Von willebrands disease Flashcards
Clinical features of VWD
Mucocutaneous bleeding
Musculoskeletal bleeding in type 3 eg haemarthrosis, soft tissue, muscle haemotaoma
Examples of mucocutaneous bleeding
Heavy menstrual bleeding
Epistaxis
Bruising
Exessive bleed from minor wounds
GI bleed
Oral cavity/post dental
Post op
post partum
Where is VWF synthesised
Megakaryocytes (platelets) and endothelial cells
Stored in Weibel-Palade bodies (endothelial cells) and alpha granules (platelets)
VWF role in clotting
Primary haemostasis - platelet adhesion and aggregation
Secondary haemostasis - cahperone to FVIII - prolongs hal life
Type I VWD
Mild to mod quant def of VWF <0.3U/ml and factor VIII
Autosomal dominant
Type 2 VWD
Autosomal dominant
Qualitative deficiency of VWF
4 subtypes
Subtypes of VWD type 2
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)
Type 3 VWD
Quantitaive absence of VWF ,1% normal and low FVIIII levels
Autosomal recessive
What are the 3 diagnostic criteria for VWD
Bleeding symptoms
FH
Labaratory results
How to assess bleeding symptoms
ISTH BAT, condensed MCMDM-1VWD BAT
Basic lab tests for VWD
FBC, PT, APTT
VWD screen - FVIII, VWF antigen, activiy
Consider PA-100 - (in vitro bleeding time) + blood type
VWF genetic testing
What test order if sus type 2 VWD
RIPA - risocetin induced platelet agglutination and multimer studies
Management aim
Raise VWF/FVIII plasma conc -> adeuqate haemoastasis
Which types of VWD are repsonsive to DDAVP/Desmopressin
Type 1,2A,2N
How does DDAVP administer /work
0.3mg/kg IV/SC
Increases FVIII/VWF in 30-60 mins
#Repeat every 12-23 hours as needed
What is tachyphylaxis and when watch for in VWD
Short term intolerance to a drug after use
After 4 doses of desmopressin
Side effects of desmopressin
Flushing
Tachycardia
Headache
Hyponatrema - restrict wtare
CI to DDAVP in VWD
Cardiac risk factors
.65 YEARS
Treatment for DDAVP non response in VWD
VWF:FVIII derived concentrate - humate P (2.4:1)or Wilate (1:1)
What factor is importnatn to monitor before surgery
FVIII
What levels of FVIII are ass w VTE
> 150%
Treatment before major surgery in VWD
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
Treatment before minor surgery in VWD
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
How often should FVIII be monitored
12 hours on day
Every 24 hours after
Adjuct treatments in VWD
Antifibrinolytics eg tranexami acid
Cryoprecipitate ig humate P unavailable
Haemorrhage -> platelet transfusion (if adequate FVIII but uncontrolled)
When use and when dont use antifibrinolytics in VWD
for GI, gynecologic and nasopharyngeal bleeding:
CI - haematuria
When monitor pregnant woman with VWD
EACH TRIMESTER
When refer pregnancy w VWD
3rd trimester values FVIII or VWF activity <0.5U/mL OR prev sev bleed hisotry, current hisotry bleeding
What factor % level means bleeding at delivery and Csection is minimal
at least 50% FVIII
Post partum monitoring in VWD
FVIII reguarly checked at term and 2 weeks therafter
- FVIII and VWF fall rpaidly
All patients take tranexamic acid home to mitigate PP haemorrhage
Treatment for heavy menstrual bleeding in VWD
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
Who develops allo antibodies to VWF and what can mean
10% of type 3
Repeated exposure to concentrated of VWF -> anaphylaxis
