Gastrointestinal Bleeding in Lupus Anticoagulant- Hypoprothrombinemia Syndrome with Atypical Chronic Myeloid Leukemia, BCR-ABL1-Negative

Case Report

Austin J Med Oncol. 2020; 7(1): 1049.

Gastrointestinal Bleeding in Lupus Anticoagulant- Hypoprothrombinemia Syndrome with Atypical Chronic Myeloid Leukemia, BCR-ABL1-Negative

Hiraga J1*, Harada Y1, Fujikami T2 and Kagami Y1

¹Department of Hematology, Toyota Kosei Hospital, Toyota, Japan

²Department of Clinical Laboratory, Toyota Kosei Hospital, Toyota, Japan

*Corresponding author: Junji Hiraga, Department of Hematology, Toyota Kosei Hospital, Japan

Received: September 18, 2020; Accepted: October 05, 2020; Published: October 12, 2020

Abstract

A 78-year-old man was transported to our hospital with dyspnea and melena. He had been administered hydroxycarbamide for Atypical Chronic Myeloid Leukemia, BCR-ABL1-negative (aCML), and edoxaban for a history of cerebral infarction. Laboratory tests showed severe anemia, prolonged prothrombin time and prolonged activated partial thromboplastin time. Plasmamixed testing indicated Lupus Anticoagulant (LA), which was confirmed using dilute Russell’s viper venom time. Coagulation factor activities were decreased and positive results were obtained for coagulation factor inhibitor activities. Lupus Anticoagulant-Hypoprothrombinemia Syndrome (LAHPS) was diagnosed. LAHPS is mostly associated with systemic lupus erythematosus or infectious diseases in young patients, but concomitant LAHPS and aCML has not previously been reported. This finding suggests that malignant neoplasms might be underlying diseases in elderly LAHPS patients.

Keywords: Lupus Anticoagulant (LA); Lupus Anticoagulant- Hypothrombinemia Syndrome (LAHPS); Atypical Chronic Myeloid Leukemia; BCR-ABL1-negative (aCML)

Introduction

Lupus Anticoagulant (LA) is defined as an immunoglobulin that inhibits phospholipid-dependent coagulation activity [1], and an association with thrombosis has been identified in antiphospholipid antibody syndrome [2,3]. Lupus Anticoagulant- Hypoprothrombinemia Syndrome (LAHPS) is defined as a syndrome of acquired hypoprothrombinemia and LA, and is associated with bleeding events as well as thrombosis [4,5]. LAHPS is a very rare disease, mostly concurrent with Systemic Lupus Erythematosus (SLE) or infectious diseases in young patients [6,7]. Recently, LAHPS has been reported concomitant with hematological malignancies, including malignant lymphoma, in elderly patients [8,9].

Atypical Chronic Myeloid Leukemia, BCR-ABL1-negative (aCML) is a rare hematological malignancy with poor prognosis [10]. The incidence is estimated as only 1–2 aCML cases for every 100 cases of BCR-ABL1-positive Chronic Myeloid Leukemia (CML), and CML has an annual incidence of 1–2 cases per 100,000 population [11]. Although an increased white blood cell count is one of the main clinical characteristics of aCML, the number of blasts is not usually increased, and no characteristic gene abnormality is observed. No standard treatment has yet been established.

Here we report a rare case of gastrointestinal bleeding in an LAHPS patient treated for aCML.

Case Presentation

A 78-year-old man was transferred to our hospital due to dyspnea and melena. He had undergone partial gastrectomy for gastric cancer 20 years earlier, in addition to catheter ablation on two occasions for paroxysmal atrial fibrillation, 3 years earlier and 8 months earlier. He had been referred to the department of hematology because of leukocytosis 2 years earlier, and had been diagnosed aCML with bone marrow aspiration, revealing a normal karyotype and negative results for gene mutation tests (BCR-ABL1, JAK2, and PDGFRA). Treatment with hydroxycarbamide was then started. He had also been receiving edoxaban due to cerebral infarction 3 months earlier. Initial laboratory tests revealed severe anemia, prolonged prothrombin time and prolonged activated partial thromboplastin time, as well as positive results from immunoassay fecal occult blood testing (Table 1). Heart failure was diagnosed and attributed to anemia caused by gastrointestinal bleeding. Computed Tomography (CT) showed hepatosplenomegaly, but no lesions characteristic of infections such as pneumonia were observed. The plasma-mixing test indicated an LA pattern (Figure 1), which was confirmed using dilute Russell’s viper venom time. As a result, LAHPS was diagnosed. Additional blood tests showed decreased coagulation factor activities of factor (F)II, FV, FVII, FVIII, FIX, and FXII, and positivity for coagulation factor inhibitor activities for FVIII inhibitor and FIX inhibitor (Table 1). Red blood cells were urgently transfused, edoxaban was discontinued, and administration of lansoprazole was initiated. Gastroscopy revealed no active bleeding, so the patient resumed eating, and was discharged. As of the time of writing, 6 months later, no obvious gastrointestinal bleeding has recurred.

Figure 1: The plasma-mixing test, indicating a lupus anticoagulant pattern.

    

    
    

    

    Figure 1: The plasma-mixing test, indicating a lupus anticoagulant pattern.

Table 1: Laboratory findings at diagnosis.



TABLECREATED







Table 1: Laboratory findings at diagnosis.

Discussion and Conclusion

Here we report a case of LAHPS in an elderly aCML patient. To the best of our knowledge, concomitant LAHPS and aCML has not previously been reported, and this case is thus considered very rare. LAHPS is defined in LA-positive individuals showing low prothrombin activity [4,5], and clinical symptoms are basically thrombotic tendencies associated with LA, but severe bleeding tendencies have also been reported. According to reports of 74 LAHPS cases, thrombotic symptoms such as arteriovenous thrombosis were observed in 13%, bleeding symptoms in 89%, and serious bleeding such as intracranical hemorrhage in 51% [4]. In this case, cerebral infarction had occurred 3 months earlier, and might have been a symptom of LAHPS.

In this case, activities of each coagulation factor were decreased, and multiple anticoagulant inhibitor activities were also detected. Prothrombin, FVIII, FIX, and FXI are reportedly significantly reduced in LAHPS cases [4]. Distinguishing LAHPS from acquired hemophilia is particularly important.

LAHPS is a very rare disease, mostly associated with SLE or infectious diseases in young patients [6,7]. In this case, however, the patient was elderly, at 78 years old, and suffered from aCML treated with hydroxycarbamide. Negative results were obtained for autoantibodies associated with SLE such as antinuclear antibody, anti-double-stranded DNA antibody, and anti-Sm antibody. No infectious lesions were observed from CT, and inflammatory reaction was also negative. Recently, cases of hematological malignancies such as multiple myeloma or malignant lymphoma with LAHPS have been reported [8,9]. Chronic myelomonocytic leukemia, a disease in the same category as aCML, has been associated with autoimmune diseases [12]. The patient in the present case also suffered from aCML, so attention must be paid to the possibility of LAHPS concomitant with hematological neoplasms.

In conclusion, we have reported a rare case of gastrointestinal bleeding in an LAHPS patient complicated with aCML. In elderly LAHPS patients, complications of malignant neoplasms should be considered.

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Citation: Hiraga J, Harada Y, Fujikami T and Kagami Y. Gastrointestinal Bleeding in Lupus Anticoagulant- Hypoprothrombinemia Syndrome with Atypical Chronic Myeloid Leukemia, BCR-ABL1-Negative. Austin J Med Oncol. 2020; 7(1): 1049.