Hemophilia A is characterized by abnormally low factor VIII (FVIII) activity; common symptoms include bleeding in various parts of the body, such as the joints and the muscles. While hemophilia is typically diagnosed in childhood, acquired hemophilia A (AHA) is more commonly diagnosed in adults.
As its name suggests, this condition is acquired rather than congenital. We know that around 50% of cases are idiopathic, while other cases are associated with an identifiable cause, such as autoimmune diseases, infection, pregnancy, and cancer. Recently, reports have emerged of AHA triggered by COVID-19 infection.
Like congenital hemophilia, the main manifestation of AHA is hemorrhage—a key symptom in around 9 in 10 patients. Oftentimes, the bleeding can be severe, especially when the disease remains undiagnosed and the patient is treatment-naive.
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Another key difference between AHA and congenital hemophilia is that it affects both sexes, with or without a family history of bleeding. In contrast, congenital hemophilia exclusively affects males with an established family history of bleeding. Nevertheless, congenital and acquired hemophilia A are similar in that they are both driven by a reduction in FVIII activity.
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“However, the clinical manifestation is not identical; in classic congenital hemophilia, usually, spontaneous bleeding into joints is typical, while in AHA, type of bleeding is different which is massive subcutaneous blood extravasations and mucosal hemorrhages,” El Demerdash and colleagues wrote in The Egyptian Journal of Internal Medicine.
An Undermanaged Condition
AHA is an extremely rare and lethal condition that is underrepresented in the medical literature. According to El Demerdash and colleagues, there are no comparative clinical studies available concerning this condition. As a result, there is no consensus on how to quantify the severity of this illness upon presentation. Management depends largely on the clinical experience of individual physicians, meaning that there is significant heterogeneity in terms of how this condition is managed and described.
Another difficulty in diagnosing AHA is that it often occurs in elderly patients, in which polypathology and polypharmacy are common. As a result, when a patient’s hemoglobin levels drop significantly, physicians are more likely to review existing illnesses and medications to identify if any of them have inadvertently contributed to this finding.
In many cases, anemia is the result of occult bleeding. This is especially true in older men who are at a higher risk of colorectal cancer. Even if physicians fail to identify the source of the anemia, they are likely to treat it symptomatically via blood transfusions. This is often sufficient to bring up hemoglobin levels, and no further investigations are carried out.
“It is important that different specialists, like emergency specialists, specialists in internal medicine, hematologists, and oncologists, acquire a more complete knowledge of the clinical and laboratory features of this disease, allowing an early diagnosis crucial for the evolution of this coagulopathy,” Dulcetti and colleagues wrote.
AHA and Lung Cancer
In SN Comprehensive Clinical Medicine, Dulcetti and colleagues described the case study of an elderly patient with lung cancer who developed AHA. The 84-year-old man was admitted into the emergency department for acrocyanosis and right upper limb pain. He denied any traumatic incidents involving his right limb. He also reported having a 1-week history of dyspnea.
The patient had a previous history of right lower lobe adenocarcinoma, which had been treated with chemotherapy and was under follow-up at a different hospital. In 2018, he suffered from acute coronary syndrome. He also had a history of chronic obstructive pulmonary disease (COPD) and hypertension.
The patient had presented to his doctor 2 weeks prior and was diagnosed with a large hematoma of the right upper limb. As a result, his doctor advised him to stop taking clopidogrel. Nevertheless, pain in the limb persisted.
Upon presentation, the patient appeared to be pale. His right upper limb was edematous. Laboratory investigations revealed normocytic normochromic anemia (hemoglobin: 7.2 g/dL). He had a prothrombin time (PT) of 12.10 s, an international normalized ratio (INR) of 1.08, and an activated partial thromboplastin time (aPTT) of 2.24 (70 s).
The immediate treatment was a transfusion of 1 U of concentrated red blood cells. A chest and upper limb CT angiogram demonstrated an actively bleeding collection in the right bicep. In addition, bleeding was detected in the VII hepatic segment from a focal hypodensity of 3.5 cm.
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“An upper limb arteriography and a superselective catheterization was performed, with subsequent embolization,” the authors of the report wrote.
Nevertheless, the patient’s hemoglobin and coagulation values remained unstable, and blood chemistry tests were repeated. These revealed hemoglobin levels of 7.1 g/dL (after blood transfusion). His PT was 12.08 s, INR was 1.07, and aPTT was 2.51 (79 s).
Upon further history-taking from his family members, his physicians learned that he had previously made 4 trips to the hospital due to acute anemia in the absence of notable trauma. His physicians initiated a new round of transfusions. A thorough coagulation screen revealed isolated FVIII deficiency, upon which he was diagnosed with AHA. The patient decided against further medical care and chose home palliative therapy.
Despite the initial difficulties that one might have in diagnosing AHA, adequate suspicions can and should be raised when presented with a coagulation profile suggestive of hemophilia; a thorough investigation should then be initiated to identify the cause for such an aberration, which when carried out correctly should lead to detection of AHA. Although AHA carries with it a significant disease burden, timely medical intervention can prevent further deterioration in quality of life and extend life expectancy.
References
Dulcetti A, Bruscia C, Malena DM, et al. Acquired hemophilia in an elderly patient with non-small cell lung cancer: a case report. SN Compr Clin Med. 2023;5(1):7. doi:10.1007/s42399-022-01330-x
El Demerdash DM, Ayad A, Tawfik N. Acquired hemophilia A (AHA): underreported, underdiagnosed, undertreated medical condition. Egypt J Intern Med. 2022;34(1):12. doi:10.1186/s43162-021-00074-9
