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Therapeutics I > Coagulation Disorders > Flashcards

Coagulation Disorders Flashcards

1
Q

What are considered coagulation disorders?

A
  1. Coagulation factor defect
  2. Quantitative or qualitative platelet defect
  3. Enhanced fibrinolytic activity

Clot and bleed disorders

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2
Q

How do you diagnose coagulation disorders?

A
  1. Detailed clinical history
  2. Physical examination
  3. Lab test results
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3
Q

What are the clinical manifestations of coagulation disorders?

A
  1. Easy bruising
  2. Bleeding after surgery and trauma
  3. Joint and muscle bleeding
  4. Mucocutaneous bleeding
  5. Asymptomatic
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4
Q

When would you use PT and INR?

A

Identifies I, II, V, VII, W

Warfarin therapy

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5
Q

When would you use aPTT?

A

Identifies I, II, V, VIII, IX, X, XI, XII

Heparin therapy and argatriban

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6
Q

When would you use platelet counts?

A

HIT (thrombocytopenia)

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7
Q

What is hemophilia?

A

Congenital deficiency in plasma coagulation protein

Recessive X-linked disease

Typically only affects males, females carriers

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8
Q

What are the types of hemophilia and how do they differ?

A

A: Deficiency in factor VIII (most common)
B: Deficiency of factor IX

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9
Q

What are the signs and symptoms of hemophilia?

A
  1. Palpable, raised ecchymosis
  2. Hemarthorses (bleeding into joint spaces) → Joint pain, swelling, erythema
  3. Muscle hemorrhage with swelling
  4. Excessive bleeding with surgery or trauma
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10
Q

How do you test for hemophilia?

A
  1. Prolonged aPTT
  2. Decreased VIII or IX
  3. Normal PT, platelet count, vWF antigen, bleeding time
  4. Consider diagnosis in any male with abnormal bleeding
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11
Q

How are decreased factor VIII or IX categorized?

A

Severe: < 0.01 units/mL (1%) of either
Moderate: Between 0.01 and 0.05 units/mL (1%-5%)
Mild: Between 0.05 and 0.4 units/mL (5%-40%)

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12
Q

What are the treatment goal of hemophilia?

A

Prevent bleeding episodes and long term sequelae

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13
Q

What are the treatments for hemophilia? Immunizations?

A

Home infusions via peripheral or central lines
Hemophilia A: Factor VIII infusions
Hemophilia B: Factor IX infusions

SubQ hepatitis A and B

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14
Q

What is the difference between on-demand and prophylaxis hemophilia treatment?

A

On-demand: administer PRN based on acute bleeding
Prophylaxis: prevention of bleeding complications

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15
Q

When would you use on-demand hemophilia treatment?

A

Perioperative period begin prior to surgery and continue 5-7 days depending on clinical response and type of surgery

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16
Q

When is hemophilia treatment prophylaxis used?

A

Severe hemophilia
A: 20-40units/kg three times per week
Extended t1/2: 25-65 units/kg every 3-5 days

B = 25-60 units/kg twice per week
Extended t1/2: 50 units/kg once weekly or 100 units/kg every 10 day

Central line starting as a 6 month old

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17
Q

What are the characteristics of plasma-derived factors?

A
  1. Derived from pooled plasma of human donors
  2. Prion disease may be present
  3. Classified based on purity
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18
Q

What are the characteristics of recombinant factors?

A
  1. Preferred over plasma-derived (lower risk of infection)

Generation products:
1st: contain human albumin as stabilizing protein
2nd: Sugar as stabilizer and human albumin in culture process
3rd: Contain no human albumin (lowest risk)

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19
Q

Each unit of Factor VIII concentrate per kg of body weight will increase the plasma factor level by ____?

A

2%

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20
Q

Each unit of Factor IX concentrate per kg of body weight will increase the plasma factor level by ____?

A

1%

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21
Q

What are some counseling points of factor VIII?

A

Degradation of the products with exposure to light

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22
Q

What is the on demand factor VIII goal for severe bleeds?

A

Peak factor levels of greater than 0.75 to 1 units/mL (75%-100%) peak plasma level

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23
Q

What is the on demand factor VIII goal for mild bleeds?

A

Goal of 0.3 to 0.5 units/mL (30%-50%) peak plasma level

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24
Q

How do you dose FVIII?

A

Dose (units) = (desired level – baseline level) x 0.5 x weight (kg)

BID

25
Q

How should FVIII be administered?

A

Continuous infusion perioperatively or in severe bleeds

Infusion rates ranging from 2 to 4 units/kg/hr

One time dose to continued dosing for 1 week or longer

26
Q

Other than Factor VIII, what are some other therapies for hemophilia A?

A

Desmopressin for minor bleeding

Antifibrinolytic therapy

27
Q

What does desmopressin do?

A

Release of vWF and Factor VIII from endogenous endothelial stores

28
Q

How is desmopressin administered? ADRs?

A

0.3 mcg/kg in 50 mL normal saline over 15-30 min

Intranasal administration can be considered (one spray if <50 kg; two sprays if >50 kg)

Tachyphylaxis, facial flushing, water retention

29
Q

What antifirinolyics can we use for hemophilia A? ADR?

A
  1. Tranexamic acid 25 mg/kg (max 1.5 g) orally Q6-8 hours
  2. Aminocaproic acid 100 mg/kg (max 6 g) IV or PO Q6 hours

Inhibits clot lysis, used as an add on

Caution in hematuria due to risk of renal obstruction

30
Q

How does Factor VIII differ from Factor IX products?

A

Higher Vd → small protein size

Increase plasma factor level by 1%

Longer half-life → BID

31
Q

How should you dose factor IX products?

A

Dose (units) = (Desired level - baseline) x weight (kg)

Recombinants must be multiplied by 1.2

32
Q

How are factor inhibitors measured?

A

Low response <5 BUs
High response >5 BUs

33
Q

Why do hemophilliacs develop factor inhibitors?

A
  1. Neutralizing antibodies for factors VIII and IX
  2. Complication of IgG therapies
  3. Higher in hemophilia A
34
Q

What are non factor treatments for hemophilia?

A

Emicizumab (Hemlibra)

PCC, aPCCs, rFVIIa

35
Q

What is Emicizumab? Indication? Dosing?

A

Monoclonal antibody that bridges factor IX and factor X → bypassing VIIIa

Prophylaxis for hemophilia A → 1 injection SC Qweek

36
Q

Should you use factors to treat acute bleeds?

A

Can’t give enough factor to neutralize antibodies to restore hemostasis → Use of PCC, aPCCs, rFVIIa would be helpful

37
Q

What is the difference between PCC and aPCCs?

A

PPC: Kcentra, inactive factors II, VII, IX, X
aPCC: FEIBA (activated factors II=X>VII=IX)

38
Q

What are the complications and ADRs of PCC and aPCC?

A

Complications: VTE and MI
ADRs: DZ, Nausea, Flushing, HA, hives

39
Q

How should you does aPCCs?

A

50-100 units/kg Q8-12 hours (max 200 units/kg/day)

40
Q

What are the uses of rFVIIa? Dose?

A

Only available at the tissue site of injury

Initial: 90 mcg/kg up to 300 mcg/kg

Short half-life dosing Q2H or continuous

41
Q

What are the types of immune modulators? What do they do?

A
  1. Cyclophosphamide
  2. IVIG
  3. Rituximab

Reduces inhibitor titers

42
Q

Discuss the inhibitor treatment algorithm for FVIII?

43
Q

How do you manage pain?

A
  1. Determine if its acute or chronic
  2. PRICE (protect, rest, ice, compression, elevation)
    3.Acetaminophen (mild); opioid (severe)
  3. NSAId not recommended routinely (COX2>1)
44
Q

How should you follow up and monitor?

A
  1. Clinical parameters (bleeding and symptoms)
  2. Plasma factor levels
  3. Diaries
  4. Physical exam and radiographic imaging
  5. Check for development of inhibitors → yearly
45
Q

What is the function of vWF?

A
  1. Promotes platelet adhesion and facilitates platelet aggregation
  2. Serves as carrier molecule for Factor VIII
46
Q

What is the most common bleeding disorders?

47
Q

What are the types of vWD?

A

Low vWF: 1 and 3
Absent: 2

48
Q

How would you diagnose vWD?

A

Ristocetin cofactor activity (RCo): functional assay of vWF activity on platelet aggregation with ristocetin

Reduced greater in type 2 vs 1 and 3

49
Q

What is the difference between type 1 and 3 vWD?

A

Both are quantitative defects

1: mild-moderate reductions in vWF
3: severe reduction in vWF

50
Q

What is type 2 vWD?

A

functional defects (reduced binding)

More severe than 1

51
Q

What are the lab analysis of vWD?

A
  1. vWF Ag levels
  2. Factors VIII assay
  3. Rco activity
  4. vWF multiuser analysis
52
Q

What drug is used to assess RCo activity?

A

Ristocetin

53
Q

What are the types of acquired vWD?

A
  1. Autoimmune disorder
  2. Drug-induced
54
Q

What are the drugs that induce vWD?

A
  1. Valproic acid
  2. Griseofulvin
  3. Hydroxyethyl starch
  4. Ciprofloxacin
55
Q

What are the treatment of vWD?

A
  1. vWF/Factor VIII replacement
  2. Desmopressin
56
Q

How can desmopressin be used for vWD?

A

Release of vWF and factor VIII

Inappropriate for type 3 since they have no vWF

57
Q

What is the algorithm of vWD?

Therapeutics I (32 decks)

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