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23 December 2020: Clinical Research  

Safety and Efficacy of Therapeutic Erythrocytapheresis Treatment in Chronic Mountain Sickness Patients in Shigatse, Tibet, China

Mingyuan NiuBCD, Shekhar SinghEF, Ma MiB, Pian BianB, Zhuoga DejiAB, Duoji MimaA, Xiankai LiACEG

DOI: 10.12659/MSM.927853

Med Sci Monit 2020; 26:e927853



BACKGROUND: Therapeutic erythrocytapheresis (TEA) is a medical technology that separates erythrocytes from whole blood and has been used in various hematological conditions. However, reports on the use of TEA to treat chronic mountain sickness (CMS) are lacking. The aim of the present study was to evaluate the efficacy, safety, and use of TEA in treatment of CMS.

MATERIAL AND METHODS: A total of 32 patients living in the Shigatse area of Tibet (altitude 4000 m) who had CMS were treated with TEA. Clinical data, CMS score, Borg dyspnea score, 6-min walking test score, and NYHA classification values were collected prior to and after TEA therapy.

RESULTS: TEA treatment significantly increased SpO₂ (93.8±2.6 vs. 80.5±5.8%, P<0.001) and decreased red blood cell (5.77±0.70 vs. 7.48±0.67×10¹²/L, P<0.001), hematocrit (53.8±5.6 vs. 69.2±4.8%, P<0.001) and hemoglobin (178±16 vs. 236±14 g/L, P<0.001). Significantly lower systolic and diastolic blood pressure were also noted (P<0.001). Echocardiography showed higher left ventricle diameter (4.6±0.4 vs. 4.4±0.5 cm, P<0.01). TEA markedly decreased CMS scores (0.45±0.85 vs. 7.58±2.31, P<0.001), Borg dyspnea scale scores (0.48±0.73 vs. 0.88±0.81, P<0.001), and NYHA classification scores (P<0.05). Additionally, there was marked improvement in the 6-min walking test scores (578.5±83.1 vs. 550.4±79.0 m, P<0.001). The procedure was well tolerated, with no complications.

CONCLUSIONS: Our novel approach of treating CMS patients with TEA safely and effectively reduced erythrocytosis, which remains a fundamental challenge in CMS patients.

Keywords: Altitude Sickness, Cytapheresis, Polycythemia, Chronic Disease, Electrocardiography, Severity of Illness Index, Tibet, vital signs


Chronic mountain sickness (CMS), or Monge’s disease, is a clinical syndrome caused by long-term living at high altitudes of more than 2500 meters. It is characterized by excessive erythrocytosis (Hb ≥190 g/L in female patients, Hb ≥210g/L in male patients) and severe hypoxemia [1]. The prevalence of CMS is variable among different populations living at different high altitudes and has been reported to be above 30% in plateau regions [2]. The Qinghai-Tibetan plateau is the highest and largest plateau in the world, with a population of >60 million. CMS is a common condition here, with incidence rates of 2.43–37.5% (at elevations 3000–4700 m), and increases with elevation. Compared to native Tibetans, CMS is more prevalent in Han male immigrants (17.8%) [3–6]. CMS not only seriously affects the health and quality of life of plateau residents, but also leads to chronic pulmonary hypertension via various cellular and molecular mechanisms [7–11]; it can cause increased ventricular afterload and finally lead to the development of life-threatening right-heart failure [12–15]. In addition, the excessive erythrocytosis of CMS increases the viscosity of blood, making it thick and sticky, which significantly increases the risk of thrombosis, leading to diseases such as myocardial infarction, pulmonary embolism, and cerebral infarction, resulting in multiorgan dysfunction and death.

Therefore, it is imperative to accurately evaluate and establish effective treatment methods for CMS. Several pharmacological approaches have been employed [1,16–18] but there is no specific medicine suitable for treatment. Phlebotomy is another frequent practice for treating CMS, in which certain volume of whole blood is removed. However, this technique not only decreases red blood mass and hemoglobin, but also causes loss of platelets, albumin, coagulation factor, and leucocytes and results in iron deficiency and volemic imbalance. Therefore, phlebotomy remains impractical for long-term management of CMS [1].

Therapeutic erythrocytapheresis (TEA) has been used as an alternative therapy to treat polycythemia rubra vera and hemochromatosis. It is a sophisticated form of phlebotomy in which cell separators remove red blood cells only, sparing platelets, albumin, and coagulation factors [19–21]. Thus, in the present study, we for the first time used TEA to treat CMS patients. The purpose of this study was to collect clinical data of patients with CMS in the Shigatse area of Tibet at an average altitude of 4000 m and to evaluate the safety and efficacy of TEA in CMS patients.

Material and Methods


This was a single-center, self-control study. All participants diagnosed with CMS and who received TEA were continuously enrolled from March to December 2018 while attending the Cardiology Department of Shigatse People’s Hospital, Tibet, China.

The study was approved by the Human Research Ethics Committee of Shigatse People’s Hospital. All participants provided written informed consent.


CMS is diagnosed when Hb is ≥190 g/L in females and ≥210 g/L in males due to chronic erythrocytosis and with severe hypoxemia. Demographic data, medical history, and smoking status were collected through questionnaire. SpO2, red blood cells, hemoglobin and hematocrit, blood pressure, liver and renal function, cardiac biomarkers, and electrolytes were regularly tested within 2 days before and after TEA. Echocardiography, 6-min walking test, the New York Heart Association (NYHA) classification, Borg dyspnea scale, and Qinghai CMS score were strictly evaluated and confirmed by 2 independent physicians before and after TEA.

Exclusion criteria were: 1) age ≤18 or ≥70 years; 2) NYHA functional class IV heart failure or severe liver or renal dysfunction; 3) cannot tolerate TEA or unable to complete the 6-min walking test; 4) coagulation disorders or high risk of bleeding; and 5) pregnant or lactating women.


The TEA technique was performed using a COBE® spectra™(TERUMO BCT) instrument and disposable closed tubes. Room temperature was kept at 25–26°C and all patients were placed in supine position. Two accesses were established on superficial veins connected to tubes, one on the left hand and the other on the right. One tube was used for outflow and the other for inflow. The COBE system software calculated exchange volume according to sex, height, weight, and hematocrit of patients. After removal of RBC, the plasma was returned with 0.9% saline as fluid compensation. Intraoperative heparin was used for anticoagulation. During the TEA procedure, the blood flow was 50–60 ml/min, circulating volume was 2500–3000 ml, and the collection time was limited to 1–2 h. Blood pressure, SpO2, and heart rate were monitored throughout.


All analyses were performed with SPSS, version 13.0 (Chicago, IL, USA). Continuous variables are expressed as mean±SD and discrete variables as percentages. The differences in continuous variables between groups were examined by paired-samples t test. The differences in discrete variables between groups were calculated by the Pearson χ2 test. A P value of <0.05 was considered significant.


We enrolled a total of 32 participants diagnosed with CMS, consisting of 5 Han immigrants (15.6%) and 27 native Tibetans (84.4%), living in the Shigatse area of Tibet at an average altitude of 4000 m. Most (96.7%) of the participants were male. The average age of the participating patients was 44 years. Most of the participants had a history of smoking (78.1%), averaging 20 cigarettes per day. The most common disease history of participants was hyperuricemia (78.1%), hypertension (46.9%), and dyslipidemia (28.1%). Two patients had history of stroke and 3 patients had history of COPD (Table 1).

An average of 1457±207 ml blood was taken out during the TEA procedure during a period of about 2 h (Table 2).

Table 3 shows the vital signs and laboratory results before and after TEA treatment. There was significant reduction in concentration of red blood cells, hemoglobin, and hematocrit after TEA treatment (P<0.001). The SpO2 significantly improved (P<0.001) and systolic blood pressure and diastolic blood pressure reduced to normal range (P<0.001) compared with the values before TEA treatment. The platelet concentration increased and there was little change in albumin, AST, ALT, and electrolytes levels, which indicate that TEA also preserves these components in blood. The decrease in PT and APTT indicate that it prevents the loss of coagulation factors. Significant decreases in serum bilirubin, uric acid, TG, LDL-C, GHbA1c (all p<0.01), creatinine, and CKMB (P<0.05) were also noted.

Table 4 illustrates the echocardiographic measurement of the patients with CMS before and after TEA treatment. Except for the change in left ventricle diameter (4.4±0.5 vs. 4.6±0.4, P<0.01) no other changes were noted after TEA.

Table 5 shows the efficacy of TEA therapy in CMS patients. The Borg dyspnea scale and Qinghai CMS score decreased significantly (both P<0.001), and the 6-min walking test scores improved significantly (P<0.001), which clearly indicates an improvement in hypoxemia in patients with CMS after treatment with TEA. An improvement in the NYHA classification indicates TEA treatment reduced the risk of heart failure (P<0.05).



The major drawback of this study is its small sample size. Wider acceptance and use as a safe and effective treatment need further larger-scale study. Additionally, patients from remote mountain areas were at times unable to be followed up regularly; therefore, we could not monitor them for long periods or record any long-term adverse effects. Additional research with a larger population is essential.


In conclusion, this study shows that TEA is an efficient and safe treatment of CMS, which not only decrease excessive erythrocytosis but also preserves the important blood components in CMS patients. Therefore, in the future, it is likely that TEA could be used as primary treatment for CMS.


1. Villafuerte FC, Corante N, Chronic mountain sickness: Clinical aspects, etiology, management, and treatment: High Alt Med Biol, 2016; 17; 61-69

2. Gonzales GF, Rubio J, Gasco M, Chronic mountain sickness score was related with health status score but not with hemoglobin levels at high altitudes: Respir Physiol Neurobiol, 2013; 188; 152-60

3. Jiang C, Chen J, Liu F, Chronic mountain sickness in Chinese Han males who migrated to the Qinghai-Tibetan plateau: Application and evaluation of diagnostic criteria for chronic mountain sickness: BMC Public Health, 2014; 14; 1-11

4. Li C, Li X, Liu J, Investigation of the differences between the Tibetan and Han populations in the hemoglobin–oxygen affinity of red blood cells and in the adaptation to high-altitude environments: Hematology, 2018; 23; 309-13

5. Fan X, Ma L, Zhang Z, Associations of high-altitude polycythemia with polymorphisms in PIK3CD and COL4A3 in Tibetan populations: Hum Genomics, 2018; 12; 1-9

6. Jiang C, Liu F, Luo Y, Gene expression profiling of high altitude polycythemia in Han Chinese migrating to the Qinghai-Tibetan plateau: Mol Med Rep, 2012; 5; 287-93

7. Grimminger J, Richter M, Tello K, Thin air resulting in high pressure: Mountain sickness and hypoxia-induced pulmonary hypertension: Can Respir J, 2017; 2017 8381653

8. Dunham-Snary KJ, Wu D, Sykes EA, Hypoxic pulmonary vasoconstriction: From molecular mechanisms to medicine: Chest, 2017; 151; 181-92

9. Wilkins MR, Ghofrani HA, Weissmann N, Pathophysiology and treatment of high-altitude pulmonary vascular disease: Circulation, 2015; 131; 582-90

10. Murray AJ, Montgomery HE, Feelisch M, Metabolic adjustment to high-altitude hypoxia: From genetic signals to physiological implications: Biochem Soc Trans, 2018; 46; 599-607

11. Neupane M, Swenson ER, High-altitude pulmonary vascular diseases: Adv Pulm Hypertens, 2017; 15; 149-57

12. Naeije R, Dedobbeleer C, Pulmonary hypertension and the right ventricle in hypoxia: Exp Physiol, 2013; 98; 1247-56

13. León-Velarde F, Villafuerte FC, Richalet JP, Chronic mountain sickness and the heart: Prog Cardiovasc Dis, 2010; 52; 540-49

14. Naeije R, Altitude and the right heart: Rev Mal Respir, 2018; 35; 441-51

15. Schreier DA, Hacker TA, Hunter K, Impact of increased hematocrit on right ventricular afterload in response to chronic hypoxia: J Appl Physiol, 2014; 117; 833-39

16. Sharma S, Gralla J, Ordonez JG, Acetazolamide and N-acetylcysteine in the treatment of chronic mountain sickness (Monge’s disease): Respir Physiol Neurobiol, 2017; 246; 1-8

17. Richalet JP, Rivera-Ch M, Maignan M, Acetazolamide for Monge’s disease: Efficiency and tolerance of 6-month treatment: Am J Respir Crit Care Med, 2008; 177; 1370-76

18. Cui J, Gao L, Yang H, Potential beneficial effects of oral administration of isoflavones in patients with chronic mountain sickness: Exp Ther Med, 2013; 7; 275-79

19. Itam KP, Okafor IM, Use of apheresis in the treatment of Haematological conditions: World Scientific News, 2016; 50; 250-65

20. Wijermans P, van Egmond L, Ypma P, Isovolemic erythrocytapheresis technique as an alternative to conventional phlebotomy in patients with polycythemia rubra vera and hemochromatosis: Transfus Apher Sci, 2009; 40; 137

21. Sundic T, Hervig T, Hannisdal S, Erythrocytapheresis compared with whole blood phlebotomy for the treatment of hereditary haemochromatosis: Blood Transfus, 2014; 12(Suppl 1); 7-12

22. Evers D, Kerkhoffs J-L, Van Egmond L, The efficiency of therapeutic erythrocytapheresis compared to phlebotomy: A mathematical tool for predicting response in hereditary hemochromatosis, polycythemia vera, and secondary erythrocytosis: J Clin Apher, 2014; 29; 133-38

23. Al-Rahal N, AlHamza F, Therapeutic erythrocytapheresis versus traditional phlebotomy in the treatment of patients with erythrocytosis: Int J Adv Res, 2016; 4; 509-15

24. Liu H, Liu H, Shen J, A clinical analysis of erythrocytapheresis for the treatment of polycythemia: Transfus Apher Sci, 2013; 48; 229-33

25. Teofili L, Valentini CG, Rossi E, De Stefano V, Indications and use of therapeutic phlebotomy in polycythemia vera: Which role for erythrocytapheresis?: Leukemia, 2019; 33; 279-81

26. Zhao Y, Zhang Z, Liu L, Associations of high altitude polycythemia with polymorphisms in EPAS1, ITGA6 and ERBB4 in Chinese Han and Tibetan populations: Oncotarget, 2017; 8; 86736-46

27. West JB, Physiological effects of chronic hypoxia: N Engl J Med, 2017; 376; 1965-71

28. Wright AD, Beazley MF, Bradwell AR, Medroxyprogesterone at high altitude. The effects on blood gases, cerebral regional oxygenation, and acute mountain sickness: Wilderness Environ Med, 2004; 15; 25-31

29. Plata R, Cornejo A, Arratia C, Angiotensin-converting-enzyme inhibition therapy in altitude polycythaemia: A prospective randomised trial: Lancet, 2002; 359; 663-66

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