Venous Thromboembolism - Management Bệnh lý nền

Introduction

Venous thromboembolism (VTE) is most commonly manifested as pulmonary embolism (PE) and deep venous thrombosis (DVT) and is associated with significant morbidity and mortality. One-third of patients present with symptoms of pulmonary embolism and ⅔ with deep vein thrombosis. It also manifests as superficial vein thrombosis (SVT), a less severe form of deep vein thrombosis.  

All patients admitted for major trauma, surgery or acute medical illness should be assessed for risk of VTE and bleeding before starting prophylaxis of VTE.  Studies show that appropriate VTE prophylaxis should be given to surgical patients in Asia who are at risk.

Deep Vein Thrombosis (DVT)  

Deep vein thrombosis is a frequent manifestation of venous thromboembolism in which there is a blood clot blocking a deep vein. Patients are generally asymptomatic with a calf deep vein thrombosis but become symptomatic with proximal extension of the deep vein thrombosis and venous outflow obstruction.  

Pulmonary Embolism (PE)  

Pulmonary embolism is the blockage of the blood vessels in the lungs that is usually due to blood clots from the veins, especially the veins in the legs and pelvis. Subsegmental pulmonary embolism is a type of pulmonary embolism that does not involve the proximal pulmonary arteries. 

Epidemiology

The annual incidence of the first symptomatic deep vein thrombosis episode in adults ranges from 50 to 100 per 100,000 population, 70% of which are hospital-acquired. At ages 20 to 45 years old, the incidence is higher in women and at ages 45 to 60 years old, the incidence is higher in men. About 60% of venous thromboembolism events occur in >65 to year-old patients. The incidence of deep vein thrombosis is higher in African Americans and lower in Asians and the incidence of venous thromboembolism is higher in winter with a peak in February.  

The rate of recurrent venous thromboembolism is approximately 10% during the first year and 30% after 5 to 8 years in patients with unprovoked deep vein thrombosis with unidentified triggering factors. The prevalence of clinically silent pulmonary embolism increases with age in patients with deep vein thrombosis and is higher in patients with proximal deep vein thrombosis.  

Venous thromboembolism is the third most common cause of acute cardiovascular disease (CVD) worldwide. It is one of the most common life-threatening cardiovascular diseases in the United States.  

In Asia, VTE has long been observed to be rare, and the lowest among the different regions. However, cases of VTE in Asia are increasing due to the aging population, higher rates of complex surgery, higher rates of caesarean deliveries, rising cases of obesity, increasing cancer cases, and lower rates of thromboprophylaxis. Currently, obstetric VTE is the leading cause of maternal death in Malaysia.

Pathophysiology

Virchow’s triad theorizes 3 factors contributing to the development of venous thromboembolism which are hypercoagulability, endothelial damage, and stasis.  

Hypercoagulability has been associated with factor V Leiden mutation and prothrombin gene mutation. Cancer also produces a hypercoagulable state due to the procoagulant activity produced by malignant cells and secondary to the effects of chemotherapeutic agents.  

The major contributing risk factors include a history of trauma, surgical procedures, spinal cord injury, long bone fractures, and previous venous thromboembolism.

Risk Factors

The transient or reversible provoking factors for the development of venous thromboembolism include surgery within the past 4 weeks (eg hip or knee replacement), major trauma, immobilization for at least 3 days, bedridden for ≥3 days, estrogen therapy, pregnancy or postpartum, cesarean section, and lengthy travel (eg airline flight >8 hours).  

The chronic or persistent provoking factors for the development of venous thromboembolism include active cancer, active autoimmune disease (eg antiphospholipid antibody syndrome, rheumatoid arthritis), chronic infections or immobility (eg spinal cord injury), and chronic inflammatory states (eg inflammatory bowel disease).    

Other risk factors for the development of venous thromboembolism include myocardial infarction (MI) or hospitalization for atrial flutter or fibrillation or heart failure (HF) within the past 3 months, increasing age, male sex, past medical history or family history of venous thromboembolism, lower limb fracture, congestive heart failure or respiratory failure, obesity, varicose veins, blood transfusion and erythropoiesis-stimulating agents, prolonged computer-related "seated immobility syndrome",  and hereditary risk factors including non-O blood type and heterozygous factor V Leiden gene polymorphism, and deficiency of antithrombin, protein C or protein S. 

Classification

Classification of Deep Vein Thrombosis
 
According to the Anatomical Level  

Accurate anatomical classification is important for diagnostic, therapeutic, and prognostic purposes as the risk of pulmonary embolism, post-thrombotic syndrome development, and overall prognosis are different depending on the affected veins. Deep vein thrombosis may be classified into proximal and distal deep vein thrombosis.

Proximal deep vein thrombosis is thrombosis of the iliac, femoral, and/or popliteal veins with or without calf deep vein thrombosis. This includes femoropopliteal deep vein thrombosis and iliofemoral deep vein thrombosis (which commonly occurs on the left).

Distal deep vein thrombosis is thrombosis confined to the calf-deep veins (eg peroneal, posterior tibial, gastrocnemius, or soleal veins). It is often associated with transient risk factors (eg recent surgery, plaster placement for limb fracture, travel).  

According to Etiology  

Deep vein thrombosis may also be classified as provoked or unprovoked based on the presence of risk factors. Unprovoked or idiopathic deep vein thrombosis is venous thrombosis without identifiable environmental or acquired risk factors. Provoked deep vein thrombosis occurs in the presence of risk factors which may be transient minor or major risk factors or persistent risk factors.  

The risk of recurrence and anticoagulation therapy will differ based on the etiology and chronicity of the risk factors. The risk of recurrence is higher when deep vein thrombosis is provoked by a persistent and progressive risk factor (eg cancer). The risk of recurrence after stopping anticoagulation is very low when deep vein thrombosis is provoked by a major transient risk factor (eg trauma, surgery, estrogen therapy, pregnancy, puerperium) provided the risk factor is no longer present. Patients with unprovoked deep vein thrombosis have an intermediate risk of recurrence.