Pancytopenia in a Case of Aplastic Anaemia/Paroxysmal Nocturnal Haemoglobinuria Unmasked by SARS-CoV-2 Infection: A Case Report
Abstract
:1. Introduction
2. Case Report
3. Discussion
4. Conclusions
Author Contributions
Funding
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Yu, J.; Yuan, X.; Chen, H.; Chaturvedi, S.; Braunstein, E.M.; Brodsky, R.A. Direct activation of the alternative complement pathway by SARS-CoV-2 spike proteins is blocked by factor D inhibition. Blood 2020, 136, 2080–2089. [Google Scholar] [CrossRef] [PubMed]
- Afzali, B.; Noris, M.; Lambrecht, B.N.; Kemper, C. The state of complement in COVID-19. Nat. Rev. Immunol. 2022, 22, 77–84. [Google Scholar] [CrossRef] [PubMed]
- Hill, A.; DeZern, A.E.; Kinoshita, T.; Brodsky, R.A. Paroxysmal nocturnal haemoglobinuria. Nat. Rev. Dis. Primers 2017, 3, 17028. [Google Scholar] [CrossRef] [PubMed]
- Shah, N.; Bhatt, H. Paroxysmal Nocturnal Hemoglobinuria; StatPearls Publishing: Tampa, FL, USA, 2022. [Google Scholar]
- Fattizzo, B.; Serpenti, F.; Giannotta, J.A.; Barcellini, W. Difficult Cases of Paroxysmal Nocturnal Hemoglobinuria: Diagnosis and Therapeutic Novelties. J. Clin. Med. 2021, 10, 948. [Google Scholar] [CrossRef]
- Parker, C.; Omine, M.; Richards, S.; Nishimura, J.; Bessler, M.; Ware, R.; Hillmen, P.; Luzzatto, L.; Young, N.; Kinoshita, T.; et al. Diagnosis and management of paroxysmal nocturnal hemoglobinuria. Blood 2005, 106, 3699–3709. [Google Scholar] [CrossRef] [PubMed]
- Devalet, B.; Mullier, F.; Chatelain, B.; Dogné, J.M.; Chatelain, C. Pathophysiology, diagnosis, and treatment of paroxysmal nocturnal hemoglobinuria: A review. Eur. J. Haematol. 2015, 95, 190–198. [Google Scholar] [CrossRef]
- Chiariello, G.; Covetti, G.; Pisano, M.C.A.; Schettini, A.; D’Aniello, T.; Nappo, R.; Aliberti, E.; Iannuzzi, A. An interesting case of atypical venous thrombosis with low red blood cells. Ital. J. Med. 2019, 14, 22–26. [Google Scholar] [CrossRef]
- Hillmen, P.; Elebute, M.; Kelly, R.; Urbano-Ispizua, A.; Hill, A.; Rother, R.P.; Khursigara, G.; Fu, C.L.; Omine, M.; Browne, P.; et al. Long-term effect of the complement inhibitor eculizumab on kidney function in patients with paroxysmal nocturnal hemoglobinuria. Am. J. Hematol. 2010, 85, 553–559. [Google Scholar] [CrossRef]
- Risitano, A.M. Paroxysmal nocturnal hemoglobinuria and other complement-mediated hematological disorders. Immunobiology 2012, 217, 1080–1087. [Google Scholar] [CrossRef]
- Kulasekararaj, A.G.; Lazana, I.; Large, J.; Posadas, K.; Eagleton, H.; Lord Villajin, J.; Zuckerman, M.; Gandhi, S.; Marsh, J.C.W. Terminal complement inhibition dampens the inflammation during COVID-19. Br. J. Haematol. 2020, 190, e141–e143. [Google Scholar] [CrossRef]
- Fattizzo, B.; Pasquale, R.; Bellani, V.; Barcellini, W.; Kulasekararaj, A.G. Complement Mediated Hemolytic Anaemias in the COVID-19 Era: Case Series and Review of the Literature. Front. Immunol. 2021, 12, 791429. [Google Scholar] [CrossRef] [PubMed]
- Otieno, S.B.; Altahan, A.; Kaweeta, F.; Karri, S.; Alnoor, F.; Johnson, R. Severe Hemolysis in a COVID-19 Patient with Paroxysmal Nocturnal Hemoglobinuria. Case Rep. Hematol. 2021, 2021, 6619177. [Google Scholar] [CrossRef] [PubMed]
- Sokol, J.; Nehaj, F.; Mokan, M.; Lisa, L.; Stasko, J. COVID19 infection in a patient with paroxysmal nocturnal hemoglobinuria: A case report. Medicine 2021, 100, e25456. [Google Scholar] [CrossRef] [PubMed]
- Pike, A.; Muus, P.; Munir, T.; Mitchell, L.; Arnold, L.; Riley, K.; Houghton, N.; Forrest, B.; Gachev, J.; Hillmen, P.; et al. COVID-19 infection in patients on anti-complement therapy: The Leeds National Paroxysmal Nocturnal Haemoglobinuria service experience. Br. J. Haematol. 2020, 191, e1–e4. [Google Scholar] [CrossRef]
- Barcellini, W.; Fattizzo, B.; Giannotta, J.A.; Quattrocchi, L.; Aydin, S.; Barone, F.; Carbone, C.; Pomponi, F.; Metafuni, E.; Beggiato, E.; et al. COVID-19 in patients with paroxysmal nocturnal haemoglobinuria: An Italian multicentre survey. Br. J. Haematol. 2021, 194, 854–856. [Google Scholar] [CrossRef]
- Araten, D.J.; Belmont, H.M.; Schaefer-Cutillo, J.; Iyengar, A.; Mattoo, A.; Reddy, R. Mild clinical course of COVID-19 in 3 patients receiving therapeutic monoclonal antibodies targeting C5 complement for hematologic disorders. Am. J. Case Rep. 2020, 12, e927418. [Google Scholar] [CrossRef]
- Schüller, H.; Klein, F.; Lübbert, M.; Prager, E.P. Hemolytic crisis in a patient treated with eculizumab for paroxysmal nocturnal hemoglobinuria possibly triggered by SARS-CoV-2 (COVID-19): A case report. Ann. Hematol. 2021, 100, 841–842. [Google Scholar] [CrossRef]
- Genthon, A.; Chiarabini, T.; Baylac, P.; Valin, N.; Urbina, T.; Pacanowski, J.; Mekinian, A.; Brissot, E.; M’Hammedi-Bouzina, F.; Lapusan, S.; et al. Severe COVID-19 infection in a patient with paroxysmal nocturnal hemoglobinuria on eculizumab therapy. Leuk. Lymphoma 2021, 62, 1502–1505. [Google Scholar] [CrossRef]
- Pravdic, Z.; Mitrovic, M.; Bogdanovic, A.; Virijevic, M.; Sabljic, N.; Pantic, N.; Vukovic, N.S. COVID-19 Presented with Deep Vein Thrombosis in a Patient with Paroxysmal Nocturnal Haemoglobinuria. Hamostaseologie 2021, 41, 397–399. [Google Scholar] [CrossRef]
- Hines, A.; Hakim, N.; Barrientos, J. COVID-19 infection presenting as paroxysmal nocturnal hemoglobinuria. Clin. Case Rep. 2021, 9, e04636. [Google Scholar] [CrossRef]
- Kamura, Y.; Sakamoto, T.; Yokoyama, Y.; Nishikii, H.; Sakata-Yanagimoto, M.; Chiba, S.; Obara, N. Hemolysis induced by SARS-CoV-2 mRNA vaccination in patients with paroxysmal nocturnal hemoglobinuria. Int. J. Hematol. 2022, 116, 55–59. [Google Scholar] [CrossRef] [PubMed]
- Portuguese, A.J.; Sunga, C.; Kruse-Jarres, R.; Gernsheimer, T.; Abkowitz, J. Autoimmune- and complement-mediated hematologic condition recrudescence following SARS-CoV-2 vaccination. Blood Adv. 2021, 5, 2794–2798. [Google Scholar] [CrossRef] [PubMed]
- Risitano, A.; Peffault de Latour, R. How we(’ll) treat paroxysmal nocturnal haemoglobinuria: Diving into the future. Br. J. Haematol. 2022, 196, 288–303. [Google Scholar] [CrossRef] [PubMed]
- Richards, S.J.; Painter, D.; Dickinson, A.J.; Griffin, M.; Munir, T.; Arnold, L.; Payne, D.; Pike, A.; Muus, P.; Hill, A.; et al. The incidence and prevalence of patients with paroxysmal nocturnal haemoglobinuria and aplastic anaemia PNH syndrome: A retrospective analysis of the UK’s population-based haematological malignancy research network 2004–2018. Eur. J. Haematol. 2021, 107, 211–218. [Google Scholar] [CrossRef] [PubMed]
Population | N° Events in the Gate | Sensibility % (LOD) | Gating Markers | GPI-Linked Markers | % Negative (PNH III) | % Defective (PNH II) | % Normal (PNH I) | Clone Size (PNH II + PNH III) |
---|---|---|---|---|---|---|---|---|
Granulocytes | 4520 | 0.66% | CD45, CD15 | FLAER | 93.5% | 2.5% | 4% | 6.5% |
Monocytes | 600 | 5.00% | CD45, CD33 | FLAER | 93.5% | 2.5% | 4% | 6.5% |
Authors | PNH Type | Clinical Presentation | History of PNH | Therapy |
---|---|---|---|---|
Kulasekararaj et al. [11] | 2 Classical PNH; 2 AA/PNH | Pt 1: F, 35 yrs, fever, sore throat, myalgia | Long-standing history (6 yrs) of classical PNH (eculizumab, then ravulizumab) | Pt 1: Ravulizumab |
Pt 2: M, 47 yrs, fever, abdominal pain, nausea, cough | Naive | Pt 2: Oxygen, Warfarin | ||
Pt 3: F, 37 yrs, fever, headache, cough, myalgia | Long-standing history (11 yrs) of AA/PNH (eculizumab) | Pt 3: Eculizumab, Blood transfusion | ||
Pt 4: M, 51 yrs, fever, cough, abdominal pain, fatigue, myalgia | No specified history of AA/PNH | Pt 4: Oxygen, Warfarin | ||
Fattizzo et al. [12] | 1 Classical PNH | Shortness of breath, asthenia, dark urine, anaemia | Long-standing history (11 yrs) of classical PNH (eculizumab) | Antibiotics, Dexamethasone, LMWH, Eculizumab, Red blood cell transfusion |
Otieno et al. [13] | AA/PNH | F, 19 yrs, tooth infection, pancytopenia and haemolysis | Naive | Eculizumab and then Ravulizumab |
Sokol et al. [14] | 1 Classical PNH | M, 27 yrs, acute onset shortness of breath, cough, blood in the urine | Naive | LMWH, Dexamethasone, Cefuroxime |
Pt 2: M, 47 yrs, fever, myalgia, dizziness | Pt 2: Long-standing history (6 yrs) of AA/PNH (eculizumab), recently MDS-transformed and awaiting BMT | Pt 2: Antibiotics. | ||
Pt 3: M, 43 yrs, breakthrough haemolysis with haemoglobinuria, respiratory failure | Long-standing history (17 yrs) of AA and haemolytic PNH (14 yrs), (eculizumab) | Pt 3: Eculizumab, Packed red cells, Antibiotics, Mechanical ventilation. Death after 23 days. | ||
Pt 4: F, 77 yrs, breathlessness and chest pain | Long-standing history (15 yrs) of AA, and symptomatic PNH (9 yrs) (eculizumab) | Pt 4: Antibiotics, Packed red cells, Eculizumab. | ||
Pike et al. [15] | 1 Classic PNH 3 AA/PNH | Pt 1: F, 61 yrs, fever, lethargy, dry cough, diarrhoea | Pt 1: Long-standing history (12 yrs) of classical PNH (ravulizumab) | Pt 1: Oxygen and Antibiotics. |
Pt 2: M, 47 yrs, fever, myalgia, dizziness | Pt 2: Long-standing history (6 yrs) of AA/PNH (eculizumab), recently MDS transformed and awaiting BMT | Pt 2: Antibiotics. | ||
Pt 3: M, 43 yrs, breakthrough haemolysis with haemoglobinuria, respiratory failure | Long-standing history (17 yrs) of AA and haemolytic PNH (14 yrs), (eculizumab) | Pt 3: Eculizumab, Packed red cells, Antibiotics, Mechanical ventilation. Death after 23 days. | ||
Pt 4: F, 77 yrs, breathlessness and chest pain | Long-standing history (15 yrs) of AA, and symptomatic PNH (9 yrs) (eculizumab) | Pt 4: Antibiotics, Packed red cells, Eculizumab. | ||
Barcellini et al. [16] | 4 Classical PNH | Pt 1: F, 55 yrs, fever, ageusia, active haemolysis | Pt 1: Naive | Pt 1: Prophylactic LMWH, Azithromycin |
Pt 2: F, 58 yrs, no new symptoms | Pt 2: Long-standing history (14 yrs) classical PNH (eculizumab, then ravulizumab) | Pt 2: Ravulizumab, Warfarin | ||
Pt 3: F, 41 yrs, no new symptoms | Pt 3: Unspecified history of therapy with ravilizumab | Pt 3: Ravulizumab, | ||
Pt 4: M, 39 yrs, fever | Pt 4: Unspecified history of therapy with eculizumab | Pt 4: Eculizumab | ||
Araten et al. [17] | 2 Classical PNH | Pt 1: F, 39 yrs, fever, fatigue | Pt 1: Long-standing history (19 yrs) classical PNH (eculizumab, then ravulizumab; fondaparinux, cyclosporine) | Pt 1: Ciprofloxacin |
Pt 2: F, 60 yrs, cough, fatigue, malaise, headache | Pt 2: Long-standing history (15 yrs) classical PNH (eculizumab) | Pt 2: Eculizumab | ||
Schuller et al. [18] | 1 Classical PNH | F, 68 yrs, mild fever, cough, sore throat, diarrhoea, haemolytic crisis, mild pancytopenia | Long-standing history (45 yrs) classical PNH, (eculizumab started in 2007) | Eculizumab, Red cell concentrates, Granulocyte colony stimulating factor, anti-inflammatory agents |
Genthon et al. [19] | 1 Classical PNH | M, 45 yrs, dry cough, myalgia, diarrhoea, fever | Long-standing history (27 yrs) classical PNH (eculizumab started in 2008) | Amoxicillin/clavulanate, Ciprofloxacin, O2 therapy, Hydroxychloroquine, Ritonavir + Lopinavir, Enoxaparin, Eculizumab, Tocilizumab |
Pravdic et al. [20] | 1 Classical PNH | M, 33 yrs, DVT left popliteal vein, fever | Long-standing history (7 yrs) classical PNH (eculizumab and warfarin started in 2015) | Amoxicillin/clavulanate, Ciprofloxacin, LMWH, Eculizumab |
Hines et al. [21] | 1 AA/PNH | M, 35 yrs, pancytopenia, melena, headache, fatigue, poor appetite | Naive | Packed red blood cells transfusion, steroid, intravenous immunoglobulin, eculizumab |
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Iannuzzi, A.; Parrella, A.; De Ritis, F.; Cammarota, A.; Berloco, L.; Paudice, F.; D’Angelo, G.; Aliberti, E.; Iannuzzo, G. Pancytopenia in a Case of Aplastic Anaemia/Paroxysmal Nocturnal Haemoglobinuria Unmasked by SARS-CoV-2 Infection: A Case Report. Medicina 2022, 58, 1282. https://doi.org/10.3390/medicina58091282
Iannuzzi A, Parrella A, De Ritis F, Cammarota A, Berloco L, Paudice F, D’Angelo G, Aliberti E, Iannuzzo G. Pancytopenia in a Case of Aplastic Anaemia/Paroxysmal Nocturnal Haemoglobinuria Unmasked by SARS-CoV-2 Infection: A Case Report. Medicina. 2022; 58(9):1282. https://doi.org/10.3390/medicina58091282
Chicago/Turabian StyleIannuzzi, Arcangelo, Antonio Parrella, Francesca De Ritis, Anna Cammarota, Lucia Berloco, Francesca Paudice, Giovanni D’Angelo, Emilio Aliberti, and Gabriella Iannuzzo. 2022. "Pancytopenia in a Case of Aplastic Anaemia/Paroxysmal Nocturnal Haemoglobinuria Unmasked by SARS-CoV-2 Infection: A Case Report" Medicina 58, no. 9: 1282. https://doi.org/10.3390/medicina58091282