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Volume: 12 Issue: 2 April 2014

FULL TEXT

LETTER TO EDITOR
Acute Cerebral Infarct With Elevated Factor VIII Level During the Thrombocytopenic Stage After Hematopoietic Stem Cell Transplant

Thromboembolism is a complication of hematopoietic stem cell transplant. However, a literature search showed no previous reports of cerebral infarction during the thrombocytopenic stage after hematopoietic stem cell transplant. A 35-year-old woman with acute lymphoblastic leukemia (precursor B-cell type) was treated with hematopoietic stem cell transplant after induction and consolidation chemotherapy. On day 2 after transplant, she was unconscious, and had urinary incontinence and left hemiplegia. A computed tomography scan of the brain showed an acute ischemic infarct in the right middle cerebral artery region and an old infarct at the left thalamus without atherosclerosis. Factor VIII level was elevated (190%; normal range, 60% to 150%). She was treated with rehabilitation and low-dose aspirin. At 6 months after transplant, the leukemia remained in remission and she had no further thromboembolic events. This case suggests that prudent treatment of patients who have hematopoietic stem cell transplant may include monitoring for thromboembolism and testing factor VIII level before transplant.


Key words : Coagulation, Clotting factors, Leukemia, Stroke

Introduction

Thromboembolism is a complication of hematopoietic stem cell transplant, and the cumulative incidence of venous thrombosis is 3.7% within 1 year and 11.8% within 14 years after transplant.1,2 The risk factors for thromboembolism include allogeneic transplant, graft-versus-host disease, and indwelling central venous catheters.1-3 Arterial thrombotic events also are a late complication after hematopoietic stem cell transplant and have a cumulative incidence of 4.1% for 14 years.4 However, a literature search showed no previous reports of cerebral infarction during the thrombocytopenic stage after hematopoietic stem cell transplant.

We treated a patient with an acute cerebral infarct during the thrombocytopenic stage after allogeneic hematopoietic stem cell transplant associated with an elevated factor VIII level.

Case Report

A 35-year-old woman with acute lymphoblastic leukemia (precursor B-cell type) was transferred to our hospital for hematopoietic stem cell transplant after induction and consolidation chemotherapy. Evaluation before transplant showed that the leukemia was in remission, and she had mild anemia and thrombocytopenia. She had no previous personal or family history of hypercoagulation or thromboembolism. She was taking prophylactic antibiotics.

The patient underwent hematopoietic stem cell transplant from a fully matched sibling donor, with total body irradiation and cyclophosphamide as the conditioning regimen. On the morning of day 2 after transplant, she was unconscious, and had urinary incontinence and left hemiplegia. Laboratory tests showed pancytopenia (white blood cell count, 0.5 × 109/L; hemoglobin, 96 g/L; platelet count, 46 × 109/L) and normal serum electrolyte levels. A computed tomography scan of the brain showed an acute ischemic infarct in the right middle cerebral artery region and an old infarct at the left thalamus without atherosclerosis. She had normal levels of protein S, protein C, anticardiolipin antibody, antithrombin III, homocysteine, and cryoglobulin; factor VIII level was elevated (190%; normal range, 60% to 150%). Factor V Leiden and prothrombin mutation tests were negative.

The patient was transferred to the medical intensive care unit. The white blood cell count recovered on day 12 after transplant and bone marrow examination showed successful engraft-ment. The level of consciousness improved gradually, but left hemiplegia persisted.

Factor VIII level increased to 207% three months after transplant. She was treated with rehabilitation therapy and low-dose aspirin. Six months after the transplant, the leukemia remained in remission and she had no further thromboembolic events.

Discussion

The patient had an acute ischemic cerebral infarct associated with a high factor VIII level during the thrombocytopenic stage after hematopoietic stem cell transplant. The patient did not receive prophylaxis for thromboembolism; despite the risk of thromboembolism after hematopoietic stem cell transplant, prophylaxis therapy is not used routinely because of the risk of bleeding.2

The risk factors for developing thromboembolism in the present patient included allogeneic transplant, indwelling central catheter, and high factor VIII level. Factor VIII is an essential clotting factor that participates in blood coagulation, and it may increase the risk of thromboembolism by increasing thrombin formation or inducing acquired activated protein C resistance.5,6 Elevated plasma factor VIII:C levels increase the risk of venous and arterial thrombosis.7-10 The increased factor VIII level in the present patient may have contributed to the development of cerebral infarction.

Prolonged anticoagulation therapy may be effective in preventing thromboembolism in patients who have high factor VIII levels.11 The present patient had no further thromboembolic events after starting low-dose aspirin therapy.

In summary, this case suggests that prudent treatment of patients who have hematopoietic stem cell transplant may include monitoring for thromboembolism. Elevated factor VIII:C is a risk factor for the development of thromboembolism, and factor VIII levels may be evaluated before transplant. Further studies are justified to evaluate the mechanism and treatment of thromboembolism during the thrombocytopenic stage after hematopoietic stem cell transplant.


References:

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Volume : 12
Issue : 2
Pages : 171 - 172
DOI : 10.6002/ect.2013.0128


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From the 1Faculty of Medicine, College of Medicine, Kaohsiung Medical University; and the 2Division of Hematology-Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
Acknowledgements: HHH and HLH designed the study and wrote the manuscript. HCW analyzed and review the data. YFT, TCL, and CSC analyzed the data and reviewed the paper. SFL proofread the manuscript. The authors have no conflicts of interest to declare. No funding was received for this study.
Corresponding author: Professor Sheng-Fung Lin, No. 100 Tzu-You 1st Road, San-Ming District, Kaohsiung 80756, Taiwan
Phone: +886 7 312 1101 (ext. 6110)
Phone: +886 7 316 2429
E-mail: shlin@cc.kmu.edu.tw