**1. Introduction**

Clotting is a physiological property of the body to form clots and thus minimize blood loss at the site of injury. Normal blood flow is kept in balance by factors that promote clotting and by antithrombotic factors. A hypercoagulable state, which may be complicated by the development of thromboembolism, is a consequence of hyperactivity of clotting promoters or anticoagulant deficiency. But the interaction between the two facets is much more complex than this, as thrombosis can be influenced by the qualitative and quantitative properties of factors, for example, their secretion, accumulation, or degradation [1].

What Virchow described in 1856 as the triad of conditions that must be met to develop venous thrombosis is accepted nowadays as hypercoagulability, vascular stasis and vascular trauma underlie the pathophysiological mechanism that explains this situation. Arterial thrombosis, on the other hand, results from the rupture of

an atherosclerotic plaque, which pierces the vascular endothelium, resulting in the formation of platelet-rich thrombus around it [1].

Thrombophilia is a hypercoagulable or prothrombotic state, which is defined as an abnormality of blood clotting, thus increasing the risk of thrombosis. It can be classified into different categories, depending on its mechanism of action, how it occurs, whether it is an acquired or an inborn disease. [Genetic vs. acquired; primary vs. secondary; permanent vs. transient; low risk vs. high risk].

The known possible causes of thrombophilia are listed in **Table 1** [3].

Type 1 or major thrombophilias are a group of rare diseases that include antithrombin deficiency, protein C deficiency, or protein S deficiency, which together occur in less than 1% of the population but account for up to 7% of patients with thrombosis [4].

Type 2 thrombophilias or minor thrombophilias are much more common, the most important example being the factor V Leiden mutation, which can be identified in 5% of the European-born population and 30–50% of patients referred for thrombophilia testing.

The prothrombin mutation affects 1–4% of the general population but is found in up to 15% of patients tested for thrombophilia. Both types of mutations are much more common in Caucasians and almost never found in patients of Asian or African descent [4].

Hereditary thrombophilias are those in which a genetic mutation inherited from one or both parents leads to a condition in which the function of certain proteins of the clotting system is impaired. The condition can be expressed as a deficiency or loss


#### **Table 1.**

*Thrombophilia causes, Robbins and Cotran pathologic basis of disease (ninth edition.) [2].*

*Anticoagulation in Thrombophilia DOI: http://dx.doi.org/10.5772/intechopen.103038*

of function, best exemplified by mutations in the antithrombin, protein C, or protein S genes, or as a gain of function, such as mutations in factor V Leiden and prothrombin 20,210 A/G. Other conditions, although less common, are the presence of abnormal levels of clotting factors, elevated homocysteine, or defects in the fibrinolytic pathway. Nowadays, we have reached a point where gene factors can be identified in up to 30% of patients with thrombophilia [5, 6].

Acquired thrombophilia is a hypercoagulable status composed of the association of a divergent group of clinical conditions, which include malignancy, pregnancy, prolonged bed rest, postoperative, nephrotic syndrome, or lifestyle risk factors, such as smoking or obesity. But the most important example is an antiphospholipid syndrome which is also included in the guidelines and should be tested for each time thrombophilia is suspected [5].

Although hypercoagulability disorders are classified as either inherited or acquired, thrombosis develops due to the interaction of both genetic and environmental factors, which has led to the development of the multiple-hit hypothesis, thus providing a possible explanation for the differences observed between subjects carrying the same gene mutation [6].

In an article by R H Thomas, the CALMSHAPES mnemonic was proposed to more easily recall the different etiologies of the hypercoagulable state, which are as follows:



#### **Table 2.**

*Prevalence of different thrombophilias and the risk of developing venous thromboembolism [3].*


Venous thromboembolism is the main and most common complication of a hypercoagulable condition, with a huge impact on any national health system. Available data from the United States estimates that venous thromboembolism is responsible for more than half a million hospitalizations annually, with an estimated cost of treatment per patient of more than \$56,000, totaling an estimated \$5–\$20 billion. The different mechanisms of occurrence of a hypercoagulable state have different penetration in the general population, with different risk rates for complications, such as venous thromboembolism, as shown in **Table 2**.
