PNH: A Rare Hematological Disease with Profound Implications for a Gastroenterologist

Abstract

Paroxysmal Nocturnal Hemoglobinuria (PNH) is a rare thrombophilic and hematopoietic stem cell disorder with an annual incidence rate of as low as 1-2 cases per million. About 16% of these patients present with visceral vein thrombosis which is the most common cause of mortality. We here present an extremely rare case of a young man presenting with extensive thrombosis of multiple visceral veins from PNH. A 36-year-old Hispanic man with no significant medical history presented to the emergency department with diffuse abdominal pain of four days duration. The patient also reported weight loss of 5lbs over the preceding one month. Initial laboratory tests revealed transaminitis; and pancytopenia with reticulocytosis, increased serum lactate dehydrogenase (LDH) and decreased serum haptoglobin levels. The patient was found to have elevated urobilinogen in urine pointing towards intravascular hemolysis. A computerized tomography (CT) scan (Figure-1) of the abdomen demonstrated extensive portal vein thrombosis (PVT), superior mesenteric vein thrombosis and bilateral renal vein thrombosis. Flow cytometry and bone marrow biopsy (Figure-2) confirmed the diagnosis of PNH. The patient underwent esophagogastroduodenoscopy for screening esophageal varices. No varices were found. The patient was started on anticoagulation and Eculizumab.Figure 1Figure 2PNH caused by mutation of the PIG-A gene, is characterized by uncontrolled complement activity with decreased CD-55 and 59 levels leading to- intravascular hemolysis, thrombosis, and bone marrow failure. Patients with PNH often present with hemoglobinuria, abdominal pain, fever, headache, and fatigue. While hepatic and cerebral veins are the most common sites of thrombosis, PVT is extremely rare with only about 12 cases reported in the literature. Sparing of hepatic vein with involvement of portal vein and mesenteric veins makes this case highly unusual. A gastroenterologist must be keenly aware and consider the diagnosis of PNH in any young patient presenting with abdominal pain and hemolysis with abdominal visceral vein thrombosis, especially in the absence of underlying cirrhosis. It is imperative that these patients are started on anticoagulation at the earliest given the high mortality. Eculizumab is a monoclonal antibody used in the secondary prevention of disease known to act by inhibiting the activation of complement cascade system. Allogeneic hemopoietic stem cell transplantation is considered for refractory cases.