Challenges in the Diagnosis and Management of Non-Severe Hemophilia

Abstract

(1) Background: Mild and moderate hemophilia, synonymous with non-severe hemophilia (NSH), are of constant interest for the clinicians. Bleeding occurs usually after trauma, injury, surgery, or inhibitor development, sometimes leading to a shift of the clinical phenotype from mild to severe, even with life-threatening and unexpected outcomes. (2) Methods: We performed a retrospective observational study conducted on 112 persons with congenital coagulopathies, 26 of them with NSH, admitted to our clinic in the period 2000 to 2022. For the diagnosis, we used laboratory studies (complete blood cell count, coagulation assays, biochemistry, thromboelastography, genetic tests) and imaging investigations (X-ray, ultrasound, CT, MRI). We selected four cases confronted with pitfalls of diagnosis and evolution in order to illustrate the sometimes provocative field of NSH. (3) Results: Confronted with challenging cases with under-, missed or delayed diagnosis and severe consequences, we aimed at presenting four such selected cases with mild or moderate hemophilia, real pitfalls in our clinical activity. (4) Conclusions: In the field of NSH, if not timely recognized, tending sometimes to remain ignored by caregivers and patients themselves, we can be confronted with challenging diagnostic situations and life-threatening bleeds.

Patient perspective on living with mild hemophilia in Germany: results from a nationwide survey

“…The proportion of hemophilia types in our patient population examined (HA: 87.5% and HB: 12.5%; 40 answers) was in line with that of the population affected (HA: 80 to 85% and HB: 15 to 20%) ( 1 ). The median age at diagnosis reported here (6.0 years) was similar to other publications (2.4 to 6.5 years), ( 9 , 10 , 21 , 22 ), and the median factor activity at diagnosis (14%) was also in line with other findings (15%) ( 21 ). One patient indicated FVIII levels within the lower limit of normal ( 4 ), and medical history suggested a possible coagulopathy.…”

“…The main reasons for diagnosis in this survey, such as familial predisposition, bleeding episodes during/after a surgery or dental treatment, and increased hematoma frequency or intensity, were also reported by other publications ( 7 , 21 ). The diagnosis of mild hemophilia is often delayed compared to that of more severe phenotypes ( 7 , 9 , 18 ) and this delay is highly dependent on a country’s economic status ( 2 , 9 ). Patients unaware of their condition may neglect symptoms until late ( 7 , 9 ).…”

“…While occurring less frequently in patients with mild or moderate HA compared to the severe form, these conditions pose a lifelong risk ( 8 ). Inhibitors can increase the severity of bleeding episodes (7) and may even shift a mild phenotype to a severe one ( 9 ), thereby complicating the treatment ( 10 ). FIX inhibitors are rare (1.5 to 3% of patients) and are almost exclusively found in patients with severe HB ( 1 , 11 ), for whom an HB-specific formal clinical guidance may be lacking due the rarity of their condition ( 12 ).…”

“…Patients with mild hemophilia or their families may initially lack awareness of the disease ( 9 ), leading to a delay in diagnosis ( 7 ). Suspicion may only be raised upon severe symptom development or complications, such as prolonged bleeding episodes after medical interventions, resulting from inadequate management.…”

Nonsevere Hemophilia: The Need for a Renewed Focus and Improved Outcomes

“…Compared with severe hemophilia, spontaneous bleeding is less common in moderate hemophilia and relatively unusual in mild hemophilia 2 ; spontaneous bleeding is generally elicited by minor trauma and may present later in life. This, in addition to lack of awareness in health care providers (HCPs) and families, 5 often leads to delayed diagnosis. In PWNSH who have an established diagnosis, comprehensive assessment of family history is vital to enable identification of potentially affected family members and offer formal genetic counseling.…”