Pulmonary embolism is defined as an obstruction of the pulmonary artery by an embolus, i.e. blood clot, that originates in deep veins of the lower limbs or pelvis, and then a part of it is detached and lodged in one of the pulmonary arteries. When it is big enough, it may obstruct the main pulmonary artery, causing a critical condition known as massive pulmonary embolism that leads to hemodynamic compromise. Clearly, the condition always starts with deep vein thrombosis (DVT), and then complicates with pulmonary embolization.
In susceptible persons with several risk factors, platelet adhesion and aggregation take place forming a platelet nidus in the veins of the lower limbs or pelvis. This may also happen to a lesser extent in the upper limb. This event precedes thrombosis, increasing platelet aggregation and recruiting a fibrin network that filters more platelets from the blood, leading to a progressive stagnation and more thrombosis. Ultimately, a whole thrombus is formed. Blood fibrinolytic substances interacts with the thrombus, and then leads to partial dissolution. Detached particles of this thrombus will form the embolizing pulmonary thrombi that obstruct the pulmonary vessels.
So, why does venous thromboembolism take place?
The most important pathogenesis mechanism, which has been well-established by evidence-based medicine, is the so called “Virchow triad”, which consists of:
- Endothelial wall injury
- Stasis i.e. prolonged recumbency
- Blood hypercoagulability
Many acquired and congenitally inherited risk factors influence blood coagulability. For instance, thrombophilia is defined as hypercoagulable conditions that predispose people to an increased risk of venous thrombosis. These conditions are classified into acquired and inherited.
The most common inherited risk factors that are incorporated in venous thromboembolism are as follows:
- Factor V Leiden
- Prothrombin gene mutation G20210A
- Protein C and S, i.e. natural anticoagulants, deficiency
- Increased blood homocysteine
- Elevated factor VIII levels
On the other hand, the most common acquired risk factors are:
- Prolonged immobilization, long travel trips more than 3 hours in susceptible individuals
- Oral contraceptive pills
- Hormonal replacement therapy
- Antiphospholipid syndrome (Lupus anticoagulant/ anticardiolipin)
- Heparin induced thrombocytopenia
- Inflammatory bowel disorders
- Central venous catheters
- Nephrotic syndrome
- Dehydration and increased blood viscosity
- Disseminated intravascular thrombosis
Hypercoagulability screening should be considered in patients with:
- Idiopathic Venous thromboembolism,
- Positive family history of venous thromboembolism,
- Early adulthood venous thromboembolism, i.e. first thrombotic event before the age of 50 years,
- thrombosis at unusual locations,
- Resistance to anticoagulation i.e. patients who experience thrombotic attacks while being properly anticoagulated medically,
- Recurrent thrombotic attacks.
1Factor V Leiden
Activated C Protein inactivates factors Va and VIIIa through this and other mechanisms to keep the blood in balance between clotting and bleeding. The autosomal dominant acquisition of a single-point mutation (FVL) in the factor V gene makes factor V resistant to inactivation by the activated C Protein. Both homozygous and heterozygous forms are present, and both result in an increased risk of venous thrombosis. The homozygous form is at much more risk, with a 50-fold to 100-fold increase versus a 3-fold to 7-fold increase in the heterozygous form.