PNH Famous Doctors Lecture Hall No. 5 Professor Han Bing: PNH Treatment-Complications

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hematopoietic stem cell gene mutation caused by erythrocyte membrane defects.
The clinical manifestations are mainly intravascular hemolytic anemia.
Typical patients have characteristic intermittent episodes Nocturnal hemoglobinuria may be accompanied by complications such as thrombosis, renal insufficiency, and pulmonary hypertension
.

This issue of "PNH Famous Doctors Lecture" Yimaitong invited Professor Han Bing from Peking Union Medical College Hospital to share on the mechanism and treatment management of PNH renal complications and pulmonary hypertension complications! Professor Han Bing, chief physician, professor, and doctoral supervisor of the Department of Hematology, Peking Union Medical College Hospital, deputy leader of the Red Blood Cell Disease Group, Chinese Medical Association Hematology Branch, Deputy Chairman of the Red Blood Cell Disease Academic Working Committee of the First Committee of the Chinese Medical Association Hematology Branch of the Chinese Medical Association, China Vice Chairman of the Second Committee of the MDS and MPN Working Group of the Anti-Cancer Association Hematology and Oncology Professional Committee Deputy Chairman of the Hemocytopenia Group/Rare Disease Group of the Chinese Society of Integrative Medicine How high is the incidence of renal complications of PNH, the first executive director of the National Chronic Disease Prevention and Treatment Branch of the Blood Branch? What is the cause? How to manage? PNH, the Chinese name is paroxysmal nocturnal hemoglobinuria.
As the name implies, red blood cells and protein are often seen in the urine of patients in clinical practice
.

Renal complications of PNH are very common
.

There are many reasons for kidney disease, for example, hemolysis can cause kidney damage
.

A large amount of hemolysis in a short period of time will cause a large amount of free hemoglobin to be released and impact the renal tubules.
When the function of the human renal tubules is damaged, the absorption capacity will decrease, which may cause kidney damage
.

If acute hemolysis is combined with infection, the burden on the patient’s kidneys will be further increased, and acute renal failure may even be induced
.

A large sample study found that 20%-30% of PNH patients will have varying degrees of kidney damage.
These patients may have proteinuria, hematuria, increased creatinine, or decreased creatinine clearance
.

Patients with severe renal dysfunction may even have renal insufficiency, especially those with aplastic anemia who use drugs such as the immunosuppressant cyclosporine, the risk of renal insufficiency is higher
.

In addition, complement activation is also related to kidney disease, which may lead to aggravated kidney damage in patients
.

For the management of PNH combined with renal insufficiency, the most important thing is to control the primary disease
.

For example, after the use of complement inhibitors, hemolytic metabolites are reduced, and the burden on the kidneys will also be reduced
.

At the same time, during hemolysis attacks, symptomatic and supportive treatments such as hydration, alkalization, and diuresis can be used to reduce the influence of prerenal factors on the kidneys and protect kidney function
.

Sodium bicarbonate, etc.
also help protect kidney function
.

In addition, pay attention to minimize the use of drugs that can cause kidney damage, and monitor changes in renal function
.

All in all, for patients with PNH combined with renal insufficiency, it is necessary to pay attention to comprehensive and multi-angle comprehensive management
.

How high is the incidence of PNH pulmonary hypertension? What is the cause? How to manage? Pulmonary hypertension is one of the common complications of PNH
.

Pulmonary hypertension may cause severe damage to the patient's heart and lung function and reduce the quality of life of the patient.
If the condition is severe, it may even cause sudden death
.

The causes of PNH pulmonary hypertension mainly include the following points: hemolysis consumes a large amount of nitric oxide (NO), which causes vascular smooth muscle dysfunction; severe anemia in patients can also cause an increase in cardiac load, which indirectly causes an increase in pulmonary vascular pressure; , Thrombosis, especially in the pulmonary blood vessels, can also aggravate pulmonary hypertension
.

Therefore, pulmonary hypertension is caused by many factors
.

For PNH pulmonary hypertension, there has been relatively little clinical attention in the past, but many patients complained of chest tightness, breathlessness, and even difficulty breathing when they went to the doctor
.

Therefore, clinicians have gradually strengthened the monitoring of pulmonary hypertension
.

In a study conducted by Peking Union Medical College Hospital, more than 500 patients were included.
After echocardiography, about 5%-10% of patients will have obvious pulmonary hypertension
.

In addition, although some patients have pulmonary hypertension, the clinical symptoms are not prominent
.

The management of PNH pulmonary hypertension usually adopts two methods: treatment of the primary disease and symptomatic treatment
.

For the primary disease, it is mainly to control hemolysis and reduce the most fundamental cause of pulmonary hypertension
.

At the same time, some symptomatic treatment drugs can be used to temporarily relieve the patient's symptoms
.

In addition, strengthening the focus on pulmonary hypertension, improving diagnostic capabilities, and early treatment is also a key to disease control
.

A clinical trial involving Peter Hillmen showed that the incidence of clinical renal (MCK) events in PNH patients was reduced by 50% after treatment with C5 complement inhibitors
.

After C5 complement inhibitor treatment, the incidence of patients with N-terminal brain natriuretic peptide water ≥160pg/ml (indicating pulmonary hypertension) decreased by 50% (from 52.
5% to 26.
3%) from baseline to 26 weeks of treatment, while the incidence of placebo did not Significant change (from 39.
4% to 43.
8%)
.

The above shows that the renal insufficiency and pulmonary hypertension of PNH patients can be improved by C5 complement inhibitor therapy
.

Regarding PNHPNH, an acquired hematopoietic stem cell gene mutation caused by a defective red blood cell membrane disease, the 10-year survival rate of domestic patients is about 70%
.

The clinical manifestations are mainly intravascular hemolytic anemia, which may be accompanied by symptoms such as thrombosis, renal insufficiency, and pulmonary hypertension
.

Typical patients have characteristic intermittent nocturnal hemoglobinuria
.

There are more male patients than females in China, and the peak age of onset is 20-40 years old
.

The patient suffers from pain and suffering for a long time, and the quality of life is low
.

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
.

References: 1.
Van Avondt K, et al.
Nat Rev Nephrol.
2019 Nov;15(11):671-692.
2.
Nong Z, et al.
Chin J Hematol, June 2012, Vol.
33, No.
6.
3 .
Jong Z, et al.
JNephrolDialy Transplant Vol.
18 No.
4 Aug.
2009.
4.
Hillmen, et al.
Am.
J.
Hematol.
85:553–559, 2010.
5.
Hill A, et al.
Br J Haematol.
2010 May ;149(3):414-25.
RECOMMEND recommended reading in the quiz 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's Status and diagnosis points 3.
PNH famous doctors lecture hall 3 | Professor Zhang Fengkui: PNH treatment and follow-up