Is intravenous (IV) iron drip a contributing factor to frequent clotting of hemodialysis (HD) lines in patients undergoing hemodialysis, particularly those with a history of thrombosis or at high risk for clotting?

Is IV Iron Causing Hemodialysis Line Clotting?

No, intravenous iron administration is not a direct cause of hemodialysis line clotting. The highest quality evidence from the PIVOTAL trial—a large randomized controlled study of 2,141 hemodialysis patients—found that proactive IV iron therapy did not independently increase the risk of vascular access thrombosis compared to reactive iron therapy (HR 1.13, P = 0.18) 1.

Evidence Against IV Iron as a Thrombotic Risk

The PIVOTAL trial specifically analyzed vascular access thrombosis (VAT) events and demonstrated that:

• Treatment arm assignment (proactive vs. reactive IV iron) was not an independent predictor of clotting in multivariate analysis 1
• Nearly one-quarter of participants (22.4%) experienced VAT over a median 2.1 years, but this occurred equally across both iron dosing strategies 1
• The trial included patients receiving substantially different iron doses, yet thrombosis rates remained similar between groups 1

Actual Risk Factors for HD Line Clotting

The PIVOTAL trial identified the true independent predictors of vascular access thrombosis 1:

High-Risk Factors:

• Arteriovenous graft use (HR 2.29, P < 0.001) 1
• Digoxin use (HR 2.48, P < 0.001) 1
• Diabetic kidney disease (HR 1.45, P < 0.001) 1
• Smoking history (HR 1.47, P = 0.004) 1
• Female sex (HR 1.33, P = 0.002) 1
• Diuretic use (HR 1.25, P = 0.02) 1

Protective Factor:

• Angiotensin receptor blocker use (HR 0.66, P = 0.01) 1

The Iron-Platelet Connection: A Theoretical Concern

While IV iron itself doesn't cause clotting, there is a nuanced relationship worth understanding:

• Iron deficiency (not iron supplementation) can cause thrombocytosis, which theoretically increases thrombotic risk 2
• Erythropoiesis-stimulating agents (ESAs) frequently induce functional or absolute iron deficiency, which may drive platelet elevation 2
• IV iron administration actually decreases platelet counts: In the DRIVE trial, patients receiving IV iron had mean platelet decreases of 29,000/μL versus no change in those not receiving iron (P = 0.017) 2

This suggests that adequate iron supplementation may actually reduce thrombotic risk by preventing iron deficiency-induced thrombocytosis 2.

Clinical Implications for Your Practice

When evaluating frequent HD line clotting:

Do not withhold IV iron based on clotting concerns 1. Instead, investigate:

1. Access type: AVGs clot more than AVFs (2.3-fold higher risk) 1
2. Medication review: Check for digoxin (2.5-fold risk) and consider ARB therapy (34% risk reduction) 1
3. Comorbidities: Diabetes and smoking significantly increase risk 1
4. Iron status: Ensure adequate iron stores to prevent iron deficiency-induced thrombocytosis 2

Continue guideline-concordant IV iron therapy to maintain transferrin saturation ≥20% and ferritin ≥100 ng/mL 3. Most hemodialysis patients require 250-1,000 mg of IV iron within 12 weeks for maintenance 4.

Important Caveats

• Monitor for iron overload by withholding IV iron when TSAT >50% and/or ferritin >800 ng/mL 3
• While excessive iron can cause oxidative stress and inflammation 5, the evidence does not support a direct thrombotic mechanism in properly dosed regimens 1
• The bundling reimbursement policy has increased IV iron use, making judicious dosing important to avoid overload 5, but clotting is not the primary concern