Acute compartment syndrome as the initial manifestation of chronic-phase chronic myeloid leukemia: a case report and review of the literature
© The Author(s). 2016
Received: 21 March 2016
Accepted: 24 June 2016
Published: 21 July 2016
Acute compartment syndrome is an orthopedic emergency requiring urgent fasciotomy to prevent irreversible damage. In hematological malignancies, acute compartment syndrome caused by severe soft tissue bleeding is extremely rare. We present a patient with chronic-phase chronic myeloid leukemia who had acute compartment syndrome caused by severe soft tissue bleeding in her right forearm.
A 72-year-old Japanese woman was referred to our hospital with swelling and pain of her right forearm without a previous history of trauma. She was diagnosed with chronic-phase chronic myeloid leukemia. Extreme thrombocytosis was present, although no evidence of acquired von Willebrand disorder was found. Compartment syndrome caused by soft tissue bleeding was confirmed. An emergency fasciotomy for decompression was conducted. However, sustained postoperative bleeding occurred and required massive red cell concentrate transfusion. As her platelet count decreased by cytoreductive therapy, complete hemostasis was achieved.
Patients with an extremely high platelet count might be at high risk for severe bleeding complications even without acquired von Willebrand disease. For the control of severe bleeding complications in patients with myeloproliferative disorder, the importance of thrombocyte reduction should be recognized.
KeywordsAcute compartment syndrome Chronic myeloid leukemia Thrombocytosis Bleeding complications
Acute compartment syndrome (ACS) most often develops after significant traumas, particularly those involving long bone fractures. This syndrome may also occur following non-traumatic causes, although such incidents are less frequent. ACS caused by leukemic infiltration of the muscles is uncommon but has sometimes been documented in acute leukemia or non-Hodgkin lymphoma [1–4]. It is rare for ACS to occur in the chronic phase of chronic myeloid leukemia (CML). Here we present a case of ACS that resulted from severe soft tissue bleeding in a patient with CML in the chronic phase.
Laboratory values on admission
White cell count (109/L)
Platelet count (109/L)
Bleeding time (seconds)
Prothrombin time (seconds)
Antithrombin III (%)
Factor VIII activity (%)
Factor XIII activity (%)
vWF: antigen (%)
vWF: Rco activity (%)
C-reactive protein (mg/dL)
Cytoreductive therapy with hydroxyurea (1500 mg/day) was initiated as the most credible therapy to reduce her platelet count, because we could not rule out the possibility of MPD which does not respond to tyrosine kinase inhibitors. An urgent orthopedic opinion was obtained, and compartment syndrome was confirmed after the compartment pressure was found to be 39 mmHg. Emergency fasciotomy for decompression of the anterior compartment was conducted, which confirmed a tense compartment and pathologically proven hematoma in the right anterior compartment. There was no evidence of leukemic cell infiltration.
Persistent local bleeding developed during the latter part of the operation despite no surgical cause. After decompression, the wound was left open and managed with a wet dressing. Sustained postoperative oozing of blood resulted in hypovolemic shock and required massive red cell concentrate transfusion for hematologic and cardiovascular resuscitation. She continued to require 4 to 8 units of red blood cell concentrate on a daily basis (in Japan, 1 unit of red cell concentrate is derived from 200 mL of donated whole blood).
She continued dasatinib therapy, with good hematological and molecular responses. She obtained complete cytogenetic response and major molecular response at 12 and 18 months, respectively, after the initiation of dasatinib administration.
With patients with MPD, common complications involve gastrointestinal bleeding or skin and mucosal bleeding [6, 7]. Although most bleeding complications are generally not severe in patients with MPD , some do experience more severe symptoms .
In our patient, an extremely high platelet count (>1000 × 109/L) and severe bleeding complications were observed. According to the World Health Organization Classification of Tumours: Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues (fourth edition), accelerated-phase CML is defined by the presence of one or more of six specific features including persistent thrombocytosis (>1000 × 109 cells/L) that is unresponsive to therapy . In our patient, her platelet count was reduced in response to a tyrosine kinase inhibitor, and this response was sustained. The diagnosis of chronic-phase CML was considered appropriate.
Acute compartment syndrome caused by soft tissue bleeding related with hematological malignancies
Elevated platelet count is regarded as a risk factor for bleeding and thromboembolic events in MPD, but the significance of a high platelet count has not been confirmed in clinical studies . Michiels et al. reported that hemorrhagic complications more often occur in patients with higher degrees of thrombocytosis than in those with lower degrees [11, 12]. Platelet dysfunction due to acquired von Willebrand syndrome (AvWS) is considered one of the reasons for bleeding tendency in patients with MPD with remarkable thrombocytosis [13, 14], owing to the increased number of platelets binding to highly prothrombotic ultra-large vWF and their removal from plasma . However, neither decreased vWF levels (antigen and activity) nor an absence of higher molecular weight vWF multimers was confirmed in our patient. These results suggest that factors other than AvWS were responsible for the bleeding tendency of our patient.
Ristocetin-induced platelet aggregation abnormality is characteristic of AvWS platelet aggregation studies in vitro. In patients with MPD, various platelet function defects including platelet hyperactivity and hypoactivity, in addition to ristocetin-induced platelet aggregation, are frequently observed [16–18]. MPD-associated platelet dysfunction might cause bleeding complications. A patient with CML with platelet function abnormalities who developed severe soft tissue bleeding followed by compartment syndrome has been reported ; this patient did not experience AvWS-related complications. Following the administration of a tyrosine kinase inhibitor, platelet function improved together with the molecular response of CML. Moreover, in four patients with MPD with acute hemorrhagic or thrombotic complications of thrombocytosis, clinical symptoms improved with correction of platelet function after plateletpheresis . These findings suggest that bleeding complications in patients with MPD could be improved by reducing the platelet count through correction of platelet dysfunction.
In the present case, prothrombin time was slightly prolonged, but activated partial thromboplastin time was within the normal range. Bleeding time was also normal, as measured using the Duke method. Our decision to perform the fasciotomy for decompression was based on these findings. However, sustained postoperative oozing occurred, and massive red cell transfusion was required. The cause of slightly prolonged prothrombin time on admission may be the decreased level of coagulation factor VII, although we did not investigate this. During our patient’s clinical course her prothrombin time quickly recovered to the normal range while oozing was still observed. Therefore, coagulation factor VII was not relevant to her bleeding tendency. In vitro platelet aggregation studies could not be conducted in our patient, but it is possible that her bleeding tendency might be caused by platelet dysfunction with MPD-associated thrombocytosis for the following three reasons: (i) although cessation of bleeding was not achieved while her platelet count remained high, hemostasis was achieved as her platelet count decreased; (ii) the abnormality of the coagulation parameters was imperceptible throughout her clinical course; and (iii) a patient with CML with platelet dysfunction reported by Ng et al. also showed a similar clinical course .
For the control of severe bleeding complications such as ACS in patients with MPD with thrombocytosis, it should be noted that bleeding tendency will probably last until the platelet count is sufficiently reduced. Because of hypovolemic shock due to sustained bleeding we hesitated to perform plateletpheresis. We should proactively consider treatment options such as plateletpheresis in addition to cytoreductive therapy before emergency fasciotomy.
Patients with an extremely high platelet count might be at high risk for severe bleeding complications such as compartment syndrome even without acquired von Willebrand disease. For the control of severe bleeding complications in patients with MPD, the importance of thrombocyte reduction should be recognized.
ACS, acute compartment syndrome; AvWS, acquired von Willebrand syndrome; CML, chronic myeloid leukemia; ET, essential thrombocytosis; MPD, myeloproliferative disorder; vWF, von Willebrand factor
The authors thank the orthopedist Dr Etsuo Shoda who performed emergency fasciotomy.
The authors received no specific grant from any funding agency.
YN and SU examined and evaluated the patient and wrote the manuscript. HM, AY, YO, TM, KN, FM, RT, DH, SI, KO, HN, YY, YI, and SK examined and evaluated the patient. All authors read and approved the final manuscript.
The authors declare that they have no competing interests.
Consent for publication
Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
- Trumble T. Forearm compartment syndrome secondary to leukemic infiltrates. J Hand Surg Am. 1987;12(4):563–5.View ArticlePubMedGoogle Scholar
- Southworth SR, O’Malley NP, Ebraheim NA, Zeff L, Cummings V. Compartment syndrome as a presentation of non-Hodgkin’s lymphoma. J Orthop Trauma. 1990;4(4):470–3.View ArticlePubMedGoogle Scholar
- Veeragandham RS, Paz IB, Nadeemanee A. Compartment syndrome of the leg secondary to leukemic infiltration: a case report and review of the literature. J Surg Oncol. 1994;55(3):198–200. discussion 200–1.View ArticlePubMedGoogle Scholar
- Scheipl S, Leithner A, Radl R, Beham-Schmid C, Ranner G, Linkesch W, et al. Myeloid sarcoma presenting in muscle-tissue of the lower limb: unusual origin of a compartment-syndrome. Am J Clin Oncol. 2007;30(6):658–9.View ArticlePubMedGoogle Scholar
- Vardiman JW, Harris NL, Brunning RD. The World Health Organization (WHO) classification of the myeloid neoplasms. Blood. 2002;100(7):2292–302.View ArticlePubMedGoogle Scholar
- Wehmeier A, Daum I, Jamin H, Schneider W. Incidence and clinical risk factors for bleeding and thrombotic complications in myeloproliferative disorders. A retrospective analysis of 260 patients. Ann Hematol. 1991;63(2):101–6.View ArticlePubMedGoogle Scholar
- Randi ML, Stocco F, Rossi C, Tison T, Girolami A. Thrombosis and hemorrhage in thrombocytosis: evaluation of a large cohort of patients (357 cases). J Med. 1991;22(4–5):213–23.PubMedGoogle Scholar
- Buss DH, Stuart JJ, Lipscomb GE. The incidence of thrombotic and hemorrhagic disorders in association with extreme thrombocytosis: an analysis of 129 cases. Am J Hematol. 1985;20(4):365–72.View ArticlePubMedGoogle Scholar
- Teng CJ, Huang CT, Huang YC, Hong YC, Wang WS, Tzeng CH. Too many platelets to cause compartment syndrome. QJM. 2011;104(11):993–4.View ArticlePubMedGoogle Scholar
- Ng AP, Servadei P, Tuckfield A, Friedhuber A, Grigg A. Resolution of platelet function defects with imatinib therapy in a patient with chronic myeloid leukaemia in chronic phase. Blood Coagul Fibrinolysis. 2009;20(1):81–3.View ArticlePubMedGoogle Scholar
- van Genderen PJ, Michiels JJ. Erythromelalgic, thrombotic and haemorrhagic manifestations of thrombocythaemia. Presse Med. 1994;23(2):73–7.PubMedGoogle Scholar
- Michiels JJ, Berneman Z, Schroyens W, Finazzi G, Budde U, van Vliet HH. The paradox of platelet activation and impaired function: platelet-von Willebrand factor interactions, and the etiology of thrombotic and hemorrhagic manifestations in essential thrombocythemia and polycythemia vera. Semin Thromb Hemost. 2006;32(6):589–604.View ArticlePubMedGoogle Scholar
- Landolfi R, Marchioli R, Patrono C. Mechanisms of bleeding and thrombosis in myeloproliferative disorders. Thromb Haemost. 1997;78(1):617–21.PubMedGoogle Scholar
- McMahon B, Stein BL. Thrombotic and bleeding complications in classical myeloproliferative neoplasms. Semin Thromb Hemost. 2013;39(1):101–11.PubMedGoogle Scholar
- Michiels JJ. Acquired von Willebrand disease due to increasing platelet count can readily explain the paradox of thrombosis and bleeding in thrombocythemia. Clin Appl Thromb Hemost. 1999;5(3):147–51.View ArticlePubMedGoogle Scholar
- Baker RI, Manoharan A. Platelet function in myeloproliferative disorders: characterization and sequential studies show multiple platelet abnormalities, and change with time. Eur J Haematol. 1988;40(3):267–72.View ArticlePubMedGoogle Scholar
- Manoharan A, Gemmell R, Brighton T, Dunkley S, Lopez K, Kyle P. Thrombosis and bleeding in myeloproliferative disorders: identification of at-risk patients with whole blood platelet aggregation studies. Br J Haematol. 1999;105(3):618–25.View ArticlePubMedGoogle Scholar
- Finazzi G, Budde U, Michiels JJ. Bleeding time and platelet function in essential thrombocythemia and other myeloproliferative syndromes. Leuk Lymphoma. 1996;22 Suppl 1:71–8.View ArticlePubMedGoogle Scholar
- Orlin JB, Berkman EM. Improvement of platelet function following plateletpheresis in patients with myeloproliferative diseases. Transfusion. 1980;20(5):540–5.View ArticlePubMedGoogle Scholar
- Cohen E, Trunzter J, Klinge S, Schwartz K, Schiller J. Acute pediatric leg compartment syndrome in chronic myeloid leukemia. Orthopedics. 2014;37(11):e1036–9.View ArticlePubMedGoogle Scholar