Diagnosis, Treatment and Prevention of DIC

Diagnosis of DIC

Diagnosis of acute DIC syndrome is greatly facilitated by the fact that, with some types of pathology, it is the only form of hemostasis disorder. In case of shock and terminal conditions, severe sepsis, massive injuries and burns, acute intravascular hemolysis and bites of vipers, disseminated intravascular coagulation is a constant component of the disease, its integral part. With all these types of pathology, DIC syndrome is diagnosed simultaneously with recognition of the underlying disease and its therapy is immediately started.

The recognition of several hemostatic disorders is associated with more serious difficulties, especially in those cases when they are sequentially layered on top of each other. Such polysyndromism is observed in diseases of the liver, leukemia, systemic lupus erythematosus, bleeding in newborns and in a number of other situations. Differential diagnosis is required for a set of tests that reflect the state of different parts of the hemostatic system. Various pathological deviations in the general coagulation tests in combination with thrombocytopenia, an increase in the plasma level of fibrinogen degradation products give in aggregate the basis for the diagnosis of DIC.

The initial laboratory diagnosis of DIC is carried out using the simplest laboratory and instrumental techniques at the patient’s bedside — the total time of blood coagulation, prothrombin and thrombin time (with an assessment of the quality of the formed clot), changes in the shape and parameters of the thromboelastogram, indications of paracoagulation tests, and platelet dynamics in the blood . This primary information can be supplemented by more accurate standardized tests – an autocoagulation test, determination of fibrinogen degradation products, quickly performed tests with snake venoms, especially a test with sand efa poison. For early diagnosis and proper treatment of patients, the determination of antithrombin III, the patient’s plasma sensitivity to heparin, is important. The diagnostic value of different tests for DIC is not the same, and each of them in a greater or lesser number of cases may not reveal abnormalities (which depends on the form and stage of DIC). In addition, the indications of each test individually may not be violated due to DIC, but for other reasons, since they are all non-specific. For example, the incidence of thrombocytopenia in DIC is very high (on average, it is detected in 95% of patients), but it can also be due to other causes (immune thrombocytopenia in systemic lupus erythematosus or in newborns, as well as those associated with heparin therapy) .

For all these reasons, the diagnosis should not be based on the indications of individual laboratory tests, but on an aggregate assessment of the results of the group of the most informative tests.

In general, experience shows that in the corresponding clinical situation and with the characteristic symptoms of DIC, the detection of at least 4-5 of the above basic and additional laboratory signs confirms the diagnosis and requires appropriate pathogenetic therapy. A dynamic study of antithrombin III and plasminogen is not only of diagnostic value (especially for the early diagnosis of DIC), but also for the reasonable treatment of patients.

Laboratory examination of patients should in no case be limited to a hemostatic system. Other definitions are extremely important: changes in hematocrit, hemoglobin and erythrocytes in the blood, arterial and venous pressure, respiratory efficiency and degree of hypoxemia, acid-base state, electrolyte balance, urine output and urinary symptoms, dynamics of creatinine and urea in the blood.

In subacute and protracted (chronic) DIC, the process often begins with a long period of hypercoagulation, phlebothrombosis – venous thrombi (Trusso syndrome) with thromboembolism and ischemic phenomena in organs appear. Without control of the hemostasis system, these initial disorders, characterized by hypercoagulation (increased blood coagulation), high spontaneous platelet aggregation, increased levels of fibrinolysis products, are often seen or associated with local thromboses. In such cases, the fight against DIC often begins late – in the terminal period, with massive and multiple thromboses of the organ and main veins, often with multiple emboli in the pulmonary artery pool (pulmonary infarction), or during the transformation of the thrombotic process into the terminal phase of acute hypocoagulation and bleeding (mainly gastrointestinal).

A protracted DIC-syndrome is observed in most oncological, immunocomplex and myeloproliferative diseases, in heart failure, in destructive-sclerotic processes in organs (cirrhosis), as well as in chronic hemodialysis, prosthetics of blood vessels and heart valves.

Many of these protracted forms of DIC syndrome have very significant qualitative features associated with the initial (background) pathology and treatment methods. Thus, DIC during erythremia and other myeloproliferative diseases and symptomatic polyglobulia is characterized by high hematocrit, increased blood viscosity, impaired microcirculation in organs, a tendency to thrombosis and heart attacks, and cerebrovascular disorders. With these forms, chronic, often asymptomatic, gastroduodenal ulcers often develop, causing profuse bleeding during heparin therapy or the transformation of DIC into the final phase. Hypertrombocytosis (increased platelet count) inherent in myeloproliferative diseases supports the tendency to thrombosis and DIC. Hemostasis disorders associated with thrombocythemia (with a platelet count of more than 1000 × 109 / L) are associated with these forms of pathology, in which thrombohemorrhagic phenomena are caused mainly by increased aggregation of blood plates and a weakening of the antithrombotic properties of the endothelium.

In contrast, in chronic renal failure, the activation of the coagulation link of hemostasis predominates, developing against the background of thrombocytopathy and often thrombocytopenia, anemia. Chronic hemodialysis steadily exacerbates all these disorders, stimulates the deposition of fibrin in the pulmonary circulation, increases the content of soluble fibrin and fibrinolysis products in the circulation. The use of plasmapheresis in complex therapy of such patients significantly reduces intoxication and microcirculation disorders.

The undulating course of DIC is often observed during destructive processes in organs, especially those associated with pathogenic microflora (staphylococcus, proteus, Pseudomonas aeruginosa) or with toxic effects. With these forms, temporary remissions are replaced by repeated acute violations of hemostasis, leading patients to death.

Treatment of DIC

The treatment of DIC syndrome presents great difficulties and is far from always successful. Mortality in acute forms is 30%. The inconsistency and insufficient reliability of the mortality data are associated, on the one hand, with the fact that patients with different severity of background diseases and with different severity of DIC are included in the statistical reports.

First of all, in the treatment of disseminated intravascular coagulation syndrome, an intensive struggle is conducted against pathological processes that cause and aggravate DIC. Such therapy should be aimed at eliminating purulent-septic processes, often underlying the DIC. In this situation, the earliest, based on clinical indications, and not on delayed bacteriological studies, antimicrobial therapy is necessary.

The reason for starting the above therapy is data on the association of DIC with infection, abortion, early discharge of amniotic fluid (especially turbid), fever, signs of a destructive inflammatory process in the lungs, abdominal cavity, urinary tract, genitals, signs of intestinal toxicoinfection, meningeal symptoms.

The rapid increase in body temperature, as well as changes in laboratory parameters of blood tests, such as leukocytosis, a shift of the leukocyte formula to the left, are an additional reason for the appointment of antibiotic therapy. As a rule, this therapy is carried out with broad-spectrum antibiotics, often γ-globulins are included in the therapy.

With staphylococcal and other bacterial destruction in organs, therapy is often effective only when large doses of antiproteases are added to antibiotics (for example, contrikal of 100,000-300,000 units / day or more). These drugs are included in the therapy in order to break down the breakdown of tissues, as well as intoxication and the entry of tissue thromboplastin into the bloodstream due to tissue destruction.

Also, the leading point in the treatment of DIC is the relief of a developing shock state, the quick elimination of which can interrupt the onset of DIC or sufficiently mitigate it. As such therapy, intravenous injections of saline solutions, jet-drop transfusions of plasma, reopoliglyukin (up to 500 ml / day), glucocorticosteroids (intravenous prednisone 80 mg) are used. When using plasma for intravenous infusions, it is necessary to add 5000 IU of heparin.

At the very first stages of the development of disseminated intravascular coagulation syndrome, a-blockers give a fairly good effect. Their action is based on improving microcirculation in organs, preventing vascular thrombosis, and reducing platelet aggregation. Trioproperazine, dibenamine, majeptil, phentolamine possess such properties, which are used in a 1% solution of 5 mg intravenously.

High efficacy of a-blockers in DIC is also noted in case of their early use. It should be noted that adrenaline and norepinephrine significantly exacerbate the DIC syndrome, enhancing both blood coagulation and platelet aggregation, as well as increasing fibrin deposition in the capillaries of the kidneys, lungs and other organs.

The microcirculation and the preservation of active platelets in the bloodstream are favorably affected by the integrated use of trental and chimes 100–200 mg intravenously repeatedly. The above drugs should be used both in the early stage of the process, and in the development of acute renal and respiratory failure, as well as during hemodialysis, plasmapheresis, and in other situations when blood comes into contact with a foreign surface.

It should be noted that heparin can increase the decrease in functionally active platelets from the bloodstream and deepen thrombocytopenia, creating a threat of bleeding in this way, and not just with an anticoagulant effect.

Dynamic monitoring of platelet content in the blood becomes extremely important in the case of DIC, including during the course of its treatment with heparin.

Heparin is often ineffective due to its late administration during the period when the formation of fibrin and platelet aggregation with their deposition in the microvasculature have already been completed, as well as due to a significant deficiency of antithrombin III and a high content of acute phase proteins blocking heparin in the blood, or from due to the formation of abnormal forms of thrombin.

With heparin therapy, the following basic rules should be followed. It is necessary to use heparin as early as possible – in the phase of hypercoagulation in doses of 20,000-40,000 units / day, and in the second (transitional) phase – in doses not exceeding 20,000 units / day.

During these periods, heparin is used to “cover” the basic therapy with freshly frozen plasma.

In the stage of hypocoagulation and bleeding, heparin is used only in small doses to “cover” transfusion therapy (2500 units before blood and plasma transfusions). In several large doses, it can be used in combination with contracal and other antiproteases.

If DIC is caused by severe bleeding, antienzymes (contracal, gordox) are included in the treatment.

In case of bleeding, reopoliglukin should not be used for the purpose of blood substitution, since it additionally violates hemostasis.

With the development of the third stage of disseminated intravascular coagulation syndrome, when profuse bleeding, clotting, severe hypocoagulation are added to this pathological condition, and also if the clinical picture is complicated by bleeding from ulcers of the gastrointestinal tract (bloody vomiting, tarry stools), severe uterine bleeding, heparin categorically contraindicated.

It should also be noted that blood loss is not always detected on time, therefore, indications for heparin withdrawal are signs of rapidly progressing hemorrhagic collapse and anemia (lowering blood pressure and tachycardia with a simultaneous drop in hematocrit, the absence of their correction during transfusions of red blood cells, albumin, and plasma).

Another contraindication is rapidly progressive thrombocytopenia, since heparin can dramatically increase this disorder.

In the phase of deep hypocoagulation, bleeding and thrombocytopenia, the most relevant is the administration of not large amounts of protease inhibitors, not heparin (contrikal 50 000-100 000 IU intravenously). With the resumption of bleeding, this dose can be repeated several times a day.

In case of disseminated intravascular coagulation syndrome, which develops against the background of bleeding or associated with destructive processes in organs, such as staphylococcal destruction of the lungs, large doses of contracal should be included in the therapy from the very beginning. This therapy not only stops the DIC, but also suppresses tissue breakdown, eliminates intoxication and the entry of thromboplastin from tissues into the blood.

Antiproteases also inhibit tissue thromboplastin production and activation of coagulation by proteases associated with cancer cells and blasts. This effect explains the possibility of stopping with contracal and other antiproteases of the DIC syndrome in acute promyelocytic leukemia. In some cases of disseminated intravascular coagulation, the combined use of contracal and heparin gives a good therapeutic effect.

Transfusion therapy is the basis for the treatment of disseminated intravascular coagulation syndrome, which ensures the correction of hemostasis; compensation of the volume of fluid in the circulation and restoration of central venous pressure, disturbed due to shock and (or) blood loss; replacement of red blood cells – red blood cells and platelets.

Some of the above goals are achieved by massive transfusions of plasma containing all components of the blood coagulation system and other plasma enzyme systems and having antiprotease activity, including a large amount of antithrombin III.

Treatment with freshly frozen plasma should begin as early as possible at the stage of hypercoagulation and continue until all the manifestations of disseminated intravascular coagulation are eliminated. It is proved that plasma helps to stop not only DIC, but also destructive processes in organs, intoxication, and immune disorders.

In the absence of freshly frozen plasma, treatment can be carried out using antihemophilic or native plasma, although these drugs are less effective.

Also in infusion therapy, in addition to plasma, saline solutions, polyglucin, albumin solution are used. Perhaps the use of reopoliglyukin, used mainly in the phase of hypercoagulation in a volume of not more than 400 ml / day. In this phase, reopoliglyukin functions not only as a blood substitute, but also as an agent that inhibits platelet and erythrocyte aggregation, improves microcirculation in organs.

During hypocoagulation and bleeding, as well as severe thrombocytopenia, it should not be prescribed, since, according to the experience of many authors, in this situation reopoliglyukin can increase bleeding and weaken the therapeutic effect of other drugs.

Anemization, a decrease in hematocrit, heavy bleeding serve as an indication for the replacement of red blood cells. To achieve this goal, a red blood cell transfusion, an erythrocyte suspension, is prescribed.

Summing up, it should be noted that during transfusion therapy of disseminated intravascular coagulation syndrome, the doctor must strive to achieve the following main goals.

  1. Rapid restoration of the volume of circulating blood and hemodynamics (cryoplasm, albumin, saline, polyglucin and reopoliglukin) and maintaining the mass of red blood cells above the critical level (for hematocrit – over 22%, for red blood cells – over 2.5 × 1012 / l).
  2. If this level cannot be reached, you should pay attention to all possible ongoing bleeding, visible or invisible.
  3. Quite often, the combined use of freshly frozen plasma and platelet concentrates (4-8 doses) can stop many of these bleeding.
  4. Even at the very latest stages of disseminated intravascular coagulation syndrome, effective stopping of bleeding, especially uterine bleeding, occurs due to the simultaneous intravenous administration of large doses of contracal (50,000-100,000 units or more; daily dose – up to 500,000 units or more).
  5. Local influences should also be used, such as irrigation of bleeding areas, erosion, wounds with hadroxone, a 6% solution of aminocaproic acid, applying biological glue to these areas.

The use of plasma and cytapheresis in the treatment of DIC

The successful effect of the use of plasmapheresis in the treatment of DIC has also been proven, especially with its protracted and recurrent forms. 600-800 ml of plasma are removed, replacing it with freshly frozen plasma. With this procedure, which can be repeated as necessary, the immune and protein complexes, activated coagulation factors are removed from the patient’s blood, and with partial cytapheresis (removal of the leukocyte layer), activated monocytes and platelet aggregates are removed.

The most relevant is the use of therapeutic plasmapheresis in protracted forms of DIC associated with renal and hepatic insufficiency, with purulent-destructive processes, as well as with chronic hemodialysis.

In chronic DIC-syndromes, a quick therapeutic effect is obtained by erythrombocytapheresis in combination with the following drugs: trental, dipyridamole, ticlopidine, a-blockers.

Acetylsalicylic acid is dangerous in acute DIC: aggravating thrombocytopathy and forming acute erosion in the stomach, it creates the prerequisites for severe massive bleeding.

Thus, the main components of the complex therapy of DIC are:

  1. treatment aimed at eliminating the causative factor; antishock therapy and maintaining the necessary volume of circulating blood: transfusion of freshly frozen plasma with heparin; the introduction of protease inhibitors and anti-bradykinin drugs (especially during destructive processes and during bleeding);
  2. earlier use of adrenergic blockers and drugs that improve microcirculation and reduce platelet loss from the bloodstream (trental, chimes, ticlodipine) is possible;
  3. replacement of erythrocyte loss and maintenance of hematocrit above 22%; in severe hypocoagulation and bleeding – transfusion of platelet concentrates, the introduction of contracal in large doses;
  4. use according to indications of plasmacytapheresis.

The next therapeutic effect is the direction to eliminate the “shock lung” and acute renal failure with the use of drugs such as lasix, osmotic diuretics, heparin, with controlled artificial ventilation, effects on the acid-base state and electrolyte balance.

In case of disseminated intravascular coagulation syndrome, the use of fibrinogen, which coagulates easily in the bloodstream, increasing microcirculation block, should be avoided.

In most cases of DIC, both fibrinolysis inhibitors of the aminocaproic acid type and activators of this system (streptokinase, urokinase) are contraindicated. Their use is fraught with dangerous complications.

When gastroduodenal hemorrhages, local influences are used as much as possible through a gastrofibroscope – covering bleeding erosions with hemostatic drugs of local action.

Patients with disseminated intravascular coagulation syndrome need intensive round-the-clock observation and treatment with monitor monitoring of respiratory and circulatory efficiency, frequent repetition of laboratory tests. Based on the foregoing, such patients should be in intensive care units or in intensive care units.

Prevention of DIC

Timely elimination of the causes of DIC, the correct treatment of the underlying disease, possibly less traumatic surgical interventions, the fight against the onset of shock and microcirculation disorders are the most important conditions for the prevention of DIC. Particularly emphasized is the need to combat septic complications after abortions, often leading to acute DIC.

In case of thrombogenic danger (advanced age, pregnancy pathology, tumor diseases), drugs that increase blood coagulation potential (synthetic hormonal contraceptives, fibrinolysis inhibitors, including aminocaproic acid) should not be prescribed.

It should be remembered that blood loss in adults, not exceeding 1 liter, must not be replaced with blood, but with albumin, plasma or blood substitutes.

In the treatment of purulent-destructive processes, which are a common cause of disseminated intravascular coagulation syndrome, along with antibiotics and other antibacterial drugs, protease inhibitors, drugs that improve the rheological properties of blood, and antithrombotic agents should be used.