[MIM 134 500, 306 700, 306 900]

(Christmas disease (hemophilia B)) 

Hemorrhagic disease due to a disorder in the production of coagulation factors: factor VIII (hemophilia A, mutations of the F8 gene on Xq28) or IX (hemophilia B, mutation of the F9 gene on Xq27): it is thus X-linked transmission (only boys are affected). 

However, 

-         it is a de novo mutation in about 1/3 of cases: there is therefore no positive family history in these cases

-         girls carrying the gene can have low levels of factor following a homozygous mutation or a predominant inactivation of a normal X chromosome. For example, in the USA, 1.7% of the population of hemophilia A and 3.2% of hemophilia B are women. Similarly, humans who are phenotypically girls but carry a single X (Turner syndrome or feminizing testicle, for example) may suffer from the disease. 

Prevalence: hemophilia A: 1 boy on 5,000; hemophilia B: 1/25.000.

Factor VIII is a protein cofactor without intrinsic activity while factor IX is a protease that requires factor VIII as a cofactor; the combination of factors VIIIa and IXa produces the tenase complex, which activates factor X to generate thrombin.

Risk of bleeding after minor trauma, or even spontaneous bleeding, depending on the residual level of the concerned clotting factor and the location of the bleeding (potentially lethal internal bleeding). 

The hemophilias (A and B) are classified into 3 groups:

•  minor hemophilia (30-40% of cases): activity levels between 5 and 30% or 0.06 to 0.4 IU/dl of the coagulation factor ; may remain subclinical; low risk hemorrhagic only after injury or surgery;
• moderate hemophilia (10 to 20% of cases): between 1 and 5% or 0.01 to 0.05 IU/dl; there may be occasional spontaneous bleeding; extended risk of bleeding  after dental procedure or surgery;
• severe hemophilia (50% of cases): level < 1 % or < 0.01 IU/dl; frequent bleeding (weekly), bleeding at the fall of the umbilical cord, risk of intracranial hemorrhage, hemarthroses (knees, elbows, ankles); risk of major spontaneous internal bleeding; potentially lethal hemorrhagic risk in case of surgery; patients who frequently receive clotting factors are at risk of developing antibodies against factor VIII or, more rarely, factor IX, which considerably complicates their treatment and anesthetic care. In those cases, it is recommended to use activated recombinant factor VII. A longterm treatment with emicizumab could also be effective.

A particular form of hemophilia B is hemophilia B Leyden which is due to a focal mutation in the promoter region of the F9 gene: this causes a deficiency in factor IX and a clinical presentation close to that of severe hemophilia in childhood. However, the increased production of androgens at puberty increases the activity of the promoter gene and therefore the level of factor IX to near 0.5 IU/dl, which reduces the occurrence of hemorrhagic signs.

There are cases of acquired hemophilia following the appearance of autoantibodies directed against factor VIII or IX. For hemophilia A (1.5 cases/1.106/year), the cause is unknown in 50 % of cases; other causes are pregnancy (10 %), autoimmune condition, hematological cancer, solid tumor or certain drugs. Signs: hematuria, cutaneous, mucosal and muscular but not articular hemorrhage. Treatment: factor VIIa.

Anesthetic implications: 

keep that diagnosis in mind in case of a prolonged APTT. Check hemostatsis, including anti-coagulation-factors antibodies; potentially lethal risk of bleeding according to the severity of hemophilia. Preoperative supplementation in hemophilia factors (or desmopressin in case of A form with a plasma levels of factor VII > 0.1 IU/dl); take advice from the hematologist who follows the child. Usual dose: bolus injection of 50 IU/kg of factor to correct the deficit followed by a continuous infusion of 2-3 IU/kg/h factor VIII or  4-8 IU/kg/h of factor IX. It is useful to add an antifibrinolytic (b.e. oral or IV tranexamic acid).

References : 

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Diagnosis and anaesthesia management of haemophilia during the neonatal period. 
Paediatr Anaesth 1998; 8:245-7.

-        Carpenter SL, Abshire TC, Anderst JD,et al. 
Evaluating for suspected child abuse : conditions that predispose to bleeding. 
Pediatrics 2013; 131: e1357-73.

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Déficits rares de la coagulation et gestes invasifs. 
Ann Fr Anesth Réanim 2013 ; 32 : 198-205.

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Gestion du péri-partum de la patiente conductrice d’une hémophilie. 
Ann Fr Anesth Réanim 2013 ; 32 : 807-10.

-        Faillace WJ, Warrier I, Canady AI. 
Paraplegia after lumbar puncture in an infant with previously undiagnosed hemophilia A.
Clin Pediatr 1989; 28:136-8.

-        Tagaya A, Miyajima M, Ito M, Nakamura L et al. 
Spontaneous spinal epidural hematoma in an infant with undiagnosed hemophilia A.
Pediatrics International 201; 52: 296-8

-        Sumie M, Toyama K, Morokawa K, Yokoo-Matsuoka T et al. 
Inadvertent bleeding in an infant after inguinal hernioplasy leads to diagnosis of hemophilia B. 
J Anesth 2012; 26: 399-300.

-        Brack A, Vögeler S, Hilpert J, Berger G ; Buhr HJ, Kolscielny J.
Acquired fator VIIII inhibitor.
Anesthesiology 2009; 111:1151-4.

-        Jedidi I, Hdiji S, Amji N, Makri F et al.
Hémophilie B acquise: à propos d’un cas et revue de la literature.
Ann Biol Clin 2011 ; 69 :685-8.

-        Tribuzi S, Naccarato A, Pelagalli L, Covotta M et al.
Acquired hemophilia A after hepatic Yttrium-90 radioembolization : a case report.
A&A Case Reports 2017; 9: 344-5.

-        James CF, Burnett EH.
Multiple anesthetic and obstetric challenges in a laboring patient with postural orthostatic tachycardia syndrome (POTS), acquired hemophilia and a rare seizure disorder.
Acta Anaesth Belg 2019; 70: 85-9.

Updated: November 2019