What is the effect of a hematocrit (red blood cell concentration) above 55% on coagulation tests, such as prothrombin time (PT) and activated partial thromboplastin time (aPTT)?

Effect of High Hematocrit (>55%) on Coagulation Tests

The excess anticoagulant in specimens with hematocrit above 55% will falsely prolong the PT and aPTT results, potentially leading to inappropriate clinical decisions regarding anticoagulation management. 1

Mechanism of Interference

When blood is collected in standard citrate tubes, the ratio of anticoagulant to plasma is critical for accurate coagulation testing. In patients with elevated hematocrit:

• The fixed volume of citrate in standard collection tubes is designed for samples with normal hematocrit (35-45%)
• With high hematocrit (>55%), there is less plasma volume in the sample but the same amount of citrate
• This creates a relative excess of anticoagulant in the plasma portion 1
• The excess citrate binds more calcium than needed, interfering with the calcium-dependent coagulation reactions measured by PT and aPTT tests

Evidence Supporting Citrate Adjustment

Research by Adcock et al. demonstrated that PT and aPTT results from non-adjusted and adjusted citrate samples were statistically different and exponentially increased with increasing hematocrit values (55%-72%) 1. This effect occurs due to:

1. Dilutional effect of reduced plasma volume
2. Interference effect of higher final citrate concentration on the clotting test result

Clinical Implications

The falsely prolonged PT and aPTT in high-hematocrit specimens can lead to:

• Misdiagnosis of coagulation disorders when none exist
• Inappropriate dose adjustments in patients on anticoagulation therapy
• Unnecessary additional testing and consultations
• Potential delay of surgical procedures 2

Guidelines for Specimen Collection

The International Society on Thrombosis and Haemostasis and other clinical guidelines recommend:

• For patients with hematocrit >55%, the citrate volume in collection tubes should be adjusted to maintain the proper anticoagulant-to-plasma ratio 3
• The formula for adjustment involves reducing the amount of citrate based on the patient's hematocrit value
• This adjustment is particularly important for patients on anticoagulation therapy, where accurate monitoring is critical 3

Contrasting Evidence

Interestingly, some research has shown unexpected results:

• A study by Marlar et al. found that while statistically significant differences were observed with citrate adjustment, some samples showed shortening rather than the expected prolongation of PT and aPTT values 4
• However, the preponderance of evidence supports the need for citrate adjustment in high-hematocrit specimens 1, 5

Special Populations

This issue is particularly important in certain patient populations:

• Patients with polycythemia vera, where hematocrit levels can exceed 60% 3
• Patients with cyanotic congenital heart disease, who may have hematocrit levels in the 55-60% range 3
• Neonates, who physiologically have higher hematocrit values

Practical Recommendations

For accurate coagulation testing in patients with hematocrit >55%:

1. Use adjusted citrate collection tubes or adjust the citrate volume manually
2. Document the high hematocrit on the laboratory requisition
3. Consider alternative monitoring methods when appropriate (e.g., anti-Xa assay for heparin monitoring) 6
4. Interpret results in the clinical context, recognizing potential interference

The answer to the question is C: The excess anticoagulant will falsely prolong the PT and aPTT.