Page 496 - Medicine and Surgery

P1: KOA
BLUK007-12 BLUK007-Kendall May 12, 2005 20:37 Char Count= 0

492 Chapter 12: Haematology and clinical immunology

normal immunoglobulins, no lytic bone lesions and no Age
renal failure. Inherited, age at presentation depends on severity.

Investigations Sex
Electropheresis of serum protein demonstrates a raised X linked; males only affected.
monoclonal band within the immunoglobulin region,
without suppression of other proteins. Aetiology
Mutations on the X chromosome including deletions,
Management frame shifts and insertions. One third of cases are new
Aproportionof patients will go on to develop multi- mutations.
ple myeloma and therefore all patients require followup
looking for any increase in monoclonal protein levels or Pathophysiology
the development of lytic bone lesions. The factor VIII complex is a cofactor in the intrinsic
pathway’s activation of factor X (see Fig. 12.12). VIII:c
is coded for on the X chromosome and it is this part of
Bleeding disorders the complex that is deficient.

Clotting disorders Clinical features
As there are various mutations there is a resultant spec-
Haemophilia A trumofclinicalseveritydependentonthelevelofnormal
VIII complex that is formed:
Definition Factor VIII levels of less than 1% present within the
An inherited coagulation disorder resulting from factor
first 2 years of life with recurrent spontaneous bleed-
VIII deficiency.
ing.
FactorVIIIlevelsoflessthan5%resultinseverebleed-

Incidence ing following injury although spontaneous haemor-
1–2 in 10,000 two thirds of whom have severe disease. rhage does occur.

INTRINSIC PATHWAY
–ve charge tissue
contact

XII XIIa
FINAL COMMON PATHWAY
XI XIa

IX IXa
Prothrombin
(II)
VIII
V
X Xa
Fibrinogen
Thrombin
(IIa)
Fibrin Figure 12.12 Factor VIII in the
coagulation cascade.