Digital Ischemia Due to Essential Thrombocythemia: A Case Report Anastasios Papadonikolakis, MD, George D. Chloros, MD, Beth P. Smith, PhD, L. Andrew Koman, MD From the Department of Orthopaedic Surgery, Wake Forest University School of Medicine, Winston-Salem, NC.
This report describes the case of a 34-year-old patient with essential thrombocythemia who presented with Raynaud’s syndrome, was refractory to medical treatment, and developed progressive digital gangrene. (J Hand Surg 2007;32A:1053–1057. Copyright © 2007 by the American Society for Surgery of the Hand.) Key words: Cyanosis, digital ischemia, essential thrombocythemia, hand, periarterial sympathectomy, platelet apheresis, Raynaud’s, thrombocytosis.
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ssential thrombocythemia (ET) is a rare chronic myeloproliferative blood disorder of unknown etiology characterized by proliferation of megakaryocytes leading to an overproduction of platelets.1 The diagnosis of ET is established in the presence of a persistent thrombocytosis of greater than 600 ! 109/L in the platelet count in the absence of a known cause. As many as two thirds of patients are asymptomatic and only receive medical attention fortuitously, as a result of thrombocytosis found from a routine blood cell count. The clinical course of ET is marked by episodes of hemorrhage or thrombosis or both. The major risk factors for thrombosis in ET are age greater than 60 years and a history of previous thrombotic episodes. In most patients, treatment with a single dose of aspirin usually results in a dramatic improvement.2 A rare case of a young patient with ET and Raynaud’s syndrome that was refractory to medical treatment and progressed to digital gangrene is presented. Treatment included urgent therapeutic platelet apheresis (TP), which lowered his platelet count, followed by periarterial sympathectomy3–5 with amputation of the necrotic tip of the middle finger. This report emphasizes the importance of performing an early aggressive TP, when other medical measures fail, to rapidly decrease the platelet count to help prevent or eventually reverse the ischemic changes. Periarterial sympathectomy is performed after a normal platelet count is achieved as an adjunctive procedure to increase nutritional collateral
flow. To our knowledge, there are no similar reports in the English literature.
Case Report The patient was a 34-year-old male with no significant past medical history other than splenectomy for a previous motor vehicle accident. He presented with a 2-week history of pain and bilateral bluish discoloration of the fingertips and toes. He reported that he began to experience throbbing pain to his fingers and toes, which started after sleeping on a cold floor. The pain was associated with numbness and tingling with decreased sensation to his fingers and toes and was exacerbated by cold. He was started on aspirin and nifedipine but experienced no significant relief. Prior to his transfer to our institution, he was seen at an outside hospital and found to have a platelet count of 1,034 ! 103/!L. It was determined that he had Raynaud’s phenomenon related to ET because all other causes of thrombocytosis were excluded. Treatment on hydroxyurea was initiated to reduce the platelet count and to prevent thrombosis. The patient was transferred to our institution for further management. On admission, the patient had cyanosis and exquisite tenderness of his distal left second and third fingers and transient areas of cyanosis and pain in his toes and right hand that resolved spontaneously. Initial treatment consisted of hydroxyurea, aspirin, and nifedipine to treat the ET. On postadmission day 5, the pain was increasing, there was cyanosis and discoloration of the left distal The Journal of Hand Surgery
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long fingers. Through a fish-mouth incision, the necrotic skin and fingertip were amputated with a saw. The middle phalanx was transected with a saw through the mid-diaphysis, leaving the flexor digitorum superficialis intact. The digital nerves were identified and trimmed proximally. The flexor digitorum profundus was pulled distally and transected. The extensor mechanism was cut at the level of amputation. A periarterial sympathectomy (Fig. 3) was performed through a zigzag incision over the index finger; both proper digital arteries were identified. The incision was extended across the palm, and the proper digital artery and the common digital artery to the long finger were also identified. Vascular loops were placed, and periarterial sympathectomy was performed using the operating microscope under magnification. Three months postoperatively, the patient is symptom-free with no evidence of ischemic changes (Fig. 4A, B). Figure 1. (A and B) Photographs showing partial necrosis of the tip of the left index finger. There are skin changes of the tip of the third left finger due to ischemia.
second and third digits, and a platelet count of 800 ! 103/!L was documented. At this point, the patient was evaluated by the senior author who believed that the patient’s fingertips were in danger of imminent gangrenous necrosis. Measures to reduce the platelet count and increase the blood flow to the distal fingertips were instituted. The patient thus received 2 TP treatments, which resulted in his platelet count reaching 348 ! 103/!L on postadmission day 8. There were no complications as a result of the procedure, and the toe ischemia resolved after the TP. His digital ischemia, however, remained unchanged (Fig. 1). An upper extremity arteriogram was performed, which showed multilevel occlusions of the proper digital palmar arteries of the second and third digits (Fig. 2). There was decreased flow to the distal phalanx. Nitroglycerin was administered, and a repeat angiogram demonstrated no significant change in the flow to the second and third digits. At this point, the patient was diagnosed with peripheral vascular disease secondary to ET, associated gangrene of his left index finger, and ischemic changes of the left middle finger. The patient was taken to the operating room, and an amputation of his left index finger through the middle of the middle phalanx was performed, along with a periarterial sympathectomy of the index and
Discussion Essential thrombocytosis is a slowly progressive disorder characterized by long asymptomatic periods punctuated by thrombotic or hemorrhagic events.1 It is a diagnosis of exclusion established in patients
Figure 2. Upper-extremity arteriogram showing multilevel occlusions of the proper digital palmar arteries of the second and third digits.
Papadonikolakis et al / Digital Ischemia Due to Essential Thrombocythemia
Figure 3. Periarterial sympathectomy: through a zigzag volar incision, the adventitia is cleaned of sympathetic fibers and connections with the nerve are severed. (Reproduced by permission from Koman LA, ed. Wake Forest University orthopaedic manual. Winston-Salem, NC: Orthopaedic Press, 2007.)
who are rarely seen by hand surgeons. Although the exact mechanism of the disease is unknown, it is believed that platelets derived from the abnormal megakaryocytes do not function properly and contribute to the clinical features of bleeding and thrombosis. There are approximately 1.5 to 2.4 per 100,000 individuals diagnosed annually with ET.6,7 The disease usually affects middle-aged to elderly individuals, with an average age at diagnosis of 50 – 60 years. ET, however, may also affect children and young adults. The major risk factors for thrombosis are age older than 60 years and previous thrombotic episode,2 whereas the advent of thrombosis appears to be unrelated to either the platelet count or hemostasis tests.8,9 Almost two thirds of patients are asymptomatic, and the most common symptoms at presentation are due to disturbances of the microcirculation, particularly fingers, toes, and central nervous system manifestations including headache, dizziness, and visual and acoustic symptoms.10 The term erythromelalgia, specific to the myeloproliferative disorders, refers to
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the occlusion of the microcirculation by platelets and is characterized by redness, congestion, and painful burning sensations of the extremities. Symptoms are characteristically relieved by cold or elevation of the extremity and are exacerbated by warmth, exercise, or standing.10 Essential thrombocythemia can also lead to painful acrocyanosis and even peripheral gangrene.11 A single dose of aspirin usually results, however, in reversal of the ischemic phenomena with resolution of erythromelalgia in the vast majority of patients within 2 to 4 days.2 Acute digital ischemia may be caused by several entities including collagen vascular diseases,12 Raynaud’s disease,13 Buerger’s disease,14 peripheral atherosclerosis,15 heparin-induced thrombocytopenia with thrombosis syndrome,16 consumption coagulopathy,17 and many others. Although rare, hematologic disorders, however, have to be considered in the differential diagnosis of acute digital ischemia. The patient described in this report was atypical, because he was free of all the aforementioned thrombosis risk factors. His painful acrocyanosis, which progressed to digital gangrene, was probably due to his Raynaud’s disease rather than to classic erythromelalgia, because his extremities were neither warm nor congested. His symptoms were exacerbated by cold and were not relieved by aspirin. Treatment of asymptomatic patients with ET remains controversial and largely problematic. Many studies have shown that the degree of platelet count elevation in ET is not an important determinant of the
Figure 4. (A and B) At 3 months, the patient is symptom-free with no evidence of ischemic changes. The operation involved the patient’s left side.
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probability or frequency of thrombotic episodes.2 Furthermore, an acute reduction of platelet count by TP is ineffective in the long-term, because of the rapid rate of production of platelets.18 The high-risk patient population (age "60 years, previous thrombotic episode), however, deserves therapeutic intervention. Cytoreductive therapy (platelet count to "600 ! 109/L) with hydroxyurea19 or anagrelide20 has been effective in preventing additional thrombotic episodes in this patient population. The current patient was managed on admission with aspirin (to reverse the platelet-mediated thrombotic effect), nifedipine (to reverse the vascular spasm), and hydroxyurea (to progressively decrease his platelet count). At this point, TP was not performed, because it was believed that this treatment would not provide a long-term benefit on the course of the disease. The patient’s pain increased, however, and there was apparent danger of imminent gangrene. Because medical treatment takes several days or even weeks to lower the platelet count, TP represents an urgent intervention in patients with ET when a rapid reduction in platelet counts is required,21 such as in a thrombotic episode, and may result in dramatic clinical improvement,22 even recovery from the gangrene.23 In addition, although a chemical sympathectomy with an axillary block may be temporarily effective in controlling extremity neuropathic pain, it was not attempted in this case, as this would not address the basis of the problem (increased platelet count), which was responsible for the patient’s urgent condition. Based on this case, TP should be initiated immediately when there are cutaneous or ischemic changes that are not responding to alternative treatment. Further delay in treatment may lead to permanent ischemic damage or gangrene. Periarterial sympathectomy is considered as an adjunct to TP to (1) maximize nutritional flow by decreasing arteriovenous shunting, (2) protect the amputation flaps, and (3) possibly decrease the intensity of pain. In the setting of worsening ischemic phenomena and a high platelet level, surgery is not an option. The patient had complete resolution of his Raynaud’s phenomenon after sympathectomy. This case highlights the need for appropriate timing of TP when other measures fail to limit the ischemic phenomena. Periarterial sympathectomy may provide a valuable adjunctive treatment option in the setting of a normal platelet count to increase the nutritional collateral flow.
Received for publication March 2, 2007; accepted in revised form May 11, 2007. No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article. Corresponding author: L. Andrew Koman, MD, Professor and Vice Chair, Department of Orthopaedic Surgery, Wake Forest University School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157; e-mail:
[email protected]. Copyright © 2007 by the American Society for Surgery of the Hand 0363-5023/07/32A07-0018$32.00/0 doi:10.1016/j.jhsa.2007.05.010
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