Contribution of genotypes in Prothrombin and Factor V Leiden to COVID‐19 and disease severity in patients at high risk for hereditary thrombophilia

Kiraz, Aslıhan; Sezer, Özlem; Alemdar, Adem; Canbek, Sezin; Duman, Nilgun; Bişgin, Atıl; Cora, Tulin; Ruhi, Hatice Ilgın; Ergören, Mahmut Çerkez; Geçkinli, Bilgen Bilge; Sağ, Şebnem Özemri; Gözden, Hilmi Erdem; Öz, Özlem; Altintas, Zuhal Mert; Yalçıntepe, Sinem; Keski̇n, Adem; Yabacı, Ayşegül; Paskal, Şeyma Aktaş; Yurekli, Ugur; Demirtas, Mercan; Evren, Emine Ünal; Hanta, Abdullah; Basdemirci, Muserref; Süer, Hüseyin Kaya; Balta, Burhan; Koçak, Nadir; Karabulut, Halil Gürhan; Çobanoğullari, Havva; Ateş, Esra Arslan; Bozdoğan, Sevcan Tuğ; Eker, Damla; Ekinci, Sadiye; Nergiz, Süleyman; Tuncali, Timur; Yagbasan, Serap; Alavanda, Ceren; Kutlay, Nüket Yürür; Evren, Hakan; Erdoğan, Murat; Altıner, Şule; Şanlıdağ, Tamer; Gönen, Gizem Akıncı; Vicdan, Arzu; Eras, Nazan; Eker, Hatice Koçak; Balasar, Özgür; Tuncel, Gülten; Dündar, Munis; Gürkan, Hakan; Temel, Şehime Gülsün

doi:10.1002/jmv.28457

Cited by 5 publications

(3 citation statements)

References 31 publications

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“…39 In this study, 4 pregnant women with FMF were admitted to the ICU, and 1 of them died. In previous studies, patients with selective IgA deficiency 40 and Factor V Leiden thrombophilia 41 had a higher risk of severe COVID-19 infection. In this study, 1 pregnant woman with selective IgA deficiency and another woman with Factor V Leiden thrombophilia needed intensive care treatment.…”

Section: Discussionmentioning

confidence: 85%

Clinical Characteristics, Outcomes, and Risk Factors for Mortality in Pregnant/Puerperal Women with COVID-19 Admitted to ICU in Turkey: A Multicenter, Retrospective Study from a Middle-Income Country

Baykara,

Arslantaş

et al. 2024

J Intensive Care Med

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Background Coronaviruses have been the cause of 3 major outbreaks during the last 2 decades. Information on coronavirus diseases in pregnant women is limited, and even less is known about seriously ill pregnant women. Data are also lacking regarding the real burden of coronavirus disease 2019 (COVID-19) infection in pregnant women from low/middle-income countries. The aim of this study was to determine the characteristics and clinical course of COVID-19 in pregnant/puerperal women admitted to ICUs in Turkey. Methods This was a national, multicenter, retrospective study. The study population comprised all SARS-CoV-2-infected pregnant/puerperal women admitted to participating ICUs between 1 March 2020 and 1 January 2022. Data regarding demographics, comorbidities, illness severity, therapies, extrapulmonary organ injuries, non-COVID-19 infections, and maternal and fetal/neonatal outcomes were recorded. LASSO logistic regression and multiple logistic regression analyses were used to identify predictive variables in terms of ICU mortality. Results A total of 597 patients (341 pregnant women, 255 puerperal women) from 59 ICUs in 44 hospitals were included and of these patients, 87.1% were unvaccinated. The primary reason for ICU admission was acute hypoxemic respiratory failure in 522 (87.4%), acute hypoxemic respiratory failure plus shock in 14 (2.3%), ischemic cerebrovascular accident (CVA) in 5 (0.8%), preeclampsia/eclampsia/HELLP syndrome in 6 (1.0%), and post-caesarean follow-up in 36 (6.0%). Nonsurvivors were sicker than survivors upon ICU admission, with higher APACHE II ( p < 0.001) and SOFA scores ( p < 0.001). A total of 181 (30.3%) women died and 280 (46.6%) had received invasive mechanical ventilation (IMV). Myocardial injury, the highest SOFA score during ICU stay, LDH levels on admission, the highest levels of AST during ICU stay, average daily dose of corticosteroids, IMV, prophylactic dose anticoagulation (compared with therapeutic dose anticoagulation), PaO2/FiO2 ratio <100, pulmonary embolism, and shock were identified as predictors of mortality. Rates of premature birth (46.4%), cesarean section (53.7%), fetal distress (15.3%), stillbirth (6.5%), and low birth weight (19.4%) were high. Rates of neonatal death (8%) and respiratory distress syndrome (21%) were also high among live-born infants. Conclusions Severe/critical COVID-19 infection during the pregnancy/puerperal period was associated with high maternal mortality and fetal/neonatal complication rates in Turkey.

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Section: Discussionmentioning

confidence: 85%

Clinical Characteristics, Outcomes, and Risk Factors for Mortality in Pregnant/Puerperal Women with COVID-19 Admitted to ICU in Turkey: A Multicenter, Retrospective Study from a Middle-Income Country

Baykara,

Arslantaş

et al. 2024

J Intensive Care Med

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“…In turn, the presence of venous thromboembolism in patients with COVID-19 was associated with an increased risk of lethal outcome [7]. The results of the large cohort study by Kiraz et al also indicate an association of carriage of the Leiden mutation with an increased risk of complications/lethality of COVID-19 [4]. There are also data indicating that patients with Leiden mutation produce higher levels of soluble fibrin, which may serve as a cofactor in tissue plasminogen activator-induced plasminogen activation, leading to a more sustained activation of fibrinolysis with the higher fibrinogen and fibrin-degradation products output [28].…”

Section: Chest X-ray Of the Patient Bilateral Pulmonary Infiltratesmentioning

confidence: 98%

“…Numerous theoretical overviews and research articles indicate the need for genetic testing in patients with COVID-19 to determine the genetic profile of proteins involved in thrombophilia [3][4][5][6][7][8][9]. This is due to the fact that the carrier of hereditary thrombophilia gene variants has been associated with a complicated course and mortality in patients with COVID-19.…”

Section: / XXVIII /mentioning

confidence: 99%

Leiden mutation (rs6025) in a severe COVID-19 pneumonia patient with Down syndrome: a clinical case

Pokhylko,

Cherniavska,

Fishchuk

et al. 2023

Med. perspekt.

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COVID-19 was first reported in December 2019 in Wuhan (Hubei Province, China). Later, the pandemic of this disease took the world by storm, challenging the medical community. Its clinical manifestations vary from asymptomatic to a severe course that requires hospitalization and intensive therapy with oxygen support. The mortality rate in patients with a severe course of COVID-19 can exceed 50% The majority of fatal cases of COVID-19 were associated with thrombotic events, despite the prophylactic use of anticoagulant therapy. Numerous theoretical overviews and research articles indicate the need for genetic testing in patients with COVID-19 to determine the genetic profile of proteins involved in thrombophilia. According to the researchers, the Leiden mutation (G1691A, rs6025) of the FV gene is one of the promising candidates for testing. The aim of the work was to demonstrate the clinical features of the severe course of COVID-19 in the presence of the Leiden mutation. 58 patients with COVID-19 of the intensive care unit were genotyped. The Leiden mutation in the heterozygous state was found only in one patient, who had Down syndrome. The Leiden mutation was detected with a frequency of 1.72% in the investigated group. The described clinical case clearly showed that individuals with Down syndrome, associated with hereditary thrombophilia are at risk of undesirable clinical consequences in the treatment of COVID-19. The condition of the patient with the Leiden mutation was severe when admitted to the hospital. The score according to the sequential organ failure assessment scale was 2 points. Bilateral multisegmental pneumonia was detected on the X-ray. On the second day after admission, due to the development of acute respiratory distress syndrome and multiple organ failure, the patient was transferred to the intensive care unit, where he received oxygen therapy through a facial mask. Medical treatment was carried out according to the protocol: non-steroidal anti-inflammatory drugs, antibacterial therapy, anticoagulants, sympatho¬mimetics, and glucocorticosteroids. Despite the medical measures taken, progression of respiratory failure, renal failure, and portal hypertension was noted. On the 11th day, the patient developed asystole. Resuscitation measures were unsuccessful. Thus, the described case of a severe course of COVID-19 in a carrier of a heterozygous variant of the Leiden mutation with Down syndrome confirms the recommendations regarding the need for genetic testing for thrombophilia in high-risk groups and the appointment of personalized measures to prevent complications.

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Deciphering the host genetic factors conferring susceptibility to severe COVID-19 using exome sequencing

Uslu,

Ozcelik,

Zararsiz

et al. 2023

Genes Immun

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Contribution of genotypes in Prothrombin and Factor V Leiden to COVID‐19 and disease severity in patients at high risk for hereditary thrombophilia

Cited by 5 publications

References 31 publications

Clinical Characteristics, Outcomes, and Risk Factors for Mortality in Pregnant/Puerperal Women with COVID-19 Admitted to ICU in Turkey: A Multicenter, Retrospective Study from a Middle-Income Country

Clinical Characteristics, Outcomes, and Risk Factors for Mortality in Pregnant/Puerperal Women with COVID-19 Admitted to ICU in Turkey: A Multicenter, Retrospective Study from a Middle-Income Country

Leiden mutation (rs6025) in a severe COVID-19 pneumonia patient with Down syndrome: a clinical case

Deciphering the host genetic factors conferring susceptibility to severe COVID-19 using exome sequencing

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