UFH Dosing in Chronic Kidney Disease
UFH does not require dose adjustment in patients with CKD, as it is primarily metabolized by the liver rather than renally excreted, making it the preferred anticoagulant when creatinine clearance falls below 30 mL/min. 1, 2, 3
Therapeutic Anticoagulation Dosing
For therapeutic anticoagulation in CKD patients, use the standard weight-based UFH protocol without dose reduction:
- Initial bolus: 80 units/kg IV (maximum 4000 units) 2, 3
- Continuous infusion: 18 units/kg/hour (maximum 1000 units/hour) 2, 3
- Target aPTT: 1.5-2.5 times control (approximately 50-70 seconds) 2, 3
Monitoring Protocol in CKD
- First aPTT measurement at 6 hours after bolus, then every 4-6 hours until stable in therapeutic range 2, 3
- Once stable, check aPTT daily 2
- Monitor platelet counts daily throughout therapy to detect heparin-induced thrombocytopenia 2
Context-Specific Adjustments for ACS/PCI
For patients with acute coronary syndromes undergoing PCI, the 2020 ESC Guidelines recommend standard dosing without CKD-specific adjustments: 4
- 70-100 U/kg IV bolus when no GP IIb/IIIa inhibitor is planned 4
- 50-70 U/kg IV bolus with GP IIb/IIIa inhibitors 4
- Followed by IV infusion until the invasive procedure 4
DVT Prophylaxis Dosing
For VTE prophylaxis in CKD patients, use standard subcutaneous dosing without adjustment:
- 5000 IU subcutaneously every 8 hours (preferred regimen) 1
- Alternative: 5000 IU subcutaneously every 12 hours (acceptable in medical patients, though less effective in surgical patients) 1
Why UFH is Preferred in Severe CKD
UFH is the anticoagulant of choice when CrCl <30 mL/min because: 1, 2, 3
- Hepatic metabolism eliminates concerns about drug accumulation 1, 5
- No dose adjustment required regardless of renal function 1, 6
- Rapid reversibility with protamine if bleeding occurs 1
Critical Warnings Specific to CKD
Bleeding Risk Considerations
CKD patients face paradoxically increased risks of both thrombosis and bleeding, making careful monitoring essential. 5, 7
- Major bleeding occurred in 1 in 3 hospitalized CKD patients receiving anticoagulation (HR 4.61) 7
- UFH use in CKD was associated with higher bleeding risk compared to enoxaparin (HR 4.79), though enoxaparin requires dose adjustment in severe CKD 7
- In STEMI patients with CKD receiving UFH boluses ≥130 IU/kg for PCI, there was markedly increased aPTT prolongation (74.1% had aPTT ratio ≥4 times control vs. 42.3% without CKD) 8
Practical Pitfall: High-Dose Boluses in CKD
When using UFH boluses ≥130 IU/kg in CKD patients (such as during PCI), expect significantly prolonged aPTTs and consider using lower end of dosing range. 8
- CKD patients had aPTT ratio of 5.1 vs. 3.4 in non-CKD patients within 6 hours post-PCI 8
- CKD was independently associated with markedly high aPTTs (OR 2.04), particularly with boluses ≥130 IU/kg (OR 3.69) 8
- This likely reflects impaired plasma protein binding and reduced UFH elimination in CKD 8
Absolute Contraindications
- Active or history of heparin-induced thrombocytopenia (HIT) - use argatroban, danaparoid, or fondaparinux instead 1, 2, 3
- Recent neuraxial anesthesia (spinal hematoma risk) 1
Monitoring Requirements
- Monitor platelet counts every 2-3 days from day 4 to day 14 for HIT detection 1
- Do not routinely monitor anti-Xa levels for prophylactic dosing 1
- For therapeutic dosing, use aPTT monitoring with laboratory-specific therapeutic ranges 3
Why Not LMWH in Severe CKD?
While LMWH is generally preferred over UFH in patients with normal renal function due to more predictable pharmacokinetics and lower HIT rates 1, LMWH accumulates in severe renal impairment (CrCl <30 mL/min) and is contraindicated. 4, 1, 3