Hemophilia B

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Retrieved

2021-01-23

Source

Orphanet

Trials

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Genes

F9, F8, COX8A, AK3, AAVS1, F2, F3, EGF, ALB, F5, SMUG1, CCHCR1, EBP, EIF2AK1, AMT, CCRL2, ST14, TFPI, IFI30, TNFRSF11A, SACM1L, FAM72B, KRT20, DCXR, POLE3, SERHL, AASDHPPT, TP53, RN7SL263P, NBEAL1

F9, F8, COX8A, AK3, AAVS1, F2, F3, EGF, ALB, F5, SMUG1, CCHCR1, EBP, EIF2AK1, AMT, CCRL2, ST14, TFPI, IFI30, TNFRSF11A, SACM1L, FAM72B, KRT20, DCXR, POLE3, SERHL, AASDHPPT, TP53, RN7SL263P, NBEAL1, RIOX1, HPS6, FAM72A, RIOX2, VIPR1, SMN2, TLR4, FCGRT, CCT, MS4A1, CD38, CFTR, CGA, CTLA4, DBP, EMD, F11, FGG, SPRR2A, G6PD, GAD1, GCY, HLA-A, IL10, KRT31, MNT, TNFRSF11B, SOX3, H3P11

Drugs

Adeno associated virus with modified transthyretin and sequence encoding factor IX variant gene, Adeno-associated viral vector containing the human factor IX gene, Albutrepenonacog alfa ( IDELVION )

Adeno associated virus with modified transthyretin and sequence encoding factor IX variant gene, Adeno-associated viral vector containing the human factor IX gene, Albutrepenonacog alfa ( IDELVION ), Anti-inhibitor coagulant complex ( FEIBA ), Antihemophilic factor / Von Willebrand factor complex (human) ( ALPHANATE, HUMATE -P ), Desmopressine acetate ( DESMOPRESSIN ACETATE AVENTIS BEHRING L.L.C., OCTIM, MINIRIN ), Eftrenonacog alfa ( ALPROLIX ), Fidanacogene elaparvovec, Fitusiran, Human coagulation factor IX (antihemophilic B factor) ( BETAFACT, ALPHANINE, NONAFACT ), Humanised monoclonal IgG4 antibody against tissue factor pathway inhibitor, Lentiviral vector encoding human coagulation factor IX, Long acting recombinantFactor VIIa-CTP3, Marzeptacog alfa (activated), Moroctocog alpha ( REFACTO AF ), Octocog alpha ( ADVATE, HELIXATE NEXGEN, KOGENATE BAYER, KOVALTRY, IBLIAS ), Pegylated recombinant factor VIIa, Pegylated recombinant human factor IX ( REFIXIA ), Recombinant adeno-associated viral vector containing a codon-optimized Padua derivative of human coagulation factor IX cDNA, Recombinant coagulation factor VIIa (rFVIIa) ( NOVOSEVEN, NOVOSEVEN RT ), Recombinant factor VIIa modified with three terminal repeats derived from the beta chain of human chorionic gonadotropin, Recombinant fusion protein linking human coagulation factor VIIa with human albumin (rVIIa-FP), Sequence-modified human recombinant factor VIIa, Vatreptacog alfa (activated), nonacog alfa ( BENEFIX ), nonacog gamma ( RIXUBIS ), recombinant adeno-associated viral vector serotype S3 containing codon-optimised expression cassette encoding human coagulation factor IX variant, recombinant human factor IX protein modified with three point mutations

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Hemophilia B is a form of hemophilia (see this term) characterized by spontaneous or prolonged hemorrhages due to factor IX deficiency.

Epidemiology

Prevalence is estimated at around 1 in 30,000 males. Hemophilia primarily affects males, but a symptomatic form of hemophilia B in female carriers (see this term) has also been described with a generally milder clinical picture.

Clinical description

In general, onset of the bleeding anomalies occurs when affected infants start to learn to walk. The severity of the clinical manifestations depends on the extent of the factor IX deficiency. If the biological activity of factor IX is below 1%, the hemophilia is severe and manifests as frequent spontaneous hemorrhage and abnormal bleeding as a result of minor injuries, or following surgery or tooth extraction (severe hemophilia B; see this term). If the biological activity of factor IX is between 1% and 5%, the hemophilia is moderately severe with abnormal bleeding as a result of minor injuries, or following surgery or tooth extraction but spontaneous hemorrhage is rare (moderately severe hemophilia B; see this term). If the biological activity of factor IX is between 5 and 40%, the hemophilia is mild with abnormal bleeding as a result of minor injuries, or following surgery or tooth extraction but spontaneous hemorrhage does not occur (mild hemophilia B; see this term). Bleeding most often occurs around the joints (hemarthroses) and in the muscles (hematomas), but any site may be involved following trauma or injury. Spontaneous hematuria is a fairly frequent and highly characteristic sign of the disorder.

Etiology

Hemophilia B is caused by mutations in the F9 gene (Xq27) encoding coagulation factor IX. Diagnosis is suspected on the basis of coagulation tests revealing prolonged blood coagulation times and can be confirmed by specific measurements of factor IX levels.

Differential diagnosis

The differential diagnosis should include von Willebrand disease (see this term) and other coagulation anomalies leading to prolonged blood coagulation times.

Antenatal diagnosis

Prenatal diagnosis is feasible through molecular analysis of chorionic villus samples. Coagulation factor assays can also be carried out on venous and umbilical cord blood samples.

Genetic counseling

Hemophilia B is transmitted in an X-linked recessive manner.

Management and treatment

Treatment revolves around substitution therapy with plasma derivatives or genetically engineered recombinant alternatives. Treatment may be administered after a hemorrhage (treatment on demand) or to prevent bleeding (prophylactic treatment). The most frequent complication is the production of inhibitory antibodies against the administered coagulation factor. Surgical interventions, most notably orthopedic surgery, may be carried out but should be conducted in specialized centers.

Prognosis

Historically, the disease course is severe and, left untreated, severe hemophilia B is generally fatal during childhood or adolescence. Insufficient or incorrect treatment of recurrent hemarthroses and hematomas leads to motor impairment with severe disability associated with stiffness, joint deformation and paralysis. However, current treatment approaches now allow these complications to be prevented and the prognosis is favorable: the earlier the substitutive therapy is received and the more adapted the treatment is to the clinical status of the patient, the better the prognosis.