Therapeutic principles
The extent of haemorrhage depends on the severity of the
factor VIII or IX deficiency and the severity of the trauma.
Therapy consists of temporarily raising the concentration of
the deficient factor, appropriate supportive measures, analge-
sia and graded physiotherapy. In minor trauma in mild
haemophilia A, infusions of a synthetic vasopressin analogue
(desmopressin, DDAVP; Chapter 36), produce a short-term
two- to four-fold increase in factor VIII. Fluid overload due to
the antidiuretic hormone action of DDAVP must be prevented
by limiting water intake. DDAVP is usually given with an
inhibitor of fibrinolysis, such as tranexamic acid. If the
haemophilia and/or trauma is severe, then infusions of factor
VIII or IX are required. Patients and their parents or other car-
ers are taught to administer these factors at home in order to
minimize delay in therapy.
FACTOR VIII
Factor VIII used to be obtained from purified pooled plasma of
blood donors, but recombinant preparations are free of poten-
tial viral pathogens, including hepatitis B, hepatitis C, HIV and
cytomegalovirus (CMV). It is given as an intravenous infusion.
It is highly bound to von Willebrand factor (95%) and is
degraded by reticuloendothelial cells in the liver. The dose of
factor VIII is calculated on the basis of the severity of the injury
and the required increase in plasma factor VIII concentration.
Transient reactions to infusions (e.g. urticaria, flushing and
headache) occur, but respond to antihistamines. Anaphylactic
reactions are rare.
FACTOR IX
Factor IX is used in patients with factor IX deficiency. It acts as
a cofactor for factor VIII and as recombinant factor IX is avail-
able for patients with haemophilia B the recombinant form
does not contain other factors or potential pathogens. Factor
IX is given as an intravenous infusion. The use and adverse
effects of factor IX are similar to those described for factor VIII.
FACTOR VIIA
Recombinant activated factor VII (rFVIIa) is a haemostatic pro-
tein. It was originally developed to treat bleeding episodes in
haemophilic patients with inhibitors against coagulation fac-
tors VIII and IX. It is used by specialists to achieve haemostasis
in several severe congenital and acquired haemorrhagic states.
APLASTIC ANAEMIA
Aplastic anaemia is characterized by pancytopenia associated
with absence of haematological precurors in the marrow. Some
cases are congenital (e.g. Fanconi’s anaemia), but many are
acquired, and in 50% of these an aetiological agent (a virus,
chemical or drug) can be implicated. Certain drugs predictably
cause aplastic anaemia if given in sufficient dose (e.g. alkylat-
ing agents, such as cyclophosphamide), others (e.g. chloram-
phenicol) may cause aplastic anaemia as an idiosyncratic type
B adverse reaction (Chapter 12).TREATMENT
Support is provided with transfusions (of red cells and platelets)
and appropriate antibiotics. Successful bone marrow transplan-
tation is curative and is the therapy of choice for young patients.
For those who are unsuitable for this treatment, or in cases
where there is no available histocompatible donor, anabolic
steroids, e.g. oxymetholoneorstanozololandepoetinand
G-CSF (see above) may reduce the requirement for transfusions.IDIOPATHIC THROMBOCYTOPENIC
PURPURAIt is important to exclude other causes of thrombocytopenia,
including drugs (e.g. quinine). Platelet transfusions are required
to control active bleeding or to cover operations. Other treat-
ment options include:- glucocorticosteroids – e.g. prednisolone: an increase in
platelet count may take one to two weeks. If steroids fail
or the disease relapses, splenectomy should be
considered. The patient should be immunized against
pneumococcal infection several weeks preoperatively.
Glucocorticosteroids should be continued after
splenectomy until the platelet count rises. - immunosuppressive drugs (Chapters 48 and 50),
especiallyvincristine, are used in refractory cases. - intravenous immunoglobulin (IVIG), rituximab, anti-CD20
antibody (Chapter 50) and ciclosporinare alternatives.
IDIOPATHICTHROMBOCYTOPENICPURPURA 395Key points
Coagulation factor therapy- Factor VIII is used to treat haemophilia A (factor IX is
used for haemophilia B) when patients present with
severe bleeding. - These factors are given intravenously and the dose is
based on the level of factor deficiency and blood loss. - Recombinant coagulation factors are free from the risk
of contamination with infectious agents, such as HIV
and hepatitis C, and cause less antibody production.
Key points
Drug-related haematological toxicity- Cytotoxic cancer chemotherapy can suppress all
haematopoietic lineages. - Drugs that cause aplastic anaemia include ticlopidine,
indometacin, carbimazole and zidovudine. - Drugs that cause agranulocytosis include, for example,
carbamazepine, propylthiouracil, NSAIDs, H 2
antagonists and antipsychotics (e.g. chlorpromazine,
clozapine). - Drugs that cause thrombocytopenia include, for
example, heparin, azathioprine, quinidine and thiazides. - Drugs that cause haemolytic anaemia include, for
example, methyldopa, β-lactams (penicillins and
cephalosporins).