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DOI: 10.1055/s-0043-1775733
Congenital Bleeding Disorders and COVID-19—A Systematic Literature Review
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Abstract
Hypercoagulability is a prominent feature of coronavirus disease 2019 (COVID-19) and can lead to fatal consequences. Although the impact of COVID-19 on several disorders is well-established, its effect on congenital bleeding disorders (CBDs) is not well-documented. To address this ambiguity, a systematic review was conducted on the available studies to determine the impact of COVID-19 and vaccination aimed to prevent COVID-19 on patients with CBDs. We performed a systematic literature review using relevant keywords and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) protocol. We conducted our search on the PubMed, Scopus, and Web of Science databases until July 2023. Out of 31 included studies, 12 case series covering 770 patients with CBD and COVID-19 were further analyzed. The majority of the patients had hemophilia A (n = 352, ∼46%) or hemophilia B (n = 74, ∼10%), while the remaining patients had von Willebrand disease (n = 43, 5.6%) or rare bleeding disorders (n = 27, 3.5%). A total of 25 deaths (3.2%) and 22 intensive care unit admissions (2.8%) were recorded. Bleeding complications were reported in the majority of the 12 case series (n = 7, 58.3%) and in most of the case reports (n = 8, ∼57%), while thrombotic complications were only reported in two studies (16.6%). The mortality rate ranged from 0% in five studies (41.6%) to 5.7% and the rate of hospitalization ranged from 0 to 40%. Bleeding complications were reported in a range of 0 to 81%, while the thrombotic complication rate in one study was 6.9%. The mortality rate varied from 0 to 5.7%, and the hospitalization rate ranged from 0 to 40%. Bleeding complications were reported in a range of 0 to 81%, while the rate of thrombotic complications in one study was 6.9%. Vaccination was reported in five case series, which included 821 patients with CBDs with the majority having hemophilia A (n = 479; 67.2%) and hemophilia B (n = 85; ∼12%). The most frequently reported side effects were myalgia (6.5%), flu-like symptoms (4.8%), fever (4.7%), and headache (4%). COVID-19 in patients with CBDs appears to provoke thrombotic complications and bleeding events more frequently, as well as a higher rate of hospitalization, which may be partially due to the increased risk of bleeding events. Although it seems that patients with CBD have lower mortality rates, further studies are necessary to fully understand this, especially considering comorbidities and low number of available studies.
Publication History
Article published online:
27 September 2023
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References
- 1 Pradhan M, Shah K, Alexander A. et al. COVID-19: clinical presentation and detection methods. J Immunoassay Immunochem 2022; 43 (01) 1951291
- 2 Zhou Y, Chi J, Lv W, Wang Y. Obesity and diabetes as high-risk factors for severe coronavirus disease 2019 (Covid-19). Diabetes Metab Res Rev 2021; 37 (02) e3377
- 3 Spyropoulos AC, Levy JH, Ageno W. et al; Subcommittee on Perioperative, Critical Care Thrombosis, Haemostasis of the Scientific, Standardization Committee of the International Society on Thrombosis and Haemostasis. Scientific and Standardization Committee communication: clinical guidance on the diagnosis, prevention, and treatment of venous thromboembolism in hospitalized patients with COVID-19. J Thromb Haemost 2020; 18 (08) 1859-1865
- 4 Schulman S, Sholzberg M, Spyropoulos AC. et al; International Society on Thrombosis and Haemostasis. ISTH guidelines for antithrombotic treatment in COVID-19. J Thromb Haemost 2022; 20 (10) 2214-2225
- 5 Dorgalaleh A, Tabibian S, Baghaipour MR. et al. Challenges and concerns of patients with congenital bleeding disorders affected by coronavirus disease 2019. Blood Coagul Fibrinolysis 2021; 32 (03) 200-203
- 6 Zülfikar HKB, Gözüdok G, Züfikar B. Medical and socio-psychological consequences of the COVID-19 pandemic on people with congenital bleeding disorders and their caregivers. CJN 2023; 2: 1-6
- 7 Dorgalaleh A, Dabbagh A, Tabibian S. et al. Patients with congenital bleeding disorders appear to be less severely affected by SARS-CoV-2: is inherited hypocoagulability overcoming acquired hypercoagulability of coronavirus disease 2019 (COVID-19)?. Semin Thromb Hemost 2020; 46 (07) 853-855
- 8 Álvarez Román MT, Butta Coll N, García Barcenilla S. et al. Registry of patients with congenital bleeding disorders and COVID-19 in Madrid. Haemophilia 2020; 26 (05) 773-778
- 9 Zaki N, Alashwal H, Ibrahim S. Association of hypertension, diabetes, stroke, cancer, kidney disease, and high-cholesterol with COVID-19 disease severity and fatality: a systematic review. Diabetes Metab Syndr 2020; 14 (05) 1133-1142
- 10 Barh D, Tiwari S, Andrade BS. et al. A novel multi-omics-based identification of symptoms, comorbid conditions, and possible long-term complications in COVID-19. Mol Omics 2021; 17 (02) 317-337
- 11 Spiezia L, Boscolo A, Poletto F. et al. COVID-19-related severe hypercoagulability in patients admitted to intensive care unit for acute respiratory failure. Thromb Haemost 2020; 120 (06) 998-1000
- 12 Dorgalaleh A, Tabibian S, Mohammadamini M. et al. Do congenital bleeding disorders have a protective effect against COVID-19? A prospective study. Int J Lab Hematol 2021; 43 (03) e124-e127
- 13 Coluccia A, Marchesini E, Giuffrida AC. et al; AICE MECCOVID-19 Study Group. Addressing the impact of SARS-CoV-2 infection in persons with congenital bleeding disorders: the Italian MECCOVID-19 study. Haemophilia 2021; 27 (04) e575-e578
- 14 Sharathkumar A, Wendt L, Ortman C. et al; National COVID Cohort Collaborative Consortium. COVID-19 outcomes in persons with hemophilia: results from a US-based national COVID-19 surveillance registry. J Thromb Haemost 2024; 22 (01) 61-75
- 15 Koc B, Zulfikar B. COVID-19 experience with inherited bleeding disorders similar to the country population. Haemophilia 2022; 28: 32
- 16 Gökçebay DG, Şenol BK, Kurtipek FB, Çulha VK, Özbek NY, Zülfikar B. The effects of coronavirus disease 2019 pandemic on patients with hemophilia and inherited bleeding disorders: results from 2 centers in Turkey. Age (years, mean ± SD). Turk Pediatri Ars 2023; 28: 14
- 17 Perdomo-Amar I, Orozco-Gonzalez C, Duque-Ortega J. et al. Characterization of inherited coagulation disorders patients and COVID-19 infection in COLOMBIA. Haemophilia 2021; 27: 51-52
- 18 Ferroudj N, Bensadok M, Daikhi F, Chennoukh K, Zidani N, Nekkal S. Patients with congenital bleeding disorders and COVID-19: from one center in Algiers, Algeria. Haemophilia 2021; 27: 161
- 19 Hermans C, Astermark J, Carvalho M. et al. Prevalence of COVID-19 related hospitalizations and mortality in adults aged ≥40 years with haemophilia: a survey from Europe. Haemophilia 2023; 29 (03) 913-916
- 20 Sikorska A, Stefanska-Windyga E, Windyga J. Clinical course of COVID-19 in patients with inherited bleeding disorders: an interim analysis of 28 cases [abstract]. Res Pract Thromb Haemost. 2021 ; 5 (Suppl 2). Accessed July 14, 2023 at: https://abstracts.isth.org/abstract/clinical-course-of-covid-19-in-patients-with-inherited-bleeding-disorders-an-interim-analysis-of-28-cases/
- 21 Yakovleva EV, Vybornykh DE, Gemdzhian EG, Zozulya NI. COVID-19 in patients with congenital bleeding disorders in Russia. Gematol Transfuziol 2023; 68 (02) 219-228
- 22 Yousefi M, Sinaei R, Zadeh AS, Farrokhnia M, Dalfardi B. Short-time safety of the Sinopharm COVID-19 vaccine in patients with hemophilia. Arch Clin Infect Dis 2021;16(06):
- 23 Karimi MSA, Haghpanah S, Zarei T, Bazrafshan A. Safety of Sinopharm covid-19 vaccine in Iranian patients with congenital bleeding disorders: a preliminary report [abstract]. ISTH; 2022 . Accessed July 14, 2023 at: https://abstracts.isth.org/abstract/safety-of-sinopharm-covid-19-vaccine-in-iranian-patients-with-congenital-bleeding-disorders-a-preliminary-report/
- 24 Arrieta V, Williams M, Mendez A, Simonella M, Bordone R. Development of factor inhibitors in congenital haemophilia patients after following COVID-19 vaccination. A Health Center experience. Haemophilia 2022; 28: 40
- 25 Atay MH, Kelkıtlı E. The practice of COVID-19 vaccination in patients bleeding disorders. J Exp Clin Med 2022; 39 (03) 767-769
- 26 Tiede A, Leise H, Horneff S. et al. Safety of intramuscular COVID-19 vaccination in patients with haemophilia. Haemophilia 2022; 28 (05) 687-693
- 27 Babaee E, Amirkafi A, Tehrani-Banihashemi A. et al. Adverse effects following COVID-19 vaccination in Iran. BMC Infect Dis 2022; 22 (01) 476
- 28 Al Khames Aga QA, Alkhaffaf WH, Hatem TH. et al. Safety of COVID-19 vaccines. J Med Virol 2021; 93 (12) 6588-6594
- 29 Dorgalaleh A, Narouei F, Asadi M, Khamsi HM, Gholami MS. Congenital bleeding disorders and COVID-19 - an emphasis on the role of thrombosis as one of the main causes of morbidity and mortality in COVID-19. Cardiovasc Hematol Disord Drug Targets 2022; 22 (02) 83-86
- 30 Coronavirus COVID-19 Global Cases. Center for Systems Science and Engineering (CSSE) at Johns Hopkins University (JHU). Accessed September 5, 2023 at: www.arcgis.com/apps/opsdashboard/index.html#/bda7594740fd40299423467b48e9ecf6
- 31 Coronavirus Age. Sex, demographics (COVID-19). Worldometer. Accessed September 5, 2023 at: https://www.worldometers.info/coronavirus/coronavirus-age-sex-demographics/
- 32 WHO. The true death toll of COVID-19: Estimating global excess mortality. Accessed September 15, 2023 at: https://www.who.int/data/stories/the-true-death-toll-of-covid-19-estimating-global-excess-mortality
- 33 Coronavirus Age, Sex, Demographics (COVID-19) – Worldometer. . Accessed September 15, 2023 at: https://www.worldometers.info/coronavirus/coronavirus-age-sex-demographics/
- 34 Girolami A, Tezza F, Scapin M, Vettore S, Casonato A. Arterial and venous thrombosis in patients with von Willebrand's disease: a critical review of the literature. J Thromb Thrombolysis 2006; 21 (02) 175-178
- 35 Dorgalaleh A, Baghaipour MR, Tabibian S. et al. Gastrointestinal bleeding in a newborn infant with congenital factor X deficiency and COVID-19-A common clinical feature between a rare disorder and a new, common infection. Int J Lab Hematol 2020; 42 (06) e277-e279
- 36 Quintavalle G, Coppola A, Ruggieri A. et al. Severe bleeding in a patient with factor XIII deficiency and COVID-19. Haemophilia 2021; 27 (01) e140-e142
- 37 Pinto Pereira J, Hantson P, Gerard L. et al. Management of COVID-19 coagulopathy in a patient with severe haemophilia A. Acta Haematol 2021; 144 (03) 319-321
- 38 Anžej Doma S, Lukič M. Severe COVID-19 infection management in a patient with mild haemophilia-a case report. Hematol Rep 2022; 14 (02) 103-107
- 39 Taranchenko YL, Martinez Garcia F, Benitez-Hidalgo O, Aguilar M, Massons J, Nuñez JH. COVID-19 infection after a total knee arthroplasty in a patient with hemophilia a: a case report. JBJS Case Connect 2020; 10 (03) 00537
- 40 Cui D, Zhang A, Liu A, Hu Q. Clinical findings in a patient with haemophilia A affected by COVID-19. Haemophilia 2020; 26 (04) e214-e216
- 41 Zanon E, Pasca S, Campello E, Spiezia L, Vettor R, Simioni P. How haemophilia A impacts severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) treatment: a case report. J Thromb Thrombolysis 2020; 50 (04) 795-798
- 42 Rivas-Pollmar MI, Álvarez-Román MT, Butta-Coll NV, Martín Salces M, García-Barcenilla S, Jiménez-Yuste V. Thromboprophylaxis in a patient with COVID-19 and severe hemophilia A on emicizumab prophylaxis. J Thromb Haemost 2020; 18 (09) 2202-2204
- 43 Dorgalaleh A, Dabbagh A, Tabibian S, Bahraini M, Rafieemehr H. Persistent hiccups in a patient with mild congenital factor V deficiency and COVID-19; clinical and laboratory finding of a rare bleeding disorder. Int J Lab Hematol 2021; 43 (02) e87-e88
- 44 Sattler L, Feugeas O, Hager C, Grunebaum L, Desprez D. COVID-19 in a pediatric patient with Glanzmann thrombasthenia. Pediatr Blood Cancer 2020; 67 (10) e28662
- 45 Tarawah R, Tarawah A. COVID-19 in von Willebrand disease type 3 child. Haemophilia 2021; 27: 140
- 46 Arun S, Cherian TG, Philip C. Multisystem inflammatory syndrome in a neonate with severe hemophilia - a diagnostic challenge in COVID times: a case report. BMC Pediatr 2022; 22 (01) 397
- 47 Vagrecha A, Stanco J, Majeed S, Kouides P, Acharya SS. Primary thromboprophylaxis in a patient with type 3 von Willebrand disease and severe COVID-19 infection. Haemophilia 2021; 27 (04) e517-e519
- 48 Urbaniak-Kujda D, Biernat MM, Skalec T, Jacków-Nowicka J, Windyga J, Wróbel T. Successful treatment of COVID-19 in a patient with severe haemophilia A on emicizumab prophylaxis in the intensive care unit. Haemophilia 2021; 27 (04) e567-e570