Paroxysmal Nocturnal Hemoglobinuria and Magnetic Resonance Imaging

Paroxysmal Nocturnal Hemoglobinuria (PNH) is a rare and complex disease characterized by a severe prothrombotic state caused by a complement system mediated hemolysis. The introduction of the anti-C5 antibody, Eculizumab, has been conducted in many Hematology units worldwide to adopt new diagnostic tools to evaluate new and old PNH patients in order to consider the adequacy of the adoption of this new drug in each case.

Magnetic Resonance Imaging (MRI) allows a more adequate and profitable approach in PNH that other radiology techniques used for this purpose. In the last four years Hematology and Radiology units in our Hospital have collaborate in the clinical evaluation of PNH patients performing MRI (cranioencephalic, thoracic and/or abdominal) in acute complications of PNH patients (9 patients) or as a programmed protocoled evaluation previous to consider Eculizumab treatment (14 patients).

The protocoled evaluation consists in thoracic and abdominal MRI evaluations in all cases, and cranioencephalic MRI (with independence of the presence of neurological symptoms) in 9 cases. The PNH patients were examined with 1.5 Teslas magnet for cranioencephalic,thoracic and abdominal MRI and with 3.0 Teslas magnet for some cranioencephalic MRI (Achieva Magnets; Philips Healthcare, Best, The Netherlands).

Different protocols designed for the study of this pathology, using morphological sequences with different empowerment, functional sequences and angiographic studies after administration of intravenous contrast (gadobutrol) have been used. In the abdominal explorations had been performed calculations of T2 * for the quantification of deposit of iron in liver and kidney.

The first group of patients (incidental studies in acute/chronic situations) included Classical and with other bone marrow failure syndrome (BMFS) Parker’s types. The second group (protocoled studies previous consideration of Eculizumab therapy) consisted on 11 Classical Parker’s type patients with active hemolysis (LDH increased 3-13 times over normal levels) and elevated PNH clone (73-99% negative GPI granulocytes by FLAER cytometry); and 3 with BMFS Parker’s type patients (LDH increased 2-6 times over normal levels) with lower PNH clone (43-50% negative GPI granulocytes by FLAER cytometry). Thrombosis was found in four cases, one in the inferior cava and and three arterial (two cerebral and one in descendent aorta). In three patients this finding implied to initiate Eculizumab therapy. Minor ischemic brain changes were displayed by three patients. None of the eighteen patients explored with thoracic MRI, displayed pulmonary hypertension signs despite the elevation of pro-BNP in eight of them. Iron overload in the liver and/or kidneys were very frequent. The finding of a reversal of the normal cortical and medullary intensities on T1 and T2 weighted images of both kidneys was evident in the majority of patients with severe PNH types. Interestingly, one patient with a chronic PNH severe form displayed no renal iron cortical after two years on Eculizumab therapy. This finding was also evident in patients with active hemolysis in the past but with very low PNH clones and clinical remission of the disease.

Many other incidental discoveries includes cholelithiasis, splenomegaly, kidney arterial vessel constriction, vascular anomalies, kidney and vesical stones, adrenal adenoma, atheromatosis at different levels, Tornwaldt cyst, hamartoma, hemangiomas and abnormal bone marrow signal.

MRI is the best imaging technique to diagnose thrombosis in PNH patients and to control evolution. Moreover, in the cerebrovascular setting allows a more fine and precise diagnosis of the minor pathologic thrombotic changes. MRI is the only imaging technique that permits to evaluate the iron overload that in some PNH cases could be underestimated and needs quelation therapy. In our opinion all new patients with classical severe hemolytic PNH must be evaluated prospectively with MRI. The collaboration of the Radiology team with the Hematologist is fundamental to acquire expertise in this rare disease.