Mean serum D-dimer level to predict in-hospital mortality in COVID-19

Hayıroğlu, Mert İlker; Çiçek, Vedat; Kılıç, Şahhan; Çınar, Tufan

doi:10.1590/1806-9282.20200896

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Revista da Associação Médica Brasileira

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ORIGINAL ARTICLE • Rev. Assoc. Med. Bras. 67 (3) • Mar 2021 • https://doi.org/10.1590/1806-9282.20200896 copy

Mean serum D-dimer level to predict in-hospital mortality in COVID-19

Authorship SCIMAGO INSTITUTIONS RANKINGS

SUMMARY

OBJECTIVE:

The prognostic effect of the mean serum D-dimer levels, which was calculated from the first five days of hospitalization of the patients, has not been elucidated. This study aimed to evaluate the effect of mean D-dimer level about in-hospital mortality in patients hospitalized due to coronavirus disease-2019 (COVID-19) infection.

METHODS:

In this observational retrospective study, we examined the in-hospital prognostic value of mean D-dimer [D-dimer^{first day}+D-dimer^{third day}+D-dimer^{fifth day})/3 on 240 consecutive adult patients with COVID-19. Patients were stratified into tertiles according to their mean D-dimer starting from the lowest one. In-hospital mortality rates were compared between tertiles and the power of the mean D-dimer level was also presented by a receiver operating curve analysis.

RESULTS:

After adjustment for confounding baseline variables, mean D-dimer in tertile 3 was associated with 4.2-fold hazard ratio of in-hospital mortality (odds ratio [OR] 4.2; 95% confidence interval [CI] 1.8–20.1, p<0.001). A receiver-operating curve analysis revealed that the optimal cutoff value of the mean D-dimer to predict in-hospital mortality was 779 μg/L with 77% sensitivity and 83% specificity (area under the curve [AUC] 0.87; 95%CI 0.81–0.94; p<0.001).

CONCLUSION:

Patients with a higher mean D-dimer level should be followed-up more closely as they may be a candidate for a more aggressive treatment modality, such as biologic agents or convalescent plasma.

KEYWORDS:
COVID-19; D-dimer; In-hospital mortality

	Mean D-dimer level through index hospitalization period
	T1, n=80	T2, n=80	T3, n=80	p-value
Baseline characteristics
Age, years	50.1±14.8	53.8±14.6	59.6±15.1	0.001
Male gender, n(%)	42 (52.5)	43 (53.8)	43 (53.8)	0.983
Hypertension, n(%)	25 (31.3)	30 (37.5)	39 (48.8)	0.071
Diabetes mellitus, n(%)	20 (25.0)	15 (18.8)	26 (32.5)	0.135
Insulin dependency, n(%)	3 (3.8)	2 (2.5)	7 (8.8)	0.158
Hyperlipidemia, n(%)	1 (1.3)	3 (3.8)	8 (10.0)	0.033
COPD, n(%)	5 (6.3)	8 (10.0)	13 (16.3)	0.121
Coronary artery disease, n(%)	3 (3.8)	5 (6.3)	14 (17.5)	0.007
Chronic renal failure, n(%)	2 (2.5)	3 (3.8)	7 (8.8)	0.158
Atrial fibrillation, n(%)	1 (1.3)	1 (1.3)	1 (1.3)	1.000
Cerebrovascular disease, n(%)	0 (0.0)	2 (2.5)	2 (2.5)	0.362
Dementia, n(%)	1 (1.3)	1 (1.3)	1 (1.3)	1.000
Cancer, n(%)	0 (0.0)	2 (2.5)	5 (6.3)	0.061
Congestive heart failure, n(%)	0 (0.0)	2 (2.6)	6 (7.5)	0.028
Smoking, n(%)	10 (12.8)	11 (13.8)	6 (7.5)	0.406
Alcohol, n(%)	12 (15.0)	16 (20.0)	13 (16.3)	0.682
Admission symptoms n(%)
Fever	27 (33.8)	45 (56.3)	47 (58.8)	0.002
Cough	46 (57.5)	45 (56.3)	44 (55.7)	0.973
Dyspnea	10 (12.5)	18 (22.5)	22 (27.5)	0.059
Diarrhea	3 (3.8)	3 (3.8)	6 (7.5)	0.454
Myalgia	25 (31.6)	27 (33.8)	26 (32.5)	0.960
Weakness	28 (35.0)	25 (31.3)	21 (26.3)	0.485
Asymptomatic	13 (16.3)	5 (6.3)	3 (3.8)	0.012
Laboratory parameters
White blood cells, cells/μL	6.0±2.4	5.8±2.7	7.4±4.3	0.070
Lymphocytes	1.5±0.7	1.5±0.7	1.1±0.7	<0.001
Platelets, cells/μL	204.6±62.1	190.8±54.9	207.2±73.8	0.408
Hemoglobin, g/dL	13.4±1.7	13.2±1.8	13.0± 1.6	0.192
Glucose, mg/dL	106.6±28.2	117.3±41.9	126.2±62.9	0.169
Lactate dehydrogenase, U/L	449.8±261.0	452.1±137.3	634.3±594.7	<0.001
Alanine aminotransferase, U/L	36.3±27.0	35.7±27.2	39.1±45.0	0.298
Aspartate aminotransferase, U/L	28.4±15.8	26.6±13.5	32.0±30.7	0.729
Creatinine, mg/dL	0.9±0.2	0.9±0.2	1.0±0.4	0.074
Potassium, mEq/L	4.2±0.3	4.1±0.3	4.2±0.5	0.264
Sodium, mEq/L	137.1±3.8	136.8±3.7	136.3±3.9	0.317
D-dimer, μg/L^{first day}	213.0±72.3	372.9±184.3	1630.1±1682.0	<0.001
D-dimer, μg/L^{third day}	213.0±71.5	383.8±114.5	1127.7±963.0	<0.001
D-dimer, μg/L^{fifth day}	279.9±61.3	390.5±137.9	1405.2±1020.3	<0.001
Mean D-dimer, μg/mL	247.4±28.3	382.4±86.4	1387.6±957.1	<0.001
C-reactive protein, mg/dL	35.3±46.5	50.0±68.5	75.8±74.8	<0.001
Albumin, g/L	42.2±6.0	40.3±5.5	37.0±6.3	<0.001
Troponin, ng/L	10.9±15.4	11.3±17.8	93.7±535.4	<0.001
Pneumonia region in the lungs
Bilateral	57 (71.3)	64 (80.0)	60 (75.0)	0.435
Left	16 (20.0)	12 (15.0)	9 (11.3)	0.307
Right	7 (8.8)	4 (5.0)	11 (13.8)	0.157

	Univariable analysis			Multivariable analysis
	p-value	OR	95%CI	p-value	OR	95%CI
Age	<0.001	1.098	1.055–1.142	0.027	1.091	1.010–1.179
Hypertension	0.017	3.019	1.214–7.509	–	–	–
Diabetes mellitus	0.028	2.729	1.114–6.684	–	–	–
COPD	<0.001	6.349	2.351–17.148	–	–	–
Coronary artery disease	<0.001	8.327	2.992–23.175	–	–	–
Chronic renal failure	0.001	8.866	2.541–30.928	–	–	–
Congestive heart failure	0.014	6.663	1.477–30.053	–	–	–
White blood cells	<0.001	1.475	1.296–1.679	<0.001	1.605	1.287–2.001
Lymphocytes	0.009	0.282	0.110–0.725	0.044	0.437	0.195–0.978
Lactate dehydrogenase	0.002	1.002	1.001–1.004	0.012	1.003	1.001–1.006
Troponin	<0.001	1.052	1.029–1.076	0.048	1.045	1.002–1.093
Albumin	<0.001	0.844	0.780–0.913	–	–	–
C-reactive protein	<0.001	1.011	1.006–1.016	–	–	–

	Mean D-dimer level through index hospitalization period
	T1, n=80	T2, n=80	T3, n=80
In-hospital mortality
Number of patients	0	3	19
Case rate, %	0.0	3.8	23.8
In-hospital mortality, OR (95% CI)
Model 1: unadjusted	1[Reference]	4.7 (1.5–8.1)	7.9 (2.2–28.2)
Model 2: adjusted for all covariate^sa	1[Reference]	2.8 (1.2–6.9)	5.2 (1.8–20.1)

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[1] * Corresponding author: drtufancinar@gmail.com