Serial values of hematologic variables and deep venous thrombosis: Red cell distribution width is associated with deep venous thrombosis

Patel, Govind R.; Mahapatra, Manoranjan; Aggarwal, Sadhna; Saxena, Renu

doi:10.1016/j.htct.2022.11.005

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Hematology, Transfusion and Cell Therapy

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Original article • Hematol., Transfus. Cell Ther. 46 (1) • Jan-Mar 2024 • https://doi.org/10.1016/j.htct.2022.11.005 copy

Serial values of hematologic variables and deep venous thrombosis: Red cell distribution width is associated with deep venous thrombosis

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Introduction

As 30 to 50% of deep venous thrombosis (DVT) cases remain idiopathic, an increased focus on hematologic variables may therefore reveal novel correlates of DVT. Very few studies have investigated the association of hematological parameters with DVT and the causal relationship between them is still to be elucidated. Therefore, we aimed to investigate the association between serial values of hematologic variables and DVT.

Methods

Complete blood count parameters were serially measured at baseline and then at approximately 3-month intervals for 12 months in 152 adults with the first episode of DVT and 152 age- and sex-matched controls. The odds ratio (OR) with the 95% confidence interval (95%CI) was calculated as a measure of association between hematological parameters and DVT.

Results

The red cell distribution width (RDW) was the only hematologic variable which showed an independent and consistent association with DVT at all time points (multivariable-adjusted OR [95%CI] 3.38 [1.28 - 8.91] at baseline, 2.24 [0.85 - 5.92] at 3 months and 2.12 [0.81 - 5.55] at 12 months for RDW > 14.0%). This association was higher for provoked DVT than unprovoked DVT and for DVT plus pulmonary embolism than DVT alone. No significant correlation was found between the high RDW and classical thrombotic risk factors, except malignancy.

Conclusions

We demonstrated an independent and consistent association of the high RDW with the first episode of DVT in adult patients. The study was probably underpowered to evaluate the association between the high RDW and recurrent DVT. Further large studies with long follow-up are needed to confirm this association.

Keywords
Deep venous thrombosis; Red cell distribution width; Hematologic variables; Venous thromboembolism; Association

Variable	Cases (n = 152)	Controls (n = 152)	p-value
Demographic characteristics
Age (years)	41.5 (31 - 50)	39.0 (32 - 50)	0.212
Male sex	88 (58)	88 (58)	1
Smoking	21 (13.8)	14 (9.2)	0.28
BMI (kg/m²)	24.8 (22.9 - 28.4)	23.5 (21.2 - 26.7)	0.136
Obesity (BMI ≥ 30 kg/m²)	20 (13.1)	11 (7.2))	0.128
Duration of DVT (days)^a a Time interval between diagnosis of DVT and enrollment into the study. )	7 (5-12)	-	-
Comorbidities^b b Hypertension, diabetes mellitus, coronary artery disease, chronic obstructive pulmonary disease, cerebrovascular disease, chronic kidney disease, dyslipidemia and others. )	48 (31.6)	-	-
DVT subtypes
DVT alone	140 (92.1)	-	-
DVT plus PE	12 (7.9)	-	-
Unprovoked DVT	72 (47.4)	-	-
Provoked DVT	80 (52.6)	-	-
Location of DVT
Lower limb DVT	138 (90.8)	-	-
-Proximal DVT	132 (95.7)	-	-
-Distal DVT	6 (4.3)	-	-
-Unilateral DVT	124 (89.9)	-	-
-Bilateral DVT	14 (10.1)	-	-
Upper limb DVT	14 (9.2)	-	-
Risk factors for DVT
Malignancy	18 (11.8)	-	-
Surgery	12 (7.9)	-	-
Trauma	4 (2.6)	-	-
Immobilization	16 (10.5)	-	-
Air travel	2 (1.3)	-	-
Pregnancy/postpartum state	12 (7.9)	-	-
Estrogen (OCP/HRT) use	12 (7.9)	-	-

Parameter	At baseline			At 3 months			At 12 months
Parameter	Cases (n = 152)	Controls (n = 152)	p-value	Cases (n = 152)	Controls (n = 152)	p-value	Cases (n = 152)	Controls (n = 152)	p-value
RBC count (10¹²/L)	4.42 (3.79 - 5.08)	4.63 (3.89 - 5.09)	0.399	4.58 (4.20 - 4.97)	4.62 (4.34 - 5.04)	0.478	4.86 (4.20 - 5.30)	4.79 (4.30 - 5.18)	0.910
Hemoglobin (g/dL)	12.6 (11.5 - 13.9)	13.0 (12.2 - 14.3)	0.179	12.9 (12 - 14.0)	13.8 (12.6 - 14.2)	0.188	13.3 (12.3 - 14.2)	13.4 (12.7 - 14.2)	0.498
Hematocrit (%)	38.2 (33.8 - 41.6)	40.4 (34.1 - 42.9)	0.456	39.8 (35.0 - 42.5)	41.9 (35.8 - 43.5)	0.198	40.0 (36.8 - 42.3)	42.5 (40.7 - 49.4)	0.749
MCV (fL)	85.5 (75.2 - 92.4)	85.4 (71.9 - 109)	0.884	85.2 (79.4 - 90.9)	85.2 (79.4 - 90.6)	0.985	85.1 (78.2 - 90.9)	85.9 (75.6 - 100)	0.417
MCH (pg)	27.0 (25.2 - 30.0)	28.2 (25.4 - 30.8)	0.359	27.7 (25.7 - 30.2)	27.5 (25.9 - 30.5)	0.885	28.2 (26.5 - 29.9)	28.2 (27.8 - 29.3)	0.796
MCHC (g/dL)	31.8 (30.1 - 33.0)	32.3 (30.6 - 32.7)	0.317	32.3 (30.7 - 33.6)	32.4 (30.8 - 33.7)	0.715	32.9 (31.2 - 33.9)	33.1 (32.1 - 34.3)	0.193
RDW (%)	15.4 (13.8 - 16.6)	13.6 (12.9 - 14.5)	< 0.001	14.5 (13.4 - 15.5)	13.7 (12.8 - 14.2)	0.001	14.3 (13.2 - 15.1)	13.7 (12.8 - 14.5)	0.011
TLC (10⁹/L)	8.03 (6.93 - 9.89)	8.50 (6.30 - 9.19)	0.476	7.33 (6.23 - 9.01)	7.66 (6.78 - 9.30)	0.700	7.40 (6.27 - 8.55)	7.88 (6.30 - 8.60)	0.925
ANC (10⁹/L)	5.31 (3.95 - 6.60)	5.03 (3.60 - 5.90)	0.187	4.48 (3.65 - 5.46)	4.69 (3.93-6.51)	0.446	4.30 (3.74 - 54.7)	4.58 (3.83 - 5.62)	0.824
ALC (10⁹/L)	2.16 (1.45 - 2.54)	2.27 (1.76 - 2.53)	0.866	1.97 (1.60 - 2.37)	1.99 (1.75 - 2.37)	0.634	1.95 (1.80 - 2.45)	1.97 (1.90 - 2.19)	0.927
AMC (10⁹/L)	0.61 (0.46 - 0.72)	0.60 (0.32 - 0.70)	0.859	0.60 (0.48 - 0.70)	0.62 (0.42 - 0.70)	0.775	0.51 (0.43 - 0.63)	0.49 (0.41 - 0.63)	0.801
Platelet count (10⁹/L)	219.5 (149.7 - 477.8)	228.5 (173.7 - 338.8)	0.600	222 (136 - 310.5)	229 (170 - 314)	0.670	223.5 (136.7 - 311.2)	225.5 (168.2 - 312.2)	0.761
MPV (fL)	9.9 (7.7 - 12.5)	9.6 (7.6 - 10.9)	0.294	9.6 (7.4 - 11.0)	9.7 (7.9 - 11.1)	0.435	9.4 (7.3 - 10.9)	9.7 (8.0 - 11.1)	0.962

Parameter	At baseline		At 3 months		At 12 months
Parameter	OR (95%CI)	p-value	OR (95%CI)	p-value	OR ((95%CI)	p-value
RBC count (10¹²/L)	0.79 (0.47 - 1.35)	0.396	0.78 (0.39 - 1.55)	0.474	1.04 (0.55 - 1.96)	0.910
Hemoglobin (g/dL)	0.83 (0.63 - 1.08)	0.180	0.81 (0.60 - 1.10)	0.188	0.88 (0.63 - 1.24)	0.494
Hematocrit (%)	0.97 (0.91 - 1.04)	0.453	0.94 (0.86 - 1.03)	0.198	0.98 (0.89 - 1.09)	0.747
MCV (fL)	1.00 (0.96 - 1.04)	0.883	1.00 (0.95 - 1.06)	0.985	0.98 (0.93 - 1.03)	0.414
MCH (pg)	0.95 (0.84 - 1.06)	0.356	0.99 (0.85 - 1.15)	0.884	0.98 (0.82 - 1.16)	0.794
MCHC (g/dL)	0.90 (0.73 - 1.04)	0.315	0.96 (0.77 - 1.19)	0.712	0.83 (0.63 - 1.09)	0.193
RDW (%)	2.20 (1.48 - 3.26)	< 0.001	1.85 (1.25 - 2.74)	0.002	1.62 (1.10 - 2.38)	0.014
TLC (10⁹/L)	1.00 (0.99 - 1.00)	0.472	1.00 (0.99 - 1.00)	0.700	1.00 (0.99 - 1.00)	0.924
ANC (10⁹/L)	1.00 (0.99 - 1.00)	0.188	1.00 (0.99 - 100)	0.442	1.00 (0.99 - 1.00)	0.822
ALC (10⁹/L)	1.00 (0.99 - 1.00)	0.864	1.00 (0.99 - 1.00)	0.631	1.00 (0.99 - 1.00)	0.926
AMC (10⁹/L)	1.00 (0.99 - 1.00)	0.857	1.00 (0.99 - 1.00)	0.773	1.00 (0.99 - 1.00)	0.799
Platelet count (10⁹/L)	0.96 (0.77 - 1.10)	0.600	0.88 (0.65 - 1.21)	0.761	0.85 (0.61 - 1.19)	0.764
MPV (fL)	1.09 (1.01 - 1.20)	0.382	1.00 (1.04 - 1.12)	0.405	1.00 (0.96 - 1.11)	0.549

DVT subgroup	Time point	RDW (%)		High RDW (> 14.0%)
		Univariate analysis	Multivariate analysis	Univariate analysis	Multivariate analysis
		OR (95%CI)	OR (95%CI)^a a adjusted for age, sex, body mass index, smoking status, red blood cell count, hemoglobin, hematocrit, platelet count, mean platelet volume, classical thrombotic risk factors (malignancy, surgery/trauma, immobilization, pregnancy/postpartum state and estrogen use), comorbidities (obesity, hypertension, diabetes mellitus, coronary artery disease, chronic obstructive pulmonary disease, cerebrovascular disease and chronic kidney disease) and C-reactive protein. )	OR (95%CI)	OR (95%CI)^a a adjusted for age, sex, body mass index, smoking status, red blood cell count, hemoglobin, hematocrit, platelet count, mean platelet volume, classical thrombotic risk factors (malignancy, surgery/trauma, immobilization, pregnancy/postpartum state and estrogen use), comorbidities (obesity, hypertension, diabetes mellitus, coronary artery disease, chronic obstructive pulmonary disease, cerebrovascular disease and chronic kidney disease) and C-reactive protein. )
All cases	At baseline	2.20 (1.48 - 3.26)	2.05 (1.33 - 3.15)	4.52 (1.84 - 11.09)	3.38 (1.28 - 8.91)
	At 3 months	1.85 (1.25 - 2.74)	1.63 (1.11 - 2.40)	3.24 (1.33 - 7.88)	2.24 (0.85 - 5.92)
	At 12 months	1.62 (1.10 - 2.38)	1.48 (1.00 - 2.17)	3.04 (1.23 - 7.50)	2.12 (0.81 - 5.55)
Unprovoked DVT	At baseline	2.10 (1.30 - 3.38)	2.09 (1.30 - 3.35)	3.05 (1.11 - 8.36)	2.78 (0.98 - 7.85)
	At 3 months	1.64 (1.10 - 2.46)	1.75 (1.16 - 2.64)	2.33 (0.84 - 6.45)	1.95 (0.52 - 7.35)
	At 12 months	1.49 (1.00 - 2.22)	1.53 (1.02 - 2.30)	2.23 (0.82 - 6.08)	1.57 (0.43 - 5.79)
Provoked DVT	At baseline	2.48 (1.57 - 3.92)	2.44 (1.22 - 4.86)	6.90 (2.36 - 20.20)	5.88 (1.26 - 27.38)
	At 3 months	2.31 (1.36 - 3.92)	1.53 (0.77 - 3.04)	4.66 (1.68 - 12.89)	2.32 (0.82 - 6.55)
	At 12 months	1.89 (1.15 - 3.10)	1.42 (0.77 - 2.60)	3.88 (1.41 - 10.67)	2.16 (0.76 - 6.14)
DVT only	At baseline	2.12 (1.42 - 3.15)	1.92 (1.24 - 2.95)	4.31 (1.74 - 10.68)	3.06 (1.13 - 8.24)
	At 3 months	1.77 (1.19 - 2.63)	1.55 (1.06 - 2.28)	3.00 (1.22 - 7.35)	1.99 (0.74 - 5.34)
	At 12 months	1.56 (1.06 - 2-29)	1.42 (0.97 - 2.09)	2.93 (1.17 - 7.30)	1.92 (0.71 - 5.19)
DVT+PE	At baseline	10.18 (1.56 - 66.28)	10.29 (1.40 - 75.44)	10.00 (1.02 - 97.50)	7.32 (0.67 - 79.43)
	At 3 months	4.31 (1.28 - 14-44)	4.12 (1.15 - 14.74)	8.63 (0.89 - 83.74)	6.62 (0.64 - 67.95)
	At 12 months	3.14 (1.10 - 8.97)	3.26 (0.98 - 10.90)	4.66 (0.72 - 30.22)	3.58 (0.44 - 28.75)

Classical risk factor	Correlation Coefficient (r)^a a Phi correlation coefficient. )	p-value
Malignancy	0.360	0.001
Surgery	0.149	0.198
Trauma	0.101	0.375
Pregnancy/postpartum state	0.180	0.114
Immobilization	0.031	0.790
Air travel	0.103	0.367
Estrogen use	0.019	0.871

Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular (ABHH) R. Dr. Diogo de Faria, 775 cj 133, 04037-002, São Paulo / SP - Brasil - São Paulo - SP - Brazil
E-mail: htct@abhh.org.br

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[1] ⁎ Corresponding author at:Department of Hematology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India. Email address: drgovindpatelbala@gmail.com (G.R. Patel).