Challenging thrombotic scenarios in the myeloproliferative neoplasms: Splanchnic vein thrombosis and others

Introduction The Philadelphia chromosome-negative myeloproliferative neoplasms (MPN), myelofibrosis (MF), essential thrombocythemia (ET), and polycythemia vera (PV), are clonal stem cell disorders characterized by overproduction of mature blood elements, splenomegaly, disease transformation (MF and acute leukemia), and a thrombotic tendency. The thrombotic tendency prevails around the time of diagnosis, often leading to the first recognition of an MPN, such as ET or PV. Affected patients are at higher risk for recurrence and are therefore treated more aggressively, often with some combination of cytoreduction, antiplatelet, and anticoagulant therapy. MPN-associated thromboses that involve the microvasculature can negatively impact quality of life, whereas macrovascular disturbances involving arterial and venous circulation impact prognosis. Despite the well-known association between MPN and its thrombotic tendency, risk factors and mechanisms are still being characterized. In addition to prior thrombosis, advanced age increases risk; leukocytosis, the JAK2 V617F mutation and its allelic burden, and cardiovascular risk factors may also influence risk. The pathogenesis of MPN-associated thrombosis has multifactorial contributions, in part from endothelial, platelet, and leukocyte activation, as well as from the elaboration of thrombogenic microparticles, activated protein C resistance, and inflammation (Figure 19.1). Diagnostic and treatment strategies for MPN-associated thrombosis are heterogeneous, in part because in most countries there are no treatment guidelines for these diseases. Important questions that need answers are the appropriate indications for MPN molecular testing in the presence of thrombosis (if an MPN is not an existing diagnosis), the ideal use of antiplatelet therapy, and the duration and type of anticoagulant (Table 19.1). MPN-associated thrombosis challenges internists, hematologists, and oncologists alike, and in this chapter, three challenging clinical scenarios are presented with guidance on management strategies. Case 1: part 1 A 70-year-old woman with hypertension and hyperlipidemia experienced redness, swelling, and pain of the right fifth digit. Initially, her symptoms responded to non-steroidal anti-inflammatory drugs, but over the next week, swelling and pain involved all fingers, and her hand had an “angry” red appearance. She was told of possible Raynaud's phenomenon, and referred to a rheumatologist. The rheumatologist felt that the appearance was inconsistent with Raynaud's, and recommended a hematology referral after noting thrombocytosis dating back for 2 years. The hematologist did not report splenomegaly, but noted a leukocyte count of 16.4 × 10⁹/L, hemoglobin of 16.6 g/dL, and platelet count of 1500 × 10⁹/L.