The seminar presentation covered hemostasis and approaches to bleeding disorders in pediatrics. It discussed the pathophysiology, clinical features, laboratory findings and management of idiopathic thrombocytopenic purpura, Von Willebrand's disease, and hemophilia. It provided an overview of hemostasis and the coagulation cascade, approaches to evaluating a child with bleeding, and specifics on selected bleeding disorders. The presentation included descriptions of laboratory tests used to evaluate coagulation factors and identify bleeding disorders.

1. SEMINAR PRESENTATION
SPHMMC
DEPARTMENT OF PEDIATRICS AND CHILD HEALTH
BY C 1 STUDENTS
MERRY KASSA
TEMESGEN GELETA
SELAHADIN GENZEB

2.  Hemostasis
 Approach to bleeding disorders in pediatrics
 Understand the pathophysiology, clinical features,
laboratory findings and management principles of;
 Idiopathic thrombocytopenic purpura
 Von Willebrand’s disease
 Hemophilia

3.  Overview of hemostasis
 Approach to a child with a bleeding disorder
 Bleeding disorder
 Vonwillebrand’s disease
 Hemophilia
 Idiopathic thrombocytopenic purpura (ITP)

4. By Mary Kassa

5.  Prothrombin time (PT) – the time it takes plasma to clot after
addition of tissue factor. This measures the quality of the extrinsic
pathway (as well as the common pathway) of coagulation.
- Normal value range = 12 – 15 sec. The speed of the extrinsic
pathway is affected by levels of functional factor VII in the body.
- PT can be prolonged due to vitamin K deficiency, warfarin therapy,
malabsorption, poor factor VII synthesis (liver disease), or increased
consumption in DIC.

6.  Partial thromboplastin time – measures the speed at which
blood clots form by means of the intrinsic and common
pathways. It measures factors I, II, V, VIII, X, XI and XII. It’s
commonly used in conjunction with PT test.
- The typical reference range is between 30 and 50 seconds.
- Prolonged PTT may indicate coagulation factor deficiency
(hemophilia A and B), use of heparin, sepsis (coagulation factor
consumption), presence of antibodies against coagulation factors

7.  International Normalized Ration (INR) – is the ratio of a
patient’s prothrombin time to a normal (controlled sample),
raised to the value of the ISI value for the analytical system
being used.
INR = (PTtest/PTnormal)ISI
- INR is typically used to monitor patients on warfarin or
related oral anticoagulant therapy. The normal range for a
person not on warfarin is 0.8 – 1.2. For people on warfarin
therapy an INR of 2.0 – 3.0 is usually targeted.
- A high INR indicates a higher risk of bleeding, while a low
INR suggests a higher risk of developing a clot.

8.  Hemostasis is the active process that clots blood in areas of blood
vessel injury to limit blood loss, yet simultaneously limits the
clot size only to the areas of injury.
 It needs to be rapid and regulated such that trauma does not
trigger a systemic reaction but must initiate a rapid, localized
response.
 If clotting is impaired, hemorrhage occurs and if clotting is
excessive, thrombotic complications ensue.

9.  The process is carefully regulated through feedback loops and
mediators to ensure appropriate response.
 The main components of the hemostatic process are the vessel
wall, platelets, coagulation proteins, anticoagulant proteins,
and fibrinolytic system.

10. PHASES OF THE HEMOSTATIC PROCESS
 Although the clotting process is a dynamic array of multiple
events, it can be viewed as occurring in four phases:
- Vasoconstriction and formation of the platelet plug
- Blood coagulation (clot formation) by the coagulation
cascade
- Termination of clotting by antithrombotic control
mechanisms
- Removal of the clot by fibrinolysis

11.  Immediately after a blood vessel loses integrity, the vascular
smooth muscle constricts automatically to result in transient
vasoconstriction and limit the blood loss
 It’s the first response in hemostasis
 The contraction results from
(1) local myogenic spasm from direct damage to the vessel
(2) Sympathetic nervous reflexes due to pain
(3) local autacoid factors from the traumatized tissues and blood
platelets

12.  Platelet plugs are structures formed due to increased
adhesion and aggregation of platelets to physically block
small holes in blood vessels.
 Normally, platelets are unable to adhere each other or to the
endothelial lining of the blood vessels. The endothelial cells
that line the vessel wall normally inhibit coagulation and
platelet aggregation and provide a smooth surface that
permits rapid blood flow.
 However, when endothelial injury occurs the endothelial cells
stop secretion of coagulation and aggregation inhibitors.

13.  After vascular injury, vasoconstriction occurs and
flowing blood comes in contact with the subendothelial
matrix protein.
 In flowing blood, when exposed to subendothelial matrix
proteins, von Willebrand factor (VWF) changes
conformation and adheres to subendothelial collagen,
while simultaneously providing the glue to which the
platelet VWF receptor (the glycoprotein Ib complex)
binds, tethering platelets to sites of injury. This process is
known as adhesion.

14.  In addition, this interaction between VWF and platelets
causes activation of the platelet, triggering secretion of
storage granules containing adenosine diphosphate (ADP),
serotonin, and thromboxane A2. This process is known as
secretion.
 Those secretions result in further vasoconstriction, as well the
expression of fibrinogen receptors on platelets.
 Fibrinogen acts as the ligand that connects two platelets, and
its activation results in the recruitment and aggregation of
other platelets to form the platelet plug. This process is
known as aggregation.

15.  The final process is procoagulant activity. Platelet
procoagulant activity is an important aspect of platelet
activation and involves
- exposure of procoagulant phospholipids (primarily
phosphatidylserine), and
- the subsequent assembly of the enzyme complexes in the
clotting cascade on the platelet surface
 These complexes are an important example of the close
interrelationship between platelet activation and activation of
the clotting cascade

17.  Blood coagulation is the process through which the liquid blood
is converted to gel (clot).
 It’s a slow but long lasting mechanism by which bleeding is
stopped and the weak platelet plug is stabilized.
 The process is mediated through the sequential activation of a
series of proenzymes or inactive precursor proteins ,called blood
clotting factors, to their active form.

18.  There are 12
blood clotting
factors in the
plasma:

19.  These proteins are synthesized in the liver in their inactive form.
 Activation of one of these factors results in activation of the next
one in the cascade, ending in fibrin clot formation.
Stages of Blood Coagulation
1. Formation of prothrombin activators through
 The intrinsic pathway
 The extrinsic pathway
2. Conversion of prothrombin into thrombin by the action of
prothrombin activators
3. Conversion of fibrinogen into fibrin thread by the action of
thrombin

20.  Activated factor X, along with Ca++ ion, Labile factor (V), and platelet
factor 3 (PF3 ) are collectively referred to as the
prothrombin activator
Prothrombin → thrombin
fibrinogen → fibrin
 fibrin threads form a meshwork that traps blood cells, platelets, and plasma
to form the blood clot.

21.  The intrinsic pathway is initiated by the exposure of factor XII
and platelets to collagen
 The extrinsic pathway is activated by tissue factor exposed at
the site of injury or tissue factor-like material
(thromboplastin)
 Both pathways converge on the activation of factor X which,
as a component of prothrombin activators, converts
prothrombin to thrombin, the final enzyme of the clotting
cascade. Thrombin converts fibrinogen from a soluble plasma
protein into an insoluble fibrin clot.

23.  Clot retraction - once the clot is formed, the platelets trapped
within it contract, shrinking the fibrin meshwork. This clot
retraction pulls the edges of the damaged vessel closer
together.
- The clot is also stabilized by squeezing serum from the fibrin
strands.
 Clot repair - PDGF stimulates rebuilding of blood vessel wall.
Fibroblasts form a tissue patch stimulated by VEGF, causing
endothelial cells to multiply and restore the endothelial lining.

24.  Virtually all procoagulant proteins are balanced by an
anticoagulant protein that regulates or inhibits procoagulant
function.
 Four clinically important, naturally occurring anticoagulants
regulate the extension of the clotting process: antithrombin III
(AT-III), protein C, protein S, and tissue factor pathway
inhibitor.
 AT-III is a protease inhibitor that regulates factor X and
thrombin

25.  When thrombin in flowing blood encounters intact
endothelium, thrombin binds to thrombomodulin, its
endothelial receptor. The thrombin–thrombomodulin
complex reduces the availability of thrombin and activates
protein C.
 In the presence of the cofactor protein S, activated protein C
proteolyses and inactivates factor V and factor VIII.
 Tissue factor pathway inhibitor limits activation of factor X.

26.  Once a stable fibrin-platelet plug is formed, the fibrinolytic
system limits its extension and lyses the clot to reestablish
vascular integrity and prevent permanent obstruction.
 This is accomplished by the enzyme plasmin, a proteolytic
enzyme that digests fibrin.
 Plasmin is found in plasma as plasminogen and is activated
by either urokinase-like or tissue-type plasminogen activator.

27.  The conversion of plasminogen into plasmin involves several
substances, including factor XII.
 The process is also regulated by plasminogen activator
inhibitors and α2-antiplasmin, as well as by the thrombin-
activatable fibrinolysis inhibitor.
 Within a few days after the blood has clotted, enough plasmin
has been formed to dissolve the clot.
 Finally, the flow of blood in and around the clot is crucial,
because flowing blood returns to the liver, where activated
clotting factor complexes are removed.

28. By TEMESGEN GELETA

29. 1. Identification
 Sex
 Age
 GA for neonates
 Address

30. Children with bleeding disorder may present with
 Epistaxis
 Gum bleeding
 Gross haematuria
 Joint pain or swelling due to Intra-articular hemorrhage, commonly
affected joints include the knees, ankles and elbows.
 Excessive bruising, ptechiae, purpura
 contusions or spontaneous haemorrhage during childhood play.
 Prolonged bleeding after after certain procedure (e.g. tooth extraction,
circumcision)
 Menorrhagia in adolescent girls

31.  Neurological symptoms due to intracranial haemorrhage
 Haematemesis,
 Melaena or frank rectal bleeding (from gastrointestinal
bleeding).
 Haemoptysis

32. We should ask the following so as to elaborate the chief complaint
 Onset of bleeding-
 age at onset,
 acute vs chronic
 Site of bleeding (mucocutanous, deep or surgical site)
 Duration of bleeding
 Associated symptoms like fatigue, headache, pain any where,
easy bruising
 History of trauma

33. Epistaxis
 Is the bleeding from single nostril or both?
 Bleeding confined to single nostril is due to local vascular problem than
systemic coagulopathy.
 In what condition does the bleeding occur?
 Dry air heating can provoke epistaxis in normal individual.
 Is the bleeding spontaneous or induced by tickling?

34. Oral mucous membrane bleeding in the form of blood blister is a
common manifestation of severe thrombocytopenia.
Such bleeding usually has predilection for sites where teeth
traumatize the inner surface of cheek.

35. Hemarthroses
 It is hallmark of hemophilia
 Can also occur in vWD type 3 and severe factor VII deficiency
Excessive bleeding following circumcision in male is usually first
symptom of hemophilia or glanzmann thromboasthenia.
Bleeding from umbilical stump is characteristic of factor VIII
deficiency or afibrinogenemia.

36.  history of infection
 history of RVI
 history of birth asyphyxia
 Hx of previous hospital visit for bleeding symptoms
 Hx of blood transfussion
 Results of previous laboratory evaluation
 Hx of anemia

37. Family hx is particularly important when hereditary diseases are
considered.
 Ask for hx of chronic maternal diseases
 Hx of bleeding disorder among family members or close
relatives.
 Common inherited bleeding disorders are
 von Willebrand disease.
 Hemophilia A (factor VIII deficiency)
 Hemophilia B (factor IX deficiency)

38. Social history
 consider the possibility of violence as the cause of excessive
bruising or bleeding (e.g. domestic violence).

39. Hx of vitamin K administration at birth or during pregnancy period
several different medications can alter the ability of the clotting
cascade to function effectively.
e.g.
warfarin,
Heparin
NSAIDs
NOACs (rivaroxaban, dabigatran, apixaban, edoxaban)
prolonged use of wide spectrum antibiotics
Patient or maternal use of anticonvulsants

40. Ask hx of herbal use
 Commonly used herbs that can cause platelet dysfuction
o Ginkgo biloba
o Ginseng

43. Don’t be confused, gingseng with Anchote(coccina abyssinica)

44.  Prenatal hx:
 hx of maternal infection during pregnancy
 condition of baby right after birth, admitted to NICU or not
 Umbilical stump bleeding

45.  Detailed nutritional hx should be asked to assess for
 Vitamin K deficiency
 Vitamin C deficiency, b/c patient may have skin bleeding cosistent with
scurvy (perifollicular purpura)
 General malnutrition

46. Hemophilia is associated with
 substantial brain dysfunction,
 problems with coordination and motor function,
 lower intelligence, academic and adaptive skills, and
 more behavioral/emotional problems

47. 1. General appearance
 Sick looking – possible causes
 DIC, infection, liver diseases
 NEC
 Well looking – possible causes
 VKDB, clotting factor deficiency
 Inherited bleeding disorders
 Immune thrombocytopenia
 Bleeding due to local trauma
2. Vital sign
 BP -
 hemophilia patients suffer from higher blood pressure levels than the general population at
all age
 Patient may be hypotensive in case of excessive overt or occult bleeding

48. 3. Systemic Inquiry
HEENT
 Head – look for
 Contusion, laceration, caputsucedanum
 Eye
 conjunctiva, intra ocular hemorrhage, jaundice
 Ear
 Asses for hemotympanema which may be caused by haemophilia or anticoagulant medication
 Ear bleeding
 Nose
 Position of septum, nasal polyp, intranasal laceration
 Throat and mouth
 Extracted tooth, bleeding of gum, sharp material in mouth or throat, laceration of oral mucosa
LGS
 Look for lymphadenopathy

49. Respiratory system
 Haemoptysis
 Breathing difficulty
 May caused by diffused alveolar haemorrhage or pulmonary
haemorrhage
 Dullness of thorax on percussion may indicate hemothorax.

50. CVS
 Osler’s node
 Janeway lesion

51. GI system
 Intraperitoneal bleeding appear as
 Abdominal tenderness
 Tense and rigid abdomen
 Rectal bleeding
 Stool color
 palpate liver and spleen

52. Muscloskeletal system
 Joint swelling or tenderness
 hemarthrosis
 Joint movement

53. Integumentary system
 Pallor
 Hematoma
 Bruising
 Ptechiae
 Ecchymosis
 Telangiectasias
 Poor wound healing

55. CNS
 Neurologic manifestations of intracranial hemorrhage
Weakness or loss of muscle strength
Loss of sight or double vision
Memory loss
Impaired mental ability
Lack of coordination

56.  CBC/platelet count
 Peripheral smear morphology
 Prothrombin time (PT)
 Partial thromboplastin time (PTT)
 Reptilase time (RT)
 Bleeding time
 Apt test

57. Differential diagnosis of purpura:
 Acute hemorrhagic edema of infancy
 Acute streptococcal glomerulonephritis
 Blood clotting disorders
 Drugs
 Hemolytic-uremic syndrome
 Henoch-Schönlein or anaphalactoid purpura.
 Hypersensitivity vasculitis
 Hypertension – malignant, pre-eclampsia and similar gestational problems
 Immune thrombocytopenic purpura
 Infection
 Disseminated intravascular coagulation / Sepsis
 Purpura fulminans from Neisseria meningiditis
 Congenital infections such as cytomegalovirus and rubella
 Rickettsial diseases
 Polyarteritis nodosa
 Thrombotic thrombocytopenic purpura
 Scurvy
 Urticarial vasculitis
 Trauma

58. Differential diagnosis for ptechiae
Infectious diseases
 Cytomegalovirus (CMV) infection
 Endocarditis
 Meningococcemia
 Mononucleosis
 Rocky Mountain spotted fever
 Scarlet fever
 Sepsis
 Strep throat
 Viral hemorrhagic fevers
Other medical conditions
 Vasculitis
 Thrombocytopenia (low platelet count)
 Leukemia
 Scurvy (vitamin C deficiency)
 Vitamin K deficiency

59. Differential diagnosis for ecchymosis
 Trauma
 Melanosis
 Cutaneous malignant melanoma
 Addison disease
 Hemachromatosis
 Wilson disease
 Drug-induced pigmentation (E.g. Hydroxychoroquine, chloroquine,
quinidine, and quinacrine can cause a blue-black pigmentation of the
extremities, face, oral mucosa, nails, and ear cartilage )

60. Differential Diagnoses for Epistaxis
 Allergic Rhinitis
 Barotrauma
 Drug toxicity
 Disseminated Intravascular Coagulation
 Nasal Foreign Bodies
 Pediatric Osler-Weber-Rendu Syndrome
 Sinusitis (Rhinosinusitis)
 Type A Hemophilia
 Type B Hemophilia
 von Willebrand Disease

61. DDX for gum bleeding
 Gingivitis
 Periodontitis
 Vitamin C deficiencies (scurvy)
 vitamin K deficiencies
 Leukemia
 Thrombocytopenia

63. Disorders of Clotting
Factors
Disorders of Platelets Disorders of the blood
vessels
Hemophila A and
Hemophilia B
ITP Henoch schonlein purpura
Factor XI deficiency Non immune platelet
destruction
Eholers danlons syndrome
Factor 2 deficiency Thrombotic
thrombocytopenic purpura
SLE
Factor XIII deficieny Congenital
thrombocytopenic
syndromes

66.  The most common cause of acute onset of
thrombocytopenia in an otherwise well child is
(autoimmune) idiopathic thrombocytopenic purpura.
 It is when the immune system directs itself against its own
platelets.
 Usually follows viral infection(EBV, rubella, varicella)
 In some patients ITP appears to arise in children infected
with Helicobacter pylori and rarely following
vaccines(Mumps, measles, rubella)

68. Acute ITP
Most common in childhood and follows infection with viruses such
as rubella, varicella, measels or EBV
Chronic ITP
 Results from immune clearance of platelets.
 Persistence of thrombocytopenia for more than 12 months from
time of presentation.
 Has a more insidious onset and is more common in females

69. Acute ITP Chronic ITP
2-4 Years old 15-40 years
Males and females equally affected More prevalent in females
Onset is sudden Onset is insidious
Lasts 1-6 months Months to year or a lifetime
History of preceding viral infections is common History of preceding viral infections is uncommon
Self limiting Tends to be relapsing and needs therapy

70.  ITP is characterized by
 Thrombocytopenia(<150,000/mm3)
 A purpuric rash
 Absence of signs of other identifiable causes of
thrombocytopenia

71.  Commonest site of bleeding;
 Cutaneous(86%)
 Nasal(20%)
 Oral(20%)
 GI/GUS(3%)

72.  1.9-6.4 per 100, 000/year in children
 3.3/100,000/year in adults
 Peak age is 1-4 year
 Boys and girls are affected equally
 Occurrence increases after season of viral respiratory illness

73.  The destruction of platelets in ITP involves autoantibodies (IgG)
to glycol proteins normally expressed on platelet membranes.
 This results in Fc receptor mediated destruction of these
antibody coated platelets by the reticuloendothelial
system(especially the spleen)
 The coating of platelets with IgG renders them susceptible to
opsonization and phagocytosis by splenic macrophages.

74.  Sign and symptoms are often preceded by viral illness
 Presentation is a sudden onset of generalized petechiae and
purpura in a previously healthy 1-4 yr old child
 Bleeding from mucous membranes is seen in third of the cases.
 Bruises occur in areas not exposed to trauma.
 Physical findings like hepatomegaly or splenomegaly are
uncommon

75.  Classsification to characterize severity of bleeding :
1.No symptoms
2. Mild symptoms: bruising and petechiae, occasional minor
epistaxis, very little interference with daily living
3. Moderate: more severe skin and mucosal lesions, more
troublesome epistaxis and menorrhagia
4. Severe: bleeding episodes—menorrhagia, epistaxis, melena

76.  Therapy does not appear to affect the natural history of the
illness.
 Spontaneous resolution occurs within 6 months
 1% of patients may develop an intracranial hemorrhage
 20% of children who present with acute ITP go on to have
chronic ITP. The older the child presents with ITP the more
likely it will develop to chronic ITP.

77.  Low platelet count (<50,000)
 Bleeding time is prolonged.
 PT and PTT are normal.
 Mild anemia may be present in some patients due to the
bleeding
 WBC and differential count is normal
 Bone marrow examination reveals increased or normal numbers
of megakaryocytes and normal myeloid & erythroid cells

78.  Many children don’t need therapy.
 Avoiding trauma and physical activity, drugs that alter platelet
function.
 Platelet transfusion may be indicated in emergency situations
but they are destroyed rapidly.

79.  IVIG- increase in platelet within 24 to 48 hours
 Steroids- increase in platelet counts seen within 2 to 3 weeks
 Anti-Rh
 Rituximab (Rituxan)- It slows the antiplatelet antibody
production.
 Splenectomy in chronic ITP
 Romiplostim (N-plate) and eltrombopag (Promacta)- stimulate
the bone marrow to produce more platelets. For treatment of ITP
that has failed other type of treatments.

80.  Von Willebrand’s disease is the most common inherited bleeding
disorder
 It is an autosomal dominant hereditary disorder
 vWF is a glycoprotein synthesized by megakaryocytes and
endothelial cells that binds to endothelial surface and activates
platelets and starts coagulation cascade.

81.  It serves as a carrier protein for factor VIII and also is a cofactor
for platelet adhesion.
 Abnormalities in vWF results in decreased adhesiveness and
prolongation of the bleeding time.

82.  There are three major types of von Willebrand’s disease.
 Type 1 partial quantitative deficiency of Vwf aka classic vWF disease(60-80%)
 Type 2 qualtitatively abnormal protein
 Type 3 complete quantitative deficiency

83.  Typical presentations of type 1 VWD include mucosal bleeding,
epistaxis, menorrhagia and easy bruising.
 In Type 3 VWD in addition to mucosal bleeding patients may
present with joint bleeding or CNS hemorrhage.

84.  The commonest hereditary bleeding disorder (3-4 out of I
00.000). And the mild type is the commonest type
 It is more common in women
 It is more severe with blood type O

85.  Bleeding in mucocutaneous surfaces is very common.
 There maybe
 epistaxis, gum bleeding and menorrhagia
 Post operative bleeding
 Very rarely purpura or hemarthrosis

86.  Unfortunately there is no single test that can reliably diagnose
VWD.
 Instead a panel of tests is usually required
 Bleeding time is prolonged but platelet count is normal in most
cases.
 PT is normal but PTT may be prolonged
 Anemia in significant bleeding

87. TYPE 1 TYPE 3 TYPE 2A TYPE 2B TYPE 2M TYPE 2N
VWF : Ag Low Absent Low Low Low Normal
or low
VWF : RCo low Absent Very low Very low Very low Normal
or low
FVIII Normal Very low Normal
or low
Normal
or low
Normal
or low
Very low
Multimer
distributio
n
Normal Absent Loss of
HMWM
Loss of
HMWM
Normal Normal

88.  Cryoprecipitate- contains intact VWF along with factor XIII and
factor VIII. It can improve bleeding time

89. Treatment VWD types Administration
Desmopressin Type 1 VWD IV
VWF concentrates Type 2 and Type 3 IV
Antifibrinolytics Mucosal bleeding, all types
of VWD
PO or IV

90.  Hemophilia is an X linked recessive hereditary bleeding
disorder caused by low factor VIII coagulant activity
(hemophilia A) and low levels of factor IX coagulant activity
(hemophilia B).
 Hemophilia C(low levels of factor XI) is not x linked(is
autosomal) and affects both genders equally.

91.  Haemophilia can also occur non-genetically
 It is a rare but potentially life-threatening bleeding disorder
caused by the development of autoantibodies (inhibitors)
directed against factor VIII and plasma coagulation factors.
 It is also known as acquired haemophilia A.

92.  The bleeding trait in hemophilia can have various degrees of
severity, depending on the character of the genetic deficiency.
 Bleeding usually does not occur except after trauma, but in some
patients, the degree of trauma required to cause severe and
prolonged bleeding may be so mild that it is hardly noticeable

93.  Mild- 5% and 40% of normal levels of active clotting factor
 Moderate- 1–5% of normal levels of active clotting factor
 Severe- less than 1% of normal levels of active clotting factor

94.  The hemophilias are rare conditions with hemophilia A about 3-
4 times more common than hemophilia B.
 Hemophilia A- 1 case per 5000 males
 Hemophilia B- 1 case in 25,000 males
 Hemopilia C – 1 case per 100,000. More common in Ashkenazi
jews with the incidence of 1-3 cases in every 1000 people
 Symptomatic hemophilia extremely rare in females

95.  Since a male receives his single X-chromosome from his mother,
the son of a healthy female silently carrying the deficient gene
will have a 50% chance of inheriting that gene from her and with
it the disease; and if his mother is affected with haemophilia, he
will have a 100% chance of being a haemophiliac
 In contrast, for a female to inherit the disease, she must receive
two deficient X-chromosomes, one from her mother and the
other from her father (who must therefore be a haemophiliac
himself)

97.  Approximately 50-60% of patients have severe hemophilia
A(<1%)
 Approximately 25-30% have moderate hemophilia and manifest
bleeding after minor trauma(2-5%)
 Those with mild hemophilia A comprise 15-20% of all people with
hemophilia(5-40%)

98.  The gene for FVIII (F8C) is located on the long arm of
chromosome X, within the Xq28 region. The gene is unusually
large, representing 186 kb of the X chromosome. It comprises 26
exons and 25 introns. Mature FVIII contains 2332 amino acids
 Approximately 40% of cases of severe FVIII deficiency arise
from a large inversion that disrupts the FVIII gene.
 Deletions, insertions, and point mutations account for the
remaining 50-60% of the F8C defects that cause hemophilia A.

99.  FVIII deficiency leads to the disruption of the normal intrinsic
coagulation cascade, resulting in excessive hemorrhage in
response to trauma and, in severe cases, spontaneous
hemorrhage.

100.  Injury
 Formation of the platelet plug
 Generation of the fibrin clot that prevents further hemorrhage
 Inadequate thrombin generation
 Failure to form a tightly cross-linked fibrin clot to support the
platelet plug
 Formation of a soft, friable clot
 Bleeding

101.  Hemorrhage sites include
 joints (the hallmark);
 muscles;
 the central nervous system (CNS);
 gastrointestinal,
 genitourinary,
 pulmonary, and
 cardiovascular systems.

102.  The clinical features of hemophilia A and B are generally
indistinguishable from each other
 Symptoms include easy bruising, intramuscular hematomas, and
hemarthroses
 Minor traumatic lacerations of the mouth (a torn frenulum) may persist
for hours or days
 Bleeding into the joints leads to synovial inflammation which leads to
further bleeding.
 This joint can become a “target joint” i.e a joint with 4 or more bleeds
within 6 months.
 Repeated bleeding leads to synovial hypertrophy,, fibrosis, and damage
to cartilage, This results in permanent deformities, misalignment, loss of
mobility, and extremities of unequal lengths.

103.  General- weakness, acutely sick looking, orthostasis
• HEENT- Pale conjutiva, frequent nosebleeds, bleeding gums,
tounge and mouth lacerations
 Chest- tachycardia
 Respiratory- tachypnea, dyspnea
• GIS- blood in the stool
• GUS- Hematuria, renal colic, and post circumcision bleeding
 Integumentery- large unexplained bruises,
 Musculoskeletal- warmth, pain, stiffness, and refusal to use joint,
limited ROM, flexed, internally rotated position of the
hips(irritation of the iliopsoas)
 CNS- lethargy, irritability or even seizures

104. Partial thromboplastin time (PTT) is prolonged.
- In severe hemophila, PTT is usually 2-3 times the upper limit of normal
•platelet count, thrombin time, prothrombin time, and bleeding
time are normal
• Factor IX coagulant activity levels are reduced in patients with
hemophilia B.

105.  To differentiate FVIII deficiency from FIX factor 8 and factor 9
assay should be performed.

106.  Early, appropriate therapy is the hallmark of excellent
hemophilia care
 Prophylaxis is the standard of care for most children with severe
hemophilia, to prevent spontaneous bleeding and early joint
deformities.

107.  Principles follow
 Life style changes- prevention of trauma
 Immunization- immunization against Hep B, because of life time exposure to blood
products
 Avoidance of drugs with risk for bleeding
 Physiotherapy
 Pharmacologic therapy

108.  Factor VIII concentrates
 Factor IX concentrate
 Recombinant activated factor VIII
 Desmopressin acetate: mild factor VIII deficiency

109.  Prognosis is good with early detection and intervention.