Bleeding in the Patient with Renal Failure

Introduction

• Over 10% of US population has some form of chronic kidney disease (CKD), and more than 350,000 persons require hemodialysis for end stage renal disease (ESRD) annually.¹
• Within the next decade, the incidence of CKD is expected to nearly double.¹
• Uremic bleeding is a well-known consequence of CKD and can result in significant morbidity and mortality.

Why Do Uremic Patients Bleed?

• No one substance has yet to be identified as the cause of uremic bleeding and the bleeding is likely to be multifactorial.
• Uremic toxin accumulation causes a disruption of von Willebrand Factor (vWF), which leads to platelets’ inability to bind.
• This means that typical coagulation studies on uremic bleeding patients (PT, PTT) will be normal.
• Bleeding time is an indirect measure of platelet function and is almost always elevated.
• Stage of kidney disease does not correlate well with bleeding risk.²

Why is Bleeding a Concern in this Population?

• A normocytic normochromic anemia is present as early as stage 3 CKD and is almost universal by stage 4.¹ An anemia of chronic disease picture may also be seen.
• These anemias are mainly due to the diseased kidney’s inability to adequately produce erythropoietin (EPO).
• Despite the defective nature of platelets described above the platelet count is usually normal.

Presentations of Uremic Bleeding

Treatment

General goals for treatment

• A patient’s dialysis access is their lifeline, and its compromise should only occur if their life is in jeopardy.
• Patients with ESRD on dialysis have very delicate fluid balance and fluid overload may be apparent on aggressive resuscitation.

Direct pressure

• Avoid placing a suture into a graft or fistula unless absolutely necessary.
• A single stitch will often work better if there is a linear tear in the access site versus a puncture.
• A tourniquet will stop the flow from a bleeding access site on the extremity but will most surely result in thrombosis of the graft or fistula.

Dialysis

• Difficult in the actively bleeding patient
• Avoid heparin
• Corrects bleeding time in 65-85% of patients
• In general, peritoneal dialysis patients have less bleeding risk than hemodialysis patients.

**Desmopressin / DDAVP

• Mechanism of action not fully known: likely increases the release of factor 8 VWF polymers from the vascular endothelium => improves platelet aggregation.
• Effective in about 50% of patients
• Dose: 0.3 mcg/kg SC or IV; onset: 1 hour; duration: 4-8 hours
• 1 dose can lead to tachyphylaxis secondary to depletion of factor VIII and vWF from endothelial stores.³
• Contraindications: polydipsia, unstable angina, or severe congestive heart failure due to its antidiuretic effect
• Special considerations: if no IV access DDAVP can be administered intranasally at a dose of 3 mcg/kg, however IV dose is preferred.

Protamine

• Heparin is frequently used during dialysis. The half-life of heparin is short (1.5 hours), thus Protamine will only be effective during the first few hours.
• Dose: 1 mg of Protamine for every 100 units of heparin given. If the heparin dose is unknown, 10-20 mg of protamine can be given.⁴
• Contraindications: Avoid in fish allergy, caution if prior vasectomy and caution in pulmonary hypertension

Estrogen

• Rarely useful in ED setting, onset: 1 day

Topical Hemostatic agents

Helpful when bleeding from dialysis access site.

Cryoprecipitate

• Contains Factor VIII, fibrinogen, Factor XIII, vWF, and fibronectin
• Dose: Use 10 bags of Cryoprecipitate over 30 mins; should see an effect within 4-12 hours⁶

Platelet Transfusion

• Only in cases of uncontrolled hemorrhage
• Platelets become dysfunctional shortly after entering uremic environment
• Use in combination with other agents (i.e. desmopressin, cryoprecipitate, and packed red blood cells).³

*Packed RBCs

• Transfuse to a level of around 10mg/dl; ensure that this is given along with DDAVP and platelets +/- cryoprecipitate.
• Remember, anemia worsens bleeding

For an algorithm on the management of uremic bleeding, check out “Evidence-based treatment recommendations for uremic bleeding” published in Nature.²

Further Reading