DR. MD.AMINUR RAHMAN

PHASE B RESIDENT

DEPARTMENT OF HAEMATOLOGY

BSMMU

Case 1: A 40-year-old patient diagnosed as severe Haemophila A

• Prophylactic FVIII was started at young age.
• standard FVIII 50IU/kg
• was switched to r FVIII-Fc

half-life 1.5-times that of FVIII

• In July 2019, he presented with radicular hyperaesthesia and pain in the right arm
• Refractory to conservative measures.
• Imaging : paramedian right-sided disc herniation at C5/C6
• Needs surgical intervention

What should be management of this patient ?

Treatment of bleeding and perioperative management in hemophilia A and B

Aims of this presentation

Management of haemophilia A and B in

• Serious or life threatening bleeding
• During major and minor surgery
• Patient with inhibitor

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ACUTE THERAPY FOR BLEEDING� Serious or life-threatening bleeding includes

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• central nervous system
• Ocular ,hip
• Deep muscle
• Intra-abdominal
• airway ,throat ,neck

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• Anemia
• Prolonged bleeding
• Iliopsoas
• Significant injuries

Timing of starting treatment

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• within 30 minutes
• At home if possible
• should not be delayed while awaiting imaging
• CT scan or MRI for head injuries
• if in doubt, treat as serious bleeding
• Give the appropriate product that is available

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Factor dosing for severe bleeding

• Hemophilia A (deficiency of factor VIII without an inhibitor) – initial dose of factor VIII of 50 units/kg to raise the factor VIII level to 100 percent.
• Formula: weight in kg x (target level-current level)x 0.5 = desired amount of factor

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For haemophilia A

• Second and subsequent doses :

depends upon half-life , usually after 8 to 12 hours.

for longer-lasting factor VIII ,10 to 20 hours

• Another option is to give the initial bolus followed by a continuous infusion

dose : 4 units/kg/hour.

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Hemophilia B

• without an inhibitor– Give an initial dose of factor IX of 100 to 120 units/kg.
• patient's weight (in kg) × desired rise in factor IX level .

Hemophilia B

• second and subsequent doses:

intervals of 18 to 24 hours.

• for longer-lasting factors -54 to 104 hours.
• Another option: initial factor IX bolus followed by

continuous infusion - 6 units/kg/hour

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Monitoring

• peak factor activity level:

5 to 15 minutes after the first dose

• Trough factor activity levels:
• (steady state levels) for continuous infusion
• In major life-threatening bleeding: trough is checked at 4 to 6 hours for factor VIII

8 to 12 hours for factor IX

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Duration of treatment

• For head trauma : for at least three days

If negative imaging.

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• Documented ICH: for three weeks

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Factor dosing for joint bleeding

• within 2 hours
• At home if possible
• For hip, iliopsoas : target factor level 80 to 100 %
• For knees, elbows or ankles : target 40 to 50 %.

Hemophilia A : 25 units/kg to raise the factor VIII level by 50 percent.

Hemophilia B : 50 to 60 units/kg to raise the factor IX level by 50 percent.

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Duration of treatment for joint bleeding

Additional doses and the duration individualized

• Single dose may be sufficient
• at 24 and 72 hours after the 1st dose.
• Hemophilia B: Initial target level 80% activity then 40 % activity
• Hip joint or acetabular hemorrhages- target (30 to 40)% for three days

Muscle/Soft tissue bleeding

• Present with aching, pain, or swelling.
• Compartment syndrome.
• Therapy : as soon as possible
• Severe muscle hematomas: target 50%
• Mild hemophilia A : DDAVP
• Surgical decompression: if medical therapy fails.
• Hemoglobin % should be monitored.

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Minor bleeding

• Epistaxis or skin bleeding.
• Local measures : ice, pressure or elevation.
• Antifibrinolytic agents
• Adjunctive local therapies
• larger volume blood loss : replacement therapy

ELECTIVE SURGERY

• comprehensive plan

Multidisciplinary team

• operative physician
• anesthesiologist
• patient/family
• hematologist
• social worker
• Laboratory monitoring of factor activity
• Immediate availability of factor.
• plasma components in resource-limited settings.

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Preoperative assessment

• General physical examination
• Systemic examination- CVS, liver disease
• Inhibitor screening with titer
• Issues related to monitoring.
• DDAVP test dose: for mild hemophilia A

one week before planned surgery

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Major surgery- includes

• Any surgery with a risk of clinically significant bleeding
• Penetration of a major body cavity
• Orthopedic surgery-commonest
• Experienced multidisciplinary team needed

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Major surgery - management

• Target factor activity level and duration of therapy are individualized.

Desired preoperative factor level

• 80 to 100% for hemophilia A
• 60 to 80% for hemophilia B
• Postoperative levels 50%
• period of 10 to 14 days.

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Subsequent dosing

• Based on the plan of care , patient's clinical status, and the measured levels.
• In bolus dosing : at 8 to 12 hours after the previous dose for factor VIII

12 to 24 hours for factor IX

In continuous infusion : started before the surgery

Recombinant factor VIIIFc fusion; PEGylated recombinant factor VIII –is being used

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Dose is calculated from

• Body weight, baseline factor level, desired factor level, volume of distribution, and presence of an inhibitor.
• Baseline factor level : 0 %
• Exception when baseline factor >20%
• Initial dose : 30 to 60 minutes before the procedure

Monitoring

• After infusion, the factor level should be checked.
• Receiving emicizumab : bovine substrate-based chromogenic factor VIII assay
• Patient with inhibitor using bypassing therapy : no coagulation test

Circumcision

• Do not administer factor prior to procedure.
• Method : Plastibell device.
• Ensure : factor is available.
• In Gomco clamp method : one dose of replacement therapy.
• Observation : post-procedure
• Prolonged bleeding : may require additional doses.

Other measures during Circumcision

• Fibrin glue (also called fibrin sealant) containing concentrated fibrinogen and coagulation factor XIII.
• Gelatin granules.
• Antifibrinolytic such as tranexamic acid or epsilon aminocaproic acid.

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Tonsillectomy

• High-risk procedure.
• Factor replacement : for severe or moderate cases.
• prolonged period : several days.
• Antifibrinolytic

Dental procedures

• Invasive dental procedures: target > 50 % for one to two days.

one infusion of factor plus antifibrinolytic therapy.

• serious risks with extraction of mandibular third molars (wisdom teeth).

due to the potential for retropharyngeal bleeding and airway compromise.

• may not require factor infusion-examples

buccal infiltration

interpapillary injection

endodontic (root canal).

Dental procedures for Mild hemophilia�

• Factor activity level above 5%
• Majority of non-surgical dental procedures can be done
• antifibrinolytic agent :

two hours before

continue for up to 7 to 10 days.

Endoscopy

• Factor replacement for moderate to severe cases
• Mild hemophilia A : DDAVP
• Biopsies may be taken
• Antifibrinolytic

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SPECIAL POPULATIONS -patient with an inhibitor

• Challenging
• Treated in a comprehensive hemophilia treatment center.
• Depend on severity of bleeding, type and titer of the inhibitor.
• low-responding : titer less than 5 BU
• high responding : more than 5 BU

• Current titer < 5 BU : factor coverage.
• Titer ≥5 BU :

serious bleeding

major surgery

bypassing product (rFVIIa products or FEIBA)

factor VIIa can directly activate factor X, bypassing the need for factors VIII and IX

• Activated PCC another option

FEIBA

Dosing of FEIBA :

50 to 100 units/kg every 6 to 12 hours

not to exceed 100 units/kg/dose or 200 units/kg/day

— Another option for a patient with hemophilia A and a high titer inhibitor

Recombinant porcine factor VIII

Plasmapheresis

Reserved for

• life-threatening
• limb-threatening bleeding and
• inhibitor titer >5 BU
• for whom bypassing therapy is not effective

High-dose factor infusion

• patients with hemophilia A or B and a low titer <5 BU
• Full replacement dose plus an additional 50 percent more factor for every BU of inhibitor.
• Example : for a 60 kg patient with factor VIII deficiency and an inhibitor of 2 BU

(60 kg x 100 x 0.5 = 3000 units of factor VIII)

plus an additional (2 BU x 60 kg x 50 x 0.5 = 3000 units of factor VIII)

total of 6000 units of factor VIII.

Management of case 1

• rFVIIIFc : 25IU/kg the day before surgery
• 50IU/kg : prior to surgery (with a target FVIII activity ⩾80)
• 37.5IU/kg : 12h after surgery
• 37.5IU/kg : daily (targeting trough levels ⩾60%)
• for 6 consecutive days
• every second day until day 10.

Outcome

• No bleeding complications
• FVIII measurements confirmed stable FVIII activity > 80%
• Discharged on day 4
• Continued FVIII treatment as mentioned above
• No further bleeding episodes.