Therapeutic plasma exchange in patients with COVID-19 pneumonia in intensive care unit: a retrospective study
Critical Care volume 24, Article number: 492 (2020)
In patients with COVID-19 pneumonia, high risk of thrombosis became a current issue, and d-dimer levels indicating fibrin degradation products (FDPs) in the plasma were found as a predictor for mortality [1, 2]. Although unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) decrease the production of FDPs by inhibiting factors Xa and II, they cannot contribute metabolization of existing FDPs. Furthermore, FDPs cannot be filtered by known cytokine filters because of their molecular weight (minimum 240 kDa) [3, 4]. Yet, FDPs can be removed by therapeutic plasma exchange (TPE) . Therefore, recently, three consecutive TPE sessions were performed in selected patients with COVID-19 pneumonia in intensive care units (ICUs) after the assessment of their clinical and coagulation status. In the study, the effect of TPE on outcomes was retrospectively investigated in patients with COVID-19 pneumonia.
All COVID-19 patients admitted to 5 different tertiary ICUs between 10 March and 10 May 2020 were evaluated, and 73 of 91 patients were included in the study. The patients who died within the first 4 days and who were still in the ICUs on 10 May were excluded. According to the Turkish Health Minister Algorithm for COVID-19, all included patients received the same antiviral (favipiravir, hydroxychloroquine, azithromycin) therapy and anticoagulant prophylaxis (UFH infusion 100 mcg/kg or LMWH 0.01 mL/kg). Since two different protocols were used in 5 ICUs, patients with d-dimer ≥ 2 in 3 ICUs had only received therapeutic anticoagulation whereas patients with d-dimer ≥ 2 in the other 2 ICUs had received TPE plus therapeutic anticoagulation. In all ICUs, for all patients in GII, echocardiography, lower extremity venous Doppler, and, if pulmonary thrombosis suspected, thorax computerized tomography angiography were performed. After collecting data, 73 patients were divided into 2 groups as group I (GI) (d-dimer < 2 mg/L) and group II (GII) (d-dimer ≥ 2 mg/L), and then GII was also divided into 2 groups as GIIa (TPE+) and GIIb (TPE−). Patients’ characteristics, respiratory and laboratory parameters, and outcomes were recorded. Propensity score matching (PSM) analysis was conducted on R v4.0.1 (0.2 caliper without replacement and nearest neighbor model, 1:1 ratio) by using 14 covariates (age, gender, CCI, APACHE II, SOFA score, lactate, leucocyte, lymphocyte, d-dimer and creatinine at the ICU admission, maximum respiratory support, the usage of steroid, IL-6 blocker, and cytokine filter).
The total mortality rate was 27.4%. Mortality rates of GI and GII were 5% and 35.9%, respectively. In GII, major thromboembolic events were not detected in any patients. The median (min-max) day for the starting TPE was 3 (2–4). In GIIa, APACHE II, SOFA scores, d-dimer and interleukin-6 (IL-6) levels at the ICU admission, and length of ICU stay were significantly higher than those of GI whereas mortality rates were similar in those groups (Table 1). The median values of the LOS-ICU in survivors and non-survivors in GII were 14 (6.5–21.5) and 15.5 (8–23), respectively (p = 0.630). In GIIa, lactate dehydrogenase (LDH), d-dimer, ferritin, IL-6, C-reactive protein (CRP), and procalcitonin levels were significantly decreased after three consecutive TPEs (Table 2). Furthermore, although ferritin level at the ICU admission was higher in GIIa, the mortality rate in both before and after PSM was higher in GIIb (45.7% and 58.3%) than in GIIa (16.7% and 8.3%) (p = 0.037, p = 0.009, respectively) (Table 1).
Some patients with COVID-19 pneumonia have a high risk of thrombosis leading to worse outcomes. Therefore, monitoring d-dimer levels is crucial. In these groups of patients, TPE seems to be a treatment which may improve outcomes by effectively removing FDPs and restoring coagulation status. We are aware that TPE may not be routinely required in these patients . However, we think that it should be featured as a part of the treatment especially in COVID-19 pneumonia patients with a high risk of thrombosis.
Availability of data and materials
All data was added as an Excel file in a supplementary information file.
Helms J, Tacquard C, Severac F, Leonard-Lorant I, Ohana M, Delabranche X, et al. High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study. Intensive Care Med. 2020;46:1089–98.
Zhang L, Yan X, Fan Q, Liu H, Liu X, Liu Z, et al. D-dimer levels on admission to predict in-hospital mortality in patients with Covid-19. J Thromb Haemost. 2020;18:1324–9.
Diab M, Platzer S, Guenther A, Sponholz C, Scherag A, Lehmann T, Velichkov I, Hagel S, Bauer M, Brunkhorst FM, et al. Assessing efficacy of CytoSorb haemoadsorber for prevention of organ dysfunction in cardiac surgery patients with infective endocarditis: REMOVE-protocol for randomised controlled trial. BMJ Open. 2020;10(3):e031912.
Walker JB, Nesheim ME. The molecular weights, mass distribution, chain composition, and structure of soluble fibrin degradation products released from a fibrin clot perfused with plasmin. J Biol Chem. 1999;274(8):5201–12.
Rimmer E, Houston BL, Kumar A, Abou-Setta AM, Friesen C, Marshall JC, Rock G, Turgeon AF, Cook DJ, Houston DS, et al. The efficacy and safety of plasma exchange in patients with sepsis and septic shock: a systematic review and meta-analysis. Crit Care. 2014;18(6):699.
Honore PM, Mugisha A, Kugener L, Redant S, Attou R, Gallerani A, De Bels D. Therapeutic plasma exchange as a routine therapy in septic shock and as an experimental treatment for COVID-19: we are not sure. Crit Care. 2020;24(1):226.
We would like to express our gratitude to our nurses who have taken care of the patients and performed TPE procedure in the ICU and COVID-19 Study Group. COVID-19 Group collaborating authors: Aylin Ogan2, Aylin Cimet Ayyildiz2, Berrin Yalcin2, Behiye Oren6, Fadıl Havas6, Sevda Dizi6, Birsen Kose6, Umran Yakici6, Cenk Sahan6, Elif Ozkilitci6, Ugur Tunali6, Deniz Gunes7, Ozlem Dincer7, Reyhan Sahin7, Duran Ozdemir7, Mehtap Selcuk8, Ceyhun Solakoglu8, Unsal Arif Turan8, Erkan Kaya8, Mustafa Emre Kavlak3, Pelin Katar3, Hande Aygun9, Kerim Cikim10, Ozkan Uysal10, Nur Ozturk Kaskir11, Aysun Soylu12.
2General Intensive Care Unit, Acibadem International Hospital, Istanbul, Turkey
3General Intensive Care Unit, Memorial Atasehir Hospital, Istanbul, Turkey
6General Intensive Care Unit, Acibadem Atakent Hospital, Istanbul, Turkey
7General Intensive Care Unit, Acibadem Bakirkoy Hospital, Istanbul, Turkey
8General Intensive Care Unit, Acibadem Kadikoy Hospital, Istanbul, Turkey
9Department of Infection Disease and Clinical Microbiology, Acibadem International Hospital, Istanbul, Turkey
10Department of Internal Medicine, Acibadem International Hospital, Istanbul, Turkey
11Department of Chest Disease, Acibadem International Hospital, Istanbul, Turkey
12Department of Biochemistry, Acibadem International Hospital, Istanbul, Turkey
There was no funding for the research reported.
Ethics approval and consent to participate
The study was approved by The Scientific Committee of the Turkish Health Ministry (2020-05-11T22_01_29).
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Gucyetmez, B., Atalan, H.K., Sertdemir, I. et al. Therapeutic plasma exchange in patients with COVID-19 pneumonia in intensive care unit: a retrospective study. Crit Care 24, 492 (2020). https://doi.org/10.1186/s13054-020-03215-8