Authors: Jessica Fujimoto, MD (EM Resident Physician, Temple EM) and Zachary Repanshek, MD (Assistant Professor of Emergency Medicine, Lewis Katz School of Medicine; Assistant Program Director, Temple EM) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital) and Brit Long, MD (@long_brit)
A clinical case
A 44yo F presents with progressive DOE for 3 weeks. She has no PMH, and she first noted dyspnea while walking upstairs 3 weeks ago. Since onset, she has been dyspneic only with exertion, but is asymptomatic at rest. She reports recent heavy menstruation, but otherwise no bleeding. She denies hematemesis, hemoptysis, or rectal bleeding. On exam, her vital signs are within normal limits with the exception of mild tachypnea, and she has pale conjunctiva. Her CBC reveals a Hgb of 2.9, with a WBC of 18.2 and a platelet count of 1042 x10^9/L.
The big question
When does thrombocytosis require emergent workup and management?
Thrombocytosis is defined as platelet count exceeding 450,000/microL.1 Typically in the ED, new thrombocytosis will be an asymptomatic lab finding.2 The two most important things to try to distinguish up front are:
- Is this a myeloproliferative/clonal or secondary/reactive thrombocytosis?
- Is the patient at risk for acute complications from this thrombocytosis?
First, rule out spurious thrombocytosis.
Then, look for evidence of reactive thrombocytosis on history, exam, and lab work. Approximately 80% of cases of thrombocytosis are reactive, even in cases of extreme thrombocytosis (i.e. platelet count >1,000,000/microL). Therefore, platelet count is not helpful in distinguishing reactive vs. clonal thrombocytosis.1,3 Things to look for on history and exam:
- Recent trauma/surgery
- History of splenectomy
- Evidence of infection or inflammation
- History of bleeding, thrombosis, or iron deficiency
- History of chronic hematologic disorder
- Complaints suggesting malignancy
- Medication use
If reactive thrombocytosis seems unlikely, then the etiology may be myeloproliferative/clonal. This DDx is suggested by:
- Chronic/persistent thrombocytosis
- CBC findings: concomitant elevation of hemoglobin, neutrophils, basophils, myeloid immaturity3
What difference does it make, anyways?
Both reactive thrombocytosis and clonal thrombocytosis may be associated with vasomotor symptoms. The key difference is that thrombotic and bleeding events are much more common in myeloproliferative thrombocytosis, whereas they are unusual in reactive thrombocytosis, regardless of platelet count.4 There is a reported 24% incidence of thrombosis in untreated high risk patients with clonal thrombocytosis.3 It is unclear what pathophysiologic mechanism is responsible for this difference in incidence of thrombotic and bleeding complications. Nonetheless, treatment of asymptomatic reactive thrombocytosis is generally not recommended.1,4
Management of myeloproliferative/clonal thrombocytosis in the ED
Asymptomatic patients may need treatment to prevent thrombotic complications. Treatment varies based on risk factors:
Thrombosis is the most concerning complication of clonal thrombocytosis. Classically, patients with essential thrombocythemia develop Budd-Chiari syndrome, or thrombotic occlusion of the hepatic vein and/or IVC. However, they may develop many types of vascular occlusion, including venous occlusion (e.g. DVT/PE) and arterial occlusion (e.g. CVA, MI, erythromelalgia). Treatment includes:
- Anticoagulation with low molecular weight heparin. NOAC’s should be avoided due to lack of data in myeloproliferative neoplasms and potential for drug interactions with JAK inhibitors7
- Cytoreductive agent (see table below), with platelet goal <400,000/microL
- ASA 81mg daily
- Immediate platelet apheresis if platelets >800,000/microL1
Bleeding is another potentially dangerous complication of essential thrombocythemia; however, serious bleeding is less common than thrombosis. Typically, it affects the nasal and buccal mucosa and the GI tract.3 Treatment includes:
- Discontinue antiplatelet medications
- Consider a cytoreductive agent (see table)
Serious bleeding in association with thrombocytosis should raise suspicion for DIC, coagulation factor deficiency, and acquired von Willebrand disease. Extreme thrombocytosis occurs in von Willebrand disease due to abnormal platelet adsorption of circulating vW factor. Treatment is immediate apheresis and cytoreductive agent.1
Vasomotor symptoms include headache, visual symptoms, lightheadedness, chest pain, acral dysesthesia, erythromelalgia (occlusion of small blood vessels, manifested by discomfort and burning sensations in the fingers or toes). These are the most common symptoms of clonal thrombocytosis. Treatment includes:
- ASA 81mg daily1
Pearls and Pitfalls
- In the ED, we must try to differentiate myeloproliferative/clonal thrombocytosis from secondary/reactive thrombocytosis.
- Reactive thrombocytosis may be secondary to trauma/surgery, splenectomy, infection or inflammation, blood loss, malignancy, medication use, etc. Reactive thrombocytosis tends to be transient, whereas clonal thrombocytosis is sustained. Platelet count does NOT help distinguish the two!
- Even in cases of extreme thrombocytosis, treatment of reactive thrombocytosis with antiplatelets or cytoreductive agents is NOT recommended.
- Given the relatively high incidence of thrombotic complications in essential thrombocythemia, high-risk, asymptomatic patients should be treated prophylactically with antiplatelet agents + cytoreductive agents.
- Essential thrombocythemia patients with acute thrombotic complications require treatment with a cytoreductive agent, anticoagulation, aspirin, and possibly apheresis.
References / Further Reading
- Tefferi, A. Approach to the Patient with Thrombocytosis. In: UpToDate, Post TW (Ed), UpToDate, Waltham, MA. (Accessed on January 30, 2017.)
- Schafer AI. Thrombocytosis. The New England Journal of Medicine. 350(12):1211-9. 2004.
- Beer PA, Green AR. Essential Thrombocythemia. In: Kaushansky K, Lichtman MA, Prchal JT, Levi MM, Press OW, Burns LJ, Caligiuri M. eds. Williams Hematology, 9e. New York, NY: McGraw-Hill; 2015. http://accessmedicine.mhmedical.com.lproxy.nymc.edu/Content.aspx?bookid=1581§ionid=101239221. Accessed January 30, 2017.
- Kaushansky K. Reactive Thrombocytosis. In: Kaushansky K, Lichtman MA, Prchal JT, Levi MM, Press OW, Burns LJ, Caligiuri M. eds. Williams Hematology, 9e. New York, NY: McGraw-Hill; 2015. http://accessmedicine.mhmedical.com.lproxy.nymc.edu/Content.aspx?bookid=1581§ionid=108081634. Accessed January 29, 2017.
- Tefferi, A. Prognosis and Treatment of Essential Thrombocythemia. In: UpToDate, Post TW (Ed), UpToDate, Waltham, MA. (Accessed on January 31, 2017.)
- Barbui T, Vannucchi AM, Buxhofer-Ausch V, et al. Practice-relevant revision of IPSET-thrombosis based on 1019 patients with WHO-defined essential thrombocythemia.Blood Cancer Journal. 2015;5(11). doi:10.1038/bcj.2015.94.
- Kreher S, Ochsenreither S, Trappe RU, et al. Prophylaxis and management of venous thromboembolism in patients with myeloproliferative neoplasms: consensus statement of the Haemostasis Working Party of the German Society of Hematology and Oncology (DGHO), the Austrian Society of Hematology and Oncology (ÖGHO) and Society of Thrombosis and Haemostasis Research (GTH e.V.).Annals of Hematology. 2014;93(12):1953-1963. doi:10.1007/s00277-014-2224-8.