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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
G6PD activity 5.3 U/g Hb (7.0-17.0)
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
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
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.
6 SCD day 18/02/2016
G6PD deficiency
• How?
– Severity
– List of drugs • Rasburicase
• Who?
• Management/prevention
7 SCD day 18/02/2016
Pathophysiology
8
Hb metHb Rase
SCD day 18/02/2016
G6PD deficiency Severity of haemolysis
• More variable picture with favism
9
• Drop of Hb about 5 g/dL, nadir at day 7
• Hemoglobinuria at the begining (Days 1-3)
• Reticulocytes count increases
• Jaundice
SCD day 18/02/2016
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)
10 SCD day 18/02/2016
13
40% 25% 10%
G6PD activity
Proc. Nati. Acad. Sc. USA 1978;75:1979-1983
Dose (Schema)
SCD day 18/02/2016
SCD day 18/02/2016 14
10% 6% 3%
G6PD activity
Proc. Nati. Acad. Sc. USA 1978;75:1979-1983
Dose (Schema)
SCD day 18/02/2016 15
40% 25% 10%
G6PD activity + quality
Proc. Nati. Acad. Sc. USA 1978;75:1979-1983
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.
16 SCD day 18/02/2016
17
G6PD deficiency Drugs that trigger haemolysis
Br J Haematol. 2014; 164: 469–480.
- In many cases haemolysis was probably triggered by the infection and not the drug.
- Possible haemolysis - Dose related - Combination of drugs - Co-morbodity
Evidence based Drug safety 2010;33-713-
SCD day 18/02/2016
Urate oxydase/G6PD deficiency
• Urate oxydase: H2O2/uric acid – Haemolysis (Haemoglobinuria)
– MetHb +++
– Half life: 18-24 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
18 SCD day 18/02/2016
19
• X-linked recessive pattern
– Haemophilia A – Affected men : 1/10 000
– Affected women (homozygotes): 1/100 000 000
– G6PD deficiency (example) – Affected men : 1/20
– Affected women (homozygotes/compound heterozygotes): 1/400
Who should be tested ?
SCD day 18/02/2016
Management (Prevention)
SCD day 18/02/2016 21
• 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: 469–480. Lancet 2008;371:64-74
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 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 18/02/2016 25
G6PD activity 5,3 U/g Hb (7.0-17.0)
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 26
G6PD activity 5,3 U/g Hb (7.0-17.0)
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 27
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 28