This document provides an overview of hemophilia, including its causes, types, severity, epidemiology, genetics, clinical manifestations, complications, diagnostic evaluation and criteria. Key points include: - Hemophilia is an inherited bleeding disorder caused by deficiencies in coagulation factors VIII or IX. - It affects males predominantly and can range from mild to severe based on residual factor activity levels. - Initial presentations often involve easy bruising, hemarthrosis or bleeding after procedures in infants/children with severe disease. - Diagnosis involves screening tests like aPTT and factor activity levels, along with family/bleeding history and genetic testing. - Complications include joint damage, infections and development of factor inhibitors

1. Dr Bikal Lamichhane
1st year Im resident
APPROACH TO HEMOPHILIA

2. INTRODUCTION
 Hemophilia typically refers to an inherited bleeding disorder caused by deficiency
of coagulation factor
 Hemophilia A – Inherited deficiency of factor VIII (factor 8 [F8]); an X-linked
recessive disorder.
 Hemophilia B – Inherited deficiency of factor IX (factor 9 [F9]); also called
Christmas disease; an X-linked recessive disorder.
 Hemophilia C – Inherited deficiency of factor XI (factor 11); also called
Rosenthal syndrome; an autosomal recessive disorder.
 Acquired factor deficiencies – caused by an autoantibody (often to factor VIII)
are sometimes referred to as acquired hemophilia

3.  Severity –
 based on the residual or baseline factor activity level
 this is expressed as a percent of normal or in international units (IU)/Ml.
1) Severe hemophilia – Severe hemophilia is defined as <1 percent factor
activity, which corresponds to <0.01 IU/mL.
2) Moderate hemophilia – Moderate hemophilia is defined as a factor activity
level ≥1 percent of normal and ≤5 percent of normal, corresponding to ≥0.01
and ≤0.05 IU/mL.
3) Mild hemophilia – Mild hemophilia is defined as a factor activity level >5
percent of normal and <40 percent of normal (≥0.05 and <0.40 IU/mL).

4. EPIDEMIOLOGY
 Hemophilia affects more than 1.2 million individuals (mostly males)
worldwide .
 Hemophilia A – Hemophilia A occurs in approximately 1 in 4000 to 1 in
5000 live male births. Hemophilia A is more common than hemophilia B
and is also more likely to be severe.
 Hemophilia B – Hemophilia B occurs in approximately 1 in 15,000 to 1
in 30,000 live male births.
 Severe hemophilia is almost exclusively a disease of males, although
females can be affected in some rare cases
 Most commonly, hemophilia is inherited ,However, sporadic disease

5. Genetics
 The factor VIII gene is located on the X chromosome.
 Haemophilia is associated with a range of mutations in the factor VIII gene.
 these include major inversions, large deletions and missense, nonsense and
splice site abnormalities.
 Sex-linked disorder:-
 all daughters of a patient with haemophilia are obligate carriers and they, in turn,
have a 1 in 4 chance of each pregnancy resulting in the birth of an affected male
baby, a normal male baby, a carrier female or a normal female.
 Antenatal diagnosis by chorionic villous sampling is possible in families with a
known mutation.

7. CLINICAL MANIFESTATIONS
 Disease severity —
 Patients with more severe hemophilia are more likely to have
spontaneous bleeding, severe bleeding, and an earlier age of first
bleeding episode begin as early as birth.
 Patients with moderate hemophilia often bleed in response to minor
intercurrent injury and invasive procedures. Bleeding is less frequent than
in severe hemophilia and typically occurs four to six times yearly.
 Individuals with mild hemophilia generally only have bleeding in response
to injury/trauma or surgery, and bleeding may not become clinically
apparent until later in life.

8. Initial presentation
 Age at first bleeding
 Most infants with severe hemophilia present within the first year to one
and a half years of life with easy bruising, hemarthrosis, bleeding due
to oral injury, or after an invasive procedure.
 Initial site of bleeding
 Intracranial bleeding ,
 Joints and muscle ,
 Epistaxis, oral and gastrointestinal bleeding .
 Genitourinary tract Initial site of bleeding

9. Sites of bleeding:-
 Infants –central nervous system, extracranial sites such as
cephalohematoma, and sites of medical interventions
including circumcision, heel sticks.
 Children –Bruising, joint bleeds, and other sites of
musculoskeletal bleeding become more common once
children begin walking.
Forehead hematomas ("goose-eggs").
 Older children and adults – joints, muscles, central
nervous system, and oral or gastrointestinal tract

11. Laboratory findings
 Activated partial thromboplastin time (aPTT):-
prolonged, however aPTT may be normal in individuals with
milder factor deficiencies (eg, factor activity level >15 percent).
 The platelet count and prothrombin time (PT) are normal in
hemophilia.
 Measurement of the factor activity level (factor VIII in hemophilia A;
factor IX in hemophilia B) shows a reduced level compared with
normal controls (generally <40 percent).
 The plasma von Willebrand factor antigen (VWF:Ag) is normal in
hemophilia
 Urinalysis is not done routinely, but if performed it may sometimes

12.  COMPLICATIONS:-
 neurologic sequelae of intracranial hemorrhage
 joint destruction from repetitive hemarthroses
 Rarely pseudotumor
 infections transmitted from plasma-derived factor products
(typically viral) and development of antibodies to factor
inhibitors (typically following factor infusions in patients with
severe disease).

13. DIAGNOSTIC EVALUATION
 Hemophilia may be suspected in any male with bleeding while a positive
family history is supportive, a negative family history cannot be used as
evidence against the diagnosis, since many cases are sporadic.
Patient and family history
 Prior bleeding symptoms should be assessed in patients who are
asymptomatic at the time of the evaluation.
 History about all potential hemostatic challenges including menstrual
cycles, dental extractions, trauma, and surgical interventions.
 Family history that includes bleeding and prior evaluations of family
members for hemophilia and other bleeding disorders

14.  Screening tests
 Including the PT, aPTT and platelet count.
 PT and platelet count are normal and the aPTT is prolonged in moderate and
severe disease.
 Factor activity levels — Factor activity levels should be measured in the
following settings
1. Male patients with a known family history of hemophilia.
2. Patients without a known familial defect who are suspected to have
hemophilia based on clinical history and/or a prolonged aPTT that corrects in
mixing studies.
3. Females identified as carriers by genetic testing, or females who potentially
may be carriers for whom genetic testing is not available.

15.  Genetic testing —
 predict the risk of inhibitor formation in the patient.
 facilitates carrier identification in female family members.

16. Diagnostic criteria
Hemophilia A –
 factor VIII activity level below 40 percent of normal (below
0.40 international units [IU]/mL), or,
 In some circumstances where the factor VIII activity level is
≥40 percent, a pathogenic factor VIII gene mutation.
 A normal VWF antigen (VWF:Ag) should also be documented
to eliminate of the possibility of some forms of VWD

17.  Hemophilia B –
 factor IX activity level below 40 percent of normal, or
 In some circumstances where the factor IX activity level is ≥40 percent, a
pathogenic factor IX gene mutation.
 Hemophilia carrier –
 requires identification of a hemophilia gene mutation.
 Factor levels are important for managing carriers, but are not optimal for
determining or eliminating the diagnosis of a hemophilia

18.  THANK YOU