What is the next step in managing a patient with sickle cell disease (SCD) and elevated D-dimer (D-dimer) levels?

Management of Elevated D-dimer in Sickle Cell Disease

For patients with sickle cell disease (SCD) and elevated D-dimer levels, the next step should be an immediate evaluation to exclude acute chest syndrome, pulmonary embolism, and other potentially life-threatening complications. 1

Initial Assessment

• Urgent clinical evaluation focusing on:

  • Respiratory symptoms (cough, shortness of breath, chest pain)
  • Fever
  • Decreasing hemoglobin levels
  • Hypoxemia
  • Extremity pain 1

• Immediate diagnostic workup:

  • Chest X-ray (to identify pulmonary infiltrates suggestive of acute chest syndrome)
  • Complete blood count with reticulocyte count
  • Oxygen saturation monitoring
  • Blood cultures if febrile 1, 2

Diagnostic Algorithm

1. If respiratory symptoms, fever, or hypoxemia are present:

   • Obtain chest X-ray immediately to evaluate for acute chest syndrome 1
   • Consider CT pulmonary angiography if pulmonary embolism is suspected, especially with markedly elevated D-dimer

2. If signs of acute chest syndrome are present (new pulmonary infiltrate on chest radiograph with fever and/or respiratory symptoms):

   • Initiate aggressive management including:
     • Supplemental oxygen
     • Broad-spectrum antibiotics
     • Pain management
     • Consider exchange transfusion for moderate to severe cases 1, 2

3. If no acute chest syndrome but persistent pain:

   • Evaluate for vaso-occlusive crisis
   • Administer prompt opioid analgesia using scheduled dosing or patient-controlled analgesia 1
   • Monitor for development of acute chest syndrome, which can develop during hospitalization for pain crisis 1

4. If no clear source identified:

   • Assess for other complications associated with elevated D-dimer:
     • Venous thromboembolism
     • Splenic sequestration (rapidly enlarging spleen and hemoglobin drop >2 g/dL)
     • Hepatic complications (acute intrahepatic cholestasis, hepatic crisis) 1, 3

Management Considerations

• For confirmed venous thromboembolism with RHC-confirmed pulmonary hypertension:

  • Consider indefinite anticoagulant therapy if no additional risk factors for hemorrhage exist 2

• For patients with increased mortality risk (defined by TRV >2.5 m/second, NT-pro-BNP >160 pg/ml, or RHC-confirmed pulmonary hypertension):

  • Hydroxyurea is strongly recommended as first-line therapy 2
  • Chronic transfusion therapy may be considered for patients who are not responsive to or not candidates for hydroxyurea 2

• For pain management during crisis:

  • Administer opioid analgesics promptly using scheduled dosing or patient-controlled analgesia 1
  • Consider adjunctive non-opioid analgesics to avoid under-treatment of pain 1

Important Caveats

• Elevated D-dimer is common in SCD patients even during steady state (non-crisis periods), but levels typically increase further during complications 4, 5
• D-dimer levels correlate with clinical status and can serve as an objective marker for vaso-occlusive crisis and other complications 5
• Serial D-dimer measurements may help monitor clinical improvement or deterioration 5
• Avoid phosphodiesterase-5 inhibitor therapy in patients with SCD who have pulmonary hypertension 2
• Regular monitoring by a hematologist is recommended for hospitalized SCD patients with elevated D-dimer to assess for developing complications 1

Long-term Considerations

• For patients with recurrent thrombotic events or persistent elevation of D-dimer with complications:
  • Consider disease-modifying therapies such as hydroxyurea, L-glutamine, crizanlizumab, or voxelotor 6
  • Evaluate for chronic pulmonary hypertension with echocardiography 2
  • Implement preventive measures including adequate hydration and avoidance of extreme temperatures 1