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Haemophilia B genetics, classification and treatment options

What is haemophilia B?
Haemophilia B is a genetic disorder caused by missing or defective clotting factor IX (FIX, or factor 9), causing prolonged and often spontaneous bleeding externally and internally into the muscles and joints.¹ Haemophilia B makes up 15–20% of all haemophilia cases.1 Approximately 70% of the haemophilia B cases are genetically inherited and have a positive family history for the disease.²

Genetics of haemophilia B
The haemophilia B gene locates on the X chromosome. Females inherit two X chromosomes, one from their mother and one from their father (XX). Males inherit an X chromosome from their mother and a Y chromosome from their father (XY). So, if a son inherits an X chromosome carrying the haemophilia B gene from his mother, he will have haemophilia B. A father with haemophilia B cannot pass it on to his sons but will pass the gene to his daughters.3

father (with haemophilia B) vs mother (not a carrier)

Because females have two X chromosomes, even if they inherit a haemophilia B gene, they have another healthy X chromosome to compensate. Instead, they will be carriers whose levels of the clotting factor IX will be around half of the normal amount and may suffer some bleeding symptoms. In that case, they will be called symptomatic carriers. Haemophilia B can occur in females if they have two copies of the haemophilia B gene, but it is very rare.4

diagram showing how haemophilia B is inherited from parents

Clotting factor IX
Factor IX is an essential clotting factor required for forming normal blood clots. In response to injury, factor IX interacts with other clotting factors to set off a chain of reactions that form a blood clot, sealing off damaged blood vessels.5

Normal levels of clotting factor IX vary between different people and range from 50–150%;4 however, in people with Haemophilia B, levels fall below 40%.6

FIX levels < 1% = Severe

Classification of haemophilia B according to FIX plasma level
The frequency and severity of bleeding correlate with clotting factor IX levels as shown below.

FIX levels < 1% = Severe

A wide phenotypic variation is observed across patients.8

Patients with mild haemophilia typically do not have spontaneous bleeds and are often underdiagnosed (sometimes not until adulthood).3 Learn more about the signs, symptoms, and diagnosis of haemophilia B.

Treatment of haemophilia B
Factor IX replacement therapy is used to prevent and treat bleeding in haemophilia B patients. The treatment principle is simply based on replacing the person’s missing factor IX with another factor IX used as a drug. People with severe and some with moderate haemophilia B should take their factor IX replacement therapy at regular intervals prophylactically to prevent spontaneous and breakthrough bleeds.6 Research has suggested that the higher a person’s factor IX level, the lower the risk of spontaneous bleeds. Your physician will select the best prophylactic regimen for you based on your bleeding phenotype, joint status, and musculoskeletal function. Besides, your individual needs, lifestyle, and preference. 6

Types of factor IX replacement therapy
This factor IX replacement therapy may be plasma-derived - concentrated from the plasma or recombinant - manufactured using recombinant DNA technology. A new generation of factor IX replacement therapy called Extended half-life (EHL) factor IX has been developed with a longer duration of action to allow haemophilia B patients a less frequent administration and offer them higher factor trough levels and higher protection against acute bleeds.6 With some EHL factor IX products, patients with haemophilia B can stay in the non-haemophilia range for significant amount of time with the once-weekly dosing. 10 This is what’s refered to by the WFH as a “ more ambitious prophylaxis ”. 6

  1. Dolan G et al., Blood Rev. 2018;32(1):52-60.
  2. Peyvandi F et al., Lancet. 2016;388(10040):187-97.
  3. Friedman KD and Rodgers GM. Inherited coagulation disorders. In: Greer JP et al, eds. Wintrobe's Clinical Hematology. 12th ed. Vol. 2. Philadelphia: Lippincott Williams & Wilkins; 2009:1379-424.
  4. World Federation of Hemophilia. Carriers and Women with Hemophilia, Montreal: World Federation of Hemophilia, 2012.
  5. Dargaud Y et al.,  Thromb Haemost. 2005;93(3):475-80.
  6. Srivastava A et al. WFH Guidelines for the Management of Hemophilia, 3rd edition. Haemophilia. 2020;26 Suppl 6:1-158.
  7. Sharathkumar AA and Pipe SW. Pediatr. Rev. 2008;29;121-130.
  8. Vyas S et al. Haemophilia 2014;20:9-14.
  9. Soucie JM et al., Blood Adv. 2018;2(16):2136-2144.
  10. Oldenburg J , Carcao M , Lentz SR , et al., Haemophilia. 2018;24(6):911-920 .