Uraemic Bleeding

Uraemic bleeding is a bleeding tendency in advanced kidney failure caused by platelet dysfunction, with a normal platelet count and normal prothrombin time and activated partial thromboplastin time.

Defects include impaired platelet adhesion and aggregation, abnormal von Willebrand factor interaction with glycoprotein Ib and IIb/IIIa, excess nitric oxide and prostacyclin, uraemic toxins (guanidinosuccinic acid), and anaemia, which reduces margination of platelets towards the vessel wall.

The tendency is worsened by heparin during dialysis, antiplatelet agents, anticoagulants, selective serotonin reuptake inhibitors and high dose beta lactam antibiotics.

Epidemiology. Clinically important in untreated uraemia (eGFR under 10 mL/min/1.73 m²) and before dialysis initiation. Gastrointestinal bleeding, intracranial haemorrhage, haemopericardium and retroperitoneal bleeds contribute substantially to dialysis mortality.

• Mucocutaneous: easy bruising, purpura, epistaxis, gum bleeding, menorrhagia, prolonged bleeding from venepuncture, fistula and needle sites.
• Gastrointestinal bleeding (angiodysplasia, gastritis, ulcer): haematemesis, melaena, anaemia.
• Haematuria, haemoptysis, haemopericardium, subdural and intracerebral haemorrhage, retroperitoneal and rectus sheath haematoma, bleeding after surgery and biopsy.

Red flags

• Haemodynamic instability, Hb fall of 20 g/L or more, melaena or haematemesis.
• Headache with neurological signs (subdural or intracerebral bleed).
• Pericardial effusion with haemodynamic compromise.
• Bleeding after kidney biopsy, tunnelled catheter or fistula surgery.

• Full blood count (platelets normal, anaemia common), prothrombin time and activated partial thromboplastin time (normal), fibrinogen, liver tests; urea and creatinine.
• Platelet function: bleeding time prolonged (not used routinely), PFA-100 closure time prolonged. Von Willebrand factor antigen is normal or high.
• Exclude other causes: disseminated intravascular coagulation, liver disease, thrombotic microangiopathy, heparin induced thrombocytopenia, anticoagulant or antiplatelet effect, acquired von Willebrand syndrome (monoclonal gammopathy), vitamin K deficiency, antibiotic effect.
• Endoscopy or imaging to locate the source in gastrointestinal, intracranial or retroperitoneal bleeding.

Differential diagnosis

• Thrombocytopenia of any cause, coagulation factor deficiency, anticoagulant excess, myeloma, amyloid, scurvy, vasculitis.

First line: reduce uraemic effect and anaemia

• Optimise dialysis: urea clearance restores platelet function in 1 to 2 days; daily dialysis for 2 to 3 days in active bleeding with heparin free technique (saline flushes 100 mL every 30 minutes, or regional citrate).
• Correct anaemia to haemoglobin 100 to 120 g/L with ESA (epoetin alfa 50 to 100 units/kg three times weekly) and iron; transfuse to haemoglobin above 70 g/L (above 80 g/L with cardiac disease) if bleeding.
• Stop or hold antiplatelets, anticoagulants, NSAIDs, selective serotonin reuptake inhibitors and other contributing drugs when safe. Give omeprazole 40 mg intravenously then 20 to 40 mg daily for upper gastrointestinal bleeding or prophylaxis.

Pharmacological haemostasis

• Desmopressin 0.3 microg/kg intravenously over 20 to 30 minutes (or subcutaneously). Onset within 1 hour, effect lasts 4 to 8 hours, repeat every 12 to 24 hours up to 3 doses; tachyphylaxis is common. Monitor sodium (restrict fluids to avoid hyponatraemia) and watch for hypotension and thrombosis. Intranasal 3 microg/kg (maximum 300 microg) if intravenous access is poor.
• Conjugated oestrogens 0.6 mg/kg intravenously daily for 5 days (onset 6 hours, peak 5 to 7 days, effect lasts 2 to 3 weeks), or oral 50 mg daily; useful for recurrent gastrointestinal bleeding and planned procedures. Avoid in thrombotic risk and hormone sensitive cancer.
• Cryoprecipitate 10 units (one pool) intravenously, effective within 1 hour, lasts 4 to 24 hours; for severe bleeding when desmopressin fails.
• Tranexamic acid with renal dose reduction: 500 mg intravenously followed by 500 mg every 12 hours in advanced kidney failure (full doses accumulate and risk seizures); avoid in haematuria with clots (obstruction) and in thrombosis risk.
• Platelet transfusion for life threatening bleeding; efficacy is limited because uraemic plasma impairs transfused platelets, so give after dialysis.
• Heparin reversal if recent dialysis: protamine 1 mg for each 100 units of heparin given in the previous 2 hours (maximum 50 mg).

Surgery and procedures

• Before biopsy or surgery: dialysis the day before with minimal heparin, desmopressin 0.3 microg/kg intravenously 30 to 60 minutes before, haemoglobin at least 100 g/L, blood pressure controlled below 140/90 mmHg.

Referral and escalation. Emergency gastroenterology, neurosurgery or interventional radiology for major haemorrhage; nephrology for dialysis adjustments; haematology for refractory bleeding or suspected paraprotein.

Special groups

• Patients on dialysis needing anticoagulation (atrial fibrillation, mechanical valve): weigh bleeding risk; use heparin free dialysis.
• Peritoneal dialysis: haemoperitoneum is common and benign if short lived (menstruation, ovulation); check for other causes if persistent.
• Children: desmopressin 0.3 microg/kg intravenously (maximum 20 microg).