Therapeutics I > Coagulation Disorders > Flashcards

Coagulation Disorders Flashcards

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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?

Study These Flashcards
A

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

BID

25
How should FVIII be administered?
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
Other than Factor VIII, what are some other therapies for hemophilia A?
Desmopressin for minor bleeding Antifibrinolytic therapy
27
What does desmopressin do?
Release of vWF and Factor VIII from endogenous endothelial stores
28
How is desmopressin administered? ADRs?
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
What antifirinolyics can we use for hemophilia A? ADR?
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
How does Factor VIII differ from Factor IX products?
Higher Vd → small protein size Increase plasma factor level by 1% Longer half-life → BID
31
How should you dose factor IX products?
Dose (units) = (Desired level - baseline) x weight (kg) Recombinants must be multiplied by 1.2
32
How are factor inhibitors measured?
Low response <5 BUs High response >5 BUs
33
Why do hemophilliacs develop factor inhibitors?
1. Neutralizing antibodies for factors VIII and IX 2. Complication of IgG therapies 3. Higher in hemophilia A
34
What are non factor treatments for hemophilia?
Emicizumab (Hemlibra) PCC, aPCCs, rFVIIa
35
What is Emicizumab? Indication? Dosing?
Monoclonal antibody that bridges factor IX and factor X → bypassing VIIIa Prophylaxis for hemophilia A → 1 injection SC Qweek
36
Should you use factors to treat acute bleeds?
Can't give enough factor to neutralize antibodies to restore hemostasis → Use of PCC, aPCCs, rFVIIa would be helpful
37
What is the difference between PCC and aPCCs?
PPC: Kcentra, inactive factors II, VII, IX, X aPCC: FEIBA (activated factors II=X>VII=IX)
38
What are the complications and ADRs of PCC and aPCC?
Complications: VTE and MI ADRs: DZ, Nausea, Flushing, HA, hives
39
How should you does aPCCs?
50-100 units/kg Q8-12 hours (max 200 units/kg/day)
40
What are the uses of rFVIIa? Dose?
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
What are the types of immune modulators? What do they do?
1. Cyclophosphamide 2. IVIG 3. Rituximab Reduces inhibitor titers
42
Discuss the inhibitor treatment algorithm for FVIII?
43
How do you manage pain?
1. Determine if its acute or chronic 2. PRICE (protect, rest, ice, compression, elevation) 3.Acetaminophen (mild); opioid (severe) 4. NSAId not recommended routinely (COX2>1)
44
How should you follow up and monitor?
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
What is the function of vWF?
1. Promotes platelet adhesion and facilitates platelet aggregation 2. Serves as carrier molecule for Factor VIII
46
What is the most common bleeding disorders?
vWD
47
What are the types of vWD?
Low vWF: 1 and 3 Absent: 2
48
How would you diagnose vWD?
Ristocetin cofactor activity (RCo): functional assay of vWF activity on platelet aggregation with ristocetin Reduced greater in type 2 vs 1 and 3
49
What is the difference between type 1 and 3 vWD?
Both are quantitative defects 1: mild-moderate reductions in vWF 3: severe reduction in vWF
50
What is type 2 vWD?
functional defects (reduced binding) More severe than 1
51
What are the lab analysis of vWD?
1. vWF Ag levels 2. Factors VIII assay 3. Rco activity 4. vWF multiuser analysis
52
What drug is used to assess RCo activity?
Ristocetin
53
What are the types of acquired vWD?
1. Autoimmune disorder 2. Drug-induced
54
What are the drugs that induce vWD?
1. Valproic acid 2. Griseofulvin 3. Hydroxyethyl starch 4. Ciprofloxacin
55
What are the treatment of vWD?
1. vWF/Factor VIII replacement 2. Desmopressin
56
How can desmopressin be used for vWD?
Release of vWF and factor VIII Inappropriate for type 3 since they have no vWF
57
What is the algorithm of vWD?
58
Therapeutics I
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