmin cleaves fibrin (original) C-terminus, produces FDP (fibrinogen degradation products), and fibrin The monomer forms a soluble complex, which interferes with the polymerization of the monomer, causes bleeding, and the high affinity of the fragments D and E with the platelet membrane causes the platelets to lose function and also causes bleeding. The plasmin can also degrade the blood coagulation factors V, VII, IX, XI. And plasma growth hormone, ACTH, insulin, etc., plasmin activates the complement system to dissolve red blood cells, release ADP and membrane phospholipids to promote blood coagulation; dissolve platelets to reduce and provide procoagulant substances, the above is DIC when thrombosis, bleeding and The pathophysiological basis of organ dysfunction.
Prevention
Obstetric disseminated intravascular coagulation prevention
Obstetrics DIC should be based on prevention. It should raise the awareness and treatment of high-risk pregnancy, childbirth, and prevent the occurrence of DIC. The characteristics of obstetric DIC are acute onset. Once DIC occurs, the birth should be terminated, the contents of the uterus should be removed, and the exogenousness should be blocked. Coagulation substances, the condition can be quickly improved, naturally relieved, and the anticoagulant is used when necessary to prevent the development of DIC.
Complication
Obstetric disseminated intravascular coagulation complications Complications, shock, pulmonary edema, hematuria
1. Shock acute DIC can cause shock. The degree of shock is not proportional to the amount of bleeding. Due to micro-thrombosis blocking the microcirculation capillary network, tissue perfusion stops, tissue necrosis can lead to shock, microcirculation and systemic shunt can also occur. Phenomenon, although the microcirculation is blocked by blood clots, the blood can be returned to the vein without capillary passage through the arteriovenous vein. The clinical manifestations may have normal arterial pressure. Actually, there is insufficient perfusion of tissue cells, so the degree of shock is different. If not timely rescue to improve the perfusion of tissue cells, dredge microcirculation, plus varying degrees of secondary fibrinolytic hemorrhage, can eventually lead to serious circulatory disorders, irreversible shock, so DIC shock is not necessarily positive with the amount of bleeding Relatedly, shock occurs rapidly, and shock occurs early and is not easy to recover.
2. Organ embolism microthrombus can involve 1 organ or multiple organs. Symptoms of microthrombus formation are different due to different parts of the blocked organs. Kidney DIC manifests as acute renal insufficiency, hematuria and less Urinary or auria, cardiac DIC manifests as acute cardiac insufficiency, arrhythmia, and even cardiogenic shock, DIC in the lungs is dyspnea, pulmonary edema and pulmonary hemorrhage, DIC in the brain can cause paralysis, convulsions and even coma Adrenal DIC can cause adrenal cortical necrosis, and pituitary necrosis can lead to Xihan syndrome.
Symptom
Obstetric disseminated intravascular coagulation symptoms Common symptoms hemoptysis and weakness, hair loss, skin bleeding spots, oliguria, dyspnea, postpartum hemorrhage
1. Hemorrhagic obstetrics DIC is the most common uterine bleeding, and often mistaken for postpartum hemorrhage of uterine contraction, delay in rescue time, uterine bleeding is characterized by continuous vaginal bleeding, varying amounts of bleeding, no blood clots, serious May be associated with skin bleeding spots, bleeding gums, hemoptysis, hematemesis, hematuria, as well as injection needle and surgical incision bleeding, bleeding.
2. Circulatory disorders due to microcirculation thrombosis, venous return flow is drastically reduced, combined with blood loss, circulation disorder, blood pressure drop, shock occurs, and a large number of platelets are destroyed, histamine and 5-tryptamine release, microvascular contraction, Aggravation of hypoxia, severely affect the main organ heart, liver, kidney and adrenal function; myocardial contraction is inhibited, heart function is reduced; kidney due to renal cortical embolism, ischemia, hypoxia, necrosis can occur and lead to acute renal failure; In the lungs, due to extensive embolization of the pulmonary capillaries, bleeding occurs and recognizes respiratory distress syndrome (ARDS), so there may be confusion, rapid pulse rate, difficulty breathing, cyanosis, oliguria or no urine.
3. The onset of disease is generally rapid onset, sudden, rapid development, amniotic fluid embolism, early exfoliation of the placenta, severe pregnancy-induced hypertension, a small number of slow consumption of coagulation factors, slower development of the disease, less bleeding, such as expired abortion, Stillbirth and so on.
Examine
Obstetric disseminated intravascular coagulation examination
1. Platelet count platelet count rapidly decreased to <100×109/L, and the disease increased to 50×109/L. The decrease of platelet indicates the convenient method of blood coagulation factor consumption. The platelet count <150×109/L is platelet. The count is small and DIC cannot be excluded.
2. The process of measuring DIC by fibrinogen is that plasma proprotein is converted into fibrin by the action of internal and external procoagulant substances, blood is continuously coagulated, and fibrin has been formed, which is dissolved due to increased plasmin activity. Therefore, DIC is mainly shown as hypofibrinogenimia, which is generally less than 1.6g/L; severe cases can be less than 1g/L.
3. Prothrombin time is measured by the preliminary screening test of exogenous coagulation system. Because of the consumption of I, II, V, VII and X factors, the activity of fibrinolytic enzyme is increased, so the prothrombin time is prolonged. 13s, if extended for more than 3s, it is abnormal.
4. Euglobulin lysis test This test is to remove the dissolved substances of the fibrin system, to understand the fibrinolytic activity, the normal value of 2 ~ 4h, when the fibrinolysis is <120min.
5. Plasma protamine paracoagulatin test (3P test) Normally, the content of soluble fibrin monomer complex in plasma is very small, 3P test is negative, soluble fibrin monomer increases in DIC, protamine sulfate (Fish protamine) can be decomposed, and the monomer complex polymerizes itself into an insoluble fibrin clot to form a jelly. This process is called a secondary solidification phenomenon, and the 3P test is positive, but when the fibrinolysis is excessive, When the fibrinolytic activity is enhanced and the fibrin is degraded to D and E fragments, the 3P test is negative, so the 3P test can predict different stages of DIC.
6. Fibrin degradation products (FDP) In the consumptive low coagulation phase and secondary fibrinolysis period, due to the consumption of platelets and coagulation factors, fibrin degradation products are excessively produced, normal 40-80 g/ml, DIC>40-80 g/ Ml.
7. Whole blood clot test If there is no fibrinogen test condition, refer to the whole blood clot test tube method: take 2 to 5 ml of the patient's blood and place it in a small test tube, place it in a tilt position, observe the time of blood coagulation, blood The standard of coagulation is that the blood clot is shaken or loosened, thereby presuming the fibrinogen content (Table 1).
8. Fibrinolytic test 2 ml of blood that has been coagulated in a normal person is added to 2 ml of blood of the patient for 30 to 40 minutes, and the blood clot of the normal person is broken, indicating that the patient has hyperfibrinoactivity.
9. Fibrin peptide (FP) A/B is first released from fibrinogen under the action of thrombin, and can be used as an early indicator of coagulation. The FDA content of normal people is <9g/L, and the early stage of DIC is up to 10 ~100 times, FPB <2, DIC increased, FPB 15 ~ 42, 41 ~ 42 peptide is a sensitive indicator of fibrinolysis.
10.D-dimer is a specific fibrin degradation product produced by lysozyme under the action of plasmin. It can reflect the formation of thrombin and the activation of plasmin. As one of the molecular indicators of hypercoagulability and fibrinolysis, the false positives in the enzyme-linked immunosorbent assay (ELISA) are significantly reduced. Bick et al. showed that the D-dimer assay has a sensitivity of 94% and a specificity of 80%. The positive predictive value is 100%.
11. Antithrombin-III (AT-III) is the most important thrombin inhibitor in the body. Due to the degradation of elastase released by persistent clotting and activated neutrophils, and the decrease in AT-III production, AT-III reduces the diagnosis of DIC and can be used as an indicator of anticoagulation efficacy.
Diagnosis
Diagnosis and differentiation of obstetric disseminated intravascular coagulation
1. Severe viral hepatitis Severe hepatitis has many similarities with DIC in clinical and laboratory tests, such as bleeding tendency, kidney damage, liver damage, altered consciousness, low blood coagulation factor and thrombocytopenia, and severe hepatitis. Whether DIC complications have occurred in the development of treatment options.
2. Thrombotic thrombocytopenic purpura (TTP) The clinical and laboratory tests of this disease have many similarities with DIC, such as bleeding tendency, kidney damage, disturbance of consciousness, thrombosis, thrombocytopenia and platelet activation, and increased metabolites.
3. Primary fibrinolysis into the disease is extremely rare, can be expressed as bleeding tendency, fibrinogen is extremely reduced and various fibrinolytic experimental indicators are abnormal, must be differentiated from secondary fibrinolysis caused by DIC, the identification points Have:
1 microcirculatory failure and embolization performance is rare;
2 In addition to the extreme low fibrinogen, the reduction of other coagulation factors is not obvious;
3 thrombocytopenia is not obvious, its activation and metabolites do not increase;
4D-dimer is mostly negative in primary fibrinolysis;
5 In addition to FPA, other coagulation factor activation molecular markers such as TAT, F1 2 and AT-III are generally normal.
