ET is a myeloproliferative disorder characterized by excess platelet production [2]. ET patients have increased risk of postoperative bleeding and thrombosis [3]. Riggeri et al. reported a retrospective survey of postoperative outcomes of polycythemia vera and ET patients [4]. In their cohort, 23 (7.3%) of 311 patients who underwent surgical interventions experienced major hemorrhagic episodes [4]. This rate was higher than that observed in normal cancer surgery (about 1%) [5]. Zhu et al. reported a case involving an ET patient with sigmoid colon cancer. Plateletpheresis was performed before surgery but anastomotic bleeding complicated the postoperative course. A systematic review of abdominal operations in four ET patients revealed that two of four patients experienced bleeding complications on the first postoperative day [3].
In laparoscopic surgery, pneumoperitoneum, the Trendelenburg position, and long surgical time could be risk factors for lower extremity venous stasis [6]. However, a meta-analysis of trials comparing laparoscopic surgery with open surgery demonstrated that laparoscopic surgery could achieve the same outcome as open surgery with regards to presence of postoperative venous thromboembolism [6]. However, to prevent thrombosis, we performed laparoscopic surgery in the leg-open position, instead of lithotomy, using an elastic stocking and intermittent pneumatic compression with pneumoperitoneum pressure of up to 8 mmHg. Small amounts of bleeding have been reported in laparoscopic surgery due to pneumoperitoneum pressure; however, treatment for ET patients involves a high bleeding risk as described above, so we also performed careful hemostasis confirmation before closing. The patient’s wound was small and less painful; she resumed walking on the first postoperative day and recovered quickly after surgery. Postoperative administration of Xa inhibitors was not generally indicated at the time, as was she, but she was fortunately discharged without complications. However, the optimal perioperative management of ET patients remains unclear, especially in the context of abdominal malignancy.
A high platelet count (> 60 × 104/μL), age > 60 years, and thrombosis history are high-risk factors for major thrombosis in ET patients [7]. Patients at high thrombosis risk should be treated with cytoreductive therapy (CRT) to reduce thrombosis risk. Presently, two CRT treatments are licensed in Japan: hydroxyurea and anagrelide [2]. Anagrelide is an orally active, platelet-lowering agent approved for first-line treatment of high-risk ET in Japan [2]. Hydroxyurea is most widely used for CRT, although long-term use may be associated with a high secondary leukemia incidence [2]. Recently, Kanakura et al. reported anagrelide efficacy in high-risk ET patients in Japan [2]. Anagrelide was approved for ET treatment in the US and Europe in 1997 and 2004, respectively, but it was not licensed in Japan until 2014. Our patient was prescribed anagrelide about 1 year before surgery; her platelet count was properly controlled. To our knowledge, ours is the first case involving laparoscopic colectomy in a patient who used anagrelide for platelet count management.
CapeOX as adjuvant therapy has a manageable tolerability profile and should be considered as a standard adjuvant treatment option in stage III colorectal cancer patients. Transient thrombocytopenia is relatively common in oxaliplatin-treated patients. Hepatotoxicity is another adverse event observed with oxaliplatin-based chemotherapy [8]. Here, we encountered a considerably decreased platelet count on starting chemotherapy with ongoing anagrelide intake. Hashiba et al. reported the outcome of discontinuing CRT in an ET patient during chemotherapy for esophageal cancer. They administered preoperative chemotherapy (cisplatin + 5-fluorouracil) accompanied by hydroxyurea discontinuation; however, platelet count increased to 116 × 104/μL after therapy [9]. Since our patient was relatively young, we suggested a method of carefully re-administering fluoropyrimidine monotherapy as adjuvant chemotherapy. However, she did not wish to resume treatment because of concerns about adverse events. Thus, the tolerability of fluoropyrimidine monotherapy is unknown as well. Chemotherapeutic strategies for ET patients should consider various events such as bone marrow suppression due to chemotherapy, thrombocytopenia caused by CRT, and elevated platelet count due to drug withdrawal.
Thus, we reported on a patient with colon cancer and ET, which are rarely observed together, who required careful perioperative management for laparoscopic surgery. We found that complications such as bleeding or thrombosis during control of the platelet count can be avoided by anagrelide administration. Contrastingly, thrombocytopenia due to anagrelide intake should be considered when chemotherapy that could cause bone marrow suppression is administered. Further studies involving this unique group of patients should focus on developing appropriate treatment strategies.
