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Table of Contents
CASE REPORT
Year : 2019  |  Volume : 9  |  Issue : 1  |  Page : 52-54

An unusual case of acute promyelocytic leukemia manifesting with pulmonary embolism


1 Department of Cardiology, Fortis Hospital, Bengaluru, Karnataka, India
2 Department of Cardiology, Sri Jayadeva Institute of Cardiovascular Sciences and Research, Mysore, Karnataka, India

Date of Web Publication10-May-2019

Correspondence Address:
Dr. Veena Nanjappa
Sri Jayadeva Institute of Cardiovascular Sciences and Research, Mysore, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/JICC.JICC_10_19

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  Abstract 


Venous thromboembolism is four fold greater in patients with cancer. 5-20% of acute promyelocytic leukemia is M3 (Hypergranular promyelocytic leukemia) variety. Hemorrhagic complications are more common than thrombosis; Coagulopathy in acute promyelocytic leukemia is a very complex disorder and is under reported. Here is a case report of a rare presentation of acute promyelocytic leukemia manifesting with pulmonary embolism.

Keywords: Acute promyelocytic leukemia, pulmonary embolism, reteplase


How to cite this article:
Aniyathodiyil G, Nanjappa V, Selvam NS. An unusual case of acute promyelocytic leukemia manifesting with pulmonary embolism. J Indian coll cardiol 2019;9:52-4

How to cite this URL:
Aniyathodiyil G, Nanjappa V, Selvam NS. An unusual case of acute promyelocytic leukemia manifesting with pulmonary embolism. J Indian coll cardiol [serial online] 2019 [cited 2019 Jul 22];9:52-4. Available from: http://www.joicc.org/text.asp?2019/9/1/52/257953




  Introduction Top


Venous thromboembolism (VTE) is four-fold greater in patients with cancer.[1] Nearly 5%–20% of acute promyelocytic leukemia is of M3 variety. Hemorrhagic complications are more common than thrombosis; coagulopathy in acute promyelocytic leukemia is a very complex disorder and is under-reported.


  Case Details Top


A 53-year-old non-smoker male presented with exertional dyspnea (New York Heart Association class III) of recent onset (12 days). He had Type 2 diabetes mellitus and hypertension since 5 years and was on treatment for the same. He had no other comorbidities. This patient was referred to us by the pulmonologist with documented evidence of pulmonary embolism (PE) on computed tomography pulmonary angiogram.

Examination of vitals showed he had tachycardia with a pulse rate of 110 bpm which was regular. Blood pressure of 110/70 mm Hg, respiratory rate-24 breaths/minute, Oxygen saturation (SpO2) at room air was 92%. His right leg was edematous, nontender with no features of cellulitis. Electrocardiogram showed sinus tachycardia with T wave inversions in inferior leads; echocardiogram revealed dilated right atrial and ventricular chambers with mild tricuspid regurgitation and pulmonary artery systolic pressure (PASP) of 75 mm of Hg. Chest radiography was normal. Ultrasonography of abdomen was normal [Figure 1].
Figure 1: Computed tomography pulmonary angiogram-bilateral sub-segmental acute pulmonary embolism

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In the emergency room, he was diagnosed with acute submassive pulmonary embolism (PE) with suspected right leg deep vein thrombosis. He was thrombolysed with reteplase 10 units two doses 30 min apart. Duplex scan of the lower limb venous system done showed subacute thrombus in the right distal superficial femoral vein and popliteal vein extending into medial calf muscular veins and proximal posterior tibial veins. Left superficial vein thrombosis was also noted. Blood investigations done revealed neutropenia with thrombocytopenia [Table 1]. Retroviral and hepatitis B antigen titres were negative and Vitamin B12 levels were normal; thrombophilia workup revealed marginal elevation of homocysteine [Table 2]. Bone marrow aspiration studies revealed acute myelocytic leukemia (AML), morphologically favoring AML-M3-(Hypergranular promyelocytic leukemia) variety. Bone marrow biopsy showed hypercellular marrow with infiltration by acute myeloid leukemic cells. Immunophenotyping revealed promyelocytes expressing CD13, CD33, CD45, CD64 and CD117. CD 55/59 were present which ruled out paroxysmal nocturnal hemoglobinuria.
Table 1: Investigations

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Table 2: Thrombophilia workup

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Adequate neutropenic precautions were undertaken. Echocardiogram on day 3 showed improved right ventricular function with a fall in PASP to 30 mm of Hg with preserved ejection fraction. His dyspnea had improved and there were no bleeding tendencies. Serial monitoring of complete hemogram was done. Post thrombolysis, patient was given subcutaneous fondaparinux injection at a dose 5 mg, once daily.

Chemotherapy was initiated with retinoic acid (all-trans retinoic acid [ATRA]) by the Oncologist. His blood counts started improving. He was also started on prophylactic flucanazole and cotrimoxazole. Repeat bone marrow aspiration a month later showed no leukemic blasts or promyelocytes. He, however, did not tolerate chemotherapy with cytarabine and daunorubicin. it was stopped midway in view of drastic drop in counts (total white blood cell count - 100 cells/cubic mm, Hb: 9 g% and platelet: 32,000 cells/cubic mm). Hence was continued on ATRA. The patient developed neutropenic sepsis and shock and was treated for the same with prolonged duration of antibiotics and supportive measures. He recovered after a prolonged intensive care unit stay. Arsenic trioxide was subsequently incorporated into the treatment in combination with ATRA keeping in line with promyelocytic leukemia treatment protocols.


  Discussion Top


VTE is four-fold greater in patients with cancer, more so in solid cancers. VTE is six-fold greater in patients receiving chemotherapy; ninetyfold greater in the first 6 weeks after oncosurgery and the risk persists up to thirtyfold till 1 year.[2] Negative D-dimer has the same diagnostic value in PE in patients with or without cancer. Positive values are taken with a “pinch of salt” as cancer can give rise to elevated values.[3]

Cancer is an adverse prognostic factor. Thirty-day mortality in patients with cancer is 26.4% and those without cancer are 4.1%.[4] Approximately 10% develop cancer (occult cancer) in next 5–10 years after an unprovoked PE, more so in the first.

The CLOT trial[5] demonstrated that low molecular weight heparin was more effective than warfarin at reducing the risk of recurrent VTE in patients with DVT/PE and active cancer. Recent guidelines on the management of acute PE are shown in [Table 3].
Table 3: Recent guidelines on management of acute PE

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5%–20% of acute promyelocytic leukemia is M3 variety characterized by t(15,17) translocation. Hemorrhagic complications are more common than thrombosis; coagulopathy is under-reported. Etiopathogenesis postulated is direct expression of tissue factors and procoagulants (annexin II receptor expression). Coagulopathy is greater with the use of ATRA, especially during induction.[6] Standard therapy for acute promyelocytic leukemia includes cytarabine, daunorubicin, with or without etoposide. Tretinoin plus concurrent anthracycline-based chemotherapy appears to be among the most effective treatments for acute promyelocytic leukemia leading to complete remission rates of 90%–95%. The addition of cytarabine decreases the risk for relapse.

In a review by Rashidi et al.[7] (n = 94 acute promyelocytic leukemia (APL)), 1 patient had PE; only one of the case had thrombosis as the initial manifestation. In two large-scale studies, the incidence of thrombosis has varied from 4.5% to 5.6%.[7],[8],[9] A high total leucocyte count, bcr3 (short) isoform of promyelocytic leukemia - retinoic acid receptor alpha (PML-RARα) transcripts, and expression of CD2 and CD 15 on leukemic cells have been found to be associated with increased risk of thrombosis.

This case is unusual because pulmonary embolism (PE) and deep vein thrombosis were the presenting manifestations of sinister leukemia. Less than 5% cases of acute myelocytic leukemia (AML) have no detectable leukemic cells on peripheral smear. Those with preceding cytopenias and hematological disease have worse prognosis even with treatment.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Heit JA, Silverstein MD, Mohr DN, Petterson TM, O'Fallon WM, Melton LJ 3rd. Risk factors for deep vein thrombosis and pulmonary embolism: A population-based case-control study. Arch Intern Med 2000;160:809-15.  Back to cited text no. 1
    
2.
Sweetland S, Green J, Liu B, Berrington de González A, Canonico M, Reeves G, et al. Duration and magnitude of the postoperative risk of venous thromboembolism in middle aged women: Prospective cohort study. BMJ 2009;339:b4583.  Back to cited text no. 2
    
3.
Douma RA, van Sluis GL, Kamphuisen PW, Söhne M, Leebeek FW, Bossuyt PM, et al. Clinical decision rule and D-dimer have lower clinical utility to exclude pulmonary embolism in cancer patients. Explanations and potential ameliorations. Thromb Haemost 2010;104:831-6.  Back to cited text no. 3
    
4.
Gussoni G, Frasson S, La Regina M, Di Micco P, Monreal M; RIETE Investigators. Three-month mortality rate and clinical predictors in patients with venous thromboembolism and cancer. Findings from the RIETE registry. Thromb Res 2013;131:24-30.  Back to cited text no. 4
    
5.
Lee AY, Levine MN, Baker RI, Bowden C, Kakkar AK, Prins M, et al. Low-Molecular-Weight Heparin versus a Coumarin for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer. N Engl J Med 2003; 349:146-153.  Back to cited text no. 5
    
6.
Runde V, Aul C, Heyll A, Schneider W. All-trans retinoic acid: Not only a differentiating agent, but also an inducer of thromboembolic events in patients with M3 leukemia. Blood 1992;79:534-5.  Back to cited text no. 6
    
7.
Rashidi A, Silverberg ML, Conkling PR, Fisher SI. Thrombosis in acute promyelocytic leukemia. Thromb Res 2013;131:281-9.  Back to cited text no. 7
    
8.
Breccia M, Avvisati G, Latagliata R, Carmosino I, Guarini A, De Propris MS, et al. Occurrence of thrombotic events in acute promyelocytic leukemia correlates with consistent immunophenotypic and molecular features. Leukemia 2007;21:79-83.  Back to cited text no. 8
    
9.
Lou Y, Mai W, Jin J. Simultaneous presentation of acute myocardial infarction and acute promyelocytic leukemia. Ann Hematol 2006;85:409-10.  Back to cited text no. 9
    


    Figures

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    Tables

  [Table 1], [Table 2], [Table 3]



 

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