Haemophilia is a group of hereditary genetic disorders that impair the body's ability to control blood clotting or coagulation, which is used to stop bleeding when a blood vessel is broken.

1. Medically compromised children
Haemophilias

2. Contents
• Introduction
• Incidence and Prevalance
• Classifications
• Haemophilia A
• Haemophilia B
• Haemophilia C
• Von Willebrands disease
• Dental care
• Medical management
• Protocols
• References

3. Introduction1
• The inherited disorders of blood coagulation present providers of health and social
care with formidable problems.
• The disorders are eminently treatable, even in their severest form.
• Untreated, they result in handicaps in early life, while proper treatment is
expensive, inadequate treatment is even more so, both to the individual and to the
community (Bhattacharya 1987).

4. • Nearly one third of cases of haemophilia occur with no preceding family
history, possibly from new genetic mutation.
• When recorded family history is available, efforts should be made to identify
female carriers. Identification depends on family history, measurement of
clotting profile and DNA analysis.

5. • World Federation of Haemophilia reported haemophilia A prevalence varied
considerably among countries, even among the wealthiest of countries.
• The prevalence (per 100 000 males)
High income countries -> 12.8 ± 6.0 (mean ± SD)
Rest of the world-> 6.6 ± 4.8

6. • Haemophilia A and B are X-linked recessive disorders that occur almost exclusively in
males.
• About 30 percent of the mutations arise de novo.
• Factor VIII gene is very large, about 186kb, with about 9kb of exons. It contains 26
exons and 25 intervening sequences or introns.
*Intron: Sequences that are joined together in the final mature RNA
*Exon is any nucleotide sequence encoded by a gene that remains present within the
final mature RNA product

7. • The size and complexity of the gene have made it difficult to pinpoint, on a routine
basis, specific mutations that result in haemophilia.
• However, the factor VIII gene has now been cloned and sequenced and numerous
specific mutations have been described .
(Williams 2001; Jayandharan et al. 2003).

8. Haemophilia A2
• Classic hemophilia
• Def’ of Fac VIII
• 80% of Hemophilia
• Inherited X-linked recessive trait
• Males affected; Females Carriers
• No male to male transmission

9. Reported haemophilia A prevalence (per 100 000 males)
Mean: 98-’06
• In US, 2006 reported prevalence -> 8.0 /100 000 males
• In UK, 2006 reported prevalence -> 20.7 / 100 000
• Highest affected Iceland-> 38% (mean)
UK-> 19 %
Croatia->18%
Ireland ->16%

10. Reported haemophilia A prevalence (per 100 000
males) : India
• 2003:0.5
• 2004: 0.9
• 2005: 1.6
• 2007: 1.7
• Mean: 1.1

11. Pattern of inheritance

12. Hemophilic M + Normal F
Males: Normal; Females: Carriers

14. Hemophilia B2
• Also known as Christmas Disease
• Named after the first pt Stephen Christmas
• Seen in 15 % Hemophiliacs,
• Def’ of Fac IX ( Plasma Thromboplastin
component)
• X-Linked Recessive trait
*First article on it was published in Brit Med J
in Christmas edition

15. Why autosomal recessive
• Both these disorders are inherited as sex linked recessive. Isolated deficiencies of
other clotting factors are less common because they are usually inherited in
autosomal recessive manner and this requires both parents to carry the abnormal
gene.

16. Hemophilia C3
• Rosenthal Disease,Def’ of Fac IX ( Plasma
Thromboplastin antecedent, Autosomal
recessive trait
• Males and Female equally affected,
• Ashkenazi Jewish Descent
• Other factor deficiencies
Fac II, V, XIII (one per one million)
Fac VII ( one per five lakh)

17. Classification of hemophilia5

18. Pro-coagulant classification2
• Severe deficiency : Levels less than 1%
• Moderate deficiency : Levels between 1%-5%
• Mild deficiency: Levels </= 5% or less than 55%

19. Bleeding episodes: Severe
• Two - four times / month
• Bleeding episodes: Spontaneous cout H/o Trauma/Injury
Common sites: Joints , muscles, Skin
• Hemarthoses are common with symptoms of Pain, Stiffness and limited motion
• Repeated episodes  Chronic musculoskeletal disease culminate in
• Debilitating painful arthritis
Commonly affected joints: Knees, elboes, ankles, hips & shoulders
• Pseudotumors occur in sev’ locations including jaw, where curretage is indicated

20. Bleeding episodes: Moderate
• 4-6 times bleeding / year
• Target joint develops Spontaneous bleeding might occur
• Bleeding episodes: Mild
• Diagnosed during presurgical evaluation
• Dentist May be 1st to identify & unmask a previously undiagnosed individual.

21. Common cause of Bleeding: mouth lacerations
• Sonis and Musselman -132 pts - factor VIII– def’ hemophilia
• "persistent oral bleeding resulted in the diagnosis of 13.6% of all cases of hemophilia."'
• 29% cases(mild hemophilia)  bleeding from the oral cavity.
• Secondary to oral bleeding,
• 78%  maxillary frenum
• 22%  tongue bleeds.

22. Summing up symptoms
• Spontaneous Haemorrhage
• Deep Hematomas and hematuria
• Gingival hemorrhage more prolonged and massive.
• Mandibular pseudo-tumor with tooth displacement
• enlargement of bony structure
• delicate trabeculae and areas of radiolucency.
• Mouth ulceration
• Increased occurrence of periodontal disease and caries due poor hygiene

23. General clinical features2,3

24. Oral symptoms

25. Von Willebrand’s disease ( vWD) 2,4
• Most common hereditary coagulation disorder occurring due to
qualitative / quantitative defect in von Willebrand’s factor( vWF)
• Incidence: 1 IN 1000, Both males n females
• Comprises of complexes of Fac VIII-vWF, which circulate in blood

26. • Caused as VIII molecule is abnormal, is usually inherited as autosomal dominant
fashion and is therefore the most common, but overall is the least severe of the
inherited clotting disorders.

27. • Most imp function: Carrier for FVIII in plasma

28. • Type 1 VWD is found in 60%-80% of patients. People with type 1 VWD have a
quantitative deficiency of VWF. Levels of VWF in the blood range from 20%-50% of
normal. The symptoms are usually mild.
• Type 2 VWD is found in 15%-30% of patients. People with type 2 VWD have a
qualitative deficiency in their VWF. Type 2 is broken down into four subtypes: type
2A, type 2B, type 2M and type 2N, depending on the presence and behavior of
multimers, molecular chains of VWF. Symptoms are mild to moderate.

29. • Type 3 VWD is found in 5%-10% of patients. People with type 3 VWD have a
quantitative deficiency of VWF. Symptoms are typically severe, and include
spontaneous bleeding episodes, often into their joints and muscles.
• Acquired VWD. This type of VWD in adults results after a diagnosis of an
autoimmune disease, such as lupus, or from heart disease or some types of cancer.
It can also occur after taking certain medications.

31. Clinical Features
• Due to impaired platelet plug formation,It leads to
-Hemorrhages from the skin and mucosa
- Easy bruising
- Epistaxis
- Prolonged bleeding after surgery
- GIT hemorrhage

32. Investigations for bleeding disorders
Screening tests
Partial
thromboplas
tin time
Prothrombin
time
Platelet
count
Ivy bleeding
time
Platelet
function
analyzer
Thrombin
time
Diagnostic tests
Platelet aggregation test Platelet release reaction Factor Assay

33. Detection of Haemophilia A Traits in Carriers: De et al. 1989
• It is known to impose a severe strain on the affected individual and his family as
well as on the blood transfusion services of the country.
• It is therefore essential to detect the potential carriers of haemophilia A, so that
they can be given precise genetic counseling.
• Blood samples are collected from normal women and obligate carriers of
haemophilia A in the reproductive age group.

34. • The obligate carriers were the mothers of known haemophiliacs who are being
treated at the center.
• Blood (4.5 ml) was divided into aliquots, one of which is taken for prothrombin
time (PT), activated thromboplastin time (APTT) and factor VIII coagulant
activity (FVIII C) measurements while the other was snap frozen and stored at -
700C for later use in factor VIII related antigen (FVIII) R: Ag) determination.

35. • The APTT was significantly higher in carriers. The levels of FVIII C and R: Ag were
significantly lower in carriers than in normal individuals.
• The ratio of FVIII C to FVIII R: Ag in carriers was 0.55 while that in normal was 1.0.
By applying the linear discriminating the result of the study indicates that the
ratio of FVIII C to FVIII R: Ag can be of use for the routine detection of obligate
carriers of haemophilia A

36. Identification of Hemophilia
• Certain options are available of identificator of carriers of severe
haemophilia.
• These include, preimplantal diagnosis of an embryo following in vitro
fertilization, fetal diagnosis of chorionic villus sampling (CVS) using DNA
technology, fetoscopy using clotting factor assay and amniocentesis in
order to obtain confirmation of fetal status.

37. • One third of haemophilia carriers have factor VIII or factor IX levels below
normal and are in danger of abnormal bleeding following injury, surgery or
dental extraction but not in pregnancy as factor VIII level rises normally
(Choudhry et al 1996; Kashyap and Choudhury 2000).

38. Complications2
• Inhibitors : 28% (severe factor VIII deficiency pts)
: 3% -5% of patients with severe factor IX deficiency.
• Accurate knowledge of the classification and level of the inhibitor is necessary for
successful treatment.
• Patients with inhibitors are divided into two general groups,
• high responders
• low responders based on the past peak anamnestic response.

39. • Low-response : Continue with factor concentrate,
• High-response : Bypassing products ( either PCC or activated PCC and recombinant
factor VIIa).
• Hemophilic patients with inhibitors pose a challenging treatment problem and
should be managed only in conjunction with a hemophilia comprehensive center,
since hemostasis may be difficult to achieve.

40. Other complications
• Arthritis & degenerative joint disease, secondary to recurrent bleeding and
bloodborne viral infections
• Hepatitis (either B or C) and resultant liver disease have been a significant source of
morbidity and mortality in this patient population.
• The human immunodeficiency virus (HIV)

41. Dental care of children
1. Recording past medical, dental & family history
2. Consultation with pediatrician
3. Dental procedures with high risk for bleeding
4. Pharmacological agents for management of bleeding
5. Application of specific dental treatment:
6. Early caries diagnosis and healing of incipient carious lesion.

42. Past medical dental and family history

43. Consultation with pediatrician
Consult request should involve:
• Number of dental procedures in treatment plan that may cause bleeding
• Plan for local anesthetic administration
• No of appointments needed to complete the treatment
• Caries activity and oral health summary of child

44. Treatment as outpatient Vs general anesthesia
▫ Depends on extent of dental treatment needed, patient behavior, and
severity of bleeding disorder.
▫ When full moth rehabilitation is needed, general anesthesia is preferred.
▫ Oral intubation is preferred over nasal intubation.

45. Dental procedures for high risk of bleeding
• Extractions
• Pulp therapy
• Class II restoration
• Administration of inferior alveolar nerve block
• Other surgical procedures

46. Pharmacological agents in the management of
bleeding.
• Epsilon aminocaproic acid
( Amicar, Aprotinin)

47. Tranexemic acid

48. Desmopressin(DDAVP, stimate) stimulates the release of factor VIII

49. Local haemostatic agents

50. ε-Aminocaproic acid
• Dose in children: 100 to 200mg/kg
upto 10 g oral before procedure
• After procedure, 50-100gm/kg upto 5
gm oral every 6 hours for 5-7 days
• If weight of child> 30kg, adult dose
i.e.3gm 4 times a day
• Adv: availability in tablet and liquid
form

51. Tranexemic acid
• Dose: 25 mg/kg immediately before
treatment
• Same continued every 8 hours for 5 to 7
days.

52. Side effect
• Headache nausea
• Dry mouth
• Avoided in case of renal and urinary tract bleeding
• Or in case of DIC

53. DDAVP(1-deamino8 p arginine vasopressin)
• Is synthetic analogue of pituitary
hormone vasopressin.
• When given IV/SC/IN, increases activity
of factor VIII and VWF through its release
from stored sites.
• Concentration used: 1.5mg/mL

54. • Peak activity : 1 hour IV/SC; 90 min IN
• Side effects:
▫ tachyphylaxis,
▫ water retention,
▫ hyponatremia,
▫ seizures.

56. Analgesia and stress management
• If patient is apprehensive, sedation can be done.
• Intra-muscular injections are avoided
• Aspirin should be avoided
• Acetaminophen and propoxypene hydrochloride can be prescribed.
• For severe pain, narcotics are given.

57. Local anesthesia
• Pdl injections are preferred
• Infiltration anesthesia, can be given, but in areas of high vascularity,
factor activity of atleast 40% should be maintained.

58. • Inferior alveolar nerve block and PSA contraindicated
• Careful aspiration before injecting.
• If aspiration is positive, replacement therapy should be given.

59. Preventive care
• Tooth brushing, flossing, topical fluoride exposure, diet counseling
• Rubber cup prophylaxis, and supragingival scaling can be done
without factor replacement

60. • Minor bleeding controlled with local measures like gauze packs and
topical application of bovine thrombin, microfibrillar collagen and
fibrin glue.

61. Periodontal therapy
• Patients requirement deep scaling, initially to supragingival and then
repeat after 7-14 days.
• Usually requires replacement therapy.

62. Restorative dental care

63. • Wedges and matrices used to papillary gingiva
• High vacuum suction and saliva ejectors and intraoral radiographs used
with caution.
• Periphery wax covering impression tray,
• subgingival tooth preparation, use retraction cords.

64. Pulp therapy
• Pulp therapy (indirect pulp capping, pulpotomy, pulpectomy) is
preferred over extraction
• Intra-pulpal injections can also be used.
• Pulpal bleeding controlled with pressure from cotton pellets

65. Oral surgery
Tooth extraction
• For simple extraction of erupted permanent and multi-rooted primary
teeth, 30-40% factor correction administered 1 hour before procedure.
• Antibrinolytic therapy started immediately after and continued for 5-7
days.
• Clear liquid diet for 72 hours.

66. • Soft pureed diet for next 1 week
• No using straws, metallic utensils, pacifiers
or bottles.
• After extraction, topical application of
thrombin or micro-fibrillar collagen

67. Haemostatic agent held in place with sutures

68. • Stomahesive (J knipper and Co) may be
placed over wound for protection
• Sutures if needed, should be absorbable

69. • Surgical extractions of impacted, partially erupted, unerupted teeth
require more extensive replacement therapy.
• Electro-surgery is preferred over conventional surgery.

70. • Extraction of single rooted primary teeth
• Depends on root development

71. Shedding of primary teeth:
• Usually does not cause bleeding
• Controlled with gauze pressure and topical application of haemostatic
agent.

72. Medical Management

74. Management of Hemophilia6,9
• Replacement of Factor VIII in Haemophilia A Management of haemophilia is almost
exclusively based on administration of commercial Factor VIII concentrates prepared
from plasma obtained from thousands of donors.
• Treatment with commercial Factor VIII concentrate presents two major problems
viz.,
(a) it is very expensive as often it has to be imported
(b) there is a high risk of contamination with hepatitis B virus, hepatitis C virus as well
as HIV, from the large number of donors.

75. • Production of good quality cryoprecipitate from plasma was achieved, as assessed
by quantitating Factor VIII coagulant activity (F VIII C) and Factor related antigen (F
VII R: Ag).
• The method used resulted in good recovery of FVIII in the cryoprecipitate containing
FVIII C: Fibrinogen 0.82±0.015 IU/mg.

76. • The method therefore appears suitable for indigenous preparation of F VIII in
standard blood banks as a replacement therapy, which is not expensive (De et
al.1989, 1991). High purity cryoprecipitate may be used in surgery (Ghosh et al.
1998).

77. Protocol for management of Hemophilia A patient

78. Management of hemophilia B

79. Management of VWD8
• Decisions about treatment for patients with vwd begin with accurate diagnosis and
complete evaluation.
• The role of oral physician, in emphasizing upon seeking history of the response to
hemostatic challenge such as dental extraction, tonsillectomy, surgical procedure,
menstruation and peripartum hemorrhage, is of utmost importance in identifying
patients with vWD.

80. • The spectrum of therapeutic interventions includes desmopressin (DDAVP) for non-exogenous
replacement therapy, and adjunctive therapy with medications that
modulate bleeding symptoms.
• To treat both the factor VIII deficiency and defect in primary hemostasis, it is
generally necessary to give a product with factor VIIIc activity that also contains
high molecular weight multimers of vWF.

81. • There are a few clotting factor concentrates that are rich in VWF, and are
recommended for patients with VWD. These therapies are given by intravenous
infusion.
• Aminocaproic acid and tranexamic acid are antifibrinolytics agents that prevent the
breakdown of blood clots. These drugs are often recommended before dental
procedures, to treat nose and mouth bleeds, and for menorrhagia. Antifibrinolytics
are taken orally, as a tablet or liquid.

82. Von willebrands disease