
==== Front
Medicine (Baltimore)
Medicine (Baltimore)
MD
Medicine
0025-7974
1536-5964
Lippincott Williams & Wilkins Hagerstown, MD

39029086
MD-D-23-10697
00088
10.1097/MD.0000000000038815
3
4800
Research Article
Observational Study
The efficacy of erythrocyte apheresis for treatment of secondary erythrocytosis: An observational study
Ma Jie MD 20259913@qq.com
a
Yin Qichao MD 13997063121@163.com
a
Ye Fang MD 1903500897@qq.com
a
Ba Zhenzhen BS 1121891754@qq.com
a
https://orcid.org/0009-0007-1290-5551
Geng Hui MD a*
a Department of Hematology, Qinghai University Affiliated Hospital, Xining, China.
* Correspondence: Hui Geng, Department of Hematology, Qinghai University Affiliated Hospital, Xining 810000, China (e-mail: gh0227@sina.com).
19 7 2024
19 7 2024
103 29 e3881528 11 2023
19 3 2024
13 6 2024
Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.
2024
https://creativecommons.org/licenses/by-nc/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal.

To evaluate the efficacy of erythrocyte apheresis on the treatment of secondary erythrocytosis. Patients with secondary erythrocytosis who had visited the Department of Hematology at the Qinghai University Affiliated Hospital between January 2021 and May 2022 were enrolled. Based on the treatment method used, the patients were divided into erythrocytapheresis group and bloodletting group. In total, 50 patients were treated using a hemocyte separator and 36 patients were treated with bloodletting. The outcomes of 2 groups were compared. Compared with the bloodletting group, the clinical symptoms improved, blood routine indicators such as RBC, Hb, and HCT significantly reduced, and the progression rate was lower in the erythrocytapheresis group. Erythrocytic apheresis is effective and safe for the treatment of secondary erythrocytosis.

erythrocyte apheresis
hemocyte separator
secondary erythrocytosis
OPEN-ACCESSTRUE
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pmc1. Introduction

As the name suggests, secondary erythrocytosis is secondary to certain diseases in which PaO2 and SaO2 levels decrease under hypoxia, leading to increased erythropoietin levels and erythropoiesis.[1] Clinical conditions that lead to secondary erythrocytosis include chronic obstructive pulmonary disease (COPD), obstructive sleep apnea hypoventilation syndrome (OSAHS), chronic mountain sickness (CMS),s and cardiovascular diseases, as well as non-compensatory factors such as kidney disease and other tumors that cause erythropoiesis.[2,3] Patients can experience damage to multiple organs, such as the heart, lungs, and brain, due to excessive increases in erythrocyte levels, which severely affects their health.[4]

The traditional clinical treatment for erythrocytosis is bloodletting.[4] In recent years, erythrocytapheresis has gradually replaced bloodletting for the treatment of erythrocytosis.[5] Erythrocytapheresis is a noninvasive procedure in which a patient’s erythrocytes are removed from the blood while being replaced with erythrocytes from blood donor. Good therapeutic results have been achieved in clinical practice since the introduction of erythrocytapheresis.[6,7]

Compared with healthy people, patients with secondary erythrocytosis mainly experience tissue hypoxia, which causes abnormally high levels of red blood cells and increased blood viscosity, leading to microcirculatory disorders, capillary stagnation, tissue hypoxia, which in turn affects the metabolism and functions of various organs.[7] Qinghai Province, located in the Qinghai Tibet Plateau, has an average altitude of >3000 m. High-altitude polycythemia is a common disease in the region.[8] At present, there is no special clinical treatment method for erythrocytosis caused by high-altitude hypoxia. For patients who continue to stay at a high altitude, treatment options primarily include: intermittent low-flow oxygen inhalation; bloodletting therapy; hyperbaric oxygen chamber; and medication therapy.[9] In the past, patients with polycythemia vera mostly used erythrocytapheresis to remove extra erythrocytes and good results were observed.[10] However, few studies have reported on the use of this technology for the treatment of secondary erythrocytosis.

Therefore, this study aimed to evaluate the efficacy of erythrocytapheresis in Chinese patients with secondary erythrocytosis. Total 50 patients with secondary erythrocytosis were enrolled and the efficacy of erythrocytapheresis was compared with traditional bloodletting therapy.

2. Patients and methods

2.1. Patients

This prospective study was approved by Ethics Committee of Qinghai University Affiliated Hospital and all patients provided informed consent. Patients with secondary erythrocytosis who had visited the Department of Hematology at the Qinghai University Affiliated Hospital between January 2021 and May 2022 were enrolled. Patients with polycythemia vera and tumors were excluded. All patients were male, 36 patients had COPD, 30 had OSAHS, and 20 had CMS, all of whom presented with varying degrees of dizziness, headache, drowsiness, poor sleep quality, and cyanosis of the skin and mucous membranes. Routine blood tests revealed hemoglobin (Hb) level > 210 g/L, with or without hypoxemia SO2% <90%, and pulmonary hypertension. All patients underwent bone marrow analysis, the detection of myeloproliferative disease (MPN)-related gene (such as JAK2 V617F), pathological cytological analysis of the bone marrow biopsies, determination of the levels of serum erythropoietin, serum iron, ferritin, and lactate dehydrogenase (LDH). All patients were examined by abdominal ultrasound or CT to exclude diseases such as polycythemia vera.

Based on the treatment method used, the patients were divided into erythrocytapheresis group and bloodletting group. Patients enrolled before the availability of hemocyte separator at our department were treated with bloodletting, while those enrolled after the availability of hemocyte separator at our department were treated with erythrocytapheresis. The erythrocytapheresis group included 50 patients (20 with COPD, 18 with OSAHS, and 12 with CMS) and the bloodletting group included 36 patients (16 with COPD, 13 with OSAHS, and 7 with CMS). The mean age of patients in the erythrocyte apheresis group was 47 years and in the bloodletting group 47 years. No significant difference was noted in Hb level between the 2 groups before treatment (230.3 ± 16.62 vs 221.6 ± 20.73 g/L) (P > .05).

2.2. Bloodletting therapy

The hemodynamics and oxygen partial pressure were improved for patients with significantly increased erythrocyte count after bloodletting. Generally, 300 to 400 mL of blood was released from the vein, after which fluids such as saline or low-molecular dextrose are administered.

2.3. Erythrocytapheresis therapy

Fresenius Kabi hemocyte separator (Fresenius Kabi, Germany) and separation pipeline were employed, and the operation procedure was follows. The hematocrit was set to decrease by 10% to 15% after the treatment, and the procedure for removing the erythrocytes was selected. The whole blood treatment volume was 1000 to 1500 mL, the flow rate was 50 to 60 mL/min, and saline was used as the replacement solution. During the treatment, 10% calcium gluconate was pumped to prevent the decrease in blood calcium. After the hemocyte separation process, the system was disconnected from the program and the blood connection was disconnected.

2.4. Routine blood examination

The routine blood examination was performed on the second day of erythrocyte apheresis and bloodletting and then repeated 3 and 6 months later.

2.5. Statistical analysis

SPSS22.0 software was used for statistical analysis. The data were expressed as the mean ± standard deviation (x¯±SD). The difference was compared by t test. P < .05 was considered to indicate significance.

3. Results

3.1. Comparison of symptom relief between the 2 groups before and after treatment

Compared with patients in the bloodletting group, headache, dizziness, and other discomfort feelings were relieved in the patients in the erythrocytapheresis group. The skin and mucous membrane cyanosis of the patients improved significantly after erythrocytapheresis.

3.2. Changes in routine blood indices before and after treatment

Red blood cells (RBC), Hb, and hematocrit (HCT) levels were significantly lower after erythrocytapheresis than before (P < .01). The routine blood indices also decreased after bloodletting (P < .01) (Fig. 1).

Figure 1. Comparison of the routine blood indices before and after treatment between the 2 study groups.

3.3. Comparison of treatment effects between the 2 groups

RBC and Hb levels decreased significantly more in the erythrocytapheresis group than in the bloodletting group after treatment (P < .01). The decrease in HCT levels was also more in the erythrocytapheresis group than in the bloodletting group (P < .05) (Fig. 2).

Figure 2. Comparison of the differences in the routine blood indices before and after treatment between 2 groups.

3.4. Adverse reactions during treatment

Two patients in the erythrocytapheresis group had hand–foot convulsions during hemocyte separation, which was considered hypocalcemia. The symptoms were relieved quickly after intravenous supplementation with 10% calcium gluconate. Three patients in the bloodletting group felt dizzy and uncomfortable after the procedure.

3.5. Follow-up examinations

The patients in 2 groups were followed up for 3 and 6 months after the treatment, and the routine blood examination was reperformed. The RBC, Hb, and HCT levels in 2 groups gradually increased compared with those after 1 day of treatment. After 6 months, the levels of the indices in the bloodletting group almost recovered to the pre-bloodletting levels, whereas those in the erythrocyte apheresis group were significantly lower than those before treatment (Fig. 3).

Figure 3. Follow-up routine blood indices in bloodletting group and erythrocytapheresis group.

4. Discussion

In this study, we successfully applied erythrocytapheresis therapy to patients with secondary erythrocytosis, especially high-altitude polycythemia in the Qinghai area. Total 50 patients with secondary erythrocytosis exhibited significant relief of clinical symptoms after the removal of extra erythrocytes through apheresis, and routine blood tests 1 day after treatment showed that RBC, Hb, and HCT levels were significantly lower than before.

The traditional venous bloodletting therapy releases 300 to 400 mL of blood each time. After blood withdrawal, the patient is supplemented with the same amount of saline or low-molecular dextran. Although this therapy can improve some symptoms of the patient, its effects last for a short period. Although bloodletting treatment method can reduce RBC, Hb, and HCT levels to a certain extent, it leads to plasma component loss, which may aggravate blood hypercoagulability and increase thrombosis risk.[11] In this study, RBC, Hb, and HCT levels decreased in 36 patients after bloodletting treatment, but the extent of the decrease was lower than that in the patients in the erythrocyte apheresis group. The treatment effect was considerably lower.

The follow-up results demonstrated that under hypoxic conditions, patients failed to improve significantly. The routine blood indicators in both groups recovered after treatment. However, the recovery was significantly less in the erythrocyte apheresis group than in the bloodletting group. The RBC, Hb, and HCT levels in the bloodletting group had almost recovered to the pre-bloodletting level after 6 months, whereas the levels of these indices in the erythrocyte apheresis group were significantly lower than those before treatment, which might reduce the thrombosis risk to some extent.

Two types of hemocyte separators are available for blood component mono-collection based on their function[12]: transfusion hemocyte apheresis and therapeutic hemocyte apheresis. Transfusion hemocyte apheresis is the collection of donor-specific blood cell components for transfusion into patients. Therapeutic hemocyte apheresis is the collection and discarding of certain blood components from patients. Therapeutic hemocyte apheresis is widely used in clinical applications, including peripheral blood hematopoietic stem cell collection and apheresis of red blood cells, platelets, granulocytes, and other hemocyte components.[13] The advantages of using a hemocyte separator for erythrocyte apheresis are high efficiency, safety, and speed in the treatment of secondary erythrocytosis, especially for patients with high-altitude polycythemia. A hemocyte separator can directly collect numerous erythrocytes from patients, thus reducing blood viscosity, improving tissue oxygen supply, and decreasing the excessive proliferation of erythrocytes in the body due to tissue hypoxia.

This study has some limitations. First, the sample size is relatively small. Second, this is a single center study. Further large-scale multi-center studies are needed to confirm the potential of erythrocytapheresis for the treatment of secondary erythrocytosis.

In conclusion, compared with traditional venous bloodletting therapy, erythrocyte apheresis is convenient, costs less, improves the efficiency of removing erythrocytes, reduces the number of times of bloodletting, shortens the treatment time, and significantly improves clinical symptoms of secondary erythrocytosis.

Author contributions

Investigation: Jie Ma, Qichao Yin, Fang Ye, Zhenzhen Ba, Hui Geng.

Conceptualization: Hui Geng.

Abbreviations:

CMS chronic mountain sickness

COPD chronic obstructive pulmonary disease

Hb hemoglobin

HCT hematocrit

OSAHS obstructive sleep apnea hypoventilation syndrome

RBC red blood cells.

This study was supported by Natural Science Foundation Project of Qinghai Province of China (2020-ZJ-956Q).

The authors have no conflicts of interest to disclose.

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

How to cite this article: Ma J, Yin Q, Ye F, Ba Z, Geng H. The efficacy of erythrocyte apheresis for treatment of secondary erythrocytosis: An observational study. Medicine 2024;103:29(e38815).
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