Thrombophilia

Thrombophilia is a disorder characterized by an increased tendency of the blood to clot rapidly, thereby increasing the likelihood of forming clots that do not dissolve easily (thrombi). The consequences of such thrombosis may be severe, as blood vessels can become partially or completely occluded.

Although thrombophilia has no definitive cure, the prognosis is favorable when diagnosed early and managed with specific treatment in addition to lifestyle modifications.

Symptoms

The most characteristic symptoms of thrombophilia include:

• Deep vein thrombosis (DVT): formation of a thrombus in a deep vein, typically in the legs or pelvis.
  • Leg swelling accompanied by pain and erythema.
  • Sensation of heaviness.
• Sudden and severe pain in an arm, leg, or abdomen.
• Dilated veins.
• Pulmonary embolism (PE): obstruction of a pulmonary artery by a blood clot originating from the legs or pelvis.
  • Sudden onset dyspnea.
  • Hemoptysis.
  • Chest pain.
• Recurrent miscarriages.

Causes

Thrombophilia is classified into two main types according to its etiology:

• Hereditary (congenital) thrombophilia: inheritance of a gene that increases the production of procoagulant proteins or reduces the activity of natural anticoagulants. This condition is present from birth.
  • Factor V Leiden mutation: the most common hereditary thrombophilia. Protein C, a natural anticoagulant, fails to inactivate factor V (a coagulation protein), increasing the risk of deep vein thrombosis.
  • Prothrombin gene mutation (G20210A): associated with elevated plasma prothrombin levels, a liver-produced protein that serves as a precursor in the coagulation cascade. It is commonly linked to pulmonary embolism, deep vein thrombosis, and spontaneous miscarriages.
  • Antithrombin III deficiency: a rare but more severe form, often associated with additional coagulation disorders. Reduced antithrombin III levels result in an imbalance between bleeding and coagulation.
  • Protein C deficiency: uncommon; increases the risk of recurrent thrombotic events due to reduced natural anticoagulant activity.
  • Protein S deficiency: also uncommon. Protein S, together with protein C, inactivates coagulation factors and prevents thrombus formation. Deficiency diminishes this protective mechanism.
• Acquired thrombophilia: the most common type. It develops secondary to various factors, including lifestyle, medications, or underlying diseases.
  • Antiphospholipid syndrome (APS): an autoimmune disorder in which the body produces antibodies against phospholipids, components of cell membranes where coagulation factors assemble, leading to increased thrombotic tendency.
  • Cancer: malignant cells release procoagulant substances, such as tissue factor, activating coagulation and inducing a hypercoagulable state that favors clot formation.
  • Hormone therapy and oral contraceptives: hormones (particularly estrogens) increase the risk of thrombosis, especially when administered orally. Transdermal administration (e.g., patches) is associated with lower systemic exposure and reduced risk.
  • Prolonged immobilization: extended periods without lower limb movement promote blood stasis and increase thrombotic risk.

Risk Factors

The risk of thrombophilia is related to its underlying causes. The likelihood increases in the following circumstances:

• Advanced age.
• Genetic predisposition:
  • Presence of Factor V Leiden mutation.
  • Presence of prothrombin gene mutation (G20210A).
  • Deficiency of antithrombin III, protein C, or protein S.
• Prolonged immobilization due to:
  • Extended hospitalization.
  • Medically prescribed bed rest.
  • Long-distance travel.
  • Sedentary lifestyle.
• Major surgery.
• Trauma.
• Cancer, particularly of the pancreas, stomach, colon, rectum, lung, kidney, ovary, and brain.
• Obesity.
• Smoking.
• Pregnancy and the puerperium.
• Antiphospholipid syndrome.
• Hormone-containing medications.
• Presence of a central venous catheter.

Complications

Thrombophilia is associated with the following complications:

• Deep vein thrombosis.
• Pulmonary embolism.
• Stroke.
• Spontaneous miscarriage.
• Preeclampsia: a syndrome occurring after 20 weeks of gestation or postpartum, characterized by hypertension and signs of renal or hepatic impairment.
• Intrauterine growth restriction (IUGR).
• Preterm birth.

Prevention

Although thrombophilia itself cannot always be prevented, the risk of clot formation may be reduced through healthy lifestyle measures. General recommendations include:

• Regular physical exercise.
• Smoking cessation.
• Maintaining a healthy body weight.
• Adhering to a balanced diet.
• Monitoring cholesterol levels.
• Adequate hydration.
• Standing up and walking every one to two hours during prolonged sitting.
• Use of compression stockings in high-risk situations.
• Early mobilization following surgery whenever feasible.

Which specialist treats thrombophilia?

Thrombophilia is diagnosed and managed within the specialties of Hematology and hemotherapy, Genetics, Immunology, and Assisted reproduction. Diagnostic testing is performed within Clinical Laboratory and Clinical Biochemistry services.