Is thrombophilia defined by a high platelet count, also known as thrombocytosis?

Thrombophilia Definition and Relationship to Platelet Count

Thrombophilia is not defined by a high platelet count (thrombocytosis). Thrombophilia refers to a group of disorders characterized by an increased tendency toward blood clotting and venous thrombosis, which can be inherited or acquired, but is not defined by platelet count abnormalities 1, 2.

What is Thrombophilia?

• Thrombophilia is broadly defined as an increased tendency toward hypercoagulability and venous thrombosis due to various inherited or acquired conditions 1
• It represents an impaired balance between stimulating and inhibitory components of the hemostasis system, resulting in increased susceptibility to thrombosis 3
• When the activation level of the hemostasis system exceeds the capacity of inhibitory components, a prethrombotic state advances to thrombosis 3

Types of Thrombophilia

Inherited (Primary) Thrombophilia:

• Factor V Leiden thrombophilia - most common inherited form 2
• Prothrombin G20210A mutation - second most common genetic form 2
• Deficiencies in natural anticoagulants:
  • Antithrombin deficiency 4
  • Protein C deficiency 4
  • Protein S deficiency 4
• Hyperhomocysteinemia 4

Acquired (Secondary) Thrombophilia:

• Antiphospholipid syndrome - characterized by thrombosis and presence of lupus anticoagulant or phospholipid-binding antibodies 4
• Other acquired conditions including:
  • Prolonged immobilization 1
  • Surgery 1
  • Trauma 1
  • Cancer 1
  • Pregnancy 1
  • Oral contraceptives 1
  • Hormone replacement therapy 1

Relationship Between Thrombophilia and Platelet Count

• Thrombophilia is not defined by platelet count abnormalities 5
• While thrombocytosis (high platelet count) can be a risk factor for thrombosis in some conditions, it is not a defining characteristic of thrombophilia 5
• In some thrombotic conditions, such as heparin-induced thrombocytopenia (HIT), there is actually a paradoxical decrease in platelet count (thrombocytopenia) despite an increased risk of thrombosis 6
• In cancer-associated disseminated intravascular coagulation (DIC), decreasing platelet count may be a marker of continuing thrombin generation and DIC, rather than a defining feature of thrombophilia 5

Laboratory Testing for Thrombophilia

• Specific laboratory tests for congenital thrombophilia include:
  • Assessment of antithrombin III, protein C, and protein S activity 3
  • Evaluation of resistance to activated protein C 3
  • Tests for hyperhomocysteinemia and prothrombin 20210A mutation 3
  • Factor V Leiden testing 7
• Platelet count is not included among the specific diagnostic tests for thrombophilia 3, 7

Clinical Implications

• Thrombophilia should be suspected in patients who develop:
  • Idiopathic venous thromboembolism at a young age 7
  • Recurrent thrombosis 7
  • Thromboses at unusual sites 7
  • Recurrent unexplained pregnancy loss 7
  • Family history of thrombotic disorders 7
• The most cost-effective approach is to initially screen for factor V Leiden, prothrombin gene mutation, hyperhomocysteinemia, and antiphospholipid antibodies as these are the most common defects causing thrombophilia 7

Common Pitfalls in Thrombophilia Assessment

• Excessive or inappropriate thrombophilia testing is of particular concern, as the net effect of current worldwide testing trends may be more detrimental than beneficial 1
• Thrombophilia testing should be targeted based on clinical presentation and family history rather than performed indiscriminately 1
• Confusing thrombocytosis (high platelet count) with thrombophilia can lead to inappropriate management decisions 5
• In patients with cancer-related DIC, a normal platelet count despite a profound decrease from a very high level may be discounted as unimportant, when it may be the only sign of DIC in some patients with malignancy 5