Severe transfusion-dependent uterine hemorrhage is a relatively uncommon complication of induction chemotherapy for leukemia. We report a case of life-threatening uterine hemorrhage in a 49-year-old woman in the setting of transfusion-refractory thrombocytopenia after completing induction chemotherapy for leukemia. She experienced dramatic breakthrough uterine hemorrhage despite multiple platelet transfusions, conjugated estrogens, and intracavitary thrombin-soaked gauze tamponade. At the point of near-exsanguination in the setting of hypotension, hematocrit of 20%, and a platelet count of 7,000/uL, she underwent bilateral uterine artery embolization which proved immediately successful. We review the literature and indications for this procedure in the oncologic patient care setting. After 2 weeks, she complained melena . SMA angiography was done. Angiography showed bleeding in ileocollic artery . We embolized by contour particles (250um-350um).

arterial embolization, leukemia, hemorrhage

Patients with Myelodysplastic Syndrome (MDS) may develop intractable bleeding at various mucosal sites at a result of chemotherapy induced thrombocytopenia, mucositis, and DIC. We report a case of a middle age perimenopausal woman with MDS who developed prolonged transfusion-refractory thrombocytopenia after completing her 2nd induction chemotherapy and 1st consolidation chemotherapy. Her post－induction course was refractory anemia, pancytopenia, Hepatic Candidiasis, acute sinusitis, Hospital aquired pneumonia, Gastrointesinal bleeding, Septic shock, multiple organ dysfunction and further complicated by life-threatening uterine hemorrhage impossible Total Abdominal Hysterectomy(TAH) due to refractory to multiple systemic hemostatic, hormonal status. Ultimately, the hemorrage resolved only with bilateral uterine artery embolization. Ealry intervention with this technique may spare future similary disposed patients prolonged MICU stays and multiple heterologous blood product transfusions.

The patient is a 49-year-old woman diagnosed with MDS RAEB-T (Refractory anemia with Exess Blast in Transformation) on September 2002. There was prior diagnosis intrauterine leiomyoma. She presented with progressive fatigue; a screening complete blood cell count(CBC) showed a pancytopenia with myeloblasts. Bone marrow biopsy/aspirate confirmed MDS RAEB-T. She underwent induction chemotherapy with idarubicin(12mg/m2) and cytosine arabinoside(100mg/m2). Post induction, she developed severe leukopenia(WBC less than 500), transfusion-dependent anemia(Hct less than 25%), and transfusion-dependent thrombocytopenia (Platelet less than 10,000) During the chemotherapy, she had continous high fever, massive and broad antibiotics was suggested. She was consulted to department of General Sergery, Opthalmology, Neuropsycology, ENT, OBGY for gastrointestinal bleeding, perianal abscess, hemorrhoid, chronic conjuctiva injection, visual hallucination, sinusitis, vaginal bleeding. At the focus of vaginal bleeding, The staff of Gyencology thought the cause of vaginal bleeding is perimenopausal irregular uterine bleeding or submucosal myoma related bleeding. And she underwent packing of the uterus with a thrombin-soaked pad. She continued to have brisk vaginal bleeding to a hematocrit of less than 20%.She also received hemostatic management with conjugated estrgens. She also required multiple heterologous blood product transfusion. Considering her status, It is impossible total abdominal hysterectomy(TAH). During continous vaginal bleeding for 4 weeks, She was transferred to the MICU because of lower GI and uterine bleeding to the point of hypotension. A vascular/interventional radiology consult was obtained at 4 weeks from initial vagial bleeding to evaluate the patient for a bilateral uterine artery and right iliac artery embolization. The embolization procedure was done utilizing polyvinyl alcohol(PVA 350-500) and Gelfoam.

and <2> illustrate the dramatic arterial blood flow in the right uterine artery following PVA/gel foam embolization. The patient experienced prompt resolution of her uterine bleeding and Gastrointestinal bleeding. Aortography, both internal iliac angiography, embolization in both uterine artery. Previous noted vaginal bleeding. Lower abdominal arotography shows some staining in uterus. Internal iliac angiography shows some bleeding in uterine area. Superselection in left uterine artery bymicrocatheter and microwire and embolization by ivalon(255um ~ 350um). Postembolization angiograghy shows no staining in left uterine artery and left femoral puncture. And right internal iliac artery angiography, and superselection in right uterine artery were done by microcatheter and microwire. And embolization by Ivalon. Post angiography shows no staining in right uterine artery

Hemorrhage is a major contributing factor to morbidity and mortality in leukemia patients [1]. In autopsy series, it is the second leading cause of death in this patient group [2].Treatment-induced thrombocytopenia, DIC, vascular wall infiltration by leukemic cells and/or fungal pathogens, and mucositis are all thought to contribute to the pathophysiology of hemorrhagic complications in leukemia patients [3,4].] Hemorrhage in leukemiapatients has been reported at multiple anatomic sites; those most commonly cited include CNS, GI tract, mucosal, pulmonary, and genitourinary, Life-threatening uterine bleeding is rarely reported in this patient population. When uterine bleeding does occur in leukemia patients, it is usually managed with conservative local (i.e., tampons, intrauterine packing) and systemic (i.e., maintaining an adequate platelet count with platelet transfusions, supplemental estrogen) measures. The case presented here was complicated by severe transfusion-refractory thrombocytopenia post induction and consolidation chemotherapy. After 4weeksher uterine bleeding started, she received aggressive and substantial hemostatic therapeutic interventions.Following her bilateral uterine artery embolization, her uterine bleeding ceased and her hematocrit stabilized. Agents employed to control systemic hemorrhaging in the setting of thrombocytopenia and leukemia have historically been applied empirically based upon their demonstrated efficacy in other clinical situations. For example conjugated estrogens were first utilized to control dysfunctional uterine bleeding [5-7]. Later, they were utilized to control hemorrhage in patients undergoing ophthalmologic surgery [8-10]. They were subsequently found to correct bleeding time abnormalities and control hemorrhagic diathesis in uremic patients [11,12]. There is scant literature documenting the efficacy of conjugated estrogens in controlling or preventing uterine hemorrhage in female leukemia patients. However, conjugated estrogens are widely utilized for this purpose based on successful past－clinical experience with this agent in the above mentioned clinical settings. The failure ofthis patient to respond promptly to conjugated estrogens meant that other agents (antifibrinolytics, rVIIa) had to be empirically employed. Antifibrionlytics have been utilized successfully to treat both dysfunctional uterine bleeding in nonleukemic patients and mucosal bleeding in leukemic patients [13,14]. Its efficacy in the setting of dysfunctional uterine bleeding attributed to inhibition of abnormally elevated intrauterine fibrinolytic activity [15]. rVIIa has been reported to control refractory uterine bleeding in at least one case of refractory thrombocytopenia in the bone marrow transplant setting [16]. Endometrial curettage and endometrial ablation are other therapies that have been used to control severe uterine bleeding in various clinical settings. Endometrial curettage is most useful in the setting of excessive menstrual or perimenstrual bleeding [17]. We conclude that uterine hemorrhage in leukemia, though relatively rare, can be life-threatening especially when compounded by transfusion-refractory thrombocytopenia. In this setting, clinicians should probably consider employing bilateral uterine artery emboilization relatively early. The need for a femoral artery sheath, in the setting of such severe thrombocytopenia, may increase the risk of periprocedural hemorrhage/hematoma. The rapid resolution of life-threatening uterine hemorrhage, as reported here, would seemingly offset this. Finally by rapidly staunching hemorrhage, this procedure has the potential to reduce the risk of transfusion-related blood borne infection and transfusion-related alloimmunization is this setting.

1. Aderka D, Praff G, Santo M, Weinberger A, Pinkhas J. Bleeding due to thrombocytopenia in acute leukemias and reevaluation of the prophylactic platelet transfusion policy. Am J Med Sci 1986; 291(3)：147-151. 2. Chang HY, Rodriguez V, Narboni G, Bodey GP, Luan MA, Freireich EJ. Causes of death in adults with acute leukemia. Medicine 2001;55(3)：259-268. 3. Stentnes KE, Godal HC, Wisloff F. Disseminated intravascular coagulation (DIC) in adult patients with acute lerukemia. Eur J Gaematol 1995;54(1)：34-38. 4. Doran HM, Sheppard MN, Collins PW, Jones L, Newland AC, Van der Walt JD Pathology of the lung in leukemia and lymphoma：a study of 87 autopsies. Histopathology 1991;18(3)：211-219. 5. Cseffalvay T, Klose S. [Estrogen-gestagen therapy with hormonally induced uterine bleeding. II. Therapeutic use of Klimovan]. Dtsch Gesundheitsw 1965;20：1334-1339. 6. Klose S, Cseffalvay T. 1965[Clinical experiences with Klimovan in the treatment of functional bleeding disorders]. Zentralbl Gynakol 1965; 87：1472-1475. 7. Pritchard JA. The management of severe anemia due to iron deficiency and benign gynecologic disease. Am J Obstet Gynecol 1965;93：617-631. 8. Avendikian H.[Prevention of hemorrhage in eyte surgery]. Klin Monatsbl Augenheilkd 1969;154：38-42. 9. Weinstein P. Treatment of ophthalmic hemorrhage by premarin. Int Z Klin MPharmakol Ther Toxikol 1969;2：72-73 10. Lang Z, Nemeth E. [Use of conjugated estrogens in ophthalmology]. Klin Monatsbl Augenheilkd 1970;156：105-109. 11. Liu YK, Kosfeld RE, Marcum SG. Treatment of uraemic bleeding with conjugated oestrogen. Lancet 1984;2：887-890. 12. Livio M, Mannucci PM, Vigano G, et al. Conjugated estrogens for the management of bleeding associated with renal failure. N Engl J Med 1986;315：731-735. 13. Gleeson NC, Buggy F, Sheppard BL, Bonnar J. The effect of tranexamic acid on measured menstrual loss and endometrial fibrionlytic enzymes in dysfunctional uterine bleeding. Acta Obstet Gynecol Scand 1994;73：274-277. 14. Nilsson IM, Andersson L, Bjorkma SE. Epsilon-aminocaproic acid (E-ACA) as a therapeutic agent based on 5 years’ clinical experience. ACta Med Scand Suppl 1966;448：1-46. 15. Gleeson N, Devitt M, Sheppard BL, Bonnar J. Endometrial fibrinolytic enzymes in women with normal menstruation and dysfunctional uterine bleeding. Br J Obstet Gynaecol 1993; 100：768-771. 16. Vidarsson B, Onundarson PT. Reconbinant factor VIIa for bleeding in refractory thrombocytopenia. Thromb Haemost 2000;83：634-635. 17. League DD. Endometrial ablation as an alternative to hysterectomy. AORN J 2003;77(2)：322-338. 18. Phelan JT, Broder J, Kouides PA. Kouides Near-fatal uterine hemorrhage during induction chemotherapy for acute myeloid leukemia：A case report of bilateral uterine artery embolization. American Journal of Hematology 77;151~155(2004)

Fig. 1 Selective microcatheterization of the left uterine arterial angiography shows staining in distal branch of left of uterine artery.

Fig. 2 Post PVA particle embolization, left uterine angiography shows no visualize uterine artery staining.

Fig. 3 selective catheterization of the left internal iliac artery post embolization. There is no filling of the uterine artery while there is opacificaton of the other internal iliac arterial branches.

Fig. 4 Right uterine arterial selective angiography shows some staining in distal right uterine artery. We embolized by contour(250um-350um)

Fig. 5 SMA angiography shows some staining in ileocolic artery.

Fig. 6. Microcatheter superselective ileocolic angiography shows focal stainig in branches.

Fig. 7 Post embolized by contour(250um-350um) angiography shows no visualized previous staining.