Ine Gruyters

Ellen Van Hemeldonck

Prof. Dr. Missant

Anesthesiology.1995 Feb;82(2):383-92.The doseThe doseThe doseThe dose----response relationship ofresponse relationship ofresponse relationship ofresponse relationship of tranexamictranexamictranexamictranexamic acid.acid.acid.acid.HorrowHorrowHorrowHorrow JC, Van Riper DF, Strong MD, Grunewald KE, JC, Van Riper DF, Strong MD, Grunewald KE, JC, Van Riper DF, Strong MD, Grunewald KE, JC, Van Riper DF, Strong MD, Grunewald KE, ParmetParmetParmetParmet JL. JL. JL. JL. RESULTS:RESULTS:RESULTS:RESULTS:The six groups presented similar demographics. Patients receiving placebo had increased postoperative D-dimerconcentration compared to groups receiving tranexamic acid. Patients receiving at least 10 mg.kg-1 tranexamic acid followed by 1 mg.kg-1.h-1 bled significantly less (365, 344, and 369 g.12 h-1, respectively, for those three groups) compared with patients who received placebo (552 g, P < 0.05). . Only initial hematocrit affected whether a patient received an allogeneictransfusion within 5 days of operation (odds ratio 2.08 for each 3% absolute decrease in hematocrit).CONCLUSIONS:CONCLUSIONS:CONCLUSIONS:CONCLUSIONS:Prophylactic tranexamic acid, 10 mg.kg-1 followed by 1 mg.kg-1.h-1, decreases bleeding after extracorporeal circulation. Larger doses do not provide additional hemostatic benefit.

� Comparison of two doses of Comparison of two doses of Comparison of two doses of Comparison of two doses of tranexamictranexamictranexamictranexamic acid in adults undergoing cardiac surgery acid in adults undergoing cardiac surgery acid in adults undergoing cardiac surgery acid in adults undergoing cardiac surgery with cardiopulmonary bypass.with cardiopulmonary bypass.with cardiopulmonary bypass.with cardiopulmonary bypass.

� Sigaut S1, Tremey B, Ouattara A, Couturier R, Taberlet C, Grassin-Delyle S, Dreyfus JF, Schlumberger S, Fischler M.

� METHODS:METHODS:METHODS:METHODS:� Patients were stratified according to transfusion risk, then randomized to two TA

doses: 10 mg/kg bolus followed by 1 mg·kg·h infusion (low dose) until the end of surgery or 30 mg/kg bolus followed by 16 mg·kg·h infusion (high dose). The primary endpoint was the incidence of blood product transfusion up to day 7. Secondary ones were incidences of transfusion for each type of blood product and amounts transfused, blood loss, repeat surgery, TA-related adverse events, and mortality.

� RESULTS:RESULTS:RESULTS:RESULTS:� The low-dose group comprised 284 patients and the high-dose one 285. The

primary endpoint was not significantly different between TA doses (63% for low dose vs. 60% for high dose; P = 0.3). With the high dose, a lower incidence of frozen plasma (18 vs. 26%; P = 0.03) and platelet concentrate (15 vs. 23%; P = 0.02) transfusions, lower amounts of blood products (2.5 ± 0.38 vs. 4.1 ± 0.39; P = 0.02), fresh frozen plasma (0.49 ± 0.14 vs.1.07 ± 0.14; P = 0.02), and platelet concentrates transfused (0.50 ± 0.15 vs. 1.13 ± 0.15; P = 0.02), lower blood loss (590 ± 50.4 vs. 820 ± 50.7; P = 0.01), and less repeat surgery (2.5 vs. 6%; P = 0.01) were observed. These results are more marked in patients with a high risk for transfusion.

� CONCLUSIONS:CONCLUSIONS:CONCLUSIONS:CONCLUSIONS:� A high dose of TA does not reduce incidence of blood product transfusion up to

day 7, but is more effective than a low dose to decrease transfusion needs, blood loss, and repeat surgery.

� Misselijk, braken, diarree

� Hoofdpijn, vertigo

� Allergische reactie, anafylaxie

� Vrouw 32 jaar

� VG: Migraine

� R/ Exacyl 0,5-1 g / d tijdens menses

Tranexamic acid and intracranial thrombosis. Rydin E, Lundberg PO

� Ernstige hoofdpijn, paresthesieën linker arm en linker been.

� + 1D: Hemiparese links en hemianopsie

� OZ:� CSV: geen bijzonderheden

� Labo: geen bijzonderheden

� Angiografie: Trombus rechter a. cerebri posterior

Man 83jr

Gekende chronische ITP

Groot hematoom R/1,5g R/1,5g R/1,5g R/1,5g ExacylExacylExacylExacyl pdpdpdpd

16m later: DVTDVTDVTDVT

Vrouw 62 jrSAB; normale coagulatie/hematologie

R/ Conservatief en R/ Conservatief en R/ Conservatief en R/ Conservatief en ExacylExacylExacylExacyl IVIVIVIV

Dag 10: Plotse retrosternale pijnDyspneuCyanoseShock

AngiogramMassieve bilaterale Massieve bilaterale Massieve bilaterale Massieve bilaterale longembolilongembolilongembolilongemboli

Man, 29 jrHemofilie AFrequente opnames navbloedingen (gewrichten,…)

R/ 1,5g R/ 1,5g R/ 1,5g R/ 1,5g ExacylExacylExacylExacyl 2/2/2/2/dddd 6 maanden later

Plotse thoracale pijn zonder T°, hoesten,..

RX –V/P scan: Meerdere Meerdere Meerdere Meerdere longembolilongembolilongembolilongemboli

Geen DVT, geen AI-aandoeningen,…

Man, 27 jr

Ongeval met blaasschade en excessieve blaasbloeding R/ Heelkunde, transfusie en R/ Heelkunde, transfusie en R/ Heelkunde, transfusie en R/ Heelkunde, transfusie en ExacylExacylExacylExacyl IVIVIVIV

6u later:Wit en koud rechter ondebreen

Angiografie: Arteriële trombose Arteriële trombose Arteriële trombose Arteriële trombose aicaicaicaic

Casus 1

Vrouw 31jrMenorrhagieën

R/ 3R/ 3R/ 3R/ 3----4g 4g 4g 4g ExacylExacylExacylExacyl pdpdpdpd tijdens tijdens tijdens tijdens mensesmensesmensesmenses

D2 Tijdelijke zwakte linker handD9 Hemiparese links

Angiografie: Trombose rechter A Trombose rechter A Trombose rechter A Trombose rechter A cerebricerebricerebricerebri media media media media

Casus 2

Vrouw 32jrMenorrhagieën

R/ 0,5R/ 0,5R/ 0,5R/ 0,5----1g 1g 1g 1g ExacylExacylExacylExacyl pdpdpdpd tijdens tijdens tijdens tijdens mensesmensesmensesmenses

na 1jaar: Paresthesieën li arm-been+1d: Hemiparese links

Angiografie: Trombose rechter A Trombose rechter A Trombose rechter A Trombose rechter A cerebricerebricerebricerebri posteriorposteriorposteriorposterior

Vrouw, 43 jr

D2 van Exacyl inname: Grand-malepilepsie

CT: Hypodense zone rechts parietaalAngiografie: SinustromboseSinustromboseSinustromboseSinustrombose

� Neurotoxiciteit bij hoge dosissen.

� Mogelijke mechanismen-> Cerebrale ischemie tgv verminderde regionale of

algemene cerebrale bloedflow-> Remming van inhibitorische corticale GABA receptoren.

� Meerdere casussen : convulsies bij hoge

dosissen TA.

-> ConvulsiesConvulsiesConvulsiesConvulsies sedert start TA bijna verdubbelingverdubbelingverdubbelingverdubbeling

-> Aanpassing dosis en convulsie rate naar baseline

-> Subanalyse: Hogere leeftijd, hogere creatinine

-> 0,9% convulsies post cardiochirurgie

-> TA is onafhankelijke risicofactor

Andere RF: hogere LT, vrouw, redo, calcificaties AoA

Vrouw 62 jrSAB; normale coagulatie/hematologie

R/ Conservatief en R/ Conservatief en R/ Conservatief en R/ Conservatief en ExacylExacylExacylExacyl IVIVIVIV

Dag 10: Plotse retrosternale pijnDyspneuCyanoseShock

AngiogramMassieve bilaterale Massieve bilaterale Massieve bilaterale Massieve bilaterale longembolilongembolilongembolilongemboli

Man, 27 jr

Ongeval met blaasschade en excessieve blaasbloeding R/ Heelkunde, transfusie en R/ Heelkunde, transfusie en R/ Heelkunde, transfusie en R/ Heelkunde, transfusie en ExacylExacylExacylExacyl IVIVIVIV

6u later:Wit en koud rechter ondebreen

Angiografie: Arteriële trombose Arteriële trombose Arteriële trombose Arteriële trombose aicaicaicaic

10 gr Exacyl ipv 1gr in shot10 gr Exacyl ipv 1gr in shot

Man 83jr

Gekende chronische ITP

Groot hematoom R/1,5g R/1,5g R/1,5g R/1,5g ExacylExacylExacylExacyl pdpdpdpd

16m later: DVTDVTDVTDVT

Casus 1

Vrouw 31jrMenorrhagieën

R/ 3R/ 3R/ 3R/ 3----4g 4g 4g 4g ExacylExacylExacylExacyl pdpdpdpd tijdens tijdens tijdens tijdens mensesmensesmensesmenses

D2 Tijdelijke zwakte linker handD9 Hemiparese links

Angiografie: Trombose rechter A Trombose rechter A Trombose rechter A Trombose rechter A cerebricerebricerebricerebri media media media media

Casus 2

Vrouw 32jrMenorrhagieën

R/ 0,5R/ 0,5R/ 0,5R/ 0,5----1g 1g 1g 1g ExacylExacylExacylExacyl pdpdpdpd tijdens tijdens tijdens tijdens mensesmensesmensesmenses

na 1jaar: Paresthesieën li arm-been+1d: Hemiparese links

Angiografie: Trombose rechter A Trombose rechter A Trombose rechter A Trombose rechter A cerebricerebricerebricerebri posteriorposteriorposteriorposterior

0,5- 1 gr Exacyl per dag0,5- 1 gr Exacyl per dag

-> ConvulsiesConvulsiesConvulsiesConvulsies sedert start TA bijna verdubbelingverdubbelingverdubbelingverdubbeling

-> Aanpassing dosis en convulsie rate naar baseline

� Anesthesiology.1995 Feb;82(2):383-92.� The doseThe doseThe doseThe dose----response relationship ofresponse relationship ofresponse relationship ofresponse relationship of tranexamictranexamictranexamictranexamic acid.acid.acid.acid.� HorrowHorrowHorrowHorrow JC, Van Riper DF, Strong MD, Grunewald KE, JC, Van Riper DF, Strong MD, Grunewald KE, JC, Van Riper DF, Strong MD, Grunewald KE, JC, Van Riper DF, Strong MD, Grunewald KE, ParmetParmetParmetParmet JL. JL. JL. JL.

RESULTS:RESULTS:RESULTS:RESULTS:� The six groups presented similar demographics. Patients receiving

placebo had increased postoperative D-dimer concentration compared to groups receiving tranexamic acid. Patients receiving at least 10 mg.kg-1 tranexamic acid followed by 1 mg.kg-1.h-1 bled significantly less (365, 344, and 369 g.12 h-1, respectively, for those three groups) compared with patients who received placebo (552 g, P < 0.05). . Only initial hematocrit affected whether a patient received an allogeneictransfusion within 5 days of operation (odds ratio 2.08 for each 3% absolute decrease in hematocrit).

� CONCLUSIONS:CONCLUSIONS:CONCLUSIONS:CONCLUSIONS:� Prophylactic tranexamic acid, 10 mg.kg-1 followed by 1 mg.kg-1.h-

1, decreases bleeding after extracorporeal circulation. Larger doses do not provide additional hemostatic benefit.

� Perioperatief bloedverlies � Hogere dosissen geen additioneel effect

� Mogelijks geen effect op transfusie en outcome

� CAVE complicaties� Hoge dosissen neurotoxisch

� Doch bij closed chamber cardiac surgery: geen verhoogd risico

� Lage/intermed/hoge dosis trombo-embogeen� Doch bij cardiale heelkunde weinig casussen, vmd door heparinisatie