Dr. Deb Talukdar is a medical doctor from New Delhi, India. His research interest includes cancer therapeutics, Parkinson’s Disease, inflammatory and immunosuppressive drugs, COVID-19 predictive modeling and vaccination program, public health research associated with DHS and rare diseases such Pulmonary arterial hypertension (PAH). Previously, he was involved in AI research at Yale University. Currently, he is affiliated with All Saints University School of Medicine in Dominica.
The life expectancy of patients with hemophilia depends on whether they receive appropriate treatment. With appropriate treatment, their life expectancy is only about 10 years shorter than that of healthy men. The high rate of death before adulthood is due to inadequate treatment. Life expectancy also depends on whether the patient has other medical diseases. The mortality rate of patients with hemophilia is twice that of healthy men, and the mortality rate of those with severe hemophilia is 4 to 6 times higher. The life expectancy of people with hemophilia was short before scientists developed factor concentrates. A spike in the hemophilia mortality rate in the 1980s was due to hepatitis and human immunodeficiency virus (HIV) infection associated with therapy. Prompt and proper treatment can reduce the chronic complications of hemophilia, such as long-term severe joint damage, and the risk for life-threatening episodes of bleeding.¹
Outlook for Patients With Hemophilia
Patients with a diagnosis of hemophilia can live a relatively normal life as long as they receive adequate treatment. They must also be educated about their condition. Those with inhibitors in their bloodstream or with highly active immunity against clotting factors are considered to be high responders. They should be vaccinated against hepatitis A and B when they receive donated clotting factors. Minor cuts can be managed with gauze and pressure bandages. Treatment, which is critical to prolonging life expectancy, consists of recombinant factors or plasma-purified products. Severe complications can lead to episodes of bleeding.
Studies have shown that inhibitors may develop in one-third to one-fifth of patients with hemophilia A. Inhibitor development is less common in those with hemophilia B. Patients with hemophilia are tested for factor inhibitors because if they are present, factor replacement therapy is required. Immune tolerance induction is effective in 70% of persons with hemophilia A. Overall, patients are advised to discuss various options with their healthcare providers, undergo therapy, and maintain a healthful lifestyle to prolong life expectancy and reduce mortality.²
Life Expectancy of Patients With Acquired Hemophilia
Acquired hemophilia A (AHA) is a rare but life-threatening disease. A study was conducted to evaluate prognostic factors in AHA. Several factors were assessed, including age, sex, underlying conditions, treatment regimen, and inhibitor titer. The all-cause mortality rate in the patients studied was 21%. Factors associated with the development of AHA were advanced age, malignancies and autoimmune disorders, and pregnancy and the postpartum period. According to the study, a relatively high inhibitor titer indicated persistent hemophilia, but the difference was not statistically significant because it did not predict the odds of mortality. The study evaluated immunosuppressive therapy and death rates in the patient population. An extensive search was conducted to identify prior reports of treatment outcomes in patients with acquired hemophilia. A treatment regimen in which cyclophosphamide or azathioprine with a steroid, intravenous immunoglobulin, rituximab, and cyclosporine were taken simultaneously was administered to 4 different groups. The dosing, duration of treatment, and frequency of medication administration varied among the patients. On the basis of the study findings, it was recommended that all patients with hemophilia receive immunosuppressive therapy.³
Changing the Prognosis of Patients With Hemophilia
Another study, conducted in patients with classic hemophilia (hemophilia A), showed a striking decrease in life expectancy among severely affected patients. Knowledge of the multiple hereditary hemorrhagic disorders occurring among mildly affected individuals was lacking, as was knowledge of the laboratory procedures used to diagnose the disease and determine its severity. Classic hemophilia was often confused with Christmas disease (hemophilia B). It was assumed that the prognosis was identical in the 2 diseases. Faulty assumptions often led to incorrect estimates regarding median life expectancy and relative mortality risk. In certain subgroups, these led to a failure to estimate the relative risk for mortality. Information pertaining to age at onset of the symptoms of classic hemophilia was lacking. Hemophilic morbidity and mortality in the first year of life, delayed or missed diagnoses, and the prevalence of hemophilia in the national population were documented. For an accurate assessment of the prevalemce of hemophilia, the study recommended that a record of patient registries be kept and tests conducted in a number of hospitals.⁴
Acquired Hemophilia A Prognosis
A study of patients with AHA evaluated anti-factor VIII immunoglobulin A (anti-FVIII IgA) autoantibodies as a prognostic factor. The overall survival of patients who tested positive for anti-FVIII IgA autoantibodies was shorter than that of patients who tested negative. FVIII inhibitor titers do not correlate with anti-FVIII IgA autoantibody titers. These autoantibodies do not neutralize FVIII activity but rather maintain or deteriorate the hemophilia pathology. The prevalent subclasses of immunoglobulin G (IgG) were IgG1 and IgG4, and they demonstrated high apparent affinities and antibody titers. Anti-FVIII IgG subclasses correlated with FVIII inhibitor titers and antibody titers, indicating that they neutralize FVIII activity. None of the anti-FVIII IgG subclasses were significant predictors of outcome. The immune response of patients with a low affinity for IgG1 antibody was earlier than that of patients with a high affinity for IgG1 antibody clusters. This indicated the presence of circulating anti-FVIII IgA antibodies at the time of diagnosis and poor recurrence-free survival. Patients in the study showed IgA antibody titers above the median titer of patients in the study cohort. The prognosis of patients who have AHA with anti-FVIII IgA is poor.⁵
- Hemophilia prognosis and life expectancy. Hemophilia News Today. Accessed August 2, 2021.
- Hemophilia. Cleveland Clinic. Accessed August 2, 2021.
- Bitting RL, Bent S, Li Y, Kohlwes J. The prognosis and treatment of acquired hemophilia: a systematic review and meta-analysis. Blood Coagul Fibrinolysis. 2009;20(7):517-523. doi:10:1097/MBC.0b013e32832ca388.
- Jones PK, Ratnoff OD. The changing prognosis of classic hemophilia (factor VIII” deficiency”). Ann Intern Med. 1991;114(8):641-648. doi:10.7326/0003-4819-114-8-641.
- Tiede A, Hofbauer CJ, Werwitzke S, et al. Anti-factor VIII IgA as a potential marker of poor prognosis in acquired hemophilia A: results from the GTH-AH 01/2010 study. Blood. 2016;127(19):2289-2297. doi:10.1182/blood-2015-09-672774.
Reviewed by Harshi Dhingra, MD, on 8/10/2021.