What causes a false negative result for hepatic Arteriovenous Malformations (AVMs) or blood clots on Computed Tomography (CT) angiography in patients with a history of vascular disease, liver disease, or hereditary hemorrhagic telangiectasia (HHT)?

False Negative Results for Hepatic AVMs or Blood Clots on CT Angiography

CT angiography can produce false negative results for hepatic AVMs primarily due to slow, intermittent blood flow through arteriovenous shunts, and for blood clots due to timing of contrast administration relative to the bleeding episode. 1

Technical Causes of False Negatives for Hepatic AVMs

Flow-Related Factors

• Slow intermittent hemorrhage through hepatic arteriovenous malformations can fail to demonstrate active extravasation on CTA, even when bleeding is occurring 1
• Dilated, tortuous, hypertrophic uterine arteries (and by extension, hepatic arteries in AVMs) can mimic extravasation, creating diagnostic confusion that may lead to underrecognition of true AVMs 1
• The intermittent nature of shunting through hepatic AVMs means that timing of image acquisition is critical—if the scan is performed during a quiescent phase, the AVM may not be apparent 1

Imaging Protocol Limitations

• Single-phase CT protocols are inadequate for detecting hepatic AVMs—multiphasic CT including noncontrast, arterial, and portal venous phases is required for 97% accuracy 1
• Failure to include all three phases (noncontrast, arterial, portal venous) significantly reduces sensitivity for detecting both AVMs and active bleeding 1

Alternative Imaging Modalities to Prevent False Negatives

Doppler Ultrasound as First-Line

• Doppler ultrasound should be the first-line investigation for hepatic vascular malformations in HHT patients, not CT angiography 1
• Doppler ultrasound provides superior sensitivity for detecting hepatic AVMs with key diagnostic findings including: enlarged hepatic artery (>6 mm), peak flow velocity >80 cm/sec, resistivity index <0.55, and intrahepatic hypervascularization 1
• Doppler ultrasound is the only imaging technique that can provide severity grading (0.5 to 4) of hepatic vascular malformations, which correlates with clinical outcome 1

When CT is Necessary

• CT or MR angiography should be reserved for cases where Doppler ultrasound is technically inadequate, when focal liver lesions require characterization, or when assessing severity and hemodynamic impact of known AVMs 1
• Multiphasic CTA with noncontrast, arterial, and portal venous phases is mandatory when CT is performed to achieve 97% accuracy for detecting vascular abnormalities 1

Clinical Context That Increases False Negative Risk

Patient-Specific Factors

• Only 8% of patients with hepatic vascular malformations are symptomatic, meaning most hepatic AVMs are hemodynamically insignificant and may not demonstrate robust flow on any imaging modality 1
• In HHT patients, hepatic AVMs are more common and symptomatic in females with ACVRL1 mutations (HHT type 2), and these patients should have heightened clinical suspicion even with negative initial imaging 2

Timing Considerations

• For suspected acute bleeding or clot detection, CTA performed too early (before sufficient extravasation) or too late (after bleeding has stopped) will be falsely negative 1
• Active extravasation is only detected in 41-74% of cases even with optimal timing, highlighting the inherent limitation of CTA for intermittent bleeding 1

Critical Pitfalls to Avoid

Dangerous Diagnostic Maneuvers

• Never perform liver biopsy in patients with proven or suspected HHT or hepatic AVMs due to catastrophic hemorrhage risk from vascular malformations 1, 3
• Do not rely solely on CT angiography for screening asymptomatic HHT patients—Doppler ultrasound is safer, more cost-effective, and provides functional information about hemodynamic significance 1

Interpretation Errors

• Do not mistake dilated tortuous hepatic arteries for active extravasation—this false positive interpretation can obscure the true diagnosis of underlying AVM 1
• Absence of active extravasation on CTA does not exclude hepatic AVMs, particularly in HHT patients where AVMs may have slow flow or be in a quiescent phase 1
• Small focal nodular hyperplasia (FNH) lesions are 100-fold more prevalent in HHT patients than the general population and should not be mistaken for malignancy or prompt unnecessary biopsy 1

Recommended Diagnostic Algorithm

For Suspected Hepatic AVMs in HHT

1. Start with Doppler ultrasound as first-line imaging in all cases 1
2. Assess hepatic artery diameter, peak flow velocity, resistivity index, and peripheral hypervascularization 1
3. Grade severity (0.5-4) to guide management and follow-up 1
4. Reserve CT or MR for focal lesion characterization or when Doppler is technically inadequate 1
5. If CT is performed, mandate multiphasic protocol (noncontrast, arterial, portal venous phases) 1

For Suspected Acute Hepatic Bleeding

1. In hemodynamically unstable patients, proceed directly to angiography for diagnosis and potential embolization 1
2. In stable patients, perform multiphasic CTA (noncontrast, arterial, portal venous) to detect extravasation and characterize vascular anatomy 1
3. If initial CTA is negative but clinical suspicion remains high, repeat imaging or proceed to angiography 1
4. Recognize that 26-59% of cases will have no active extravasation even with optimal imaging timing 1