Použití hemostatik v bezkrevní medicíně

Prezentace na téma: "Použití hemostatik v bezkrevní medicíně"— Transkript prezentace:

1 Použití hemostatik v bezkrevní medicíně
Seidlová a kol. KARIM FN Brno, ARO II FN Brno, LF MU Brno

2 Skutečnost, která měla zůstat před veřejností utajena, byla vážná nemoc následníka trůnu Alexeje Nikolajeviče (1904–1918). Tento malý chlapec trpěl totiž zákeřnou hemofilií, jakékoli sebemenší poranění mu mohlo způsobit dlouhodobé krvácení. Roku 1909 měl carevič malou nehodu, která mu však v souvislosti s jeho chorobou velmi přitížila. Nikdo si nevěděl rady. Nakonec byl povolán sám Rasputin, kterému se podařilo svými modlitbami a hypnotickými schopnostmi chlapce uzdravit. Je otázka, zda-li to byla pouhá náhoda, či zda měl Rasputin opravdu takový léčitelský dar. Důležité je ale to, že od té doby mu byli car s carevnou velmi nakloněni a nedali na něj dopustit. Wikipedia:

3 hemostatika místní (hemostyptika)
HEMOSTATIKA Heterogenní skupina látek užívaných u stavů spojených s nadměrným krvácením hemostatika celková hemostatika místní (hemostyptika)

4 HEMOSTATIKA Působí několika mechanismy:
přímým vazoaktivním účinkem či mechanicky stlačením cévy podporou destičkových mechanismů tvorby trombu náhradou/dodáním či zvýšením aktivity koagulačních faktorů potlačením zvýšené antikoagulační aktivity antifibrinolytickým účinkem

5 Koagulační kaskáda For internal use - not for distribution 5 5
Key Message The haemostatic cascade comprises of a series of known phases or steps. Presentation Notes Now that the presenter has given the audience a clearer picture of the reasons for using a haemostat, and explained how all haemostats are NOT the same, the presenter can overview the process of haemostasis to the audience using this diagram. Clinical Notes The coagulation cascade is a series of physiological reactions which result in the production of a clot that prevents further bleeding. When blood vessels are cut or damaged, the loss of blood from the system must be stopped before shock and possible death occur. The ability of the body to control the flow of blood following vascular injury is paramount to continued survival. The process of blood clotting and then the subsequent dissolution of the clot following repair of the injured tissue is termed haemostasis. After vessel injury, the initial component of haemostasis is vasoconstriction (contraction of the blood vessel as a means of restricting blood flow or blood loss). This limits the flow of blood to the wound area, slowing the flow of blood through the vessels and minimizing blood loss. The next component is platelet plug formation, where platelets adhere; aggregate at the site of injury; and then bind to collagen that becomes exposed following rupture of the endothelial cell lining of vessels. This initial binding forms a temporary, loose platelet plug (a loose clump of activated platelets that acts to form a physical barrier limiting blood loss after injury). The third component of haemostasis is coagulation and fibrin clot formation. For this to happen, prothrombin is converted to thrombin, which acts upon soluble fibrinogen in the blood to form fibrin monomers. These polymerise to form an insoluble fibrin clot (the clot is also referred to as a fibrin mesh). Following tissue repair the clot must be dissolved. This is achieved via fibrinolysis, which is the fourth component of haemostasis. The dissolution of the clot occurs, from within, when an enzyme called plasmin dissolves the fibrin mesh, as well as the platelets held within it. Once plasmin has completely dissolved the clot, normal blood flow through the vessel will resume. 5 5

6 Koagulační kaskáda a antikoagulanty
For internal use - not for distribution Koagulační kaskáda a antikoagulanty THROMBIN INHIBITORS HEPARIN WARFARIN Zabraňují tvorbě fibrinové sraženiny tPA uPA Aktivují plasmin, který rozpouští fibrinovou sraženinu Key Message The haemostatic cascade comprises of a series of known phases or steps. Presentation Notes This slide enables the presenter to point out that certain (necessary) drug therapies, may impact negatively on certain aspects of the haemostasis cascade. For instance, after a total knee or hip replacement, patients are given anticoagulants in order to avoid post-operative blood clot formation. This may result in a difficulty in achieving haemostasis, however, this situation can be resolved by using an appropriate haemostat. Clinical Notes Platelet inhibitors are a broad spectrum of pharmaceutical agents whose use is growing rapidly, particularly in cardiovascular medicine. Drugs such as clopidogrel (Plavix) have assumed a pivotal role in cardiology and clinical medicine, but they also pose a challenge. There is a fundamental paradox between the need to prevent coronary thrombosis and the need for therapeutic haemostasis. The most important complication of platelet inhibitor therapy is bleeding. Clopidogrel is an irreversible inhibitor of the ADP receptor on platelet membranes. When ADP binds to platelets they are activated and aggregate. This leads to amplification of the coagulation response. Clopidogrel interferes with this process. Aspirin inhibits platelet activation by inhibiting the activity of cyclooxygenase and reducing the production of TXA2 by platelets. Aspirin also reduces endothelial cell production of prostacyclin (PGI2), an inhibitor of platelet aggregation and a vasodilator. Drugs such as warfarin and heparin are anticoagulants. Heparin binds to, and activates, antithrombin III which then inhibits the serine proteases of the coagulation cascade. As well as being given as a drug, heparin is abundant in the granules of mast cells that line the vasculature. Warfarin prohibits coagulation by inhibiting vitamin K-dependent reactions that are necessary for the function of thrombin, and factors VII, IX, and X. Because of the mode of action it takes warfarin several days to reach maximum effect. For this reason, heparin is normally administered first, followed by warfarin. Plasminogen activators, such as tPA are highly selective for the degradation of fibrin in clots. They are extremely useful for restoring the patency of the coronary arteries following thrombosis, in particular during the short period following myocardial infarction. PLAVIX ASPIRIN Zabraňují tvorbě „destičkové ucpávky“ PLATELET INHIBITORS 6 6

7 Koagulační kaskáda a hemostatika
For internal use - not for distribution Koagulační kaskáda a hemostatika vazokonstrikce, trombo fa II, aktivace koag. desmo, terli Nutný pro tvorbu fibrinové sraženiny. fibrinogen Aktivuje přímo fa X, spolu s TF rozbíhá koag. kaskádu rFVIIa brání fibrinolýze. antifibrinolytika Key Message Each haemostat technology has a specific role and MOA in the haemostatic cascade. Presentation Notes This slide sets out the specific MOA of each haemostat technology relevant to the haemostatic cascade, and gives the presenter the opportunity to talk through these in more detail. Depending on available time the presenter can cover this in more or less detail. NOTE: When the slide initially appears, ‘SYNTHETIC SEALANTS’ also appears (in a blue text box) – away from the haemostatic cascade – to show that they do not interfere with the haemostatic cascade. Clinical Notes ORC products such as SURGICEL* NU-KNIT or SURGICEL* FIBRILLAR Absorbable Haemostats, absorb blood, which acts on the cellulose in the hemostat, turning it into cellulosic acid (the substance responsible for the bactericidal qualities of SURGICEL* haemostats). As well as being bactericidal, the lower pH at the wound site (caused by the development of cellulosic acid) leads to local vascular constriction, which helps limit blood loss from the wound site. Platelets adhere to the structure of the ORC haemostat, which provides a matrix for platelet adhesion and aggregation, allowing the coagulation cascade to rapidly perform its functions. Gelatine (eg SPONGOSTAN*) and collagen products will adhere to the wound site, absorbing blood on contact and providing a matrix for platelet adhesion to help the body achieve haemostasis. When used with thrombin, a flowable gelatine like SURGIFLO* Hemostatic Matrix will also aid in fibrin clot formation. Thrombin/gelatine combinations facilitate blood clotting by converting fibrinogen to fibrin as well as aiding mechanical haemostasis. A fibrin sealant (eg QUIXIL® or EVICEL™) mimics the final steps of the physiologic coagulation cascade to achieve haemostasis. A fibrin sealant will function independently of the body’s coagulation mechanism and will work even in patients with coagulopathies, or those receiving heparin or anti-coagulants. The velocity of the primary reaction between thrombin and fibrinogen has been shown to be dependent on the concentration of thrombin, so surgical sealants that are formulated with a high concentration of human thrombin (eg QUIXIL® or EVICEL™) will have a very rapid primary reaction. doplnění koagulačních faktorů. koag. fa stabilizuje fibrin. fa XIII 7

8 přehled látek použitelných celkově
Analoga vasopresinu: desmopresin terlipresin Vitamin K Etamsylat Krevní deriváty: koagulační faktory vyrobené z plazmy rekombinantní

9 Koagulační kaskáda a hemostatika
For internal use - not for distribution Koagulační kaskáda a hemostatika Působí vasokonstrikci, přímo na destičky, aktivuje fa VIII desmopresin terlipresin Key Message Each haemostat technology has a specific role and MOA in the haemostatic cascade. Presentation Notes This slide sets out the specific MOA of each haemostat technology relevant to the haemostatic cascade, and gives the presenter the opportunity to talk through these in more detail. Depending on available time the presenter can cover this in more or less detail. NOTE: When the slide initially appears, ‘SYNTHETIC SEALANTS’ also appears (in a blue text box) – away from the haemostatic cascade – to show that they do not interfere with the haemostatic cascade. Clinical Notes ORC products such as SURGICEL* NU-KNIT or SURGICEL* FIBRILLAR Absorbable Haemostats, absorb blood, which acts on the cellulose in the hemostat, turning it into cellulosic acid (the substance responsible for the bactericidal qualities of SURGICEL* haemostats). As well as being bactericidal, the lower pH at the wound site (caused by the development of cellulosic acid) leads to local vascular constriction, which helps limit blood loss from the wound site. Platelets adhere to the structure of the ORC haemostat, which provides a matrix for platelet adhesion and aggregation, allowing the coagulation cascade to rapidly perform its functions. Gelatine (eg SPONGOSTAN*) and collagen products will adhere to the wound site, absorbing blood on contact and providing a matrix for platelet adhesion to help the body achieve haemostasis. When used with thrombin, a flowable gelatine like SURGIFLO* Hemostatic Matrix will also aid in fibrin clot formation. Thrombin/gelatine combinations facilitate blood clotting by converting fibrinogen to fibrin as well as aiding mechanical haemostasis. A fibrin sealant (eg QUIXIL® or EVICEL™) mimics the final steps of the physiologic coagulation cascade to achieve haemostasis. A fibrin sealant will function independently of the body’s coagulation mechanism and will work even in patients with coagulopathies, or those receiving heparin or anti-coagulants. The velocity of the primary reaction between thrombin and fibrinogen has been shown to be dependent on the concentration of thrombin, so surgical sealants that are formulated with a high concentration of human thrombin (eg QUIXIL® or EVICEL™) will have a very rapid primary reaction. 9

10 Analoga vasopresinu DESMOPRESIN (ADIURETIN, MINIRIN SD inj.)
syntetický oligopeptid MÚ: mobilizace faktoru VIII ve tkáních minimální vazokonstrikční účinek prodloužený eliminační poločas Indikace: - profylaxe krvácení u hemofilie A u von Willebrandovy choroby další indikace (diabetes insipidus) Aplikace: nitrožilní infuze

11 Analoga vasopresinu TERLIPRESIN (REMESTYP inj.)
syntetický oligopeptid ( aktivní látka - vazopresin - vzniká biotransformací v játrech) vazokonstrikční a hemostatický účinek vazokonstrikci zesiluje oxytocin a metylergometrin dlouhý účinek 2-5 hodin Indikace: - profylaxe a terapie krvácení z trávicího a urogenitálního ústrojí Aplikace: nejčastěji formou krátkodobé infůze s opakováním

12 Zesílení adhezibility trombocytů
For internal use - not for distribution Koagulační kaskáda a hemostatika Zesílení adhezibility trombocytů Etamsylate Key Message Each haemostat technology has a specific role and MOA in the haemostatic cascade. Presentation Notes This slide sets out the specific MOA of each haemostat technology relevant to the haemostatic cascade, and gives the presenter the opportunity to talk through these in more detail. Depending on available time the presenter can cover this in more or less detail. NOTE: When the slide initially appears, ‘SYNTHETIC SEALANTS’ also appears (in a blue text box) – away from the haemostatic cascade – to show that they do not interfere with the haemostatic cascade. Clinical Notes ORC products such as SURGICEL* NU-KNIT or SURGICEL* FIBRILLAR Absorbable Haemostats, absorb blood, which acts on the cellulose in the hemostat, turning it into cellulosic acid (the substance responsible for the bactericidal qualities of SURGICEL* haemostats). As well as being bactericidal, the lower pH at the wound site (caused by the development of cellulosic acid) leads to local vascular constriction, which helps limit blood loss from the wound site. Platelets adhere to the structure of the ORC haemostat, which provides a matrix for platelet adhesion and aggregation, allowing the coagulation cascade to rapidly perform its functions. Gelatine (eg SPONGOSTAN*) and collagen products will adhere to the wound site, absorbing blood on contact and providing a matrix for platelet adhesion to help the body achieve haemostasis. When used with thrombin, a flowable gelatine like SURGIFLO* Hemostatic Matrix will also aid in fibrin clot formation. Thrombin/gelatine combinations facilitate blood clotting by converting fibrinogen to fibrin as well as aiding mechanical haemostasis. A fibrin sealant (eg QUIXIL® or EVICEL™) mimics the final steps of the physiologic coagulation cascade to achieve haemostasis. A fibrin sealant will function independently of the body’s coagulation mechanism and will work even in patients with coagulopathies, or those receiving heparin or anti-coagulants. The velocity of the primary reaction between thrombin and fibrinogen has been shown to be dependent on the concentration of thrombin, so surgical sealants that are formulated with a high concentration of human thrombin (eg QUIXIL® or EVICEL™) will have a very rapid primary reaction. 12

13 Etamsylat (DICYNONE inj, tbl.)
působí hemostaticky prostřednictvím destiček: zesiluje adhezi trombocytů neovlivňuje koagulační faktory Užití: operační obory, interna, gynekologie a porodnictví, popáleninová medicína profylaxe a terapie: kapilárního krvácení krvácení ze silně prokrvených tkání menoragie periventrikulární krvácení u nedonošených a novorozenců pomocné léčivo při trombocytopenii Aplikace: nitrožilně, nitrosvalově, perorálně, lokálně

14 podílí se na účinku protrombinu (II) a je nutný pro syntézu VII, IX, X
For internal use - not for distribution Koagulační kaskáda a hemostatika/vitamin K podílí se na účinku protrombinu (II) a je nutný pro syntézu VII, IX, X Vitamin K Key Message Each haemostat technology has a specific role and MOA in the haemostatic cascade. Presentation Notes This slide sets out the specific MOA of each haemostat technology relevant to the haemostatic cascade, and gives the presenter the opportunity to talk through these in more detail. Depending on available time the presenter can cover this in more or less detail. NOTE: When the slide initially appears, ‘SYNTHETIC SEALANTS’ also appears (in a blue text box) – away from the haemostatic cascade – to show that they do not interfere with the haemostatic cascade. Clinical Notes ORC products such as SURGICEL* NU-KNIT or SURGICEL* FIBRILLAR Absorbable Haemostats, absorb blood, which acts on the cellulose in the hemostat, turning it into cellulosic acid (the substance responsible for the bactericidal qualities of SURGICEL* haemostats). As well as being bactericidal, the lower pH at the wound site (caused by the development of cellulosic acid) leads to local vascular constriction, which helps limit blood loss from the wound site. Platelets adhere to the structure of the ORC haemostat, which provides a matrix for platelet adhesion and aggregation, allowing the coagulation cascade to rapidly perform its functions. Gelatine (eg SPONGOSTAN*) and collagen products will adhere to the wound site, absorbing blood on contact and providing a matrix for platelet adhesion to help the body achieve haemostasis. When used with thrombin, a flowable gelatine like SURGIFLO* Hemostatic Matrix will also aid in fibrin clot formation. Thrombin/gelatine combinations facilitate blood clotting by converting fibrinogen to fibrin as well as aiding mechanical haemostasis. A fibrin sealant (eg QUIXIL® or EVICEL™) mimics the final steps of the physiologic coagulation cascade to achieve haemostasis. A fibrin sealant will function independently of the body’s coagulation mechanism and will work even in patients with coagulopathies, or those receiving heparin or anti-coagulants. The velocity of the primary reaction between thrombin and fibrinogen has been shown to be dependent on the concentration of thrombin, so surgical sealants that are formulated with a high concentration of human thrombin (eg QUIXIL® or EVICEL™) will have a very rapid primary reaction. 14

15 Vitamin K KANAVIT inj, gtt
vitamin rozpustný v tucích dietní potřeba nízká - syntéza střevní mikroflórou Hypovitaminóza: - širokospektrá antibiotika - malabsorpce tuků - novorozenci (chybí kolonizace bakteriemi) MÚ: podílí se na účinku protrombinu (F II) a F VII, IX, X je nutný pro jejich syntézu (krok postribozomální modifikace) Indikace: - krvácení při koagulopatiích antidotum při předávkování p.o. antikoagulancii Aplikace: nitrožilně, nitrosvalově, perorálně

16 Koagulační kaskáda a hemostatika/krevní deriváty
For internal use - not for distribution Koagulační kaskáda a hemostatika/krevní deriváty Nutný pro tvorbu fibrinové sraženiny. fibrinogen Aktivuje fa X, s TF rozbíhá proces koagulace rFVIIa Key Message Each haemostat technology has a specific role and MOA in the haemostatic cascade. Presentation Notes This slide sets out the specific MOA of each haemostat technology relevant to the haemostatic cascade, and gives the presenter the opportunity to talk through these in more detail. Depending on available time the presenter can cover this in more or less detail. NOTE: When the slide initially appears, ‘SYNTHETIC SEALANTS’ also appears (in a blue text box) – away from the haemostatic cascade – to show that they do not interfere with the haemostatic cascade. Clinical Notes ORC products such as SURGICEL* NU-KNIT or SURGICEL* FIBRILLAR Absorbable Haemostats, absorb blood, which acts on the cellulose in the hemostat, turning it into cellulosic acid (the substance responsible for the bactericidal qualities of SURGICEL* haemostats). As well as being bactericidal, the lower pH at the wound site (caused by the development of cellulosic acid) leads to local vascular constriction, which helps limit blood loss from the wound site. Platelets adhere to the structure of the ORC haemostat, which provides a matrix for platelet adhesion and aggregation, allowing the coagulation cascade to rapidly perform its functions. Gelatine (eg SPONGOSTAN*) and collagen products will adhere to the wound site, absorbing blood on contact and providing a matrix for platelet adhesion to help the body achieve haemostasis. When used with thrombin, a flowable gelatine like SURGIFLO* Hemostatic Matrix will also aid in fibrin clot formation. Thrombin/gelatine combinations facilitate blood clotting by converting fibrinogen to fibrin as well as aiding mechanical haemostasis. A fibrin sealant (eg QUIXIL® or EVICEL™) mimics the final steps of the physiologic coagulation cascade to achieve haemostasis. A fibrin sealant will function independently of the body’s coagulation mechanism and will work even in patients with coagulopathies, or those receiving heparin or anti-coagulants. The velocity of the primary reaction between thrombin and fibrinogen has been shown to be dependent on the concentration of thrombin, so surgical sealants that are formulated with a high concentration of human thrombin (eg QUIXIL® or EVICEL™) will have a very rapid primary reaction. doplnění – aktivace koagulačních faktorů. feiba, protromplex stabilizuje fibrin. fa XIII 16

17 Krevní deriváty FIBRINOGEN - koagulační faktor I
EPTACOG ALFA - aktivovaný koagulační faktor VII ANTIHEMOFILICKÝ GLOBULIN - koagulační faktor VIII koagulační faktor IX kombinované přípravky - faktory II, VII, IX, X

18 Krevní deriváty připravované z plazmy
ošetřené protivirově antibakteriálně, lyofilizované rekombinantní získávané metodami genetického inženýrství

19 Nutný pro tvorbu fibrinové sraženiny.
For internal use - not for distribution Koagulační kaskáda a hemostatika/ fibrinogen Nutný pro tvorbu fibrinové sraženiny. fibrinogen Key Message Each haemostat technology has a specific role and MOA in the haemostatic cascade. Presentation Notes This slide sets out the specific MOA of each haemostat technology relevant to the haemostatic cascade, and gives the presenter the opportunity to talk through these in more detail. Depending on available time the presenter can cover this in more or less detail. NOTE: When the slide initially appears, ‘SYNTHETIC SEALANTS’ also appears (in a blue text box) – away from the haemostatic cascade – to show that they do not interfere with the haemostatic cascade. Clinical Notes ORC products such as SURGICEL* NU-KNIT or SURGICEL* FIBRILLAR Absorbable Haemostats, absorb blood, which acts on the cellulose in the hemostat, turning it into cellulosic acid (the substance responsible for the bactericidal qualities of SURGICEL* haemostats). As well as being bactericidal, the lower pH at the wound site (caused by the development of cellulosic acid) leads to local vascular constriction, which helps limit blood loss from the wound site. Platelets adhere to the structure of the ORC haemostat, which provides a matrix for platelet adhesion and aggregation, allowing the coagulation cascade to rapidly perform its functions. Gelatine (eg SPONGOSTAN*) and collagen products will adhere to the wound site, absorbing blood on contact and providing a matrix for platelet adhesion to help the body achieve haemostasis. When used with thrombin, a flowable gelatine like SURGIFLO* Hemostatic Matrix will also aid in fibrin clot formation. Thrombin/gelatine combinations facilitate blood clotting by converting fibrinogen to fibrin as well as aiding mechanical haemostasis. A fibrin sealant (eg QUIXIL® or EVICEL™) mimics the final steps of the physiologic coagulation cascade to achieve haemostasis. A fibrin sealant will function independently of the body’s coagulation mechanism and will work even in patients with coagulopathies, or those receiving heparin or anti-coagulants. The velocity of the primary reaction between thrombin and fibrinogen has been shown to be dependent on the concentration of thrombin, so surgical sealants that are formulated with a high concentration of human thrombin (eg QUIXIL® or EVICEL™) will have a very rapid primary reaction. 19

20 FIBRINOGEN - koagulační faktor I Fibrinogen, Haemocomplettan
naprosto zásadní v procesu koagulace Pro tvorbu stabilní hemostatické zátky rezistentní k předčasné fibrinolýze je nutné dostatečné množství trombinu. Pro jeho vznik je nezbytný dostatek koagulačních faktorů, kde klíčovou roli představuje dostatečná hladina fibrinogenu. (Blombach 1989, Carr and Alving 1995, Collet 2003, Allen 1999, Blomback 1994, Carr 1994)

21 Fibrinogen HES může falešně zvýšit hladinu fibrinogenu !

22 po setkání s TF rozbíhá celý proces kosgulace i bypass cestou
For internal use - not for distribution Koagulační kaskáda a hemostatika/ rFVIIa aktivuje fa X po setkání s TF rozbíhá celý proces kosgulace i bypass cestou rFVIIa Key Message Each haemostat technology has a specific role and MOA in the haemostatic cascade. Presentation Notes This slide sets out the specific MOA of each haemostat technology relevant to the haemostatic cascade, and gives the presenter the opportunity to talk through these in more detail. Depending on available time the presenter can cover this in more or less detail. NOTE: When the slide initially appears, ‘SYNTHETIC SEALANTS’ also appears (in a blue text box) – away from the haemostatic cascade – to show that they do not interfere with the haemostatic cascade. Clinical Notes ORC products such as SURGICEL* NU-KNIT or SURGICEL* FIBRILLAR Absorbable Haemostats, absorb blood, which acts on the cellulose in the hemostat, turning it into cellulosic acid (the substance responsible for the bactericidal qualities of SURGICEL* haemostats). As well as being bactericidal, the lower pH at the wound site (caused by the development of cellulosic acid) leads to local vascular constriction, which helps limit blood loss from the wound site. Platelets adhere to the structure of the ORC haemostat, which provides a matrix for platelet adhesion and aggregation, allowing the coagulation cascade to rapidly perform its functions. Gelatine (eg SPONGOSTAN*) and collagen products will adhere to the wound site, absorbing blood on contact and providing a matrix for platelet adhesion to help the body achieve haemostasis. When used with thrombin, a flowable gelatine like SURGIFLO* Hemostatic Matrix will also aid in fibrin clot formation. Thrombin/gelatine combinations facilitate blood clotting by converting fibrinogen to fibrin as well as aiding mechanical haemostasis. A fibrin sealant (eg QUIXIL® or EVICEL™) mimics the final steps of the physiologic coagulation cascade to achieve haemostasis. A fibrin sealant will function independently of the body’s coagulation mechanism and will work even in patients with coagulopathies, or those receiving heparin or anti-coagulants. The velocity of the primary reaction between thrombin and fibrinogen has been shown to be dependent on the concentration of thrombin, so surgical sealants that are formulated with a high concentration of human thrombin (eg QUIXIL® or EVICEL™) will have a very rapid primary reaction. 22

23 EPTACOG ALFA - aktivovaný koagulační faktor VII(NovoSeven)
Eptakog alfa (aktivovaný) je rekombinantní koagulační faktor VIIa s molekulovou hmotností asi 50 000 daltonů vyrobený pomocí genového inženýrství z ledvinových buněk mláďat křečků (BHK buňky). Registrovaný pro léčbu hemofilie,

24 rFVIIa Hemostatický efekt rFVIIa spočívá tedy hlavně ve zvýšení tvorby trombinu na povrchu aktivovaných destiček. Toto množství trombinu pak zajistí: další aktivaci destiček, zvýšení adhese a agregace destiček, tvorbu dostatečně pevné fibrinové zátky, dostatečnou aktivaci TAFI a FXIII rFVIIa zvyšuje tvorbu iniciálního trombinu a zkracuje tak čas nutný k aktivaci dostupných destiček a to v místě poranění cévy, kde dochází k expresi TF Hemostatický efekt rFVIIa spočívá tedy hlavně ve zvýšení tvorby trombinu na povrchu aktivovaných destiček. Toto množství trombinu pak zajistí: další aktivaci destiček, zvýšení adhese a agregace destiček, tvorbu dostatečně pevné fibrinové zátky, dostatečnou aktivaci TAFI a FXIII a to v místě poranění cévy, kde dochází k expresi TF

25 Současné terapeutické indikace rFVIIa dle SPC
NovoSeven je určen k léčbě krvácivých příhod a pro prevenci krvácení při operacích nebo invazivních procedurách u následujících skupin pacientů: pacienti s vrozenou hemofilií s inhibitory proti koagulačním faktorům VIII nebo IX > 5 BU pacienti s vrozenou hemofilií, u kterých se očekává vysoká anamnestická odpověď na faktor VIII nebo IX pacienti se získanou hemofilií pacienti s vrozeným nedostakem faktoru VII pacienti s Glanzmannovou trombastenií s protilátkami k GP IIb-IIIa a/nebo HLA a s předchozí nebo přítomnou afinitou k transfuzi krevních destiček

26 rFVIIa u nehemofilických pacientů Přehled indikací, kde byly prezentovány nebo publikovány zkušenosti s rFVIIa při terapii krvácení (event. zde probíhají klinická zkoušení): ICH trauma PPH kardiochirurgie závažná krvácení při chirurgických výkonech trombocytopenie a trombastenie porušená funkce jater pacienti léčení orálními antikoagulancii stavy po transplantaci kostní dřeně přehled hlavních klinických zkoušení s rFVIIa se zaměřením na bezpečnostní profil (Levi 2006)

27 doplnění koagulačních faktorů
For internal use - not for distribution Koagulační kaskáda a hemostatika dodání koag. fa fa VIII a IX Key Message Each haemostat technology has a specific role and MOA in the haemostatic cascade. Presentation Notes This slide sets out the specific MOA of each haemostat technology relevant to the haemostatic cascade, and gives the presenter the opportunity to talk through these in more detail. Depending on available time the presenter can cover this in more or less detail. NOTE: When the slide initially appears, ‘SYNTHETIC SEALANTS’ also appears (in a blue text box) – away from the haemostatic cascade – to show that they do not interfere with the haemostatic cascade. Clinical Notes ORC products such as SURGICEL* NU-KNIT or SURGICEL* FIBRILLAR Absorbable Haemostats, absorb blood, which acts on the cellulose in the hemostat, turning it into cellulosic acid (the substance responsible for the bactericidal qualities of SURGICEL* haemostats). As well as being bactericidal, the lower pH at the wound site (caused by the development of cellulosic acid) leads to local vascular constriction, which helps limit blood loss from the wound site. Platelets adhere to the structure of the ORC haemostat, which provides a matrix for platelet adhesion and aggregation, allowing the coagulation cascade to rapidly perform its functions. Gelatine (eg SPONGOSTAN*) and collagen products will adhere to the wound site, absorbing blood on contact and providing a matrix for platelet adhesion to help the body achieve haemostasis. When used with thrombin, a flowable gelatine like SURGIFLO* Hemostatic Matrix will also aid in fibrin clot formation. Thrombin/gelatine combinations facilitate blood clotting by converting fibrinogen to fibrin as well as aiding mechanical haemostasis. A fibrin sealant (eg QUIXIL® or EVICEL™) mimics the final steps of the physiologic coagulation cascade to achieve haemostasis. A fibrin sealant will function independently of the body’s coagulation mechanism and will work even in patients with coagulopathies, or those receiving heparin or anti-coagulants. The velocity of the primary reaction between thrombin and fibrinogen has been shown to be dependent on the concentration of thrombin, so surgical sealants that are formulated with a high concentration of human thrombin (eg QUIXIL® or EVICEL™) will have a very rapid primary reaction. doplnění koagulačních faktorů feiba, protromplex 27

28 Koagulační faktor VIII Koagulační faktor IX
Jako substituční léčba u hemofiliků

29 kombinované přípravky (Protromplex, Feiba..)
faktory II, VII, IX, X získané z plazmy určené k léčbě krvácení především při předávkování antikoagulanciemi

30 Koagulační kaskáda a hemostatika
For internal use - not for distribution Koagulační kaskáda a hemostatika brání fibrinolýze. antifibrinolytika Key Message Each haemostat technology has a specific role and MOA in the haemostatic cascade. Presentation Notes This slide sets out the specific MOA of each haemostat technology relevant to the haemostatic cascade, and gives the presenter the opportunity to talk through these in more detail. Depending on available time the presenter can cover this in more or less detail. NOTE: When the slide initially appears, ‘SYNTHETIC SEALANTS’ also appears (in a blue text box) – away from the haemostatic cascade – to show that they do not interfere with the haemostatic cascade. Clinical Notes ORC products such as SURGICEL* NU-KNIT or SURGICEL* FIBRILLAR Absorbable Haemostats, absorb blood, which acts on the cellulose in the hemostat, turning it into cellulosic acid (the substance responsible for the bactericidal qualities of SURGICEL* haemostats). As well as being bactericidal, the lower pH at the wound site (caused by the development of cellulosic acid) leads to local vascular constriction, which helps limit blood loss from the wound site. Platelets adhere to the structure of the ORC haemostat, which provides a matrix for platelet adhesion and aggregation, allowing the coagulation cascade to rapidly perform its functions. Gelatine (eg SPONGOSTAN*) and collagen products will adhere to the wound site, absorbing blood on contact and providing a matrix for platelet adhesion to help the body achieve haemostasis. When used with thrombin, a flowable gelatine like SURGIFLO* Hemostatic Matrix will also aid in fibrin clot formation. Thrombin/gelatine combinations facilitate blood clotting by converting fibrinogen to fibrin as well as aiding mechanical haemostasis. A fibrin sealant (eg QUIXIL® or EVICEL™) mimics the final steps of the physiologic coagulation cascade to achieve haemostasis. A fibrin sealant will function independently of the body’s coagulation mechanism and will work even in patients with coagulopathies, or those receiving heparin or anti-coagulants. The velocity of the primary reaction between thrombin and fibrinogen has been shown to be dependent on the concentration of thrombin, so surgical sealants that are formulated with a high concentration of human thrombin (eg QUIXIL® or EVICEL™) will have a very rapid primary reaction. stabilizuje fibrin. fa XIII 30

31 Antifibrinolytika kys. p-aminobenz. (Pamba) kys
Antifibrinolytika kys. p-aminobenz. (Pamba) kys. tranexamová(Cyklokapron, Exacyl) - inhibitory plazminogenu - spíše u primárních poruch fibrinolýzy - u traumat?

32 Antifibrinolytika

33 Faktor XIII (Fibrogammin)
- je zodpovědný za stabilizaci fibrinu - u traumat?... v dávce? ...

34 LOKÁLNÍ HEMOSTATIKA Používají se samostatně u lehčích a méně rozsáhlých krvácivých stavů (chirurgie, ORL - epistaxe apod.) v kombinaci s adekvátní hemostatickou celkovou léčbou s chirurgickým výkonem a event. radiologickými intervencemi Rychlý účinek a snadná aplikace Obecně dobrá snášenlivost Minimum nežádoucích účinků vč. imunogenních

35 TROMBIN / ŽELATINA KOMBINACE
For internal use - not for distribution Koagulační kaskáda a hemostatika/lepidla Nízké pH způsobuje vasokonstrikci. Vytváří matrici pro zachytávání a seskupení trombocytů. Celulóza Pomáhá při tvorbě fibrinové sraženiny. TROMBIN / ŽELATINA KOMBINACE Vytváří matrici pro zachytávání a seskupení trombocytů. ŽELATINA či KOLAGEN Poskytuje všechny složky potřebně pro vytvoření fibrinové sraženiny. FIBRINOVÉ LEPIDLO Key Message Each haemostat technology has a specific role and MOA in the haemostatic cascade. Presentation Notes This slide sets out the specific MOA of each haemostat technology relevant to the haemostatic cascade, and gives the presenter the opportunity to talk through these in more detail. Depending on available time the presenter can cover this in more or less detail. NOTE: When the slide initially appears, ‘SYNTHETIC SEALANTS’ also appears (in a blue text box) – away from the haemostatic cascade – to show that they do not interfere with the haemostatic cascade. Clinical Notes ORC products such as SURGICEL* NU-KNIT or SURGICEL* FIBRILLAR Absorbable Haemostats, absorb blood, which acts on the cellulose in the hemostat, turning it into cellulosic acid (the substance responsible for the bactericidal qualities of SURGICEL* haemostats). As well as being bactericidal, the lower pH at the wound site (caused by the development of cellulosic acid) leads to local vascular constriction, which helps limit blood loss from the wound site. Platelets adhere to the structure of the ORC haemostat, which provides a matrix for platelet adhesion and aggregation, allowing the coagulation cascade to rapidly perform its functions. Gelatine (eg SPONGOSTAN*) and collagen products will adhere to the wound site, absorbing blood on contact and providing a matrix for platelet adhesion to help the body achieve haemostasis. When used with thrombin, a flowable gelatine like SURGIFLO* Hemostatic Matrix will also aid in fibrin clot formation. Thrombin/gelatine combinations facilitate blood clotting by converting fibrinogen to fibrin as well as aiding mechanical haemostasis. A fibrin sealant (eg QUIXIL® or EVICEL™) mimics the final steps of the physiologic coagulation cascade to achieve haemostasis. A fibrin sealant will function independently of the body’s coagulation mechanism and will work even in patients with coagulopathies, or those receiving heparin or anti-coagulants. The velocity of the primary reaction between thrombin and fibrinogen has been shown to be dependent on the concentration of thrombin, so surgical sealants that are formulated with a high concentration of human thrombin (eg QUIXIL® or EVICEL™) will have a very rapid primary reaction. Vytváří matrici pro zachytávání a seskupení trombocytů. Pomáhá při tvorbě fibrinové sraženiny při kombinaci s trombinem. ŽELATINOVÉ PASTY SYNTETICKÁ LEPIDLA 35

36 Situace, kdy tradiční hemostatické techniky nemusí být vždy efektivní
For internal use - not for distribution Situace, kdy tradiční hemostatické techniky nemusí být vždy efektivní Rozptýlené krvácení z velké plochy Krvácení z jednoho zdroje Izolované nebo rozptýlené krvácení z těžce viditelného zdroje Izolované nebo rozptýlené krvácení z těžce dostupného zdroje Key Message Traditional methods of haemostasis are not always practical or effective. They are useful in many situations but may become impractical, or even clinically inadvisable in others. Presentation Notes This slide allows the presenter to talk about situations where traditional haemostasis is not effective. The slide only gives the minimal heading/explanation for each of the four instances to avoid overcrowding the slide – so the presenter needs to be able to contextualise each point comfortably by expanding as per the clinical notes below. Clinical Notes Traditional haemostasis is not always effective when there is: Diffuse bleeding from a broad surface area – which would preclude the use of isolated ligature/occlusion methods or the use of energy-based systems (ie electrocautery). Bleeding from an isolated source – where placement of a suture or the use of energy would not be practical because of the risk of damage to fragile tissue or to adjacent critical structures. Isolated or diffuse bleeding from a poorly visualised source – where “blind” placement of a suture or the application of coagulating energy would also risk injury to important adjacent structures Isolated or diffuse bleeding from an anatomical location that is not easily approached – with standard instruments for placement of sutures, clips; or with standard methods of haemostasis. 36

37 Místo krvácení Vlastnosti produktu
For internal use - not for distribution Ne všechna hemostatika jsou stejná. Výběr nejvhodnějších hemostatik vyžaduje pečlivé zvážení dvou aspektů: Místo krvácení 1 Key Messages A surgeon needs to chose the correct/best haemostat for the type of procedure being performed. Not all haemostats are the same. The site of bleeding and the product characteristics are two important factors in the decision making process about which haemostat or sealant is most appropriate. Presentation Notes The point of this slide is to strongly introduce the proposition that, when using a haemostat, it is vital to choose the most appropriate solution for each situation, in order to maximise surgical and clinical benefits. It is suggested that the presenter delivers this slide by starting with, something like ,‘It is important to understand that different haemostats produce different clinical outcomes when used in different surgical situations’. Then ,‘Therefore, selecting the best haemostat option will result in the optimal surgical outcome’. Finally – the most important point – ‘Appropriate haemostat selection is dependant upon two main factors’ (cue the two numbered bullets) – ‘The site from which bleeding is occurring; and the features of the product that may be used’. Clinical Notes The choice of the most appropriate haemostat or sealant requires careful consideration of two main aspects: The site of bleeding The product features Vlastnosti produktu 2 37

38 Mechanismus hemostázy
For internal use - not for distribution 2 Vlastnosti produktu Mechanismus hemostázy Funkční vlastnosti Forma Ostatní faktory Key Message Haemostats can be categorised by mechanism of action (MOA), application format, functional attributes and other product factors – and these will help the surgeon work out which haemostat or sealant provides the best solution for any particular bleeding site/scenario. Presentation Notes This is a straightforward slide – where the presenter simply needs to explain that, one way of deciding which haemostat or sealant is most appropriate for any particular bleeding site or scenario, is by considering mechanism of action (MOA), application format, functional attributes and other product factors. Once again, there are too many factors to talk through on one slide, so the next four slides presents these by category. It is suggested that the presenter actually says something like, “Here’s a table showing the different product features – but, as there’s a lot of information here – let’s look at it section by section”. The most important element of the next few slides is that the presenter ensures the audience understands the following – a good understanding of product features is of paramount importance in choosing the correct heamostat or sealant. 38

39 Mechanismus hemostázy
For internal use - not for distribution 2 Vlastnosti produktu Mechanismus hemostázy Funkční vlastnosti Forma Ostatní faktory Mechanismus hemostázy Pasivní (pomáhá při tvorbě „destičkové ucpávky“) Aktivní (pomáhá při tvorbě fibrinové sraženiny) Kombinovaný Key Message Haemostats can be categorised by mechanism of action (MOA) – and this will help the surgeon work out which haemostat or sealant provides the best solution for any particular bleeding site/scenario. Presentation Notes Some products (like SURGICEL* or SPONGOSTAN*) aid platelet plug formation. Some products (like QUIXIL® or EVICEL™) aid fibrin clot formation; and some combination products have both MOAs. This slide gives the presenter the opportunity to differentiate these different product categories by MOA. Clinical Notes Certain products will accelerate haemostasis more than others because of their MOA, but there are financial implications associated with the use of more advanced haemostats. Clearly identifying the haemostatic requirements for different bleeding sites/episodes will enable the clinician to choose the optimal product for each specific instance. For example, a passive product can usually be used successfully when bleeding is relatively mild, whereas an active or combination product may be required for moderate or heavy bleeding. 39

40 Mechanismus hemostázy
For internal use - not for distribution 2 Vlastnosti produktu Mechanismus hemostázy Funkční vlastnosti Forma Ostatní faktory Forma Tkanina Tkaná Netkaná Pasta Tekutina Houba Želatinová Kolagenová Key Message Haemostats can be categorised by application format – and this will help the surgeon work out which haemostat or sealant provides the best solution for any particular bleeding site/scenario. Presentation Notes This is another straightforward slide – where the presenter needs to explain that, another way of deciding which haemostat is most appropriate for any particular bleeding site or scenario, is by application format. So some products are fabric based (eg SURGICEL*) – and these can be woven (eg SURGICEL* NU-KNIT) or non-woven (eg SURGICEL* FIBRILLAR). Some products are flowable (eg SURGIFLO*) and these can take the form of a paste (which can be spread with fingers) or a slurry (which is applied with a syringe). Some products are liquid (eg QUIXIL® or ETHICON OMNEX*) and these can be applied via a drip (to give controlled delivery) or via a spray (which will give broad coverage). Some products are presented in a sponge format (eg SPONGOSTAN* Gelatin Sponge) and these can be made of gelatine or collagen. 40

41 LOKÁLNÍ HEMOSTATIKA celulóza želatina kolagen fibrinová lepidla
syntetická lepidla kombinace

42 Oxidovaná celulóza (Surgicel, Nu-Knit )
sterilní vstřebatelná tkanina při styku s krví vytváří želatinovou hmotu trombofilní vstřebávání 7-14 dnů některá baktericidní

43 Resorbovatelná želatina) (SPONGOSTAN, GELASPON, SURGIFLO)
vepřová purifikovaná želatina sušená - nasává krev působí tlakem na cévu zachytává trombocyty vstřebávání 4-6 týdnů jako pasta(tamponáda krvácení z kostí) (Surgiflo, Floseal)

44 Kolagen (Avitene, Gentafleece, Hydrosorb)
z purifikovaných zvířecích šlach sušený, zmražený, dehydrovaný jako matrice pro zachytávání trombocytů vstřebávání 8-10 týdnů

45 Fibrinová lepidla (Evicel, Tissucol)
Dvousložkové lepidlo 1. fibrinogen a fa VIII 2. trombin a vápník reakce během vteřin simuluje proces srážení obsahuje antifibrinolytickou složku aktivní i u léčených antikoagulanciemi vstřebávání jako fyziologická sraženina

46 Kombinace (TachoSil, FloSeal)
mechanické působení matrice biologické působení trombinu a/nebo fibrinogenu

47 Syntetická lepidla (Omnex)
nepůsobí na hemostázu vytváří pevné spojení nebo utěsnění jen některá enzymaticky odbouratelná

48 Vývoj Hemostatik HEMOSTATICKÁ FUNCE CENA INTENZITA KRVÁCENÍ % PŘÍPADŮ
For internal use - not for distribution Vývoj Hemostatik ŽELATINA STD. ORC KOŇSKÝ KOLAGEN NU-KNIT ORC VEPŘOVÝ KOLAGEN FIBRILLAR ORC PASTY + Trombin €€€ FIBRINOVÁ LEPIDLA KOMBINACE PASTY € €€ HEMOSTATICKÁ FUNCE Key Message Different surgical haemostasis needs require different product technologies, and these will cost more as they need to become increasingly technical to cope with required haemostatic specifications Presentation Notes It is important for the presenter to carefully explain this MATRIX so that customers can understand the different haemostatic needs and the different haemostats available – so that the cost implications for higher specification haemostats are clear. The headings and arrows appear click by click (heading and arrow together) so that the presenter can talk through the process – something like this … As bleeding intensity increases, so there is the need for a greater haemostatic capacity and capability in order to effectively manage the increased bleeding challenge. Products that need to have a higher technical specification in order to effectively manage more challenging bleeding scenarios tend to be more expensive (because they are more complex). If the bleeding intensity is lower, then the haemostatic cost will also be lower (as more ‘traditional’ haemostats such as SURGICEL* will suffice). The number of cases is indirectly proportional to the bleeding intensity. This means that there are many more cases of mild-moderate bleeding, and less cases of severe bleeding, which require advanced haemostats. Finally (as the products vs € overview is clicked in) the presenter can talk through an overview of the products/effectiveness for different levels of bleeding/cost. Currently clinicians may use a SURGICEL* type product for low intensity bleeding, and an advanced product (eg Floseal or Tachosil) for moderate bleeding. However, some less expensive haemostats will handle cases of moderate bleeding intensity just as well as more expensive advanced haemostats (eg SURGICEL* Fibrillar will handle moderate bleeding as effectively as Floseal or Tachosil and is much less costly). CENA INTENZITA KRVÁCENÍ % PŘÍPADŮ 48

49 For internal use - not for distribution
Doba Absorpce 2 4 6 ORC Želatina Kolagen Týdny Key Message The longer a haemostat stays inside the body, the higher the risk is that a tissue reaction will be caused due to the presence of a foreign body. Presentation Notes This slide gives the presenter the opportunity to explain that the risk of a foreign body reaction increases with the amount of time a haemostat stays inside the body. This should be a straight forward point to make using the graph that appears on the first click. Clinical Notes ORC reabsorbs in 1-2 weeks, gelatine in 3-4 weeks and collagen in 6-8 weeks. NOTE: some 1st generation synthetic sealants are not reabsorbable (eg BioGlue). However, ETHICON OMNEX* – the 2nd generation synthetic sealant – is reabsorbed over 24 – 36 months. Čím déle zůstanou hemostatika v lidském těle, tím vyšší risk negativní reakce. NOTE: Some (1st generation) synthetic sealants are not reabsorbable. ETHICON OMNEX* (2nd generation synthetic sealant): reabsorbed in 24–36 months. 49

50 Děkuji za pozornost