Venous Thromboembolism - Management Disease Background

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 DVT. It also manifests as superficial vein thrombosis (SVT) of the arms and legs and rarely develops into a DVT.

 

Venous Thromboembolism - Management_Disease Background

Epidemiology

The annual incidence of the first symptomatic DVT episode in adults ranges from 50-100 per 100,000 population, 70% of which are hospital-acquired. VTE is slightly more common in men. 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. Incidence of VTE increases with age, with 60% of VTE events occur in >65 to year-old patients. The incidence of DVT is higher in African Americans and lower in Asians and the incidence of VTE is higher in winter with a peak in February. 

Pulmonary embolism is more frequent in the older age groups than DVT. The prevalence of clinically silent pulmonary embolism increases with age in patients with DVT and is higher in patients with proximal DVT. VTE is the third most common cause of acute cardiovascular disease worldwide. It is one of the most common life-threatening cardiovascular diseases in the United States and with increasing incidence and mortality rates in Asia. 

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 VTE which are hypercoagulability, vascular 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 VTE. VTE can also be spontaneous or unprovoked in 20-40% of cases.  

Risk Factors

The transient or reversible provoking factors for the development of VTE include surgery within the past 4 weeks (eg hip or knee replacement [lower limb orthopedic procedure]), general anesthesia >30 minutes, major trauma, immobilization for at least 3 days, bedridden for ≥3 days, oral contraceptives or hormone replacement therapy  (eg Estrogen therapy), pregnancy or postpartum, cesarean section, acute inflammation, indwelling venous catheters, travel-associated immobility (5-6 hours), Heparin-induced thrombocytopenia (HIT), medications (eg Tamoxifen, Lenalidomide, erythropoietin, L-asparaginase).

The chronic, non-reversible or persistent provoking factors for the development of VTE include active cancer, active autoimmune disease (eg antiphospholipid antibody syndrome, rheumatoid arthritis, systemic lupus erythematosus, immune/thrombotic thrombocytopenic purpura), chronic infections or immobility (eg spinal cord injury), chronic inflammatory states (eg inflammatory bowel disease), morbid obesity (body mass index [BMI] >40), nephrotic syndrome, and recurrent long-haul flights.

Other risk factors for the development of VTE 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 VTE, lower limb fracture, congestive HF 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 DVT
 
According to the Anatomical Level  

Accurate anatomical classification is important for diagnostic, therapeutic, and prognostic purposes as the risk of pulmonary embolism, postthrombotic syndrome development, and overall prognosis are different depending on the affected veins. DVT may be classified into proximal and distal DVT. 
 
Proximal DVT is thrombosis of the iliac, femoral, and/or popliteal veins with or without calf DVT. The clinical manifestations of proximal DVT involve the whole leg. This includes femoropopliteal DVT and iliofemoral DVT (which commonly occurs on the left). 

Distal DVT is thrombosis confined to the calf-deep veins (eg peroneal, posterior and anterior tibial, gastrocnemius, or soleal veins). The clinical manifestations of distal DVT are localized to the calf. It is often associated with transient risk factors (eg recent surgery, plaster placement for limb fracture, travel). 

According to Etiology  

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

Transient minor risk factors that favor continuing anticoagulation include minor surgery <30 minutes, hospitalization <3 days, reduced mobility ≥3 days due to acute illness, lower extremity injury without fracture with reduced mobility ≥3 days, and long-haul flight.

Transient major risk factors that favor limited-duration anticoagulation include major surgery >30 minutes, hospitalization or reduced mobility ≥3 days, due to acute illness, trauma with fractures, Estrogen therapy, pregnancy or puerperium. 

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 DVT is provoked by a persistent and progressive risk factor (eg cancer). The risk of recurrence after stopping anticoagulation is very low when DVT 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 DVT have an intermediate risk of recurrence.