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Therapeutics I > Blood Clots > Flashcards

Blood Clots Flashcards

1
Q

What is the difference between hemostatic and pathologic?

A

H: form rapidly and remain localized
P: Form slowly, impair blood flow and cause complete vessel occlusion

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2
Q

What factor allows crosslinking of fibrin?

A

XIIIa creates a meshwork of fibrin

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3
Q

What are Vitamin K dependent factors?

A

II, VII, IX, and X

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4
Q

What are the contact activation factors?

A

XI, XII, prekallikrein, HMW kininogen

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5
Q

What are the thrombin sensitive factors?

A

V, VIII, XIII, fibrinogen

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6
Q

What are the antithrombic substances?

A
  1. Thrombomodulin/Protein C and S
  2. Antithrombin
  3. Heparin sulfate
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7
Q

What are the components of the fibrinolytic system?

A

Plasminogen –(tPA)–> Plasmin → fibrin degradation products (D-dimer)

Regulated by plasminogen activator inhibitor-1 (tPA) andα2-antiplasmin (plasmin)

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8
Q

What is Virchows triad?

A

Thrombus is caused by:
1. Endothelial injury
2. Venous stasis
3. Hypercoagulability

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9
Q

What is blood stasis?

A

Decrease or cessation of blood flow

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10
Q

What are examples of blood stasis?

A
  1. Acute med inllness
  2. Surgery
  3. Paralysis
  4. Immobility
  5. Obesity
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11
Q

What is vascular injury?

A

Intact vascular endothelium separates flowing blood from sub endothelial vessel wall → preventing blood loss through clot formation

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12
Q

What are examples of vascular injury?

A
  1. Orthopedic surgery
  2. Trauma
  3. Indwelling venous catheters
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13
Q

What is hypercoagulabilty?

A

Increased tendency to form blood clots

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14
Q

Examples of hypercoagbulabilty?

A
  1. Lupus anticoags
  2. Pregnancy
  3. Drugs therapy
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15
Q

What are the drugs associated with hypercoagulabilty?

A
  1. Estrogen contain contraceptives and replacement therapies
  2. Tamoxifen
  3. Raloxifene
  4. Cancer therapy
  5. HIT
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16
Q

What are the OACs?

A
  1. Warfarin (Coumadin)
  2. Dabigatran (Pradaxa)
  3. Apixaban (Eliquis)
  4. Edoxaban (Savaysa)
  5. Rivaroxaban (Xarelto)
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17
Q

What are the PACs?

A
  1. Heparin
  2. Low molecular weight heparin: Enoxaparin (Lovenox); Tinzaparin (Innohep); Dalteparin (Fragmin)
  3. Fondaparinux (Arixtra)
  4. Argatroban (Acova)
  5. Bivalirudin (Angiomax)
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18
Q

ADRs of UFH? Dosing? Indications?

A

ADRS; bleeding, HIT, osteopenia

Round to the nearest 100 units

IV or SQ ideal for CrCl<30 or unstable patients

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19
Q

What is the most common complication of HIT?

A

VTE

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20
Q

How do you prevent and manage HIT?

A

Confirm heparin antibody testing

D/C all heparin sources, if on warfarin temporary interrupt and reverse vitamin K

Initiate DTI

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21
Q

What is considered thrombocytopenia?

A

Alt <150 or decrease of 30050%

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22
Q

What are the 4 T score? How are they scored?

A
  1. Thrombocytopenia
  2. Timing
  3. Thrombosis
  4. Other potential causes of Thrombocytopenia

Low (3 or less) – no further workup
Moderate (4-5) or high (6-8) – further workup (heparin antibodies)

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23
Q

What is the onset of HIT usually?

A

5-10 days after first dose

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24
Q

What are the DDIs of DOACS?

A

PgP
Rivaroxaban and apixaban (CYP3A4)

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25
Q

What drugs require parenteral AC for 5 days before use?

A

Dabigatran and edoxaban

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26
Q

What DOAC requires food?

A

Rivaroxaban 15 mg and 20 mg tabs taken with food

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27
Q

ADRs of DOAcs?

A

Bleeding

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28
Q

Why doesn’t LMWH need monitoring?

A

More predictable dose response

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29
Q

ADRs of LMWH?

A

Bleeding, HIT, osteopenia

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30
Q

Types of LMWH?

A
  1. Enoxaparin (Lovenox);
  2. Tinzaparin (Innohep);
  3. Dalteparin (Fragmin)
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31
Q

How should LMWH be dosed? CIs?

A

Renal dose adjustment necessary at CrCl < 30mL/min

CI in dialysis/ESRD

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32
Q

What LMWH are not commonly used in practice?

A

Dalteparin and Tinzaparin

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33
Q

What kind of dosing in enoxaparin?

A

TBW and not adjusted for treatment dosing

Round to nearest syringe size

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34
Q

When would fondaparinux be used? ADRs?

A

CI is CrCl <30mL/min

Used in patients with HIT

ADRs: bleeding

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35
Q

What are the D/FDIs for warfarin?

A
  1. Fluconazole
  2. Amiodarone
  3. Bactrim
  4. Flagyl (Metronidazole)
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36
Q

What is the warning of warfarin use?

A

Narrow TI requiring frequent monitoring

Bleeding, purple toe syndrome, skin necrosis

Do not adjust more often than Q3 days

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37
Q

What are INR goals for warfarin?

A

2-3

2.5-3.5 for mechanical valves

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38
Q

Onset of warfarin?

A

6 days for full effect

It takes longer for warfarin to affect INR

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39
Q

What foods are considered high in vitamin K?

A

Dark leafy green veggies

Very high >200mcg
high 100-200 mcg

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40
Q

What should we assess when doing warfarin counseling?

A
  1. Lab monitoring
  2. Drug interactions
  3. Food interactions
  4. Dosing frequency
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41
Q

How do you evaluate non valvular AF for antithrombic therapy?

A

CHA2DS2-VAsc Score
HAS BLED

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42
Q

How do you evaluate valvular AF or mitral valve stenosis for antithrombic therapy?

A
  1. Anticoagulant indicated
  2. Warfarin INR 2-3 or 2.5-3.5 for mechanical mitral valves
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43
Q

What does the CHA2DS2-VAsc Score factor in? When would we recommended anticoagulant in A fib/flutter?

A
  1. Age
  2. Sex
  3. CHF
  4. HTN
  5. Stroke,TIA, VTE
  6. AS
  7. Diabetes

Score of ≥2 in men or ≥3 in women

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44
Q

What do you do if there was a Score of 1 in men and 2 in women in CHA2DS2 VASC

A

Oral anticoagulant to reduce thromboembolic stroke risk may be considered

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45
Q

What do you do if there was a Score of 0 in men and 1 in women in CHA2DS2 VASC

A

Omit anticoagulat therapy

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46
Q

What factors does HAS BLED factor in?

A
  1. Uncontrolled HTN >160
  2. Renal and liver disease
  3. Stroke history
  4. Major bleed or predisposition
  5. Labile INR
  6. > 65YO
  7. Medication risk for bleeding
  8. Alcohol use
47
Q

What are choice of anticoags for A fib/flutter ?

A

1st lie: NOAC
Mechanical valve: warfarin

48
Q

What are the DOAC for Afib/flutter?

A

Apixaban (Eliquis)
Dabigatran (Pradaxa)
Edoxaban (Savaysa)
Rivaroxaban (Xarelto)

49
Q

Dosing of Eliquis? Indication for reduction? Reduced dose?

A

5 mg BID

2/3 factors present:
≥80 YO
sCr ≥1.5 mg/dL
≤60 kg
OR
PGP and strong CYP3A4 inhibitors

2.5 mg BID

50
Q

Dosing of Pradaxa? Indication for reduction? Reduced dose?

A

150 mg BID

CrCl 15-30 OR CrCl 30-50 w/ dronedarone or ketoconazole

75 mg BID

51
Q

Dosing of Savaysa? Indication for reduction? Reduced dose?

A

60 mg QD, CI if CrCl ≥95

CrCl 15-50

30 mg QD

52
Q

Dosing of Xarelto? Indication for reduction? Reduced dose?

A

20 mg QD w/ food

CrCl 15-50

15 mg QD w/ food

53
Q

What are the VTE events?

A

DVT and PE

54
Q

DVT virchow triad

A
55
Q

What are the proximal veins affected by DVT and PE?

A

Popliteal
Femoral
Iliac

56
Q

What are the distal veins affected by DVT and PE?

A

Anterior and posterior tibial
Peroneal
Gastrocnemius

57
Q

What are DVT presentations and how do you diagnose?

A

Unilateral leg pain and swelling

Wells score

58
Q

What are PE presentations and how do you diagnose?

A

Chest pain, SOB, tachypnea, tachycardia

Wells score

59
Q

What are the diagnostic tests we can do for VTE?

A
  1. D Dimer (Negative is for ruling, but positive doesn’t equal VTE)
  2. Doppler (enhance pulse sounds)
  3. CUS (proximal, whole leg)
  4. CTPA
60
Q

Algorithm for VTE prophylaxis?

A
61
Q

Who qualitifes fo VTE prophylaxis?

A

Best: Early ambulation sufficient for low risk patients

62
Q

Non pharm for VTE prophylaxis?

A
  1. Compression stockings
  2. IPC devices
  3. IVC filters
63
Q

What are the pham treatments for VTE?

A
  1. LMWH
  2. UFH
  3. Fondaparinux
  4. Rivaroxaban
64
Q

How should you assess medical patients on whether or not they qualify for VTE prophylaxis?

A

Padua predication score (VTE Risk): High risk ≥4
IMPROVE score (Bleeding risk): High risk ≥7 (mechanical>pharm)

65
Q

How should you assess surgical patients on whether or not they qualify for VTE prophylaxis?

A

Caprini score (complex)

Curent guideline: initiate 6-12 hrs post op

66
Q

How should Acutely ill hospitalized medical patients undergo VTE prophylaxis?

A

Increased VTE risk: prophylaxis with LMWH, UFH, fondaparinux, rivaroxaban

67
Q

How should the critically ill undergo VTE prophylaxis?

A

Prophylaxis with LMWH or UFH

68
Q

How should non-ortho surgery VTE prophylaxis?

A

Mod-high risk with no bleed: LMWH or UFH +IPC

69
Q

How should ortho surgery VTE prophylaxis?

A

THA or TKA: LMWH, fondaparinux, UFH, apixaban, dabigatran, rivaroxaban, warfarin, aspirin x 10-14 days min (up to 35 days)

70
Q

What is the dosing for VTE prophylaxis?

A

UFH: 5000u Q8-12H
Enoxaparin: 40mg QD, 30 mg BID
Fondaparinux: 2.5 mg QD
Rivaroxaban: 20 mg QD

71
Q

What does the duration of VTE prophylaxis look like?

A

Generalsurger: until patients can ambulate
Ortho surgery: 15-42 days
Mechanical: Through period of increased risk

72
Q

What are the stages fo VTE treatment?

A
  1. Initiation
  2. Treatment
  3. Extended
73
Q

What occurs during Initiation phase of VTE treatment?

A

5-21 days
The initial provision of anticoagulants following VTE diagnosis

74
Q

What occurs during treatement phase of VTE treatment?

A

3 months

The period after initiation that completes treatment for the acute VTE event

75
Q

What occurs during extended phase of VTE treatment?

A

3 months-no planned stop date
The period of anticoagulant use at full or reduced dose for the goal of secondary prevention

76
Q

What amplifies the outcomes of VTE?

A
  1. Major transient risk factor (present within 3 months of diagnoses)
  2. Minor transient risk factor (2 months)
  3. Persistent risk factor
  4. Unprovoked VTE
77
Q

Describe the VTE treatment and prevention?

A

Slide 50 as well

78
Q

What is the treatment guidelines for acute DVT of leg or PE?

A

DOAC>warfarin

If warfarin used, bridge with LMWH, fonadparinux, or UFH x 5days and until INR ≥2 for 24 hr
LMWH and fondapairnux >UFH
INR goal 2-3

79
Q

What is the treatment guidelines for proximal DVT of leg or PE?

A

Provoked: treat x 3 month
First unprovoked: 3 months
Recurrent unprovoked: extended therapy

80
Q

VTE treatment guidelines for PE?

A

Acute PE w/ Hypotonesion (<90) w/o high bleed risk: systemic thrombolytic

Acute PE w/ Hypotonesion (<90) w high bleed risk: catheter directed thrombolysis

81
Q

VTE treatment guidelines for upper extremity DVT?

A

Axillary or other proximal wings: LMWH or fondaparinux > UFH for 3 months

82
Q

What anticoagulant require a nomogram for VTE treatment?

A

Heparin and argatroban

83
Q

Enoxaparin dosing for VTE treatment?

A

1mg/kg Q12h or 1.5mg/kg Q24h

CrCl< 30mL/min: 1mg/kg Q24h

84
Q

Dabigatran dosing for VTE treatment?

A

150 mg po BID

CrCl <30mL/min: Avoid use

85
Q

Rivaroxaban dosing for VTE treatment?

A

15 mg po BID x 21 days, then 20 mg po once daily

CrCl <30mL/min: Avoid use

86
Q

Apixaban dosing for VTE treatment?

A

10 mg po BID x7 days, then 5 mg po BID

No adjustment for renal dysfunction

87
Q

Edoxaban dosing for VTE treatment?

A

60 mg PO QD
CrCl 15-50mL/min: 30mg once daily
CrCl <15mL/min: Avoid use

CI CrCl≥95

88
Q

Wha is the starting dose of warfarin?

A

5 mg QD

89
Q

What are the goals and monitoring objectives of blood clot therapy?

A
  1. Clinical surveillance (Clot reduction, bleeding)
  2. Labs (coagulant specific, Hgb, HCT)
  3. Continuation (A fib/flutter, VTE)
90
Q

How should you monitor DOACs?

A

Adherence with therapy
Bleeding risk assessment
CrCl/renal function
Drug interaction eval
Examination for ADR and effeciveness
Final assessment and recommendations regarding the need for ongoing DOAC therapy

91
Q

What are the labs we look for when monitoring Acs?

A
  1. aPTT (UFH)
  2. PT/INR (warfarin)
  3. Anti-Xa levels (Most reliable for DOAC monitoring): Useful for enoxaparin in obese, pregnant, CrCl <30
92
Q

What are the anticoagulant reversal agents?

A
  1. Protamine
  2. FFP
  3. Vitamin K
  4. PCCs
  5. Idarucizumab (Praxbind)
  6. rFVII
  7. Andexanet alpha (Andexxa)
93
Q

What is the reversal for UFH and LMWH?

A

Protamine

94
Q

What are the reversal doses of protamine fro UFH and enoxaparin?

A

UFH: 1 mg/100u of heparin (reserves only heparin given in the last 2-2.5 hr due to short half life of heparin)

Enoxaparin:
Dose within last 8 hours: 1 mg protamine per 1 mg enoxaparin
Dose > 8 hours ago: 0.5 mg protamine per 1 mg enoxaparin

Administer over at least 10 min to reduce hypotension

95
Q

ADRs of administrating protamine?

A

Hypotension, bradycardia, flushing, anaphylaxis, cariogenic pulmonary edema, and vasocanstriction

96
Q

What is FFP? What is is used for?

A

Derived from whole blood (non specific clotting factor)

Take >24hrs to reverse INR

Higher transfusion volumes

97
Q

What factors does vitamin K?

A

II, VII, IX, X

98
Q

ADRs of vitamin K?

A

Anaphylaxis

99
Q

How is vitamin K dosed?

A

Combined w/ FFP or PCC

100
Q

What are the inactive PCC?

A

3 F: Bebulin, Profilnine
4 F: Kcentra

101
Q

What are the active PCC?

A

4F: FEIBA

102
Q

What is in 3F products?

A

II, IX, X

103
Q

What is in 4F products?

A

II, VII, IX, X

104
Q

When is PCC used?

A

Warfarin and Xa inhibitors

Higher factor concentrations compared to FFP

Varies from 25-50 units/kg based on situation, anticoagulant used, and INR

105
Q

What is Idarucizumab used for? Dose?

A

Praxbind → reversal of free or thrombin-bound dabigatran

2.5 g IV x 2 doses 15 minutes apart

106
Q

What is rFVIIa used for? ADR?

A

Activates the coagulation cascade via the extrinsic pathway (hemophiliac bleeding)

ICH off-label: 90 mcg/kg once

Rapid INR reduction → rebound INR

107
Q

What is Andexxa? Dosing?

A

Modified recombinant form of Factor Xa specific for Xa inhibitors

108
Q

Know site of action of anticoagulant reversal?

A
109
Q

What are steps of VKA reversal?

A
  1. Administer Vit K w or w/o concomitant agents based on severity
  2. Use 3F or 4 F PCC > FFP
  3. Inactivated 4-Factor PCC > activated 4-Factor PCC > 3-Factor PCC > FFP PCC
  4. Recommend against rFVII
110
Q

What are the recommendations of DOAC reversal?

A

Acute ingestion: activated charcoal

Factor Xa inhibitors: PCC and ANdexxa
Dabigatran: Indarucizumab, 4F-PCC, Hemodialysis (last resort)

111
Q

T/F: Reversal of Xa inhibitors and DTIs are guided by lab parameters?

A

FALSE guided by bleeding

112
Q

When only use Praxbind in neurocritical care if: Alternatives?

A
  1. Dose administered within 3-5 half-lives
    OR
  2. Renal insufficiency leading to exposure >3-5 half-lives

4F-PCC (if not available)
Hemodialysis if renal insufficiency or DTI OD and Praxbind not available

113
Q

Describe the algorithm of reversal DOAC treatment?

A

Therapeutics I (32 decks)

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