DIC

What is DIC?

DIC-syndrome is the most common type of hemostasis pathology. Its basis is the generalized coagulation of blood in the vessels of the microvasculature with the formation of a large number of microthrombi and blood cell aggregates. In this case, normal blood circulation is blocked in most organs and systems, leading to the development of deep dystrophic changes in them. Following intense blood coagulation, hypocoagulation (a decrease in the ability of blood to coagulate), thrombocytopenia (a decrease in the number of platelets per unit volume of blood), and hemorrhage (bleeding) develop. The syndrome occurs with a wide variety of diseases, always leading to a loss of the liquid properties of the blood and a violation of its circulation in the capillaries, which is incompatible with the normal functioning of the body. At the same time, the severity, prevalence and speed of the development of DIC is very diverse – from fulminant deadly forms to latent (latent) and protracted ones, from generalized coagulation to regional and organ thrombohemorrhages.

Causes of DIC

1. The frequency of DIC is not uniform for different types of pathology. With some diseases and effects, it necessarily arises and becomes an integral part of the pathological process, with others it is less common.
2. More often, DIC syndrome is caused by the following pathological processes and effects.- Generalized infections and septic conditions (bacteremia, viremia – the presence of viruses in the blood), including during abortion, childbirth, with prolonged catheterization of blood vessels. In septic shock, acute DIC occurs always. Infections are associated with most cases of DIC in newborns.
   – All types of shock, such as hemorrhagic, traumatic, burn, anaphylactic (occurring with allergies), septic and cardiogenic. DIC is a compulsory shock companion of any origin. Moreover, the severity of the syndrome in question is directly proportional to the severity and duration of the shock condition.
   – Surgical interventions that are especially traumatic for the patient (especially for malignant neoplasms, operations on parenchymal organs, the use of APC and intravascular interventions). Bleeding, collapse massive blood transfusions speed up the DIC.
   – DIC syndrome is accompanied by any terminal condition.
   – DIC-syndrome always develops if a patient develops acute intravascular hemolysis (destruction of cells inside the blood vessels), including incompatible transfusions (blood transfusions that are not suitable for this patient by group).
   – Obstetric pathology, in particular placenta previa, premature detachment of the placenta or its manual separation, blockage of the uterine vessels with amniotic fluid, fetal death. In all these conditions, severe DIC syndrome is recorded in 20-35% of cases.

Pathogenesis during DIC

The reasons that can cause the development of a patient with DIC syndrome are currently known to a huge amount. Despite this, the basis for the formation of disseminated intravascular coagulation syndrome is the activation of the blood coagulation system and platelet hemostasis by various factors of endogenous origin, i.e., factors that form directly in the human body. These factors primarily include: tissue thromboplastin, the breakdown products of tissues and blood cells, fragments of damaged vascular endothelium (their inner membrane). The last condition for the development of this pathology can occur in the case of exposure to an infectious agent, immune complexes, components of the complement system and other factors. In addition, the following exogenous factors (which enter the human body from outside) play an important role in the mechanism of DIC, the presence of which also activates the blood coagulation system: a variety of bacteria and viruses, rickettsia, drugs, substances used as blood substitutes, amniotic fluid, poisons of various snakes, deep circulatory disorders (including with excessive blood loss), hypoxia (decreased oxygen supply) of tissues, acidosis (disturbance of the acid-base balance in the body ), microcirculatory disorders, primary or secondary depression of anticoagulant mechanisms (antithrombin III deficiency) and components of the fibrinolytic system (deficiency of plasminogen and its activators, a sharp increase in antiplasmin activity), insufficient functional ability or generalized lesion of the vascular endothelium, decrease in its antithrombotic activity. Perhaps the combined participation of several of these mechanisms.

The central place in the development of disseminated intravascular coagulation syndrome is given to excessive synthesis in the vascular bed of thrombin, which leads to thrombinemia, as well as depletion of the anticoagulant blood system. The appearance of thrombin in circulation is a necessary condition for both the transformation of fibrinogen into fibrin and the “bonding” of blood cells (platelets and red blood cells).

In most cases of disseminated intravascular coagulation, tissue thromboplastin (factor III coagulation) acts as the initiator of the pathological process. In combination with the coagulation factor VII, it promotes the activation of factor X. Tissue thromboplastin enters the bloodstream from damaged and degraded tissues, which occurs during injuries, operations, necrosis and destruction of tissues of bacterial origin, during childbirth with amniotic fluid. With the participation of activated platelets, tissue thromboplastin can also be produced by damaged vascular endothelium with immune and immunocomplex lesions, endothelial damage by toxins, and hemolysis products. From blood cells, as is known from the recent toxicosis of pregnant women, with infection of amniotic fluid, cesarean section, heavy bleeding, intensive massage of the uterus. Occasionally, DIC develops during normal delivery.

• Tumors, especially hemoblastoses, leukemia or high viscosity syndrome, cancer of the lung, liver, pancreas, prostate, kidney. In acute leukemia, DIC at different stages of the disease is detected in 33-45% of patients, in acute promyelocytic leukemia in most patients.
• Various diseases leading to the destruction of the liver, kidneys, pancreas and other organs and their systems.
• Burns of various origins, such as thermal, chemical burns of the esophagus and stomach, especially with severe hemolysis.
• Immune and immunocomplex diseases, including systemic lupus erythematosus, rheumatism, rheumatoid arthritis with visceral lesions, Shenlein-Genoch hemorrhagic vasculitis, glomerulonephritis.
• Hemolytic uremic syndrome.
• Allergic reactions of medicinal and any other origin.
• Heavy bleeding.
• Thrombotic thrombocytopenic purpura.
• Snake poisoning.
• Transfusion of large volumes of blood; the introduction of hemo-preparations containing activated coagulation factors.
• Treatment with drugs that cause platelet aggregation, increase blood coagulability and reduce its anticoagulant and fibrinolytic potentials, especially with their combined use (a-adrenostimulants, synthetic progestins, aminocaproic acid and other fibrinolysis inhibitors).
• Improper use of fibrinolytics and anticoagulants in doses that cause depletion of the reserve of antithrombin III and the fibrinolytic system.
• Treatment with defibrinating drugs – arvin, ankrod, defibrase, reptilase (therapeutic DIC).
• Multiple and giant angiomas (such as Kazabah-Merritt).

Currently, the first place among the causes of the development of DIC (disseminated intravascular coagulation) is occupied by generalized infections, both bacterial and viral, as well as septicemia. They account for 30-40% of all cases of this pathology, and more than 70% in the neonatal period. In the latter case, the pathology under consideration is called “malignant purpura of the newborn.” Bacteremia is often the cause of obstetric thrombohemorrhagic syndrome. The sudden spread of infection from the genital tract, both independent and with infected amniotic fluid, forms the most severe forms of postpartum DIC. Such infection should always be thought of in case of early rupture or tearing of the amniotic membrane, the appearance of unmotivated tachycardia in the woman in labor and the fetus, an increase in temperature above 38 ° C after the amniotic fluid leaves, its unpleasant odor, increased white blood cell count in the amniotic fluid, and an increase in leukocytosis in the mother’s blood. However, it should be remembered that with the early development of septic shock, an increase in temperature and leukocytosis in a woman in labor may not be. Early, only macrophages (monocytes) are capable of producing tissue thromboplastin, and this process plays an important role in the mechanism of the DIC syndrome in bacteremia, endotoxinemia, immune and immunocomplex diseases, and some other forms of pathology. Preliminary removal of these cells from the bloodstream in such cases prevents the development of DIC or sharply weakens it.

DIC in malignant tumors is associated with activation of coagulation by special enzymes associated with tumor cells, their contact activation of platelets, and the production of tissue thromboplastin by many tumors. However, for many types of cancer, the production of the bulk of tissue thromboplastin is also carried out by monocytes. This activation process is attenuated by warfarin and enhanced in the presence of heparin.

More rarely, DIC-syndrome is associated with alternative blood coagulation pathways, which are included under the influence of intracellular and tissue enzymes, as well as enzymes produced by bacteria and which are part of snake venoms.

The main role in the development of certain types of disseminated intravascular coagulation syndrome is not tissue thromboplastin, but the activation of the coagulation process of a contact nature, which occurs during hemodialysis, extracorporeal circulation, and artificial heart valves.

During the progression of DIC, the decrease in the blood level of the main physiological anticoagulant, which is antithrombin III, is increasing. This substance is used to inactivate coagulation factors. Similarly, the components of the fibrinolysis system are consumed.

Bleeding with DIC is caused by impaired blood coagulation, aggregation, and an intensive decrease in the bloodstream of the most complete platelets, and blockade of the remaining platelets. Heavy bleeding with DIC often stops or stops by transfusion of platelet concentrates.

The mechanism of development and the severity of DIC syndrome depend on the violation of microcirculation in organs and the degree of their dysfunction. Permanent companions of DIC are shock lung, acute renal failure, and other organ disorders. Their development is associated with a massive blockade of the microvasculature with clots formed by blood clots, stasis of blood cells due to shifts in the rheological properties of blood and hemodynamics, and erythrocyte swelling.