Central Retinal Vein Occlusion in Acute Promyelocytic Leukemia and Heterozygosis’ for Factor V Leiden and Methylentetrahydrofolate Reductase (MTHFR) Gene Mutations

Case Report

Austin J Clin Case Rep. 2014;1(1): 1003.

Central Retinal Vein Occlusion in Acute Promyelocytic Leukemia and Heterozygosis’ for Factor V Leiden and Methylentetrahydrofolate Reductase (MTHFR) Gene Mutations

Natasa Colovic1,2,*, Nada Suvajdzic -Vukovic1,2, Natalija Kosanovic-Jakovic1,3, Predrag Miljic1,2, Irena Djunic2, Ana Vidovic1,2 and Dragica Tomin1,2

1Department of Medicine, University of Belgrade, Belgrade, Serbia

2Department of Hematology, Clinical Center for Serbia, Belgrade, Serbia

3Department of Clinic for Eye disease/medical retinal CCS, Serbia

*Corresponding author: Natasa Colovic, Department of Medicine, University Belgrade, Dr. Subotica 8, 11010 Belgrade, Serbia.

Received: April 15, 2014; Accepted: May 02, 2014; Published: May 09, 2014


We present a 45-year-old man with low-risk acute promyelocytic leukemia in whom thrombosis of central retinal vein occurred a year after establishing diagnosis, during molecular remission while being on maintenance therapy with all-trans-retinoic acid, purinethol and methotrexate. As major risk factors leading to central retinal vein occlusion (CRVO) we identified heterozygosity for factor V Leiden (G1691A) and methylentetrahydrofolate reductase (C677T) gene mutations. Moreover, hyperhomocysteinemia of moderate degree, low plasma folate level and arterial hypertension appeared contributory factors. Hyperhomocysteinemia could be attributed to both methylentetrahydrofolate reductase (C677T) gene mutation and methotrexate administration. Screenings for inherited and acquired thrombophilia are mandatory for all patients with unusual thrombotic events such as CRVO whether they have history of leukemia or not.

Keywords: Central Retinal Vein Occlusion; Acute Promyelocytic Leukemia; All-Trans-Retinoic Acid; Factor V Leiden Mutation; MTHFR C677 Mutation


APL: Acute Promyelocytic Leukemia; APTT: Activated Partial Thromboplastin Time; ATRA: All Trans Retinoic Acid; CRVO: Central Retinal Vein Occlusion; KCT: Kaolin Clotting Time; MTHFR: Methylentetrahydrofolate Reductase; PCR-RFLP: Polymerase- Chain-Reaction-Restriction Fragment Lenght Polymorphism; WBC: White Blood Cells


Thrombosis may be a presenting manifestation at diagnosis in a significant proportion of patients with acute promyelocytic leukemia (APL) (up to 9.6%). However, a similar rate of thrombosis can occur during treatment of APL [1-5]. A major cause of thrombosis in APL is hypercoagubility typical of the disease itself and probably enhanced with all-transretinoic treatment [1,3-5].

Case Report

A 45-year-old man was diagnosed with APL in December 2010. His past medical history was significant only for arterial hypertension of 6-year duration. Both family and personal history of thrombosis were negative. Physical examination at admission was unremarkable except arterial tension of 160/100 mm Hg. A full blood count showed a white blood cell count (WBC) of 1.3x109/l, hemoglobin of 135 g/l and platelets of 165x109/l. There were 10% of atypical promyelocytes and blasts in peripheral blood. Blasts and promyelocytes comprising 44% of nucleated cells in a bone marrow aspirate were strongly myeloperoxidase positive. The immunophenotype of bone marrow blast cells was as follows: (alfaMPO, CD117, CD33, CD13, CD2)+ and (HLA-DR, CD34)-. Cytogenetic analysis of bone marrow cells revealed 46XY,t(15;17)(q22:q11-21)[5]/46,XY[25]. PML/RARA fusion transcript was of bcr1 type. The patient was diagnosed as low-risk APL. Coagulopathy was present with D-dimer 701µg/L (normal: < 240 ¯g/L ), prothrombin time (PT) 69% (normal: 75-120%), activated partial thromboplastin time (APTT) 27 sec (normal: 25-35 sec) and fibrinogen 2.41 g/l (normal: 2-4 g/L). The patient was treated according to the PETHEMA LPA 99 protocol (4). Prophilactic tranexamic acid was not administered in induction phase according to the reccomendations (4). He achieved cytologic and cytogenetic remission after induction treatment. Furthermore, he received three courses of consolidation chemotherapy according to the same protocol achieving molecular remission. In May 2011 he was started on the maintenance therapy with all-trans- retinoicacid (ATRA), purinethol and methotrexate. However, in January 2012 the patient exhibited a decrease in visual acuity progressing to severe loss of vision on left eye after a week interval. Ophtalmological examination performed 7 days after the onset of visual deterioration detected ischemic central retinal vein occlusion (CRVO) in the left eye; the finding in the right eye was normal (Figure 1).

Citation: Colovic N, Suvajdzic-Vukovic N, Kosanovic-Jakovic N, Miljic P, Djunic I, et al. Central Retinal Vein Occlusion in Acute Promyelocytic Leukemia and Heterozygosis’ for Factor V Leiden and Methylentetrahydrofolate Reductase (MTHFR) Gene Mutations. Austin J Clin Case Rep. 2014;1(1): 1003. ISSN 2381-912X