Essential thrombocytosis (ET), also known as essential thrombocythemia, is a rare chronic myeloproliferative disorder characterized by persistent elevated platelet counts (>450 × 109/L).1 Patients are often asymptomatic, but most have a tendency toward thrombosis and, to a lesser extent, hemorrhage affecting the cerebral, coronary, and peripheral vessels.2 Patients with ET have high incidence of coronary artery disease and acute myocardial infarction requiring coronary artery bypass graft (CABG) surgery. Guidelines for the management of patients with ET undergoing cardiopulmonary bypass (CPB) is limited with most evidence suggesting perioperative cytoreductive therapy only for patients deemed “high risk” for thrombotic events.2 Here, we present a case of a patient with ET with only a mild elevation in platelets deemed “low risk” for thrombotic complications who was found to have a small intracardiac thrombus around the pulmonary artery catheter (PAC) before initiation of CPB. A written informed consent was obtained from the patient for publication of this case report
A 71-year-old man with non–ST-segment–elevation myocardial infarction presented for CABG surgery. His medical history was notable for ET, non–insulin-dependent diabetes mellitus, chronic kidney disease not requiring dialysis, and multiple sclerosis.
In terms of his ET, he has a known JAK2 (janus kinase 2) mutation with platelet counts ranging from 500 to 1000 × 109/L. He had been maintained on 81 mg of aspirin daily without a history of thrombotic or hemorrhagic complications. He had never received hydroxyurea or phlebotomy treatment for his ET.
Patient was initially admitted to the hospital for 5 days before surgery with diagnosis of non–ST-segment–elevation myocardial infarction. Patient was started on a heparin infusion, but dual antiplatelet therapy was deferred by his primary team due to a right upper extremity hematoma the patient developed from a recent fall. On the day of surgery, the patient had a platelet count of 455 × 109/L, received his daily aspirin of 81 mg, and was on a heparin infusion. He did not receive prophylactic cytoreductive therapy for his ET due to a platelet count that was only mildly elevated and lacked of a history of thrombosis. Standard American Society of Anesthesiologists monitors, intravenous access, and an arterial line were established. Induction of anesthesia and placement of a Multi-Lumen Access Catheter and a non–heparin-coated PAC (Swan-Ganz VIP Five Lumen Catheter; Edwards Lifesciences LLC, Irvine, CA) under ultrasound and transesophageal (TEE) guidance were uneventful. Blood aspiration and saline flush of all lumens were immediately performed after line placement.
Initial TEE scans soon after line placement revealed strand-line echogenic materials that appeared to be attached to the PAC in the right atrium that was concerning for early thrombus (Figure). This material was not observed on preoperative transthoracic echocardiogram. The thrombus did not extend into the right ventricle. No other intracardiac thrombus was visualized on TEE. The PAC along with the attached thrombus was removed from the introducer. A thin fibrinous clot was observed attached to the tip of the PAC. Repeat TEE after PAC removal did not show evidence of residual intracardiac thrombus, and a new PAC was placed. Before aortic cannulation, 20,000 U of unfractionated heparin was administered. An activated clotting time of 473 seconds was achieved. CPB and CABG surgery were uneventful. There was no development of thrombus within the CPB circuit. TEE after CPB did not show evidence of intracardiac thrombus or thrombus attached to the PAC. The patient’s postoperative course was uneventful and without evidence of thrombotic or embolic events. Patient was extubated on postoperative day 1 and discharged to a rehabilitation facility on postoperative day 8.
ET, sometimes termed essential thrombocythemia or primary thrombocytosis, is a chronic myeloproliferative disorder characterized as a persistent elevated platelet count (>450 × 109/L).1 Most patients with ET are asymptomatic but can develop thrombotic or hemorrhagic complications.2,3 These complications are increased during the perioperative period especially among patients undergoing cardiac surgery requiring CPB.3
The exact mechanism of ET remains unclear. Excessive production of platelets from megakaryocytes can be caused by autonomous production, increased sensitivity to cytokines (interleukin-3), decreased inhibition of platelets by inhibiting factors (such as transforming growth factor-β), or defects in the accessory cell microenvironment.4,5 A mutation is found in the JAK2 gene (JAK2V617F) in 40%–50% of patients.6 A high JAK allelic burden in ET patients is correlated with increased risk of thrombosis.6–8 An elevated platelet count is a key hallmark of ET, but thrombocytosis has not been clearly associated with occurrence of thrombosis.7 Patients with ET have both thrombotic and hemorrhagic complications. The mechanism appears to be related to platelet dysfunction rather than just the increased number of platelets.7 Leukocytosis may represent an additional risk factor for thrombosis because ET patients with leukocyte counts >11 × 109/L are at higher risk for major thrombotic events compared to those with leukocyte counts <8 × 109/L.9 Of note, our patient did not have evidence of leukocytosis before surgery. Other factors increasing the risk of thrombotic events in ET patients are summarized in the Table.
Because cardiovascular events represent the leading cause of morbidity and mortality in ET, the criteria for stratifying ET patients are based on these clinical end points. Patients with ET who are >60 years of age and with a history of thrombotic event are considered “high risk,” while patients with neither are considered “low risk.”10 Based on retrospective studies and clinical trials, high-risk ET patients have better outcomes and less thrombotic complications if treated with antiplatelet therapy and cytoreductive therapy compared with antiplatelet therapy alone, with a platelet goal of <400–450 × 109/L being a frequent target. ET patients <60 years of age with no history of thrombosis are considered to be at low risk of thrombosis. These patients are generally only on low-dose aspirin.7
Reduction of platelets is essential for high-risk patients undergoing cardiac surgery and should be started before the procedure and continued postoperatively. Chemical treatment options include hydroxycarbamide, anagrelide, and interferon-α.1 Harrison et al11 found that hydroxycarbamide is superior to anagrelide with lower incidences of arterial thrombosis and hemorrhage.12 In a cardiac patient requiring urgent surgery, platelet pheresis is effective in rapidly reducing platelet counts and can be performed for patients scheduled for CABG.11 While thrombotic complications are increased for ET patients during the perioperative period, the optimal platelet count for safe surgery remains unclear with platelet counts ranging from 350 to 1000 × 109/L.4 Darwazah et al4 reviewed 16 published case reports of patients with ET undergoing cardiac surgery requiring CPB. Of these 16 patients, 5 had major complications, all of whom had platelet counts >800 × 109/L despite receiving platelet reduction therapy.
For management of PAC thrombus, we elected to remove the PAC with the thrombus from the introducer given the relative small size of the thrombus. Although the small thrombus was removed from the patient attached to the PAC via this method, other parts of the thrombus may have dislodged from the PAC because it was exiting the introducer sheath. This may explain that, although we observed thrombus in the right atrium inferior vena cava junction via the TEE, we were only able to retrieve thrombus attached to the tip of the PAC after it was removed.
Fortunately, evidence of thromboembolic complications including but not limited to pulmonary hypertension, right heart strain, hypoxia, or systemic embolism during the intraoperative and postoperative course was not observed. While we elected to simply remove the clot by removing the PAC from the introducer, other potential methods for clot retrieval, including aspirating the clot from the PAC ports, surgically removing the clot from the PAC, and removing the PAC along with the introducer sheath to prevent dislodging the thrombus, could have been performed.
Last, it is important to note that, while ET does increase thrombotic complications during CPB, the exact cause of the PAC thrombus in our patient cannot be determined. Our patient only had a modest elevation in platelet count (455 × 109/L), which is significantly lower compared to the platelet counts (>800 × 109/L) of reported ET patients undergoing cardiac surgery with perioperative thrombotic complications.4 He also had additional risk factors for developing a PAC thrombus including the use of a non–heparin-coated PAC, cardiovascular disease, and chronic kidney disease.13 Thus, it is possible that the patient’s ET and subsequent PAC thrombus were coincidental.
In conclusion, we have presented a case of a patient with ET with near-normal platelet counts of 455 × 109 who developed an intracardiac thrombus on a PAC. To our knowledge, this is the first case report describing a patient with ET who did not have a history of thrombotic complications with platelet counts <500 × 109 who subsequently developed a thrombotic complication during cardiac surgery. Our case highlights the potential for ET patients with near-normal platelet counts and with no history of thrombosis who undergo cardiac surgery to experience thrombotic events. Cytoreduction in addition to antiplatelet therapy should at least be considered in this patient population undergoing cardiac surgery.
Name: Shu Y. Lu, MD.
Contribution: This author helped design the study and prepare the manuscript.
Name: Kenneth T. Shelton, MD.
Contribution: This author helped prepare the manuscript.
Name: Michael G. Fitzsimons, MD.
Contribution: This author helped prepare the manuscript.
This manuscript was handled by: Kent H. Rehfeldt, MD.
1. Beer PA, Green AR. Pathogenesis and management of essential thrombocythemia. Hematology Am Soc Hematol Educ Program. 20091:621–628.
2. Tefferi A, Thiele J, Orazi A, et al. Proposals and rationale for revision of the World Health Organization diagnostic criteria for polycythemia vera, essential thrombocythemia, and primary myelofibrosis: recommendations from an ad hoc international expert panel. Blood. 2007;110:1092–1097.
3. Ruggeri M, Rodeghiero F, Tosetto A, et al.; Gruppo Italiano Malattie Ematologiche dell’Adulto (GIMEMA) Chronic Myeloproliferative Diseases Working Party. Postsurgery outcomes in patients with polycythemia vera and essential thrombocythemia: a retrospective survey. Blood. 2008;111:666–671.
4. Darwazah AK, Madi H, Zagha R, Hawash Y. Off-pump myocardial revascularization in a high-risk patient with essential thrombocythemia. Tex Heart Inst J. 2014;41:537–542.
5. Kralovics R, Passamonti F, Buser AS, et al. A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med. 2005;352:1779–1790.
6. Antonioli E, Guglielmelli P, Poli G, et al.; Myeloproliferative Disorders Research Consortium (MPD-RC). Influence of JAK2V617F allele burden on phenotype in essential thrombocythemia. Haematologica. 2008;93:41–48.
7. Vannucchi AM. Insights into the pathogenesis and management of thrombosis in polycythemia vera and essential thrombocythemia. Intern Emerg Med. 2010;5:177–184.
8. Vannucchi AM, Antonioli E, Guglielmelli P, et al. Clinical profile of homozygous JAK2 617V>F mutation in patients with polycythemia vera or essential thrombocythemia. Blood. 2007;110:840–846.
9. Palandri F, Polverelli N, Catani L, Ottaviani E, Baccarani M, Vianelli N. Impact of leukocytosis on thrombotic risk and survival in 532 patients with essential thrombocythemia: a retrospective study. Ann Hematol. 2011;90:933–938.
10. Marchioli R, Finazzi G, Landolfi R, et al. Vascular and neoplastic risk in a large cohort of patients with polycythemia vera. J Clin Oncol. 2005;23:2224–2232.
11. Harrison CN, Campbell PJ, Buck G, et al.; United Kingdom Medical Research Council Primary Thrombocythemia 1 Study. Hydroxyurea compared with anagrelide in high-risk essential thrombocythemia. N Engl J Med. 2005;353:33–45.
12. Cortelazzo S, Finazzi G, Ruggeri M, et al. Hydroxyurea for patients with essential thrombocythemia and a high risk of thrombosis. N Engl J Med. 1995;332:1132–1136.
13. Cronin B, Maus T, Maruszak B, Manecke G. Early thrombosis and non-heparin-coated pulmonary artery catheters. J Cardiothorac Vasc Anesth. 2017;31:e62–e63.