Background
A number of studies have found a significant increased risk for deep venous thromboembolism (VTE), and/or pulmonary embolism in people with obesity [
1‐
6]. A hazard ratio of 2.7 for a body mass index >40 has been reported by the Atherosclerosis Risk in Communities (ARIC) and the Cardiovascular Health Study (CHS) [
2].
Besides obesity, many other factors contribute to increasing the VTE risk: smoking, increasing age, patients with factor V Leiden or pro-thrombin gene mutation [
7] and oral contraceptive therapy [
8].
Patients who had a VTE episode are usually treated with oral anticoagulants. Their use is challenging because the therapeutic range is narrow and dosing is affected by multiple factors including genetic variation, drug interactions, and diet [
9]. Moreover, compared to normal weight, obese and morbidly obese patients had a decreased initial response to warfarin [
10,
11].
Prothrombin time is an assay evaluating the extrinsic pathway of coagulation. The international normalized ratio (INR) is used to standardize the prothrombin time and the optimal intensity of anticoagulant therapy corresponds to a target INR of 2.5 (range, 2.0 to 3.0) [
12].
Both prophylaxis and treatment of VTE and pulmonary embolism (PE) with anticoagulants are associated with significant risks of major and fatal hemorrhage. Both anticoagulant treatment and lifestyle changes should be individualized to prevent further complications [
9,
12].
Two major factors that may lead to poor INR control are failure to take warfarin appropriately and very low dietary vitamin K intake/vitamin K deficiency. The nutritional management of these patients is therefore extremely complicated.
We hereby describe a case of pulmonary embolism in an obese patient providing key insights into treatment with medical nutrition therapy and anticoagulants.
Conclusion
This case study presents the nutritional issues of anticoagulants in the setting of obesity. We present a case of a 52 year old female patient with obesity and hypertension taking anticoagulants due to a history of a recent PE treated in our NU outpatient service.
She had no inherited thrombophilia nor a previous hospitalization, immobility, trauma, surgery, malignancy or infection before the PE, and we hypothesize that perhaps this adverse event might have been caused by the combination of obesity, oral contraceptive therapy and sedentary lifestyle. Indeed, there is strong evidence that oral contraceptives entail a statistically significant risk of VTE, which is particularly high among women with high body mass indices and a history of cigarette smoking [
21,
22]. Previous studies demonstrate that oral contraceptives modify the effect of obesity on the risk of venous thrombosis, with a 10-fold increased risk among women on oral contraceptives with a BMI >25 kg/m
2 compared to normal weight women not using oral contraceptives [
8,
23].
Obesity is considered a risk factor for VTE and PE and is associated with an increase of procoagulant factors (factor VII, factor VIII, factor XII and fibrinogen) [
24‐
26] and with venous stasis [
2] in turn increasing the thrombotic risk (Virchow’s triad). Analysis of data from the National Hospital Discharge Survey indicated an increased relative risk for VTE (RR 2.50, 95 CI 2.492.51) and PE (RR 2.21, 95 % CI 2.202.23) in subjects with obesity [
27].
Our patient reported a long history of obesity and 7 months before the PE episode she was put on a low calorie diet without a formal nutritional assessment of her specific nutritional needs.
As shown in Table
1, the diet before the PE did not satisfy fiber, protein and micronutrients needs for this patient likely due to the low fruit and vegetable intake.
The “Longitudinal Investigation of Thromboembolism Etiology (LITE)” prospective study [
28] found a diet with more fruits, vegetables, and fish, and less red and processed meat was associated with a lower VTE incidence. Data about the relationship of diet to VTE risk comes from: historical observations about the incidence of PE under wartime conditions, including food rationing in early 20th century European cities; prospective observational studies of diet and lifestyle factors associated with VTE [
9]; case–control studies of VTE patients looking at lipid profiles, inflammation markers, and coagulation variables; comparisons among the general population on various diets regarding lipid profiles, inflammation markers, and coagulation variables [
9]. It is possible that the link between diet and VTE is potentially through other aspects of their lifestyle: people who are less health conscious may be less concerned about a healthy diet and may place less importance as well on physical activity, exposing them to a greater risk of prolonged non-pulsatile venous blood flow and consequent valve pocket hypoxemia. According to the valve cusp hypoxia hypothesis (VCHH) deep venous thromboembolism may occur wherever sustained non-pulsatile venous blood flow leads to suffocating hypoxemia in the valve pockets, resulting in hypoxic injury to and hence death of the inner endothelium of the cusp leaflets [
9].
Furthermore both diets before and after the PE were very high in sodium intake, which would be inappropriate in a patient with a long history of hypertension. Our patient also had hyperhomocysteinemia, despite vitamin B12 and folate supplementation. High plasma concentration of homocysteine may be due to genetic defects in the enzymes involved in homocysteine metabolism (i.e. homozygosity for the thermolabile variant of methylene tetrahydrofolate reductase, MTHFR -TT genotype), nutritional deficiencies in vitamin cofactors (folate, vitamin B6, and vitamin B12 [
29‐
32]), or other factors including some drugs such as oral contraceptives. Given her absence of MTHFR mutation, it is most likely her hyperhomocysteinemia was due to both the long-term oral contraceptive therapy and to a low folate diet. Since prothrombotic effects of homocysteine have been demonstrated [
33‐
36], it is important to include this parameter in the nutritional assessment. Indeed, a proper assessment of patients with obesity should include vitamin status especially in those at risk of subclinical deficiencies.
This case illustrates the need for a thorough medical nutrition assessment in the management of patients with obesity. Weight loss therapy, cannot be focused only on lowering calories, but should include care to meet macro and micronutrients recommendations even through supplementation, if necessary.
A vitamin K free diet, such as Table
1(b), is very often prescribed to patients who had a PE and are on warfarin. Individuals on warfarin generally are sensitive to fluctuations in vitamin K intake, and adequate INR control requires close attention to the amount of vitamin K ingested from dietary and other sources [
37]. This case report highlights the need for a change in the clinical approach of patients taking warfarin. The aim of nutritional therapy should be to keep dietary intake of vitamin K constant rather than to exclude it completely from the diet, which is not uncommon in the clinical practice. Several studies have demonstrated the relationship between vitamin K intake and INR control [
38‐
40] in particular suggesting patients should be advised to consume a healthy diet, and they should not avoid fruits and vegetables for fear of altering the INR.
Despite the evidence, it is common practice to suggest vitamin K free diets to all patients on oral anticoagulants therapy. The main consequence of this recommendation is the exclusion of vegetables and fruit from the diet, resulting in nutrient deficiencies and impaired health status. We should not forget that eliminating these very important food groups puts our patients at further risk.
In the field of cardiovascular risk and diseases, medical nutrition therapy plays a crucial role in providing both prevention and therapy. A correct and complete nutritional assessment is essential for effective therapy. Nutritional intervention should be tailored to the individual patient and should provide the correct amount of macronutrients, micronutrients and vitamin or mineral supplementation if needed.