Talk on understanding and management of hemophilia , a rare and poorly understood disorder.

2.  17 y/o male presented in Impending shock
,with c/c of Abdominal pain vomiting and
hematemesis.

3.  Pain described as “sharp, stabbing, 9/10”in the
epigastric region with radiation to the back and peri
umbilical region, and associated with multiple
episodes of large amount of dark colored vomiting .
 Vomitus was large in amount non projectile , dark
colored .
 Denies trauma to abdomen, dysuria, diarrhea,
afebrile, hematuria. Last PO was day before
admission.

4.  Patient was seen initially, and received
Morphine 12mg IV total and Dilaudid 1mg IV
with minimal pain control.
 Labs, CT Abd/Pelvis were done, and patient
was transferred to a tertiary care center with
diagnosis of Acute Pancreatitis.
 Patient had similar episode 5 yrs ago and
required Treatment with Factor 8 infusions

5.  Hemophilia A- diagnosed at 2 months old
when immunizations caused excessive
bleeding at the sites.

6.  Medications: Factor 8 1000 units IV
Monday/Wednesday/Friday- patient
noncompliant.
 “only when he feels like he needs it”

7.  Physical Examination
 Vital Signs- T-98.6F , PULSE-148 , B.P.- 90/54
 General: Severe pain ,Curled up , Jaundiced.
 HEENT: NC/AT, EOMi b/l, PERRLa, Salem Sump tube in Left Nare,
OP clear, MMM
 Neck: no LAD, supple
 CV: Tacycardia , Flow murmur.
 Lungs: CTA b/l, no wheezes
 Abdomen: Periumbilical tenderness ++, (+)distention, Voluntary
guarding, (+)rebound, hypoactive BS, no ecchymosis .
 Skin: cool , dry , no rashes
 Extremities: no c/c/e

8.  Respiratory:
 B/L dullness at both lung bases and diminished breath sounds consistent with B/L
pleural Effusion.
 Initial RR of 40 Br per min no distress.
 Infectious:
 Pt was always afebrile
 Patient was initially started on Meropenum 1g IV q8h on 11/9/09 for prophylaxis as
per ID team.
 Cardiovascular:
HR 100-120.
 GI ;-
 Strict I/Os being obtained, with u/o monitored via Foley, Salem Sump in place to
monitor Gastric Aspirate without Lavages.
 u/o replaced with D5 ½ NS @60cc/hr and TPN (TPN started 11/11), and Gastric
Aspirate replaced 1:1 with NS +20mEq KCl IVF.

9.  Hematology:
 Labs: 6.5 >8.5/25<agg N-66 L-21M-12 Retic 2 fibrinogen 464, LDH- 242 PT- 11.2
INR- 1.03 PTT-29.1 on 11/11, D-dimer- 3.74 (high) on 11/10
 Factor 8 levels-
› 11/8- 2 %  20%--> 54%--> 89% (normal= 50-150%)
 Patient initially received 2 units pRBCs on 11/8 and is subsequently managed with
Factor 8 3000units TID (8am, 4pm,12am)
 Daily CBC, coags, fibrinogen, factor 8.

10.  Metabolic/Alimentary :
 Patient went for PICC line placement .
 TPN was started on Day 3 of admission .
 Daily Amylase, Lipase levels drawn trending downward since
admission
 A/L- 1106/>1200  1010/>1200 1323/1153  703/389 
417/181

11.  Pain
 Initially received morphine 12mgIV total and
Dilaudid 1mg IV at Nyack hospital on day of
admission. In WMC, initially was managed with
morphine and Dilaudid for pain. Pain management
consulted and patient placed on Morphine PCA on
11/10 at an initial rate of 0.5mg q12min, and was
increased to 0.7mg q12min on11/11.
 Patient is responding to morphine PCA and zofran.
Currently abdominal pain less severe than on
admission.

12.  11/8: CT abdomen (at WMC)- intramural duodenal hematoma
which extends from 1st and 4th portion associated with mass
effect on duodenal lumen. Also large hemoperitoneum and
lower density within in the retroperitoneum
 11/7: CT Abd/Pelvis with contrast (at Nyack Hospital)- marked
eccentric thickening of the wall of the duodenum extending from
the duodenal bulb through the proximal jejunum, measures
5cm.Ecentric narrowing of the lumen of the duodenum. No
contrast has passed out of the stomach: gastric outlet
obstruction

13. Figure 16. Duodenal hematoma. CT scan obtained with oral and intravenous contrast
material shows marked focal duodenal wall thickening (arrow). Free fluid and fat
stranding are seen in the right paracolic gutter (arrowhead) and anterior abdomen.

14.  The hemophilia's are a group of related bleeding
disorders that most commonly are inherited.
Inherited bleeding disorders include abnormalities
of coagulation factors and platelet function.

15. Disease Factor deficiency Inheritance
Hemophilia A VIII X linked recessive
Hemophilia B IX X linked recessive
Hemophilia C XI Autosomal
recessive
Parahemophilia V Autosomal
recessive

17.  The earliest references to hemophilia can be
found in second century Jewish writings.

18.  First coined by Schonlein in
1820s.
 Originally termed “Haemorraphilia”
i.e. love for haemorrhages but
over time contracted to
Hemophilia.

19. Distribution Clotting factor
activity
Severe hemophilia 50% <1%
Moderate hemophilia 10% 1-5%
Mild hemophilia 30-40% 5-40%
The severity of hemophilia is defined by the
measured level of clotting factor activity.

20.  Severe: <1%
› Hemarthrosis with minimal trauma
 Moderate: 1 to 5%
› Intermediate symptoms with fewer hemarthroses
 Mild: >5%
› Joint bleeds rarely develop except with
significant trauma

21.  Males within a family have the same level of deficiency
because they share the same genetic defect.

22.  The combined incidence of hemophilia A and B is 1 in 5000 live
male births.
 80 percent have hemophilia A, two-thirds of whom have severe
disease.
 In contrast, almost one-half of individuals with hemophilia B have
moderate or mild disease
 Hemophilia A and B of comparable severity bleed with similar
frequency

23.  The Leyden phenotype of hemophilia B is characterized by severe
hemophilia in childhood that becomes mild after puberty.
 Coinheritance of the factor V Leiden mutation and other
prothrombotic markers occurs in a small proportion of patients with
severe hemophilia A . The presence of such prothrombotic
conditions partially counteracts the bleeding tendency of
hemophilia, resulting in fewer bleeding episodes and a later onset
of first bleeding

24.  Family hx
 newborns traverse delivery and the first few months of life without
detection, despite the presence of severe factor VIII or IX deficiency
 Subgaleal or intracranial hemorrhage (3-5%) perinatal period .
 Hx of difficult delivery or use of a suction Seizures (acute intracranial
hemorrhage)long-term compl. (psychomotor retardation and CP)
 Undiagnosed hemophiliacs in association with circumcision [50%].

25.  More often, severe hemophilia A and B become symptomatic within the
first two years of life.
 In those carrying prothrombotic risk factors (eg, factor V Leiden, protein C
deficiency), the first bleeding episode occurred significantly later.
 Common presentations - Dental procedures , excessive bruising ,
hematomas, or hemarthroses with activities considered normal for age
 The onset of disease occurs later in patients with moderate and mild
hemophilia.
 Moderate and mild hemophilia -age 14 to 62 years , have very few or no
bleeding episodes, ccur only with trauma or surgery .

26.  Very rare.
 Following genetic mechanisms-
› Lyonization of factor VIII or IX alleles in carriers.
› Hemizygosity of X chromosome in females with
Turner’s syndrome.
› Female progeny of hemophilia carriers & affected
haemophiliac male.

27.  80 percent of hemorrhage occurs in the joints; the ankles are most
commonly affected in children, and the knees, elbows, and ankles
in adolescents and adults .
Head and neck —
-Epistaxis
-Bleeding from the oral mucosa and teeth following minor trauma
or dental procedures.
-In addition, coughing or vomiting can produce bleeding into the
posterior pharynx, which can lead to airway compromise or airway
obstruction.

30.  Hemarthroses —
 Bleeding originates from the synovial vessels, and hemorrhage occurs within the joint cavity.
 Chronically hemarthrosis is the initiating event in hemophilic arthropathy.
 The clinical manifestations vary by age -
Infant-decreased usage, bigger – prodromal stiffness and joint warmth swelling and pain
One joint is usually affected at a time, but multiple bleeding sites are not uncommon.
 Skeletal muscle —
 hematoma formation most often affects the quadriceps, iliopsoas, and forearm. Iliopsoas muscle
.
 May be large and may compromise neurovascular structures and produce a compartment
syndrome.
 Untreated hemorrhage may lead to the formation of a pseudotumor with hematoma surrounded
by a fibrous membrane.
 Recurrent hemorrhage is common.

31.  Lesions from blood in the stool to life threatening 3rd spacing.
 Bleeding into the abdominal wall can produce severe pain that
often is misdiagnosed as an acute appendicitis.
 Patients with hemophilia also can develop hematomas of the bowel
wall, producing symptoms that mimic acute appendicitis or produce
obstruction or intussusception.
 The diagnosis of "pseudo-appendicitis" usually can be made with
CT scan, but occasionally surgery is required to confirm the
diagnosis.
 Bleeding into the retroperitoneal space can also occur.

32.  Hematuria is a frequent manifestation of severe
hemophilia; usually.
 Benign and not associated with progressive loss of
renal function .
 Arise from the kidneys or bladder
 May persist for days or weeks.
 Ureteral obstruction with colic may occur when clots
form.

33.  Posttraumatic bleeding — Patients with hemophilia seldom bleed from small cuts
or venipuncture, but hemorrhage out of proportion to injury occurs after larger
injuries. Delayed bleeding is common; it can be massive or may persist as
continuous oozing for days or weeks. Delayed bleeding can occur in patients with
mild hemophilia after minor surgical procedures such as tooth extraction.
 It was hypothesized that Tissue factor is normally down-regulated during wound
healing in order to prevent thrombosis of newly-formed vessels, but renders those
with hemophilia vulnerable to hemorrhage during the healing process.

35.  Late complications —
 Joint destruction due to hemarthroses, leading to a number of orthopedic abnormalities
 Transmission of blood-borne infection
 Development of inhibitor antibodies.
 Hemophilic arthropathy —
 As blood is catabolized, it is absorbed by synovium
 Iron is toxic to cells – synovial cells disintegrate releasing lysosomes which destroy
cartilage and inflame synovium
 Hypertrophic, hypervascular synovium
 Chondrocytes also affected
 FIBROSIS

36.  Infection — patients treated with older factor VIII or IX
concentrates were at high risk for infection with hepatitis A, B, C,
and D and with HIV . Most patients were infected with hepatitis
C virus (HCV), and HIV infection occurred in an average of 50
percent of patients overall . Co infection with HCV and HIV is a
concern

37. Three phases
1.Following first episodes
of hemarthrosis
absorption of blood is
incomplete, the retained
blood produces
chronic inflammation. Iron
is deposited into the synovium and
chondrocytes of the articular cartilage.

38. 2. Chronic proliferative
synovitis-
characterised by
presence of chronic
synovitis, pain,
fibrosis and
progressive joint
stiffness.

39. 3. Chronic hemophilic arthropathy-characterised by
progressive and erosive destruction of joint cartilage,
narrowing of joint space,subchondral cyst formation,
and eventual collapse and ankylosis of the joint.
MRI is superior to standard radiography
for assessment of early arthropathy.

40.  Careful review of the family history Screening test Specific
Assay
 Family history —
 Mother can be identified as a carrier because of the presence of
abnormal bleeding in other members of her family.
 One-third have a negative family history; thus, lack of a family
history is of little value in excluding the possibility of hemophilia.

41.  Three initial tests should be performed: platelet count, prothrombin time (PT), and activated
partial thromboplastin time (aPTT).
 A normal platelet count, normal PT, and a prolonged aPTT are characteristic of hemophilia A,
hemophilia B, and heparin therapy .
 An abnormal test occurs in individuals who have less than approximately 30 percent of the
mean normal concentration of factor VIII;
 Mild hemophiliac B may have normal or near normal aPTTs. Thus, in undiagnosed mild bleeding
disorders, a factor IX assay should be performed even if the aPTT is normal.
 Prolonged aPTT but not the PT.- acquired inhibitors to factor VIII and IX, and deficiency
of factor XII, prekallikrein, or high molecular weight kininogen (abnormal bleeding does not occur
with these deficiencies).
 Normal platelet count, normal PT, and a prolonged aPTT- is seen in
antiphospholipid antibodies who have a tendency to thrombosis rather than bleeding.

42.  Specific assays for the factors that can produce an isolated prolonged aPTT are
performed in the order of their statistical frequency (ie, factor VIII, IX, and XI).
 Another method for the measurement of factor VIII is a chromogenic substrate
assay
 Highly specific but complicated assays using ELISA also have been developed.

43. Patients with von Willebrand disease tend to have a different pattern of bleeding from
hemophilia .
The most sensitive laboratory test for the diagnosis of von Willebrand disease is the
ristocetin cofactor assay.
GREY ZONE - Type 2N von Willebrand disease (qualitative defect of VWF)
 Bleeding in these patients is caused by low factor VIII levels (5 to 15 percent of normal)
and mimics the findings seen in mild hemophilia.
 Type 2N von Willebrand (normal VWF level ,low factor VIII ) v/s Hemophilia –
 Female pt. mild bleeding
 Autosomal Inheritance.

44.  The mean concentration of immunologic and pro-coagulant factor VIII in the plasma of heterozygous
carriers is approximately 50 percent that of normal women.
 The demonstration of subnormal levels strongly suggests the presence of the carrier state, but the
presence of normal levels does not reliably exclude it.
 At least 50 percent of obligate carriers of hemophilia B have a factor IX level below 60 percent.
 DNA-based techniques are the preferred method.
 Genetic analysis of the human factor VIII and IX genes also has resulted in accurate prenatal diagnosis.
 Studies are performed by amniocentesis or, less often, a chorionic villus sample obtained in the
eleventh to twelfth gestational week

45.  Reason- Extreme degrees of X chromosome inactivation (lyonization) and other genetic
factors may lead to very low clotting factor levels in heterozygous carriers, with associated
bleeding phenomena.
 While clotting factor levels from 0.40 to 0.05 IU/mL were increasingly associated with
prolonged bleeding from small wounds, tonsillectomy, tooth extraction, and operations.
 It was concluded that clotting factor levels should be obtained in all carriers preceding a
medical or surgical intervention in order to assess their risk of bleeding.

46.  Circumcision — male infants born to known or suspected carrier mothers should
not be circumcised until hemophilia has been excluded. Assays can be performed
on cord blood.
 Use of fibrin glue is safe, lessens the need for factor substitution after circumcision,
and markedly reduces the high cost of treatment
 Routine immunizations —
 May be given in the deep subcutaneous tissue.
 The smallest gauge needle should be , pressure for five minutes.
 The live oral polio attenuated vaccine is contraindicated in an infant when there is an
immunocompromised household member (eg, HIV-infected hemophilic)
 Dental care — Dental care is essential for individuals with congenital bleeding
diatheses. Early infant dental intervention is recommended to teach proper tooth
brushing and ensure adequate household water fluoridation.
 Exercise regimen that excludes contact sports (eg, tackle football) should be
encouraged as a daily routine.

47.  Hemophilia is often called the disease of kings
because it was carried by many members of
Europe’s royal family.
 Queen Victoria of England was a carrier of
haemophilia.

48.  Clotting factor concentrates are given to prevent
bleeding and to limit existing hemorrhage.
 Available products —
 Commercial fractionation of cryoprecipitate yielded
the first generation of lyophilized factor VIII
concentrate. They resulted in an approximate 100-
fold increase in concentration of factor VIII over
fresh frozen plasma.
 Plasma derived factors by 1970-80’s (HepC and HIV
infection occurred in up to 50 percent.)
 Recombinant human factor- 1st , 2nd ,3rd gen.
(depending upon purity and stability 1/2life)

49. Fundamentals
 Replacement therapy- Replacement of FVIII or IX
to hemostatically adequate plasma levels.
 Knowledge of the half-life, volume of distribution,
patient’s inhibitor status and appropriate
replacement material is necessary.
Table-Biodynamic properties of coagulation factors of concern in replacement therapy
Factor
Hemostatic level
(U/dL)
Biologic half life (hr)
FVIII 25-30 12
FIX 15-30 24

50.  Types of factor replacement-
› Treatment on demand.
› Prophylaxis.

51.  For mild to moderate haemorrhages, achieve
FVIII levels of 30-40 U/dL or FIX levels of 30
U/dL.
 For life threatening haemorrhages,
immediately correct factor level to 100-150
U/dL and maintain level between 80-100
U/dL for 5-7d followed by vigorous
maintenance.

52.  Early joint or muscle bleeding-- achieve factor levels of 30 to 40 percent.
 More severe muscle hematomas and those undergoing dental surgery usually are treated to
achieve levels of 50 percent.
 Severe or potentially serious episodes ( Intracranial or intraabdominal hemorrhage) OR
bleeding in areas such as the face, neck, and hip require correction to 80 to 100 percent until the
hemorrhage has resolved.
 Most orthopedic surgery can be managed with initial levels of 80 to 100 percent followed in a
few days by minimum levels of at least 30 percent; an exception occurs at times of wound or
joint manipulation when a level of at least 50 percent is necessary.
 To achieve hemostasis for major surgical procedures, an initial level of 60 to 100 percent is
achieved. This level is followed by a prophylactic level of 30 to 50 percent until the wound is
healed, typically 10 to 14 days.
 Factor levels should be checked to ensure the effectiveness of the calculated dose.
 Continuous infusion of factor VIII -maintain the level initially achieved by bolus infusion. Patients
undergoing major surgery or those with major hemorrhage at risk of rebleed may benefit
from such continuous therapy.

53.  Factor VIII replacement--
 IV administration of 0.5 international units/kg of factor VIII will
increase circulating factor VIII levels by ~1 international units/dL (ie, 1
percent).
 Dose of F VIII (international units) = Weight (kg) x (Desired %
increase) x 0.5
 In our pt.- had to increase the factor VIII level by 80 percent (eg, from
2 to 100 % ,Wt-50 kg, the required IV dose is 2000 IU )

54.  Manco-Jonson et al in their prospective,
randomised, controlled clinical trial showed 83%
reduction in risk for joint damage (evaluated
by MRI) in the prophylaxis group as
compared to on-demand group. In 14% cases
of MRI changes, there was no evidence of any
previous clinical hemarthrosis.

55.  Fischer et al in their long term outcome
study over 22yr showed that
prophylaxis improves clinical
outcome without significantly
increasing treatment cost.

56.  Primary prophylaxis - therapy initiated in young
patients who have hemophilia before joint damage
 High cost of primary prophylaxis – the long term
cost savings may be greater with primary
prophylaxis as joints are preserved, lives are more
productive, expensive surgical interventions
avoided.

57. › Scheduled infusion therapy at an early age
before bleeding has regularly occurred to convert
patient from severe deficient state to moderate
deficient
› Goal: suppression of spontaneous bleeding
episodes
› Frequency: 2 to 3 times weekly to keep trough
factor VIII or IX levels at 2-3%
› Use of IVAD necessary in some patients

58. When to start primary prophylaxis ?
 no consensus!!
 Start before 3 years of age, usually around
14-18 mo, at the time that the child begins to
walk.
Secondary prophylaxis
 In patients with “target joints” who are having
recurrent events.
 Coagulation factors are administered as in
primary prophylaxis but over limited period of
3-6 months.

59. › Scheduled infusion therapy at any age after
bleeding has regularly occurred or after injury
to convert patient from severe deficient state
to moderate deficient
› Prior to sports activity
› Goal: suppression of spontaneous bleeding
episodes or rebleeding
› Frequency: 2 to 3 times weekly to keep
trough factor VIII or IX levels at 2-3%
› Use of IVAD necessary in some patients

60.  Administered by subcutaneous
access port of a central venous
line.
 Dose and rate adjusted to ensure
that nadir before next infusion is
>1U/dL.
 May still require additional
replacement.

61.  Tailored to patient’s bleeding pattern, joint
involvement and individual needs.

62.  Inhibits fibrinolysis of thrombus by plasmin.
 Uses - mucosal bleeding, oral, nasal and menstrual
loss.
 Tranexamic acid -effective topically
as a mouth wash
 C/I in hematuria.
Dose
 Tranexamic acid
› oral- 25 mg/kg/dose every 6-8hr.
› iv - 10 mg/kg/dose every 6-8hr.
 EACA
› Oral - 100-200mg/kg initially followed by
50-100mg/kg/dose every 6hr
› iv - 100mg/kg/dose every 6hr.

63. Cryoprecipitate
 Prepared by slowly thawing fresh frozen
plasma at 2-4`C, then harvesting the
precipitate by centrifugation.
 Cryo prepared from 200ml of FFP
contains 80-100 U of FVIII, ~250mg
fibrinogen and useful amounts of FXIII
and vWF per 10-15ml of precipitate.
 Use thawed cryo within 4hr.
 Can be stored at -18`C for 1yr.
PLC

64.  Types
› On basis of source of origin.
› On basis of purity:
intermediate, high, ultrahigh.
 The safety data to date favour recommendation to
exclusively use recombinant products.
 Infuse FVIII by slow IV push at a rate not to exceed
100 units per minute in children.

65.  Analogue of Vasopressin w/o AD effect.
 Action - Increases circulating factor VIII levels two to four times above
baseline and four to six times above baseline in those who begin with
factor VIII levels more than 9 percent of normal.
 Intravenously, subcutaneous injection, or by intranasal spray.
 Uses –
 1.Mild Hemophilia
 2.Pre procedure or acute bleeding setting.
 Effect -An increase in factor VIII levels is expected in 30 to 60 minutes
after the infusion, and the response persists for 6 to 12 hours
 S/E to watch out for – Hyponatremia , tacyphylaxis.

66.  Action- enhances clot stability - inhibit
fibrinolysis by inhibiting plasminogen activation
in the fibrin clot.
 Use- therapeutic adjuncts to stabilize clots in
areas, such as the oral cavity ,difficult episodes
of epistaxis and menorrhagia.
 Orally or intravenously, short half-lives.

67. Activated Prothrombin complex concentrates
 Have increased amounts of activated FVIIa, factor X &
thrombin.
 APCC are effective even in patients with high titer
inhibitors.
 risk of thrombosis.
Polyethylene glycol conjugation (Pegylation)
 Increases size, decreases renal excretion, extends half
life.
Polysialic acid polymers
 Forms a “watery cloud” around the target molecule
 Biodegradable.

68.  Bypasses the FVIII-dependent step
in factor X activation
 Primary use- Hemophilia with inhibitors.
 Other uses- control bleeding in traumatic
coagulopathies, thrombocytopathies, liver disease,
liver transplantation, spontaneous intracerebral
hemorrhage and patients undergoing cardiac
surgery.
 Dose-90mcg/kg 2hrly till hemostasis.
**

69.  Ex vivo gene therapy in which cells from the intended recipients are
explanted, genetically modified to secrete factor VIII or IX, and
reimplanted into the donor
 In vivo injection of factor VIII or IX encoding vectors into the recipient.
Vectors incorporating factor VIIa, a protein to which factor VIII-deficient
and factor IX-deficient subjects have immunologic tolerance, have also
been employed
 The goal of therapy does not have to be restoration of normal factor
levels; conversion from a severe (factor VIII <1 percent) to a mild
phenotype (factor VIII >5 percent) would be sufficient to produce
dramatic improvement.

70.  Analgesics (acetaminophen alone or with
codeine), ice packs ( 5 minutes on, 10 minutes
off, for as long as the joint feels hot), avoidance
of weight bearing and immobilisation.
 Factor replacement- most important
 Synovectomy-
types
Arthroscopic
Chemical
Radiosynovectomy

71.  Arthrocentesis
› Reserved modality
 Physiotherapy
 Reconstructive surgery
Management of hemophilic arthropathy.

72.  Hip joint or acetabular hemorrhages may result in increased intraarticular
pressure and osteonecrosis (aseptic necrosis) of the femoral head .
 Rx-Twice-daily infusion therapy designed to sustain a factor level above a
minimum of 20 percent for at least three days should be given, along with
enforced bed rest.
 Hip hemarthrosis may be difficult to differentiate from an iliopsoas bleed,
but the following may be helpful:
1.An iliopsoas bleed limits primary hip extension, whereas hemarthrosis makes
any motion of the hip excruciatingly painful.
2.An iliopsoas bleed may lead to decreased sensation over the ipsilateral thigh
because of compression of the sacral plexus root of the femoral nerve.
3.Ultrasonography may demonstrate a hematoma in the iliopsoas region.

73. Do the 5! is a list of 5 things one can
do to help live a long and healthy life. The
NHF started the idea for Do the 5!
1. Get an annual comprehensive check-up at a hemophilia
treatment centre.
2. Get vaccinated - Hepatitis A and B are preventable.
3. Treat bleeds early and adequately.
4. Exercise and maintain a healthy weight to protect the
joints.
5. Get tested regularly for blood-borne infections.

74. Inhibitors
 Alloantibodies directed against FVIII or FIX
 Clinical hallmark- failure to respond to routine replacement
therapy.
 Incidence - hemophilia A ~30%;
hemophilia B ~3%.
 Low titer (<5 BU); usually transient.
 High titer (>5 BU); persistent.
 Screen once every 3-12 months or every 10-20 exposure days
and prior to surgery or when clinical response to adequate
treatment is sub-optimal.

75.  Low titer- high dose factor replacement.
 High titer
› continuous FVIII infusion.
› bypassing agents- recombinant factor VIIa or
activated prothrombin complex concentrates.
› Immune tolerance induction (ITI)
› Rituximab- limited data (only 18 patients)

76. Immune Tolerance Induction
 Immune system desensitisation technique
intended to eradicate inhibitor.
 Success of ITI ~90% over 6-12 months for
alloFVIII antibody inhibitors.

77. 
FACTOR VIII
(50.0-150.0)
%157.0 H ---160.0--- H 186.0 ---H 132.0---
131.0---142.0----100.0---171.0 H ---175.0 H -
--126.0---89.0---54.0---110.0---20.0