Download Obesity and Venous Thromboembolic Disease

Obesity and Venous
Thromboembolic Disease
Angel Galvez MD PhD
Oncology Specialists SC
Lutheran General Hospital
VTE: Epidemiology
5 million DVT’s
900,000
PE’s
290,000 fatalities
Heit J. Blood. 2005;106:910.
Virchow’s Triad
Vessel wall damage
Venous Stasis
Small thrombi not washed away
Accidental trauma
Surgical trauma
- Hip surgery
- Knee surgery
- CNS surgery
- Cancer
Viscosity increased
Immobilization
Important Factors in
Thrombogenesis
Blood Hypercoagulability
Increase in fibrinogen activated coagulation factors, platelets
Decrease in natural coagulation inhibitors
Impaired fibrinolysis
Examples of medical conditions with
increased risk of thrombosis
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Trauma
Malignancies
Surgery
Congestive heart failure
Chemotherapy administration
Pregnancy
Acquired coagulation
abnormalities (APS)
• Inherited coagulation
abnormalities
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Oral contraceptives
Nephrotic syndrome
Myeloproliferative disorders
Plasma cell dyscrasias
Inflammatory bowel disease
Heparin induced
thrombocytopenia.
• PNH
• Obesity
From: Prevalence of Overweight and Obesity in the United States, 1999-2004
JAMA. 2006;295(13):1549-1555. doi:10.1001/jama.295.13.1549
Relative risks of pulmonary embolism and deep venous thrombosis according
to age among obese and non-obese patients
Pulmonary embolism
Deep venous thrombosis
Obese vs non-obese
Obese vs non-obese
Age groups
Relative risk
(95% CI)
Relative risk
(95% CI)
<40 y
5.19
(5.11–5.28)
5.20
(5.15–5.25)
40–49 y
1.94
(1.91–1.97)
2.13
(2.11–2.15)
50–59 y
1.25
(1.23–1.27)
1.67
(1.65–1.68)
60–69 y
1.42
(1.40–1.44)
1.88
(1.87–1.90)
70–79 y
2.07
(2.04–2.10)
1.89
(1.87–1.91)
>80 y
3.15
(3.08–3.22)
2.16
(2.12–2.20)
All ages
2.18
(2.16–2.19)
2.50
(2.49–2.51)
CI = confidence interval.
Paul Stein et al. The American Journal of Medicine. September 2005. Volume 118, Issue 9,
Mechanism for the observed association between obesity and VTE
• More body fat (specially abdominal fat) might limit venous return
• Leptin
• Levels elevated in obesity
• Associated with increased ADP induced platelet aggregation
• It correlates with low tPA and high levels of PAI 1 inhibitor
• TNF-a and TGF-b produced in visceral fat
• Elevated concentrations of PAI 1 inhibitor
• High Factor VII, Factor VIIIa, Fibrinogen and von Willebrand F.
• Chronic condition associated to obesity are associated to increase risk of
VTE disease
• Life style factors: decreased physical activity
Blood flow through a normal blood vessel.
Endothelium
Subendothelium
Primary hemostasis I
Laminin
Tissue Factor
Fibronectin
Vitronectin
Collagen
Von Willebrand
Factor
Thrombospondin
Primary hemostasis II
Obesity
TxA2
ADP
Laminin
Tissue Factor
Fibronectin
Vitronectin
Serotonin
PGG2, PGH2
Collagen
Von Willebrand
Factor
Thrombospondin
Primary hemostasis III
Tissue Factor
Collagen
Von Willebrand
Factor
Thrombospondin
Natural anticoagulants:
Fibrinolysis
Alpha-2 antiplasmin
Obesity
Fibrin
Fibrinogen
Thrombin
Plasminogen
F Va
Platelets
F VIIIa
PAI 1
IX
tPA
FVII
Xa
II
IXa
FVIIa
Tissue Factor
Obesity
X
Subendothelium
Platelets
Thrombus formation
ADP
Platelet
activation
Platelet
aggregation
Collagen
TXA2
Thrombin
Tissue
Factor
Plasma
Clotting
cascade
Fibrinogen
Fibrin
THROMBUS
Prothrombin
• How can we reduce risk of thrombosis in obesity?
• Weight loss
• Diet and exercise
• Thromboprophylaxis
Effect of weight loss (by diet and exercise) on hemostatic
profile and recurrence of VTE disease
• Folsom et al (loss of 9.5Kg average)
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FVII, tPA, PAI-1. No changes in Fibrinogen
• Marckmann et al (loss of 13.6 Kg average)
• F VII 12%, Fibrinogen 6%, PAI 1 35%
• Rissanen et al (loss of 10 Kg average)
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FVII,
PAI 1, No changes in Fibrinogen
• How can we reduce risk of thrombosis in obesity?
• Weight loss
• Diet and exercise
• Thromboprophylaxis
Challenges of chemical thromboprophylaxis in obese patients.
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High risk (Caprini score of 4 or higher)
Different volume of distribution of anticoagulants
Morbidly obese patients excluded in most of clinical trials
In some cases, there is a need to check PTT, heparin anti Xa or
LMWH anti Xa
• Not enough data on use of novel anticoagulants in morbidly obese
patients.
Venous thromboembolism prevention in bariatric surgery
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Risk stratification
Mechanical thromboprophylaxis
Early ambulation
Chemical thromboprophylaxis
VTE Thromboprophylaxis
Enoxaparin
Dalteparin
VTE treatment
BMI 30-39
Use standard regimen:30 mg/12 hours
or 40 mg daily
BMI >40
40 mg /12 hours
High VTE risk (bariatric surgery with
BMI >50
60 mg/12 hours
1 mg/Kg every 12 hours
Once daily dose not recommended
BMI >40 consider checking anti Xa
BMI 30-39
Use standard regimen: 5000 u/day
BMI >40
30% increase to 6500 u/day
Extended treatment of VTE in cancer
patients
200u/Kg/day first month
150u/Kg/day subsequent months
Meta-analysis of VTE thromboprophylaxis in obese patients with orthopedic
surgery in different novel anticoagulants.
Novel anticoagulant use in treatment of VTE disease in
morbidly obese patient
• Although obese patients were not excluded from clinical trials of novel
anticoagulants, there is not enough data at this time to support the use of a fix
dose of a novel anticoagulant in the treatment of VTE disease in morbidly
obese patients.
Obesity and Cancer
• Cancer is a major risk factor for VTE disease
• Obesity increases the likelihood of suffering cancer
Cancer associated to high BMI
Endometrial cancer
Ovarian cancer
Postmenopausal breast cancer
Cervical cancer
Esophageal cancer
Gallbladder cancer
Colon cancer
Liver cancer
Leukemia
Thyroid cancer
• Obesity increases risk of venous thromboembolic disease.
• The increased risk of VTE events in obesity is multifactorial.
• Weight loss leads to reversal of some of the changes in coagulation parameters
seeing in obese patients.
• Pharmacological thromboprophylaxis in obese patient is effective and safe but
might requires adjustment in the dose of the anticoagulant in use.
• The efficacy and safety of using fix dose anticoagulants in patients with morbidly
obese patients is not clearly established and requires further study.
• Obese patients have a higher risk of suffering certain malignancies that when
concurrent with obesity lead to a even much higher risk of suffering VTE events.
Summary slide