Hemophilia VWD thrombocytopenia

1. Approach To Child with
Bleeding Tendency
Halima Al.Dhali
98181

2. Case Scenario
Parents brought a 3 year old girl to emergency room with
history of bruising on her lower limbs and chest for the last 4
days. The bruises were not painful but were increasing in
number every day. No active bleeding seen. Child otherwise
very active and playful.
What further history you would like to obtain from parents?
What else you will be searching in your examination?
What investigations you will order?

3. History
•Patient ID,
•PRESENTING COMPLAINT
– NATURE OF BLEED
 Onset – Acute
bleeds >> Acquired disorder
– Bleeding since
birth >> Congenital disorder
Site – Superficial: skin,
mucosa
(nasal,gingival) >> Platelet
– Deep: joint,
muscle >> Coagulopathy
 Other types of bleed
 – Hematemesis,Hematuria,
Hematochezia, Melena,
epistaxis
 Preceding/Precipitating
event - Trauma, surgery,
dental procedure
 Duration and frequency –
bleeding that stops and recur
quickly → Coagulopathy
• Associated symptoms
• nausea, vomiting, headache,
weakness
• postural giddiness, pallor,
fatigue, chest pain,, palpitations,
joint swelling
• Review of systems
PAST MEDICAL HISTORY
• Previously Diagnosed Bleeding
disorder (eg Hemophilia, ITP)
• Liver disease
• Renal disease
• Malignancies(leukemia,
neuroblastoma)
• Infections
• Connective tissue disorders
Autoimmune
Previous admissions,
surgeries and blood
transfusion

4. History
Prenatal, perinatal and postnatal Hx
 Postcircumcision bleeding
 Birth cephalohematoma
 Umbilical stump bleeding or delayed stump separation
Nutritional Hx
 Protein malnutrition
 Vitamin C deficiency, or scurvy
 Vitamin K deficiency >>bacterial overgrowth, celiac disease, chronic
pancreatitis, inflammatory bowel disease.
Developmental Hx
 gross motor (to corroborate the described mechanism of injury)

5. History
FAMILY HISTORY
• consanguinity >> autosomal recessive inherited bleeding
disorder
• Known bleeding disorder or other heritable medical disorder
that may predispose to bruising (eg, Ehlers-Danlos syndrome,
osteogenesis imperfecta).
• Male relatives affected (Hemophilia, X-linked Recessive trait)
• Female relatives - Menstrual and Obstetric Hx
• males and females affected >>an autosomal disorder such as
von Willebrand factor deficiency
• autosomal dominant traits such as hereditary hemorrhagic
telangiectasia
Social Hx
• child’s behavior and the family’s methods of discipline

6. Examination
 General appearance: dysmorphisms , built.
 Vital signs
 Growth parameters: malnutrition
 General examination: hydration, pallor, jaundice, lymphadenopathy
 Skin :Telangiectasia, Petechiae, Purpurae, Ecchymoses, Hematoma
(size, location, pattern)
 Mucosae : Nasal (Epistaxis), Gingival bleeding
 The musculoskeletal system : Intramuscular Bleed, Hemearthrosis
Joint contractures ( chronic hemearthroses) , joint hypermobility, skin
laxity and bony deformity
 GI system: Hepatosplenomegaly

7. petechiae
 Pinpoint flat round red spots under the skin
surface caused by intradermal hemorrhage
(bleeding into the skin)

8. Purpura
 Purpura is purple-colored spots and patches
that occur on the skin, and in mucus me
Group of adjoining petechiae

9. Ecchymoses
 Isolated lesion larger than petechiae
 ( larger than 1cm)

10. Bleeding Disorder
Coagulation
Factor
• Deficiency in coagulation Factor
Blood Vessels
Integrity
• Weak vessele
• Inflammation
Platelet
disorder
• Decrease number
• Abnormal function

11. Platelet
 Its called thrombocyte from megakaryocte
 Life span 8- 10 days
 One third of them sequestered in spleen
 production control by thromboprotein
 Normal Range150-400 X 109/L
 Less than 150X 109/L , thrombocytopenia.

12. Causes of Thrombocytopenia
Decrease
platelet
production
Increase
platelet
consumpti
on
Splenic
Sequestratio
n
Dilution
-Bone marrow
failure
-Aplastic
syndrome
-cyanotic
congenital heart
D
_Infection(HIV,C
MV, Episten Barr
viruse
-Drug(heparin-
Anti-biotic –
quinidine)
-Idiopathic
thrombocytopen
ic purpura (ITP)
-Neonatal
alloimmune
thrombocytopen
ia (NAIT)
-SLE
-Disseminated
intravascular
coagulation
(DIC)
-Sepsis
-Increase
pooling in
spleen
Hypersplenism
Infection
Inflammatio
n
Congestion
Red cell
disorders
Storage
diseases
-Massive Blood
transfusion

13. manifestations of
thrombocytopenia
 Petechiae
 Bruises or purpura
 Bleeding of mucous membranes: epistaxis,
gingival bleeding
 Acute gastrointestinal bleeding
 Hematuria
 Acute CNS hemorrhage: the rarest but MOST
FEARED consequence of low platelets

14. Degree of trauma and bleeding
Platelet Count Risk of bleeding Example
Less than 80×10^9 Primary hemostasis
impaired
After Major trauma,
Surgery
Less than 50×10^9 Spontaneous bleeding
mostly in Skin
Petechiae ,purpura
Less than 20×10^9 Noticeable hemorrhage
Seen in skin and
mucosa
Epistaxis
Gingival bleeding

15. Immune Thrombocytopenic (ITP)
 isolated thrombocytopenia with normal bone
marrow and in the absence of other causes of
thrombocytopenia.
 Usually follow an acute viral infection
 IgG,IgM that bind platelet membrane, result in
Fc receptor mediated splenic destruction

16. signs, symptoms, and
precipitating factors
 Abrupt onset, Purpura
 Epistaxis
 Bruising tendency
 Gingival bleeding
 Recent live virus immunization
 Recent viral illness mainly after1-4 week
 Normal RBC,WBC count
 Sever type of thrombocytopenia
 Adenopathy or hepatosplenomegaly is unusual

17. Diagnosis
 Usually based on clinical presentation
 Platelet Count low
 Atypical finding-Do Bone marrow Examination(
Increase megakaryocyte, Normal
Erythroid,myloid element).
 In ITP shows increased megakaryocytes and
normal erythroid and amyloid elements.
 (WBC,RBC,Hb) Normal
 Normal pt aptt time

18. Our patient:
Hb: 11g/dL
WBC 5x109/L with normal differential
Platelets 4 x109/L
PT and APTT = normal

19. Treatment
 Optimal treatment is Controversial
 80% of children will have spontaneous
resolution(few weeks).
 child with mild bleeding(bruising,petechia) no
treatment required.
 Severe and moderate bleeding with platelet
count less 10,000mm
Treatment option

20.  Prednisone for 2 weeks
 IVIG for(1-2 Days)expensive,
 Platelet transfusion: Actively bleeding patients
with thrombocytopenia central nervous
system bleeding
 Splenectomy (life threating condition/not
responding to other medication)
Decrease
clearance of
sensitized
platelet

21. Coagulation Disorder
 Hemophilia
 Von Willebrand Disease

22. Hemophilia
 an inherited (genetic) disorder
 blood doesn't clot normally because it lacks
sufficient blood-clotting proteins (clotting
factors).
 you may bleed for a longer time after an injury
than you would if your blood clotted normally.

23. Types of hemophilia
Types Hemophilia A Hemophilia B
inheritance X-linked X-linked
Factor Deficiency factor8 factor9
Bleeding site Muscle, joints ,surgical Muscle, joints ,surgical
Prothrombin time Normal Normal
Activated partial
thromboplastin time
prolong prolong

24. Hemophilia A
Hemophilia B

25. Clinical Manifestation
 Bleeding In soft Tissue ,GI ,Hip ,Joint, elbow ,
and ankle Joint.
 Spontaneous joint bleeding occur when child
begin to walk
 Intracranial hemorrhage uncommon(important
cause of death)
 Petechiae usually do not occur in patients with
hemophilia

26.  Musculoskeletal (joints) - Tingling, cracking, warmth, pain,
stiffness, refusal to use the joint (young children)
 Central nervous system (CNS) - Headache, stiff neck,
vomiting, lethargy, irritability, spinal cord syndromes
 Gastrointestinal (GI) - Hematemesis, melena, frank red
blood per rectum, abdominal pain
 Genitourinary - Hematuria, renal colic, post-circumcision
bleeding
 Other - Epistaxis, oral mucosal hemorrhage, hemoptysis,
dyspnea (hematoma leading to airway obstruction)
 contusions, excessive bleeding with routine dental procedures

27. Severity, Factor Activity, and
Hemorrhage Type
Classification Factor Activity% Cause of
hemorrhage
Mild 5-40% Major trauma,
surgery
Moderate 1-5% Mild to moderate
trauma
Severe < 𝟏 Spontaneous

28. Diagnosis
 CBC(normal platelet count)
 Coagulation Study:(aPTT) is prolonged,
the bleeding time and prothrombin time are
normal
 Factor 8,9 assay:levels are compared with a
normal pooled-plasma standard
 Mixing study

29. Mixing Study

30. Management
 Prevention of trauma is important
 Should avoid Aspirin and other NSAID
 Iv infusion whenever there is any bleeding
 recombinant FVIII concentrate for haemophilia A
 recombinant FIX concentrate for haemophilia B
 Highly purified, virally inactivated plasma-derived
products should be used if recombinant products are
unavailable

31. Von Willebrand Disease
 VWF found in( Endothelia cell,
Megakaryocyte).
 Two Rules :Carrier Molecule for factor 8
 Promote platelet Adhesion
 An Inherited bleeding disorder
 Women are worse affected than men
 3types ( 1,2,3)
 Either Qualitative or Quantitative Disorder

32. Type1 Type2 Type3
Quantitative
partial Deficiency
70-80%
-Mild clinical
symptoms
-Autosomal
Dominant
Functional
abnormality
15-20 %
-Mild-Moderate
-Autosomal
Recessive/Dominan
t
- 4 subtypes (2A
,2B,2M,2N)
Complete
Deficiency
Most Sever Type
-Autosomal
Recessive
-Similar to
hemophilia A

33. Manifestations
 Wide variation in Clinical Manifestation (even
in the same family).
 Many children are asymptomatic .
 Increased or easy bruising
 Recurrent Epistaxis.
 Post-operative bleeding( Tonsillectomy –dental
Extraction )

34. Laboratory finding
 Factor 8 levels are low.
 The APTT may be prolonged .
 VWF levels are low .
 Platelet count is normal (except in type 2B)

35. Management
 DDAVP (Desmopressin Acetate)
-synthetic form of vasopressin
Stimulate release of VWF from cells after 30min (for type1) .
 Purified plasma-derived concentrates
of vWF/FVIII are used for treatment of bleeds and for
surgical prophylaxis when DDAVP is ineffective or contraindicated
 Prophylactic (antifibronolytics ), before
dental Extraction .

36.  A five-year-old child who is not
clinically ill but presents with
moderate mucocutaneous purpura in
the wake of a viral infection

37. A male infant who is starting to
walk and presents with a
painful swollen joint after a fall