Blast Cell Arterial Embolus in Acute Myelogenous Leukemia

Accepted Manuscript Blast-Cell Arterial Embolus in Acute Myelogenous Leukemia Matthew Carnevale, MD, John Phair, MD, Patricia Yau, MD, Karan Garg, MD PII:

S0890-5096(18)30808-2

DOI:

10.1016/j.avsg.2018.07.067

Reference:

AVSG 4068

To appear in:

Annals of Vascular Surgery

Received Date: 28 June 2018 Accepted Date: 16 July 2018

Please cite this article as: Carnevale M, Phair J, Yau P, Garg K, Blast-Cell Arterial Embolus in Acute Myelogenous Leukemia, Annals of Vascular Surgery (2018), doi: https://doi.org/10.1016/ j.avsg.2018.07.067. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Blast-Cell Arterial Embolus in Acute Myelogenous Leukemia Matthew Carnevale MD1, John Phair MD 2, Patricia Yau MD 3, Karan Garg MD 1,2

3 1. Albert Einstein College of Medicine, 1300 Morris Park Avenue Bronx, NY 10461, USA

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2. Department of Cardiovascular and Thoracic Surgery, Montefiore Medical Center, 3400 Bainbridge Ave, Bronx, NY 10467, USA

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3. Department of General Surgery, Montefiore Medical Center, 3400 Bainbridge Ave, Bronx, NY 10467, USA

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Keywords: embolism, acute myelogenous leukemia (AML), blast cell, embolectomy

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Will be presented at the Eastern Vascular Society Annual Meeting 2018 Corresponding author:

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Dr. John Phair, MD

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[email protected]

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Blast-Cell Arterial Embolus in Acute Myelogenous Leukemia

21 ABSTRACT

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The link between coagulatory dysfunction in acute leukemias is well known, with patients having an

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increased risk of bleeding as well as thrombosis. Arterial thrombosis is particularly rare in this population

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however with only a few reported cases in the literature. We report the case of acute arterial occlusion

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secondary to a leukoblastic embolus causing limb threatening ischemia in a patient with acute

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myelogenous leukemia. The patient was successfully treated surgically by open superficial femoral artery

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thrombectomy, common femoral endarterectomy with patch angioplasty, and percutaneous tibial

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embolectomy.

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30 INTRODUCTION

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Hematologic malignancies are well known to disrupt the delicate balance between bleeding and

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thrombosis in acute myelogenous leukemia (AML). These patients have been shown to be at increased

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risk of thrombotic events. The leukostasis seen with hyperleukocytosis in these patients can precipitate

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arterial thrombus formation. We report a case of acute arterial occlusion secondary to a leukoblastic

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embolus causing limb threatening ischemia.

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CASE REPORT

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A 78-year-old female with refractory AML and no other significant past medical history presented to the

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emergency department in blast crisis with worsening left lower extremity pain and decreased motor

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function of three days duration. Physical exam revealed a cool, dusky left foot with weakness and

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decreased sensation in her toes. The patient had palpable right lower extremity pulses, but absent pulses

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on the left. An ultrasound revealed occlusions of the left common femoral, proximal superficial femoral,

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anterior tibial and dorsalis pedis arteries. Pertinent labs included a WBC count of 172,000 with 54%

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blasts. The patient’s condition was managed surgically by open superficial femoral artery thrombectomy,

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common femoral artery endarterectomy and patch angioplasty, and percutaneous tibial artery

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embolectomy. The patient recovered uneventfully and was transferred to the Oncology unit for induction

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of high dose cytarabine therapy. Surgical pathology revealed that the occlusion was secondary to

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embolization of a blast cell thrombus.

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We performed an extensive literature search using the Pubmed database as well as a query of Vascular

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and Hematology related journals and were unable to find more than a few cases of blast cell embolism

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with resulting acute arterial occlusion. Furthermore, only a subset of those cases involved surgical

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intervention. A few papers presented leukostasis in small blood vessels as a result of hyperleukocytosis

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in the setting of all-trans retinoic acid therapy. Other papers established that leukemia and

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hyperleukocytosis can be associated with DVT formation, pulmonary embolism, and coagulopathy. The

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following search terms were used: “blast cell embolism”, “embolization”, “leukocytosis”, “acute

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myelogenous leukemia”, “thromboembolization”, and “acute arterial occlusion”.

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DISCUSSION

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Cases of patients with AML presenting with acute arterial blast cell emboli are very sparse in the

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literature. Here we present a patient with refractory AML who developed limb ischemia secondary to a

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blast cell embolus. For limb salvage, the patient required open femoral and popliteal thrombectomy,

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common femoral endarterectomy and patch angioplasty as well as tibial embolectomy.

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Hematologic malignancies are well known to interfere with normal hemostasis as well as thrombosis and

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often result in thrombotic events. Patients with AML have been shown to be at increased risk of

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thrombosis, especially after treatment with all-trans retinoic acid . This thrombophilic predisposition

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typically manifests as venous thromboembolism and rarely results in arterial occlusion. Leukemic cells

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have increased procoagulant activity including altered expression of tissue factor, cancer procoagulant,

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proteolytic and fibrinolytic enzymes and inflammatory cytokines able to activate the clotting cascade .

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This thrombogenic propensity is compounded by the effect of chemotherapeutic agents which are toxic to

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the vascular endothelium and can lead to a decrease in physiologic anticoagulant levels .

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Arterial thrombi, colloquially known as white thrombi are platelet and fibrin rich aggregations that that lack

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a significant erythrocyte component unlike red thrombi which occur in the venous circulation. The

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pathologic basis for the formation white thrombi is believed to be due to the sedimentation of leukocytes

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secondary to the severe levels of leukocytosis seen in patients with leukemia . The occurrence of this

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phenomenon in large vessels is very rare. Arterial thromboembolism in the lower extremities has been

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reported in patients with AML only five times

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The earliest reported case of an arterial blast cell embolus occurred in 1986 when a 42-year-old

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Caucasian female with AML presented with occlusion of her distal aorta extending into her right iliac

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artery. She was treated with surgical thrombectomy but died 10 days later of respiratory failure.

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Postmortem examination revealed multiple thrombi composed of fibrin and leukemic cells in the aortic

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wall .

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In 1994 another case was reported in which a 74-year-old man with a history of stable left calf

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claudication reported increased pain with ambulation as well as anorexia, nausea and vomiting. His left

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leg was found to be cold and dusky below the knee with absent popliteal and pedal pulses. Further

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workup revealed a diagnosis of AML and he was treated medically and discharged 17 days later with

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improvement in his claudication .

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The third case of leukoblastic arterial thrombosis occurred in 1996 when a 42-year-old man with AML

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presented with leg pain of 2 days duration. He was found to be absent of tibial and pedal pulses on the

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right side and angiography confirmed thrombosis in his popliteal artery. He was treated unsuccessfully

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with thrombolysis and three attempts at thrombectomy however ultimately required a supracondylar

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amputation. The patient achieved remission after chemotherapy but died 2 years later from diffuse

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alveolar hemorrhage following a bone marrow transplant .

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The fourth case was reported in 2007 when a 57-year-old man with AML who presented with a 6-hour

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history of a painful, cold and pale right leg. Examination revealed a palpable pulse in his right femoral

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artery but absent distal pulses in the affected limb as well as an ankle brachial index of 0.2. He was

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initially treated conservatively with leukapheresis but deteriorated clinically the following day, with pulses

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in his right leg no longer palpable. He was treated with emergent iliofemoral and femoral-popliteal arterial

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thrombectomy. A white clot was removed from the bifurcation of his right common iliac artery with

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immediate improvement in perfusion of the limb .

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The most recent case of arterial blast cell embolization reported occurred in 2016 when a 50-year-old

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female with AML who presented with acute onset pain in her left leg that lasted 5 days. She had a cold

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and pale left leg with absent femoral, popliteal, posterior tibial and dorsalis pedis pulses. CT angiography

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revealed a partial filling defect in the aorta, just proximal to the bifurcation with distal reconstitution from

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collaterals of the contralateral limb. Echocardiography revealed a large mobile thrombus in the left

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ventricle. Aortic and ilio-femoral thrombectomy was done to salvage the limb and heparin was started to

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treat the cardiac thrombus .

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The mechanism of arterial occlusion proposed in the previously reported cases was leukostasis

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secondary to leukocytosis. Another important mechanism by which blast cells may favor thrombus

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formation is by damaging arterial walls by competing for oxygen in the microcirculation . The previously

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reported cases of acute lower extremity arterial occlusion in patients with AML were treated with various

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combinations of conservative management and thrombectomy. Given the rarity of patients with AML

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presenting with occlusion of large arteries, there is no established approach to treatment. However, since

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heparinization is futile in these patients and thrombolysis is generally contraindicated, surgical

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thrombectomy may be required in cases of limb threatening ischemia.

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CONCLUSIONS

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This case represents a rare presentation of acute arterial occlusion due to a blast cell embolism. AML is

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often associated with thromboembolism; however, this usually occurs in the venous circulation. Large

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artery embolization due to AML is thus rarely seen in the clinical setting. Thrombectomy, endarterectomy

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and patch angioplasty are surgical options that may be useful adjuncts to chemotherapy when presented

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with limb ischemia due to acute arterial embolization in hematologic malignancies.

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Figure 1: Photomicrograph of arterial thrombus showing fibrin rich aggregate and leukoblastic cells.

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