Clotting the Gaps in VWD Care: Elevating Diagnostic Awareness and Treatment Planning With Modern Therapeutic Approaches

Chair, Maissaa Janbain, MD, MSCR, discusses von Willebrand disease in this CME/MOC/NCPD/IPCE activity titled “Clotting the Gaps in VWD Care: Elevating Diagnostic Awareness and Treatment Planning With Modern Therapeutic Approaches.” For the full presentation, downloadable Practice Aids, and complete CME/MOC/NCPD/IPCE information, and to apply for credit, please visit us at https://bit.ly/3U7KaEH. CME/MOC/NCPD/IPCE credit will be available until July 11, 2025.

1. Clotting the Gaps in VWD Care
Elevating Diagnostic Awareness and
Treatment Planning With Modern
Therapeutic Approaches

Maissaa Janbain, MD, MSCR
Associate Professor of Clinical Medicine
Director

Tulane University

Deming Department of Medicine
Section of Hematology &

Medical Oncology - Louisiana Center
for Bleeding & Clotting Disorders

New Orleans, Louisiana

Copyright © 2000-2024, Peerview

2. Our Goals for Today

Increase your awareness of some barriers to optimal VWD care,
including short-comings with lab based diagnosis and
uncertainties among clinicians

Augment your ability to utilize validated tools for the diagnosis
and classification of VWD

Sharpen you skills for developing individualized treatment plans
using modern therapeutics, including with VWF/FVIII concentrates
Enhance your ability to address practical aspects of VWD care,
such as patient education, care coordination and safety
considerations in collaboration with other healthcare providers

Copyright © 2000-2024, Peerview

3. Test Your Knowledge and Earn Credit as You Go!

Answer
the baseline
question
for each module

to evaluate
your knowledge
and skills

Review
the supporting
evidence
and get expert
insights within
the module

Answer the
question again
to demonstrate

what you
have learned

Each correct
answer counts
towards your
post-test
completion

PeerView.com/GXU827

PeerView.com

Copyright © 2000-2024, PeerView

4. Module 1

Acknowledging Challenges and
Barriers to Diagnosing VWD

Associate Professor of Clinical Medicine

Director

Tulane University

Deming Department of Medicine

Section of Hematology & Medical Oncology - Louisiana Center for Bleeding
& Clotting Disorders

New Orleans, Louisiana

Go online to access full CME/MOC/NCPD/IPCE information, including faculty disclosures.

Copyright © 2000-2024, PeerView

5. An Overview of von Willebrand Disease’?

Ii A Historical Outlook

+ Discovered in 1924

+ Named after Dr. Erik von Willebrand

* Index case: a 5-year-old Finnish girl
named Hjôrdis

+ Today found in up to 1% of the US
population

— Approx. 3.2 million (or 1 in every 100)
people have VWD

— Occurs equally in men and women

1. Mat von Wiobrand disease? Centos for Disease Control and Prevention website pm ede goninebdd facts hi %
2. Bharat PK ot al. Indian J Pharm Sci 2011:73:7-16 PeerView.com

PeerView.com/GXU827 Copyright © 2000-2024, PeerView

6. An Overview of von Willebrand Disease’?

r Molecular Underpinnings of
VWD

VWF Monomer VWF Dimer
+ VWF isa large protein |
+ The larger the multimer the better —
the VWF is going to bind to i ee
platelets and bridge them to the site —
VWF Multimer

of bleeding with collagen in the
subendothelial matrix

+ VWF is synthesized in the
endothelial cells

+ ADAMTS-13 protein regulates the
secretion of VWF into plasma

ADAMTS-13 cleaves unusually large
of VWF

1. Mat von Webra disease? Centers for Disease Control and Prevention west, tw. goninebdd tte Ni fi
2 Bharat PK ot al. Indian J Pharm Sci 2011:73:7-16 PeerView.com

PeerView.com/GXU827 Copyright © 2000-2024, PeerView

7. Classifying von Willebrand Disease?

(Condition ] [Prevalence ) | Description

Partial quantitative VWF deficiency

pi ER (75% of symptomatic patients with VWD)
Decreased VWF-dependent platelet adhesion with selective
Type ZA: 10%: 15% deficiency of high-molecular-weight multimers
Type 2B 5% Increased affinity for platelet GP1b
MWF-dependent platelet adhesion without selective deficiency of

Type 2M Rate high-molecular-weight | multimers
Type 2N Rare Markedly decreased binding affinity for FVIII

Type 3

1. Wat i von Morand disease? Centers for Disease Control and Prevention website tw. goninebdd wc fts hi -
2 Lirop D. Blood. 2013:122:3785-3740, PeerView.com

PeerView.com/GXU827 Copyright © 2000-2024, PeerView

8. Classifying von Willebrand Disease: Type 1 and 31

A e
TS SISSI
Endothelial cell Weibel-Palade body

1. Branchford BR etal. Homatology Am Soc Hematol Educ Program. 2012:2012:161-167. PeerView.com

PeerView.com/GXU827 Copyright © 2000-2024, PeerView

9. Classifying von Willebrand Disease: Type 21

Type 2A VWD: Absent high- and intermediate-
weight multimer leading to decreased platelet
binding; abnormal multimer

2

Type 2N VWD: No binding to FVIII, manifests
‘similarly to hemophilia; normal multimer

Fe »
Platelet binding site Dee 2 pr Qualitative VWF Defect a
WF monomer
Pa Ee Bär pe
NET ao te Es

‘Mutated VWF
prevents
binding to
vu

Type 2B VWD: Increased platelet binding, gain- ‘Type 2M VWD: Decreased platelet binding, loss-
‘of-function mutation; abnormal multimer, ‘of-function mutation in GP'1b-a binding site;
thrombocytopenia normal multimer

1. Branchford BR et a. Hematology Am Soc Homatol Educ Program. 2012.2012:161-167. PeerView.com

PeerView.com/GXU827 Copyright © 2000-2024, Peerview

10. The Impact of Age on VWF Levels!

Age Only

VWF/FVIII Levels Increase With Age

+ High variability of VWF levels across age
groups

+ Possible modifier of the clinical bleeding
phenotype during life

+ Physiological/pathological conditions can
temporarily increase VWF levels (eg,
pregnancy, postpartum, oral contraceptive,
inflammation)

VWF activity, units/dL.
385838

VWF activity, units/dL.
8 8 8 8

‘Age Only Full Model

Full Model

Age,
Full Model

oa 0 © &
Age, y Age, y
al. J Thromb Hoomost. 2020:19-96-106.

1. Biguzzi €,

PeerView.com/GXU827

D 0 0 © 100
Age, y

PeerView.com

Copyright © 2000-2024, PeerView

11. The Impact of Blood Type on VWF Levels!

O vs non-O Blood Groups
and VWF Levels
+ Blood group O associated
with lower VWF levels

VWF levels in normal
individuals with blood group
O overlap with VWF levels

Vicenza Score

9 © #0 150 200 250
Lowest VWF, units/dL.

in patients with mild type 1 zo

VWD, making the diagnosis Se

of type 1 VWD particularly 3, =

challenging E,
3:
$7 © do wo æ ao
a Lowest VWF, units/dL.

1. Mehic D et al. Blood. 2023:142(suppl1):1249. PeerView.com

PeerView.com/GXU827 Copyright © 2000-2024, PeerView

12. Summary of Challenges and Barriers
to Timely gnosis of VWD

WD is challenging to diagnose owing to disease heterogeneity"

No single laboratory test can determine the presence or absence of functional
WF and pre/post-analytic factors can result in falsely low VWF levels23

On average, patients experience a 1.8-year delay from initial bleeding symptoms
to diagnosis of VWD*

Inadequate use of diagnostic and assessment tools lead to under- or misdiagnosis
of VWD4

00006

1. Sidono RE et a Hasmophi. 201723743-749.2, Keesler DA et a. Ros Pract Thromb Hoomost 2018 234.41 7:
3, Colonne CK et al. J Blood Med. 2021;12:755-768, 4, Sidonio RF et a. J Blood Med. 2019.2020:1-11. PeerView.com

PeerView.com/GXU827 Copyright © 2000-2024, PeerView

13. Module 2

New Rules for Diagnosing VWD:
Guidelines, Tools, and Techniques

Associate Professor of Clinical Medicine

Director

Tulane University

Deming Department of Medicine

Section of Hematology & Medical Oncology - Louisiana Center for Bleeding
& Clotting Disorders

New Orleans, Louisiana

Go online to access full CME/MOC/NCPD/IPCE information, including faculty disclosures.

© 2000-2024, PeerView

14. Recognizing and Diagnosing VWD: Case Discussion

O Questions to Consider

Cap 4a

A 15-year-old female presents
with severe bleeding after a + What symptoms should raise
dental procedure. suspicion of a bleeding disorder?

History + What testing should be done to

establish a diagnosis of VWD or rule

Heavy menstrual bleeding which
has improved on combined oral
contraceptive pill out differential diagnoses?
Diagnosed with iron deficiency

anemia

Easy bruising

No relevant family history

PeerView.com

PeerView.com/GXU827 Copyright © 2000-2024, Peerview

15. VWD Differential Diagnoses

hat Else Could it Be?

+ Factor X deficiency

« Factor XI deficiency

+ Hemophilia A

+ Hemophilia B

* Bernard-Soulier syndrome
+ Platelet function defects

+ Antiplatelet drug ingestion
+ Fibrinolytic defects

PeerView.com

PeerView.com/GXU827 Copyright © 2000-2024, PeerView

16. 2008

minutes

Condensed
MCDMCM
+ Developed in

+ Administration
time ~10

Bleeding Assessment Tools’?

PBQ
(pediatric)

+ Developed in
2009

SELF BAT

+ Developed in
2013

+ Administration
time ~10

minutes

+ Developed in
2010

+ Administration
time -20
minutes

+ Administration
time -20
minutes

For patients with a low probability of VWD, guidelines recommend BATs as an initial
screening test to determine who needs specific blood testing

For patients with an intermediate-high probability (eg, family history of VWD), guidelines
do NOT recommend BATs to determine the need for laboratory testing

1. Rodeghier F et al. J Thromb Haemost 2010:82083-2085, 2. James PD et al. Blood Adv. 2021:5:280-300, PeerView.com

PeerView.com/GXU827

Copyright © 2000-2024, PeerView

17. Useful Tests for Diagnosing VWD'

Genetic Testing

Laboratory Tests
+ VWF antigen? (VWF:Ag) + ASH/ISTH/NHF/WFH 2021
+ WF ristocetin cofactor assay? (VWF:RCo) Se recommend the use
* indil a of targeted genetic testing over
WE Binding 10 mutant GP ibe QuE al LD-RIPA for patients suspected
+ VWF binding to recombinant GPlba (VWF: GPIbR) of type 2A or 28 VWD
+ VWF collagen binding assay (VWF:CB)
+ VWF propeptide (VWFpp) + For patients suspected of type
+ Low dose ristocetin-induced platelet agglutination? 2N WD, either VWF:FVIIIB or
(LD-RIPA) targeted genetic testing (if
+ Factor VIII clotting assay? (FVIII:C) ele tecommenied
+ VWF factor VIII binding assay (VWF:FVII/B)

+ voy ala a
1 ames PD at a Blood Adv 2021:5:200:00. PeerView.com

PeerView.com/GXU827 Copyright © 2000-2024, Peerview

18. Diagnostic Algorithm for VWD12

Type 1 WWD

‘Type 2M VWD

Ratio of FVII:C
WWE Ag

wer
Reduced

Type 2N VWD H Low VWF
1. Figure adapted rom: Leobeok FWG ota. N Engl J Med, 2016:375-2067-2080, 2. James PO et dl. Blood Adv, 2021:5:280-300. PeerView.com

PeerView.com/GXU827 Copyright © 2000-2024, PeerView

19. It Takes a Team to Diagnose VWD'

Specialists diagnosing female patients with Specialists diagnosing male patients with VWD
VWD (N = 9,793) (N =3,834)
60
* 40
€
€
5
& 20

Hospitalists/ERs were responsible for approximately half of all VWD diagnoses; 21% of
patients were diagnosed by hematologists, and 16%-17% by primary care physicians

1. Sidonio RF etal, Haemophilia, 2017:23:743-749. PeerView.com

PeerView.com/GXU827 Copyright © 2000-2024, PeerView

20. Case-Based Take-Homes on
Recognizing and Diagnosing VWD

Take-Home Points ya

=)
(mad 4a

A 15-year-old female y Use bleeding assessment tools
presents with severe un o
bleeding after a dental v Use specific lab tests for VWD at initial
procedure. diagnosis
SE v 22 sets of subnormal results (ideally 3 months
Additional tests showed: apart)
+ BAT score of 8
+ Positive bleeding score, v Know how to approach patients with VWF
warranting further levels that are initially abnormal and then
hemostatic testing normalize with age

Low VWF plasma levels

PeerView.com

PeerView.com/GXU827 Copyright © 2000-2024, PeerView

21. Module 3

Facing the Next Hurdle:
Acknowledging Management
Challenges in VWD

Associate Professor of Clinical Medicine

Director

Tulane University

Deming Department of Medicine

Section of Hematology & Medical Oncology - Louisiana Center for Bleeding
& Clotting Disorders

New Orleans, Louisiana

Go online to access full CME/MOC/NCPD/IPCE information, including faculty disclosures.

Copyright © 2000-2024, Peerview

22. First
Le)

Advances in the Management of VWD

Pasteurized
Pool's FVIIIVWE WWF with Recombinant

cryoprecipitate available in low FVIIL Vir tested TWF in

used for WD Germany evaluated phase 3 trial

Oper

Plasma and VWF cultured VWF gene ADAMTS-13
Cohn's fraction 1 from human discovered identified option Late POA opp approved
used for VWD endothelial cells VWD

PeerView.com/GXU827

PeerView.com

Copyright © 2000-2024, PeerView

23. Impact of a VWD Diagnosis on Bleeding Episodes:
Analysis of Medical Insurance Claims Data!

Frequency of bleeding episodes in female Frequency of bleeding episodes in male
patients (N = 3,912) patients (N = 1,564)
1% VWD Claim 1% VWD Claim
50 1 50 :
i
1
40 1
x '
x A 1
ö = 30 26 MH
E 3 i
3 Ë 20 y 18
E 13 1
1
10 O : >
1 3 23
; 1 A En
12 mo prior to 0-12 mo after 12-24 mo after 12 mo prior to 0-12 mo after 12-24 mo after
diagnosis diagnosis diagnosis diagnosis diagnosis diagnosis
=Total mibleed =2bleeds 3+ bleeds mTotal m1bleed m2bleeds m3+ bleeds

Frequency of bleeds before and after VWD diagnosis suggests lack of guidance and
‘aggressive’ treatment approaches

1. Sidonio RF etal, Haemophilia, 2017:23:743-749. PeerView.com

PeerView.com/GXU827 Copyright © 2000-2024, PeerView

24. Impact of a VWD Diagnosis on Types of Bleeding Episodes:

Analysis of Medical Insurance Claims Data!
Type of bleeding episodes in female patients

Type of bleeding episodes in male patients
(N = 6,732) (N = 2,667)
1 VWD Claim 1# VWD Claim
40 H
ss
30 H
pa
En
3
&

10 |

4 | A

: £6 1110 Biot ss
o

6 mo priorto ” 0-6 mo after 7-12 mo after 13-18 mo after 19-24 mo añor
diagnosis diagnosis diagnosis diagnosis diagnosis

6 mo priorto 0-6 mo after 7-12 mo after 13-18 mo after 19-24 mo after

diagnosis diagnosis diagnosis

diagnosis diagnosis
Total

‘Heavy menstrual bleeding Total mEpistaxis
wEpistaxis = Prolonged bleeding = Prolonged bleeding "Gl bleeds
"GI bleeds "Gum bleeds ™Gum bleeds

1. Sidonio RF etal, Haemophilia, 2017:23:743-749. PeerView.com
PeerView.com/GXU827

Copyright © 2000-2024, PeerView

25. Challenges of Gl Bleeds in VWD1-3

Understanding GI Bleeding
in VWD |

+ Recurrent GI bleeding often results from

‘vascular malformations (anglodysplasla) Normal Endothelial Cell VWF-Deficient Endothelial Cell
= Linked to the loss of high-molecular- es
weight multimers of VWF a vea MEGA

+ Affects up to 38% of patients with WWD
= Most frequently affects type 3, 2A, and 28
+ Diagnosis of angiodysplasia-related Gl
bleeding is challenging
- Lesions often located in small intestine,
not visualized by conventional endoscopy
- Requires active bleeding for identification
and use of multiple GI investigations with
‘conventional or video capsule endoscopy

+ Treatment involves treating the bleed and the
Underlying disorder to prevent recurrent Gl
bleeds

1. Ghomenki NLJ et a. Hematology Am Soc Hematol Educ Program. 2022:1624-630. 2. Oran E etal. Export Rov Hematol. 2023:16:575:584, A
3, Makis M ot al. Hoomophiia, 2014:21:338-342, PeerView.com

PeerView.com/GXU827 Copyright © 2000-2024, PeerView

26. Who is Involved in Managing VWD-Related Bleeds?"

Specialists managing bleeding episodes in Specialists managing bleeding episodes in

female patients (N = 1,799) male patients (N = 382)
1% VWD Claim 1! VWD Claim
504% :
40
x
PE
E
5
¿20
é
10
0
6 mo porto” 0:5 mo post 7-12 mo post 13-18 me” 19-24 mo 6 mo porto 0-8 mo post 7-12 mo post 13-18 mo 19-24 mo
diagnosis diagnosis diagnosis post post diagnosis diagnosis diagnosis post post
diangosis diagnosis diagnosis diagnosis
'Hospitalists/ER physician
mHospitalsis/ER physician "OB/GYN rey cación
= Primary care physician = Hematologist SE
Ear, nose, throat physician Rar neo ices ee

1. Sidonio RF et al. Haemophilia, 2017:23:743-749, PeerView.com

PeerView.com/GXU827 Copyright © 2000-2024, PeerView

27. To Improve the Management of VWD, We Need to Address
These Challenges and Unmet Needs1*

Diagnostic delays result in more bleeding episodes and high ER visits, which persist even
after diagnosis of VWD, suggesting inadequate management of VWD

Lack of standardized approaches/clear guidance on when and how to treat VWD, in part
due to heterogeneity of the disease, leading to frustration from providers and patients

Challenges related to the need for IV infusions with available therapies, including
resistance among patients to adopt these treatments

Difficult to measure success of therapy due to absence of long-term impacts of bleeding
in patients with VWD (except for iron deficiency anemia)

VWD in women is often more clinically severe due to menorrhagia and poses unique
challenges, especially during pregnancy

6600066

‘Sidono RF et al. Hoemophäo.201723:743-749. 2. De Woo EM et al. Thromb Hoemost. 20108:1452-1459.
van Hom ES et a Haemophie, 2022.26 197-214. 4, Son RF a al Blood. 2020-13 (supp1 128-398. Du Petal. Cin App! Thromb Hemost. 202228 m
Du P ot al Value Heath, 2022:25:369-370, PeerView.com

PeerView.com/GXU827 Copyright © 2000-2024, PeerView

28. Module 4

Examining the Evidence With
Modern Therapeutics in VWD

Associate Professor of Clinical Medicine

Director

Tulane University

Deming Department of Medicine

Section of Hematology & Medical Oncology - Louisiana Center for Bleeding
& Clotting Disorders

New Orleans, Louisiana

Go online to access full CME/MOC/NCPD/IPCE information, including faculty disclosures.

000-2024, PeerView

29. Desmopressin: How Does it Work?!

Releases pre-formed stores of
FVIII and VWF from the
endothelium

Effective in majority of patients
with VWD

Enhances interaction between Binding to VWF receptors on

platelets and the VWF platelets

Associated with adverse effects and tachyphylaxis

1. Ozgenene 8 et al. Postgrad Med J. 2007:83:159-163, PeerView.com

PeerView.com/GXU827 Copyright

30. VWF Concentrates for the Management of VWD!

+ Patients with von Willebrand disease usually have both low VWF and Factor VIII
+ Available VWF concentrates have varying amounts of VWF as well as Factor VIII

VWF Plasma Concentrates

IS)
© ©

To reduce potential thrombogenicity, guidelines recommend:
+ Levels remain below 250% for FVIII and 200% for VWF:RCo

+ FVIII:C concentration between 50 U/dL and 150 U/dL during the
postoperative period

1.Comel NT et al. Blood Adv. 2021:5301-325. PeerView.com

PeerView.com/GXU827 Copyright © 2000-2024, PeerView

31. Overview of VWF Concentrates:
Plasma-Derived and Recombinant!-5

Recombinant

Plasma-Derived VWF-Containing FVIII Concentrates QUE

Humate Alphanate Wilfactin Vovendi

Precipitation/ion lon exchange +
exchange and affinity
size-exclusion CT chromatography

Multiple Precipitation!
precipitation heparin ligand CT

7 Chinese hamster
Purification method ovary cell line

Solvent detergent, Solvent detergent, Solvent detergent,

Viral inactivation Pasteurization fay eal best dry pass Not required
VWF:Rco/VWF:Ag 0.91 0.43 0.9-1 0.95 1.16
'VWF:Roo/FVIII:C ratio 2.88 0.82 1 50 No FVIII
Ultralarge multimers Absent Absent Absent Absent Present

Yes Yes Yes

FDA approved

1, Sidono RF et al Blood Ad. 2024:1405-1414. 2. Humat-P Presebing Information. hips wav da govimeda/73587\download?atachment 3. Alphanate
ProsctingInormaton.Mipa wma. ta gowmeda/717S3!sonnload?atiachmont&, Wiate Pressing ornato. itp Ka govimeda/77812Gowibad. en
5. VonvendiPrescribing Information. tps www {da.govimedia/S4863/download attachment. PeerView.com

PeerView.com/GXU827 Copyright © 2000-2024, Peerview

32. Long-Term Efficacy of On-Demand, Prophylaxis,
and Surgical Prophylaxis With Humate P1

Pooled Hemostatic Efficacy of Pasteurized pdVWF/FVIII

3.9% 0.4% 5.6% 0.7% 1.4% 0.5%

95.7%

43 patients
144 prophylactic
uses
2 studies

264 patients
1,351 treated
bleeds
4 studies

339 patients
420 procedures

8 studies

On-Demand Long-Term Prophylaxis Surgical Prophylaxis

M Excellentgood MM Moderate/poor/no response N/A

1. Etingshausen CE etal. ISTH 2023. Abstract PB1245, PeerView.com

PeerView.com/GXU827 Copyright © 2000-2024, PeerView

33. Long-Term Safety Profile of Humate P1

(1990-June 2022)
4,930,932 single dose exposures

Exposure Data
ee 17,751 ,356,642 IU VWF of pasteurized pdVWFIFVIII distributed

ADR Cases
1,296 ADR cases identified in the PV database
for the period June 1982-June 2022

205 cases of
hypersensitivity
reaction*

$ U Y

* Thromboembolism. hypersensitivity. inhibitor development, and ial ransmission are key sks of pasteurized pSVWF/FVIL®Inhibtor cases include FVII and VWF
‘nhibtorsn both hemophaa A and VWD patents dueto reporung methods m
1. Etingshausen CE etal. ISTH 2023. Abstract PB1245. PeerView.com

122 cases of inhibitor 0 confirmed cases of
development®” viral transmission*

58 cases of
thromboembolism®

PeerView.com/GXU827 Copyright © 2000-2024, PeerView

34. Recombinant VWF Concentrates

Recombinant VWF

Vovendi

Purification method Chinese hamster ovary

cell ine
Viral inactivation Not required
VWF:Rco/VWF:Ag 1.16
'VWF:Rco/FVIII:C ratio. No FVIII
Ultralarge multimers Present
FDA approved Yes

PeerView.com/GXU827

Recombinant VWF Concentrates

No exposure to human protease ADAMTS13
during production process

Contains intact high-molecular-weight and ultra-
large multimers

Hemostatic Efficacy, Safety, and PK of rVWF

192 bleeding episodes treated with rVWF
100% reported successful treatment
Treatment rated as excellent in 97.5% of minor
bleeds and 96.7% of moderate bleeds

Median of 2 infusions (range:1-3) required to
control major bleeds

PeerView.com

Copyright © 2000-2024, PeerView

35. Other Therapies Used in the Management of VWD

Other Options/A:

Antifi ibrinolytics
Prevent the breakdown of blood clots once they have started to form
+ Support the body's natural clotting mechanisms
+ Can be used alone in some cases (eg, mild mucosal bleeding; heavy
menstrual bleeding)
- Tranexamic acid
- Aminocaproic acid

Hormonal therapy

Estrogen or combined estrogen-progestogen preparations can increase
VWF levels

Useful for reducing menorrhagia severity in women with VWD

PeerView.com

PeerView.com/GXU827 Copyright © 2000-2024, Peerview

36. Ongoing Innovation in VWD: A Look at the Pipeline

Class Agent

Vonvendi

Emicizumab

VGA039

BT200

VWF

FVIII mimetic

Anti-protein S monoclonal
antibody

Anti-VWF aptamer; shields
VWF from platelets

Patients 12-18 years old
with severe VWD

22 years old with severe
VWD type 3

Patients 18-60 years old
with symptomatic VWD

Patients with type 2B
VWD and some patients
with type 3

Phase 3

Phase 1

Phase 1

Phase 1

PeerView.com/GXU827

PeerView.com

Copyright © 2000-2024, PeerView

37. Module 5

Enhancing Patient Outcomes With Team-
Based Strategies & Modern Therapeutics

Associate Professor of Clinical Medicine

Director

Tulane University

Deming Department of Medicine

Section of Hematology & Medical Oncology - Louisiana Center for Bleeding
& Clotting Disorders

New Orleans, Louisiana

Go online to access full CME/MOC/NCPD/IPCE information, including faculty disclosures.

Copyright © 2000-2024, Peerview

38. Case Discussion on Collaborative VWD Management

©
Ce

A 28-year-old male diagnosed
with severe VWD type 1 who is
not a good responder to
DDAVP.

+ He has a planned dental
procedure for which he needs
prophylaxis.

PeerView.com/GXU827

Questions to Consider pm

What are the goals of therapy?

Which treatment option is likely to provide
the best protection against bleeds during
his procedure?

What are the dosing, administration, and
safety considerations

PeerView.com

Copyright © 2000-2024, PeerView

39. General Guidelines for VWD Management!

Condition Treatment (+ Aminocaproic or Tranexamic Acid for Mucosal Bleeding)

Typen Desmopressin usually works in majority of cases
yp For major surgery, VWF replacement may be preferable

1 2A Desmopressin rarely effective
Bid Infuse VWF (plasma-derived FVIII concentrate or VWF)

T 2B Desmopressin maybe deleterious (may lower platelets, cause clots)
ype Infuse VWF (plasma-derived FVIII concentrate or VWF)

Desmopressin rarely effective
Infuse VWF (plasma-derived FVIII concentrate or rVWF)

Type 2N Infuse VWF (plasma-derived FVIII concentrate or rVWF)

Type 3

3
8
iS
=

1. Connel NT eta. Blood Adv. 2021:5:301-95. PeerView.com

PeerView.com/GXU827 Copyright © 2000-2024, PeerView

40. ASH/ISTH/NHF/WFH 2021 Guidelines
for Unique Bleeding Situations!

ASH ISTH NHF
WFH Guidelines

Heavy Menstrual
Bleeding

; Target VWF activity
Target VWD activity and FVIII activity

0.50 IU/mL. (troughs) Target VWF activity

and ) [U/mL for at least 0.50-1.50 IU/mL
Antifibrinolytic 3 days, extended

needed

1. Connell NT et al. Blood Adv. 2021:5:301-325, PeerView.com

PeerView.com/GXU827 Copyright © 2000-2024, PeerView

41. PeerView.com/GXU827

Goals of VWD Treatment

Increase VWF Replace VWF
+ Desmopressin + Plasma-derived VWF
+ Recombinant VWF

Raise FVIII
+ Often used in type 2/3 VWD

Stabilize Clot
+ Use antifibrinolytics (tranexamic acid, epsilon aminocaproic acid)

PeerView.com

Copyright © 2000-2024, PeerView

42. Patient Education and Shared Decision-Making

Steps to Shared Decision-Making

Step 1. Seek patient's participation

Step 2. Help patient explore, compare treatment options
Step 3. Assess patient's values and preferences

Step 4. Reach decision with patient

Step 5. Evaluate patient's decision

PeerView.com

PeerView.com/GXU827 Copyright © 2000-2024, PeerView

43. Case Discussion on Collaborative VWD Management

O Take-Home Points
A 28-year-old male + Treatment choices should consider patient and product-
diagnosed with severe specific considerations (eg, bleeding risk; thrombosis)
VWD type 3 who has not

had sufficient bleed + Based on guideline recommendations, prophylaxis with

control with DDAVP. factor concentrate targeting 20.50 IU/mL and
antifibrinolytic therapy should be initiated in preparation

+ He has a planned dental for the procedure

procedure for which he

needs prophylaxis * Encourage obtaining PK measurement to determine
procedural plan

PeerView.com

PeerView.com/GXU827 Copyright © 2000-2024, PeerView

44. Final Take-Homes on the Diagnosis
and Management of VWD

Guidelines for VWD Diagnosis Guidelines for VWD Management

+ Use bleeding assessment tools

+ Use specific lab tests for VWD at
initial diagnosis
Know how to approach patients with
VWF levels that are initially abnormal
and then normalize with age
Use genetic testing in the diagnosis of
VWD subtypes

PeerView.com

PeerView.com/GXU827 Copyright © 2000-2024, PeerView