Is the Detection of Factor IX Inhibitors in Hemophilia B Orphan than Factor VIII Inhibitors in Hemophilia A? A Concise, Systematic Review

2020 ◽  
Vol 20 (3) ◽  
pp. 185-190
Author(s):  
Hassan Mansouritorghabeh ◽  
Seyedeh T. Mohades
Keyword(s):  
Factor Viii ◽  
Hemophilia A ◽  
Factor Ix ◽  
Hemophilia B ◽  
World Federation ◽  
Health Provider ◽  
Comprehensive Review ◽  
Significant Challenge ◽  
The World ◽  
The Mean

Objective: Development of inhibitors in hemophilia A and B comprise significant challenge for patients, hematologists, and health provider systems. It has recommended by the World Federation of Hemophilia (WFH) to check inhibitors every 3-4 months. The incidence of inhibitor in hemophilia B is lower than hemophilia A. Here, it tried to unravel whether the detection of inhibitors in hemophilia B neglected compared to hemophilia A or not? Methods: A comprehensive review carried out using six international and local medical search engines on published contributions about inhibitors in hemophilia A and B in Iran. Results: From 699 titles, 12 relevant papers were selected. The mean of factor VIII inhibitors in hemophilia A was 14.8%. The mean of factor IX inhibitors in hemophilia B was 6%. The minimum and maximum reported percentages of factor VIII inhibitors were 4% and 19.6%, while the minimum and maximum of reported percentages of factor IX inhibitors were 0% and 11.8%, respectively. The inhibitors in hemophilia A had reported in 6 papers. One paper had covered the inhibitors in hemophilia B. There were five papers on inhibitors in both hemophilia A and B. The comparison between the reported patients showed that 3020 patients with hemophilia A and 314 patients with hemophilia B had studied. Conclusion: Consistent with the lower frequency of hemophilia B and the lower development of inhibitors in hemophilia B compared to hemophilia A, it was concluded that hemophilia B had not neglected in Iran. It seems to be rational that each country, check rates of detection of inhibitors in hemophilia B to identify whether it has neglected or not.

Prophylactic Infusion Regimens in the Management of Hemophilia

1999 ◽  
Vol 82 (08) ◽  
pp. 525-530 ◽  
Author(s):  
Rolf Ljung
Keyword(s):  
Factor Viii ◽  
Prophylactic Treatment ◽  
Hemophilia A ◽  
The United States ◽  
Factor Ix ◽  
Advisory Council ◽  
World Health ◽  
World Federation ◽  
Severe Hemophilia ◽  
The World

IntroductionThe goal of prophylactic treatment of hemophilia is to convert the severe form of the disorder into a milder form by administration of factors VIII or IX. The rationale behind this is that chronic arthropathy, the hallmark of hemophilia after repeated bleedings, is less frequent and less severe in moderate hemophilia (i.e., factor VIII or factor IX concentrations of 1% to 4% of normal) than in severe hemophilia (i.e., factor VIII/factor IX concentrations lower than 1% of normal).1 Keep in mind, however, that prophylactic treatment also provides protection from all other forms of hemorrhage that may occur spontaneously or as a result of trivial trauma in the untreated hemophilic child. Today, prophylactic treatment is available to only a few hemophilia patients in the world, although it is recommended by the World Health Organization (WHO) and the World Federation of Haemophilia (WFH): “Since the main goal is to prevent joint bleeding and its sequelae, prophylaxis should be considered optimal management for persons with severe hemophilia A or B (i.e., with basal factor VIII and/or factor IX levels <1% of normal). Treatment should be started at the age of 1-2 years and be continued indefinitely. Where prophylaxis is not feasible or appropriate, on-demand therapy should be given.”2 In the United States, the Medical and Scientific Advisory Council of the National Hemophilia Foundation has recommended that “prophylaxis should be considered the optimal therapy for children with severe hemophilia A or B.”3 The aim of this chapter is to discuss prophylactic infusion regimens in the management of hemophilia.

Prevalence of Coronary Heart Disease in Patients with Hemophilia: a Nationwide Study in Brazil.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3495-3495
Author(s):  
Claudia Bley ◽  
Fabio P S Santos ◽  
Antonio E P Pesaro ◽  
Ricardo Helman ◽  
Sergio A Oliveira ◽  
...  
Keyword(s):  
Risk Factors ◽  
Surgical Treatment ◽  
Factor Viii ◽  
Antiplatelet Therapy ◽  
Hemophilia A ◽  
Factor Ix ◽  
Hemophilia B ◽  
Factor Activity ◽  
Positive History ◽  
History Of

Abstract Abstract 3495 Poster Board III-432 Background It is well known that patients with hemophilia (both A and B) have a lower incidence of coronary artery disease (CAD). However, patients with hemophilia may develop atherosclerosis, and with increases in life expectancy it is possible that the incidence of CAD may increase in these patients. There are no studies analyzing the prevalence of CAD in patients with hemophilia and possible risk factors. Aims To determine the prevalence of CAD in patients with hemophilia treated in Brazil. Methods All patients with hemophilia in Brazil receive therapy with Factor VIII or Factor IX at government-designed hemophilia centers. We thus contacted all centers in Brazil by e-mail and information from databases concerning health information for all patients was reviewed by the responsible physician at each center. A questionnaire about risk factors for CAD and history of coronary events was sent to patients that had a positive history of CAD. Results There are 6,881 patients registered with a diagnosis of hemophilia A and 1,291 patients with a diagnosis of hemophilia B in Brazil. Fifty-six percent of hemophilia centers answered the query, and information on 71.7% of patients with hemophilia A (4,934 patients) and 61.4% of patients with hemophilia B (792 patients) was reviewed. There were only 3 patients (0.05%) with a positive history of CAD. Their clinical characteristics are summarized in Table 1. During surgical treatment for CAD, replacement with Factor VIII and Factor IX was done by continuous infusion to increase Factor activity to 80-100%. Antiplatelet therapy was used in all patients at some point, and one patient (#1) developed hemarthrosis after two months of ASA. Patient #3 did not start antiplatelet therapy after CABG, and developed thrombosis of the graft. ASA and clopidogrel were started after percutaneous coronary angioplasty. Conclusion We found a very low incidence of CAD in hemophiliac patients, even after doing a nationwide survey that included more than 5,000 patients. No information about risk factors can be gleaned due to the small number of patients. Surgical treatment after increasing factor activity appears to be safe in such patients. Despite a theoretical risk for increased bleeding, therapy with antiplatelet agents appears to be necessary in hemophiliac patients with CAD. Disclosures: No relevant conflicts of interest to declare.

Immunologic aberrations, HIV seropositivity and seroconversion rates in patients with hemophilia B

Blood ◽  
1987 ◽  
Vol 70 (1) ◽  
pp. 276-281
Author(s):  
DB Brettler ◽  
F Brewster ◽  
PH Levine ◽  
A Forsberg ◽  
S Baker ◽  
...  
Keyword(s):  
Factor Viii ◽  
Male Volunteer ◽  
Hemophilia A ◽  
High Titer ◽  
Factor Ix ◽  
Hemophilia B ◽  
Clotting Factor ◽  
Immunodeficiency Virus ◽  
And Function ◽  
Factor Concentrate

Because there have been reports that factor IX concentrate is less immunosuppressive and therefore factor IX users have less immunologic aberrations, we have studied a group of 22 patients with hemophilia B and six patients with factor VIII deficiency and high titer inhibitors with respect to lymphocyte numbers and function, human immunodeficiency virus (HIV) serology, and factor usage. This group was compared to 111 patients with hemophilia A and a group of 28 healthy male volunteer controls. When the study began in 1983, the majority of patients with hemophilia B and with higher titer factor VIII inhibitors were seronegative, 77% and 83% respectively, as compared to only 30% of patients with hemophilia A. At that time the factor IX users also had milder immune aberrations than the hemophilia A group. However, with time and increasing clotting factor concentrate usage, seroconversion and more striking abnormalities in immune function have occurred in the hemophilia B group. In a subgroup of 16 patients with hemophilia B studied twice, the incidence of seropositivity increased from 31% in 1983 to 69% in 1985. We thus conclude that factor IX concentrate in itself is not less immunosuppressive than factor VIII concentrate. Seroconversion in factor IX concentrate users appears to be lagging behind seroconversion in factor VIII concentrate users, perhaps secondary to the lower cumulative dosage of concentrate that patients with hemophilia B utilize.

scholarly journals Collected Experience of the Pennsylvania Hemophilia Program

1977 ◽  
Author(s):  
S.S. Shapiro ◽  
M.E. Eyster ◽  
J. Lewis
Keyword(s):  
Factor Viii ◽  
Hemophilia A ◽  
Severe Disease ◽  
Factor Ix ◽  
Hemophilia B ◽  
Home Therapy ◽  
Product Usage ◽  
Number Of Patients ◽  
Total State ◽  
Actual Prevalence

The Pennsylvania Hemophilia Program was initiated in March 1973, with the establishment of 9 Hemophilia Centers throughout the state. From an initial enrollment of 150, the number of patients has grown to 669 as of October 1976. Of these, 491 have Hemophilia A and 91 have Hemophilia B, a prevalence rate of 4.2 and 0.76 per 100,000, respectively in the total state population of some 11,800,000. A total of 210 patients (36%) with Hemophilia A or B are on home therapy programs. Two hundred fifty-five patients with Hemophilia A (52%) have severe disease, of whom 160 (63%) are on home therapy. Thirty-six patients with Hemophilia B (40%) have severe disease, of whom 22 (61%) are on home therapy. The remaining patients are treated in-center as necessary. Thirty-seven patients (7.5%) with Hemophilia A have inhibitors to Factor VIII, while only 1 of 91 patients with Hemophilia B has an inhibitor to Factor IX. Total Factor VIII and Factor IX usage for hemophiliacs in the past year was 15,040,000 and 1,282,000 biological units, respectively. At current prices, this represents $1.5 million for Factor VIII and approximately $150,000 for Factor IX. The average annual use of Factor VIII in severe Hemophilia A, excluding surgery, was 44,300 units/patient for patients on home therapy and 32,000 units/patient for patients on Center therapy. These figures are roughly comparable when corrected for patient age (14% of home therapy patients but 28% of Center therapy patients under the age of 10). These observations suggest that the actual prevalence rates of Hemophilia A and B are lower than previously quoted, that more patients with milder disease exist than expected and that home and Center therapy require equal product usage.

MOLECULAR ANALYSIS OF COAGULATION FACTOR VIII AND IX GENES BY DNA PROBES

1987 ◽  
Author(s):  
C de la Salle ◽  
M J Baas ◽  
L Grunebaum ◽  
R Gialeraki ◽  
T Mandalaki ◽  
...  
Keyword(s):  
Factor Viii ◽  
Hemophilia A ◽  
Cdna Probe ◽  
Coagulation Factor ◽  
Molecular Study ◽  
Large Deletion ◽  
Factor Ix ◽  
Hemophilia B ◽  
Factor Viii Gene ◽  
Genomic Probe

About 250 individuals belonging to 44 families with hemophilia A or B were studied in our laboratory. The detection of carriers was first established by pedigree analysis of each family . and coagulation and immunological assays of factor VIII or IX. The availability of specific probes for the molecular study of these two genes makes possible a diagnosis with certainty in the case of informative families. 25 families of hemophilia A were studied. For each person, blood was collected into EDTA and leucocyte DNA was extracted, digested by restriction endonucleases, electrophoresed in 0.9 % agarose gels and transferred to nitrocellulose filters by Southern blotting. Two probes were used for the analysis of factor VIII gene. The St 14 probe (J.L. Mandel) located on the q28 region of the X chromosome and closely linked to the gene, determines a restriction fragment length polymorphism (RFLP) when the DNA is digested by the enzyme TaqI. The p114-12 genomic probe (Genentech) corresponding to the exons 17 and 18 of the factor VIII gene, reveals a RFLP in the DNA digested by the enzyme BclI. 19 families -of hemophilia B were studied. A total factor IX cDNA probe was used for the screening of potential deletions in the case of hemophiliacs with circulating antibodies. A genomic probe containing the exons II, III and IV of factor IX was used to detect the TaqI RFLP. For the study of factor VIII gene, the extragenic probe St 14 gives a very high percentage of informativity (about 90 %) but recombination can occur between the probe and the gene. The p 114-12 probe, which is used to confirm the results given by the St 14 probe, gives about 20 % informativity. In our study, we were able to diagnose carrier state with certainty in 92 % of the families. For hemophilia B, the genomic probe gives about 40 % informativity. A large deletion of the region of the factor IX gene has been found in one family and remains to be mapped. In conclusion, carrier detection and prenatal diagnosis can be established with certainty by molecular studies in most cases of hemophilia A using the St 14 probe, with a 5 % risk of recombination when the BclI RFLP cannot confirm. This diagnosis is possible in about 40 % of the cases of hemophilia B.

scholarly journals Immunologic aberrations, HIV seropositivity and seroconversion rates in patients with hemophilia B

Blood ◽  
1987 ◽  
Vol 70 (1) ◽  
pp. 276-281 ◽  
Author(s):  
DB Brettler ◽  
F Brewster ◽  
PH Levine ◽  
A Forsberg ◽  
S Baker ◽  
...  
Keyword(s):  
Factor Viii ◽  
Male Volunteer ◽  
Hemophilia A ◽  
High Titer ◽  
Factor Ix ◽  
Hemophilia B ◽  
Clotting Factor ◽  
Immunodeficiency Virus ◽  
And Function ◽  
Factor Concentrate

Abstract Because there have been reports that factor IX concentrate is less immunosuppressive and therefore factor IX users have less immunologic aberrations, we have studied a group of 22 patients with hemophilia B and six patients with factor VIII deficiency and high titer inhibitors with respect to lymphocyte numbers and function, human immunodeficiency virus (HIV) serology, and factor usage. This group was compared to 111 patients with hemophilia A and a group of 28 healthy male volunteer controls. When the study began in 1983, the majority of patients with hemophilia B and with higher titer factor VIII inhibitors were seronegative, 77% and 83% respectively, as compared to only 30% of patients with hemophilia A. At that time the factor IX users also had milder immune aberrations than the hemophilia A group. However, with time and increasing clotting factor concentrate usage, seroconversion and more striking abnormalities in immune function have occurred in the hemophilia B group. In a subgroup of 16 patients with hemophilia B studied twice, the incidence of seropositivity increased from 31% in 1983 to 69% in 1985. We thus conclude that factor IX concentrate in itself is not less immunosuppressive than factor VIII concentrate. Seroconversion in factor IX concentrate users appears to be lagging behind seroconversion in factor VIII concentrate users, perhaps secondary to the lower cumulative dosage of concentrate that patients with hemophilia B utilize.

An immunological Method for Detection of the Carrier of Hemophilia B

1976 ◽  
Vol 36 (02) ◽  
pp. 441-450 ◽  
Author(s):  
Matsuzo Matsuoka ◽  
Masakazu Ito ◽  
Kaoru Takahashi ◽  
Nobuo Sakuragawa
Keyword(s):  
Factor Viii ◽  
Hemophilia A ◽  
Neutralization Test ◽  
High Specificity ◽  
Factor Ix ◽  
Hemophilia B ◽  
Precipitation Reaction ◽  
Immunological Study ◽  
Severe Hemophilia ◽  
Heterologous Antibody

SummaryThis paper presents the results of an immunological study of hemophilia B and its carriers which used two kinds of antibodies, a heterologous antibody of high specificity and a homologous antibody developed in a patient with severe hemophilia B.1. The factor IX related antigen for hemophilia B could be determined by a neutralization test and not by a precipitation reaction.2. The activity of factor IX in a definite carrier of hemophilia B was significantly lower than that of factor VIII in a definite carrier of hemophilia A.3. In hemophilia B, there were no differences between the factor IX antigen determined by either the heterologous rabbit antibodies or the homologous antibodies. And there was no discrepancy between the factor IX antigen and the factor IX activity. Therefore, we cannot use this discrepancy for the detection of a carrier of hemophilia B.4. However, there was a discrepancy between the factor IX antigen determined by the neutralization test and the factor IX procoagulant activity in the patients of both hemophilia BM and hemophilia B+. The identical results were obtained in the cases of carriers of both hemophilia BM and hemophilia B+. These facts are very useful for the detection of carriers of hemophilia BM and hemophilia B+.

scholarly journals Factor VIII products: key aspects of development, clinical research and use (part 1)

2021 ◽  
Vol 21 (1) ◽  
pp. 39-49
Author(s):  
Zh. I. Avdeeva ◽  
A. A. Soldatov ◽  
V. P. Bondarev ◽  
V. D. Mosyagin ◽  
V. A. Merkulov
Keyword(s):  
Factor Viii ◽  
Replacement Therapy ◽  
Blood Clotting ◽  
Hemophilia A ◽  
Clinical Manifestations ◽  
Current Data ◽  
Clotting Factor ◽  
World Federation ◽  
The World ◽  
Blood Clotting Factor

According to the World Federation of Hemophilia (WFH), there are currently about 400 thousand patients with hemophilia in the world. Severe clinical manifestations of the disease associated with a genetically determined deficiency of blood clotting factor activity require continuous replacement therapy with blood clotting medicines. Long-term use of protein-based medicines often leads to the formation of specific antibodies, which causes a decrease in or loss of efficacy of the medicine or results in severe adverse reactions, including anaphylaxis. Therefore, it is important to search for new optimal approaches to hemophilia treatment, which requires the development of new blood clotting factor products, improvement of the production technology for already authorised products, as well as the use of non-factor products. The aim of the study was to present the results of the analysis of key issues related to the development and characteristics of plasma-derived and recombinant factor VIII products, new approaches to hemophilia A treatment, including the use of non-factor products. The review summarises current data on the etiology, clinical manifestations, and complications of hemophilia A treatment. It provides information on the blood clotting factor products (plasma-derived and recombinant) used as replacement therapy. It also provides information on advanced research projects for the development of new biotechnology-derived products which have good prospects of successful clinical use.

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