VTE Risk in Medical Illness & Pregnancy

VTE risk is a common, but preventable, complication

Although many associate venous thromboembolism (VTE) with recent trauma or surgery, 50% to 70% of symptomatic cases, as well as the majority of cases of fatal pulmonary embolism (PE), occur in medical (nonsurgical, nontrauma) patients.^{3, 61} In addition, in many instances, VTE is idiopathic.⁶⁵ Because of the often silent nature of VTE, the first sign of a problem may be a clinically significant event, such as PE.

Immobilisation increases the risk of VTE

Hospitalised medical patients are often immobile because of weakness, reduced alertness, or nerve injury. In addition, patients in critical care settings are often bedridden. Even in the absence of medical illness, lack of mobility can lead to venous stasis and VTE, as can occur during long-distance air travel.^{1, 63}

Patient-related, predisposing characteristics that increase risk of VTE^{3, 64, 246}

Recent surgery or major trauma
Immobility or paralysis
Malignancy
Previous VTE
Older age, particularly ≥ 75 years
Oestrogen therapy (contraceptives or hormone replacement)
Obesity
Central vein catheterisation
Varicose veins
Inherited or acquired thrombophilia
First-degree relative with history of VTE

Age, in particular, is a one of the most important risk factors for VTE. The risk increases exponentially over time, from a negligible rate in children under 15 (<5 per 100,000) to a rate of ~500 per 100,000 in those over 80.^{65, 66}

Hospitalised patients often have multiple risk factors for VTE

Patients hospitalised because of medical illness often have multiple risk factors for VTE, and these risks are generally cumulative.^{3, 64} Accordingly, all patients should be evaluated for their risk of VTE at the time of hospital admission. This evaluation should be repeated whenever there is a significant change in a patient’s clinical status.⁶⁴

Preventive treatment can reduce incidence of VTE

Prospective studies have shown that hospitalised medical patents at high risk who do not receive preventive anticoagulant therapy develop deep vein thrombosis (DVT) in the calf in 10% to 15% of cases. The same studies revealed an incidence of proximal DVT in 2% to 5% and of PE in 0.3% to 1.5%.^{64, 67, 68}

Studies have also shown that anticoagulant prophylaxis reduces the risk of symptomatic VTE in hospitalised medical patients.⁶⁹ Despite the clear need for prophylactic care to prevent VTE in high-risk medical patients, a recent multinational, cross-sectional audit⁵⁷ revealed that approximately 42% of hospitalised medical patients at risk received appropriate VTE prophylaxis. This report — from the ENDORSE survey — revealed wide variation between countries in the use of preventive therapy for VTE. In general, more severely ill patients were more likely to be treated with medication to prevent VTE.¹⁶⁴ Therefore, timely risk assessment and preventive therapy is the optimal therapeutic approach.³

Conditions associated with an increased risk of bleeding in hospitalised medical patients¹⁷⁹

According to the UK’s recent update of the National Institute for Health and Clinical Evidence (NICE) guidelines, approximately 10,000 lives could be saved each year if patients were assessed for their risk of developing blood clots at the time of hospital admission.^{179, 246} These guidelines also suggest that all patients with reduced mobility for 3 days be considered at risk for VTE.²⁴⁶

Fear of causing bleeding is a possible reason why clinicians tend to underuse therapy to prevent VTE. The IMPROVE (International Medical Prevention Registry on Venous Thromboembolism) registry provides data to help assess the risk of bleeding in hospitalised medical patients. Results from this observational study of over 10,000 patients who were not bleeding at the time of admission revealed the following risk factors:¹⁷⁹

Active gastroduodenal ulcer
Bleeding during the 3 months before admission
Platelet count <50 x 109 cells/L
Advanced age
Renal failure
Hepatic failure
Central venous catheter
Rheumatic disease
Cancer at the time of hospital admission
Male sex

VTE risk associated with cancer

Cancer, in particular, is a major risk factor, as 1 in 5 diagnosed cases of VTE occurs in a person with cancer,^{62, 234} and VTE is a leading cause of death in patients with cancer. The incidence of symptomatic VTE in patients with malignancies ranges from 4% to 20% depending on the study.⁶²

Certain medications used to treat cancer, such as tamoxifen and erythropoietin, increase the risk of VTE. In addition, novel chemotherapeutic agents that suppress blood vessel formation (eg, thalidomide, lenalidomide, and bevacizumab) have been associated with a high rate of VTE.^{62, 70}

In a multinational survey of VTE risk and prophylactic treatment involving over 37,000 hospitalised medical patients, 34% of those with an active malignancy were considered at risk for VTE based on American College of Chest Physicians (ACCP) guidelines. (In this survey, 44% of these patients actually received appropriate VTE prophylaxis.)¹⁶⁴

Certain cancers are associated with higher VTE risk

The risk of thrombosis is greatest in the first year after the diagnosis of cancer malignancy.^{71, 72} Certain cancers are associated with a higher VTE risk (eg, pancreatic, gastric, colon, brain, kidney, ovarian, prostate, haematologic, and lung), and metastatic disease confers a greater risk than primary tumours.⁶² The same predisposing factors that elevate the risk of VTE in surgical patients and in hospitalised patients without cancer augment the overall risk in patients with cancer.⁶²

A validated predictive model for VTE risk in cancer patients receiving chemotherapy enables clinicians to determine whether patients are at particularly high risk for VTE.²¹⁴

Predictive Model for Chemotherapy-Associated VTE
Patient Characteristic	Risk Score
NOTE: high risk defined as risk score ≥ 3. Abbreviation: VTE, venous thromboembolism
Site of cancer Very high risk (stomach, pancreas) High risk (lung, lymphoma, gynaecologic, bladder, testicular)	2 1
Prechemotherapy platelet count ≥ 350,000/µL	1
Haemoglobin < 10g/dL or use of RBC growth factors	1
Prechemotherapy leukocyte count > 11,000/µL	1
Body mass index ≥ 35 kg/m²	1

VTE risk in heart failure

Hospitalised patients with heart failure are at increased risk for VTE. Both DVT and pulmonary embolism (PE) are associated with significant morbidity and mortality in this patient population. Other conditions and comorbidities commonly associated with heart failure and linked to increased VTE risk include the use of pacemakers, implantable defibrillators and central venous catheters.²⁴⁷

VTE risk in pregnancy

The risk of VTE significantly increases during pregnancy, and this risk can persist for up to 6 weeks after delivery. This heightened risk is primarily a result of hypercoagulability induced by hormonal changes, which can be present as early as the first trimester. A personal history of thrombosis and a personal history of inherited or acquired thrombophilia are also important risk factors for VTE during pregnancy. Other risk factors include cardiovascular conditions, including heart disease and hypertension; well-recognised general VTE risks such as reduced mobility, obesity, active cancer, and critical care unit admission; haematologic disorders such as anaemia and sickle cell disease; systemic disorders such as diabetes and lupus; and miscellaneous factors such age over 35, dehydration and smoking.^{182, 208, 246}

Pregnancy and delivery complications have been reported to further elevate VTE risk. These complications include multiple births, pre-eclampsia, caesarean delivery, postpartum infection, postpartum bleeding and blood transfusion.^{208, 246}

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Article references

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Venous thromboembolism: A condition in which a blood clot (thrombus) forms in a vein, which in some cases then breaks free and enters the circulation as an embolus, finally lodging in and completely obstructing a blood vessel, e.g., in lungs causing a PE. The term encompasses both DVT and PE.
Venous stasis: The presence of an abnormally low rate of blood flow in the veins. This can be caused by, for example, the use of a tourniquet or prolonged immobility.
Prophylaxis: The prevention of a disease or pathological condition.
Venous catheter: A tube inserted into a vein to deliver medication (such as chemotherapy) to a patient.
American College of Chest Physicians: Multidisciplinary international medical society based in Northbrook, Illinois, USA, that focuses on the treatment and prevention of all diseases of the chest. It has over 16,000 active members with physicians representing all chest medicine disciplines. Publishes the journal Chest.
Hypercoagulability: A potentially dangerous state of an increased tendency for blood to coagulate, even within blood vessels. Hypercoagulability can be an inherited condition (e.g., Factor V Leiden mutation) or acquired through circumstance (e.g., cancer).