Glucose-6-P-dehydrogenase deficiency

Béatrice GULBIS, M.D., PhD

1 1

SCD day 18/02/2016

SCD woman has to be tested for G6PD deficiency?

1. Yes

2. No

3. I don’t know

SCD day 18/02/2016 2

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

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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.

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G6PD deficiency

• How?

– Severity

– List of drugs • Rasburicase

• Who?

• Management/prevention

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Pathophysiology

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Hb metHb Rase

SCD day 18/02/2016

G6PD deficiency Severity of haemolysis

• More variable picture with favism

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• 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)

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40% 25% 10%

G6PD activity

Proc. Nati. Acad. Sc. USA 1978;75:1979-1983

SCD day 18/02/2016

12

40% 25% 10%

G6PD activity

Proc. Nati. Acad. Sc. USA 1978;75:1979-1983

Dose

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

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10% 6% 3%

G6PD activity

Proc. Nati. Acad. Sc. USA 1978;75:1979-1983

Dose (Schema)

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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.

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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

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• 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

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Who should be tested ?

SCD day 18/02/2016

Management (Prevention)

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• 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

SCD woman has to be tested for G6PD deficiency?

1. Yes

2. No

3. I don’t know

SCD day 18/02/2016 22

SCD woman has to be tested for G6PD deficiency?

1. Yes

2. No

3. I don’t know

SCD day 18/02/2016 23

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

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 29