Toepassing van plasmafactoren voor de hemostase - Huidige inzichten in de hemostatische balans

Maat: px

Weergave met pagina beginnen:

Download "Toepassing van plasmafactoren voor de hemostase - Huidige inzichten in de hemostatische balans"

Joke Meyer
5 jaren geleden
Aantal bezoeken:

1 Klinisch Transfusieonderwijs NVB-TRIP 2018 Toepassing van plasmafactoren voor de hemostase - Huidige inzichten in de hemostatische balans Dr. Erik AM Beckers Internist-hematoloog/transfusiespecialist

2 2 Disclosure belangen spreker bijeenkomst NVB-TRIP symposium 2018, Ede 16 mei 2018 Naam: dr. Erik AM Beckers, internist-hematoloog/transfusiespecialist Voor bijeenkomst mogelijk relevante relaties Bedrijfsnamen Sponsoring of onderzoeksgeld Honorarium of andere (financiële) vergoeding Bayer Roche, Pfizer, Bayer, Sanquin, CSL Behring. (Transparantieregister)

3 3 De hemostatische balans 1. Wat zegt het oude leerboek over stolling? 2. Wat zegt het nieuwe leerboek over stolling? 3. Welke lab.testen zijn er, wat wordt er gemeten? 4. Plasma, plasma-producten en nieuwe geneesmiddelen 5. Wat missen we?

4 Stollingscascade 4

5 Coagulation model 5

6 Coagulation model 6 aptt: factors VIII, IX, XI en XII PT: factors II, V, VII en X (1572) Vit K dependent factors: II, VII, IX en X (1972)

7 Coagulation model 7 Waar is factor XII? Waar is factor IV? Waar is factor VI?

8 Coagulation model 8 PT, aptt, TT Wat testen we niet? Vaatwand, endotheel Bloedplaatjes Von Willebrand factor FXIII

9 9 1. Adhesion, aggregation of platelets >>>>>> primary hemostasis 2. Thrombin generation and clotting >>>>>> secondary hemostasis 3. Fibrinolysis Mean object of coagulation is : to preserve the circulation of blood

10 Trombocyten functie Beschadiging endotheel - Plaatjes adhesie en vormverandering - Plaatjes activatie en secretie - Plaatjes aggregatie - Interactie met stolfactoren

11 11

12 12

13 13 Congenital Bleeding Disorders 1. Platelet disorders 2. Common inherited coagulation disorders 1. Von Willebrand disease (VWD), 2. Hemophilia A and B, 3. Fibrinogen disorders, 3. Rare inherited coagulation disorders 1. FXIII 2. FXI 3. factor VII 4. FV 5. FII 6. Combined factor deficiencies 4. Hyperfibrinolysis PAI-1 deficiency alpha-2 anti-plasmin deficiency

14 Wat kan het laboratorium bieden? Screen Confirm Primair Hb/trombocyten#/MPV/dif Bloedingstijd PFA (Platelet Function Analyzer) Multiplate Verify Now ROTEM 2. Secundair PT/INR aptt & aptt 1:1 Trombinetijd ROTEM Trombinegeneratie test vwf activiteit en antigeen Trombocyten aggregatie/release testen mbv licht/luminescentie detectie Flowcytometrie Elektronenmicroscopie (EM) Fibrinogeen FVIII FIX Overige stollingsfactoren FXIII & Fibrinolyse markers axa activiteit Diluted Trombinetijd 3. Vasculair Bloedingstijd -

15 Wat kan het laboratorium bieden? Screen Confirm Primair Hb/trombocyten#/MPV/dif Bloedingstijd PFA (Platelet Function Analyzer) Multiplate Verify Now ROTEM vwf activiteit en antigeen Trombocyten aggregatie/release testen mbv licht/luminescentie detectie Flowcytometrie Elektronenmicroscopie (EM) Volbloed, geen voorbereiding nodig

16 Hb/plt/MPV/dif PFA Bloedingstijd Multiplate ROTEM Verify Now

19 Flowcytometrie: Bestudering plaatjesmembraan markers 19

20 EM

21 ROTEM: Meetprincipe volbloedtest, visco-elastisch

22 22

23 Normale patiënt Kaoline TF PLt remmer Fibrinolyse remmer

24 UITSLAGEN

25 Bloedplaatjes tekort

26 ROTEM 26 ROTEM: detectie van trombocytopenie en

27 27 Congenital Bleeding Disorders 1. Platelet disorders 2. Common inherited coagulation disorders 1. Von Willebrand disease (VWD), 2. Hemophilia A and B, 3. Fibrinogen disorders, 3. Rare inherited coagulation disorders 1. FXIII 2. FXI 3. factor VII 4. FV 5. FII 6. Combined factor deficiencies 4. Hyperfibrinolysis PAI-1 deficiency alpha-2 anti-plasmin deficiency

28 INDICATIONS FOR PLASMA THERAPY 28

29 29 Use of fresh frozen plasma Contraindications Do not use fresh frozen plasma in the following circumstances: when you can correct coagulopathy effectively with specific therapy, such as vitamin K, cryoprecipitate, factor VIII or other specific factor concentrates in plasma exchange procedures except for treatment in thrombotic thrombocytopenic purpura treatment of immunodeficiency states when you can safely and adequately replace blood volumes with volume expanders, such as 0.9% Sodium Chloride Injection, Hartmann s Solution, or appropriate colloids.

30 30 Use of fresh frozen plasma FFP is indicated for patients with a coagulopathy who are bleeding or at risk of bleeding, and where a specific therapy or factor concentrate is not appropriate or unavailable. FFP may be indicated to replace labile plasma coagulation factors during massive transfusion, cardiac bypass, liver disease or acute disseminated intravascular coagulation in the presence of bleeding and abnormal coagulation. It is appropriate to use FFP in cases of warfarin overdose with life threatening bleeding in addition to Prothrombinex Complex Concentrates (PCC) (vitamin K-dependent factor concentrates eg Prothrombinex-VF). Where PCCs are not available, FFP is suggested in patients with life threatening or clinically significant bleeding; and for urgent preoperative warfarin reversal. (1) Fresh frozen plasma is an accepted treatment for patients with TTP in plasma exchange

31 31 Congenital Bleeding Disorders 1. Platelet disorders 2. Common inherited coagulation disorders 1. Von Willebrand disease (VWD), 2. Hemophilia A and B, 3. Fibrinogen disorders, 3. Rare inherited coagulation disorders 1. FXIII 2. FXI 3. factor VII 4. FV 5. FII 6. Combined factor deficiencies 4. Hyperfibrinolysis PAI-1 deficiency alpha-2 anti-plasmin deficiency PLTs, DDAVP Suppletie Factoren Plasma transfusie Tranexaminezuur

32 32 Deficiency coagulation factors Anticoagulation factors Thrombosis Bleeding Balancing by suppletion coagulation factors or by lowering anticoagulation

33 New products 33 Extended T1/2 fusion with IgG fusion with albumin pegylation Bispec mab FIX/FX TFPI inhibitors sirna antithrombin

34 Mechanism ACE910 = emicizumab Bispecific antibody 34

35 35 Congenital Bleeding Disorders 1. Platelet disorders 2. Common inherited coagulation disorders 1. Von Willebrand disease (VWD), 2. Hemophilia A and B, 3. Fibrinogen disorders, 3. Rare inherited coagulation disorders 1. FXIII 2. FXI 3. factor VII 4. FV 5. FII 6. Combined factor deficiencies 4. Hyperfibrinolysis PAI-1 deficiency alpha-2 anti-plasmin deficiency PLTs, DDAVP Suppletie Factoren Plasma transfusie Tranexaminezuur EN HET ENDOTHEEL DAN?

36 Glycocalix 36

37 37 Unifying: severe trauma, sepsis, MI and PCAS Liver transplant, postpartum hemorraghe, cardiosurgery???

38 38 Consumption coagulopathy And Less PAI-1 Less alfa2-antiplasmin

39 39 Fibrinolytic shutdown Hyperfibrinolysis

40 40

41 41

42 42 Wat missen we? Trombine generatie test En plasmine generatie test?

Vergelijkbare documenten

Verworven stollingsinhibitoren. Marc Jacquemin

Verworven stollingsinhibitoren Marc Jacquemin 1 ALLO-immune respons tegen toegediende stollingsfactoren hemofilie A behandeld met FVIII antistoffen tegen FVIII 2 GEEN mutatie in de genen van stollingsfactoren