Tabac : Facteur de risque de thrombose veineuse

Pr R. HabbalCentre de cardiologie CHU Ibn Rochd. Casablanca

* Gazeuse (CO2, CO, NO, NO2…) * Particulaire (aérosols très fins)

Epidémiologie au Maroc

Tabac et risque de thrombose veineuse : mythe ou réalité ?

To investigate the association between

smoking and the risk of VTE among

middle-aged men and women.

1) Smoking and venous thrombo embolism a Danish follow-up study

Severinsen MT, Department of Clinical Epidemiology, Aarhus University Hospital, Aalborg, Denmark. J Thromb Haemost. 2009 Aug;7(8):1297-303

OBJECTIVE

◦ Danish prospective study 'Diet, Cancer and Health'.

◦ 1993 to 1997

◦ 27,178 men and 29,875 women,

◦ 50-64 years

1) Smoking and venous thrombo embolism a Danish follow-up study

◦641 incident cases of VTE were verified.

◦Positive association between current smoking and VTE,

OR 1.52 (1.15-2.00) for smoking women

OR 1.32 (1.00-1.74) for smoking men

Positive dose-response relationship.

◦Former smokers had the same hazard as never

smokers.

J Thromb Haemost. 2009 Aug;7(8):1297-303

RESULTS

- Smoking was an independent risk factor for VTE

- Former smokers have the same risk of VTE as never

smokers, indicating the potential benefits of smoking

cessation.

1) Smoking and venous thrombo embolism a Danish follow-up study

J Thromb Haemost. 2009 Aug;7(8):1297-303

To conduct a prospective, population-based cohort

study to investigate the association between cigarette

smoking and the risk of incident VTE.

2) Cigarette smoking and the risk of venous thromboembolism: the Tromsø Study

OBJECTIVES :

J Thromb Haemost. 2012 Oct;10(10):2068-74

– Information on smoking habits was assessed by self-

administered questionnaires in 24 576 subjects

– 25-96 years

– 1994-1995

– Incident cases of VTE were registered until the end of

follow-up at 1 September 2007 (median of 12.5 y)

PATIENTS/METHODS:

2) Cigarette smoking and the risk of venous thromboembolism: the Tromsø Study

J Thromb Haemost. 2012 Oct;10(10):2068-74

◦389 incident VTE events (1.61 per 1000 pers-y)◦Heavy smokers (> 20 pack-years) compared with

never smokers. HR : 1.46 (1.04-2.05) for total VTE, HR :1.75 (1.14-2.69) for provoked VTE

RESULTS :

J Thromb Haemost. 2012 Oct;10(10):2068-74

2) Cigarette smoking and the risk of venous thromboembolism: the Tromsø Study

◦The risk of provoked VTE increased with more pack-years of smoking (P = 0.02). 

◦Smoking was not associated with risk of unprovoked VTE.

◦Association between pack-years of smoking and VTE disappeared when occurrence of cancer or myocardial infarction.

RESULTS :

J Thromb Haemost. 2012 Oct;10(10):2068-74

2) Cigarette smoking and the risk of venous thromboembolism: the Tromsø Study

BACKGROUND

The evidence for an association between smoking

and venous thrombosis (VT) is inconsistent, and

its mediation pathways remain to be fully

elucidated.

3)The association of smoking with venous thrombosis in women. A population-based, case-control study

Thromb Haemost. 2013 Mar 7;109(5)

A population-based, case-control study was

conducted in healthcare system in Washington State.

Cases were women aged 18-90 years who

experienced a validated incident deep vein

thrombosis or pulmonary embolism between

January 1, 1995, and December 31, 2009.

METHODS :

Thromb Haemost. 2013 Mar 7;109(5)

3)The association of smoking with venous thrombosis in women. A population-based, case-control study

◦ Controls were randomly selected from members of the healthcare system. 

◦ Smoking status (current, former, never) was assessed from medical records review and, for a subset, also by telephone interview.

◦ Multivariable logistic regression was used to estimate odds ratios (OR) associated with smoking status. 

METHODS :

Thromb Haemost. 2013 Mar 7;109(5)

3)The association of smoking with venous thrombosis in women. A population-based, case-control study

RESULTS : ◦We identified 2,278 cases and 5,927 controls.◦Subjects comprised mostly postmenopausal white

women with a mean age of 66 years and a current smoking prevalence of 10%.

◦ Compared to never-smokers, current and former smokers were at higher risk of VT (adjusted OR 1.21, [CI] 1.02-1.44 and OR 1.15, CI 1.03-1.29.

◦ These associations were attenuated for potential mediators (cardiovascular disease, congestive heart failure, cancer, recent hospitalisations and physical activity): OR 1.02 CI (0.83-1.25) and 0.95 CI (0.83-1.08).

Thromb Haemost. 2013 Mar 7;109(5)

The modestly increased risk of VT in women who are current or former smokers might be explained by the occurrence of smoking-related diseases and decreased physical activity.

Our results do not support a direct biological effect of smoking on the risk of VT that is clinically relevant

Thromb Haemost. 2013 Mar 7;109(5)

3)The association of smoking with venous thrombosis in women. A population-based, case-control study

La relation existe entre les fumeurs et la thrombose veineuse

Mais elle est atténuée quand elle est ajustée avec des maladies potentielles (Maladie cardio-vasculaire, cancer…)

Relation indirecte

Tabac et risque de thrombose veineuse : mythe ou réalité ?

Interactions composantes du tabac et facteurs de

coagulation

carbon monoxide, a product of cigarette smoking, has been demonstrated to enhance plasmatic coagulation in vitro via modulation of a heme associated with fibrinogen.

We hypothesized that plasmatic hypercoagulability and formation of carboxyhemefibrinogen (COHF) detected would be observed after cigarette smoking 

1) Tobacco smoke-induced hypercoagulation in human plasma: role of carbon monoxide

Blood Coagul Fibrinolysis. 2013 Feb 21

Smoking participants (n : 20) two cigarettes consumed within 90 min : plasma collected and normal participant (n = 20) plasma was also obtained.

Thrombelastographic analyses revealed that plasma obtained from smokers had an 86% greater velocity of clot growth and 65% larger clot strength than normal participant plasma.

Tobacco smoke-induced hypercoagulation in human plasma: role of carbon monoxide

Blood Coagul Fibrinolysis. 2013 Feb 21

We conclude that smoking induced a

hypercoagulable state and COHF formation in an important portion of participants tested.

Future investigations of the effects of smoking, plasmatic hypercoagulation and COHF formation are planned in populations with established atherosclerotic/ thrombotic disease

Tobacco smoke-induced hypercoagulation in human plasma: role of carbon monoxide

Blood Coagul Fibrinolysis. 2013 Feb 21

2) Exposure to acrolein by inhalation causes platelet activation

The purpose was to determine whether CO and NO diminished fibrinolysis by enhancement of α₂-antiaplasmin via a putative heme group.

3) Carbon monoxide and nitric oxide modulate α₂-antiplasmin and plasmin activity: role of heme

Blood Coagul Fibrinolysis. 2011 Dec;22(8):712-9

CO significantly enhanced α₂-antiplasmin activity, but decreased plasmin activity.

NO decreased both α₂-antiplasmin and plasmin activity.

Diminished fibrinolysis

Blood Coagul Fibrinolysis. 2011 Dec;22(8):712-9

3) Carbon monoxide and nitric oxide modulate α₂-antiplasmin and plasmin activity: role of heme

Objective : ◦ Smokers exhibit higher circulating levels of tissue factor (TF)

than do non smokers, but the underlying mechanisms have not been reported.

◦ we investigated whether exposure of human monocyte/macrophages to tobacco smoke induces their release of MVs and whether these MVs are procoagulant.

Arterioscler Thromb Vasc Biol. 2010 September ; 30(9): 1818–1824.

4) Tobacco Smoke Induces the generation of Progoagulant Microvesicles from Human Monocyte/Macrophages

RESULTS :◦ Exposure of human monocytes and

macrophages to tobacco smoke extract significantly increased their total and TF-positive MV generation.

4) Tobacco Smoke Induces the generation of Progoagulant Microvesicles from Human Monocyte/Macrophages

Arterioscler Thromb Vasc Biol. 2010 September ; 30(9): 1818–1824.

Monoxide de carbone: entraine un état d’hypercoagulable et la formation de COHF

Acroleine : active les plaquettes Monoxide de carbone et Nitric oxide diminuent la

fibrinolyse L’exposition des monocytes et des

macrophages humaines au tabac augmente signifiquement le facteur Tissulaire et la génération des MV.

Interactions composants du tabac et facteurs de coagulation

Tabagisme et Warfarine

• Retrospective observational study among 350 patients receiving a stable dose of warfarin for at least 2 weeks. The primary objective of the study was to assess the relationship between clinical factors, including smoking with non therapeutic INR results. Based on a univariate analysis, smoking was not significantly associated with non therapeutic INR.

Effect of Smoking on INR

.   McGriff-Lee  NJ et al. Ann Pharmacother 2005 3912 1996-2002

Prospective observational study among 80 patients with heart failure receiving warfarin therapy to assess the relationship among various clinical factors, including smoking with non therapeutic INR (defined as having > 25% of INR out of range throughout the study period). Using the Pearson correlation method, the authors found no significant relationship of smoking and non therapeutic INR

Effect of Smoking on INR

Pamboukian  SV et al. Clin Cardiol 2008 311 30-34

BACKGROUND: Chronic smoking, theoretically, can interfere with

warfarin metabolism through enzyme-inducing effects of polycyclic aromatic hydrocarbons.

However, clinical evidence of interactions between warfarin and smoking are inconclusive.

This study aimed to systematically review all relevant clinical evidence of this interaction.

Assessing Evidence of Interaction Between Smoking and Warfarin:A Systematic Review and Meta-analysis

CHEST. 2011;139(5):1130-1139

METHODS: We performed a systematic search using

computerized databases, from 1966 to December 2008.

Keywords included "warfarin" with "smoking," "tobacco," "cigarette," and "polycyclic aromatic hydrocarbons."

All articles were reviewed independently by two investigators for study design, population, outcomes, and quality of evidence.

Assessing Evidence of Interaction Between Smoking and Warfarin:A Systematic Review and Meta-analysis

RESULTS: Of the 1,240 studies retrieved one experimental:

pharmacokinetic study and 12 cross-sectional studies.

“smoking was associated with a 12.13% (95% CI, 6.999-17.265; P < .001) increase in warfarin dosage requirement and an additional 2.26 mg (95% CI, 2.529-7.042; P = .355) per week compared with nonsmoking”.

Assessing Evidence of Interaction Between Smoking and Warfarin:A Systematic Review and Meta-analysis

Date of download: 3/19/2013

Copyright © American College of Chest Physicians. All rights reserved.

From: Assessing Evidence of Interaction Between Smoking and Warfarin: A Systematic Review and Meta-analysis

CHEST. 2011;139(5):1130-1139. doi:10.1378/chest.10-0777

Pooled estimate of percentage change in warfarin dose.

Date of download: 3/19/2013

Copyright © American College of Chest Physicians. All rights reserved.

From: Assessing Evidence of Interaction Between Smoking and Warfarin: A Systematic Review and Meta-analysis

CHEST. 2011;139(5):1130-1139. doi:10.1378/chest.10-0777

Pooled estimate of additional milligrams of warfarin required.

Conclusion : Evidence suggests that smoking may

potentially cause significant interaction with warfarin by increasing warfarin clearance, which leads to reduced warfarin effects.

Assessing Evidence of Interaction Between Smoking and Warfarin:A Systematic Review and Meta-analysis

Effet du tabac sur l’INR : les anciennes études ne montraient pas de relation

Tabagisme et warfarine : relation évidente par augmentation de la clearance et réduction de son l’effet

Tabagisme et Warfarine

conclusion