High Definition Contrast-Enhanced MR Imaging in Paroxysmal Nocturnal Hemoglobinuria (PNH) Suggests a High Frequency of Subclinical Thrombosis.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired disorder characterized by intravascular hemolysis and venous thrombosis. Thrombosis is the most feared complication in PNH and is reported to occur in >40% of patients. Proposed mechanisms of thrombosis include depletion of the coagulation regulator nitric oxide (NO) by intravascular hemolysis and increased sensitivity of PNH platelets to activation. The occurrence of subclinical thrombosis in PNH patients has not been previously studied using modern imaging techniques. In order to evaluate for subclincal thrombosis we evaluated PNH patients with a comprehensive state-of-the-art MRI protocol (which included the use of both blood pool and conventional Gadolinium based contrast agents) for the detection of subclinical thromboses and its sequelae. The detailed protocol consisted of:

• lung perfusion and pulmonary MRA,

• cardiac MR - including quantitative studies of both ventricles, right heart flow dynamics and delayed enhancement for the detection of left ventricular damage, and

• abdominal MR for the assessment of hepatic and portal venous systems and kidneys.

10 PNH patients (median age 31.5 yrs) with large PNH clones but without previous clinical evidence of venous or arterial thrombosis underwent imaging. Five (50%) of the patients were on primary anticoagulant prophylaxis with warfarin. There was evidence of significant renal hemosiderosis, which was distributed throughout the cortices, in 8/10 patients. Two patients had small myocardial scars suggestive of previous unsuspected ischemic damage. Six patients had sub-segmental perfusion defects mainly distributed in the peripheries of the lung fields indicative of previous small pulmonary emboli. No such subclinical thromboses would be anticipated in an age-matched control population. 8 patients had mildly reduced right ventricular ejection fractions (mean 42.2±1.8%; normal range 48–63%). The plasma B-type natriuretic peptide (BNP) level was high in all 10 patients (median 29.4pmol/l; range 18.7–373.90; normal subjects 4.89±1.00pmol/l). BNP has been shown to increase in proportion to right ventricular dysfunction in pulmonary hypertenstion. No intraabdominal defects were identified with the current protocol. In summary, we identified abnormalities suggestive of previous subclinical thromboses in 6 of 10 hemolytic PNH patients by high-resolution MR imaging, including in patients on primary prophylaxis with warfarin. Effective prevention of thrombosis is an important aspect of the therapy in PNH.