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Obesity and thrombosis
Explains the link between obesity and blood clots, and the treatment options for obese patients with a blood clot.

Introduction Are people who are obese more at risk of developing venous thromboembolism (VTE), including deep-vein thrombosis (DVT) and pulmonary embolism (PE), than people who are not obese? And are obese patients undergoing surgery more likely to develop VTE as a consequence, compared with nonobese surgical patients? This article examines the links between obesity and VTE, and goes on to address important questions about whether obese patients require different drug treatments and regimens to prevent and to treat blood clots, compared with nonobese patients. Obesity is usually defined in terms of body mass index (BMI), a measure of body fat that takes into account height as well as weight. An adult with a BMI of 30 kg/m² or more is considered to be obese. A BMI between 25 and 30 kg/m² signifies that the individual is overweight but not obese, while a BMI of less than 25 (but above 18.5) kg/m² implies a normal weight. It should be remembered that the risks of VTE associated with being obese may also apply to some extent in those who are overweight but not actually obese. A simple BMI calculator is available online at the website of the US National Heart, Lung, and Blood Institute, at www.nhlbisupport.com/bmi.

The links between obesity and VTE
What is the evidence that people who are obese have a higher risk of developing VTE? There are conflicting findings from different studies. Of the larger studies that have been performed, one found that obese people were 2.4 times as likely as nonobese people to develop DVT, after accounting for other risk factors. Another study, in women, found that those who were obese were 2.9 times as likely as nonobese women to develop PE, the most serious complication of DVT. In contrast, a major study of postmenopausal women found no significantly increased risk of thrombosis among those in the higher-weight group (with a BMI of 27 kg/m² or more–the cut-off level in this study) compared with those with a lower BMI, although the researchers acknowledged that the number of thrombosis events in the study was small, and the study was not optimally designed to detect risk factors.

The evidence similarly varies for obesity increasing the risk of VTE after surgery. However, researchers who conducted an analysis of all relevant published studies recently concluded: “The evidence suggests that obesity… is associated with higher rates of postoperative DVT, although the actual extent of the impact is difficult to quantify.”

Overall, the evidence seems to point toward obesity being a risk factor for thrombosis. The American Obesity Association is unequivocal on its website, stating that “obesity increases the risk of DVT,” and that “patients with obesity have an increased risk of DVT after surgery.” The Coalition to Prevent DVT, which comprises more than 60 professional organizations, also includes obesity in its list of risk factors.

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Preventing clots in obese patients undergoing surgery
Patients undergoing surgery are known to have an elevated risk of developing a blood clot. For this reason, all surgical patients are usually given preventive (or prophylactic) therapy, typically with a low-molecular-weight heparin (LMWH). (To learn more about the prevention and treatment of VTE, read our report on this topic). For most patients, a standard fixed dose is sufficient. But do obese patients need a larger dose than nonobese patients, in order to obtain the same beneficial effect from the drug? There is evidence that they do: two studies of LMWHs found that the larger the patient, the lower the overall anticlotting activity.

Such findings suggest that weight-based dosing (giving a dose per kg of the patient’s body weight) might be preferable to fixed dosing (a standard dose per person) in obese patients. Two studies in patients undergoing weight loss surgery (a gastric bypass or “stomach stapling”) have recently investigated this further. In the first, involving patients with an average BMI of above 50 kg/m², there were significantly fewer DVTs occurring after surgery among those given a higher than usual dose of a LMWH, compared with those given a lower dose. However, a similar study of a different LMWH in severely obese patients (BMI above 36 kg/m²) found no significant differences in the number of thrombotic events between two groups of patients given different doses.

The latest guidance for specialists, issued by the American College of Chest Physicians (ACCP) in 2004, adopts a pragmatic view, stating: “In the absence of clear data, it seems prudent to consider a 25% increase in the thromboprophylactic dose of LMWH in very obese patients.” Dosing decisions concerning obese patients undergoing other types of surgery than “stomach stapling” or with a medical condition need to be taken on an individual basis.

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Do obese patients with VTE warrant different treatment than nonobese patients?
Do the same considerations apply to the initial treatment of clots? Is weight-based dosing safe and effective in obese patients? Body weight and overall volume of blood are not directly proportional to each other, so it is theoretically possible that dosing per kg could lead to obese patients receiving too much of the drug than their bodies can cope with (conversely, giving a standard fixed dosed to an obese patient is likely to lead to underdosing).

The evidence currently available from clinical trials is limited. One study concluded that body weight (up to 190 kg— the highest weight in the study) did not influence the anticlotting response to weight-based doses of LMWH. Similarly, another study suggested that there was no need to modify the currently recommended dose of a LMWH for obese patients. More recently, a study of a LMWH concluded that giving the drug in weight-based doses in obese patients was effective and safe—even though the total dose given often exceeded the recommended maximum daily dose, because of the patients’ weights. Importantly, in these studies, the use of higher total doses based on weight did not lead to an increase in major bleeding.

However, these studies included few patients with a total body weight of more than 150 kg or a BMI of 50 kg/m² or more. The ACCP guidelines therefore suggest that, in such patients, the anticlotting activity of the drug should be monitored and the dose reduced if necessary to lower the risk of bleeding.

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How can further clots be prevented?
As well as treatment to dissolve the blood clot, patients with thrombosis will receive longer-term treatment to prevent further clots developing. For most patients, the ACCP recommends treatment with blood-thinning pills (e.g. warfarin) for 3–12 months, the duration depending on factors such as the likely cause of the original clot. LMWH is an alternative treatment if blood thinning pills are not suitable for a patient or cause unacceptable side effects.

Throughout the treatment period, the anticlotting activity of the drug in the individual patient will be regularly assessed and the dose adjusted if necessary to keep the activity within a certain range (not so low to be ineffective but not so high as to cause side effects such as bleeding). This need for careful and regular monitoring applies to all patients: there is no reason to treat obese patients differently from nonobese patients.

The ACCP also advises the use of elastic compression stockings to help prevent further clots. It recommends that a stocking with a pressure of 30–40 mmHg at the ankle be worn for 2 years after a DVT, unless the physician considers the patient inappropriate for compression therapy. (Again, you can learn more about the prevention and treatment of VTE in our report on this topic).

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Summary

• Although there is some conflicting evidence, obesity is widely considered to be an independent risk factor for thrombosis.
  
  
• Obese patients undergoing surgery may require higher doses of preventive anticlotting drugs than nonobese patients.
  
  
• During the initial treatment of a blood clot, careful monitoring of the anticlotting activity of the drug is recommended in very obese patients (BMI 50 kg/m² or more), to ensure that they are not being given doses that are too small or too large.
  
  
• For the prevention of further clots, there is no reason to treat obese patients differently from nonobese patients.

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References
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