1. ISTH International Society on Thrombosis and Haemostasis

2. ISTH Russian Association on Thrombosis Haemostasis and Vascular Pathology n.a. A.A.Schmidt-B.A.Kudryashov First Moscow State Medical University n.a. I.M.Setchenov

3. RUSSIAN ASSOCIATION ON THROMBOSIS, HEMORRAGE AND VASCULAR PATHOLOGY named after А. А. SCHMIDT - B.А.KUDRYASHOV

6. ISTH International Society on Thrombosis and Haemostasis EDUCATIONAL COURSE Thrombosis, Thrombophilias, DIC and Thrombolytic Therapy. Moscow 17-19 September 2014

7. YOU ARE WELCOME !!!

8. DIC and HOW WE UNDERSTAND it in RUSSIA I.N.Bokarev Moscow ISTH EDUCATIONAL COURSE 17.09.2014

9. TFPI AT APC XIIa XII KallikreinPrekallikrein HMWK

10. Tissue factor molecule

12. НАРУШЕНИЯ ГЕМОКОАГУЛЯЦИИ ВЫЗЫВАЮТ: ГЕМОРРАГИИ ТРОМБОЗЫ ДВС-СИНДРОМ

14. ИНТЕНСИВНОСТЬ ВНУТРИСОСУДИСТОГО МИКРОСВЕРТЫВАНИЯ КРОВИ МОЖНО ОПРЕДЕЛИТЬ на основании измерения фибринопептида А D-димера b - тромбоглобулина 4-го фактора тромбоцитов

15. DIC Syndrom

17. Волтер Сиггерс 1910-1996

19. The reasons of my presentation: 1. To restrict the unnecessary use the DIC expression, to remind how it was originated. 2. To resolve debatable questions on definitions and detection of DIC by introducing the conception of the Constant Intravascular Microcoagulation. 3. Stop to use the term “hypercoagulability”

20. The reasons of my presentation: 1. To restrict the unnecessary use the DIC expression, to remind how it was originated. 2. To resolve debatable questions on definitions and detection of DIC by introducing the conception of the Constant Intravascular Microcoagulation. 3. Stop to use the term “hypercoagulability”

21. DIC - is a very dangerous state. For the Doctor the DIC diagnosis requires a very quick actions, because the patient can die during several hours.

22. Prevalence of DIC People who arrive to hospital 1 in 1000 G. Мuller-Веrghaus 1in 867 J.Zilbut Acute leukemia - 15-20% Septicemia (if it is Gram-negative or Gram-positive microbes) - 30-50% Severe injury - 50-70 % M. Levi

23. D. McKay Term of DIC was proposed in USA by young American pathologist Donald МсКау in 1950, when he made the autopsy. D. МсКау discovered a lot of thrombus in the vessels in the body of woman, who had died in obstetric hospital because of bleeding disorders. He proposed the term- Disseminated Intravascular Coagulation which was coined.

24. The senior collegues of D.McKay - С.Schneider and W. Siggers made public this term. The term DIC - syndrome got wide use in medicine after 4th American congress of obstetricians in 1951 where С.Schneider and W. Siggers reported the case of D.McKay.

25. Walter Siggers 1910-1996

26. Schneider CL. “Fibrin embolism”(disseminated intravascular coagulation) with defibrination as one of the end results during placenta abruptio. Surg.Gynec.Obstet.92:27-34. Jan 1951 Schneider CL : Fibrin embolism (disseminated intravascular coagulation) and the etiology of eclampsia. J. Obst. Gynaec. Brit Emp. 58: 538-554.Aug.1951

27. DIC attracted high attention of the medicine By : 1.Its dangerous to the life 2.Unusual way of development- thrombosis induced bleeding

28. - Н. Lasch - consumption coagulopathy - H. Selye and М.Machabeli - thrombo- hemorragic syndrom - С. Оwen and W. Воwie - Intravascular blood coagulation and fibrinolysis

30. С. Оwen in his experimental works with the animals, when he infused thromboplastin to the dogs, had got not the bleeding, but increase some of the procoagulant in their blood. Those data allowed him to say, that the DIC may be the chronic- and from those time appeared new term- the “Chronic DIC- syndrome”. It was done in 1970-th.

32. The reasons of my presentation: 1. To restrict the unnecessary use the DIC expression, to remind how it was originated. 2. To resolve debatable questions on definitions and detection of DIC by introducing the conception of the Constant Intravascular Microcoagulation. 3. Stop to use the term “hypercoagulability”

33. Types of the DIC- syndrome Compensated and decompensated DIC G. Мuller-Веrghaus Chronic, subacute, Acute DIC С. Оwen Evident and latent DIC F.Тауlor Pre-DIC Consumption Coagulopathy - Н. Lasch Thrombo-hemorragic syndrom - H. Selye and М.Machabeli,

34. The finding of D.McKay and C.Owen very much stimulated the investigation of the process of fibrin formation. By B. Blomback, M. Blomback, B. Lipinsky and V. Gurevich, U. Abildgaard, P. Gaffney, S. Niewiarovsky, K.Rucinski and others. was proposed the methods to detect FDP, soluble fibrin-monomer, D-dimer, β-thromboglobulin, the platelets factor - 4 and at last TPP, for the investigation of the fibrin formation. And the investigations in this area began to be done.

35. The possibility of determination the markers of fibrin-formation and the activity of platelets component of blood coagulation made it possible to found out the difference in their intensity and to suggest that they are relatively independent from each other. Investigations, that we had done on the large body of patients with chronic pathology, gave us the information about the fibrin formation and platelet activity as the parts of intravascular microcoagulation at patients with different diseases.

36. We studied the state of intravascular fibrin formation with the help of TPP( thrombus protein precursor), which detect the fibrin-monomer without fibrinopeptids А and В. We took the patient with the opposite clinical picture- thrombosis and bleeding. The level of TPP was measured at the patients with acute coronary syndrome and at the hemophiliac. In the blood of people, who had the hemophilia, the level of TPP was higher, than it was at the healthy people

37. INTENSITY OF INTRAVASCULAR MICROCOAGULATION MAY BE MEASURED BY the level of: Fibrinopeptide- A D-dimer b - thromboglobulin Platelet factor- 4

39. Constant intravascular microcoagulation Constant presence of the markers of intravascular coagulation in plasma of healthy and sick people gave us the reason to think, that the intravascular microcoagulation of the blood is going permanently, and there is need to show its existence by the term “Constant intravascular microcoagulation”- CIMC.

40. Grades OF the CONSTANT INTRAVASCULAR MICROCOAGULATION of BLOOD 1-st grade NORMAL CIMC Levels of CIMC markers are “ normal”. 2-nd grade TRANSIENT INCREASED CIMC Levels of CIMC markers increased, but it is unstable and does not produce special clinical changes in the main disease picture. 3-d grade SUSTAINED INCREASED CIMC Levels of CIMC-markers is increased. This state is stable, but does not have special clinical manifestations. There is hope,that Its regulation may be important and may increase the positive outcome of the disease. 4 th grade CIMC- DIC-SYNDROM Increase of the constant intravascular coagulation is going sharply and produce the impact on the organs function, threatening to the life of the patients ( DIC-syndrom)

41. DEFINITION of DIC DIC is the phenomena of acute and intensive formation of intravascular microclots, that are generated in the microvessels level. They can get different morphologic structure, different forms of clinical manifestation and lead to acute dysfunction of organs and tissues is the threat to life.

42. Constant intravascular microcoagulation DIC-syndrome is only the highest stage of CIMC, where the increase of its intensity is an independent cause of the damage of body-organs and body-tissues and may manifest itself by the bleeding, multiple organ damage, hypotony, micro- and macro- thrombosis and its different combinations.

43. It may be used by the doctor in the following way: - He will know, that the blood in the body is clotting constantly, and that the patients with the chronic disease every time have the permanent increase of the blood clotting. The term “ hypercoagulation” is unnecessary. - Doctor must know, that the possibility of thrombosis depends from the main disease and from the ability of the patients blood to coagulate (thrombophilia).

44. CIMC conception resolves all debatable questions on definition and get the practicaly useful information about DIC There is no need to look for the chronic DIC, as the clotting of blood is going constantly.

45. The reasons of my presentation: 1. To restrict the unnecessary use the DIC expression, to remind how it was originated. 2. To resolve debatable questions on definitions and detection of DIC by introducing the conception of the Constant Intravascular Microcoagulation. 3. Stop to use the term “hypercoagulability”

46. Identification of the level of the markers of the intravascular blood microcoagulation couldn’t help to the doctor to predict the speed of progress of increasing of intravascular microcoagulation for reaching the 4-th stage of CIMC, which is the synonym of the acute DIC.

47. At each morbid events which characterized by high risk of DIC’s development, such as sepsis and other infections, neoplasms, traumatic and surgical tissue damage, obstetrical pathology, vascular lesions and vessels anomaly, autoimmune diseases, allergic reactions, the expectation of the development of DIC by the doctors must be constant. Only than it will be possible to do the right and early recognition of DIC.

48. Diagnosis of DIC Level of fibrinogen Level of platelets Progressive reduction of their level in combination with the clinical picture should be the reason for diagnosis of DIC and for the beginning of therapy.

49. We HOPE, that the use of the conception of Constant Intravascular Micro Coagulation will help You to treat Your patients.

50. Thank You For Your Attention !