Abnormal uterine bleeding due to uremia-induced thrombocytopathy

Specialty: Hematology.

• Uterine hemorrhage due to uremic platelet dysfunction
• nephropathic menorrhagia

Why it occurs

• Advanced chronic renal failure / Uremia (the systemic accumulation of uremic toxins, specifically guanidinosuccinic acid and phenol, severely alters platelet function by interfering with the binding of von Willebrand factor to the glycoprotein GPIIb/IIIa, decreasing the intraplatelet synthesis of thromboxane A2 and altering intracellular calcium transport, causing a clinical hemorrhagic diathesis that manifests with persistent uterine mucosal bleeding)
• Hemolytic uremic syndrome / HUS (thrombotic microangiopathy with acute renal failure and functional failure of the remaining platelets)
• Diffuse segmental lupus glomerulonephritis with secondary platelet dysfunction
• Overdosage of aspirin or clopidogrel in patients with advanced chronic kidney disease.

Initial workup

Venous blood gases and ionogram to evaluate uremia and metabolic acidosis; complete blood count with manual platelet count (usually shows normal or only slightly decreased platelet count, contrasting with severe bleeding, confirming qualitative platelet dysfunction); iron profile, ferritin and serum erythropoietin levels; platelet functional testing using platelet function analyzer (PFA-100, typically prolonged for collagen/epinephrine and collagen/ADP cartridges in uremia); bleeding time (historically prolonged, although with low current clinical reproducibility); Extremely high blood urea nitrogen (BUN) and plasma creatinine levels with estimated glomerular filtration rate <15 mL/min/1.73m².

Standard management

• Desmopressin / DDAVP — intravenous administration at a dose of 0.3 μg/kg diluted in physiological solution, or intranasally; immediately induces endothelial release of large multimers of von Willebrand factor and factor VIII, temporarily shortening bleeding time and controlling uremic menorrhagia for a period of approximately 4 to 8 hours
• Conjugated estrogens — administered intravenously or orally; provide longer hemostatic control, up to 1 to 2 weeks, by partially restoring platelet adhesion function to the subendothelium in uremic patients
• Recombinant human erythropoietin / Epoetin alfa — optimization of hematocrit above 30% using EPO physically displaces platelets towards the periphery of the marginal blood flow of the vessel, mechanically favoring their interaction with the damaged endothelium and improving global hemostasis
• Tranexamic acid (oral or intravenous antifibrinolytic, requiring a drastic dose adjustment according to the glomerular filtration rate due to the risk of systemic accumulation and neurological toxicity).