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

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).

von Willebrand Disease Qualitative or quantitative deficiency of von Willebrand factor

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

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

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

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

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

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

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

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

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

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)

Antifibrinolytics Contraindications GU bleeding (risk of obstruction) Acute thrombosis

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

Desmopressin Adverse effects Hyponatremia/fluid shifts Tachyphylaxis Rare thrombotic events

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

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 12-20 hours) Bolus dose to 100% pre-procedure

FIX Replacement Products Short acting (t½ 18-24 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

Bypassing Agents FEIBA Factors II, VII(a), IX, X 50-100 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

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

Take Home Bleeding disorders are variable and complex but manageable Do not hesitate to call us! The Hemophilia Center 503-494-7378