Can a patient with sickle cell disease who develops a right atrial (RA) clot and subsegmental pulmonary embolism start on a Direct Oral Anticoagulant (DOAC), such as Apixaban (apixaban), for treatment?

Anticoagulation for Sickle Cell Disease with Right Atrial Clot and Subsegmental PE

Yes, start a DOAC for this patient with sickle cell disease who has developed venous thromboembolism (right atrial clot and subsegmental pulmonary embolism), provided there are no additional bleeding risk factors. 1, 2

Guideline-Based Recommendation

The American Society of Hematology 2019 guidelines specifically address anticoagulation in SCD patients with VTE 1:

• For first provoked VTE in adults with SCD, use defined periods of anticoagulation (3-6 months) rather than indefinite therapy 1
• The panel considers SCD itself a chronic underlying risk factor for VTE 1
• Anticoagulation should continue as long as any provoking risk factor remains present 1

The American Thoracic Society provides complementary guidance 1, 2:

• For SCD patients with RHC-confirmed pulmonary hypertension AND venous thromboembolism without additional bleeding risk factors, indefinite anticoagulation is suggested 1, 2
• This reflects that the benefits of preventing recurrent VTE (13.8% reduction) and possibly lower mortality outweigh the increased bleeding risk (2.4% increase) 1

DOAC Selection and Practical Considerations

DOACs are preferred over warfarin for VTE treatment in the general population, and this preference extends to SCD patients 1:

• Apixaban and rivaroxaban are the most studied DOACs in this context 3, 4
• Account for renal function when selecting a DOAC: avoid edoxaban if CrCl >95 mL/min due to decreased efficacy 1
• Consider drug-drug interactions and ability to take oral medications 1

Special Considerations for This Case

The presence of a right atrial clot warrants particular attention 1:

• Right atrial thrombi can be either in-transit emboli from deep vein thrombosis or formed in situ
• Both scenarios require full-dose anticoagulation
• The subsegmental PE confirms this is part of a venous thromboembolic process requiring treatment

Duration of therapy depends on whether this VTE is provoked or unprovoked 1:

• If provoked (e.g., central line, recent surgery, prolonged immobilization): treat for 3-6 months 1
• If unprovoked or if the patient has pulmonary hypertension confirmed by right heart catheterization: consider indefinite anticoagulation 1, 2
• Continue anticoagulation as long as any provoking factor persists 1

Evidence from Clinical Practice

Real-world data on DOACs in SCD patients with VTE shows 3, 4:

• In a prospective cohort of 12 SCD patients treated with rivaroxaban, no major bleeding occurred, though 50% had minor bleeding 3
• A retrospective study found similar VTE recurrence rates between DOACs (27%) and warfarin (20%), with comparable bleeding rates 4
• These recurrence rates are higher than in the general population, emphasizing the need for close monitoring 4

Critical Pitfalls to Avoid

Do not withhold anticoagulation due to concerns about bleeding in SCD 1:

• While SCD patients have both prothrombotic and bleeding tendencies, the mortality risk from recurrent VTE justifies anticoagulation 1
• The increased stroke risk in SCD does not contraindicate anticoagulation for VTE unless there is active intracranial hemorrhage or cerebral amyloid angiopathy 1

Assess bleeding risk factors before initiating therapy 1:

• Consider concurrent medications that increase bleeding risk (NSAIDs, antiplatelet agents) 1
• Evaluate for existing conditions that increase bleeding risk 1
• Use shared decision-making to discuss benefits versus harms 1

Monitor for treatment failure 4:

• VTE recurrence rates in SCD patients on anticoagulation are higher than the general population (20-27% vs. 3-4%) 5, 4
• If recurrent VTE occurs on a DOAC, consider switching to a different DOAC or to warfarin with therapeutic INR monitoring 4

Concurrent SCD Management

Continue or optimize disease-modifying therapy for SCD 2, 6:

• Hydroxyurea remains first-line therapy and should be continued 2, 6
• Maintain adequate hydration to prevent sickling, but use diuretics cautiously if needed for volume overload 6
• Maintain oxygen saturation ≥90% at rest, with exertion, and during sleep 6