Pathogenesis

• Multifactorial, though the principal contributor is platelet dysfunction due to both decreased platelet aggregation and impaired platelet adhesiveness.
• Key causative factors for platelet dysfunction include intrinsic platelet factors (abnormal protein expression and production) and extrinsic factors (uremic toxins, increased nitric oxide production, etc.).

Clinical Manifestations

• Typically cutaneous bleeding, including easy bruising and mucosal bleeding.
• Less commonly manifests as epistaxis or hematuria.

Management

• Therapy is indicated in patients with renal failure who are actively bleeding or who are about to undergo a surgical procedure. Of note, platelet dysfunction from uremia is much worse in acute renal failure than in chronic renal failure.
• Platelet function is improved by maintaining the hematocrit >30% with either red cell transfusions (if acutely bleeding) or with erythropoietin.
• Transfusion with non-uremic platelets may also be helpful.
• Dialysis, if indicated, reduces bleeding time in approximately 2/3 of uremic patients.
• DDAVP 0.3 mcg/kg IV q12 hours x 2 doses (tachyphylaxis typically occurs after 2 doses). This is the most rapid therapy.
• Conjugated estrogen 0.6 mg/kg IV Qday x 5 days (if persistent bleeding after dialysis, DDAVP). The duration of action is one week or more after therapy ends.
• Cryoprecipitate 10 units (1 adult dose) for those with ongoing bleeding despite above treatments.

Hedges SJ et al.  Evidence-based treatment recommendations for uremic bleeding.  Nat Clin Pract Nephrol 2007; 3:138