Can Polycythemia Vera Cause Abnormal Uterine Bleeding?
Yes, polycythemia vera can cause abnormal uterine bleeding in females of reproductive age, primarily through two mechanisms: acquired bleeding diathesis from platelet dysfunction and acquired von Willebrand disease, and as a consequence of anticoagulation therapy used to manage thrombotic risk.
Direct Hematologic Mechanisms
Acquired Bleeding Disorders in PV
Platelet dysfunction in PV creates a pro-hemorrhagic state through multiple qualitative defects including poor platelet aggregation in response to various agonists (thrombin, ADP, epinephrine, collagen), abnormally low intraplatelet levels of adenine nucleotides and serotonin, and impaired binding to fibrinogen due to decreased GP IIb/IIIa expression 1.
Acquired von Willebrand disease occurs in more than one-third of patients with PV and has been directly associated with bleeding diathesis 1. This condition is characterized by decreased large von Willebrand factor multimers and increased cleavage products, particularly when extreme thrombocytosis is present (platelet count ≥1000 × 10⁹/L) 1, 2.
The pathogenesis involves abnormal adsorption of large von Willebrand proteins to clonal platelets, which exposes protein cleavage sites and enhances proteolysis 1.
Iatrogenic Bleeding from Anticoagulation
Treatment-Related AUB
Abnormal uterine bleeding occurs in 9-14% of the general female population of reproductive age, which is significantly exacerbated by oral anticoagulants 1. Since PV patients frequently require anticoagulation therapy for thrombosis prevention or treatment, this represents a major clinical concern.
In women of reproductive age on anticoagulation for venous thromboembolism, rivaroxaban was associated with prolonged menstrual bleeding (>8 days) in 27% versus 8.3% with VKA (P = 0.017), increased need for menorrhagia-related medical or surgical intervention (25% vs. 7.7%, P = 0.032), and more adaptations of anticoagulant therapy (15% vs. 1.9%, P = 0.031) 1.
Registry data report a 32% incidence of abnormal uterine bleeding in women of reproductive age (n = 178) on factor Xa inhibitors 1.
Clinical Context in PV Pregnancy Studies
In pregnancy outcome studies of PV patients, major bleeding complications occurred in 2-25% of cases across different cohorts, though these were not specifically characterized as uterine bleeding 1.
The use of aspirin therapy, which is recommended for all PV patients without contraindications 2, 3, can further contribute to bleeding risk including abnormal uterine bleeding.
Management Approach for Women with PV and AUB
Initial Assessment
Pregnancy testing must be performed in all reproductive-age women with abnormal uterine bleeding 4, 5.
Combined transabdominal and transvaginal ultrasound with Doppler is the first-line imaging study to identify structural causes 4.
Complete blood count with platelets should be obtained to assess for extreme thrombocytosis (≥1000 × 10⁹/L) suggesting acquired von Willebrand disease 1, 2.
Treatment Modifications
For women with PV on anticoagulation experiencing AUB, reassess the indication for ongoing anticoagulation therapy and consider discontinuation if appropriate 1, 5.
The levonorgestrel-releasing intrauterine device (LNG-IUD) is the preferred treatment option for AUB in women with PV, as it reduces menstrual blood loss by 71-95% with minimal systemic absorption, making it safer in the context of thrombotic risk 5.
Avoid NSAIDs and tranexamic acid in PV patients due to the association with thrombosis risk, particularly arterial events 1, 5. This is critical since PV already carries a 16% risk of arterial thrombosis at or before diagnosis 2.
Cytoreductive Therapy Considerations
Pegylated interferon-α should be considered as first-line cytoreductive therapy in young women of reproductive age with PV rather than hydroxyurea, as it may help control both the myeloproliferative process and reduce bleeding complications 6, 3.
Cytoreductive therapy can normalize platelet counts and potentially reverse acquired von Willebrand disease, as this condition characteristically corrects with platelet count normalization 1.
Important Caveats
The paradoxical nature of PV creates both thrombotic and hemorrhagic risks simultaneously—patients may experience both arterial/venous thrombosis (26% 20-year risk) and bleeding complications 2, 3.
Women should be counseled about the risk of increased menstrual bleeding while on anticoagulation and monitored carefully, especially during the first cycles after anticoagulation initiation 1.
If AUB persists despite medical management or if endometrial sampling shows hyperplasia or malignancy, referral to a gynecologist is mandatory 4.