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ASPHO Lectures 2021 > Inherited Bleeding Disordrs > Flashcards

Inherited Bleeding Disordrs Flashcards

(53 cards)

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1
Q

Prophylaxis dosing for Hemophilia A?

A
  • Factor VIII 25-40 IU/kg/dose 3x per week OR QOD

- some centres start with weekly dosing and escalate with bleeds

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2
Q

Prophylaxis dosing for Hemophilia B?

A
  • Factor IX 50-100IU/kg/dose 2x per week

- Some centres start with weekly dosing and escalate

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3
Q

What is a target joint?

A

-Multiple bleeds in the same joint: 3 bleeds in 6 months or 4 in a year

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4
Q

Options for management of chronic arthropathy in hemophilia?

A
  • Medical: Initiation of secondary prophylaxis
  • Surgical: Synovcectomy (open, arthroscopic, radioisotopic)
  • Other: Pain management, physiotherapy, casting, bracing, orthotics, walking/mobility aids
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5
Q

Management of intracranial bleeding in hemophilia with factor replacement?

A
  • 100% correction for at least 2 weeeks

- Continue treatment with prophylaxis dosing indefinitely

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6
Q

Management of retroperitoneal bleeding in hemophilia with factor replacement?

A
  • 80% correction for at least a few days

- Follow-up with short-term prophylaxis (weeks)

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7
Q

Management of muscle bleed in hemophilia with factor replacement?

A

-40-60% correction at least until can utilize muscle with no pain

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8
Q

Management of joint bleed in hemophilia with factor replacement?

A
  • 40-60% correction

- 1-3 doses generally suffice

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9
Q

Management of mucosal bleed in hemophilia with factor replacement?

A
  • 30-50% correction

- Add antifibrinolytics

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10
Q

Management of subcutaneous hematoms in hemophilia with factor replacement?

A
  • Observation generally sufficient

- Large hematomas in “bad” locations (e.g. buttocks) need factor

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11
Q

Management of surgery in hemophilia with factor replacement?

A
  • 100% correction pre-op

- Maintain trough of 50% until risk for bleeding is over

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12
Q

Factor recovery dosing for Factor VIII? Factor IX?

A

Factor VIII: 1 IU/kg increases factor level by ~2%
Factor IX: 1 IU/kg increases factor level by ~1% for all plasma-derived factor IX products; 0.7% for rFIX (3 available products e.g. Benefix)

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13
Q

What is desmopressin?

A

An analogue of anti-diuretic hormone

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14
Q

How does desmopressin work in hemophilia? When is it used? Why do desmopressin challenge?

A

-Increases circulating vWF thereby increasing FVIII levels in most patients with mild hemophilia A
-Not indicated in Factor IX deficiency/Hemophilia B
-Only effective in mild hemophilia A; generally for
mucocutaneous bleeding and minor procedures (dental)
-Desmopressin challenge first because some mild mutations are non-responsive

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15
Q

Important adverse effects of desmopressin?

A
  • Hyponatremia in patients <3 years

- Some patients develop hypotension and flushing –> first dose should be administered in clinic

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16
Q

Surgical management in hemophilia?

A
  • Ensure patient does not have an inhibitor
  • Replace factor to 100% immediately prior to procedure
  • Repeat bolus doses to maintain a trough >50% until bleeding risk has passed
  • Can use continuous infusion if many days of factor will be needed (major surgery)
  • Antifibrinolytic drugs can be added, especially for mucous membrane surgery
  • Factor VIII: 50IU/kg immediately prior to procedure, followed by 50IU/kg q12h (can adjust to maintain a trough >50%). Continuous infusion would be (~3IU/kg/hr) to maintain a trough > 50%
  • Factor IX: 120-140 IU/kg of rFIX (or 100 IU/kg of pdFIX) immediately prior to procedure, followed by same dose q12-24h. Continuous infusion would be 6IU/kg/hr to maintain a trough >50%
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17
Q

Management of dental extractions in hemophilia?

A
  • Factor replacement correction to 80-100%
  • Add antifibrinolytic agent (tranexamic or aminocaproic acid)
  • Pressure gauze
  • Desmopressin (not fully reliable)
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18
Q

Management of hematuria in hemophilia?

A
  • Factor replacement correction to 80-100%
  • Hydration at 1.5-2x maintenance
  • Antifibrinolytics CONTRAINDICATED
  • Desmopressin not reliable enough
  • Limited data for glucocorticoids, though often given
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19
Q

Causes of failure of factor replacement?

A
  • Insufficient factor dose (weight based)

- Development of inhibitor

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20
Q

Management of factor replacement failure?

A
  • Test for inhibitor immediately
  • For bleeding, treat with bypassing agent
  • For patients on prophylaxis, suspend therapy
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21
Q

How do inhibitors complicate the management of hemophilia?

A
  • Bleeds are more difficult to treat
  • Prophylaxis not nearly as effective
  • Patients with inhibitors have higher morbidity and mortality
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22
Q

Patient related risk factors for inhibitor development? Treatment related risk factors for inhibitor development?

Study These Flashcards
A

-Patient related:
–Severity of hemophilia
(severe>moderate>mild)
–Family history (identical twin>sibling>uncle or grandfather)
–Molecular defect (large deletion>nonsense>inversion>missense)
–Race (Black>White)

-Treatment related: Product type?; number of exposure days; intensity of exposure; cumulative exposure

23
Q

Which type of genetic mutation has highest rate of inhibitors?

Study These Flashcards
A

Large deletions

24
Q

What test to diagnose inhibitors?

Study These Flashcards
A

Bethesda Assay

25
Management of transient inhibitors?
- Clinically insignificant - Found during routine surveillance - No specific treatment - continue to use standard factor replacement, observe, follow titre
26
Differences between high titre and low titre inhibitors?
- High titre: >5 BU, always high responders (rapid anamnestic response - if give factor VIII, level will rise), must use bypassing agents to treat and/or prevent bleeding - Low titre: <5 BU, low responder (no anamnestic response), can be treated with factor replacement at higher than usual doses
27
Management of patients with inhibitors?
-Eradication of inhibitor using ITI, bleed management
28
What is immune tolerance therapy? When is tolerance achieved?
- Regular (usually daily) infusions of FVIII (or rarely FIX) to "educate" immune system to become tolerant of factor replacement in patients with inhibitors - Over 6-18 months - Tolerance achieved when patient has a recovery of >66% and a half-life of >6 hours - There are different regimens
29
Bleed management in low titre, low responder patients?
- Can use standard factor VIII replacement therapy but need higher doses - No validated formula, but can multiple inhibitor titre by IU/kg that you would give to a non-inhibitor patient - Re-check inhibitor titre to ensure not rising (anamnesis)
30
Bleed management in high titre patients?
- Must use bypassing agents - -Anti-inhibitor coagulant complex (a.k.a. activated prothrombin complex concentrates (APCC)) - -Recombinant activated factor 7/rFVIIa
31
Management of inhibitor patients?
rFVIIa - Bleed treatment: 90-120mcg/kg/dose is US licensed dose - repeated q2-3h until bleed resolution - -Outside US, 270mcg/kg/dose is licensed - Surgical ppx - Ppx - licensed outside US APCC - Bleed treatment: 50-100IU/kg/per dose q8-12h. Not to exceed 200IU/kg/day - Surgical ppx - PPx - 75 IU/kg qod Desmopressin ineffective in inhibitor patients!
32
What is in APCCs?
Plasma-derived mixture of factors II, VII, IX and X (some activated)
33
How common is von Willebrand disease?
- 1% of population by lab testing | - 1/500 symptomatic ("real cases")
34
Symptoms of vWD?
- Mostly mucocutaneous bleeding, except type 3 which also has hemophilia-like bleeding - Epistaxis, easy bruising, oral bleeding, post-surgical (oropharyngeal) bleeding - Menorrhagia and post-partum bleeding in females of child-bearing age
35
Function of vWF?
- Platelet binding | - Carrier molecular for FVIII
36
What factors can increase vWF?
- Physiologic stress - DDAVP - Estrogen - Pregnancy - Acute phase reactant
37
vWF binds to platelets via ________.
Glycoprotein 1b receptor
38
Inheritance and physiologic defect of Type 1 vWD?
Type 1 - Autosomal dominant - Heterozygous defect with reduced production of normal vWF
39
Inheritance and physiologic defect of Type 2A vWD?
Type 2a - Autosomal dominant - Multimerization defect with absent large/intermediate size multimers
40
Inheritance and physiologic defect of Type 2B vWD?
- Autosomal dominant - Gain of function mutation in VWF (too adherent to platelets so large multimers are attached to platelets and not circulating)
41
Inheritance and physiologic defect of Type 2M vWD?
- Autosomal dominant | - Loss of function mutation (opposite of 2B) - vWF doesn't bind well to platelets
42
Inheritance and physiologic defect of Type 2N vWD?
- Autosomal dominant - Compound heterozygotes with type 1 | - Loss of vWF binding function to FVIII
43
Inheritance of Type 3 vWD?
- Autosomal recessive | - Absence of vWF production
44
VWF antigen (VWF:Ag) test?
Immunologic test for the presence of vWF in plasma (doesn't assess function)
45
Ristocetin cofactor activity (VWF:Rcof)
-Platelet aggregration based test assessing vWF platelet binding function
46
Diagnostic tests for vWD?
- VWF:Ag - VWF:Rcof - Factor VIII activity - vWF multimer analysis - RIPA (2B)
47
Treatment options for vWD?
- Increase circulating vWF - -Desmopressin (releases stored vWF from Weibel-Palade bodies in endothelium) - Type 1 and maybe type 2A - -Replacement with plasma-derived vWF concentrate - Inhibit fibrinolysis - -Antifibrinolytics - Hormonal therapy - -Effective for menorrhagia management - --Estrogen increases vWF and FVIII - --Reduced blood flow to endometrium - Topical therapy - -Antifibrinolytics for oral bleeding - -Topical thrombin for oral or nose bleeding - -Cellulose or collagen embedded gauze
48
Most common genetic aberrations in severe hemophilia A?
- 40-50% have intron 22 inversion in the factor VIII gene | - 50% have a specific point mutation in exons or at splice junctions in the factor VIII gene
49
How many patients with severe hemophilia will develop an intracranial hemorrhage in the first year of life?
5%
50
Symptoms of retroperitoneal/iliopsoas muscle bleed?
- Pain in flank, groin or rarely thigh (referred pain) - Pain exacerbated and localized to RLQ by extending the leg (stretching the muscle) - Difficulty walking (typically walk hunched over to relax the iliopsoas)
51
Why are factor levels not reliable enough for pre-natal testing?
- Factor IX levels physiologically low in fetuses | - Factor VIII levels falsely elevated
52
What is primary prophylaxis? Secondary? Tertiary?
- Primary proph: Initiation of factor prior tto any joint bleeding, or before second joint bleed/any obvious joint disease - Secondary proph: After second joint bleed/onset of joint disease in order to prevent further bleeding - Tertiary proph: After onset of joint disease
53
Indications for prophylaxis?
- In severe hemophilia to prevent hemophilic arthropathy - no later than after 2 joint bleeds, can be prior to any - Moderate hemophilia who bleed frequently

ASPHO Lectures 2021 (10 decks)

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