CC BY
8Received by the Editor 23.11.2020
IRSTI 76.03.49
UDC616.15-07 (075.8)
CLINICAL - DIAGNOSTIC CRITERIA OF DIC SYNDROME
G. Husainova
NcJSC «Astana Medical University» Nur-Sultan city, Kazakhstan
The article presents data from modern literature on clinical-diagnostic criteria of DIC syndrome. The mechanism, clinical symptoms, diagnostic methods of DIC are described in article.
Keywords: disseminated intravascular coagulation (DIC), blood hypocoagulation, blood hypercoagulation, diagnostic criteria.
КЛИНИКО-ДИАГНОСТИЧЕСКИЕ КРИТЕРИИ ДВС - СИНДРОМА
Г.С.Хусаинова
НАО «Медицинский университет» Нур-Султан, Казахстан
В статье представлены данные современной литературы по клинико-диагностическим критериям ДВС синдрома. Описаны подробно механизм, клинические симптомы, методы диагностики ДВС синдрома.
Ключевые слова: диссеминированное внутрисосудистое свертывание (ДВС), гиперкоагуляция крови, гипокоагуляция крови, диагностические критерии.
ЦШ¥С - СИНДРОМЫНЬЩ КЛИНИКАЛЬЩ ДИАГНОСТИКАЛЬЩ КРИТЕРИЙЛЕР
Г.С.Хусаинова
«Астана медицина университет! КеАК, Н^р-С^лтан к;., Казахстан
Макалада КЩ¥С- синдромына казiргi эдебиеттен алынган акпарат ^сынылган. КШ¥С- синдромынын механизмi диагностика жолдары клиникалы; симптомтары толы; керсетшген.
ТYЙiцдi сездер: кантамыршшк шашыранды ^йю синдромы (КЩ¥С), каннын гиперкоагуляциясы, канньщ гипокоагуляциясы, диагностикалы; критерийлерi.
In many diseases, accompanied by the destruction of red blood cells, leukocytes, platelets and tissues and/or hyperproduction of apoprotein III stimulated endothelial cells, monocytes and macrophages (this reaction is mediated by the action of antigens and interleukins), develops DIC-syndrome, significantly aggravating the course of the pathological process and even leading to death of the patient. DIC-syndrome is a nonspecific general pathological process associated with the entry of, into the bloodstream, blood coagulation activators and platelet aggregation, disseminated microcoagulation of blood, activation and depletion of plasma proteolytic systems, the consumption of physiological anticoagulants and coagulation factors, the formation in the microcirculation zone of micro-clots and aggregates of blood cells, resulting in the development of microcirculation blockade in target organs, hypoxia, dystrophy and deep dysfunction of these organs. [1-4] Currently, DIC syndrome is detected in more than 100 different diseases. Especially often it occurs during transfusion of incompatible blood, extensive injuries, frostbite, burns, prolonged surgical interventions on the lungs, liver, heart, prostate gland, all types of shock, crash syndrome (prolonged compression of the limbs), as well as in obstetric practice when amniotic fluid saturated with platelet thromboplastin of placental origin enters the mother's bloodstream. In this case, hypercoagulation occurs, which due to the intensive consumption of platelets, fibrinogen, factors V, VIII, XIII, etc. as a result of intensive intravascular coagulation is replaced by secondary hypocoagulation until the complete inability of the blood to form fibrin clots, which leads to difficult bleeding therapy [5-9].
The main links of the pathogenesis of DIC syndrome:
- initial activation of the hemocoagulation cascade and platelets by endogenous factors: tissue thromboplastin, leukocyte proteases, tissue breakdown products, tumor procoagulants;
- persistent thrombinemia with increased levels of its markers in the blood (rfmc and D-dimers);
- depletion of the system of physiological anticoagulants with a significant decrease in
plasma levels of antithrombin III, protei n C, plasminogen and increased levels of thrombomodulin in blood plasma;
- systemic vascular endothelial damage and reduction of its antithrombotic potential;
- formation of blood micro-clots and blockade of microcirculation in target organs (brain, adrenal glands, kidneys, liver, stomach and intestines (sub-syndrome of multi-organ failure) with the development of dystrophic and destructive disorders in them).
- activation of fibrinolysis in the zone of microcirculation blockade and depletion of its reserves in the General circulation;
- consumption of hemocoagulation factors and thrombocytopenia (I-patia) consumption, leading to systemic bleeding and terminal hypocoagulation up to complete non-coagulability of blood (hemorrhagic phase of the syndrome);
- violation of the barrier function of the gastric and intestinal mucosa with the transformation of aseptic DIC syndrome into septic;
- secondary severe endogenous intoxication [10-13].
Stages of DIC syndrome.
During DIC-syndrome there are several stages characterized by certain disorders of
hemocoagulation and clinical picture.
I stage of DIC-syndrome - phase of hypercoagulation.
The duration of this phase varies widely and is usually inversely proportional to the magnitude of the extreme factor and the degree of activity of the blood clotting system. This phase can develop very rapidly with rapid and significant activation of the coagulation system with massive disseminated intravascular coagulation and severe shock.
The period of hypercoagulation is characterized by activation of plasma systems of blood coagulation, intravascular aggregation of platelets and other blood elements, violation of microcirculation in different organs as a result of blockade of the vascular bed by fibrin masses and cell aggregates.
The phase of hypercoagulation can also develop gradually with slow intake of small doses of prothrombinase. However, the slow flow can end in an explosion with the rapid development of DIC syndrome. In addition to disseminated intravascular coagulation, in some cases only local limited intravascular coagulation and thrombosis are observed.
II stageof DIC syndrome - phase hypocoagulation, which is replaced by a phase of hypercoagulability and due to the consumption of a significant part of body of fibrinogen, factors XIII, V, VIII, and other procoagulants and platelets. At the same time, pathological blood coagulation inhibitors accumulate in the blood, in particular, the degradation products of fibrin and fibrinogen (PDF), which cause an increase in anticoagulant activity of the blood. Intravascular coagulation also causes activation of the fibrinolytic system, leading to the dissolution of blood clots and creating prerequisites for the development of hemorrhagic syndrome.
The inclusion of mechanisms that cause hypocoagulation has a certain sequence and significance throughout the process: depletion of blood clotting mechanisms-accumulation of fibrin degradation products — activation of the fibrinolytic system.
There are a number of important patterns in the development of DIC syndrome. The first of them is that with the development of disseminated intravascular coagulation, the depletion of antithrombin III reserves occurs, which accounts for more than 80 % of the total anticoagulant potential of plasma. By itself, a pronounced deficiency of antithrombnia III is incompatible with life due to multiple thrombosis. In DIC-syndrome, antithrombin III in the phase of hypercoagulation and the transition period is spent on inactivation of blood clotting factors (already in the phase of hypocoagulation, the depletion of antithrombin III reserves is noted). In the event that the concentration of antithrombin III decreases (less than 20 % of the norm), heparin loses its anticoagulation, antithrombotic properties, which determines the ineffectiveness of heparin therapy, which is the basic method of treatment of DIC syndrome. The second important regularity is that following the activation of fibrinolysis, the reserves of this system are gradually depleted due to the consumption of plasminogen from the blood. Therefore, clots devoid of plasminogen are poorly lyzed
even against the background of a large number of fibrinolysis activators, which determines the weak action of streptokinase or urokinase and requires a certain therapeutic correction.
III stage of DIC syndrome occurs as the process proceeds, if it does not end in death. In this stage, in one way or another, there is a restoration of the function of organs, which depends on the degree of their defeat (dystrophic changes, sclerosis, etc.). The stage may end in complete recovery. It is possible to develop severe complications in the absence of DIC-syndrome as such-renal, liver failure, neurological, cardiac and other complications [14-19].
Causes of death in acute DIC syndrome:
1. The death of the organism can occur instantly when the Magistral vessels of vital organs are blocked.
2. If the body does not die in the first minutes from blockage of blood vessels by blood clots, the lethal outcome can be determined by the development of severe hemorrhagic syndrome in the form of local bleeding at the site of vascular damage (surgery, injury) or generalized bleeding, hemorrhages in the internal organs.
3. In a later period, death is possible due to severe dysfunction of individual organs (kidneys, liver, lungs, spleen, myocardium, brain, pituitary gland, adrenal glands, digestive tract). Knowledge of these circumstances determines the choice of therapeutic tactics.
In the pathogenesis of DIC syndrome, it is necessary to point out another important mechanism. When the blood coagulation system is activated through a single push-key-hageman factor-kallikrein-kinin and fibrinolytic systems are activated, as well as the complement system, which in turn activates the prostaglandin system [21-24].
Causes of acute and subacute DIC syndrome
■ Infectious-septic:
■ bacterial;
■ viral;
■ toxic-shock (including abortion).
■ Traumatic and tissue destruction:
■ burn;
■ long-term compression syndrome;
■ massive injuries;
■ with necrosis of tissues and organs (acute toxic liver dystrophy, necrotic pancreatitis, acute myocardial infarction, etc.);
■ in acute intravascular hemolysis, including transfusions of incompatible blood;
■ in traumatic operations;
■ with massive blood transfusions;
■ in hematologic malignancies, especially acute promyelocytic leukemia;
■ in acute radiation sickness.
■ Obstetric and gynecological:
■ with amniotic fluid embolism (especially infected);
■ with early detachment of placenta;
■ atony and uterine massage;
■ with intrauterine fetal death and retention;
■ with eclampsia;
■ shock (in all terminal States);
■ In the process of intensive chemotherapy;
■ In organ transplantation.
The clinical picture consists of signs of the main (background) disease that caused the development of intravascular coagulation of the blood and the DIC-syndrome itself [7,10,20].
Features of diagnosis of acute DIC syndrome.
The diagnosis is based on the identification of those diseases and influences in which the DIC syndrome naturally develops.
Laboratory signs are multidirectional shifts in the coagulating blood system, passing into deep
hypocoagulation, an increase in the plasma content of products of enzyme degradation of fibrin (PDF), determined immunologically or by the test of adhesion of Staphylococcus (TAS). As a result of intensive intravascular coagulation and fibrinolysis in the circulation, the content of not only coagulation factors and platelets, but also the most important anticoagulants-antithrombin III (heparin cofactor), proteins C and S, as well as plasminogen (profibrinolysin) and its activators (plasma precallycrein, high molecular weight kininogen, etc.) decreases.
In connection with the blockade of microcirculation and hypoxia of the organs, violations of the gas composition of the blood, acid-base balance, and later the plasma content of creatinine, urea (acute renal insufficiency), bilirubin (hemolysis, liver damage) increases.
Features of the course of subacute DIC syndrome.
Characterized by a longer than in acute DIC syndrome, the initial period of hypercoagulation is asymptomatic or manifested by thromboses and microcirculation disorders in the organs (congestion, anxiety, a sense of unaccountable fear, decreased diuresis, edema, protein in the urine). The diagnosis is based on the identification of a combination of symptoms of the underlying disease with thrombosis (or) hemorrhages of different localization (bruises, especially at the injection sites, thrombosis in the places of venepunctions) and signs of microcirculation disorders in the organs. In the study of blood reveal the change of phases of hyper-and hypocoagulation, multidirectional shifts of coagulation tests, Hyper-or moderate hypofibrinogenemia, frequent hypertrombocytosis.
Paracoagulation tests (ethanol, protamine-sulfate, etc.) are consistently positive; plasma PDFs are elevated.
In chronic DIC syndrome, long-term wave-like fibrination is accompanied by persistent thrombemia, expressed dysfunction of target organs with minimal and monoorganized hemorrhagic symptoms, but with the simultaneous occurrence of thrombosis of the main veins.
Causes of chronic (prolonged) DIC syndrome:
- chroniosepsis, including protracted septic endocardit;
- chronic immune and immunocomplex diseases;
- chronic viral diseases (hepatitis, HIV, etc.);
- tumor processes (cancer, lymphoma, leukemia, etc.) [25-27].
Features of the course of chronic DIC syndrome.
Against the background of signs of the underlying disease, there is marked hypercoagulation of the blood (rapid coagulation in the veins-spontaneous and with their puncture; needles, test tubes), hyperfibrinogenemia, inclination to thrombosis, positive paracoagulation tests (ethanol, protamine sulfate, etc.). Bleeding time for Duke and Borchgrevink is often shortened, the platelet content in the blood is normal or elevated. Often reveals their spontaneous hyperaggregation - small flakes in the plasma.
In some forms, there is an increase in hematocrit, a high level of hemoglobin (160g/l or more) and red blood cells (more than 5x1012/l), slowing ESR (less than 4-5 mm/h). In some cases, manifest unmotivated multiple venous thrombosis, including unrecognized cancer of different localization (trusseau syndrome), with immune vasculitis, colagenosis, etc. in other cases, hemorrhages, petechiae, cysts, bleeding from the nose and gums, etc. (in combination with thrombosis and without them). [31,32].
Thus, the diagnosis of DIC syndrome is based primarily on a situational basis, with the identification of all possible conditions and types of pathology, including critical conditions in which the development of this syndrome is natural, taking into account the manifestations of its clinical manifestation and data of laboratory examination of patients.
All these three approaches have their own meaning and complement each other. For example, acute DIC syndrome often debuts with profuse bleeding, accompanies shock of any etiology, quickly leads to multiple organ failure, and these situations do not need laboratory confirmation of the diagnosis and unjustified loss of time, but in early pathogenetic therapy. The role of laboratory diagnostics in this case is important to clarify the severity and stage of development of this syndrome by the degree of consumption of the main components of the hemostatic system (platelets, fibrinogen, physiological anticoagulants (antithrombin III, protein C), as well as in the selection and evaluation
of the effectiveness of therapy.
The overwhelming importance in the laboratory diagnosis of DIC does not belong to the detection of Hyper - or hypocoagulation shifts and hypofibrinogenemia (which is typical for fulminant forms of the disease and the terminal phase of deep blood incoagulability), and the identification of thrombocytopenia, a high level of thrombinemia markers (soluble fibrin and D-dimer), and, importantly, the consumption of physiological anticoagulants, the rate of reduction which, along with the depth of thrombocytopenia and the severity of clinical manifestations, reflects the severity of the DIC [33,34].
When recognizing and monitoring acute and subacute DIC syndromes, it is always necessary to take into account the possible impact on the results of studies of heparinemia (in the analysis of blood obtained through a heparinized catheter or in heparin therapy), hemodilution observed in massive infusion therapy, hypercitratemia and a number of plasma substitutes, especially reopoliglyukin[28, 29,35].
Literarysource
1. Баркаган З.С. ДВС-синдром и тромботическая тромбоцитопеническая пурпура в гематологические заболевания/Проблемы клинической медицины. - 2015. - №1. - С. 22-24.
2. Гематология. Руководство/Под редакцией Мамаева Н.Н.-М.: Издательство Спец-Лит, 2019. - C.44.
3. Гематология. Национальный гид./Под редакцией О.А. Рукавицина. - M.: Издательство: ГЭОТАРД-Медиа, 2019. - С.87
4. Levi M, Ten Gate H. Disseminated intravascular coagulation.//N. EngJMed. - 2010. - V. 341. - P. 586-592.
5. Лабораторная диагностика нарушений обмена железа: Учебное пособие/Долгов Б.Б., Луговская С.А. и др.-М.: Издательство Триада, 2016. - 112 с.
6. Лабораторная гематология/Луговская С.А., ПочтарМ.Е. и др. -М.: Издательство:Триада, 2017.- 128с.
7. Гематологический атлас/ Луговская С.А., Почтар М.Е. и др. -М.: Издательство: Триада, 2016.-
135с.
8. Волкова С.А., Боровцов Н.Н. Основы клинической гематологии, 2016. 156 с.
9. Блиндарь В.Н. Гематологические методы исследования. -М.: Издательство: Медицинское информационное агентство России, 2020 - 187с.
10. Гематология: национальный справочник [Электронный ресурс] / Под ред. О.А. Рукавицина. - М.: ГЕОТАР-Медиа, 2017. - 784 с.
11. Levi M, Ten Gate H. Disseminated intravascular coagulation.// NEngJMed. - 2016. - V. 341. - P.586-592. [PubMed].
- Цитогенетическая диагностика гематологических заболеваний/Соколова Т.А., Котловский Ю.Б. и др. М.: Издательство: AcademyAeshetic, 2017. - 67c.
12. Definition, clinical and laboratory rnteria DIC syndrome./Taylor F.B., Jr, Toh C.H., Hoots W.K., Wada H.//Thromb Haemost. - 2015. - V. 86. - P. 1327-1330[PubMed].
13. Gando S. Disseminated intravascular coagulation in traumapatients.//Thromb Hemost. - 2015. - V. 27. - P. 585-592. [PubMed].
14. Атлас гематологии, 4-изд., Доп. - Тверь: ИздательствоТриада Тверь, 2016.
15. Рафтери Э. Т., Лим Э. Дифференциальный диагноз.-М.: Медпресс-информ, 2018.-511 с.
16. Шимура М., ВадаХ., Вакита Ю.//Гематология. - 2017. - Т. 55.- С. 169-174.
17. Кравченко С. К., аль-Ради Л. С., Моисеева Т. Н. Тромботические осложнения у больных с опухолями лимфатической системы //Гематология и трансфузиология.- 2015. - № 2. - С. 3-10.
18. Esmon C. T. Role of coagulation inhibitors in inflammation.//Thromb. Haemast. - 2017. - V. 29. - S90-4[PubMed].
19. Васильев С.А., Виноградов В.Л., Карабудагова З.К. Структура и функция тромбоцитов //Гематология и трансфузиология. - 2015. - № 5. - С. 4-10.
20. Кречетова А.В., Галстян Г.М., ВасильевС.А. Система свертывания крови при сепсисе //Гематология и трансфузиология. - 2017. - № 5. - С. 20-35.
21. Шишина Р. Н., Мукова Л. А., Пронин В. Ю. Морфологическая характеристика эритроцитов периферической крови пожилого, старческого и долгожителя (по данным компьютерных исследований) //Клиническая лабораторная диагностика. - 2018. - № 1. - С. 38-43.
22. Levi M. Diagnosis and treatment of disseminated intravascular coagulation.//Int J Lab. Hematol. - 2017. -V. 36. - P. 228-36 [PubMed].
23. Долгов В. В., Свирин П. В. Лабораторная диагностика нарушений гемостаза. - М.: Триада, 2015. -227с.
24. Папаян Л. П. Новое в представлении о процессе свертывания крови.// Трансфузиология. - 2014. - Т. 5, № 3. - С. 7-22.
25. Байдурин С. А. Методология клинической диагностики и принципы синдромной диагностики внутренних болезней:Учебное пособие.- Астана, 2018.-150 с.
26. Гематология: Новейший справочник /Под общ. Ред. К. М. Абдулкадыровой.- Москва: Изд-во Эксмо; СПб .: Издательство Сова, 2016.-928 с.
27. Внутренние болезни в вопросах и ответах: учебник для медицинских вузов /Под ред.Ковалев Ю.А. -Санкт-Петербург: ООО «Издательство Фолио», 2015. - 656 с.
28. Момот А. П., Беспалова О. В., Воробьева Е. Н. Терапия антикоагулянтами непрямого действия: лабораторный контроль. //Материалы Региональной научно-практической конференциию - Кемерово, 23-25 сентября 2018 г. - С. 64-65.
29. Levi M., Opal S.M. Coagulation abnormalities in critically ill patients.//Crit Care. - 2016. - V. 10. - P. 222 [PubMed].
30. Angstwurm M.W., Dempfle C.E. New disseminated intravascular coagulation score.//Crit care Med. - 2016. - V. 34. - P. 314-320[PubMed].
31. Wilde J.T. Plasma D-dimer levels and their relationship to serum fibrinogen in hypercoagulable states. //Haematologia. - 2019. - V. 71. - P. 65-70[PubMed].
32. Cauchie P., Сauchie Ch. Diagnosis and prognosis of DIC syndrome.//Hematol. - 2016. - V. 81. - P. 414419 [PubMed].
33. Sivula M., Tallgren M. Modified score for DIC in the critically ill.//Intensive Care Med. - 2015. - V. 31. -P. 1209-1214 [PubMed].
34. Esmon C.T. Role of coagulation inhibitors in inflammation.Thromb.//Haemost. - 2015. - V. 86. - P. 51-56 [PubMed].
Corresponding author: Khusainova Gulbana Sagatovna - Associate Professor of the Department of Internal Diseases No. 1 of the NcJSC "Astana Medical University"; husgul777@mail.ru
