Steel to heal? MPD surgical conundrums

Surgical interventions in the BCR-ABL–negative chronic myeloproliferative disorders (MPDs) of essential thrombocythemia (ET) and polycythemia vera (PV) are inherently challenging based on the intrinsic risk of both disorders for thrombotic and/or hemorrhagic events. Baseline risks for arterial and/or venous thrombotic events have classically been associated with 2 main features: increasing age in MPD patients (> 60 years of age) and prior vascular events, with potential contributions from cardiovascular risk factors and extreme thrombocytosis (> 1000-1500 × 10⁹/L).¹  Newly identified vascular risk factors, leukocytosis²  and high JAK2^V617F allele burden,³  also appear to have predictive value. Current short-term management strategies for PV and ET patients have been directed at (1) control of erythrocytosis, (2) near universal antiplatelet therapy, and (3) the addition of myelosuppressive therapy to normalize thrombocytosis in intermediate and high-risk patients. Optimal perioperative management of MPD patients has largely been based on clinical experience and anecdotal evidence, with published reports of the high risk of vascular complications (24%) in patients undergoing therapeutic splenectomy⁴  urging caution when operating on this group.

Ruggeri and colleagues have assembled a retrospective analysis of 311 operative interventions in 255 MPD patients, with a risk of vascular events in 16.8% of cases, despite perioperative heparin (54.3%), antiplatelet therapy (15.4%), and/or cytoreduction (74%). These sobering results were found despite the fact that the vast majority of these surgical interventions were elective (91.9%) and conducted when a maximal amount of surgical prophylaxis was employed. There are limits in the interpretation of this data: given the multicenter, retrospective nature of this report, the preoperative prophylaxis employed was heterogeneous, making it difficult to ascertain which aspects of prophylaxis (heparin, antiplatelet therapy, cytoreduction, or a combination thereof) were most effective. The complexity of predicting which patient will have an event was further corroborated by the lack of an observed correlation between known risk factors (such as age, white cell or platelet count, hematocrit, type of MPD, sex, or prior vascular event) and developing a thrombosis. These results highlight our incomplete understanding about the origin of vascular events in MPD patients, weaknesses in the ability of our current management strategies to identify patients at risk, and the incomplete ability of currently available agents for MPDs to prevent vascular complications.

Management of MPD patients undergoing elective or emergent surgery is challenging, and the data from Ruggeri and colleagues suggest that despite optimal efforts, there will be a greater risk of vascular events. Defining the optimal perioperative prophylaxis (antiplatelet therapy, perioperative heparin, cytoreduction to a normal platelet count, and/or control of erythrocytosis) will require prospective comparison with defined regimens. In addition, the development of more efficacious targeted therapy for MPDs (ie, JAK2 inhibitors⁵ ) may have a greater impact on preventing vascular events than do current modalities.