Overwhelming Paroxysmal Nocturnal Haemoglobinuria in a Patient with Low-Risk Myelodysplastic Syndrome and Long-Term Anticoagulation for Sick Sinus Syndrome

Abstract

Paroxysmal nocturnal haemoglobinuria (PNH) is a rare form of acquired Coombs negative haemolytic anaemia manifested by the clinical triad of intravascular haemolysis, venous thrombosis and cytopenia. At the molecular level PNH is defined by a clonal expansion of hematopoietic stem cells having undergone somatic mutation of the X-chromosome gene PIG-A. Here we report the case of an 80-year old female patient known for sick sinus syndrome for more than 30 years and low-risk myelodysplastic syndrome (MDS) with uneventful course over the past two years. In good health she underwent her fifth lead replacement under short-term reversal of anticoagulation. Two weeks later she presented at the emergency room for epigastric pain, vomiting and fever. Work up revealed extensive right jugular vein thrombosis, Coombs-negative haemolytic anaemia and acute renal failure. Paroxysmal nocturnal haemoglobinuria was suspected and confirmed by flow cytometric FLAER-assay, which detects clonal deficiency of glycosyl-phosphatidyl-inositol linked surface proteins on monocytes and granulocytes. Thus, search of a PNH clone with FLAER was reliable in the presence of RBC-transfusions and ongoing intravascular haemolysis. Though stabilization of haemolysis was achieved, renal failure progressed and the patient deceased suddenly at the 11th day of hospitalization. Short-term reversal of anticoagulation and functionless retained pacing leads may have catalyzed thrombosis in our MDS patient with a large glycosyl-phosphatidyl-inositol (GPI) deficient clone. In MDS patients under long-term anticoagulation any short-term reversal of anticoagulation for surgical procedures should be preceded by FLAER analysis to uncover an emerging GPI-deficient clone since recent developments in the treatment of this condition allow prevention of intravascular haemolysis and thrombosis by halting the complement cascade at the C5 level with targeted immunotherapy.