From the Guidelines
A hypercoagulable workup is not routinely recommended before initiating hormone replacement therapy (HRT) for most patients, but selective screening may be considered for individuals with a personal or strong family history of venous thromboembolism (VTE) or known thrombophilia. The decision to perform a hypercoagulable workup should be based on a thorough assessment of the patient's risk factors for thrombosis, as outlined in the guidelines on diagnosis and management of acute pulmonary embolism by the European Society of Cardiology 1.
Risk Factors for VTE
The guidelines highlight several risk factors for VTE, including:
- Primary factors such as antithrombin deficiency, protein C deficiency, and factor V Leiden mutation
- Secondary factors such as trauma, surgery, immobilization, advanced age, malignancy, and oral contraceptives
- The risk of VTE is also increased in pregnant women and those using oral contraceptives, particularly third-generation oral contraceptives containing desogestrel or gestodene 1
Selective Screening
If a hypercoagulable workup is warranted, it should include tests for:
- Factor V Leiden mutation
- Prothrombin G20210A mutation
- Protein C and S deficiency
- Antithrombin deficiency
- Antiphospholipid antibodies This selective approach is recommended because routine screening is not cost-effective and may identify incidental abnormalities of unclear significance 1
HRT and VTE Risk
The increased risk of VTE with HRT is primarily associated with oral estrogen therapy, which undergoes first-pass hepatic metabolism that increases production of clotting factors 1. Transdermal estrogen, on the other hand, bypasses this first-pass effect, resulting in minimal impact on coagulation. Therefore, transdermal estrogen is preferred over oral formulations for patients with elevated thrombotic risk. Patients should be counseled about VTE symptoms and risk reduction strategies regardless of whether testing is performed.
From the Research
Hypercoagulable Workup Prior to HRT Initiation
- The risk of venous thromboembolism (VTE) is increased with the use of hormone replacement therapy (HRT) due to blood hypercoagulability 2.
- HRT may particularly affect women with prothrombotic mutations, such as factor V Leiden, resulting in a 15-fold increased risk of VTE 3.
- Different HRT regimens can influence the haemostatic balance, with significant decreases in antithrombin and protein S, and increases in fibrin degradation products and prothrombin fragment 1+2 4.
Coagulation Parameters and HRT
- HRT reduces the inhibitory potential of coagulation, with the effect related to the type of oestrogen/progestin combination administered 4.
- The procoagulant activity of HRT may translate into clinical manifestations in thrombosis-prone individuals 4.
- Changes in coagulation parameters, such as prothrombin time and activated partial thromboplastin time, can occur during replacement therapy with human recombinant growth hormone in growth hormone deficient adults 5.
Diagnostic Approach
- An isolated prolonged activated partial thromboplastin time (APTT) can be caused by various factors, including lupus anticoagulants, anticoagulant treatment, and deficiencies of specific coagulation factors 6.
- A diagnostic algorithm can be used to differentiate between these causes and ensure correct therapeutic follow-up 6.