A ten-year-old boy presents with a haemarthrosis. A diagnosis of haemophilia A is suspected.
How common are the inherited disorders of coagulation and how does the clinical phenotype vary?
Inherited deficiencies may occur in any of the coagulation factors. However, the commonest inherited bleeding disorder is von Willebrand’s disease, which is reported to affect as many as 1% of the general population. This is usually due to a quantitative deficiency in von Willebrand factor but may be due to a qualitative defect. This is usually a clinically mild bleeding disorder producing mucosal bleeding. Menorrhagia may be problematic and a significant number (17%) of women with menorrhagia and no primary gynaecological pathology have an undiagnosed bleeding disorder, with von Willebrand’s disease being the most frequent.1 The next most common disorder is haemophilia A, the deficiency of factor VIII (FVIII), followed by haemophilia B (deficiency of factor IX). The remaining inherited coagulation deficiencies are rare, although many exhibit autosomal recessive inheritance and thus are more prominent in communities where consanguinity occurs. The features of these rare inherited coagulation factor deficiencies are summarized in Table 5.1.2
Table 5.1Rare inherited coagulation factor deficiencies (adapted from 1) |Favorite Table|Download (.pdf) Table 5.1 Rare inherited coagulation factor deficiencies (adapted from 1)
|Factor deficiency ||Prevalence ||Clinical phenotype ||Screening coagulation tests ||Treatment |
|Fibrinogen (factor I) ||1 in 1 000 000 ||Variable, spontaneous bleeding, umbilical and mucosal and ICH ||Prolonged PT, APTT, TT ||Personal and family history of bleeding important. Virally inactivated concentrate not licensed in Europe. Cryoprecipitate for emergencies – not virally inactivated. Aim for level of 1 g/l |
|Prothrombin (factor II) ||1 in 2 000 000 (rarest) ||Hypoprothrombinaemia (type 1); dysprothrombinaemia (type 2); mucosal and soft tissue bleeding, haemarthrosis ||Usually prolonged PT and APTT ||No specific concentrates. Prothrombin-complex concentrates treatment of choice; can use virally inactivated FFP. Levels 20–30 IU haemostatic |
|Factor V ||1 in 1 000 000 homozygote ||Moderately severe bleeding disorder – bruising and mucous membrane, haemarthrosis and muscle bleeds less common ||Prolonged PT and APTT, exclude combined FV and FVIII deficiency ||No concentrate available. Virally inactivated FFP. Minimum haemostatic level 15 U/dl |
|Combined FV and FVIII deficiency ||1 in 1 000 000 ||Easy bruising and epistaxis, post-operative bleeding ||Prolonged PT and disproportionately prolonged APTT ||Treat spontaneous bleeding with FFP and FVIII concentrate – aim for recombinant FVIII 30–50 U/dl depending on severity and 25 U/dl factor V |
|Factor VII deficiency ||1 in 300 000–1 in 500 000 for severe deficiency ||Bleeding spectrum variable mucous membrane, CNS bleed if severe ||Prolonged PT, normal APTT ||FVII concentrates, FFP if no alternative, prothrombin-complex concentrates, tranexamic acid. Levels 10–15 U/dl haemostatic |
|Factor X deficiency ||I in 1 000 000 homozygous; heterozygous 1 in 500 but usually asymptomatic ||Significant bleeding if severe, usually mucosal ||Prolonged PT and APTT ||Tranexamic acid, virally inactivated FFP, ...|