Venous thromboembolism risk score during hospitalization in pregnancy: results of 10694 prospective evaluations in a clinical trial

Barros, Venina Isabel Poço Viana Leme de; Igai, Ana Maria Kondo; Baptista, Fernanda Spadotto; Bortolotto, Maria Rita de Figueiredo Lemos; Peres, Stela Verzinhasse; Francisco, Rossana Pulcinelli Vieira

doi:10.1016/j.clinsp.2023.100230

Venina Isabel Poço Viana Leme de Barros ^⁎⁎ Corresponding author. E-mail address: venina.barros@hc.fm.usp.br (V.I.P.V.L. de Barros).

Guarantor statement

project conception

implementation

development

approval

data analysis and manuscript writing

collaboration regarding the final approval of the version to be published

Hospital das Clínicas, Universidade de São Paulo (HCUSP), São Paulo, SP, Brazil

https://orcid.org/0000-0002-5157-1597

Ana Maria Kondo Igai

project conception

implementation

development

approval

collaboration regarding the final approval of the version to be published

Hospital das Clínicas, Universidade de São Paulo (HCUSP), São Paulo, SP, Brazil

https://orcid.org/0000-0003-3569-3559

Fernanda Spadotto Baptista

project conception

implementation

development

approval

data analysis and manuscript writing

collaboration regarding the final approval of the version to be published

Hospital das Clínicas, Universidade de São Paulo (HCUSP), São Paulo, SP, Brazil

https://orcid.org/0000-0002-5251-2556

Maria Rita de Figueiredo Lemos Bortolotto

project conception

implementation

development

approval

Hospital das Clínicas, Universidade de São Paulo (HCUSP), São Paulo, SP, Brazil

https://orcid.org/0000-0001-6674-051X

Stela Verzinhasse Peres

manuscript revision

sample size calculation

statistical analysis

collaboration regarding the final approval of the version to be published

Hospital das Clínicas, Universidade de São Paulo (HCUSP), São Paulo, SP, Brazil

https://orcid.org/0000-0001-8120-2920

Rossana Pulcinelli Vieira Francisco

data analysis and manuscript writing

manuscript revision

sample size calculation

statistical analysis

collaboration regarding the final approval of the version to be published

Hospital das Clínicas, Universidade de São Paulo (HCUSP), São Paulo, SP, Brazil

https://orcid.org/0000-0002-9981-8069

⁎ Corresponding author. E-mail address: venina.barros@hc.fm.usp.br (V.I.P.V.L. de Barros).

Conflicts of interest

VENINA BARROS - speaker of Sanofi-Aventis, Cardinal Health and CSL-Viphor

High-risk factors (Score 3)	Moderate-risk factors (Score 2)	Low-risk factors (Score 1)
Previous VTE	Previous VTE associated with a triggering factor	Dehydration
Recurrent VTE		Smoker (> 20 cigarettes/day)
VTE during gestation or after delivery		Multiple pregnanc
VTE linked to the use of hormones		Hyperemesis
		Age ≥ 35y and < 40y
		Parity ≥ 3 deliveries
		Any surgical procedure in the gestation or puerperium
		Gross varicose veins
*High-risk thrombophilia*	*Thrombophilia*
Homozygous Factor V Leiden	Homocysteine > 15 ΜmoL/L
Homozygous mutant prothrombin gene	Heterozygous Leiden factor
Antithrombin deficiency	Heterozygous mutant prothrombin
Thrombophilia association	Protein C deficiency
Antiphospholipid syndrome	Protein S deficiency
Antiphospholipid syndrome	Suspected APS
*Cardiopathies*	*Clinical conditions*
Mechanical valve prostheses	Cancer (in the previous 6 months)
Atrial fibrillation or flutter	Chemotherapy (within 6 months)
Cyanotic cardiopathies	Cyanotic pneumopathy
Intracavitary thrombosis	Paraplegia
Severe ventricular dysfunction	Pyelonephritis/pneumonia/puerperal infection
Severe dilation of heart cameras	Puerperal hemorrhage >1000 mL
	Age ≥ 40y
	BMI ≥ 40 kg/m²
	Immobility in bed more than 4 days before cesarean section
*Other systemic diseases:*		*Risk of bleeding*
Nephrotic proteinuria (≥3.5g/24 hours prior to gestation or during the first trimester)		Preferably using mechanical methods
		Active bleeding
Sickle-cell anemia		Active peptic ulcers
Systemic lupus erythematosus^b b Disease activity requiring hospitalization.		Uncontrolled systemic arterial hypertension (> 180 × 110 mm Hg)
Acute rheumatological disease^b b Disease activity requiring hospitalization.
Intestinal inflammatory disease^b b Disease activity requiring hospitalization.		Coagulopathy (thrombocytopenia < 70,000 or INR > 1.5)
Digestive tract cancer (pancreas and stomach); lung cancer		Allergy or heparin thrombocytopenia
Digestive tract cancer (pancreas and stomach); lung cancer		Renal insufficiency (creatinine > 1.5)
*Immobility in bed for longer than 1 week with BMI ≥ 30 kg/m* ²		Cranial or ocular surgery < 2 weeks
		Cerebrospinal fluid flap < 24h
*Morbidity in previous gestation with positive thrombophilia (genetic and/or acquired)*		Hepatic/cerebral metastasis
Previous stillbirth without malformations
Placental abruption
Severe placental impairment:
Zero or reverse diastole in the umbilical artery
Restricted fetal growth (p < 3)
Oligoamnios

Risk factors	VTE score ≥ 3 (n = 1626)		VTE score < 3 (n = 9068)		Total (n = 10694)		OR (95% CI)	p
	n	%	n	%	n	%
Age ≥35y and ≤39y	433	26.6	1663	18.3	2096	19.6	1.6 (1.4-1.8)	<0.001
Parity ≥3	419	25.8	811	8.9	1230	11.5	3.5 (3.1-4.0)	<0.001
Age ≥40y	321	19.7	439	4.8	760	7.1	4.8 (4.1-5.6)	<0.001
Multiple pregnancy	182	11.2	513	5.7	695	6.5	2.1 (1.7-2.5)	<0.001
BMI ≥40 kg/m²	294	18.0	375	4.1	668	6.2	5.1 (4.3-6.0)	<0.001
Surgical procedure	109	6.7	337	3.7	446	4.2	1.9 (1.5-2.3)	0.002
Severe infections	144	8.9	208	2.3	352	3.3	4.1 (3.3-5.1)	<0.001
Cancer	110	6.8	53	0.6	163	1.5	12.3 (8.8-17.2)	<0.001
Smoking >20 cigarettes	51	3.1	101	1.1	152	1.1	2.9 (2.0-4.0)	<0.001
Chemotherapy	60	3.7	14	0.2	74	0.7	24.8 (13.8-44.4)	<0.001
Sickle cell disease	67	4.1	5	0.1	72	0.7	77.9 (31.3-193.6)	<0.001
Lupus*	44	2.7	21	0.2	65	0.6	12.0 (7.1-20.2)	<0.001
Nephrotic proteinuria	49	3.0	4	0.0	53	0.5	70.4 (25.4-195.4)	<0.001
Immobility ≥7d and BMI ≥30 kg/m²	37	2.3	15	0.2	52	0.5	14.0 (7.7-25.7)	<0.001
Hyperemesis	8	0.5	36	0.4	44	0.4	3.4 (1.1-10.6)	0.03
Postpartum hemorrhage	26	1.6	15	0.2	41	0.4	9.8 (5.2-18.5)	<0.001
Immobility ≥4 days pre-cesarean	26	1.6	11	0.1	37	0.3	13.4 (6.6-27.1)	<0.001
Varices	9	0.6	23	0.3	32	0.03		0.045
Paraplegy	24	1.5	7	0.1	31	0.3	19.4 (8.3-45.1)	<0.001
Previous VTE (triggering factors)	22	1.4	21	0.2	43	0.4	5.9 (3.2-10.8)	<0.001
Ventriculomegaly	51	3.1	7	0.1	58	0.5	41.9 (19-92.5)	<0.001
Severe dilation of heart chambers	87	5.4	17	0.2	104	1.0	30.1 (17.8-50.7)	<0.001
Pulmonary hypertension	94	5.8	31	0.3	125	1.2	17.9 (11.9-26.9)	0.63
Cyanotic pneumopathy	1	0.1	5	0.1	6		1.1 (0.1-9.5)	0.921
Stillbirth	21	1.3	8	0.1	29	0.3	14.8 (6.5-33.5)	<0.001
Placenta abruption	5	0.3	2	0.0	7	0.1	14.0 (2.7-72.1)	0.002
Placental insufficiency	5	0.3	1	0.0	6	0.1	28.0 (3.5-239.5)	0.002
Fetal growth restriction	8	0.5	6	0.1	14	0.1	7.5 (2.6-21.6)	<0.001
Cancer (stomach)	3	0.2	1	0.0	4	0.0	16.8 (1.7-161.2)	<0.015
Hemolytic anemia	11	0.7	2	0.0	13	0.1	30.9 (6.8-139.4)	<0.001
Rheumatologic diseases (other than lupus)	10	0.6	4	0.0	14	0.1	14.0 (4.4-44.8)	<0.001
Inflammatory bowel disease	8	0.5	7	0.1	15	0.1	6.4 (2.3-17.7)	<0.001
VTE previous (postpartum)	8	0.5	0	0.0	8	0.1	41.4 (12.4-138.6)	<0.001
VTE (No triggering factors)	16	1.0	7	0.1	23	0.2	12.9 (5.3-31.3)	<0.001
VTE (with hormones)	3	0.2	0	0.0	3	0.0		<0.001
Homocysteine	1	0.1	1	0.0	2	0.0	5.6 (0.3-89.2)	0.224
Factor V Leiden heterozygous	4	0.2	3	0.0	7	0.1	7.4 (1.7-33.3)	0.009
Prothrombin heterozygous	1	0.1	3	0.0	4	0.0	1.9 (0.2-17.9)	0.591
Protein C	0	0.0	3	0.0	3	0.0
Antiphospholipid syndrome	2	0.1	5	0.1	7	0.1	2.2 (0.4-11.5)	0.337

Anticoagulation	N	%
Ambulation	453	29.5
Enoxaparin 20 mg	30	2.0
Enoxaparin 40 mg	630	41.1
Enoxaparin 60 mg	262	17.1
Enoxaparin 80 mg	45	2.9
Others	114	7.4
Total	1534	100
Missing	92	5.7

Risk factors for major bleeding	N	%
Drugs	65	4.2
PROM	61	3.7
Renal insufficiency	43	2.8
Placenta previa	35	2.3
Active bleeding	34	2.2
Hypertension	26	1.7
Coagulopathy	25	1.6
Metastasis	7	0.4
Coughing	2	0.1
Stomach ulcer	1	0.06
Total	299	19.5

Type of evaluation	TEV SCORE
	< 3		≥ 3		Total
	n	%	n	%	n	%
Hospitalization antepartum
Total clinical treatment^a a p < 0.001 for total clinical treatment versus total postpartum VTE score of ≥ 3.	2790	78.3	774	21.7^a a p < 0.001 for total clinical treatment versus total postpartum VTE score of ≥ 3.	3564	34.2
Postpartum
Cesarean section^b b Cesarean section: 65.8% (524/796) in the high-risk group versus 56.3% (3411/6048) in the low-risk group (p < 0.001).	3411	86.6	524	13.3	3935
Forceps	299	92.5	24	7.4	323
Vaginal delivery	2338	90.4	248	9.5	2586
Total postpartum	6048	88.3	796	11.6	6844	65.7
Total	8838	100	1570	100	10408	100

Risk factors	VTE score ≥ 3 (N = 1626)		VTE score < 3 (N = 9068)		OR (95% CI)	Interaction	Prevalence ratio
Risk factors	VTE score ≥ 3 (N = 1626)		VTE score < 3 (N = 9068)		OR (95% CI)	OR (95%CI)	PR (95% CI)
	N	%	N	%
*Age ≥ 35 and ≤ 39y*	433	18.3	2096	19.6	1.6 (1.4-1.8)
Interaction with BMI ≥ 40 kg/m²						20.64 (14.34-29.71)	5.94 (5.34-6.61)
Interaction with surgical procedure						4.47 (2.94-6.8)	3.03 (2.36-3.89)
Interaction with stillbirth						25.16 (2.81-225.33)	5.83 (3.75-9.07)
Interaction with severe infection						308.67 (42.54-2239.50)	7.41 (6.92-7.94)
*Age ≥ 40y*	321	4.8	760	7.1	4.8 (4.1-5.6)
Interaction with parity ≥ 3						28.41 (20.18-40)	6.72 (6.14-7.36)
Interaction with surgical procedure						29.07 (9.76-86.53)	6.35 (5.12-7.86)
Interaction with severe infection						28.73 (8.09-101.95)	6.54 (5.05-8.48)
Interaction with multiple pregnancy						48.8 (20.7-115.05)	6.97 (5.13-9.49)
Interaction with BMI ≥ 40 kg/m²						28.73 (CI 8.09-101.95)	6.54 (CI 5.05-8.48)
*Multiple pregnancy*	182	5.7	695	6.5	2.1 (1.7-2.5)
Interaction with postpartum hemorrhage						35,99 (4.33-299.14).	6 (2.69-13.37)
*Cancer*	110	0.6	163	1.5	12.3 (8.8-17.2)
Interaction with chemotherapy						43.86 (20.91-91.96)	6.12 (5.54-6.76)

N	Date	Age (y)	Weight (kg)	BMI (kg/m²)	Risk factors	VTE score	Type of VTE	Evolution
1	25/09/2015	37	73	29	Twins, premature rupture of membranes, chorioamnionitis, bed rest, c-section, uterine atony, hysterectomy, septic shock, blood transfusion	9	PE ‒ 7^th day PS	Alive
2	30/06/2016	29	78	27	Fetal malformation, c-section	0	PE and DVT ‒ 7^th day PS	Alive
3	10/09/2016	28	73	25	Twins, difficult extraction, c-section, asthma	1	PE and DVT ‒ 11^th day PS	Alive
4	21/02/2017	34	60	28	Chronic renal insufficiency, seizure 25^th day post-normal delivery, rehospitalization	3	DVT ‒ 39^th PS	Alive
5	05/03/2017	33	67	31	Chronic renal insufficiency, c-section, neonatal death, depression (total bed rest), enoxaparin 100 mg	3	PE and DVT ‒ 14^th day PS.	Alive
6	26/06/2017	41	91	33	Increased age, gross varicose veins, suboptimal dose of heparin	3	Superficial thrombophlebitis ‒ 10^th day after vaginal delivery	Alive
7	22/01/2018	30	66	23	Surgery in pregnancy (correction of meningomyelocele) postoperative vomiting, bed rest, dehydration	2	Cerebral venous thrombosis ‒ 7^th PS (seizure)	Alive
8	18/03/2018	42	105	35	Increased age, gross varicose veins in left leg	3	Superficial thrombophlebitis ‒ 2^nd day post-normal delivery	Alive
9	25/09/2018	31	112	38	Emergency c-section, uterine atony, hemorrhage, multiparity, DVT in the first trimester of pregnancy, autoimmune disease, smoking, withholding of anticoagulation for 3 days after c-section	7	PE ‒ 26^th day PS	Alive
10	04/02/2018	34	120	38	Metastatic colon cancer, previous VTE, c-section in the 35^th week of pregnancy, sepsis, enoxaparin 40 mg/day	7	Vena cava Thrombosis (post-mortem diagnosis).	Dead ‒ 15^th day PS

[1] ⁎ Corresponding author. E-mail address: venina.barros@hc.fm.usp.br (V.I.P.V.L. de Barros).

Brasil

Brasil

Venous thromboembolism risk score during hospitalization in pregnancy: results of 10694 prospective evaluations in a clinical trial

Abstract

Objectives

Methods

Results

Conclusions