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Anemia and Enhancement of Coagulation Are Associated during Severe COVID-19 Infection

T. Helin1, M. Lemponen1, T. Lahtiharju1, R. Lassila2, L. Joutsi-Korhonen1

1Coagulation Disorders Unit, HUS Diagnostics Center, HUSLAB, Helsinki University Hospital and University of Helsinki, Helsinki, Finland, 2Coagulation Disorders Unit, Helsinki University Hospital, Research Program Unit in Systems Oncology, University of Helsinki, Helsinki, Finland

Abstract Number: PB0204

Meeting: ISTH 2021 Congress

Theme: COVID and Coagulation » COVID and Coagulation, Clinical

Background: Coagulation disturbances are common during severe COVID-19 infection. While classic disseminated intravascular coagulation (DIC) is rare, inflammation markedly enhances coagulation activity in certain COVID-19 patients.

Aims: We examined laboratory markers in hospitalized patients during the first wave of the pandemic in Finland to differentiate between patients of severe phenotype (ICU-admitted vs.ward patients) using inflammatory and coagulation markers, and blood cell counts.

Methods: We analyzed a wide panel of routine coagulation tests from anonymously collected samples of 78 hospitalized COVID-19 patients treated in specific wards, either in ICU(n=34) or medical wards (n=44), at Helsinki University hospital in April-May 2020. These data were supplemented with the laboratory information system results, including complete blood count, creatinine and C reactive protein (CRP).

Results: Inflammatory and coagulation markers were elevated in most patients: CRP in 94%, fibrinogen 77%, D-dimer 74%, FVIII 52% and platelet count in 37%. Anemia and decreased erythrocyte count were common, especially in men (73% vs, 44% in women; Table). Men admitted to the ICU during their hospital stay presented with higher platelet count, leukocytes, and FVIII but lower hemoglobin. Also, both men and women in ICU had higher fibrinogen and D-dimer (p<0.01). Not a single patient exhibited DIC criteria, but 31% had D-dimer level of at least 1.5 mg/L. Antithrombin was reduced in 47% of the patients but did not distinguish severity. In contrast, high D dimer and the presence of anemia clearly associated with severity. Patient age and FVIII levels were also higher in anemic patients (Figure), and among ICU-admitted patients.

N Mean Median SD Min Max Ref interval Below ref interval, N (%) Above ref interval. N (%)
Prothrombin time (%) 75 101 100 24 23 171 70-130% 4 (5.3%) 8 (10.7%)
APTT (s) 67 40 34 17 18 103 28-37 s 2 (3.0%) 19 (28.4%)
FVIII (IU/mL) 69 183 177 106 30 489 60-160% 9 (13.0%) 36 (52.2%)
Fibrinogen (g/L) 74 5.8 5.8 2.3 0.4 12.3 2.0-4.0 g/L 2 (2.7%) 57 (77.0%)
D dimer (mg/l) 78 2.2 .9 6.5 0.2 56.7 < 0.5 mg/L – 58 (74.4%)
Antithrombin (U/mL) 66 0.82 0.88 0.33 0.07 1.49 0.85-1.25 U/mL 31 (47%) 4 (6.1%)
CRP (mg/L) 76 81 56 84 4 398 < 4 mg/L – 71 (94.4%)
Hgb women (g/dL) 34 11.7 12.0 1.5 8.4 14.0 11.7-15.5 g/dL 16 (44.1%) 0 (0%)
Hgb men (g/dL) 44 12.0 12.3 2.2 7.3 17.2 13.4-16.7 g/dL 32 (72.7%) 1 (2.3%)

Laboratory findings in hospitalized COVID-19 patients

Stacked histogram of hemoglobin distribution among patients (A), hemoglobin across different D dimer levels (B), FVIII (C) and (D) D-Dimer according to their anemia status. Anemia was defined as Hgb below reference interval. The highest D-dimer result of 57 mg/L is not shown. Variables presented were selected according to medians with significant difference (Mann Whitney U test). The number of patients with anemia was 48/78 (62%) in total, men 32/44 (72%), women 16/34 (47%), ICU-patients 27/34 (79%), non-ICU patients 7/44 (16%). Lines, reference intervals; Thick line in box, median; box, first and third quartiles; whiskers, range; outlier ≥1.5 box lengths from median, circle; extreme outlier ≥3.0 box lengths from median, asterisk.

 

Conclusions: High inflammatory response, translated to elevated FVIII, fibrinogen and D-dimer and characterized hospitalized COVID-19 patients. In our patients, contrary to earlier reports, anemia was common, especially in men, and associated with coagulation activity, suggesting the role of red cells on COVID-19 pathology. We aim to further detect cell-derived microvesicles in these patients.

To cite this abstract in AMA style:

Helin T, Lemponen M, Lahtiharju T, Lassila R, Joutsi-Korhonen L. Anemia and Enhancement of Coagulation Are Associated during Severe COVID-19 Infection [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/anemia-and-enhancement-of-coagulation-are-associated-during-severe-covid-19-infection/. Accessed August 16, 2022.

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