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Bleeding Risks With Renal Disease
Introduction
Renal disease has long been associated with a bleeding diathesis; Morgagni described the association of uremia and bleeding as early as 1764. Although dialysis and erythropoietin-stimulating agents (ESAs) have greatly decreased this bleeding tendency, bleeding is still reported in 24%–50% of patients with chronic renal failure with a fivefold increased risk of intracranial hemorrhage. The etiology of bleeding is multifactorial, as the complex interplay of components of the coagulation system get interrupted by uremia, dialysis, medications, and even the underlying anemia can tip the balance to the prothrombotic state in underlying renal disease. This chapter will focus on the hemostatic disorders associated with chronic renal disease, the laboratory findings, and the management of bleeding in these patients.
Pathophysiology
Uremic patients demonstrate disordered platelet/vessel interaction and disturbances in various stages of platelet function, which unfortunately is not reflected in the commonly used hemostatic parameters such as routine PT/aPTT testing.
Vessel Wall–Related Factors
There are abnormal platelet–vessel wall interactions due to decreased functional GpIIb/IIIa complex and decreased binding of fibrinogen and von Willebrand factor (VWF) to GpIIb/IIIa receptors, thereby impairing platelet adhesion. This could be related to uremic toxins, as it usually improves with dialysis.
Biochemical Changes Due to Uremia
Guanidinosuccinic acid (GSA) (a derivative of l -arginine) and l arginine, are both precursors of nitric oxide (NO) and tend to accumulate in uremic plasma. NO production is thereby increased in uremic patients, which leads to increased cyclic guanosine monophosphate (GMP), producing vascular relaxation and decreased platelet aggregation. GSA also impairs the secondary wave of ADP-induced platelet aggregation. Uremic toxins are also thought to impair the release and synthesis of thromboxane A2 due to dysregulated prostaglandin metabolism in platelets in advanced renal disease, which improves with dialysis.
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