How I diagnose and treat venous thromboembolism in sickle cell disease

Arun S. Shet and Ted Wun

Article Figures & Data



  • Table 1.

    Alterations in the coagulation system in humans with SCD

    Biochemical evidence of coagulation activationIncreased levelsDecreased levelsSteady stateAcute crisisReference
    FXa generation
     Tissue factor pathway+++18, 68
     Intrinsic pathway (FXII, HMWK, prekallikrein)31, 32
    Thrombin/fibrin generation
     Prothrombin fragment F1.2+++70
     Fibrinopeptide A+71
     Thrombin antithrombin complexes+++68
    Changes in anticoagulant protein levels
     Protein C and S72, 73
     ATIII and heparin cofactor II74, 75
    Changes in fibrinolytic protein levels
     Plasminogen activator inhibitor 1+++76, 77
    Other plasmatic factors
    Cellular factors contributing to coagulation
     Platelet number and size++*22
     Platelet activation and function+++80
     Red blood cell activation (PS exposure and adhesion)++81
     Leukocyte activation (TF exposure)+++20
     Endothelial activation (TF exposure and adhesion)+++17
     Cell-derived microparticles+++21
    • +, increased compared with controls; −, decreased compared with controls; ATIII, antithrombin III; FVIII, factor VIII; FXa, factor Xa; FXII, factor XII; HMWK, high-molecular-weight kininogen; PS, phosphatidylserine; TF, tissue factor; VWF, von Willebrand factor.

    • * Variable findings.

  • Table 2.

    Summary of the approach to diagnosis and treatment of VTE in SCD

    VTE diagnosis and treatment approaches in SCD
    Diagnosis• Compression ultrasonography (±Doppler) for deep venous thrombosis
    • CTPA with nonionic low-osmolality contrast media
      o We do not routinely recommend red cell transfusion prior to contrast
      o Although less frequently performed V/Q scanning has clinical utility, especially when tested serially
    • D-dimer is routinely elevated in SCD precluding the high negative predictive value advantage this biomarker has in other settings
    Treatment• Treatment as per ACCP 2016 guidelines with full-dose anticoagulation
      o Potential for increased risk of bleeding in patients with MRA evidence for Moya Moya syndrome
    • Heparin, DOAC, or vitamin K antagonists are therapeutic options
    • In line with ACCP 2016 guidelines, our initial choice of anticoagulant is a DOAC if not contraindicated
    • Anticoagulate for at least 3 mo for VTE event
    • Consider extended anticoagulation in those with low bleeding risk even if the event was provoked by hospitalization for medical illness
    • Continue anticoagulation for catheter-associated upper-extremity thrombosis until catheter removal
    • Adapted from Wun and Brunson.9

    • MRA, magnetic resonance angiography.