Thromboembolism 

Thromboembolism encompasses two interrelated conditions that are part of the same spectrum, deep venous thrombosis (DVT) and pulmonary embolism (PE). PE is the obstruction of blood flow to one or more arteries of the lung by a thrombus lodged in a pulmonary vessel, as shown in the image below.

PE and DVT can occur in the setting of disease processes, following hospitalization for serious illness, or following major surgery. In 1856, Virchow demonstrated that 90% of all clinically important PEs result from DVT occurring in the deep veins of the lower extremities, proximal to and including the popliteal veins. However, emboli also can originate from the pelvic veins, the inferior vena cava, and the upper extremities.^{[1, 2, 3, 4, 5]}

Thromboembolic disease is the third most common acute cardiovascular disease, second to cardiac ischemic syndromes and stroke. Both DVT and PE frequently remain undiagnosed because they may be unsuspected clinically. The spectrum of disease ranges from clinically unsuspected, to clinically unimportant, to massive embolism causing death. Untreated acute proximal DVT causes clinical PE in 33-50% of patients. Untreated PE often is recurrent over days to weeks and can either improve spontaneously or cause death.

American Academy of Orthopaedic Surgeons Guidelines

The clinical practice guideline published in 2009 by the AAOS regarding the prevention of pulmonary embolism in patients undergoing total hip replacement (THR) or total knee replacement (TKR) includes the following recommendations^{[6, 7, 8, 9]} :

• Mechanical prophylaxis and early mobilization are recommended for all patients.
• The following statements summarize the recommendations for chemoprophylaxis:

  • Patients at standard risk of both PE and major bleeding should be considered for aspirin, low-molecular-weight heparin (LMWH), synthetic pentasaccharides, or warfarin with an international normalized ratio (INR) goal of less than or equal to 2.0.
  • Patients at elevated (above standard) risk of PE and at standard risk of major bleeding should be considered for LMWH, synthetic pentasaccharides, or warfarin with an INR goal of less than or equal to 2.0.
  • Patients at standard risk of PE and at elevated (above standard) risk of major bleeding should be considered for aspirin, warfarin with an INR goal of less than or equal to 2.0, or none.
  • Patients at elevated (above standard) risk of both PE and major bleeding should be considered for aspirin, warfarin with an INR goal of less than or equal to 2.0, or none.

Recent studies

Markel et al reported on a 2008 survey of American Association of Hip and Knee Surgeons, exploring venous thromboembolism protocols for lower-extremity total joint surgery. More than 70% reported that their primary hospital now mandates prophylaxis for venous thromboembolism. Low-molecular-weight heparin was considered to be the most efficacious, but aspirin was considered the easiest to use with the lowest risks of bleeding and wound drainage. Warfarin was the most used agent in hospital prophylaxis, and 90% of respondents targeted an international normalized ratio of 1.6 to 2.5.^[10]

Merli et al reviewed clinical studies of oral anticoagulants for venous thromboembolism prevention in orthopedic surgery and compared them with large observational registries. Results from phase II/III studies, according to the authors, suggest that new oral anticoagulants may provide an efficacious alternative in prevention of venous thromboembolism in orthopedic surgery and have had a good overall safety profile, with no evidence of increased hepatotoxicity. Comparison with large observational registries, however, revealed differences between real-life patient populations, and differences in endpoint definitions also prevented indirect comparison of agents. The authors added that specific compliance and postmarketing safety issues (especially liver enzyme monitoring requirements) need to be clarified before these agents can be widely accepted in routine clinical practice.^[11]

A prospective open cohort study developed a new clinical risk prediction algorithm (QThrombosis) to asses the risk of developing venous thromboembolism. Using routinely collected data from 564 general practices in England and Wales, this study found that independent predictors at 1 and 5 years included age; body mass index; smoking status; hospital admission in past 6 months; history of varicose veins, congestive cardiac failure, chronic renal disease, cancer, chronic obstructive pulmonary disease, or inflammatory bowel disease; and current prescriptions for antipsychotic drugs in both men and women. Oral contraceptive use, tamoxifen use, and hormone replacement therapy were noted as independent predictors in women. This risk assessment can help identify patients at high risk of venous thromboembolism and may help determine a course of treatment.^[12]

A review of a clinical practice guideline from the American College of Physicians reports that in nonsurgical patients, heparin prophylaxis has no significant effect on mortality and it led to more bleeding and bleeding events, suggesting it is of little or no benefit overall. In addition, no improvements in clinical outcomes were found with mechanical prophylaxis, which also resulted in an increase in lower-extremity skin damage in stroke patients.^[13]

Hypercoagulability or obstruction leads to the formation of thrombus in the deep veins of the legs, pelvis, or arms. As the clot propagates, proximal extension occurs, which may dislodge or fragment and embolize to the pulmonary arteries. This causes pulmonary artery obstruction, and the release of vasoactive agents (ie, serotonin) by platelets increases pulmonary vascular resistance. The arterial obstruction increases alveolar dead space and leads to redistribution of blood flow, thus impairing gas exchange due to the creation of low ventilation-perfusion areas within the lung.

Stimulation of irritant receptors causes alveolar hyperventilation. Reflex bronchoconstriction occurs and augments airway resistance. Lung edema decreases pulmonary compliance. The increased pulmonary vascular resistance causes an increase in right ventricular afterload, and tension rises in the right ventricular wall, which may lead to dilatation, dysfunction, and ischemia of the right ventricle. Right heart failure can occur and lead to cardiogenic shock and even death. In the presence of a patent foramen ovale or atrial septal defect, paradoxical embolism may occur, as well as right-to-left shunting of blood with severe hypoxemia.

Frequency

United States

Epidemiologic studies of thromboembolism in Massachusetts and Minnesota find the incidence of venous thromboembolism to be about 1 in 1000 per year. Approximately 5 million cases of deep venous thrombosis and about 600,000 cases of pulmonary embolism occur per year.

International

Thromboembolism has a significant impact on morbidity and mortality internationally. A large survey from Sweden documented confirmed deep venous thrombosis in 1.6 in 1000 per year. The Scandinavian literature also documents that 3-4% of patients who died within 3 months of a fractured neck of the femur died of fatal pulmonary embolism.

Mortality/Morbidity

About one third of PE cases are fatal. Sixty-seven percent of these are not diagnosed premortem, and 34% occur rapidly. A high rate of clinically unsuspected DVT and PE leads to significant diagnostic and therapeutic delays, and this accounts for substantial morbidity and mortality.

Thromboembolic disease accounts for approximately a quarter of a million hospitalizations in the United States yearly and for about 5-10% of all deaths.

Race

The incidence of thromboembolism is higher in African Americans than it is in whites. Asians have a lower incidence than both African Americans and whites.

Sex

Pulmonary embolism occurs more frequently in men than in women.

Age

Age is a risk factor for thromboembolic disease. The risk of thromboembolic disease is greater in older patients than in younger patients. It doubles with each decade in persons older than 40 years.