What labs should I order for a patient on anticoagulation therapy with hematuria?

Laboratory Evaluation for Hematuria in Anticoagulated Patients

Order a complete blood count (CBC) with hemoglobin, PT/INR or aPTT (depending on anticoagulant type), urinalysis with microscopy, urine culture, and serum creatinine immediately. 1

Essential Initial Laboratory Tests

Hemoglobin and Blood Count

• Obtain a baseline hemoglobin and serial measurements to assess for significant blood loss, as a hemoglobin drop ≥2 g/dL is associated with significantly increased mortality risk, particularly in patients with cardiovascular disease. 1
• Pre-resuscitation hemoglobin may be artificially elevated due to hemoconcentration, so serial measurements are critical. 1

Anticoagulant Activity Assessment

For patients on warfarin:

• Order PT/INR to assess anticoagulation level and guide management decisions. 1

For patients on direct oral anticoagulants (DOACs):

• Request PT and/or aPTT as initial screening tests, though interpretation has important limitations. 1
• For dabigatran specifically, a thrombin time (TT) is highly valuable—a normal TT excludes clinically relevant dabigatran levels. 1
• If available, specialized quantitative assays (dilute thrombin time for dabigatran, anti-Xa assays for factor Xa inhibitors) provide more precise drug level measurement. 1
• The International Society on Thrombosis and Haemostasis recommends considering reversal for serious bleeding when DOAC levels exceed 50 ng/mL. 1

Urinalysis with Microscopy

• Perform complete urinalysis with microscopic examination to assess red blood cell count per high-power field, presence of dysmorphic RBCs or red cell casts (suggesting glomerular source), and presence of white blood cells or bacteria. 2
• Ensure a clean-catch specimen; consider catheterization if necessary to obtain an adequate sample. 2
• Examine the sample tube for clots and review the smear to exclude platelet aggregates that could cause false thrombocytopenia. 1

Urine Culture

• Order urine culture to definitively rule out urinary tract infection as a benign cause of hematuria. 2

Renal Function Assessment

• Measure serum creatinine to assess renal function, which is particularly important for patients on dabigatran (renally cleared) and to help differentiate glomerular from non-glomerular bleeding sources. 1, 2
• Elevated creatinine combined with proteinuria, dysmorphic RBCs, or red cell casts suggests glomerular disease. 2

Additional Coagulation Studies (If Indicated)

When to Order Extended Coagulation Panel

• If disseminated intravascular coagulation (DIC) is suspected in severe bleeding, add fibrinogen and D-dimers or fibrin monomers. 1
• Important caveat: Routine coagulation panels (PT/PTT/TT/fibrinogen) are frequently overordered—fibrinogen is normal in 98% of cases and critically low (<100 mg/dL) in only 0.6%, almost always associated with active bleeding. 3
• Do not routinely order TT and fibrinogen unless there is clinical suspicion for DIC or heparin effect. 3

For Patients on Heparin

• If heparin-induced thrombocytopenia (HIT) is suspected based on timing and degree of platelet drop, order anti-PF4 antibodies if the 4T score is intermediate (4-5) or high (≥6). 1

Critical Pitfalls to Avoid

• Never attribute hematuria solely to anticoagulation without thorough evaluation—30% of anticoagulated patients with hematuria have significant underlying urologic pathology, including malignancy in up to 7% of cases with gross hematuria. 2, 4, 5, 6
• Do not delay urologic evaluation while waiting for laboratory results in patients with gross hematuria—urgent referral is mandatory regardless of anticoagulation status. 2
• Laboratory testing should not take precedence over clinical assessment of life-threatening bleeding. 1
• Hematuria occurring within the first 72 hours of anticoagulation initiation is more common and dose-dependent, but still requires full evaluation. 7

Interpretation Algorithm

If urinalysis shows:

• Significant proteinuria, dysmorphic RBCs, red cell casts, or elevated creatinine → glomerular source likely → nephrology referral indicated. 2
• Normal-shaped RBCs, minimal/no proteinuria, normal creatinine → urologic source likely → urgent urology referral required. 2

If hemoglobin drops ≥2 g/dL or transfusion of ≥2 units RBCs required:

• This constitutes major bleeding with significantly increased mortality risk—immediate intervention and possible anticoagulant reversal consideration. 1