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Venous thromboembolism (VTE) is a multicausal disease that manifests in the form of deep
vein thrombosis (DVT) and pulmonary embolism. The basic principle of VTE is that a blood
clot has formed in the veins.

Etiology of VTE

The risk of VTE increases with age. Age can also be a precursor to
other predisposing factors such as decreased mobility, increased occurrence of
risk-enhancing diseases, decreased muscular tone and the acquisition of other
risk factors.1


Underlying medical conditions
Immobilisation that causes lack of movement or stasis in the limbs can
increase the risk of VTE occurrence because stasis leads to reduced blood
circulation. Pregnancy increases the risk of VTE events as well. Risk for VTE
is highest during the third trimester. Most thrombotic events take place in the
left leg. This is related to the gravid uterus pressing against the common iliac
vein. Venous thrombosis due to pregnancy is rare, however in approximately
half of the thrombotic events concerning women are related to pregnancy. Risk
of thrombosis during pregnancy is affected by the abnormalities in
prothrombin and increases during the absence of antithrombin.1


Surgery and trauma
In the absence of antithrombotic prophylaxis, the risk for VTE postsurgery is 50% higher. Surgery alone significantly increases the risk of
thrombotic events. Even with anticoagulants as prophylaxis, the risk of VTE
after surgery remains high. Arthroscopic knee surgery is a surgical procedure
that is most often associated with VTE.2


Cancer increases risk for thrombotic events through several
mechanisms. Production of tissue factors by malignant cells sets precedence
for procoagulant state due to humoral factor. Besides, large tumours may
become a mechanical factor in venous thrombosis because they can cause
venous compression and venous obstruction. Other determinants in the risk for
VTE in cancer patients are the stage and type of the tumour, anticancer
therapy (chemotherapy, hormonal therapy, angiogenesis inhibitors, and
supportive therapy), surgery, and prothrombotic abnormalities.3

all of which increase the risk for thrombotic events if present. This was observed in a minority of individuals and the risk is doubled in those with prothrombotic risk factors. 1. it is worth noting that alcohol consumption appears to possess a protective effect. increases the risk of VTE. However other methods of travel also can result in thrombosis. The risk of pulmonary embolism increases with the increase in flight duration.6 Medication and lifestyle habits 1.6.1 1. Other variables that should be taken into account are presence of prothrombotic genetic variants.3 Oral contraceptives Oral contraceptives that contain oestrogen have several effects on the coagulation system. However.1 Long-distance travel Air travel has been known to present a high risk for pulmonary embolism. usage of oral contraceptives.1 Risk for VTE is increased in prolonged periods of immobilisation. whether in patients with or without systemic lupus erythematodes. regardless of frequency and intensity of the exercise. smoking. Not only the duration of travel but the conditions in air travel. hence increasing the risk of a thrombotic event.5 Antiphospholipid antibodies The presence of antiphospholipid antibodies.6.1 1.1 1.2 Lifestyle The risk for venous thrombosis is decreased in those who practice physical exercise.6. increasing levels of procoagulant factors and reducing levels of natural anticoagulants. results in hypercoagulation.The mode of treatment also influences the risk of cancer in causing VTE.7 Genetics . 1. weight (there is higher risk in the obese) and height. and use of oral contraceptives. Central venous catheters are identified as the most significant cause of symptomatic thrombosis in the arm. Those that contain third-generation progestrogens present a higher prothrombotic effect than those containing second-generation progestrogens. Regular alcohol consumption has some protective effect but this effect is most pronounced in those who consume two to four glasses of alcohol per day.2 Other lifestyle factors include obesity. such as hyperbaric hypoxia.

which causes the .5 The initiation phase begins with the FVIIa/TF (tissue factor) complex activating small amounts of factor IX and X. where activated protein C (APC) inactivates factor Va. protein C.1 1. High levels of factor VIII are related to the ABO blood type. Fibrinolytic factors Risk for venous thrombosis is increased with high levels of thrombin activatable fibrinolysis inhibitor (TAFI). Factor Xa associates with factor FVa to form prothrombinase complexes on the TF-bearing cells. and its cofactor S causes hypercoagulation and leads eventually to thrombosis. Platelets become adherent to collagen and other extracellular components at the site of injury. Factor V Leiden is a mutation of the gene that is found in 20% of patients with venous thrombosis. the higher the risk for venous thrombosis. thus increasing the risk for venous thrombosis twentyfold compared to individuals without both mutation.1 Hyperhomocysteinaemia There is a connection between elevated homocysteine levels in the plasma and venous thrombosis. are responsible for elevated risk for venous thrombosis.8.Deficiencies of natural coagulation inhibitors such as antithrombin. Haemostasis occurs as a result of the formation of an impermeable platelet and fibrin plug at a site of injury.8 Other abnormalities in the plasma 1. There are several key steps in the coagulation process.3. Mutation of the untranslated part of the prothrombin 20210A gene causes increased prothrombin levels that is related to the increased risk of venous thrombosis. The mutation causes a resistance to APC. These deficiencies are rare but considered as strong genetic risk factors.8. notably factors VIII. IX and XI as well as prothrombin and fibrinogen.1 2.2 High level of clotting factors Excess of clotting factors responsible for coagulation. The mutation is located in a part of the gene that encodes for one of the cleavage sites of factor V.0 Pathophysiology The key to venous thromboembolism is haemostasis. It also requires the procoagulant substances to not only be activated but also remain localised at the site of injury.1 1. Both factor V Leiden and prothrombin 20210A is not an uncommon mutation and can occur together as compound heterozygotes.4 1.8. The higher the level of homocysteine in the plasma.

Excess thrombin from the propagation phase has been proposed to activate TAFI.activation of other platelets and promotes secretion of partially activated FV. Hypercoagulability and thus thrombotic events occur when the fibrinolytic system fails to be activated. which will dissolve the fibrin mesh by degrading it into soluble end products known as fibrin split products or fibrin dissolution products.5 Fibrinolytic system is responsible for clot dissolution. Under normal circumstances. Factor XIIIa covalently seals the fibrin strands together until they form a meshwork that surrounds and envelopes the aggregated platelets to form a stabilised clot. The activating factors that come into initial contact with the platelets that were attracted to the collagen are thus sequestered and does not allow for further coagulation. the second is the supply of additional FIXa by platelet-bound FXIa. Usually FXa is protected from inhibition by plasma protease inhibitors and this prevents formation of clots. Plasminogen is converted to plasmin by tissue plasminogen activator and urokinase plasminogen activator.5 Thrombin generated by TF-bearing cells induces a higher level of procoagulant activity by activating more platelets in the vicinity of the injury site. This sets the stage for thrombin activation on a massive scale and constitutes the amplification stage. which are platelets and FVIII complexed with von Willebrand factor (vWF) are sequestered. rather the site of initiation of the coagulation eventually gets ‘paved over’ by platelets and fibrin. the presence of inhibitors of the plasma protease will cause the activity of FXa to be localised to the surface on which it was formed. The coagulation process does not immediately halt.5 The propagation phase consists of several key events. and the third event is where FXa rapidly associates with platelet surface FVa to mass-produce thrombin in a short time with enough magnitude to cause fibrinogen to clot. However. forming fibrin strands.5 The final step is the conversion of fibrinogen to fibrin that is mediated by thrombin.0 Clinical importance VTE can be managed through several steps: conventional anticoagulants that consist of unfractionated heparin. Plasminogen activator inhibitor-1 inhibits plasminogen activators while antiplasmin inhibits plasmin activity.6 3. The first is the binding of activated FIXa to FVIIIa on the surface of the platelet. Factor Xa that dissociates from the cells that carry TF is rapidly inhibited in the fluid phase by TF pathway inhibitors (TFPI) or antithrombin (AT). which protects the clot from proteolysis. Thrombin also activates factors V and VIII on the platelet surface as well as FXI. the TF pathway does not cause clot formation because the important clotting factors. which has since been replaced by low molecular .

it will be too costly to maintain. The articles used consist of journal articles. METHODS The articles used for this report are not older than the year 2005. The articles that were used as reference for the report are not confined to a particular type. LMWH also poses some disadvantages of its own. Not only is extensive monitoring required. It possesses several disadvantages: slow onset of action. ‘venous thrombosis’ and ‘VTE’.8 As both LMWH and warfarin possess their own advantages and disadvantages. The search engine that is used is Google. tertiary source was used in the introduction part of the article only. Warfarin is the most common oral anticoagulant used for the management of VTE. Besides that. narrow therapeutic window. food and drug interaction.weight heparin (LMWH) and vitamin K antagonists such as warfarin. LMWH is costeffective compared to unfractionated heparin as initial therapy. but tertiary sources such as clinical practice guidelines and textbooks were not used in the comparative review of LMWH and warfarin. However. most compared LMWH and warfarin. The online scientific databases used to search and obtain the journals are ScienceDirect and PubMed. there is need to review both treatment options for VTE. and wide interindividual dosing differences. However in the long run.7 However. The main search keywords used during the information sourcing process are ‘venous thromboembolism’. The anticoagulant effect of LMWH is not as easily reversed as warfarin. There were also randomised trials that were considered as the best primary source that were used as reference for this report. LMWH is not adequate for patients with renal insufficiency as it is renally excreted. They are sourced online through various search engines and databases. The dosage for LMWH must be adjusted to suit the body weight of patients as different weight constitutes different risk of bleeding from LMWH against oral anticoagulants. but warfarin resistance and optimal warfarin initiation dose are also a concern. References: .

Long-term Lowmolecular-weight heparin versus usual care in proximal-vein thrombosis patients with cancer. Hull RD. Hoffman M. Risk factors for venous thromboembolism.129-35. Am J Med. 5. van Sluis GL. J Thromb Haemost. Genetics of venous thrombosis. 2009.41-8. 2009:7(1). In: van Beek EJR.4-13. What does it take to make the perfect clot? Arterioscler Thromb Vasc Biol. Oudkerk M.1062-72.301-4. J Thromb Haemost. 6. Rijken DC. 8. Deep vein thrombosis and pulmonary embolism. 3. p. Dear R. 7. 2009:26(2). 2006:119. Reitsma PH. Carman TL. Circulation.1. 4.6-16. et al.. Brant RF. Ltd. Büller HR. . Rosendaal FR. Cancer and thrombosis: from molecular mechanisms to clinical presentations. Cleveland Clin J Med. New insights into the molecular systems of the fibrinolytic system. Babu B. Mah AF.I-9-I-6. Cancer and clots: all cases of venous thromboembolism are not treated the same. Rosendaal FR.246-54. 2. USA: John Wiley & Sons. J Thromb Haemost. 2003:107. Buller HR. Kamphuisen PW. Chapter 1: Causes of venous thrombosis. 2006:26. Burke N. Spencer FA. Anderson FA. Pineo GF. van Doormal FF. Lijnen HR. 2009:7. 2007:5(1). Monroe DM.