Treatment of disseminated intravascular coagulation syndrome

Treatment of the syndrome of disseminated intravascular coagulation (DVS-syndrome, thrombohemorrhagic syndrome). Dvs-syndrome is observed in many diseases and all terminal states. It is characterized by disseminated intravascular coagulation and aggregation of blood cells, activation and depletion of components of coagulation and fibrinolytic systems (including physiological anticoagulants), microcirculation disorders in organs with their dystrophy and dysfunction, pronounced inclination to thrombosis and bleeding. Microthrombogenesis and microcirculation blockade can spread to the entire circulatory system with a predominance of the process in the target organs (or shokorganah-lungs, kidneys, liver, brain, stomach and intestines, adrenal glands, etc.) or in separate organs and body parts (regional forms) . The process can be acute (often fulminant), subacute, chronic and recurrent with periods of exacerbation and subsidence.

Etiology, pathogenesis. Acute DVS-syndrome accompanies severe infectious-septic diseases (including abortions, during childbirth, in newborns - more than 50% of all cases), all types of shock, destructive processes in organs, severe injuries and traumatic surgical interventions, acute intravascular hemolysis (Including incompatible hemotransfusions), obstetric pathology (previa and early detachment of the placenta, embolism with amniotic fluid, especially infected, manual placenta separation, hypotonic bleeding, uterine massage with its atony), massive blood transfusion (danger increases with use of blood for more than 5 days Storage), acute poisoning (acids, alkalis, snake venoms, etc.), sometimes acute allergic reactions and all terminal conditions. The pathogenesis of the syndrome in most cases is associated with a massive influx of blood clotting stimulants (tissue thromboplastin, etc.) and platelet aggregation activators from the tissues into the blood, damage to a large area of ​​the vascular endothelium (bacterial endotoxins, immune complexes, complement components, cell and protein decay products) . In infectious-septic processes, blood coagulation stimulators and enzymes that damage the walls of microvessels are also intensively produced by macrophages (monocytes) and neutrophils; Secreted by the latter, elastase plays an important role in the formation of a pulmonary distress syndrome (shock lung).

Subacute DVS-syndrome, which is replaced by acute in the terminal phase, is observed with a lighter flow of all the diseases listed above, as well as with late toxicosis of pregnancy, fetal death, leukemia, immunocomplex diseases (subacute forms of hemorrhagic vasculitis), temolitikouremic syndrome (acute DIC-syndrome).

Chronic DVS-syndrome often complicates malignant neoplasms (lung, kidney, prostate, liver, etc.), chronic leukemia, all forms of blood clotting (erythremia, erythrocytosis), hyperthrombocytosis (with platelet count in blood more than 8-109 L, chronic Cardiovascular and pulmonary heart disease, chroniosepsis, vasculitis, giant hemangiomas (Kazabakh-Merritt syndrome), and massive blood contact (especially repeated) with a foreign surface-hemodialysis in chronic renal failure and extracorporeal circulation apparatus-also leads to chronic DIC syndrome.

Pathogenetically, a special form associated with a decrease in the antiaggregatory potential of the vascular wall and blood is thrombotic thrombocytopenic purpura (Moshkovich disease).

Schematically, the pathogenesis of DIC syndrome can be represented by the following sequence of pathological disorders: activation of the system, hemostasis with phase change of hyper and hypocoagulation - intravascular coagulation, platelet and erythrocyte aggregation - microthrombin of vessels and microcirculation blockage in organs with their dysfunction and dystrophy - depletion of coagulation components Blood and fibrinolysis systems, physiological anticoagulants (antithrombin III, proteins C and S), a decrease in platelet count in the blood (thrombocytopenia of consumption). The toxic effect of protein decay products accumulating in large quantities both in blood and in organs as a result of the sharp activation of proteopytic systems (coagulation, kallikreinkinin, fibrinolytic, complement, etc.), the disturbance of blood supply, hypoxia and necrotic changes in tissues, often Weakening of detoxification and excretory functions of the liver and kidneys. This proteolytic explosion with the accumulation of toxic products of protein decay in the blood and extravascular space served as the basis for the development and use of a number of new effective methods for treating the DIC syndrome - plasmapheresis and transfusions of fresh native or fresh frozen plasma, high-dose aantiproteases, the use of extracorporeal blood purification methods and Etc.

Symptoms, course. The clinical picture consists of the signs of the main (background) disease, which caused the development of intravascular coagulation of blood, and the DVS-syndrome itself. The latter in its development is the following stages: 1 - hypercoagulation and thrombosis; II - the transition from hyper-to hypocoagulation with multidirectional shifts of different coagulation parameters; III - deep hypocoagulation (up to complete blood coagulability and severe thrombocytopenia); IV - reverse development of DIC syndrome.

In acute DVS-syndrome, the first short-term phase is often seen. For its detection, one should pay attention to easy thrombosis of punctured veins and needles in blood sampling for tests, very fast blood clotting in test tubes (despite its mixing with citrate), the appearance of unmotivated thromboses and signs of organ failure (eg, decreased diuresis due to microcirculation disturbance in Kidneys as an early sign of developing kidney failure). Most acute DIC syndrome is first detected at the time of multiple hemorrhages at injection sites, palpation, below the place of the cuff for measuring blood pressure, in the sloping parts of the body; With prolonged and often repeated bleeding from the sites of puncture of the skin on the fingers or in the area of ​​the ulnar fold, a sharp increase in the bleeding of the diffuse type from the operating wounds; With bleeding from the uterus (during labor, after abortion, etc.) without visible local causes, bleeding serous membranes, poor coagulability of leaky blood (small, rapidly lysing clots, complete incoherence). Often there are nasal and gastrointestinal hemorrhages, signs of disturbance of microcirculation in organs - lungs (sudden development of frequent ineffective breathing, cyanosis, wheezing), kidneys (drop in diuresis, protein and erythrocytes in urine), brain (retardation, congestion), adrenal (Repeated drops in blood pressure), liver (pain in the right hypochondrium, hyperbilirubinemia, jaundice). It can be dominated by one or other organ disorders.

Laboratory signs are multidirectional shifts in the blood coagulation system, which turn into deep hypocoagulation (inhibition of blood clotting and plasma in partial thromboplastin test, autocoagulation test, thromboelastogram, lengthening of thrombin and prothrombin time, decrease in plasma clotting factors (including fibrinogen), increased spontaneous Platelet aggregation (flakes in the plasma) in combination with thrombocytopenia, increased content of broken (fragmented) erythrocytes in the blood, positive results of one or more paracoagulation tests revealing the circulation in the blood of active thrombin and soluble complexes of fibrin monomers (FMCM) - ethanol, As a result of intensive fibrinolysis, the plasma content of enzyme degradation products of fibrin (PPF) is determined immunologically or by the test of staphylococcus (TCC) adhesion, As a result of intensive intravascular coagulation and fibrinolysis, the circulation of not only coagulation factors Blood and platelets, but also the most important anticoagulants - antithrombin III (cofactor of heparin), proteins C and S, as well as plasminogen (profibrinolysin) and its activators (plasma precalycrein, high-molecular kininogen, etc.).

In connection with the blockade of microcirculation and hypoxia of the organs, violations of the gas composition of blood, acid-base balance, later the content of plasma creatinine, urea (acute renal failure), bilirubin (hemolysis, liver damage) increases.

Thus, acute DVS-syndrome is a serious catastrophe of the organism, placing it on the line between life and death, characterized by severe phase disorders in the hemostatic system, thrombosis and hemorrhage, impaired microcirculation and severe metabolic disturbances in organs with pronounced dysfunction, proteolysis, Intoxication, development or deepening of shock phenomena (hemocoagulation-hypovopaemic nature).

Diagnosis. Early diagnosis is situational in nature and is based on the identification of those diseases and effects in which the DIC syndrome (infection-septic processes, all types of shock and severe hypovolemia, acute intravascular hemolysis, a number of obstetric pathology, etc.) naturally develops. In all these cases, early preventive therapy of DIC-syndrome is necessary before the development of marked clinical and laboratory signs. In the presence of causative factors causing the DIC-syndrome, the development of the latter becomes unquestionable with the appearance of hemorrhages of different localization, signs of acute respiratory failure (tachypnea, choking, cyanosis), acute renal or hepatorenal insufficiency, amplification and recurrence of the phenomena of shock, various disorders of various parameters Blood coagulability, the transition of hypercoagulation into deep hypocoagulation, in combination with the aggregation in the plasma of blood cells (turbidity, flakes) and thrombocytopenia. The type of bleeding is mixed (see Hemorrhagic diathesis and syndromes in the chapter "Blood system diseases"). In addition, the DIC syndrome is documented by positive paracoagulation tests (ethanol, protamine sulfate, beta-naphthol, ortho-phenanthroline), detection of an elevated plasma content of the PDP (rapid test-staphylococcus adhesive test), serum detection after clotting of blocked fibrinogen by adding poison to it Snake sandy efa (formation in the serum of the second bunch). All these tests are quick to be done, but therapy should not be postponed until they are performed.

Treatment of acute DVS-syndrome should be directed first of all to the rapid elimination of its cause. Without early-initiated successful etiotropic therapy, one can not count on saving the patient's life. Patients need immediate direction or transfer to the intensive care unit, mandatory involvement of reanimatologists-transfusiologists and specialists in the pathology of the hemostatic system to the treatment process. The main pathogenetic methods of treatment are anti-shock measures, intravenous drip of heparin, jet transfusions of fresh native or freshly frozen plasma if necessary with plasma replacement, fight with blood loss and deep anemization (blood substitutes, fresh blood citrate, erythrocytes), acute breathing disorders (early connection of artificial ventilation) And acid-base balance, acute renal or hepatorenal insufficiency.

Heparin should be administered intravenously drip (in isotonic sodium chloride solution, with plasma, etc.), in some cases in combination with subcutaneous injection of it into the cellulose of the anterior abdominal wall below the umbilical line. Intramuscular injections are not recommended because of the different rate of resorption of the drug (which makes its dosing difficult), easy formation in the conditions of development of the DIC syndrome of extensive, infected with hematomas. The dose of heparin varies depending on the form and phase of the DIC syndrome: in the stage of hypercoagulability and at the beginning of the initial period with the blood coagulation still sufficiently preserved, its daily dose in the absence of copious initial bleeding can reach up to 40 000-60 000 U (500-800 U / Kg). If the onset of DIC-syndrome is accompanied by profuse bleeding (uterine, from an ulcer or decaying tumor, etc.) or there is a high risk of its occurrence (for example, in the early postoperative period), the daily dose of heparin should be reduced by 2-3 times. In these situations, as in the phase of deep hypocoagulation (II-111 stage of DIC syndrome), the administration of heparin is mainly used to cover plasma and blood transfusions (for example, 2500-5000 units of heparin are injected at the beginning of each transfusion with drip along with hemopreparation).

If there are bloody proteins in the blood of the acute phase (for example, in acute infectious-septic processes, massive destruction of tissues, burns), the doses of heparin, on the contrary, should be the highest, as these proteins bind heparin and prevent its anticoagulant action. Insufficient effect of heparin can be associated with blockade and a decrease in the plasma content of the patient's plasma cofactor - antithrombin III. Therefore, often a significant increase in the effectiveness of treatment is achieved not by escalating doses of heparin, but by early connection of jet transfusions of fresh native or freshly frozen plasma (up to 800-1600 ml per day in 2-4 doses). Such transfusions are shown in all stages of the DIC syndrome, they compensate for the lack of all components of the clotting and fibrinolytic systems, including antithrombin III and proteins C and S (depletion of which in the DIC syndrome is particularly intense - several times faster than all procoagupants) , Allow the introduction into the bloodstream of a complete set of natural antiproteases and factors that restore the antiaggregatory activity of the blood and thrombose resistance of the endothelium.

In a number of cases (especially with infectious-toxic forms of DIC-syndrome), transfusion of fresh-frozen or fresh native plasma is performed after plasmapheresis sessions - removing 600-1000 ml of the patient's plasma (only after stabilizing hemodynamics!). In DVS-syndrome of infectious-septic nature and development of pulmonary distress syndrome, plasmacytapheresis is shown, since in the pathogenesis of these forms an important role is played by leukocytes, some of which begin to produce tissue thromboplastin (mononuclears), and others-esterases that cause interstitial pulmonary edema (neutrophils) . These methods of plasma therapy and plasma substitution significantly increase the effectiveness of treatment of DIC syndrome and its diseases, reduce several times the mortality rate, which makes it possible to consider them as the main method of therapy for patients with this hemostasis disorder. With significant anemia, transfusions of fresh canned blood (daily or up to 3 days of storage), erythrocyte mass and erythrocyte suspension are added to this therapy (the hematocrit indicator should be maintained above 25%, the hemoglobin level is more than 80 g / l, the erythrocytes - 3 (1012 / L) It should be remembered that excessively abundant blood transfusions (especially canned blood for more than 3 days of storage) exacerbate the DIC syndrome (syndrome). Massive transfusion), therefore, during the transfusion therapy, a certain restraint is necessary, a strict account of the amount of transfused blood, its components and blood substitutes, as well as blood loss, loss of body fluids, diuresis.It should be remembered that acute DVS-syndrome is easily complicated by pulmonary edema, therefore Significant overload of the circulatory system in the syndrome are dangerous.

In the III stage of DIC syndrome and with pronounced proteolysis in tissues (gangrene of the lung, necrotic pancreatitis, acute dystrophy of the liver, etc.), plasmapheresis and jet transfusions of freshly frozen plasma (under cover of small doses of heparin - 2500 units per infusion) are combined with repeated intravenous injection of large Doses of kontrikal (up to 300 000- 500 000 units or more) or other antiproteases. In the late stages of the development of DIC syndrome and its varieties occurring against the background of bone marrow hypoplasia and dysplasia (radiation, cytotoxic diseases, leukemias, aplastic anemia), it is also necessary to transfuse platelet concentrates to stop bleeding (see Leukemia Acute, Radiation Disease in the Chapter "Diseases of the blood system").

An important link in complex therapy is the use of disaggregants and drugs that improve microcirculation in organs [quarantil, dipyridzmol in combination with trental; Dopamine - with renal insufficiency, k-adrenoblockers (sermion), ticlopidine, defibrotide, etc.]. An important component of therapy is the early connection of artificial ventilation. The elimination of the patient from shock is facilitated by the use of antioopioids - naloxane, etc.

Transition to the hypocoagulation and hemorrhagic phase occurs either gradually or suddenly (often with transformation into an acute DIC syndrome). Quite often (especially with infectious-septic, neoplastic forms) repeated phases of hyper- and hypocoagulation.

Subacute DIC-Syndrome. Symptoms, course. The initial period of hypercoagulation is asymptomatic or manifested by thrombosis and microcirculatory disturbances in the organs (congestion, anxiety, a sense of unaccountable fear, a decrease in diuresis, swelling, protein and cylinders in the urine) is longer than with an acute DIC syndrome.

Diagnosis is based on the identification of a combination of symptoms of the underlying disease with thrombosis and (or) hemorrhages of different locations (bruises, especially at the injection sites, thromboses in venipuncture sites) and signs of microcirculation disorders in the organs. In the study of blood, there is a change in the phases of hyper- and hypocoagulation, multidirectional shifts in coagulation tests, hyper- or moderate hypofibrinogenemia, and often hyperthrombocytosis. Paracoagulation tests (ethanol, protamine sulfate, etc.) are stably positive; The plasma in the plasma is increased.

Treatment - joining the therapy of the main disease of intravenous and subcutaneous heparin injections of heparin (daily dose from 20 000 to 60 000 units), disaggregants (dipyridamole, trental, etc.). Rapid reduction or weakening of the process is often achieved only with plasmapheresis (removal of 600-1200 ml of plasma daily), replacing partially fresh, native or freshly frozen plasma, partially with blood substitution solutions and albumin. The procedure is conducted under the cover of small doses of heparin. Chronic DVS-syndrome. Symptoms, course. Against the backdrop of signs of the main disease, marked hypercoagulability of blood (rapid coagulation in the veins-spontaneous and puncture, needles, test tubes), giperfibrinogenemia, inclination to thrombosis, positive paracoagulation tests (ethanol, protamine sulfate, etc.) is noted. The bleeding time according to Duke and Borchgrevink is often shortened, the content in the blood of platelets is normal or elevated. Often their spontaneous hyperaggregation is detected - small flakes in the plasma. In a number of forms, there is an increase in hematocrit, a high level of hemoglobin (160 g / l and more) and erythrocytes (more than 5 (1012 / l)), slowing of ESR (less than 4-5 mm / h) .In some cases, unmotivated multiple thrombosis of veins, Including in cases of unrecognized cancer of different locations (Tissaurd syndrome), with immune vasculitis, collagenosis, etc. In other cases, hemorrhages, petechiae, bruises, nosebleeds and gums, etc., are easily present (in combination with thromboses and without them ).

Treatment is the same as in subacute form. With polyglobulosis and thickening of the blood - bleeding, leeches, cytapheresis (removal of red blood cells, platelets and their aggregates), hemodilution (reopoliglyukin intravenously up to 500 ml daily or every other day). With hyperthrombocytosis - desaggregants (acetylsalicylic acid 0.3-0.5 g daily, trental, etc.).