Thrombophilia

Thrombophilia or hypercoagulable state is a clinical condition characterized by a tendency to develop venous and (less frequently) arterial thrombosis. Thrombosis is defined as the obstructive clot formation within a vessel. 

Since the first observation of Virchow, three major pathogenic causes of thrombosis have been identified: changes in the vessel wall, in the blood flow and in the blood composition. Although all these mechanisms may contribute to thrombosis, arterial events are mainly determined by changes in the vessel wall, in particular atherosclerosis, while stasis and prothrombotic blood abnormalities play a major role in venous thrombosis. 

The most common conditions associated with thrombophilia are deep vein thrombosis (DVT) and pulmonary embolism (PE), which are referred to collectively as venous thromboembolism (VTE). 

• DVT usually occurs in the legs, and is characterized by pain, swelling and redness of the limb. It may lead to long-term swelling and heaviness due to damage to valves in the veins. 
• The development of a venous thromboembolic episode (VTE) is often the result of multiple risk factors, including both congenital procoagulant defects and enviromental factors such as age, male sex, obesity, exposure to “risk periods” of immobilization, trauma, cancer, pregnancy, use of exogenous hormones or chemotherapy.  

Thrombophilia can be congenital or acquired. Congenital thrombophilia refers to inborn conditions (and usually hereditary, in which case "hereditary thrombophilia" may be used) that increase the tendency to develop thrombosis, while, on the other hand, acquired thrombophilia refers to conditions that arise later in life.

Hereditary thrombophilia

Hereditary thrombophilia is a genetically determined increased risk of thrombosis; acquired or secondary thrombophilia is a physiologic or pathologic condition that predispose affected persons to thromboembolic diseases. Hereditary thrombophilia should be suspected in persons with a family history of thrombosis, especially if the thrombotic events occurred in young patients or when trigger factors are absent or minimal. A congenital or acquired hypercoagulable state should also be suspected in the case of idiopathic recurrent VTE or in thrombosis involving atypical locations, like upper extremities, visceral veins (hepatic, portal, mesenteric) or cerebral veins.

Acquired thrombophilia

While not specifically addressed herein, many other acquired conditions can increase the risk of thrombosis, such as acquired abnormalities in coagulation proteins (e.g. deficiencies in the natural anticoagulants, activated protein C resistance in the absence of FVL) and certain diseases (e.g. myeloproliferative neoplasms, paroxysmal nocturnal hemoglobinuria, cancer). Some medications increase thrombosis risk, including exogenous hormones and chemotherapy. Acquired characteristics such as smoking, obesity, increasing age and pregnancy also increase risk.

Tests for thrombophilia include complete blood count (with examination of the blood film), prothrombin time, partial thromboplastin time, thrombodynamics test, thrombin time and reptilase time, lupus anticoagulant, anti-cardiolipin antibody, anti-β2 glycoprotein 1 antibody, activated protein C resistance, fibrinogen tests, factor V Leiden and prothrombin mutation, and basal homocysteine levels. Testing may be more or less extensive depending on clinical judgement and abnormalities detected on initial evaluation. For hereditary cases, the patient must have at least 2 abnormal tests plus family history.

There is no specific treatment for thrombophilia, unless it is caused by an underlying medical illness (such as nephrotic syndrome), where the treatment of the underlying disease is needed. In those with unprovoked and/or recurrent thrombosis, or those with a high-risk form of thrombophilia, the most important decision is whether to use anticoagulation medications, such as warfarin, on a long-term basis to reduce the risk of further episodes. This risk needs to weighed against the risk that the treatment will cause significant bleeding, as the reported risk of major bleeding is over 3% per year, and 11% of those with major bleeding may die as a result.

Thrombophilia may be associated with several diseases including:

Antiphospholipid syndrome

Antiphospholipid syndrome or antiphospholipid antibody syndrome (APS or APLS), is an autoimmune, hypercoagulable state caused by antiphospholipid antibodies. APS provokes blood clots (thrombosis) in both arteries and veins as well as pregnancy-related complications such as miscarriage, stillbirth, preterm delivery, and severe preeclampsia (a disorder of pregnancy characterized by the onset of high blood pressure). Thrombosis in APS can happen either spontaneously or with a triggering factor (viral infections, such as the cytomegalovirus (CMV) or parvovirus B19).