The appropriate next step would be to test for the JAK2 V617F mutation. This patient likely has polycythemia vera (PV), a myeloproliferative neoplasm (MPN). Symptoms include generalized pruritus that often worsens after bathing, erythromelalgia (a burning sensation in the palms and soles), and hypermetabolic symptoms such as fever, weight loss, and sweating. On physical examination, patients may have plethora and hepatosplenomegaly. Twenty percent of patients experience arterial or venous thrombosis as their initial symptom. PV and the other MPNs predispose to the development of the Budd-Chiari syndrome (BCS), which is characterized by hepatic venous outflow tract obstruction (including the suprahepatic inferior vena cava) and other intra-abdominal thromboses, such as thrombosis of the portal, superior mesenteric, or splenic vein. Abdominal pain, ascites, liver and spleen enlargement, and portal hypertension occur with symptomatic BCS. Ninety-five percent of patients with PV have the JAK2 mutation, so it is an appropriate confirmatory test for suspected PV. Anticoagulant therapy is recommended for all patients with BCS regardless of whether an underlying prothrombotic disorder is discovered. Phlebotomy to normalize the hematocrit (goal <45% in men, <42% in women) is indicated, and adding the myelosuppressive agent hydroxyurea to phlebotomy decreases thrombotic events in patients with PV.

Bone marrow aspirate and biopsy findings are nonspecific in PV; they may show an increased number of megakaryocytes in a moderately to markedly hypercellular marrow and an increase in reticulin. Because they are not diagnostic and the procedure is invasive, bone marrow biopsy is typically unnecessary and is not an appropriate early diagnostic test.

Although factor V Leiden is a risk factor for venous thromboembolism, it would not explain the patient's erythrocytosis, leukocytosis, or thrombocytosis. Therefore, it is not a helpful test to perform in this patient.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal stem cell disorder that should be considered in patients with hemolytic anemia, pancytopenia, or unprovoked atypical thrombosis. Thrombotic complications of PNH may occur in atypical locations, such as the hepatic veins (BCS) or mesenteric or cerebral circulation, and develop more frequently in patients with large PNH clones. PNH is diagnosed by flow cytometry, which can detect CD55 and CD59 deficiency on the surface of peripheral erythrocytes or leukocytes. Erythrocytosis, leukocytosis, thrombocythemia, and generalized pruritus are not typical for PNH.