Thrombotic Disorders (Hypercoagulable States)

Hypercoagulable states (also known as thrombophilias) are hematological conditions characterized by an increased tendency toward thrombosis (formation of blood clots).

The causes may be hereditary or acquired. The most common hereditary cause is the Factor V Leiden mutation.

Clinically, hypercoagulable states manifest with thrombotic episodes that obstruct blood vessels and may lead to organ damage.

Prevalence and Risk

Among cardiovascular diseases, venous thromboembolism (VTE) ranks second after myocardial infarction in frequency.

Up to 4% of strokes are associated with thrombophilia.

In more than 80% of patients with thrombosis, one or more predisposing risk factors are identified.

Hereditary Thrombophilia

Factor V Leiden mutation – the most common hereditary form, relatively frequent in the Caucasus and the Middle East.

In heterozygotes, the risk of venous thrombosis increases by 5–7 times, while in homozygotes, by 50–80 times.

It leads to deep vein thrombosis, pulmonary embolism, and in women, pregnancy complications such as miscarriages, placental insufficiency, and preeclampsia.

Prothrombin G20210A mutation – increases prothrombin levels and predisposes to both venous and arterial thromboses.

Deficiencies of natural anticoagulants – antithrombin, protein C, and protein S.

During pregnancy, thrombophilia markedly increases the risk of deep vein thrombosis and pulmonary embolism.

Management of pregnant women with thrombophilia requires close medical supervision and often prophylactic therapy with low-molecular-weight heparin (LMWH), which is safe for both mother and fetus.

Acquired Thrombophilia

Antiphospholipid syndrome (APS) – the most common acquired form.

It is an autoimmune disorder in which the body produces antiphospholipid antibodies that interfere with normal coagulation and increase the risk of thrombosis (both venous and arterial).

The syndrome may be primary (idiopathic, ~50% of cases) or secondary, developing in association with other autoimmune diseases (e.g., systemic lupus erythematosus, rheumatoid arthritis), malignancies, pregnancy or postpartum state, or as a drug-induced reaction.

Clinical manifestations: deep vein thrombosis, pulmonary embolism, ischemic stroke, myocardial infarction, and, in women, recurrent miscarriages and pregnancy complications.

Diagnosis: requires at least one clinical manifestation and one positive laboratory test (lupus anticoagulant, anticardiolipin, or anti–anti-β2-glycoprotein I antibodies), confirmed twice at least 12 weeks apart.

Treatment aims to prevent recurrent thrombosis and manage pregnancy complications.

Anticoagulant therapy is standard; in pregnant women, a combination of low-molecular-weight heparin and low-dose aspirin is recommended.

Malignancies – tumors may secrete procoagulant substances or compress blood vessels, impairing blood flow.

Thrombosis is most commonly observed in adenocarcinomas, particularly of the lung, pancreas, and colon.

Estrogen exposure – pregnancy, estrogen-containing contraceptives, and hormone replacement therapy increase the risk of thrombosis.

Hyperhomocysteinemia – a condition characterized by elevated levels of homocysteine in the blood.

It may result from both genetic and acquired causes.

Homocysteine metabolism depends on several vitamins, particularly B6, B12, and folic acid. Deficiency of these vitamins or mutations such as the MTHFR gene mutation may lead to elevated homocysteine levels.

Increased homocysteine is an independent risk factor for thrombosis, as it damages the vascular endothelium and promotes thrombus formation (deep vein thrombosis, pulmonary embolism, stroke, myocardial infarction).

Diagnosis is based on measuring plasma homocysteine concentration.