1. Paroxysmal Nocturnal Hemoglobinuria and Thrombosis Before and After Eculizumab
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Cristina Muñoz-Linares, MD1*, Miguel Pastrana, MD2*, Emilio Ojeda, MD, PhD1*, Rafael Fores, MD1*, Martin Cabero, MD1*, Daniel Morillo, MD1*, Guiomar Bautista, MD1*, Belen Navarro, MD1*, Isabel Krsnik, MD, PhD1*, Santiago Gil, MD, PhD1*, Carmen Regidor, MD1*, Almudena de LaIglesia, MD1*, Jose Luis Bueno, MD, PhD1*,
Jose A Garcia-Marco, MD, PhD1 and Jose Rafael Cabrera, MD, PhD1*
1Hematology, Hospital Puerta de Hierro Majadahonda, Majadahonda, Spain
2Radiology, Hospital Puerta de Hierro Majadahonda, Majadahonda, Spain
*Non-ASH member
Background: 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 57 patients with PNH clone were evaluated in our Hematology Unit. According with PNH Parker´s Classification, most of the patients were Classic type (30 patients), and the remaining included in the other subsets: 20 in the Setting of Another Bone Marrow Failure syndrome (BMFS) and 7 Subclinical.
Methods: 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 anticoagulation.
Results: 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 (view infra). 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.
Conclusion: 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.
Inferior cava vein thrombosis resolved after initiaton of Eculizumab
The patient is a 34 year old male. He was diagnosed as Severe Aplastic Anemia in 2002 and treated with immunosuppressors. Until now in treatment on Cyclosporine A. First hemoglobinuria episode occurred in summer Transfused occasionally. PNH clone of 10% diagnosed in In January 2010 began with very intense hemoglobinuria that lasts for several days and is admitted at the Hospital for acute renal failure. The creatinine was 9.4 mg/dL and creatinine clearance of 6.9 milliliters by minute. He required hemodialysis and transfusional support. The Minimum level of Hemoglobin was 6.7 g/dL and the lactic dehydrogenase was elevated six times over the normal level. In this episode a Retinal thrombosis was discovered. He received Treatment with Corticoids and Cyclosporine A. He was discharged, and the hemoglobinuria persists several days more. In January 2010 anticoagulation with warfarin was initiated. Then, the PNH clone was 76% in granulocytes by FLAER. The Local Committee did not accept the Eculizumab treatment proposed by Hematologists at that moment. In February 2011, it is evaluated by radiology: an inferior cava vein thrombosis was evident despite the anticoagulation therapy. He began on treatment with Eculizumab because this thrombosis. In May, three months later from the Eculizumab beginning, the thrombosis was resolved.
Thrombosis in the series before Eculizumab treatment
Parker’s Classification
Classic
BMFS
Subclinical 30 20 7
Thrombosis cases (%)
12 (40)
4 (20)
4 (28)
Thrombotic episodes:
Deep calf
Multiple cerebral ischemic infarcts
Large Cerebrovascular
Budd-Chiari
Portal
Retinal
Cava
Pulmonary thromboembolism
Myocardial infarction
Arterial ischemia
Skin ischemic 25 5 3 2 1
2 (1 death)
3 (1 death)
2 (1 amputation)
2 (vasculitis, livedo reticularis) 6
1 (1 death)
3 (2 death)
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Reference:
Parker C, Omine M, Richards S, et al. Blood. 2005;106:
Disclosures:
Emilio Ojeda: Alexion Pharma: Consultancy, Honoraria.