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Obesity and Venous Thromboembolic
Disease
Angel Galvez MD PhD
Oncology Specialists SC
Lutheran General Hospital
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VTE: Epidemiology
5 million DVT’s
900,000 PE’s
290,000 fatalities
Heit J. Blood. 2005;106:910.
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Venous Stasis Small thrombi not washed away
Viscosity increased
Immobilization
Virchow’s Triad
Vessel wall damage
Accidental trauma
Surgical trauma
- Hip surgery
- Knee surgery
- CNS surgery
- Cancer
Blood Hypercoagulability Increase in fibrinogen activated coagulation factors, platelets
Decrease in natural coagulation inhibitors
Impaired fibrinolysis
Important Factors in
Thrombogenesis
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Examples of medical conditions with increased risk of thrombosis
• Trauma• Malignancies• Surgery• Congestive heart failure• Chemotherapy administration• Pregnancy• Acquired coagulation
abnormalities (APS)• Inherited coagulation
abnormalities
• Oral contraceptives• Nephrotic syndrome• Myeloproliferative disorders• Plasma cell dyscrasias• Inflammatory bowel disease• Heparin induced
thrombocytopenia.• PNH• Obesity
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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
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Relative risks of pulmonary embolism and deep venous thrombosis according to age among obese and non-obese patients
Age groups
Pulmonary embolism Deep venous thrombosis
Obese vs non-obese Obese vs non-obese
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,
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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
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Endothelium
Subendothelium
Blood flow through a normal blood vessel.
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Von Willebrand Factor
Fibronectin Collagen
Vitronectin
Laminin
Thrombospondin
Tissue Factor
Primary hemostasis I
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Serotonin
TxA2ADP
Von Willebrand Factor
FibronectinCollagen
Vitronectin
Laminin
Thrombospondin
PGG2, PGH2
Tissue Factor
Primary hemostasis II
Obesity
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Von Willebrand Factor
Collagen
Thrombospondin
Tissue Factor
Primary hemostasis III
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Subendothelium
FVIIa
XaX
IXa
FVII
Thrombin
II
Platelets
F VIIIa
F Va
FibrinogenFibrin
IX
Tissue Factor
Platelets
Plasminogen
tPA
PAI 1
Alpha-2 antiplasmin
Natural anticoagulants: Fibrinolysis
Obesity
Obesity
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Thrombus formation
Collagen
TissueFactor
Thrombin
Plateletactivation
Prothrombin
ADP
TXA2
PlasmaClottingcascade
THROMBUS
Fibrinogen Fibrin
Plateletaggregation
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• How can we reduce risk of thrombosis in obesity?
• Weight loss• Diet and exercise
• Thromboprophylaxis
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Effect of weight loss (by diet and exercise) on hemostatic profile and recurrence of VTE disease
• Folsom et al (loss of 9.5Kg average)• 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)• FVII, PAI 1, No changes in Fibrinogen
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• How can we reduce risk of thrombosis in obesity?• Weight loss
• Diet and exercise
• Thromboprophylaxis
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Challenges of chemical thromboprophylaxis in obese patients.
• 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.
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Venous thromboembolism prevention in bariatric surgery
• Risk stratification• Mechanical thromboprophylaxis• Early ambulation• Chemical thromboprophylaxis
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VTE Thromboprophylaxis VTE treatment
Enoxaparin
BMI 30-39 Use standard regimen:30 mg/12 hours or 40 mg dailyBMI >40 40 mg /12 hoursHigh VTE risk (bariatric surgery with BMI >5060 mg/12 hours
1 mg/Kg every 12 hoursOnce daily dose not recommendedBMI >40 consider checking anti Xa
Dalteparin
BMI 30-39 Use standard regimen: 5000 u/dayBMI >40 30% increase to 6500 u/day
Extended treatment of VTE in cancer patients200u/Kg/day first month150u/Kg/day subsequent months
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Meta-analysis of VTE thromboprophylaxis in obese patients with orthopedic surgery in different novel anticoagulants.
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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.
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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
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Summary slide
• 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.