von Willebrand disease Type III a rare case

1. Dr.SUNIL S VAIDYA(MDDCH)
Deptofpaediatrics
Ashwini SahakariRugnalay
Dr. MANDAR HAVAL
(DCH DNBFELLOWINNEONATOLOGY).
THE BLEEDING CHILD

2. 3 years old female child brought
by Father
c/o- Bleeding from the nose and
mouth since evening

3. • Patient was apparently alright and
playful when mother noticed profuse
bleeding from the nose and mouth.
• Bleeding was sudden in onset. It went on
to continue for almost thirty min to one
hour when father took her to ASR
pediatric casualty

4. • No h/o fever with rash
• No h/o petechiae , purpura
• No h/o malena ,bleeding from other
sites
• No h/o trauma , surgical procedure
• No h/o medications ( aspirin , warfarin
, heparin)
• No h/o joint swelling , bone pain
• No h/o Haematuria
• No h/o Jaundice , Oedema

5.  Past h/o similar episode of nasal bleeding 1 yr back. She
had been investigated at that time.
CBC
Hb- 7 g/dl ,
TLC 7900 cells/ cu mm
platelets 376000 ;
clumps of platelets noted on ps
PT –INR Normal
PTTK Prolonged
BT Prolonged ,
Patient then received PCV, FFP,& Inj Vit K and
discharged

6.  Pt had 2nd episode 6month back
She received inj vitamin K , PCV and FFP
transfusion at that time again and
discharged.
 And for 3rd episode she was referred to ASR
Solapur.

7.  No history of similar complaints in any of the family
member of patient.
 Child is born out of third degree
consanguinous marriage.

8.  Registered pregnancy.
 2 TT inj taken,received iron & folic
acid.
 No H/o HTN , DM , fever with rash .
 No H/o medication

9.  Full term ,2.6kg,Cried immediately after
birth, born vaginally at Govt .Hospital
 Uneventful Natal History. (No h/o
cephalhematoma , jaundice , bleeding , No
history of prolonged bleeding from
umbilical stump)

10.  Not much eventful.
 No history of easy bruising or bluish
discoloration on knees and elbow when
baby started crawling

11.  Completed up to date .
 No h/o hematoma on the Site of
injection given

12.  All milestones achieved at appropriate age .

13. Father farmer by occupation , mother housewife.
According to modified kuppaswamy
classification upper middle class

14. Conscious , well oriented to person., time
Afebrile
HR 126/min
RR 26/min
BP 84 /56 mm of Hg in rt arm supine position
Pallor +
No icterus , cyanosis , oedema , LNpathy .
Height 98 cm (85 %centile)
Weight 16 kg (>85 %centile)

15.  Normal face, hair normal ,
 Fontanel fused .
 Eyes , ears Normal
 Nose – Epistaxis +
 Throat -Normal
 Bleeding from upper gums present.
 No bleeding from other mucosal sites.
 Neck Normal .
 No petechiae , purpura , ecchymoses.
 Spine , bone , joint normal , no tenderness or swelling.

16.  CVS – S1S2 Heard Normal
-No murmur.
 RS – Air entry b/l equal.
-Clear.
 P/A – Soft
-non tender
-no hepato splenomegaly.
 CNS – Tone , power ,reflexes - Normal

17.  CBC – Hb - 9.8 g/dl
- TLC - 8600 cells /cu mm
- Platelet - 372000 / cu mm.
- Seen in clums on PS
 PT- INR – 14.4 sec(Pt)
-13.5 sec (Control)
-Index- 93.75%
-INR- 1.07 (N)
 PTTK - 94.7 sec(Pt)
- 32.2 sec(Control)
 Bleeding time - > 10 min

18.  PT is normal ( VII, X , II , V and
fibrinogen)
 APTT – INCREASED ( Factor XII, XI ,
IX, VIII, X , V, II and fibrinogen)

19.  If there is unexplained prolongation of PT, PTT, or
thrombin time, a mixing study is usually performed.
Normal plasma is added to the patient’s plasma, and
the PT or PTT is repeated. Correction of PT or PTT by 1
: 1 mixing with normal plasma suggests deficiency of a
clotting factor, because a 50% level of individual
clotting proteins is sufficient to produce normal PT or
PTT. If the clotting time is not corrected or only
partially corrected, an inhibitor is usually present.

20.  PT – TEST - 10sec , CONT – 11sec
 APTT – TEST – 72sec , CONT – 33sec
 APTT correction studies –
½ test + ½ control – 34 sec
½ test + ½ aged serum – 83 sec (Factor 9)
½ test + ½ adsorbed plasma – 41 sec (Factor 8 )

21. Factor VIII Assay – 3.3 %
(50 -150% U/ ml)

23. 1) BLEEDING TIME –
INCREASED with –Functional platelet
disorders
- thrombocytopenias
- vonWillebrand Disease
2) vWF acts as a chaperone for F VIII
so decreased levels of vWF leads
to deficiency of Factor VIII

24.  In vWD there are two conditions where factor VIII
is LOW
1)vWD TYPE 2N
2)vWD TYPE 3
 The distinguishing point in these two conditions
is vWF Ag Assay.

25. vWF antigen Assay – <1%
(N 50 – 154 %)

27. Diagnosis???

28. von Willebrand disease
Type III

29.  Most common inherited bleeding disorder
 Autosomal inheritance
 Due to either qauntitative or qualitative abnormality of
vonWillebrand factor

30.  1931 - Dr Erik von Willebrand first decribed this
condition as hereditary pseudohaemophilia.
•1970- Discovery of facor
producing the disease
described by vonWillebrand
and was named after him.
•1980-vWF gene was cloned

31.  Large multimeric glycoprotein
 Synthesized in-Platelets (α granules)
-Endothelial cells(Weibel palade bodies

32. Vascular injury
vWf adheres to subendothelial matrix
Conformational change in the vWF
Adhesion of the platelets to vWF through GlIb and
activation of the platelets
Recruitment of additional platelets & exposing platelets to
membrane phosphatidylserine which is important step for
Factor V & VIII bdependent steps in coagulation cascade

33. vWF also serves as the carrier protien for Factor
VIII. A severe deficiency of vWF causes
secondary deficiency of Factor VIII due to
proteolytic degradaion of Factor VIII even though
gene for Factor VIII is normal .

34. Clinical manifestions
- Excessive bruising
- Epistaxis
- Menorrhagia
- Procedures – Tonsillectomy
- Tooth extraction etc.

35. Type I
• Most common
(85%)
• Autosomal
dominant
• Reduiced quantity
of vWF but not
absent
• Type 1c variant
(accelerated
clearance of vWF)
• Desmopressin is
effective
Type II
• Qualitative
abnormality of
vWF
• Autosomal
dominant
• Four subtypes
Type III
(Most severe)
• Rare(I 1:5,00,00 0)
• Autosomal recessive
• Undetectable levels
of the vWF &low
levels of VIII
• MC presentation
Epistaxis
Menorrhagia
• Present in early age
group
• Rarely can have
IC/muscle/joint
bleed lik
haemophilia
• Desmopresin not
effective

36. Type II A
• Lacks high or
intermidiate
vWF multimer
due to
abnormal
proteolysis or
reduced
secretion.
• Desmopressin
not much
useful
• vWF
replacement
therapy in
significant
bleeding
Type II B
• Mutation
leading to
hyperactive
vWF
• Abnormal
vWF bind
spontaneously
with platelets
& rapidly
cleared from
circulation
leading to
thrombicytope
nia.
• Desmopressin
NEVER TO BE
USED
Type II M
• Due to
decresed
platelet
binding
function of
vWF
• Levels of vWF
activity are
significantly
lower than
vWF:Ag
• Desmopresin
not musch
useful even
though release
is normal due
to absence of
binding
Type II N
• Decreased
binding of
vWF to VIII
but normal
binding with
platelets
• AKA-
Autosomal
haemophilia
• Although
desmopresin
release abn
vWF, sustained
VIII levels may
be occasionally
inadequate for
normal
haemostasis

37.  Monoclonal gammopathy: vWF neutralized by
paraprotein (?)
 Autoimmune disorders: Autoantibody to vWF
 Myeloproliferative disorder: large multimers absorbed
onto neoplastic cells (platelets?)
 Cardiovascular diseases (AS, VSD, etc): High shear
stress causes unfolding/proteolysis of large multimers
 Hypothyroidism: Decreased release of vWF from
endothelial cells
 Treatment varies depending on cause/mechanism

38.  DDAVP releases vWF from endothelial cells
 Can be given IV or intranasally
 0.3 mcg/kg IV, or 150 mcg per nostril
 Typically causes 2-4 fold increase in blood levels of
vWF (in type 1 vWD), with half-life of 8+ hours
 Response to DDAVP varies considerably
 Administration of a trial dose necessary to ensure a
given patient responds adequately
 Peak response
 Duration of response

39. Sr.no Type Response
1 I Usually effective
2 II A Usually ineefective
3 II B May be contraindicated
4 II M Predicted to be effective
5 II N Rarely effective
6 III Ineffective

40.  Type 2 or 3 vWD
 Active bleeding
 Surgery or other invasive procedure
 Type 1 vWD with inadequate response to DDAVP

42. THANK YOU !!!