From the Guidelines
Paroxysmal nocturnal hemoglobinuria (PNH) thrombosis requires immediate anticoagulation therapy and long-term complement inhibition to prevent further thrombotic events and reduce the risk of morbidity and mortality. The treatment for PNH thrombosis typically involves anticoagulation therapy with low molecular weight heparin (such as enoxaparin 1mg/kg twice daily) or direct oral anticoagulants (such as apixaban 5mg twice daily or rivaroxaban 20mg daily) 1.
Key Considerations
- Additionally, complement inhibitor therapy with eculizumab (900mg IV every 2 weeks after loading doses) or ravulizumab (dosing based on weight, administered every 8 weeks after loading) is essential to prevent further thrombotic events by blocking terminal complement activation 1.
- Patients should receive meningococcal vaccination before starting complement inhibitors due to increased infection risk.
- For acute thrombosis, thrombolysis may be considered in severe cases.
- Long-term management includes indefinite anticoagulation and complement inhibition therapy.
Pathophysiology
PNH thrombosis occurs because the abnormal blood cells in PNH lack proteins that normally protect them from complement activation, leading to hemolysis and a hypercoagulable state.
Risk Factors
The thrombosis risk in PNH is particularly high in hepatic, cerebral, and abdominal veins, with potentially life-threatening consequences if not promptly treated 1.
Treatment Implications
Diagnosing the underlying aetiological factor for developing PNH thrombosis is important, since it may have therapeutic or prognostic implications, and the presence of a prothrombotic disorder may influence the duration of anticoagulant treatment 1.
From the FDA Drug Label
PNH in pregnancy is associated with adverse maternal outcomes, including worsening cytopenias, thrombotic events, infections, bleeding, miscarriages, and increased maternal mortality, and adverse fetal outcomes, including fetal death and premature delivery The answer to Pnh thrombosis is that it is associated with thrombotic events in pregnancy, as stated in the drug label for ravulizumab (IV) 2.
From the Research
PNH Thrombosis Overview
- PNH thrombosis is a major clinical manifestation of Paroxysmal Nocturnal Hemoglobinuria (PNH), affecting up to 40% of individuals with the disease 3.
- Thrombosis in PNH is thought to occur through complement-mediated mechanisms, which is different from other thrombotic disorders 4.
- Venous thrombosis is more prevalent in PNH patients, often affecting unusual sites such as intrabdominal and hepatic veins 3, 5.
Pathogenesis of Thrombosis in PNH
- Complement activation, endothelial dysfunction, hemolysis, impaired bioavailability of nitric oxide, and activation of platelets and neutrophils are implicated in the pathogenesis of thrombotic events in PNH patients 3.
- A vicious cycle involving the coagulation cascade, complement system, and inflammation cytokines is established in PNH patients, contributing to thrombosis 3.
- Deficiency of glycosylphosphatidylinositol (GPI)-anchored proteins, such as CD55 and CD59, on erythrocytes leads to intravascular hemolysis and thrombosis upon complement activation 5, 6.
Treatment and Management of PNH Thrombosis
- Complement inhibitors, such as eculizumab and ravulizumab, have revolutionized the care of patients with PNH and thrombosis, reducing the number of thromboembolic events 4, 3.
- Anticoagulants, such as warfarin and low-molecular-weight heparin, and direct oral anticoagulants (DOACs) may be used in combination with complement inhibitors in patients who develop thrombotic events 3, 7.
- However, there is limited data on the use of DOACs in patients with PNH, and large-scale studies are required to gather more information 7.