DIC-syndrome in adults

DIC-syndrome (a syndrome of disseminated intravascular coagulation) - consumption coagulopathy, developing with the participation of the antigen-antibody reaction and accompanied by thrombus formation in capillaries and small vessels with depletion and impaired formation of all factors.

[1], [2], [3], [4]

Causes of the dIC-syndrome in adults

DIC-syndrome can develop with very many diseases; endotoxins, amniotic fluid, stroma or hemolysate of erythrocytes, catecholamines, developing hypovolemia, decreased blood flow, hypoxia, etc. May be responsible for initiation of the process. In addition to hemorrhages, DIC syndrome can be manifested by vascular hypotension and multiple organ failure.

DIC-syndrome complicates many pathological conditions: all forms of shocks, diseases accompanied by the development of the intoxication syndrome (primarily due to the damage to the liver that produces virtually all factors of blood coagulation), blood thickening, slowing of blood flow, with massive transfusion of protein preparations, especially blood and its components. All these conditions have in their pathogenesis the factors of violation of hemopoiesis, blood thickening, activation of the reticulo-endothelial and immune systems. In this case, with the participation of the antigen-antibody reaction, thrombus formation takes place in capillaries and small vessels. The process consumes a very large number of clotting factors that do not have time to be produced by the liver, especially if it is functional deficiency. Therefore, in large vessels, on the contrary, hypocoagulation and a tendency to bleeding due to afibrinogenemia is noted, since it is the fibrinogen that suffers to a greater extent and serves as a differential criterion in the laboratory diagnosis of ICE syndrome in the coagulogram. The total amount of fibrinogen decreases (other factors, including prothrombin, also decrease), there is an increase in partial thrombin time, thrombin time, prothrombin time, fibrinogen degradation products.

[5], [6], [7], [8]

Pathogenesis

Preservation of the aggregate state of blood is provided by 3 functionally different systems that make up the biological system of blood coagulation:

1. coagulating - forming a thrombus;
2. anticoagulant (anti-coagulant) - preventing thrombus formation;
3. fibrinolytic - dissolving the already formed thrombus.

All these factors are in a state of dynamic equilibrium.

There are two main mechanisms of hemocoagulation: primary, vascular-platelet (STH), and secondary, enzymatic-coagulative (FCG), hemostasis.

STG is carried out at the level of microcirculation and plays an important role in the system of hemostasis. Its main stages are:

• adhesion (adherence to damaged vascular endothelium) platelets;
• aggregation (gluing) of platelets;
• the release of biologically active substances (BAS, mainly serotonin and thromboxane) that cause the formation of the primary hemostatic thrombus.

Activation of STH is facilitated by vasoconstriction, acidosis, slowing of blood flow, increase in blood viscosity, catecholamines, thrombin, ADP, etc., but inhibit its fibrinogen cleavage products, salicylic acid, butadione, quarantil, papaverine, euphyllin, low molecular weight dextrans.

The PCG is mainly carried out in veins and arteries by the interaction of plasma (denoted by Roman) and platelet (denoted by Arabic numerals) clotting factors.

The process of blood coagulation includes 3 phases: the formation of thromboplastin, thrombin and fibrin. The process of blood coagulation begins with damage to the vascular endothelium, vasoconstriction, activation of Hageman's factor. There is stimulation of STH, the formation of the primary hemostatic thrombus and the formation of tissue thromboplastin (1st phase, it lasts 5-8 minutes). The other two phases flow quickly (in a few seconds). Thrombin, formed at the end of the 2 nd phase, converts fibrinogen into fibrin. Approximately 20 minutes after the formation of a loose fibrin clot begins its retraction (compaction), which completely ends after 2.5-3 hours.

[9], [10], [11]

Anticoagulant system

Primary anticoagulants include AT III, heparin, proteins C and B. AT III provides 80% anticoagulant activity of blood plasma. The second most important is heparin (formed in the mast cells of the liver, endothelium of the vessels, REM cells), which activates AT III, blocks the formation of thrombin, disrupts the synthesis of blood thromboplastin, simultaneously prevents the release of serotonin from platelets, inhibits the conversion of fibrinogen to fibrin. In small doses, it activates, in large doses it inhibits fibrinolysis. The low molecular weight fraction of heparin is most active. Proteins C and B are also synthesized in the liver with the participation of vitamin K, are inhibitors of f. V and VIII and together with AT III interfere with the formation of thrombin.

Secondary anticoagulants are formed during blood clotting. These properties are the products of fibrin degradation (PDF, they activate fibrinolysis), AT I, metafactor V, etc.

[12], [13], [14], [15]

Fibrinolytic system

Fibrinolysin (plasmin) is an active proteolytic enzyme that performs the lysis of organized fibrin and fibrinogen. It is formed from profibrinolysin (plasminogen) under the action of cellular and plasma activators. Inhibitors of fibrinolysis are antiplasmin, antitrypsin I, a2-macroglobulin, as well as platelets, albumin, pleural exudate, semen.

Anticoagulant and fibrinolytic hemostasis systems are rapidly depleted in ICE syndrome.

[16], [17], [18], [19], [20], [21]

Symptoms of the dIC-syndrome in adults

DIC-syndrome is caused by a sharp decrease in functionally active capillaries in all organs and tissues due to stasis of erythrocytes, with the development of a hypoxic syndrome of the hemic type and the formation of a decompensated metabolic acidosis. The capillary blood flow in the lungs with the development of respiratory distress syndrome and kidneys with the development of Gasser's syndrome (hemolytic-uremic) is more affected. B. These organs are revealed arteriovenous shunts, which in a greater degree violates gas exchange, and in the kidneys develops cortical necrosis. Even with timely treatment begun in intensive care, the mortality rate is more than 60%.

Symptoms of DIC syndrome are caused by the aggregation of blood cells, clotting, thrombosis of the blood and lymphatic channels, as well as the resulting ischemic and congestive phenomena. The greatest danger is presented by generalized diffuse thrombosis at the level of the terminal microcirculatory unit providing transcapillary exchange: oxygenation, intake and removal of metabolic products. Blockade of organ microcirculation in cases of maximum severity is manifested by ODN, OPN, OPECHN, cerebral insufficiency (coma), catabolic syndrome. Bleeding to the adrenal glands in children leads to acute adrenal insufficiency with clinical symptoms of an uncontrollable collapse.

[22], [23], [24]

Stages

There are 4 stages of DIC syndrome:

• I - hypercoagulation;
• II - consumption coagulopathy, in which the consumption of thrombocytes and coagulation material progresses, fibrinolysis is activated;
• III - marked hypocoagulation, active fibrinolysis, afibrinogenemii;
• IV - restorative or phase of residual thrombosis and blockade.

The course of DIC syndrome can be acute, subacute and chronic; some also give off a lightning form.

At the first stage, the centralization of blood circulation is observed. Skin is hyperemic or pale, cyanosis of nails and mucous membranes is noted. At II stage the skin becomes pale, cold, with a marble pattern. Appears purple. In girls outside the time period appears menses.

In Stage III, the above changes are most pronounced. The marbling of the skin intensifies, it becomes cold, pale-cyanotic, with hypostases. Purple and bleeding from the intestine, nose and other organs predominate. There are arterial hypotension, hypothermia, anuria, metabolic acidosis. A prognostically bad sign is the appearance in patients of such symptoms as "bloody tears", "bloody sweat".

In IV stage with effective treatment of purpura gradually subsides. Protective mechanisms ensure recanalization, melting of blood clots, elimination of fibrin. Leading in the IV stage are asthenic syndrome, vegetative-vascular dystonia, dystrophy with a decrease in MT, polyhypovitaminosis, as well as functional changes in various "shock" organs - kidneys, liver, brain, etc., as much as possible Damaged by thrombosis, dystrophy, fat infiltration.

[25], [26], [27]

Forms

Lightning and acute forms of DIC syndrome are observed in sepsis, extensive injuries, burns accompanied by shock. The clinical picture of increasing toxicosis, cerebral edema and lungs, acute cardiac, cardiopulmonary, renal, hepatic-renal insufficiency prevails. The process is always accompanied by increasing bleeding tissues, profuse bleeding. Subacute and chronic thrombosis usually occurs with the predominance of I and II stages of DIC syndrome, often detected only by laboratory diagnostic methods. The possibility of hypercoagulation and the presence of real conditions for thrombosis may be indirectly indicated by erythrocytosis more than 5 million in 1 μl, hemoglobin level above 160 g / l, sharply accelerated ESR, high hematocrit, presence of hyperfibrinogenemia, significant changes in CBS.

Diagnostics of the dIC-syndrome in adults

The laboratory diagnosis of the developed manifestations of DIC syndrome should be based on several positive tests:

1. thrombocytopenia + prolongation of clotting time (VSC) + positive coagulation test (PKT) + hypofibrinogenemia + AT III deficiency;
2. thrombocytopenia + elongation of activated partial thromboplastin time (APTT) + thrombin test extension + decrease in AT III level + increase in the level of fibrin degradation products (PDF). The absence of hypofibrinogenemia and a decrease in the concentration of other coagulation factors does not exclude ICE.

Depending on the stage of DVS-syndrome, laboratory tests vary as follows:

• I stage: shortening of bleeding time, VSC, AChTV + hyperfibrinogenemia + hyperthrombocytosis + spontaneous platelet aggregation + increase in PDP + positive PBC.
• II stage: thrombocytopenia + decrease in platelet aggregation and PTI + thrombin test extension + further increase in PDP + sharply expressed PCT + fibrinogen in norm + decrease in level of AT III and protein C.
• III stage: abrupt extension of VSC + hypo- or afibrinogenemia + deep thrombocytopenia + decrease in all coagulation factors + AT III deficiency + negative PCT.

[28], [29], [30], [31]

Treatment of the dIC-syndrome in adults

Treatment of DIC syndrome is usually conducted in the ICU and is aimed at removing the formed blood clots, preventing new ones, restoring blood circulation and hemostasis.

Active antibacterial and other etiotropic therapy. It should be taken into account that some antibiotics (ristomycin, aminoglycosides) increase platelet aggregation, others (ampicillin, carbenicillin, cephalosporins) weaken it.

Rapid removal of patients from the state of shock, elimination of other circulatory disorders, hypovolemia, correction of metabolic and electrolyte disorders by IT.

Appointment of disaggregant, anticoagulant, fibrinolytic and substitution therapy.

In the first stage of ICE, heparin has a therapeutic value. It is administered in a daily dose of 100-300 U / kg (4-6 injections or evenly drip at a rate of 15-20 U / kg per hour); possibly intradermal administration. Since the medium-molecular heparin does not inhibit platelet-vascular hemostasis, mainly thrombogenesis is inhibited, when the vascular wall (septic shock) is damaged, it is better to use low-molecular forms - fractiparin (0.1-0.3 ml 1-2 times a day), calciparin and others .

It is advisable to use antiplatelet agents (quarantil, trental, euphyllin), weak fibrinolytic agents (nicotinic acid, complamine) and blood rheology improving agents (rheopolyglucin), restoring bcc (albumin). In recent years, the disaggregation activity of small doses of acetylsalicylic acid has been established (1-3 mg / kg 1 time per day). To thrombolytics (streptase, cabakinase, etc.) in pediatric practice are extremely rare, although with clearly controlled by laboratory and instrumental methods of thrombogenic blockade of vessels, their administration is justified in the first 4 hours from the moment of thrombosis and ischemia.

In the II stage of DVS-syndrome, a dynamic control of the coagulogram (VSC should be within 10-20 min) is necessary. Deficiency of plasma coagulation factors and AT III can be eliminated by transfusion of its concentrate, FFP, cryoprecipitate. To reduce the activity of STH, dicinone, doxium, disaggregants (quarantil, anginin, parmidin) are used. The greatest difficulties arise in the III stage of DVS-syndrome. First, enter FFP in large doses (30 ml / kg per day or more). It is useful shredienie cryoprecipitate, then pour a solution of glucose with vitamins, a solution of soda. In recent years, an OVC is often carried out in the volume up to the OCT with a repetition of the procedure after 12-24 hours. When conducting (LDZ in young children, it is possible to use plasma from one donor.

Erythrocyte mass is prescribed with a substitution goal at hemoglobin level <80 g / l, erythrocytes - <2.5-10 ¹² / l. A suspension of platelets is used if their blood level becomes less than 30 109 / L (2-6 doses per day drip). The introduction of GCS (10-Z0 mg / kg per day in terms of prednisolone, fractional or pulse therapy - metipred) is shown.

As a rule, such patients are immediately transferred to mechanical ventilation. It is advisable to use inhibitors of proteolysis (counter virus - 500-1000 ATU / kg, pantripin - 5000-10 000 ATU / kg, trachylene, gordoks - 10 000-20 000 ATU / kg) drip intravenously 2-3 times per day or continuously.

ACC is only applied topically (inside, intrapleural). For local hemostasis, bandages with thrombin, dicinone, androxone, doxum, as well as fibrin film, hemostatic sponge are used.

In the IV stage of the DIC-syndrome, angioprotectors - stugerone, prodektin, and also komplamin (theonikol) are added to restore blood microcirculation. Apply drugs nootropilovogo series (aminalon, piracetam), etc.

Thus, the treatment of DIC syndrome is usually actively carried out only with its obvious clinical manifestations (bleeding and thrombogenic organ failure), in other cases attention should be paid to the treatment of the underlying disease, improvement of lung ventilation and the state of central and peripheral hemodynamics.