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Hypercoagulable states

Last updated: May 28, 2021

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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.

The etiology of thrombophilia can be classified into two categories:

Thrombophilia is characterized by recurrent thromboembolism.

Pathophysiology of hereditary thrombophilia [1][2][3]
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%

Pathophysiology of acquired thrombophilia [4][5][6]
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
Obesity

Antiphospholipid syndrome

Nephrotic syndrome

Oral contraceptive pills (OCPs) or hormone replacement therapy (HRT)

Heparin-induced thrombophilia
Pregnancy
Advanced age [5]
  • 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

Approach

Special considerations

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

References:[7]

Consider prophylaxis in the following high-risk groups:

  • Postoperative patients
  • Prolonged immobilization or hospitalization
  • Malignancy
  • Orthopedic conditions
  1. Colman RW. Hemostasis and Thrombosis: Basic Principles and Clinical Practice. Lippincott Williams & Wilkins ; 2006
  2. Den Boer NC, Van der Heiden C, Leijnse B, Souverijn JHM. Clinical chemistry: an overview . Plenum Press ; 1989
  3. Kumar A, Afreen S, Mohd Yusuf, Gupta A. Mechanism and pathophysiology of activated protein C-related factor V leiden in venous thrombosis. Asian Journal of Transfusion Science. 2012; 6 (1): p.47. doi: 10.4103/0973-6247.95053 . | Open in Read by QxMD
  4. Kim JY, Khavanin N, Rambachan A, et al. Surgical duration and risk of venous thromboembolism. JAMA Surg. 2015; 150 (2): p.110-117. doi: 10.1001/jamasurg.2014.1841 . | Open in Read by QxMD
  5. Blokhin IO, Lentz SR. Mechanisms of thrombosis in obesity. Curr Opin Hematol. 2015; 20 (5): p.437-444. doi: 10.1097/MOH.0b013e3283634443 . | Open in Read by QxMD
  6. Esmon CT. Basic Mechanisms and Pathogenesis of Venous Thrombosis. Blood Rev. 2009; 23 (5): p.225–229. doi: 10.1016/j.blre.2009.07.002 . | Open in Read by QxMD
  7. Tchaikovski SN, Rosing J. Mechanisms of estrogen-induced venous thromboembolism. Thromb Res. 2010; 126 (1): p.5-11. doi: 10.1016/j.thromres.2010.01.045 . | Open in Read by QxMD