Introduction
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired haemolytic anaemia caused by somatic mutation in the phosphatidylinositol glycan-complementation class A gene, resulting in absence of a key complement regulatory protein, CD59.
Thrombosis occurs in up to 40% of PNH patients; it usually involves abdominal and cerebral veins and it is the leading cause of death disease related.
Methods
We describe the response to Eculizumab (Soliris, Alexion) in 28 years old male with PNH diagnosed as a consequence of Budd Chiari Syndrome, acute liver dysfunction, mild haemolytic anaemia and thrombocytopenia.
Results
The patient was admitted to the gastroenterology department with acute abdominal pain, fatigue, hemolytic anaemia, thrombocytopenia and transaminitis. Abdominal doppler ultrasonography (US) was immediately performed with detection of Budd Chiari Syndrome, portal vein thrombosis, initial portal hypertension and ascites.
He was started on low dose low molecular weight heparin (platelets < 40x10^9/L), but despite anticoagulation progressive liver damage occurred, with poor pain control and worsening ascites. At the same time, we observed rapid exacerbation of thrombocytopenia and increasing in hemolysis tests with lactate dehydrogenase (LDH) reaching 1766 U/L, unresponsive to steroids administration. Bone marrow biopsy was negative but peripheral blood flow cytometry characterized a large PNH clone (85% total red blood cells). Furthermore, liver biopsy identified advanced stage of idiopathic cirrosis.
Eculizumab therapy was then initiated at a dose of 600 mg weekly for 4 weeks and then 900 mg every 14 days. During the first month, transaminases progressively normalized and platelets settled permanently above 40x10^9/L, allowing therapeutic dose of anticoagulation. LDH dropped from basal value of >1000U/L to 600U/L and progressive reduction in abdominal pain was observed.
Recanalization of portal vein thrombosis was found out at the US doppler after 6 weeks of anticoagulation, but recanalization of sovraepatic veins was not yet detectable.
Conclusions
Currently, after 17 Eculizumab administrations, platelets are 44 x 10^9/L, Hb 11.9 g/dl, AST 26 mg/dl, ALT 55 mg/dl, GGT 123 mg/dl, LDH 518 U/L. No further thrombotic episodes occurred, no ascites was detected as well as portal hypertension signs, performing ultrasonography monitoring.
This case shows that Eculizumab can block intravascular haemolysis and platelet consumption and can improve hepatic failure, allowing full dose of anticoagulant as therapy for current thrombosis or as prophylaxis for future events.
Disclosures:
No relevant conflicts of interest to declare.
A Novel Culprit in a Patient with Budd-Chiari Syndrome