Abstract

Thrombosis, mainly venous but also arterial, is the leading threat in Paroxysmal Nocturnal Hemoglobinuria (PNH) patients, caused by the continuous hemolysis. It constitutes the first cause of death in all reported series. Since 1964, a total of 56 patients with PNH clone were evaluated in our Hematology Unit. According with PNH Parker´s Classification, most of the patients were Classical type (28 patients), and the remaining included in the other subsets: 21 in the setting of another bone marrow failure syndrome (BMFS) and 7 subclinical.

Since November 2007, Eculizumab (an anti-C5 antibody) is employed in the disease to abrogate the hemolysis in our patients. In the last years, sixteen patients have been treated with this drug in our series. PNH patients previously anticoagulated with warfarin because thrombosis, continued on therapy after the addition of Eculizumab. Also, patients with more than 50 % PNH clone (established by Cytometry with FLAER on granulocytes) and platelets >50 x109/L received oral anticoagulation.

The incidence and localization of thrombotic events in the patients without Eculizumab was as follows:

Parker’s Classification Classical BMFS Subclinical 
28 21 
Thrombosis cases (%) 14 (50) 4 (20) 2 (33) 
Thrombotic episodes: 26 
Deep calf 
Multiple cerebral ischemic infarcts 2 (1 death) 
Large Cerebrovascular 
Budd-Chiari 1 (1 death)  
Portal 2 (1 death)   
Retinal   
Cava   
Pulmonary thromboembolism 2 (1 death)   
Myocardial infarction 3 (1 death)   
Arterial ischemia 2 (1 amputation)   
Skin ischemic 2 (vasculitis, livedo reticularis)   
Parker’s Classification Classical BMFS Subclinical 
28 21 
Thrombosis cases (%) 14 (50) 4 (20) 2 (33) 
Thrombotic episodes: 26 
Deep calf 
Multiple cerebral ischemic infarcts 2 (1 death) 
Large Cerebrovascular 
Budd-Chiari 1 (1 death)  
Portal 2 (1 death)   
Retinal   
Cava   
Pulmonary thromboembolism 2 (1 death)   
Myocardial infarction 3 (1 death)   
Arterial ischemia 2 (1 amputation)   
Skin ischemic 2 (vasculitis, livedo reticularis)   

After introduction of Eculizumab, sixteen patients have been treated with this drug and active thrombosis resolved in all cases, as was the case of a patient with a large persistent thrombosis in the inferior cava vein despite the isolated anticoagulation therapy. Only one patient on Eculizumab therapy experienced a thrombotic event and suffered a transient ischemic attack with aphasia after a prolonged catheter ablation procedure for an atrial fibrillation. This patient had previous signs of small vessel disease in MR imaging techniques. The episode occurs despite heparin anticoagulation and anticipated additional Eculizumab dose and resolves thereafter.

Eculizumab had a clear favourable impact in preventing thrombosis complications in our series of PNH patients. Careful monitoring of LDH levels and shortening the Eculizumab interval doses it is indicated in any chirurgical or invasive procedures in these patients.

Disclosures:

Pastrana:Alexion Pharmaceuticals: Speakers Bureau. Ojeda:Alexion Pharmaceuticals: Consultancy, Speakers Bureau.

Author notes

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Asterisk with author names denotes non-ASH members.