Baylor University Medical Center Proceedings July 2017 - 343

Treatment of chronic lymphocytic leukemia/small
lymphocytic lymphoma presenting simultaneously
with acquired hemophilia and warm autoimmune
hemolytic anemia
Chelsea Williams, DO, Christian Cable, MD, and Julia Choi, MD

Since both acquired factor VIII inhibitor in non-hemophiliac patients and
warm autoimmune hemolytic anemia are uncommon disorders with no
case-controlled trials, managing these diseases can be challenging. We
present a case of a 75-year-old man in whom both diseases were present
simultaneously with life-threatening bleeding. This case is an example of
the successful initial management and long-term treatment of acquired
hemophilia A, warm autoimmune hemolytic anemia, and chronic lymphocytic leukemia/small lymphocytic lymphoma with rituximab, prednisone,
and cyclophosphamide.

n acquired factor VIII inhibitor in non-hemophiliac
patients has a mortality of 8% to 22% and has a low
occurrence rate of approximately 1 out of 1,000,000
people per year (1). Autoimmune hemolytic anemia is
also an uncommon disorder that occurs in 1 to 3 persons out
of 100,000 per year with a mortality of about 11% (2). Since
controlled trials are unavailable for both diseases because of
their rarity, management can be challenging, especially if the
diseases present simultaneously with life-threatening bleeding.
CASE PRESENTATION
A 75-year-old man with type 2 diabetes mellitus and chronic kidney disease was transferred to Scott & White Memorial
Hospital from an outside facility with weight loss, bruising,
and swelling of his left arm (Figure 1). An ultrasound of the
left upper extremity was concerning for a subcutaneous hemorrhage. A computed tomography scan of the chest, abdomen,
and pelvis was negative for hematoma but showed periaortic lymphadenopathy (largest 1 cm) and splenomegaly (20
cm), concerning for lymphoma. He had multiple laboratory
abnormalities including a hemoglobin of 6.6 g/dL, an activated partial thromboplastin time of 91.1 sec, undetectable
haptoglobin, elevated lactate dehydrogenase, and a positive
direct antiglobulin speciﬁc for IgG. Flow cytometry performed
on peripheral blood was consistent with chronic lymphocytic
leukemia (CLL). The white blood cell count of 5.4 and the
absolute lymphocyte count within normal limits at 2.42 made
the clinical diagnosis consistent with CLL/small lymphocytic
lymphoma (SLL). A Coombs test was positive for IgG, diagnosing warm autoimmune hemolytic anemia (WAHA). To
Proc (Bayl Univ Med Cent) 2017;30(3):343-345

Figure 1. Subcutaneous hemorrhaging in our patient with a factor VIII inhibitor.

evaluate the activated partial thromboplastin time, a mixing
study was performed and did not correct appropriately. The
factor VIII concentration was 0%, and the factor VIII inhibitor
titer was elevated at 18.4 Bethesda units/mL, consistent with
acquired hemophilia A (AHA). Bone marrow results (Figure
2) and immunohistochemical stains (Figure 3) corroborated
the diagnoses.
Initial treatment consisted of prednisone therapy (1 mg/kg
daily) and transfusion support with red blood cells. Recombinant factor VII was utilized for acute bleeding. The patient's
hemolysis resolved on prednisone, but he continued to be dependent on transfusions with progressive subcutaneous hemorrhaging. Cyclophosphamide (100 mg daily) and rituximab
therapy (375 mg/m2 weekly for 2 weeks) were initiated. One
week later, the patient's factor VIII concentration had improved
to 5%, and his factor VIII inhibitor titer had decreased to 1.5
Bethesda units/mL. He was continued on cyclophosphamide
and prednisone at discharge; 2 months later, he had a factor
VIII inhibitor titer of 0.25 Bethesda units/mL and factor VIII
activity of 34%. Factor VIII activity eventually normalized,
From the Department of Hematology/Oncology, Baylor Scott and White Health,
Temple, Texas.
Corresponding author: Chelsea Williams, DO, Department of Hematology/
Oncology, Baylor Scott and White Health, 2401 S. 31st Street, Temple, TX 76508
(e-mail: chelsea.williams@bswhealth.org).
343

Table of Contents for the Digital Edition of Baylor University Medical Center Proceedings July 2017