1. Periprocedural Management of Patients with Bleeding Disorders
DATE: November 2, 2018 PRESENTED BY: Bethany Samuelson Bannow, Assistant Professor, Hematology

2. Objectives
Review common bleeding disorders including von Willebrand disease and hemophilia with and without inhibitors.
Briefly review selected rare bleeding disorders including qualitative platelet defects, FXI deficiency and acquired hemophilia.
Discuss the use of prohemostatic therapies including clotting factor infusions, desmopressin and antifibrinolytic agents as well as a brief discussion of newer agents (emicizumab).

3. von Willebrand Disease
Qualitative or quantitative deficiency of von Willebrand factor

4. von Willebrand Disease
Mucocutaneous bleeding
Traumatic bleeding/excessive bruising
Heavy menstrual bleeding
Low platelet counts or FVIII levels (similar to hemophilia) may be seen

5. von Willebrand Disease Treatment
Antifibrinolytic therapies
Desmopressin- intranasal or infusion
Factor replacement with Humate P

6. Hemophilia Deficiency of FVIII (hemophilia A) or FIX (hemophilia B)
<1% - severe disease
1-5% - moderate disease
>5% - mild disease
Traumatic bleeding can be seen in all severities

7. Hemophilia Joint or musculoskeletal bleeds Chronic arthropathy
Trauma-induced bleeding
Intracranial hemorrhage

8. Hemophilia Treatment Factor replacement Goal 100% for most procedures
Antifibrinolytics may be used as adjunctive tx
Desmopressin may be used in mild disease

9. Inhibitors in Hemophilia
30% of FVIII deficiency
May be to all factor or exogenous only
Bleeding may be extremely difficult to control
Bypassing agents required
FEIBA or Novoseven

10. Rare Disorders – FXI deficiency
Bleeding symptoms
Highly variable
Do not correlate to factor level
Trauma-induced
Treatment options
Replacement (FFP only in US)
Antifibrinolytics +/- low dose novoseven

11. Rare Disorders – Platelet Disorders
Bleeding symptoms
Difficult to characterize, variable
Can be quite severe
Treatment options
Platelet transfusion*
Antifibrinolytics
Desmopressin

12. Rare Disorders – Acquired Hemophilia
Presentation
Low FVIII in a patient w/o bleeding history
Skin & soft tissue bleeding
Treatment options
Immunosuppression
Novoseven or obizur

13. Antifibrinolytics Clot stabilizers Systemic and topical benefits
Tranexamic acid
Oral TID or IV (bolus +/- drip)
Epsilon aminocaproic acid
Oral q4h or IV (bolus followed by drip)

14. Antifibrinolytics Contraindications GU bleeding (risk of obstruction)
Acute thrombosis

15. Desmopressin Release of endogenous FVIII and VWF stores
Mild hemophilia and vWD
Uremic platelets & other qualitative disorders
Stimate*
Intranasal, 1 hour prior
Desmopressin
IV 30 min prior

16. Desmopressin Adverse effects Hyponatremia/fluid shifts Tachyphylaxis
Rare thrombotic events

17. vWF Replacement Products
Typically include VWF + FVIII (Humate P®)
40-60 RCo units/kg 30 min prior
Redose 8-12 hours later
Humate P® Package Insert

18. FVIII Replacement Products
Short-acting (t½ 8-12 hours)
Dose to 100% (50u/kg) IV 30 min prior to procedure
Continuous drip vs bolus q12-24 hours post
Extended half-life (t½ hours)
Bolus dose to 100% pre-procedure

19. FIX Replacement Products
Short acting (t½ hours)
Dose to 100% (100u/kg) IV 30 min prior
Daily dosing post
Extended half-life (t½ up to 100 hours)
Dose to 100% pre-procedure
Redosing variable

20. Bypassing Agents FEIBA Factors II, VII(a), IX, X
u/kg pre-procedure, q12-24 hours
Novoseven
Activated FVIIa
90mcg/kg pre-procedure & q2 hours
Obizur – porcine FVIII
Only approved in acquired hemophilia
Generally better to delay procedure

21. Emicizumab Monoclonal antibody Functionally replaces FVIII
Approved in inhibitor (and noninhibitor!) patients
Interferes with factor assays
Little data on periprocedural management
Makris, Blood 2016

22. Take Home Bleeding disorders are variable and complex but manageable
Do not hesitate to call us!
The Hemophilia Center