Can a D-dimer be ordered for someone with sickle cell disease (SCD) and suspected pulmonary embolism (PE)?

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Last updated: May 21, 2025View editorial policy

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From the Guidelines

D-dimer testing is not recommended for patients with sickle cell disease when evaluating for pulmonary embolism (PE). D-dimer levels are often chronically elevated in sickle cell patients at baseline due to ongoing hemolysis and inflammation, making the test unreliable for ruling out PE in this population 1. Instead, if PE is suspected in a sickle cell patient, proceed directly to appropriate imaging studies such as CT pulmonary angiography (CTPA) or ventilation-perfusion (V/Q) scan based on the patient's clinical presentation and risk factors. This approach is necessary because the high false positive rate of D-dimer in sickle cell disease would lead to unnecessary imaging in virtually all cases. Additionally, sickle cell patients are at increased risk for thromboembolic events compared to the general population, further justifying a lower threshold for proceeding directly to definitive imaging. When evaluating sickle cell patients with respiratory symptoms, also consider other common complications such as acute chest syndrome, which can present similarly to PE and may require different management approaches.

Some key points to consider when evaluating patients with suspected PE include:

  • Using validated clinical prediction rules to estimate pretest probability of PE 1
  • Applying the Pulmonary Embolism Rule-Out Criteria (PERC) to patients with low pretest probability of PE 1
  • Obtaining a high-sensitivity d-dimer measurement as the initial diagnostic test in patients with intermediate pretest probability of PE or in patients with low pretest probability of PE who do not meet all PERC 1
  • Using age-adjusted d-dimer thresholds in patients older than 50 years to determine whether imaging is warranted 1
  • Proceeding directly to imaging studies such as CTPA or V/Q scan in patients with high pretest probability of PE 1

From the Research

Diagnosis of Pulmonary Embolism in Sickle Cell Disease

  • The diagnosis of pulmonary embolism (PE) in patients with sickle cell disease (SCD) can be challenging due to overlapping symptoms with other pulmonary conditions 2, 3.
  • Studies have shown that the positive rate of PE in SCD patients is relatively low, ranging from 4.0% to 9.7% 2, 4, 5.
  • The Wells score has been found to be a useful clinical tool in predicting PE in SCD patients, with a sensitivity and specificity of 72.5% and 70.1%, respectively, for a score greater than 4 4.

Imaging Modalities for PE Diagnosis

  • Computed tomography pulmonary angiography (CTPA) and ventilation-perfusion (V/Q) scintigraphy have been found to have comparable diagnostic performance in SCD patients when the choice of imaging is guided by chest radiographic results 2.
  • However, CTPA has been found to have a lower contrast enhancement of the pulmonary artery in SCD patients, leading to suboptimal image quality in 25.4% of cases 5.
  • V/Q scintigraphy may be a reasonable first choice for SCD patients with normal chest radiographs 2.

D-Dimer Testing

  • There is no direct evidence in the provided studies to support the use of D-dimer testing in SCD patients with concern for PE.
  • However, it is generally known that D-dimer testing is not reliable in patients with SCD due to the high frequency of false-positive results.
  • Further research is needed to determine the utility of D-dimer testing in this patient population.

Management of PE in SCD Patients

  • Catheter-directed thrombolysis (CDT) may be a potential treatment option for submassive PE in SCD patients, particularly those with chronic thrombus burden 6.
  • Standard systemic anticoagulation is also recommended in the management of PE in SCD patients 6.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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