Haemophilia

Dr. Deepanshi Sharma (P.T)

Assistant Professor
 INTRODUCTION
• Haemophilia is a largely inherited bleeding disorder of variable severity.
• There are two main types: haemophilia A, caused by a clotting factor VIII
deficiency, and haemophilia B (also referred to as Christmas disease) which is
caused by a factor IX deficiency. The deficiency can be quantitative or
qualitative, meaning the factor can be inadequate in terms of quantity or
function.
• The severity of both diseases is generally dependent on the levels of factor VIII
or IX. Laboratory factor levels are reported as a percentage of normal factor
activity, with the normal range between 50 and 150%. This can also be
converted into international units, where 100% factor activity is equal to 1.00
U/ml.
• Roughly half of haemophilia patients are classed as having severe disease, with
factor levels below 1%. The remaining haemophilia patients are classed as
either moderate, with factor levels of 1-5%, or mild, with levels from 5 to 50%.
 Aetiology
• Haemophilia A is caused by mutations in the factor VIII gene, whilst

haemophilia B is caused by mutations in the factor IX gene.

• Both genes are mapped to the X chromosome and are passed down in

a recessive fashion, so males with a single mutation will have the disease,

whilst females, with two X chromosomes, will be carriers for the disease.

• In the rare case of a female having a homozygous mutated factor gene,

inherited from an affected father and a carrier mother, it has been

observed that they can present with haemophilia symptoms.

• Occasionally, haemophilia can be acquired due to the formation of auto

antibodies targeting factor VIII or IX, or as a result of malignancy.

 Clinical features
• Haemophilia can present differently depending on
patient age and disease severity.
• Typically, inherited cases present at younger ages
and acquired cases occur in older individuals. More
severe disease, characterised by lower factor levels,
often presents earlier in life (even as early as during
delivery).
• On the other hand, mild haemophilia patients often
do not realise they have the disease, and only present
after a bleed following major trauma or surgery, or
precipitated by drugs such as non-steroidal anti-
inflammatories (NSAIDs) or aspirin.
 History
• Severe haemophilia will typically present early with spontaneous or prolonged
bleeding.5
• Typical symptoms of haemophilia may include:
• Severe epistaxis
• Bleeding gums
• Haematuria: gross or microscopic (i.e. detected on dipstick).
s
• Intra-articular or intramuscular bleeds: commonly affected joints include the knees,
ankles and elbows.
• Excessive bruising/ecchymoses, contusions or spontaneous haemorrhage during
childhood play.
• Prolonged bleeding after a surgical or dental procedure, or post-venepuncture.
• Other less common bleeding presentations include:
• Intracranial haemorrhage: presenting with neurological symptoms.
• Haematemesis, melaena and frank rectal bleeding (from gastrointestinal bleeding).
• Haemoptysis
• Compartment syndrome
• When taking a history, other important areas to
cover include:
• Secondary symptoms such as fatigue or frequent
infections, as they may indicate alternative diagnoses (e.g.
haematological malignancy).
• Drug history: several different medications can alter the
ability of the clotting cascade to function effectively (e.g.
warfarin, aspirin, NOACs).
• Social history: consider the possibility of violence as the
cause of excessive bruising or bleeding (e.g. domestic
violence).
• Family history: given that most haemophilia is inherited,
it’s essential that you take a comprehensive family history.
 Differential diagnoses
• The haemostatic and fibrinolytic systems within the body normally counteract each
other to maintain balance. Several medical conditions can result in loss of this
balance, resulting in excessive bleeding.
• Common differential diagnoses for haemophilia include:
• von Willebrand’s disease (VWD): especially subtype 2N
• vitamin K deficiency (vitamin K is crucial for the synthesis of many clotting factors)
• disorders of the fibrinolytic system
• hepatic disease (many clotting factors, as well as several anticoagulative proteins,
are synthesised in the liver)
• deficiencies of specific clotting factors
• Platelet disorders can also present similarly to haemophilia, although platelet
deficiencies typically cause petechial haemorrhages and ecchymoses (bruising)
rather than the haematomas and haemarthroses which are more characteristic of
clotting factor deficiencies.
• Iatrogenic causes of spontaneous or prolonged bleeding are also a possibility in
patients being treated with anticoagulants or antiplatelets.
 Investigations
• Full blood count and extended clotting screen
• It is important to carry out a full blood count
(FBC) and extended clotting screen in any patient
presenting with unexplained spontaneous or
prolonged bleeding symptoms.
s This can help
diagnose haemophilia and rule out many of the
differential diagnoses.
• Findings associated with haemophilia include:
• Reduced haemoglobin and low haematocrit on
FBC: can indicate a recent or chronic bleed.
• Normal platelet count on FBC.
 Investigations
• Normal prothrombin time (PT), bleeding time (BT),
fibrinogen levels and von Willebrand factor levels.
• Prolonged activated partial thromboplastin time
(APTT): although this can be normal in mild disease.
• Reduced factor VIII or factor
s IX activity level: for
haemophilia A or B respectively.
• PT measures the extrinsic and common pathways.
APTT measures the intrinsic and common pathways.
Both factor VIII and IX form part of the intrinsic
clotting pathway, so deficiencies affect the APTT
reading.
 Management
(Prophylaxis)

• Prophylactic treatment is given in order to prevent disease, in this case bleeding events.

Prophylaxis also helps to preserve long-term joint function by reducing episodes of

haemarthrosis.

• Severe forms of haemophilia can require prophylactic factor infusions, replacing the missing or
s
non-functional clotting factor, in order to prevent frequent haemarthroses or other bleeding

episodes. Factor infusions should ideally be administered until the child reaches physical

maturity, but are often continued long-term, under the continuous review of a haematologist.

• The genetically engineered factor injections are given as a slow intravenous bolus and in some

cases may be required up to three times a week. These doses should be tailored to the patient,

such as administration just prior to a child’s physical education lessons.

• Patients with severe haemophilia are at high risk of bleeding during and after

surgery. For this reason, their factor activity should be increased to 50-100% for 2-7

days before surgery, and closer to 100% for surgery on the brain or prostate.

Tranexamic acid can be considered as this inhibits fibrinolysis without increasing

thrombosis risk in healthy individuals.

• Patients should also avoid competitive contact sports and unnecessary manual

labour, as these increase the risk of haemarthroses and head injuries. Other

exercises, including racquet sports or swimming, should be encouraged.

• To protect against bloodborne diseases, all patients and carers that may inject blood

products should be vaccinated against hepatitis A and hepatitis B. In haemophilia

patients, these immunisations should be given subcutaneously rather than

intramuscularly to avoid bleeding and haematoma formation.

 Acute bleeds
• For any bleeding episodes, normal physical methods of bleeding
cessation should be advised. Depending on the severity of
bleeding, patients may need factor infusions, fresh frozen
plasma or cryoprecipitate.
• For major haemorrhage, including those involving the central
nervous, gastrointestinal and genitourinary systems the aim is to
correct factor levels to 100%.
• For minor haemorrhages, such as haemarthrosis, oral mucosal
and intramuscular bleeds, the aim is to increase factor levels to
30-50%. These raised factor levels should be maintained through
further infusions for several days.
• If possible, coagulation tests and a group and save
sample should be taken prior to treatment, however, these
investigations should not delay treatment.
• Haematomas and haemarthroses can be very painful
and require analgesic treatment. The oral route is
preferred, although NSAIDs should be avoided as they
increase the risk of gastrointestinal bleeding.
Intramuscular opiates should also be avoided as this
mode of delivery can result in intramuscular bleeding
and haematoma formation.
s
• It is possible to treat acute bleeds in mild haemophilia A
patients with desmopressin (DDAVP), which stimulates
von Willebrand factor (vWF), which in turn promotes
factor VIII activity.
 Genetic counselling and pregnancy
• As haemophilia has an X-linked recessive inheritance
pattern, a daughter of a male haemophilia patient will
be a carrier whilst a son will be unaffected, as they
inherit their father’s normal
s
Y chromosome.
• There is a 50% chance that a daughter of a female
carrier will be a carrier and a 50% chance that a son
will be affected. This information should be discussed
with any haemophilia patients or carriers looking to
have a child.
• Genetic testing and counselling should be made available to
prospective parents. During pregnancy, the fetus can be tested for
a haemophilia mutation via:
• Chorionic villus sampling at 11-14 weeks: removing a small
portion of the placenta for testing.
• Amniocentesis at 15-20 weeks: sampling the amniotic fluid for
testing.
• Both procedures carry small risks of premature labour and
miscarriage, which should be assessed by the family prior to the
procedure. The obstetric haematology team should be involved in
the management of pregnancy and birth.
• A haemophilia diagnosis should be made as soon as possible after
delivery, by testing of uncontaminated cord blood. Recombinant
factor should be administered immediately after a positive
haemophilia diagnosis.
 Complications

• If untreated, severe disease, and repeated

bleeding into joints, can lead to arthropathy
(painful and reduced range of movement),
joint deformity, soft tissue haemorrhages,
retroperitoneal bleeds or haematoma
formation. These can present as surgical
emergencies and may require operative
intervention.
THANK YOU