Von willebrand disease

1. CASE & TOPIC PRESENTATION
DEPARTMENT OF HAEMATOLOGY
WARD 37, CMC
Dr. Samee M Adnan
Resident (Phase A), Neuromedicine

2. PARTICULARS OF THE PATIENT
 Name: Saiful Islam
 Age-11 years
 Address: Ukhiya, Cox’s Bazar
 Occupation: Student
 Date of admission: 25th August, 2019

3. Master Saiful Islam, 11 years of age, normotensive,
nondiabetic, known case of haemophilia, hailing
from ukhiya, cox’s bazar admitted into haematology
ward, CMC, through transfer from neurosurgery
ward on 25th August, 2019 with the complaints of:
 Weakness of both lower limbs & difficulty in
walking for last one & half months.
 Inability to void urine for same duration.

4. According to the statement of patient’s attendant he
was diagnosed as a case of hemophilia 6 years
back & was poorly compliant to treatment.
One & a half month back, while playing football on
field he sustained an injury on the back.
After the incident, he suddenly developed weakness
of both lower limbs, which is gradually increasing.
For last 1 month he is completely unable to move
his legs, is unable to walk even with the help of
others & completely bed ridden.
For last 1 month, he experiences numbness of both
lower limbs equally.
There is no complaints regarding his upper limbs.

5. He also complains of difficulty in voiding & urinary
retention for same duration. With the complaint of
retention he was admitted into Cox’s bazar medical
college & hospital, where he was catheterized &
referred to CMC for further treatment. He was also
unable to pass stool.
For last 15 days he developed multiple lesions in the
oral cavity & lips which has made chewing &
swallowing foods difficult.

6. On query, there is no history of fever, weight loss,
cough, generalized body ache, palpitation &
weakness, nodular swelling or heaviness anywhere
in body prior to the trauma. There is no history of
skin rash, bleeding spots & photosensitivity.
He was administered with factor VIII, only a handful of
times after initial diagnosis.
One of his maternal uncles has hemophilia. None of
his other family members has such illness.
He belongs to low socioeconomic status.
He is immunized as per immunization schedule.

7. GENERAL EXAMINATION

8.  The patient is ill looking, emaciated, co-operative,
bed ridden .
 There is mild anaemia, multiple oral thrush in the
tongue & lips. There is no jaundice, cyanosis,
clubbing, koilonychia , leukonychia, oedmema,
bony tenderness, signs of dehydration.
 Urinary cathter & IV cannula in situ.
 The blood pressure was 90/60 mm HG, pulse 98
bpm, Respiratory Rate 24/min,Temp-98.4 F.
 There is no thyromegaly.
No significant lymphadenopathy.
No raised JVP.

9. SYSTEMIC EXAMINATION

10. NEUROLOGICAL EXAMINATION
 Higher cerebral functions: Intact.
 Cranial nerves including fundoscopy: Normal.
 Motor system:
 Muscle tone: Decreased in both lower limbs, normal in
upper limbs.
 Muscle power: Diminished (grade 0/5) in both lower
limbs, normal in both upper limbs.
 Wasting: Present around the muscles of both knee
joints.

11.  Reflexes:
 Co-ordination: Normal in upper limbs, but could not
be elicited on lower limbs due to weakness.
 Gait: Could not be elicited.
 Rombergism: Could not be elicited.
 Involuntary movements: absent.
 Cerebellar functions: Intact.
 Sensory System: Sensory perception of all
modalities are impaired below Lumber 1
dermatome & intact above it.
Jerks Biceps Triceps Supinat
or
Knee Ankle Planter
Right Normal Normal Normal Absent Absent Extensor
Left Normal Normal Normal Absent Absent Equivocal

12. Other systemic examination reveals no abnormality.

13. PROVISIONAL DIAGNOSIS

14. Spinal Cord compression due to hematoma with
hemophilia with oral candidiasis

15. DIFFERENTIAL DIAGNOSIS

16. Von Willebrand Disease

17. INVESTIGATIONS

18. CBC

19. 26/08/19

20. 14/09/19

21. 21/09/19

22. 25/09/19

23. APTT
26/08/19 08/09/19 14/09/19
Control 28s 32s 28s
Patient 46s 104s 46s

24.  Serum ferritin: 370 ng/ml
 RBS: 7.73 mmol/L
 ALT: 58 U/L
 USG of W/A: Findings suggestive of cystitis

25. MRI OF DORSO-
LUMBAR SPINE

26. FACTOR VIII
ASSAY

27. FINAL DIAGNOSIS

28. Spinal Cord compression due to hematoma (From
Thoracic 10 to Lumber 2 vertebra) with hemophilia
A with oral candidiasis

29. VON WILLEBRAND DISEASE

30. VON WILLEBRAND FACTOR
 Multimeric protein that mediates adhesion of
platelets at sites of vascular injury
 Collagen
 Glycoprotein Ib receptor
 High molecular weight multimers are more effective at
binding platelets
 Carrier for coagulation factor VIII
 vWF exists as a set of multimers of different sizes.
(Largest are responsible for platelet adhesion &
aggregation)

31. SOURCES

35. CLEARANCE
 Macrophages in liver and spleen are believed to
internalize and clear circulating vWF.
 The half-life of the plasma-derived therapeutic vWF
is approximately 12 to 14 hours.

36. VON WILLEBRAND DISEASE
 Incidence – Most commonly inherited bleeding
disorder affecting 0.1-1%
 Prevalence- prevalence of symptom is much lower
0.01%
 Due to incomplete penetrance and mild cases pt
are asymptomatic until investigated
 Gender- either gender affected as it is Autosomal
disorder. (Autosomal dominant inheritance)

37. CLINICAL FEATURES

38. TYPES OF VWD

39. CONT.

40. ACQUIRED VON WILLEBRAND SYNDROME

41. DIAGNOSTIC EVALUATION
 CBC profile can normal but may have
 Microcytic anaemia due Iron deficiency due to blood
loss
 Thrombocytopenia Type 2B
 APTT normal in majority except Type 2N severe
Type 1 and Type 3

42. CONFIRMATION OF DIAGNOSIS
 vWF Antigen levels (vWF:Ag) Enzyme-linked
immunosorbent assay (ELISA) or latex immunoassay (LIA)
method is used. Normal range is 50 to 200 IU/dL.
 Ristocetin cofactor activity assay (vWF:RCo) determines
the capacity of vWF to agglutinate exogenous platelets in the
presence of Ristocetin. Normal range is 50 to 200 IU/dL.

43. CONT.
 vWF:RCo/VWF:Ag ratio assesses the ratio of vWF activity to
antigen in plasma. A ratio of <0.6 is indicative of a qualitative
vWF deficiency. A value of <0.6 is seen in all type 2 vWD
subtypes.
 Factor VIII coagulant assay (FVIII:C) measures the plasma
concentration of FVIII. To assay the ability of plasma to
shorten PTT of FVIII-deficient plasma. Normal range is 50 to
200 IU/dL

44. CONT.
 vWF multimer analysis is a qualitative assay that
determines the size distribution of vWF multimers.
Protein electrophoresis method is used.

45. TREATMENT
 Local measures and antifibrinolytic agent (e.g.
tranexamic acid for mild bleeding).
 DDAVP infusion for those with type 1 VWD. This
releases VWF from endothelial cells 30 minutes
after intravenous infusion.
 High‐purity VWF concentrates for patients with
very low VWF levels. Plasma‐derived factor
VIII/VWF concentrates are used. Recombinant
VWF is now in clinical trials.