Von willebrands disease

Question 2

Clinical features of VWD

Answer 2

Mucocutaneous bleeding
Musculoskeletal bleeding in type 3 eg haemarthrosis, soft tissue, muscle haemotaoma

Question 3

Examples of mucocutaneous bleeding

Answer 3

Heavy menstrual bleeding
Epistaxis
Bruising
Exessive bleed from minor wounds
GI bleed
Oral cavity/post dental
Post op
post partum

Question 4

Where is VWF synthesised

Answer 4

Megakaryocytes (platelets) and endothelial cells
Stored in Weibel-Palade bodies (endothelial cells) and alpha granules (platelets)

Question 5

VWF role in clotting

Answer 5

Primary haemostasis - platelet adhesion and aggregation
Secondary haemostasis - cahperone to FVIII - prolongs hal life

Question 6

Type I VWD

Answer 6

Mild to mod quant def of VWF <0.3U/ml and factor VIII
Autosomal dominant

Question 7

Type 2 VWD

Answer 7

Autosomal dominant
Qualitative deficiency of VWF
4 subtypes

Question 8

Subtypes of VWD type 2

Answer 8

a) 2A – abnormal assembly or reduced half-life of high molecular weight multimers (HMWM)
b) 2B – increased binding of VWF to platelets causing depletion of HMWM and thrombocytopenia
c) 2M – decreased binding of VWF to platelets but with normal VWF multimers distribution
d) 2N – markedly decreased binding of VWF to Factor VIII, causing low plasma factor VIII levels (autosomal recessive)

Question 9

Type 3 VWD

Answer 9

Quantitaive absence of VWF ,1% normal and low FVIIII levels
Autosomal recessive

Question 10

What are the 3 diagnostic criteria for VWD

Answer 10

Bleeding symptoms
FH
Labaratory results

Question 11

How to assess bleeding symptoms

Answer 11

ISTH BAT, condensed MCMDM-1VWD BAT

Question 12

Basic lab tests for VWD

Answer 12

FBC, PT, APTT
VWD screen - FVIII, VWF antigen, activiy
Consider PA-100 - (in vitro bleeding time) + blood type
VWF genetic testing

Question 13

What test order if sus type 2 VWD

Answer 13

RIPA - risocetin induced platelet agglutination and multimer studies

Question 14

Management aim

Answer 14

Raise VWF/FVIII plasma conc -> adeuqate haemoastasis

Question 15

Which types of VWD are repsonsive to DDAVP/Desmopressin

Answer 15

Type 1,2A,2N

Question 16

How does DDAVP administer /work

Answer 16

0.3mg/kg IV/SC
Increases FVIII/VWF in 30-60 mins
#Repeat every 12-23 hours as needed

Question 17

What is tachyphylaxis and when watch for in VWD

Answer 17

Short term intolerance to a drug after use
After 4 doses of desmopressin

Question 18

Side effects of desmopressin

Answer 18

Flushing
Tachycardia
Headache
Hyponatrema - restrict wtare

Question 19

CI to DDAVP in VWD

Answer 19

Cardiac risk factors
.65 YEARS

Question 20

Treatment for DDAVP non response in VWD

Answer 20

VWF:FVIII derived concentrate - humate P (2.4:1)or Wilate (1:1)

Question 21

What factor is importnatn to monitor before surgery

Answer 21

FVIII

Question 22

What levels of FVIII are ass w VTE

Answer 22

> 150%

Question 23

Treatment before major surgery in VWD

Answer 23

Loading Dose 40-60 U/kg
Maintenance Dose 20-40 U/kg q8 – q24 hrs
Therapeutic goal Trough VWF:RCo and FVIII >0.50 U/mL for 7–14 days

Question 24

Treatment before minor surgery in VWD

Answer 24

Loading Dose 30-60 U/kg
Maintenance Dose 20-40 U/kg q12 – q48 hours
Therapeutic goal Trough VWF:RCo and FVIII >0.50 U/mL for 3–5 days

Question 25

How often should FVIII be monitored

Answer 25

12 hours on day Every 24 hours after

Question 26

Adjuct treatments in VWD

Answer 26

Antifibrinolytics eg tranexami acid Cryoprecipitate ig humate P unavailable Haemorrhage -> platelet transfusion (if adequate FVIII but uncontrolled)

Question 27

When use and when dont use antifibrinolytics in VWD

Answer 27

for GI, gynecologic and nasopharyngeal bleeding: CI - haematuria

Question 28

When monitor pregnant woman with VWD

Answer 28

EACH TRIMESTER

Question 29

When refer pregnancy w VWD

Answer 29

3rd trimester values FVIII or VWF activity <0.5U/mL OR prev sev bleed hisotry, current hisotry bleeding

Question 30

What factor % level means bleeding at delivery and Csection is minimal

Answer 30

at least 50% FVIII

Question 31

Post partum monitoring in VWD

Answer 31

FVIII reguarly checked at term and 2 weeks therafter - FVIII and VWF fall rpaidly All patients take tranexamic acid home to mitigate PP haemorrhage

Question 32

Treatment for heavy menstrual bleeding in VWD

Answer 32

 Combined oral contraceptive pill  Hormonally coated intrauterine device (Mirena)  Endometrial ablation  Hysterectomy (last resort)  Note: hormonal therapy increases VWF and FVIII levels  DDAVP, antifibrinolytics or both may be effective

Question 33

Who develops allo antibodies to VWF and what can mean

Answer 33

10% of type 3 Repeated exposure to concentrated of VWF -> anaphylaxis