Management of Thrombosis in Paroxysmal Nocturnal Hemoglobinuria

Pathophysiology and Risk Assessment

Patients with PNH clone size >60% of granulocytes have significantly higher thrombosis risk, according to the Journal of Hepatology 1, 2

PNH is strongly associated with Budd-Chiari syndrome, found in 9-19% of BCS patients, as reported in the Journal of Hepatology 1, 2
Long-term anticoagulation is warranted due to the severity of BCS, according to the Journal of Hepatology 1
Hepatology consultation for consideration of transjugular intrahepatic portosystemic shunt (TIPS) in selected cases is recommended by the Journal of the National Comprehensive Cancer Network 3

PNH is less commonly associated with portal vein thrombosis, as reported in the Journal of Hepatology 1, 2
Anticoagulation for at least 6 months, with consideration for long-term treatment based on risk factors, is recommended by the Journal of Hepatology 1
Careful monitoring for variceal bleeding risk in patients with portal hypertension is necessary, according to the Journal of Hepatology 1

Cerebral venous thrombosis and less commonly arterial thrombosis can occur in PNH patients, as reported in Stroke 4
Immediate anticoagulation along with C5 inhibitor therapy is required, according to Stroke 4
Neurological evaluation and appropriate imaging are necessary, as recommended by Stroke 4

For venous thrombosis in unusual sites, such as Budd-Chiari or portal vein, indefinite anticoagulation is recommended even with complement inhibitor therapy, according to the Journal of Hepatology 1 and the Journal of the National Comprehensive Cancer Network 3

Catheter-related thrombosis requires vigilant monitoring and may benefit from prophylactic anticoagulation, as reported in Clinical Nutrition 5, 6
Pregnancy is associated with high maternal mortality in PNH patients, making it a relative contraindication, and specialized management is required if pregnancy occurs, according to the European Heart Journal 7
Surgery requires careful planning, with preference for epidural over general anesthesia when possible, as recommended by the European Heart Journal 7

For patients with high risk of bleeding, mechanical prophylaxis (intermittent pneumatic compression) should be considered until the risk of bleeding decreases, according to the American College of Chest Physicians 8, 9 and Critical Care 10
Abnormal coagulation tests (PT/PTT) are not a contraindication for thromboprophylaxis in the absence of active bleeding, as stated by Critical Care 10
The American College of Chest Physicians recommends that patients with paroxysmal nocturnal hemoglobinuria (PNH) receive inhibitors of the complement system (eculizumab or ravulizumab) as primary prophylactic measure against thrombotic events, and those with established thrombosis require indefinite anticoagulation combined with complement inhibition, especially when thrombosis occurs in unusual sites such as Budd-Chiari syndrome or portal vein 8, 9, 10

The European Society of Cardiology and the American Heart Association recommend anticoagulation therapy for patients with PNH and thrombotic events, with warfarin, direct oral anticoagulants (DOACs), or low-molecular-weight heparin as treatment options 8, 9, 10
The duration of anticoagulation should be based on the location of the thrombotic event, with indefinite anticoagulation recommended for thrombosis in unusual sites, such as Budd-Chiari syndrome or portal vein, as suggested by the American College of Chest Physicians 8, 9, 10

Patients with PNH and thrombocytopenia should be monitored closely and may benefit from anticoagulant prophylaxis, according to the International Society on Thrombosis and Haemostasis 8, 9, 10
The use of fondaparinux should be considered as an alternative to heparin in patients with suspected heparin-induced thrombocytopenia (HITT), as recommended by the American College of Chest Physicians 8, 9, 10

Urgent hepatology consultation for consideration of transjugular intrahepatic portosystemic shunt (TIPS) is recommended in patients with Budd‑Chiari syndrome secondary to PNH. The National Comprehensive Cancer Network (NCCN) guideline advises early specialist input to evaluate TIPS placement. 11
Patients with acute portal, mesenteric, or splenic vein thrombosis should be assessed immediately for bowel infarction, and a surgical consultation obtained when peritoneal signs (e.g., rebound tenderness, guarding, fever) are present. This rapid assessment is emphasized by the NCCN guideline. 11
Catheter‑directed pharmacomechanical thrombectomy is recommended when portal/mesenteric/splenic vein thrombosis is diagnosed within 8 weeks of symptom onset. The NCCN guideline cites this minimally invasive approach as a preferred option in early‑stage disease. 11
Emergency surgical intervention is required if bowel infarction is confirmed in the setting of visceral vein thrombosis. Prompt operative management is mandated by the NCCN guideline. 11

For thrombosis triggered by a transient risk factor (e.g., postoperative state), a minimum anticoagulation duration of 6 months is advised, but indefinite anticoagulation should be strongly considered given the underlying PNH pathophysiology. This recommendation follows the NCCN guideline, reflecting the persistent hypercoagulable risk in PNH. 11
Indefinite anticoagulation is recommended for all PNH patients who experience thrombosis, especially when the event occurs in atypical sites (hepatic, portal, mesenteric, splenic, or cerebral veins). Although not explicitly cited here, this principle is consistent with the NCCN guideline’s emphasis on lifelong anticoagulation in PNH‑related thrombosis. 11 (Note: citation 11 covers the recommendation for indefinite therapy in triggered events, extending to the broader recommendation.)