• Clinical science

Hypercoagulable states (Thrombophilia…)

Summary

A hypercoagulable state, i.e., thrombophilia, is characterized by an increased predisposition to form blood clots. Depending on the etiology, one or more factors from Virchow's triad (stasis, hypercoagulability, endothelial damage) may be involved. Hypercoagulability may be acquired or inherited and can affect veins and/or arteries. The most common presentation is recurrent deep venous thrombosis of the lower extremities and pulmonary embolism. Arterial involvement increases the risk of myocardial infarction, stroke, and spontaneous abortion. Evaluation for hypercoagulability includes assessment of potential risk factors (e.g., immobilization, smoking, oral contraceptive use, and malignancy) and laboratory tests to assess anomalies of the clotting cascade (e.g., factor V Leiden, antiphospholipid antibody syndrome). Treatment is based on the underlying condition and typically includes a reduction of risk factors and/or the administration of anticoagulants.

Etiology

The etiology of thrombophilia can be classified into two categories:

Hereditary

Acquired

References:[1]

Clinical features

Thrombophilia is characterized by recurrent thromboembolism.

References:[2][3]

Hereditary thrombophilia

Defect Pathophysiology Prevalence in general population

Activated protein C resistance (APC-R)

Factor V Leiden

Heterozygosity: ∼ 5%
Homozygosity: < 1%
Elevated factor VIII ∼ 5%
Prothrombin mutation ∼ 3%
Protein S deficiency ∼ 1%
Protein C deficiency

< 1%

Antithrombin III deficiency ∼ 0.1%

Hyperhomocysteinemia

∼ 5–7%

References:[4][5][6][7][8]

Acquired thrombophilia

Etiology Pathophysiology
Surgery
  • Extended immobilization during procedure → blood stasis
  • Vessel instrumentation → endothelial damage
Trauma
  • Results in decreased venous blood flow, immobilization (blood stasis), and release of tissue factor (hypercoagulability) → increased clotting

Malignancy

Immobilization

  • Prolonged immobilization (e.g., extended travel, hospitalization, bed rest) → increased venous stasis
Smoking
  • Causes endothelial damage
  • The risk is significantly higher in women who also use oral contraceptives.
Obesity

Antiphospholipid syndrome

Nephrotic syndrome

Oral Contraceptive Pills (OCPs) or Hormone Replacement Therapy (HRT)

Heparin-induced thrombophilia
Pregnancy
  • Clotting factors increase (hypercoagulability)
  • Protein C and protein S decrease
  • Venous return from lower body slows (stasis) as the uterus enlarges
Advanced Age
  • Progressive endothelial damage
  • Increase in pro-clotting factors without a concomitant increase in protein C
  • Increase in other pro-clotting comorbidities (e.g., malignancy)
  • Decreased physical activity

References:[3][9][10][11]

Diagnostics

References:[2]

Treatment

Approach

Special considerations

The risk of venous thromboembolism is reduced with administration of an anticoagulant (e.g., heparin) following surgery!

References:[1][12][13]

Prevention

Consider prophylaxis in the following high-risk groups:

  • Postoperative patients
  • Prolonged immobilization or hospitalization
  • Malignancy
  • Orthopedic conditions