Original Article

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Blood Res 2023; 58(2):

Published online June 30, 2023

https://doi.org/10.5045/br.2023.2022201

© The Korean Society of Hematology

Efficacy of plasmapheresis in neutropenic patients suffering from cytokine storm because of severe COVID-19 infection

Alireza Sadeghi1, Somayeh Sadeghi2, Mohammad Saleh Peikar1, Maryam Yazdi3, Mehran Sharifi1,4, Safie Ghafel5, Farzin Khorvash6, Behrooz Ataei2, Mohammad Reza Safavi7, Elahe Nasri2

1Department of Internal Medicine, School of Medicine, 2Infectious Diseases and Tropical Medicine Research Center, 3Child Growth and Development Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease, 4Cancer Prevention Research Center Seyed Al-Shohada Hospital, 5Mycology Reference Laboratory, Research Core Facilities Laboratory, 6Acquired Immunodeficiency Research Center, 7Department of Anesthesiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

Correspondence to : Elahe Nasri, M.D.
Infectious Diseases and Tropical Medicine Research Center, Isfahan University of Medical Sciences, Hezar Jerib Avenue, Isfahan 81746-73461, Iran
E-mail: elahe.nasri@yahoo.com

Received: October 9, 2022; Revised: April 11, 2023; Accepted: April 19, 2023

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Background
With the emergence of the coronavirus disease 2019 (COVID-19) and inability of healthcare systems to control the disease, various therapeutic theories with controversial responses have been proposed. Plasmapheresis was administered as a medication. However, the knowledge of its efficacy and indications is inadequate. This study evaluated the use of plasmapheresis in critically ill patients with cancer.
Methods
This randomized clinical trial was conducted on 86 patients with malignancies, including a control group (N=41) and an intervention group (N=45) with severe COVID-19 during 2020-21. Both groups were treated with routine medications for COVID-19 management according to national guidelines, and plasmapheresis was applied to the intervention group. C-reactive protein (CRP), D-dimer, ferritin, lactate dehydrogenase, hemoglobin, and white blood cell, polymorphonuclear, lymphocyte, and platelet levels were measured at admission and at the end of plasmapheresis. Other variables included neutrophil recovery, intensive care unit admission, intubation requirements, length of hospital stay, and hospitalization outcomes.
Results
CRP(P<0.001), D-dimer (P<0.001), ferritin (P=0.039), and hemoglobin (P=0.006) levels were significantly different between the groups after the intervention. Neutrophil recovery was remarkably higher in the case than in the control group (P<0.001). However, plasmapheresis did not affect the length of hospital stay (P=0.076), which could have significantly increased survival rates (P<0.001).
Conclusion
Based on the study findings, plasmapheresis led to a significant improvement in laboratory markers and survival rate in patients with severe COVID-19. These findings reinforce the value of plasmapheresis in cancer patients as a critical population suffering from neutropenia and insufficient immune responses.


Keywords: COVID-19, Plasmapheresis, Survival, Neutropenia

Article

Original Article

Blood Res 2023; 58(2): 91-98

Published online June 30, 2023 https://doi.org/10.5045/br.2023.2022201

Copyright © The Korean Society of Hematology.

Efficacy of plasmapheresis in neutropenic patients suffering from cytokine storm because of severe COVID-19 infection

Alireza Sadeghi1, Somayeh Sadeghi2, Mohammad Saleh Peikar1, Maryam Yazdi3, Mehran Sharifi1,4, Safie Ghafel5, Farzin Khorvash6, Behrooz Ataei2, Mohammad Reza Safavi7, Elahe Nasri2

1Department of Internal Medicine, School of Medicine, 2Infectious Diseases and Tropical Medicine Research Center, 3Child Growth and Development Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease, 4Cancer Prevention Research Center Seyed Al-Shohada Hospital, 5Mycology Reference Laboratory, Research Core Facilities Laboratory, 6Acquired Immunodeficiency Research Center, 7Department of Anesthesiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

Correspondence to:Elahe Nasri, M.D.
Infectious Diseases and Tropical Medicine Research Center, Isfahan University of Medical Sciences, Hezar Jerib Avenue, Isfahan 81746-73461, Iran
E-mail: elahe.nasri@yahoo.com

Received: October 9, 2022; Revised: April 11, 2023; Accepted: April 19, 2023

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background
With the emergence of the coronavirus disease 2019 (COVID-19) and inability of healthcare systems to control the disease, various therapeutic theories with controversial responses have been proposed. Plasmapheresis was administered as a medication. However, the knowledge of its efficacy and indications is inadequate. This study evaluated the use of plasmapheresis in critically ill patients with cancer.
Methods
This randomized clinical trial was conducted on 86 patients with malignancies, including a control group (N=41) and an intervention group (N=45) with severe COVID-19 during 2020-21. Both groups were treated with routine medications for COVID-19 management according to national guidelines, and plasmapheresis was applied to the intervention group. C-reactive protein (CRP), D-dimer, ferritin, lactate dehydrogenase, hemoglobin, and white blood cell, polymorphonuclear, lymphocyte, and platelet levels were measured at admission and at the end of plasmapheresis. Other variables included neutrophil recovery, intensive care unit admission, intubation requirements, length of hospital stay, and hospitalization outcomes.
Results
CRP(P<0.001), D-dimer (P<0.001), ferritin (P=0.039), and hemoglobin (P=0.006) levels were significantly different between the groups after the intervention. Neutrophil recovery was remarkably higher in the case than in the control group (P<0.001). However, plasmapheresis did not affect the length of hospital stay (P=0.076), which could have significantly increased survival rates (P<0.001).
Conclusion
Based on the study findings, plasmapheresis led to a significant improvement in laboratory markers and survival rate in patients with severe COVID-19. These findings reinforce the value of plasmapheresis in cancer patients as a critical population suffering from neutropenia and insufficient immune responses.

Keywords: COVID-19, Plasmapheresis, Survival, Neutropenia

Fig 1.

Figure 1.Consort diagram of the studied population.
Blood Research 2023; 58: 91-98https://doi.org/10.5045/br.2023.2022201

Table 1 . Demographic, medical, and on-admission clinical characteristics of the studied groups..

Intervention group (N=45)Control group (N=41)Pa)
Demographic characteristics
Age (yr), mean±standard deviation51.55±8.0752.60±8.450.486b)
Gender, N (%)Female23 (51.1)17 (41.5)0.370
Male22 (48.9)24 (58.5)
Medical characteristics
Chronic medical conditionsDM6 (13.3)4 (9.8)
HTN5 (11.1)3 (7.3)
RA1 (2.2)0 (0)
DLP1 (2.2)0 (0)
Hypothyroid1 (2.2)0 (0)
IHD0 (0)2 (4.9)
Health status, N (%)Diseased37 (82.2)36 (87.8)0.470
Healthy8 (17.8)5 (12.2)
Type of malignancyALL1 (2.2)2 (4.9)
AML6 (13.3)9 (22.0)
Aplastic anemia2 (4.4)1 (2.4)
Breast cancer4 (8.9)2 (4.9)
CLL5 (11.1)5 (12.2)
Lymphoma5 (11.1)4 (9.8)
MDS1 (2.2)1 (2.4)
MM4 (8.9)4 (9.8)
Unknown new case2 (4.4)2 (4.9)
Ovarian cancer1 (2.2)0 (0)
Pancreatic cancer1 (2.2)0 (0)
Refractory All1 (2.2)0 (0)
TTP1 (2.2)0 (0)
Colon cancer1 (2.2)2 (4.9)
Gastric cancer1 (2.2)4 (9.8)
Clinical characteristics
On-admission oxygen saturation (%), mean±standard deviation78.16±10.2979.68±10.750.323
The severity of lung involvement (%), mean±standard deviation18.01±4.0217.40±4.340.353

a)Chi-square test or Fisher’s exact test for qualitative variables and Mann–Whitney’s test for quantitative variables. b)Independent t-test..

Abbreviations: ALL, acute lymphoblastic leukemia; AML, acute myelogenous leukemia; CLL, chronic lymphocytic leukemia; DLP, dyslipidemia; DM, diabetes mellitus; HTN, hypertension; IHD, ischemic heart disease; ITP, idiopathic thrombocytic purpura; MDS, myelodysplastic syndrome; MM, multiple myeloma; RA, rheumatoid arthritis; TTP, thrombocytopenic thrombotic purpura..


Table 2 . Clinical indexes, laboratory findings, and ventilator parameters before and after plasma exchange..

Plasma exchange group (N=45)Control group (N=41)P2
Mean±SDMedian (Q1, Q3)Mean±SDMedian (Q1, Q3)
CRP (mg/L)Before108.21±33.61121.2 (80.1, 137)--
After15.65±26.196 (2, 14)72.42±22.0771 (58, 86)<0.001
P1<0.001
D-dimer (mg/L)Before984.19±783.31850 (200, 1,700)--
After957.67±714.07700 (350, 1,600)2,641.86±2,723.331,600 (1,150, 3,152)<0.001
P10.472
Ferritin (ng/mL)Before6,780.70±12,019.871,656.5 (637.5, 6,637)--
After5,275.60±9,139.491,346 (630, 4,655)6,470.25±17,332.622,747.5 (1,329, 5,400)0.039
P10.042
LDH (U/L)Before1,269.53±1,242.82869 (648.5, 1,395)--
After1,098.34±1,173.67715.5 (532.5, 1,132.5)1,350.02±1,645.29780 (670, 1,422.5)0.228
P10.004
WBC (per microliter)Before13.70±29.077.4 (3.65, 11.05)--
After15.24±28.318.2 (3.6, 16.1)10.51±16.475.5 (2.48, 11.4)0.129
P10.319
Hemoglobin (g/dL)Before11.35±3.4911.3 (8.9, 13.25)--
After10.88±2.2611 (8.9, 12.8)9.50±2.019.4 (7.85, 10.95)0.006
P10.735
PMN (%)Before74.64±21.6183.6 (69, 87.425)--
After71.71±21.2978.85 (66.75, 83.875)61.99±27.5168.1 (47.4, 85.95)0.126
P10.153
Lymph (%)Before15.79±16.0310.4 (5.1, 18.45)--
After17.41±17.0012.7 (8.675, 21.875)23.37±18.3323.6 (7.8, 32.8)0.081
P10.592
PLT (per microliter)Before122.11±86.74129 (29.5, 189)--
After126.03±88.54115 (47, 212)126.24±166.8985 (27, 168.5)0.271
P10.44

Abbreviations: CRP, C-reactive protein; IQR, interquartile range; LDH, lactate dehydrogenase; P1, Wilcoxon’s test for within-group comparisons; P2, Mann–Whitney’s test for between-group comparisons; PLT, platelet; PMN, polymorphonuclear cells; Q1, the first quartile; Q3, the third quartile; SD, standard deviation; WBC, white blood cells..


Table 3 . Complications related to the interventions..

Plasma exchange group (N=45)Control group (N=41)Pa)
Neutrophil recovery, N (%)Yes0 (0)11 (26.8)<0.001
No45 (100.0)30 (73.2)
ICU admission, N (%)Yes33 (73.3)22 (53.7)0.057
No12 (26.7)19 (46.3)
Intubation, N (%)Yes4 (8.8)0 (0)0.118
No0 (0)0 (0)

a)Chi-square test or Fisher’s exact test for qualitative variables and Mann–Whitney’s test for quantitative variables..


Table 4 . The logistic regression assessment of plasmapheresis impact..

Plasma exchange group (N=45)Control group (N=41)P
Length of hospital stay (day), median (IQR)10 (6, 18.5)8 (6.5, 15.5)0.076a)
Vitality, N (%)
Dead13 (28.9)30 (73.2)<0.001b)
Alive32 (71.1)11 (26.8)

a)Breslow test, b)logistic regression adjusted for disease history..

Abbreviation: IQR, interquartile range..


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