Role of red blood cells in clinically relevant bleeding tendencies and complications

Lassila, Riitta; Weisel, John W.

doi:10.1016/j.jtha.2023.05.009

Cited by 11 publications

(5 citation statements)

References 54 publications

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“…During acute COVID‐19, an increased D‐dimer value is the most typical net finding of the coagulopathy, 38 and prolonged elevation has been reported up to 4 months after initial infection 14,16 . Furthermore, in a previous study, low hemoglobin has been associated with high FVIII activity and D‐dimer levels, 31 compatible with the procoagulant role of red blood cells 39 . Hypercoagulation in acute COVID‐19 is driven by the interaction between thrombosis and inflammation 10 .…”

Section: Discussionmentioning

confidence: 93%

Complete blood count, coagulation biomarkers, and lung function 6 months after critical COVID‐19

Kattainen,

Pitkänen,

Reijula

et al. 2024

Acta Anaesthesiol Scand

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BackgroundUnderstanding the recovery of post‐COVID‐19 organ dysfunction is essential.We evaluated coagulation 6 months post‐COVID‐19, examining its recovery and association with lung function.MethodsPatients treated for COVID‐19 at intensive care units between 3/2020 and 1/2021 were analyzed for complete blood count (CBC) and coagulation biomarkers (prothrombin time activity (%) (PT%), activated partial thromboplastin time (APTT), fibrinogen, coagulation factor VIII (FVIII), antithrombin (AT), and D‐dimer) during the 6 months post‐hospitalization. Results were compared with acute phase values and correlated with pulmonary function tests (PFT), including forced vital capacity (FVC) and hemoglobin‐corrected diffusing capacity percentage of predicted (DLCOc%), recorded 6 months post‐hospitalization. We examined the association between coagulation biomarkers and DLCOc% using linear regression with age, sex, and invasive mechanical ventilation (IMV) duration, and FVIII (correlated with DLCOc%) as covariates.ResultsMost CBCs and coagulation biomarkers had median values within the normal range. However, only 21% (15/70) of patients achieved full normalization of all biomarkers. Compared to acute COVID‐19, hemoglobin, PT%, and AT increased, while leukocytes, fibrinogen, FVIII, and D‐dimer decreased. Despite decreased levels, FVIII remained elevated in 46% (31/68), leukocytes in 26% (18/70), and D‐dimer in 27% (18/67) at 6 months. A weak negative correlation (r = −0.37, p = .036) was found between DLCOc% and FVIII. Multivariable analysis revealed a weak, independent association between DLCOc% and FVIII. Excluding patients with anticoagulation therapy, FVIII no longer correlated with DLCOc%, while AT showed a moderate correlation with DLCOc%.ConclusionOnly a few patients had normal CBC and coagulation biomarker values 6 months after critical COVID‐19. A weak negative correlation between DLCOc% and FVIII suggests that deranged coagulation activity may be associated with reduced diffusing capacity.

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Section: Discussionmentioning

confidence: 93%

Complete blood count, coagulation biomarkers, and lung function 6 months after critical COVID‐19

Kattainen,

Pitkänen,

Reijula

et al. 2024

Acta Anaesthesiol Scand

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“…Anemia, which refers to low levels of healthy red blood cells or hemoglobin, was associated with increased bleeding in our study. Red blood cells contribute not only to transporting oxygen but also to initiating hemostasis together with platelets and to stabilizing fibrin and clot structure ( Lassila and Weisel, 2023 ). Their role has made anemia an independent risk factor for major bleeding during anticoagulant therapy.…”

Section: Discussionmentioning

confidence: 99%

Construction of a risk scoring system using clinical factors and RYR2 polymorphisms for bleeding complications in patients on direct oral anticoagulants

Jang,

Kim,

Choi

et al. 2023

Front. Pharmacol.

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Introduction: Bleeding is one of the most undesirable complications of direct oral anticoagulants (DOACs). While the ryanodine receptor (RYR2) has been related to cardiac diseases, research on bleeding complications is lacking. This study aimed to elucidate the association between RYR2 and bleeding risk to develop the risk scoring system in patients treated with DOACs.Methods: This study was a retrospective analysis of prospectively collected samples. We selected ten SNPs within the RYR2 gene, and two models were constructed (Model I: demographic factors only, Model II: demographic and genetic factors) in multivariable analysis. Independent risk factors for bleeding were used to develop a risk scoring system.Results: A total of 447 patients were included, and 49 experienced either major bleeding or clinically relevant non-major bleeding. In Model I, patients using rivaroxaban and experiencing anemia exhibited an increased bleeding risk after adjusting for covariates. Upon incorporating genetic factors into Model I, a significant association with bleeding was also observed in cases of overdosing on DOACs and in patients with a creatinine clearance (CrCl) < 30 mL/min, in addition to rivaroxaban and anemia (Model II). Among genetic factors, RYR2 rs12594 GG, rs17682073 AA, rs3766871 GG, and rs6678625 T alleles were associated with bleeding complications. The area under the receiver operating characteristic curve (AUROC) of Model I was 0.670, whereas that of Model II increased to 0.803, demonstrating better performance with the inclusion of genetic factors. Using the significant variables in Model II, a risk scoring system was constructed. The predicted bleeding risks for scores of 0, 1–2, 3–4, 5–6, 7–8, and 9–10 points were 0%, 1.2%, 4.6%, 15.7%, 41.7%, and 73.3%, respectively.Conclusion: This study revealed an association between RYR2 and bleeding complications among patients taking DOACs and established a risk scoring system to support individualized DOAC treatment for these patients.

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“…Anaemia predisposes to bleeds due to impaired primary haemostasis and may diminish physiological red blood cell-mediated thrombin generation. [14][15][16] Most people with anaemia do not bleed overtly, even while on OAC, but continued occult bleeding consumes iron and haemoglobin. However, the reserve of the red cells is unavailable upon an emergent bleeding event, and anaemia in anticoagulated patients exposes them not only to bleeding events, but also to stroke and mortality.…”

Section: Discussionmentioning

confidence: 99%

Associations of anaemia with bleeding and thrombotic complications in patients with atrial fibrillation treated with warfarin: a registry-based nested case–control study

Helin,

Raatikainen,

Lehto

et al. 2023

BMJ Open

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ObjectivesWe studied association of laboratory testing beyond the international normalised ratio (INR) with bleeding and stroke/transient ischaemic attack (TIA) outcomes in patients with atrial fibrillation treated with warfarin.DesignThis was a retrospective nested case–control study from the Finnish Warfarin in Atrial Fibrillation (FinWAF) registry (n=54 568), reporting the management and outcome in warfarin-anticoagulated patients. Associations of blood count test frequency and results were assessed together with risk of bleeding or stroke/TIA during 5-year follow-up.SettingNational FinWAF registry, with data from all six hospital districts. Follow-up period for complications was 1 January 2007–31 December 2011.ParticipantsA total of 54 568 warfarin-anticoagulated patients.ResultsThe number of patients with bleeding was 4681 (9%) and stroke/TIA episodes, 4692 (9%). In patients with bleeds, lower haemoglobin (within 3 months) preceded the event compared with the controls (median 126 vs 135 g/L; IQR 111–141 g/L vs 123–147 g/L, p<0.001), while patients with stroke/TIA had only modestly lower INR (median 2.2 vs 2.3; 1.8–2.6 vs 2.1–2.7, p<0.001). When the last measured haemoglobin was below the reference value (130 g/L for men, 120 g/L for women), the OR for a bleeding complication was 2.9 and stroke/TIA, 1.5. If the haemoglobin level was below 100 g/L, the complication risk increased further by 10-fold. If haemoglobin values were repeatedly (more than five times) low during the preceding 3 months, future OR was for bleeds 2.3 and for stroke/TIA 2.4.ConclusionsThe deeper the anaemia, the higher the risk of bleeding and stroke/TIA. However, INR remained mainly at its target and only occasionally deviated, failing to detect the complication risk. Repeated low haemoglobin results, compatible with persistent anaemia, refer to suboptimal management and increased the complication risk in anticoagulated patients.

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Role of red blood cells in clinically relevant bleeding tendencies and complications

Cited by 11 publications

References 54 publications

Complete blood count, coagulation biomarkers, and lung function 6 months after critical COVID‐19

Complete blood count, coagulation biomarkers, and lung function 6 months after critical COVID‐19

Construction of a risk scoring system using clinical factors and RYR2 polymorphisms for bleeding complications in patients on direct oral anticoagulants

Associations of anaemia with bleeding and thrombotic complications in patients with atrial fibrillation treated with warfarin: a registry-based nested case–control study

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