PNH Famous Doctors Lecture Session 7 Professor Guangsheng He: Treatment of PNH-Pregnancy

The peak age of onset of paroxysmal nocturnal hemoglobinuria (PNH) is 20-40 years old
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And 20-40 female patients are in childbearing age, then, can PNH patients become pregnant, and how should PNH patients in pregnancy be treated? In this issue of "PNH Famous Doctors Lecture", Yimaitong invited Professor He Guangsheng from Jiangsu Provincial People's Hospital to share on PNH pregnancy related issues! Professor Guangsheng He Chief Physician, Associate Professor, Master's Tutor, Deputy Director, Department of Hematology, Jiangsu Provincial People's Hospital Chief Expert, Department of Hematology, Second Affiliated Hospital of Xuzhou Medical University Member of the Standing Committee of the Professional Committee, Chairman of the Anemia Branch of the Jiangsu Research Hospital Association, Chief Expert of the Department of Hematology, Nanjing Hospital Affiliated to Nanjing University of Traditional Chinese Medicine.
Are PNH patients suitable for pregnancy? How does PNH affect pregnancy? The pregnancy problem of PNH patients is a huge challenge.
In clinical work, such questions are often received from patients.
However, if PNH patients are planning to become pregnant, it is not recommended
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For pregnant women, pregnancy is an important predisposing factor that leads to PNH hemolysis.
After pregnancy, patients will have more frequent hemolytic episodes, and the severity of the episodes will increase, which will eventually lead to anemia and increased bleeding
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At the same time, the risk of thrombosis in PNH patients after pregnancy will increase significantly.
Existing data show that the mortality or disability rate of pregnant women due to thrombosis will reach more than 20%
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For fetuses, anemia will occur after maternal hemolysis, which will lead to placental ischemia and hypoxia, which will further affect fetal development and cause spontaneous abortion or death of the fetus.
About 60%-70% of fetuses can be delivered at term
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However, even if the fetus can be delivered at full term, due to the mother’s hemolytic anemia, the newborn will have low birth weight, and some fetuses may weigh less than three kilograms
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Therefore, it is not recommended for PNH patients to become pregnant
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Precautions for PNH patients after pregnancy If the patient becomes pregnant unexpectedly and has a strong desire to give birth, strict follow-up inspections are required
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Pregnant PNH patients need to undergo the following examinations once a week or every 10 days: ① routine blood and reticulocyte testing; ② coagulation function testing (including D-dimer testing); ③ biochemical function testing (including lactate dehydrogenase ( LDH) level test); ④Urine routine test
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Blood routine and reticulocyte test mainly reflect the patient's anemia.
Reticulocytes can also reflect the compensation of hematopoietic function, that is, whether there is bone marrow hematopoietic failure
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D-dimer is an indicator of thrombosis.
Infertility in most women is related to the state of hypercoagulability in the body (increased D-dimer).
D-dimer can reflect the state of thrombosis and guide clinicians to intervene, but Because warfarin poses certain safety risks to pregnant women and fetuses, it is not recommended to use warfarin intervention for pregnant patients.
It is recommended to use low molecular weight heparin.
The dosage and frequency of use can be referred to the D-dimer level and closely monitored during use
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The level of LDH can reflect the occurrence of hemolysis in patients and guide clinicians to further medication
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In addition, urine routine and renal function can also reflect the occurrence of hemolysis
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 The risk of death and disability in pregnant PNH patients and the risk of fetal death and developmental abnormalities are related to hemolysis, anemia and thrombosis
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Hemolysis is difficult to control, but after hemolysis causes anemia, red blood cell transfusion needs to be carried out in time.
70g/L is the safe level of blood red for pregnant women with PNH
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At this level, pregnant women can maintain a good functional state, and the placenta will basically not continue to be hypoxic, which has a certain supporting effect on fetal development
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Moreover, after the hemoglobin level is stabilized, the bone marrow hematopoietic demand will be correspondingly reduced, and the PNH cells produced by the bone marrow will also be reduced, which will eventually reduce the onset of hemolysis
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Therefore, pregnant women with PNH should increase the amount of blood transfusion during pregnancy to ensure that their hemoglobin level is above 70g/L
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Significance of the application of C5 monoclonal antibody to the pregnancy of PNH patients The emergence of C5 monoclonal antibody has greatly improved the pregnancy of PNH patients, and pregnancy in PNH patients is one of the indications for the use of C5 monoclonal antibody
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The first patient who participated in the C5 monoclonal antibody clinical trial led by Professor Peter Hillmen from the University of Leeds Hospital in the United Kingdom grew up and participated in the C5 monoclonal antibody clinical trial of a PNH patient with pregnancy.
The patient had three successful pregnancies in the past, each time from pregnancy The C5 monoclonal antibody was used throughout the process of delivery, the process was very stable, and the child's developmental status was also very good
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 After using C5 monoclonal antibody in PNH pregnant patients, hemolysis can be controlled, anemia will be improved, hemoglobin level will be normal, the placenta is not ischemic, not hypoxic, the development is intact, and the fetus is also intact
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The mother's body is also relatively safe, and can be pregnant normally and give birth at full term just like a normal person
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In terms of safety, after the patient's consent, the C5 monoclonal antibody test for cord blood and postpartum breast milk was performed, and it was found that the content of C5 monoclonal antibody in the cord blood and breast milk was minimal, and it had little effect on the fetus
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About PNH paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hematopoietic stem cell gene mutation caused by erythrocyte membrane defects.
The 10-year survival rate of domestic patients is about 70%
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The clinical manifestations are mainly intravascular hemolytic anemia, which may be accompanied by symptoms such as thrombosis, renal insufficiency, and pulmonary hypertension
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Typical patients have characteristic intermittent nocturnal hemoglobinuria
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There are more male patients than females in China, and the peak age of onset is 20-40 years old
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The patient suffers from pain and suffering for a long time, and the quality of life is low
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Many patients are in the golden age of their lives.
As the backbone of their families, they have lost their labor force due to illness, causing a great social burden
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References: 1.
Baiset al.
Eur J Obstet Gynecol Reprod Biol 1994; 53: 211-4.
2.
Bjørge L, Ernst P, Haram KO.
Acta Obstet Gynecol Scand 2003; 82: 1067-71.
3.
Ray et al.
Haemostasis 2000; 30 :103–117.
4.
Fieniet al.
Obstet Gynecol Surv 2006; 51: 593-601.
5.
de Guibert, et al Haematologica 2011; 96(9) Guidelines for the diagnosis and treatment of rare diseases (2019 edition).
6.
Journal of Hematology & Oncology (2018) 11:33.
Consensus of Chinese experts on diagnosis and treatment of PNH.
The quiz RECOMMEND recommended reading 1.
PNH lecture hall 1st period | Professor Fu Rong: the pathogenesis and treatment mechanism of PNH 2.
PNH lecture hall 2nd period | Professor Zhang Fengkui: PNH status and diagnosis points 3.
PNH famous doctor lecture hall 3 | Professor Zhang Fengkui: PNH treatment and follow-up 4.
PNH famous doctor lecture hall 4 | Professor Han Bing: PNH treatment-complications 5.
PNH famous doctor lecture hall 5 Issue | Professor Han Bing: PNH Treatment-Complications 6.
PNH Famous Doctors Lecture Session 6 | Professor He Guangsheng: PNH Treatment-Transplantation Chapter "Read the original text", we make progress together