Glucose-6-P-dehydrogenase deficiency. Béatrice GULBIS, M.D., PhD

Transcription

1 Glucose-6-P-dehydrogenase deficiency Béatrice GULBIS, M.D., PhD SCD day 18/02/2016 1

2 1. Yes 2. No SCD woman has to be tested for G6PD deficiency? 3. I don t know SCD day 18/02/2016 2

3 Haemolytic crisis related to a G6PD deficiency. % MetHb > 12% - I treat with methylene blue 1. Yes 2. No 3. I don t know SCD day 18/02/2016 3

4 G6PD activity 5.3 U/g Hb ( ) 1. Means G6PD deficiency 2. For interpretation, expressed as a percentage of reference value 3. For interpretation use another RBC enzyme 4. I can t give an interpretation SCD day 18/02/2016 4

5 G6PD deficiency and haemolysis 1. Infection is not a trigger 2. Drug dose has no influence 3. Drug schema has no influence 4. Co-morbidity has no influence 5. All propositions are uncorrect SCD day 18/02/2016 5

6 G6PD deficiency Favism has been first reported as an allergic reaction In the 50s, US troops going to Korea were preventively treated by primaquine. A significant amount of soldiers became jaundiced and anaemic. SCD day 18/02/2016 6

7 G6PD deficiency How? Severity List of drugs Rasburicase Who? Management/prevention SCD day 18/02/2016 7

8 Pathophysiology Hb methb Rase SCD day 18/02/2016 8

9 G6PD deficiency Severity of haemolysis Drop of Hb about 5 g/dl, nadir at day 7 Hemoglobinuria at the begining (Days 1-3) Reticulocytes count increases Jaundice More variable picture with favism SCD day 18/02/2016 9

10 Severity of haemolysis Factors Inherited RBC integrity (red cell ageing, other defects) Enzyme defect (G6PD activity/quality) Individual pharmacokinetic Acquired Drug dose and metabolism Additional oxidative stress (infection ) Existing anaemia Age of the patient (co-morbidities) SCD day 18/02/

11 Proc. Nati. Acad. Sc. USA 1978;75: G6PD activity 40% 25% 10% SCD day 18/02/

12 Proc. Nati. Acad. Sc. USA 1978;75: Dose G6PD activity 40% 25% 10% SCD day 18/02/

13 Proc. Nati. Acad. Sc. USA 1978;75: G6PD activity Dose (Schema) 40% 25% 10% SCD day 18/02/

14 Proc. Nati. Acad. Sc. USA 1978;75: G6PD activity Dose (Schema) 10% 6% 3% SCD day 18/02/

15 Proc. Nati. Acad. Sc. USA 1978;75: G6PD activity + quality 40% 25% 10% SCD day 18/02/

16 G6PD deficiency Drugs that trigger haemolysis No test is available In vitro in vivo Individual drug metabolization, etc. (see additional factors) Favism Severely deficient patients Vicine, convice, ascorbate and L-DOPA. SCD day 18/02/

17 G6PD deficiency Drugs that trigger haemolysis Evidence based Drug safety 2010; Possible haemolysis - Dose related - Combination of drugs - Co-morbodity - In many cases haemolysis was probably triggered by the infection and not the drug. Br J Haematol. 2014; 164: SCD day 18/02/

18 Urate oxydase/g6pd deficiency Urate oxydase: H 2 O 2 /uric acid Haemolysis (Haemoglobinuria) MetHb +++ Half life: H Malignancies + chemotherapy Anaemic patients Risk of renal insufficiency MetHb and methylene blue Recommendations G6PD activity has to be tested Normal > 60% (steady state) Conclusion (+ internal standard) < 30% Likelihood of haemolytic crisis 30-60% Low Likelihood of haemolytic crisis SCD day 18/02/

19 Who should be tested? X-linked recessive pattern Haemophilia A Affected men : 1/ Affected women (homozygotes): 1/ G6PD deficiency (example) Affected men : 1/20 Affected women (homozygotes/compound heterozygotes): 1/400 SCD day 18/02/

20 Who should be tested? SCD day 18/02/

21 Management (Prevention) MAKE THE DIAGNOSIS and PREVENTION Avoid oxidative stressors HAEMOLYSIS: MAKE THE DIAGNOSIS and Stop the drug If severe anaemia Blood transfusion Recommendations cut-off Hb 7 g/dl If rapid decrease in Hb and haemoglobinuria cut-off 9 g/dl If acute renal failure Haemodialysis might be required Br J Haematol. 2014; 164: Lancet 2008;371:64-74 SCD day 18/02/

22 1. Yes 2. No SCD woman has to be tested for G6PD deficiency? 3. I don t know SCD day 18/02/

23 1. Yes 2. No SCD woman has to be tested for G6PD deficiency? 3. I don t know SCD day 18/02/

24 Haemolytic crisis related to a G6PD deficiency. % MetHb > 12% - I treat with methylene blue 1. Yes 2. No 3. I don t know SCD day 18/02/

25 Haemolytic crisis related to a G6PD deficiency. % MetHb > 12% - I treat with methylene blue 1. Yes 2. No 3. I don t know SCD day 18/02/

26 G6PD activity 5,3 U/g Hb ( ) 1. Means G6PD deficiency 2. For interpretation, expressed as a percentage of reference value 3. For interpretation use another RBC enzyme 4. I can t give an interpretation SCD day 18/02/

27 G6PD activity 5,3 U/g Hb ( ) 1. Means G6PD deficiency 2. For interpretation, expressed as a percentage of reference value 3. For interpretation use another RBC enzyme 4. I can t give an interpretation SCD day 18/02/

28 G6PD deficiency and haemolysis 1. Infection is not a trigger 2. Drug dose has no influence 3. Drug schema has no influence 4. Co-morbidity has no influence 5. All propositions are uncorrect SCD day 18/02/

29 G6PD deficiency and haemolysis 1. Infection is not a trigger 2. Drug dose has no influence 3. Drug schema has no influence 4. Co-morbidity has no influence 5. All propositions are uncorrect SCD day 18/02/