A 73-Year-Old Man With Extensive Bruising

Lauren Banaszak, MD

@LaurenBzak, @uw_IMresidency
Hematology/Oncology Fellow, University of Wisconsin-Madison
Madison, WI

A 73-year-old man presented to his primary care provider for evaluation of easy bruising. He was in his usual state of health until 10 days prior to presentation when he noticed bruising of his bilateral upper extremities associated with mild swelling and discomfort. He initially attributed this to musculoskeletal pain from doing yardwork, but the bruising and pain did not improve.

The patient denied any personal or family history of bleeding disorders. His medical history was otherwise remarkable for osteoarthritis of the bilateral knees and obesity. He underwent a tooth extraction and an inguinal hernia repair several years ago, which were not complicated by bleeding. He reported taking ibuprofen sparingly in the 10 days prior for his upper extremity pain but denied any other new medications. He was not on any prescription medications, other over-the-counter medications, or herbal supplements. He otherwise denied fevers, chills, night sweats, change in weight, shortness of breath, chest pain, abdominal pain, change in urination, new joint pain, skin rashes, and other bleeding symptoms including epistaxis, mucosal bleeding, hematemesis, hemoptysis, melena, hematochezia, and hematuria.

Upon presentation, vital signs were normal. His physical examination was notable for scattered large ecchymoses involving the right upper arm, left upper arm, chest, and abdomen. A comprehensive metabolic panel was within normal limits, and the remainder of the laboratory workup was remarkable for the following:

	Value	Range
White blood cell count	5.5 K/μL	3.8-10.5 K/μL
Hemoglobin	15.2 g/dL	13.6-17.2 g/dL
Platelet count	236 K/μL	160-370 K/μL
International normalized ratio	1.0	0.9-1.2
Activated partial thromboplastin time (APTT)	75.1 seconds	28-37 seconds
APTT after mixing study	62.0 seconds	28-37 seconds
Factor VIII activity	3.2%	60-180%
Fibrogen	219 mg/dL	200-400 mg/dL

What is the most appropriate next step in treating this patient?

Answer: C

This patient has acquired hemophilia A due to autoantibodies directed against coagulation Factor VIII. Given the absence of active bleeding, he should be treated with immunosuppression using steroids to eliminate the autoantibody and minimize bleeding risk.

Acquired hemophilia A is an uncommon disorder that most often presents in the elderly with a slight male predominance. While acquired hemophilia A can be associated with pregnancy, autoimmune disorders, and malignancy, approximately half of cases are idiopathic. Most patients present with bleeding symptoms in the absence of a previous history of abnormal bleeding. In contrast to congenital hemophilia, hemarthroses are uncommon, and most patients present with spontaneous subcutaneous bleeding in atypical locations such as the upper extremities, chest, and abdomen. Mucosal bleeding (gastrointestinal, urogenital, and lung) and intracranial bleeding can also occur. A small minority of patients present with isolated laboratory abnormalities and no bleeding.¹

APTT measures the activity of the common and intrinsic coagulation pathways. Isolated elevation in APTT can be caused by factor deficiency (Factors VIII, IX, XI, or XII), exposure to certain medications (such as heparin), or can be acquired due to a lupus anticoagulant or more rarely via a direct Factor VIII inhibitor. An isolated prolonged APTT in a patient without a personal history of bleeding should raise suspicion for acquired Factor VIII deficiency, leading to acquired hemophilia A. To distinguish an acquired inhibitor against Factor VIII from a factor deficiency, a mixing study is performed by combining equal volumes of pooled normal plasma with the patient’s plasma and then repeating the APTT test. An APTT that remains prolonged after mixing with normal plasma suggests the presence of a Factor VIII inhibitor, whereas correction of the APTT after mixing with normal plasma suggests a Factor VIII deficiency. If the APTT is corrected, it is important to incubate the sample for one or two more hours to assess whether APTT would prolong again, indicating a slow inhibitor that had initially corrected. The Bethesda assay can be used to identify and quantify autoantibody titer level.²

The first step in treating acquired hemophilia A is to identify and manage any acute bleeding. A detailed history, a comprehensive physical exam, and a review of medications, prior surgeries, and recent and chronic medical problems can provide insightful information about the potential causes of the acquired deficiency. Diagnostic laboratory work-up includes CBC and coagulation studies. First-line therapy depends on the degree of illness. In the absence of acute hemorrhage, immunosuppression therapy should be initiated to reduce bleeding risk and induce a remission. First-line therapy should be individualized based on prognostic information at the time of diagnosis. For patients with a Factor VIII activity level higher than 1 percent and titer level lower than 20 Bethesda units, treatment should consist of high-dose steroids for three to four weeks. For patients with a Factor VIII activity level lower than 1 percent or titer level higher than 20 Bethesda units, treatment should consist of steroids plus either cyclophosphamide or rituximab for three to four weeks.³

More serious bleeding may require bypassing agents, such as recombinant activated Factor VII and activated prothrombin concentration complex, or recombinant factor VIII. Desmopressin is not recommended in the management of bleeding associated with acquired hemophilia A.³

This patient has no evidence of active bleeding. Thus, recombinant Factor VIII or recombinant activated Factor VII are not indicated at this time. A Factor VIII autoantibody was ultimately detected at a titer level of 10 Bethesda units. The patient should thus be treated with steroid monotherapy for three to four weeks.

Sborov DW, Rodgers GM. . Br J Haematol. 2013;161:157-165.
Franchini M, Lippi G. . Blood. 2008;112:250-255.
Tiede A, Collins P, Knoebl P, et al. . Haematologica. 2020;105:1791-1801.

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