Late Replacement Therapy Tied to Poor Outcomes Following Bleeds
Serious bleeds are often a fatal complication in people with hemophilia if not managed early, a 10-year study from Senegal shows.
These findings highlight the need for prompt diagnosis of severe bleeding and early administration of replacement therapy to lower the risk of mortality. In resource-limited countries, increasing patients’ and their families’ awareness of life-threatening bleeding is key to lessen its severity.
The study, “Life-threatening bleeding in patients with hemophilia (PWH): a 10-year cohort study in Dakar, Senegal,” was published in the journal Hematology.
People with hemophilia A and B lack specific proteins that are essential for blood clot formation and preventing excessive bleeding. Factor VIII (FVIII) is missing or is defective in people with type A, while people with hemophilia B lack factor IX (FIX).
Patients with severe hemophilia are at risk of life-threatening bleeding, with bleeds affecting the central nervous system (CNS, brain and spinal cord) being the most serious.
While advances in past decades have reduced the risk of life-threatening bleeding in patients living in the developed world, this risk still exists in countries where treatment access is limited.
In this observational study, researchers at the Hemophilia Treatment Center, National Blood Transfusion Center, in Dakar, Senegal, assessed the incidence, risk factors, treatment, and outcome of Senegalese hemophilia patients with life-threatening bleeds.
In total, they analyzed data from 274 patients (mean age of 16.45 years) — 241 (87.9%) with hemophilia A and 33 (12.1%) with hemophilia B — who were followed for 10 years (2012-21) at the Dakar Hemophilia Treatment Center. A family history of hemophilia was found in 151 patients.
The mean annual bleeding rate (ABR) was 1.65, but for patients with severe disease the ABR was 2.83. Over half of the patients (79.2%) received replacement therapy with clotting factors.
Inhibitors — neutralizing antibodies that may render conventional replacement therapies ineffective — were detected in 13 out of 274 patients (4.7%). All patients were negative for HIV and hepatitis C virus.
Over the course of 10 years, researchers observed 31 cases of severe bleeding in 22 individuals (mean age 15.6 years), corresponding to an incidence of 8.03%. Seventeen of the 22 patients had severe hemophilia (77.3%), and the remaining five (22.7%) had moderate disease.
The prevalence of life-threatening bleeds was higher among patients on on-demand treatment compared with those on low-dose preventive therapy (11.8% vs. 5.3%). Only one patient with a life-threatening bleeding was positive for inhibitors.
Bleeds in the CNS were the most frequent and accounted for 54.8% of all life-threatening bleeds when considering the whole group. Patients often had a delay of 78.9 hours since they developed the first signs before reaching the emergency room.
Sixteen of the 22 patients received emergency replacement therapy with clotting factors, while six remained untreated. Three patients underwent physiotherapy for an average of seven months.
Thirteen patients survived, and 11 reached complete remission. Two patients achieved partial remission with sequelae, or physical consequences. The mortality rate of life-threatening bleeds was 0.32 deaths per 100 person-years, and cerebral hemorrhage was the major cause of death (77.7%).
Person-years is a composite measure that reflects both the number of people and the amount of time each person was followed. For example, 100 person-years pertains to data gathered by following 100 people for one year.
Researchers observed a significant correlation between late administration of replacement therapy — two hours after the start of symptoms — and mortality. The time from diagnosis to death averaged at 23.7 hours (range from one hour to five days).
Overall, these findings show that life-threatening bleeding “is a serious complication in hemophilia if not managed early,” the researchers wrote.
“CFC [clotting factor concentrates] substitution is needed as soon as the diagnosis is suspected to lower the risk of morbidity and mortality. A good awareness of patients and their families would further reduce this incidence,” they wrote.