Page 363 - Essential Haematology

Chapter 26 Coagulation disorders / 349

Table 26.1 Correlation of coagulation factor
activity and disease severity in haemophilia A
or B .

Coagulation factor
activity (percentage
of normal) Clinical manifestations
< 1 Severe disease
Frequent spontaneous
bleeding into joints,
muscles, internal
organs from early life
Joint deformity and
crippling if not
adequately prevented
or treated
1 – 5 Moderate disease

Figure 26.6 Haemophilia A: X - ray of the knee joints
shows destruction and narrowing of the left joint Bleeding after minor
space. trauma
Occasional
spontaneous episodes
> 5 Mild disease
Carrier d etection and a ntenatal d iagnosis Bleeding only after
signifi cant trauma,
Carriers are detected with DNA probes. A known surgery

specific mutation can be identified (Fig. 26.7 ) or

restriction fragment length polymorphisms within
or close to the factor VIII gene allow the mutant
allele to be tracked. Chorionic biopsies at 8 – 10 bleeding or when haemorrhage is occurring at a

weeks ’ gestation provide sufficient fetal DNA for dangerous site, the factor VIII level should be ele-

analysis. Antenatal diagnosis is also possible follow- vated to 100% and then maintained above 50%
ing the demonstration of low levels of factor VIII when acute bleeding has stopped, until healing has
in fetal blood obtained at 16 – 20 weeks ’ gestation occurred. On average, factor VIII infusion produces

from the umbilical vein by ultrasound - guided a plasma increment of 2 U/dL per unit infused per
needle aspiration. This method is now only used if kilogram body weight. Roughly, the dose to be

DNA analysis is uninformative (1% of carriers). infused (units) = (weight (kg) × increment needed
(U/dL))/2.
Recombinant factor VIII and plasma - derived
Treatment

purified factor VIII preparations, which are heat
Most patients in developed countries attend special- and solvent - detergent treated, are available for
ized haemophilia centres where there is a multidis- clinical use and have never transmitted viral
ciplinary team dedicated to their care. Bleeding infections.
episodes are treated with factor VIII replacement 1 - Diamino - 8 - D - arginine vasopressin (DDAVP;
therapy and spontaneous bleeding is usually con- desmopressin) provides an alternative means of
trolled if the patient s factor VIII level is raised to increasing the plasma factor VIII level in milder
’
30 – 50% of normal. Guidelines exist for the plasma haemophiliacs. Following the intravenous adminis-
level to be achieved for different types of haemor- tration of this drug, there is a two - to fourfold rise

rhage. For major surgery, serious post - traumatic maximum at 30 – 60 min in the patient ’ s own factor