|Year : 2010 | Volume
| Issue : 4 | Page : 567-569
Acute Budd-Chiari syndrome as an initial presentation of acute promyelocytic leukemia
Sanjay Bandyopadhyay, Debottam Bandyopadhyay
Department of Medical Gastroenterology, School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education and Research, Kolkata - 700020, India
|Date of Web Publication||24-Feb-2011|
1B/3, Uttarpara Housing Estate, 88 B, G T Road, P.O.- Bhadrakali, Dist. Hooghly, Pin - 712232, West Bengal
Source of Support: None, Conflict of Interest: None
Budd-Chiari syndrome (BCS) is the constellation of clinical signs and symptoms resulting from occlusion of two or more hepatic veins, often due to an underlying thrombophilic disorder. Acute myeloid leukemia has been rarely reported to be associated with hepatic vein thrombosis due to hyperleukocytosis, hyperfibrinolysis and disseminated intravascular coagulation. We report a case of acute promyelocytic leukemia where the clinical onset of the hematological disease was with acute BCS.
Keywords: Acute promyelocytic leukemia, Budd-Chiari syndrome, thrombophilia
|How to cite this article:|
Bandyopadhyay S, Bandyopadhyay D. Acute Budd-Chiari syndrome as an initial presentation of acute promyelocytic leukemia. J Can Res Ther 2010;6:567-9
| > Introduction|| |
Chronic myeloproliferative disorders and inherited thrombophilias are the main causes of hepatic vein occlusion.  Several subtypes of acute myeloid leukemia (AML) are occasionally associated with thrombotic events. Of them, acute promyelocytic leukemia (APML) is recognized to be a classic thrombo-hemorrhagic syndrome. , We report a case of APML in a 14-year-old male where thrombosis of right hepatic vein (RHV), middle hepatic vein (MHV) and inferior vena cava (IVC) gave rise to acute Budd-Chiari syndrome (BCS) with fatal termination.
| > Case Report|| |
A 14-year-old male presented with epigastric pain and rapid development of abdominal distension for 1 week. Two weeks prior to this, he had noticed progressive fatigue, low-grade fever and passage of dark urine. He had ignored these symptoms and took multivitamins at home. No antecedent history of abdominal trauma or hepatotoxic drug intake was reported. He never had any major medical or surgical illness. Personal and family history was non-contributory.
On examination, a temperature of 100ºF was recorded with tachypnea and tachycardia. He was pale with an icteric tinge of conjunctiva. His abdomen was diffusely tender without rigidity or rebound tenderness. Ascites was also noted. He had soft tender hepatomegaly (span of 18 cm at right midclavicular line) with a smooth surface. There was no splenomegaly, abdominal lump, dilated cutaneous veins or back veins. Rest of the examination was unrevealing.
At admission, investigations revealed low hemoglobin, neutrophilic leukocytosis and thrombocytopenia [Table 1]. Peripheral blood smears showed marked aniso-poikilocytosis without any abnormal cells. Serum biochemical parameters (fasting plasma glucose, urea, creatinine, sodium, potassium) were normal. Liver panel revealed a moderate rise in bilirubin, very high serum aminotransferases, slight elevation of alkaline phosphatase, normal serum albumin and a prolonged prothombin time. Abdominal ultrasound showed marked hepatomegaly with smooth surface and regular margin, moderate ascites, and normal biliary tree and portal vein. However, both the RHV and MHV were not visualized. Color and pulse Doppler study revealed absent flow in both RHV and MHV, and dilated tortuous left hepatic vein with increased flow velocity [Figure 1]. A large, organized thrombus was also detected in the intra-hepatic part of IVC with near complete occlusion of the lumen with diminished flow and loss of triphasic pattern of venous waveform [Figure 2]. Multiple dilated subcapsular collaterals were seen in the liver. A contrast-enhanced computed tomography (CECT) scan showed diffuse perfusion defect of the right lobe of liver with sparing of the caudate and left lobe [Figure 3]. Doppler screening of leg veins did not reveal any evidence of past or recent thrombus. Esophago-gastroduodenoscopy did not show any varix. A diagnosis of acute BCS was made and the patient was treated with intravenous heparin (20,000 U/day) for 4 days followed by oral anticoagulant.
|Table 1: Hematological, biochemical and coagulation parameters during hospital stay|
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|Figure 3: CECT abdomen showing the venous infarction affecting the right lobe|
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Over the next week, ascites progressively increased, accompanied by further worsening of his liver function [Table 1]. A fall in WBC count with marked fall in hemoglobin and platelet numbers were seen on the third day. A repeat peripheral blood smear after 1 week showed very low leukocyte count with a few myeloblasts and promyelocytes. Bone marrow aspiration study was done under the cover of fresh frozen plasma. Smear showed marrow elements completely substituted by promyelocytes and myeloblasts (~40% of marrow cytology), conforming to FAB, AML-M3 [Figure 4]. Immunocytochemistry confirmed the myeloid origin of blast cells (CD 13+, CD 33+, MPO+) and cytogenetic evaluation revealed the presence of t(15;17) translocation. Taken together these findings, the leukemia was confirmed to be of acute promyelocytic type. Diagnostic investigations did not substantiate the possibility of disseminated intravascular coagulation (DIC) [Table 1] and he was switched back to intravenous heparin because of difficulty in assessing the response to oral anticoagulant in the presence of liver failure. Chemotherapy regimen was planned but unfortunately his condition further deteriorated and he rapidly became comatose. A non-contrast cranial CT did not reveal any intracranial bleed. Ultimately, the patient succumbed to liver failure.
|Figure 4: Photomicrograph showing promyelocytes with enlarged nuclei, prominent nucleoli and prominent intracytoplasmic granules|
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The risk of venous thrombosis associated with the hematological malignancies like acute leukemia, lymphoma, and multiple myeloma is considerable and, in fact, exceeds that for many solid tumors  Hyperleukocytosis with intravascular leukocyte thrombi formation, hyperfibrinolysis, non specific proteolytic activity and DIC have been implicated in the pathogenesis of thrombosis.  The type of AML most frequently associated with DIC and thrombi formation is the promyelocytic type (prevalence of 8-42%).  Treatment with differentiating agents (all trans retinoic acid or arsenic trioxide) can reverse the coagulopathy seen in APML in 4-5 days, along with giving a >90% complete remission rate.  Thus, the current guideline on management for APL is to start this form of therapy as soon as the diagnosis is suspected.
| > Discussion
Only two cases of acute BCS associated with APML have so far been reported; , of them, one was associated with microgranular variant of APML.  In both these cases, the diagnosis was made at autopsy and both were associated with DIC.
The case we presented here has much peculiarity. Firstly, clinical onset of the hematologic disease was with thrombosis of hepatic veins and IVC, manifesting as BCS. No other risk factor for visceral venous thrombosis could be identified. Second, the initial blood picture was not suggestive of APML. Only the dramatic fall in hemoglobin and platelets in due course (coupled with appearance of abnormal cells of WBC lineage) drew our attention to a possibility of hematological disorders and we undertook bone marrow aspiration study. Also, the occurrence of venous thrombosis in this case was not associated with any other laboratory evidence of DIC.
The objective in having the case reported is to emphasize the importance of recognition of this rare complication and to provide differentiation therapy early in its course.
| > References|| |
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]