The principle of treatment should take into account both the symptoms and the root cause, and treat both the cause and the effect.
1.Remove the cause of the disease
For example, active and effective control of infection, early delivery of the fetus, placenta and removal of uterine contents, anti-shock, even removal of the uterus, obstetric placental abruption, fetal death in utero, infected abortion, hemorrhagic shock, etc. are prone to DIC, therefore, on the basis of active prevention of the original disease, we should deepen the understanding of the susceptibility of the disease. Therefore, based on the active prevention of the original disease, we should deepen the understanding of the susceptibility to disease, and at the same time, we should pay attention to the prevention and control of acidosis, improve hypoxia, and prevent hemolysis.
2.Improve microcirculation
Improving the perfusion of microcirculation is a prerequisite for preventing and treating DIC. First of all, the blood volume should be replenished to keep the blood flow of microcirculation smooth, with appropriate replenishment of compound sodium lactate solution, whole blood and glucose (dextran solution), increasing blood volume can release the spasm of small arteries, reduce blood viscosity and hypercoagulability, and promote the evacuation of coagulated platelets and red blood cells, especially dextran has the function of repairing vascular endothelial cells, but Dextran 40 (low molecular dextran) has a molecular weight of 40,000, although it has a good effect on expanding and unblocking the microcirculation, but when there is a serious bleeding tendency, it is appropriate to use medium dextran 70 (molecular dextran), and pay attention to correcting acidosis and water-electrolyte imbalance while replenishing blood volume, and avoid applying all drugs that promote blood coagulation, such as vasoconstrictors and high-dose adrenocorticotropic hormones, because high doses have an inhibitory effect on the The effect of reticuloendothelial system.
3.Application of heparin
Heparin is a commonly used and effective anticoagulant, the effect is to block the coagulation process and prevent the consumption of platelet clotting factors, but it is not effective for the formed microthrombus.
(1) Indications: If the diagnosis of DIC is clear and the cause of the disease cannot be controlled rapidly, heparin should be used immediately, the earlier the better, applied in the blood is in a hypercoagulable state, with the following symptoms combined with laboratory tests, and the best effect of heparin within 10 min, 1 h of the appearance of symptoms.
① Platelets fall 150×109/L (100X109 domestic??) below and bleeding spots or petechiae on the skin.
②Blood is in hypercoagulable state, blood is viscous in venous blood sampling, blood pressure drops.
(③) Intractable shock, shock is not proportional to blood loss.
④ Platelets and coagulation factors, rapid decline in fibrinogen, persistent intravascular coagulation.
(5) Persistent bleeding caused by depletion of coagulation factors, bleeding without clotting.
(2) Contraindications.
(1) Significant bleeding tendency or underlying bleeding disorders.
(2) Tuberculosis cavity bleeding, ulcerative bleeding, severe liver disease or hypertensive encephalopathy with bleeding tendency.
③ Shortly after surgery, or if there is a huge bleeding wound that has not been perfectly hemostatic.
(iv) Disseminated intravascular coagulation has transitioned to the hyperfibrinolytic stage.
(3) The application of heparin in obstetric complications: combined with the fact that obstetric DIC mostly occurs during labor and delivery, and there is a huge placental abruption surface after delivery, whether heparin is applicable, according to the summary reports of domestic and foreign literature, the following insights are given on the aforementioned several obstetric complications that induce DIC.
① early placental abruption: its main symptoms are overt and covert bleeding, mostly occurring in hypertensive women, severe cases of fetal death in utero, the percentage of fetal death in utero is 0,12% abroad and 0,17% to 0,23% in Beijing Maternity Hospital, thrombocytopenia, hypofibrinogenemia, domestic and foreign consensus in a large number of blood transfusions, transfusion of fresh frozen plasma can increase clotting factors, improve fibrinogen, as soon as possible The coagulation factors can return to normal naturally after the delivery is over and the fetus and placenta are late, so there is no need to apply heparin to avoid aggravating the bleeding. 10U fresh frozen plasma transfusion is reported abroad to increase fibrinogen by 1g/L, but there are also reports that small doses of heparin 25mg given before delivery did not increase postpartum bleeding.
②Fetal death in utero: In 1959, Pritchard reported that fetal death in utero stays in utero for more than 4 weeks and hypofibrinogenemia occurs in almost 25% of cases, so heparin should be infused before the stillbirth lesion is cleared, and then labor should be induced to clear the fetal material when fibrinogen returns to normal.
③ Infectious abortion and miscarriage: infectious abortion is mainly the active control of infection after the removal of fetal material in the uterus, DIC can disappear naturally, a variety of abortions including midterm pregnancy induction, the cause of DIC is related to the surgical measures taken, according to an industrial city of California, Ingwood Hospital (1980-1981): the incidence of attraction scraping DIC is 8/100,000, dilation to remove Fetal material scraping DIC incidence of 191/100,000, high tension saline induction of labor DIC incidence of 658/100,000, although there are no detailed statistics reported in China, according to the Beijing Medical Association of several large hospitals in Beijing (1983), although high tension saline induction of labor has long been abandoned, but coriander and smallpox powder protein (smallpox powder) induction of labor also have DIC incidence, the incidence of DIC in mid-expectancy is significantly higher than early aspiration abortion.
④Shock: more common in obstetrics is hemorrhagic shock, once DIC occurs, a vicious circle is formed, especially acidosis inhibits heart and brain function and inhibits the activity of heparin, treatment actively corrects acid to replenish blood volume, transfuse fresh frozen plasma to block the vicious circle, heparin needs to be added in large amounts in acidosis.
⑤ Amniotic fluid embolism: Although uncommon, but the death rate can be as high as 80%, the main symptoms are sudden respiratory distress, chills, shock, bleeding and the degree of shock is not proportional, domestic and foreign unanimously advocate the application of heparin as soon as possible, the best effect is applied within 10 min after the onset of symptoms, the symptoms can be typical without waiting for laboratory results, such as the application of heparin, bleeding still can not be controlled, the uterus should be removed to block the source of clotting activity The Beijing Maternity Hospital once performed hysterectomy in the delivery room for a case of maternal blood pressure 0, which saved the patient, and the literature statistics of amniotic fluid embolism DIC timely application of heparin to increase the survival rate.
(4) The dosage and usage of heparin: a single dose can be calculated as 0,5-1mg per kg of body weight [each (mg) is equivalent to 125U], intravenous drip can take effect immediately, but the effective time is short, need to continue intravenous drip or every 4-6 hours to give once to maintain effective anticoagulation level, 24h dosage can be around 200mg, the first time with heparin 50mg added to 100ml of glucose solution. After rapid intravenous drip, 100-200mg of heparin should be added to 1000ml of glucose solution or isotonic saline and drip slowly to maintain 24h or intermittent intravenous drip, obstetric DIC occurs mostly during delivery, after the delivery of the fetus, placenta and retained fetus, the exogenous pro-coagulant substances are cleared and the coagulation phenomenon can be relieved naturally, so heparin is mostly taken intermittently, and the first drip can be taken before there is no laboratory result. Heparin is generally excreted in 4-6h, but in renal impairment, its half-life can be extended, the use of the process requires that the clotting time is maintained within 15-30min, if the clotting time is extended, the interval must be extended according to the extended time to decide to extend or reduce the amount of discontinuation, otherwise, until the application of the condition improves, bleeding stops, blood pressure stability before gradually stopping the drug.
The main adverse effect of heparin is bleeding. In 1996, Dr. Turpie from Canada reported in the Second Great Wall International Symposium on Interventional Cardiology that the adverse effect of heparin bleeding is due to the binding of heparin to platelets and inhibition of their function. Heparin also binds to endothelial cells and macrophages, which is the dose-dependent mechanism of heparin clearance, so heparin has obvious limitations, while the low molecular weight heparin developed in trial now binds less to plasma proteins, endothelial cells and platelets, and its clearance mechanism is not dose-dependent, so it has a better dose-effect relationship than heparin, so its Therefore, it has a better dose-effect relationship than heparin, so its adverse effects of bleeding are rare, and we look forward to the early promotion of low-molecular-weight heparin.
Heparin has no direct anticoagulant effect, but needs to combine with antithrombin III (ATIII) to play anticoagulant effect, if the patient’s original ATIII level is low or obviously depleted in the course of DIC, the effect of heparin will be affected, so it should be supplemented with fresh frozen plasma drip, which contains a considerable amount of ATIII can be synergistic with heparin, if the heparin used is found to be excessive, use sulfate If an overdose of heparin is found, fisetin sulfate (fisetin) can be used to counteract it. 1 mg of fisetin sulfate (fisetin) intravenously can counteract 1 mg of heparin.
The easiest way to determine the efficacy of the treatment is by dynamic testing of platelet count or dynamic monitoring of ATIII levels.
4.Anti-thrombin III (ATIII) therapy for DIC patients is at a low level due to ATIII depletion, ATIII therapy alone 1600-3000 U/d for 2 days can replace heparin treatment, and the combination of heparin and ATIII therapy has the adverse effect of bleeding.
5, active protein-C compound acetylsalicylic acid (APC) impaired liver function, infection, can make compound acetylsalicylic acid (APC) level decreased, cytokines such as TNF make PC activity decreased, compound acetylsalicylic acid (APC) can inhibit chronic and acute coagulation, fibrinolytic activity, compound acetylsalicylic acid (APC) 5000 ~ 10000ug/d for 2 days, on placenta The compound acetylsalicylic acid (APC) is a safe, effective and beneficial drug for the treatment of DIC.
6.Anti-platelet coagulation drugs
As mentioned before, dextran can reduce the adhesion and coagulation of red blood cells and platelets, because of its negative charge, the general dosage should not exceed 1000ml, dipyridamole (Pansentin) has the effect of platelet coagulation, inhibit the activity of platelet diesterase, the common dose is 200-400mg/d, but anti-DIC platelet coagulation using a large dose of 600mg drip is appropriate, it is also believed that it may be This drug has enhanced the role of prostacyclin (endogenous prostacyclin), and aspirin together with the dosage can be reduced by half, now aspirin advocated with a small dose of 60 ~ 80mg / d, mainly blocking the production of thromboxane and no effect on PGl2 synthase, high dose of both to be inhibited, because the sensitivity of thromboxane cyclooxygenase to aspirin than prostacyclin cyclooxygenase.
7.Supplementation of coagulation factors
The period of consumptive hypocoagulation is an appropriate time to supplement coagulation factors, which are blood components often transfused in obstetrics.
(1) transfusion of fresh blood and fresh frozen plasma: transfusion of fresh blood or stock blood not more than 3 days, in addition to replenishing blood volume, but also replenish a variety of coagulation factors consumed during DIC, but the best effect of transfusion on the basis of anticoagulation, first with heparinization or exogenous procoagulant substances have been removed such as placental abruption has been delivered, fresh frozen plasma is superior to blood in terms of volume expansion because of the absence of cellular components and contains a large amount of antithrombin III, which can be used with Heparin synergistic anticoagulation blocking the continued consumption of coagulation factors, no aggravation of coagulation concerns.
(2) Fibrinogen: When DIC bleeding is not only, fibrinogen drops to 1.25~1g/L, fibrinogen can be transfused, and transfusion of fibrinogen 2g can improve blood fibrinogen 1g/L. If transfusion of thrombinogen complex is not less than 400U is appropriate, but lack of factor VIII, sometimes need to add factor VIII preparation and platelet transfusion.
(3) Platelet transfusion: If platelets fall to 50×109/L, and bleeding is significantly increased, platelet concentrate can be transfused, and platelets isolated from each 500ml of fresh blood is 1U, and each unit of platelet transfusion can improve platelets by 7500μl.
(4) cold precipitate (cryopreacipitate): containing coagulation factors I, V, VIII, XIII, each unit can increase fibrinogen 100mg/L, and can improve the level of factor VIII, but the blood products have the risk of transmission of hepatitis, AIDS, especially fibrinogen products should be with attention.
8.Antifibrinolytic application
Applicable to the late stage of DIC, secondary fibrinolysis period, when secondary hyperfibrinolysis has become the main cause of bleeding, can be used on the basis of heparinization of antifibrinolytic drugs, euglobulinolysis <120min can be used alone, the following four types of antifibrinolytic agents commonly used in clinical practice.
(1) peptidase inhibition (aprotinin): is a kind of earth kinase (natural protein hydrolase) inhibition coin agent, molecular weight 6512, now commercially available peptidase concentration and activity, to kinase release enzyme inactivation unit (KIU) expressed.
The application of peptidase not only reduces the consumption of coagulation factors, but also prevents secondary bleeding due to the activation of coagulation and fibrinolytic system. The first dose of domestic trypsin (trypsin inhibitor) (trasylol) is 80,000 to 120,000 U, which is injected intravenously, and then 10,000 U is injected intravenously every 2 hours until the bleeding stops.
(2) tranexamic acid (hemostatic cyclic acid): tranexamic acid (hemostatic cyclic acid) can form a reversible complex with fibrinogen, thus causing structural changes in fibrinogen and preventing the formation of fibrin, and at high doses, it can directly inhibit fibrin and fibrinolysis by anti-fibrinolytic activity, and has a direct effect on trypsin and fibrin, so its anti-fibrinolytic effect is stronger than that of aminocaproic acid (6-aminocaproic acid) by 6-10 times. The common dose of tranexamic acid (haemostatic cyclic acid) is 0,5-1,0g/time, 2-3 times a day by intravenous infusion, which can be changed to 0,5-1g orally 3-4 times a day when the bleeding situation improves.
(3) Aminohexanoic acid (6-aminohexanoic acid): the first synthetic antifibrinolytic agent molecular weight 131, hemostatic effect is weaker than aminolevulinic acid (hemostatic aromatic acid), the initial dosage of 4-6g added in 50% glucose solution and saline 100ml, 15-30min drip, maintenance amount of 1g per hour, depending on the condition of its maintenance time, the daily amount of no more than 20g is appropriate, oral each time 2g, 3-4 times / d. ～(4) Aminobenzoic acid
(4) aminomethyl benzoic acid (p-aminomethyl benzoic acid, PAMBA): antifibrinolytic effect is 3 times stronger than EACA, toxicity is lower, not easy to form thrombosis, excretion is slow, within 24h with the drug 70% of the original form of excretion from the urine, 30% of inactive metabolites excretion, intravenous dosage again 0, 1 ~ 0, 3g plus 50% glucose solution or saline 10～20ml dilution, slow intravenous push, then 0,1g maintenance, day dosage not more than 0,6g, oral 3 times / d, each time 0,25～0,5g.
Fibrinolytic enzyme and thrombin both belong to double-chain serine proteolytic enzymes, both of which act on specific sites of fibrin and fibrinogen respectively. When coagulation factor VII is activated, the blood is coagulated through the endogenous coagulation system, and the fibrin activity may be enhanced through kinase, and thrombin and thrombin are produced almost simultaneously, holding a balanced state, but in the process of DIC there is both hypercoagulation and Fibrinolytic staggered hypercoagulation, and lost the normal equilibrium, so in the application of heparin anticoagulation need to be in the early DIC hypercoagulation period, do not lose a good opportunity to control coagulation because of bleeding, do not use antifibrinolytic agents to stop bleeding, aggravating fibrin deposition.