Blood Clots Flashcards
What is the difference between hemostatic and pathologic?
H: form rapidly and remain localized
P: Form slowly, impair blood flow and cause complete vessel occlusion
What factor allows crosslinking of fibrin?
XIIIa creates a meshwork of fibrin
What are Vitamin K dependent factors?
II, VII, IX, and X
What are the contact activation factors?
XI, XII, prekallikrein, HMW kininogen
What are the thrombin sensitive factors?
V, VIII, XIII, fibrinogen
What are the antithrombic substances?
- Thrombomodulin/Protein C and S
- Antithrombin
- Heparin sulfate
What are the components of the fibrinolytic system?
Plasminogen –(tPA)–> Plasmin → fibrin degradation products (D-dimer)
Regulated by plasminogen activator inhibitor-1 (tPA) andα2-antiplasmin (plasmin)
What is Virchows triad?
Thrombus is caused by:
1. Endothelial injury
2. Venous stasis
3. Hypercoagulability
What is blood stasis?
Decrease or cessation of blood flow
What are examples of blood stasis?
- Acute med inllness
- Surgery
- Paralysis
- Immobility
- Obesity
What is vascular injury?
Intact vascular endothelium separates flowing blood from sub endothelial vessel wall → preventing blood loss through clot formation
What are examples of vascular injury?
- Orthopedic surgery
- Trauma
- Indwelling venous catheters
What is hypercoagulabilty?
Increased tendency to form blood clots
Examples of hypercoagbulabilty?
- Lupus anticoags
- Pregnancy
- Drugs therapy
What are the drugs associated with hypercoagulabilty?
- Estrogen contain contraceptives and replacement therapies
- Tamoxifen
- Raloxifene
- Cancer therapy
- HIT
What are the OACs?
- Warfarin (Coumadin)
- Dabigatran (Pradaxa)
- Apixaban (Eliquis)
- Edoxaban (Savaysa)
- Rivaroxaban (Xarelto)
What are the PACs?
- Heparin
- Low molecular weight heparin: Enoxaparin (Lovenox); Tinzaparin (Innohep); Dalteparin (Fragmin)
- Fondaparinux (Arixtra)
- Argatroban (Acova)
- Bivalirudin (Angiomax)
ADRs of UFH? Dosing? Indications?
ADRS; bleeding, HIT, osteopenia
Round to the nearest 100 units
IV or SQ ideal for CrCl<30 or unstable patients
What is the most common complication of HIT?
VTE
How do you prevent and manage HIT?
Confirm heparin antibody testing
D/C all heparin sources, if on warfarin temporary interrupt and reverse vitamin K
Initiate DTI
What is considered thrombocytopenia?
Alt <150 or decrease of 30050%
What are the 4 T score? How are they scored?
- Thrombocytopenia
- Timing
- Thrombosis
- Other potential causes of Thrombocytopenia
Low (3 or less) – no further workup
Moderate (4-5) or high (6-8) – further workup (heparin antibodies)
What is the onset of HIT usually?
5-10 days after first dose
What are the DDIs of DOACS?
PgP
Rivaroxaban and apixaban (CYP3A4)
What drugs require parenteral AC for 5 days before use?
Dabigatran and edoxaban
What DOAC requires food?
Rivaroxaban 15 mg and 20 mg tabs taken with food
ADRs of DOAcs?
Bleeding
Why doesn’t LMWH need monitoring?
More predictable dose response
ADRs of LMWH?
Bleeding, HIT, osteopenia
Types of LMWH?
- Enoxaparin (Lovenox);
- Tinzaparin (Innohep);
- Dalteparin (Fragmin)
How should LMWH be dosed? CIs?
Renal dose adjustment necessary at CrCl < 30mL/min
CI in dialysis/ESRD
What LMWH are not commonly used in practice?
Dalteparin and Tinzaparin
What kind of dosing in enoxaparin?
TBW and not adjusted for treatment dosing
Round to nearest syringe size
When would fondaparinux be used? ADRs?
CI is CrCl <30mL/min
Used in patients with HIT
ADRs: bleeding
What are the D/FDIs for warfarin?
- Fluconazole
- Amiodarone
- Bactrim
- Flagyl (Metronidazole)
What is the warning of warfarin use?
Narrow TI requiring frequent monitoring
Bleeding, purple toe syndrome, skin necrosis
Do not adjust more often than Q3 days
What are INR goals for warfarin?
2-3
2.5-3.5 for mechanical valves
Onset of warfarin?
6 days for full effect
It takes longer for warfarin to affect INR
What foods are considered high in vitamin K?
Dark leafy green veggies
Very high >200mcg
high 100-200 mcg
What should we assess when doing warfarin counseling?
- Lab monitoring
- Drug interactions
- Food interactions
- Dosing frequency
How do you evaluate non valvular AF for antithrombic therapy?
CHA2DS2-VAsc Score
HAS BLED
How do you evaluate valvular AF or mitral valve stenosis for antithrombic therapy?
- Anticoagulant indicated
- Warfarin INR 2-3 or 2.5-3.5 for mechanical mitral valves
What does the CHA2DS2-VAsc Score factor in? When would we recommended anticoagulant in A fib/flutter?
- Age
- Sex
- CHF
- HTN
- Stroke,TIA, VTE
- AS
- Diabetes
Score of ≥2 in men or ≥3 in women
What do you do if there was a Score of 1 in men and 2 in women in CHA2DS2 VASC
Oral anticoagulant to reduce thromboembolic stroke risk may be considered
What do you do if there was a Score of 0 in men and 1 in women in CHA2DS2 VASC
Omit anticoagulat therapy
What factors does HAS BLED factor in?
- Uncontrolled HTN >160
- Renal and liver disease
- Stroke history
- Major bleed or predisposition
- Labile INR
- > 65YO
- Medication risk for bleeding
- Alcohol use
What are choice of anticoags for A fib/flutter ?
1st lie: NOAC
Mechanical valve: warfarin
What are the DOAC for Afib/flutter?
Apixaban (Eliquis)
Dabigatran (Pradaxa)
Edoxaban (Savaysa)
Rivaroxaban (Xarelto)
Dosing of Eliquis? Indication for reduction? Reduced dose?
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
Dosing of Pradaxa? Indication for reduction? Reduced dose?
150 mg BID
CrCl 15-30 OR CrCl 30-50 w/ dronedarone or ketoconazole
75 mg BID
Dosing of Savaysa? Indication for reduction? Reduced dose?
60 mg QD, CI if CrCl ≥95
CrCl 15-50
30 mg QD
Dosing of Xarelto? Indication for reduction? Reduced dose?
20 mg QD w/ food
CrCl 15-50
15 mg QD w/ food
What are the VTE events?
DVT and PE
DVT virchow triad
What are the proximal veins affected by DVT and PE?
Popliteal
Femoral
Iliac
What are the distal veins affected by DVT and PE?
Anterior and posterior tibial
Peroneal
Gastrocnemius
What are DVT presentations and how do you diagnose?
Unilateral leg pain and swelling
Wells score
What are PE presentations and how do you diagnose?
Chest pain, SOB, tachypnea, tachycardia
Wells score
What are the diagnostic tests we can do for VTE?
- D Dimer (Negative is for ruling, but positive doesn’t equal VTE)
- Doppler (enhance pulse sounds)
- CUS (proximal, whole leg)
- CTPA
Algorithm for VTE prophylaxis?
Who qualitifes fo VTE prophylaxis?
Best: Early ambulation sufficient for low risk patients
Non pharm for VTE prophylaxis?
- Compression stockings
- IPC devices
- IVC filters
What are the pham treatments for VTE?
- LMWH
- UFH
- Fondaparinux
- Rivaroxaban
How should you assess medical patients on whether or not they qualify for VTE prophylaxis?
Padua predication score (VTE Risk): High risk ≥4
IMPROVE score (Bleeding risk): High risk ≥7 (mechanical>pharm)
How should you assess surgical patients on whether or not they qualify for VTE prophylaxis?
Caprini score (complex)
Curent guideline: initiate 6-12 hrs post op
How should Acutely ill hospitalized medical patients undergo VTE prophylaxis?
Increased VTE risk: prophylaxis with LMWH, UFH, fondaparinux, rivaroxaban
How should the critically ill undergo VTE prophylaxis?
Prophylaxis with LMWH or UFH
How should non-ortho surgery VTE prophylaxis?
Mod-high risk with no bleed: LMWH or UFH +IPC
How should ortho surgery VTE prophylaxis?
THA or TKA: LMWH, fondaparinux, UFH, apixaban, dabigatran, rivaroxaban, warfarin, aspirin x 10-14 days min (up to 35 days)
What is the dosing for VTE prophylaxis?
UFH: 5000u Q8-12H
Enoxaparin: 40mg QD, 30 mg BID
Fondaparinux: 2.5 mg QD
Rivaroxaban: 20 mg QD
What does the duration of VTE prophylaxis look like?
Generalsurger: until patients can ambulate
Ortho surgery: 15-42 days
Mechanical: Through period of increased risk
What are the stages fo VTE treatment?
- Initiation
- Treatment
- Extended
What occurs during Initiation phase of VTE treatment?
5-21 days
The initial provision of anticoagulants following VTE diagnosis
What occurs during treatement phase of VTE treatment?
3 months
The period after initiation that completes treatment for the acute VTE event
What occurs during extended phase of VTE treatment?
3 months-no planned stop date
The period of anticoagulant use at full or reduced dose for the goal of secondary prevention
What amplifies the outcomes of VTE?
- Major transient risk factor (present within 3 months of diagnoses)
- Minor transient risk factor (2 months)
- Persistent risk factor
- Unprovoked VTE
Describe the VTE treatment and prevention?
Slide 50 as well
What is the treatment guidelines for acute DVT of leg or PE?
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
What is the treatment guidelines for proximal DVT of leg or PE?
Provoked: treat x 3 month
First unprovoked: 3 months
Recurrent unprovoked: extended therapy
VTE treatment guidelines for PE?
Acute PE w/ Hypotonesion (<90) w/o high bleed risk: systemic thrombolytic
Acute PE w/ Hypotonesion (<90) w high bleed risk: catheter directed thrombolysis
VTE treatment guidelines for upper extremity DVT?
Axillary or other proximal wings: LMWH or fondaparinux > UFH for 3 months
What anticoagulant require a nomogram for VTE treatment?
Heparin and argatroban
Enoxaparin dosing for VTE treatment?
1mg/kg Q12h or 1.5mg/kg Q24h
CrCl< 30mL/min: 1mg/kg Q24h
Dabigatran dosing for VTE treatment?
150 mg po BID
CrCl <30mL/min: Avoid use
Rivaroxaban dosing for VTE treatment?
15 mg po BID x 21 days, then 20 mg po once daily
CrCl <30mL/min: Avoid use
Apixaban dosing for VTE treatment?
10 mg po BID x7 days, then 5 mg po BID
No adjustment for renal dysfunction
Edoxaban dosing for VTE treatment?
60 mg PO QD
CrCl 15-50mL/min: 30mg once daily
CrCl <15mL/min: Avoid use
CI CrCl≥95
Wha is the starting dose of warfarin?
5 mg QD
What are the goals and monitoring objectives of blood clot therapy?
- Clinical surveillance (Clot reduction, bleeding)
- Labs (coagulant specific, Hgb, HCT)
- Continuation (A fib/flutter, VTE)
How should you monitor DOACs?
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
What are the labs we look for when monitoring Acs?
- aPTT (UFH)
- PT/INR (warfarin)
- Anti-Xa levels (Most reliable for DOAC monitoring): Useful for enoxaparin in obese, pregnant, CrCl <30
What are the anticoagulant reversal agents?
- Protamine
- FFP
- Vitamin K
- PCCs
- Idarucizumab (Praxbind)
- rFVII
- Andexanet alpha (Andexxa)
What is the reversal for UFH and LMWH?
Protamine
What are the reversal doses of protamine fro UFH and enoxaparin?
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
ADRs of administrating protamine?
Hypotension, bradycardia, flushing, anaphylaxis, cariogenic pulmonary edema, and vasocanstriction
What is FFP? What is is used for?
Derived from whole blood (non specific clotting factor)
Take >24hrs to reverse INR
Higher transfusion volumes
What factors does vitamin K?
II, VII, IX, X
ADRs of vitamin K?
Anaphylaxis
How is vitamin K dosed?
Combined w/ FFP or PCC
What are the inactive PCC?
3 F: Bebulin, Profilnine
4 F: Kcentra
What are the active PCC?
4F: FEIBA
What is in 3F products?
II, IX, X
What is in 4F products?
II, VII, IX, X
When is PCC used?
Warfarin and Xa inhibitors
Higher factor concentrations compared to FFP
Varies from 25-50 units/kg based on situation, anticoagulant used, and INR
What is Idarucizumab used for? Dose?
Praxbind → reversal of free or thrombin-bound dabigatran
2.5 g IV x 2 doses 15 minutes apart
What is rFVIIa used for? ADR?
Activates the coagulation cascade via the extrinsic pathway (hemophiliac bleeding)
ICH off-label: 90 mcg/kg once
Rapid INR reduction → rebound INR
What is Andexxa? Dosing?
Modified recombinant form of Factor Xa specific for Xa inhibitors
Know site of action of anticoagulant reversal?
What are steps of VKA reversal?
- Administer Vit K w or w/o concomitant agents based on severity
- Use 3F or 4 F PCC > FFP
- Inactivated 4-Factor PCC > activated 4-Factor PCC > 3-Factor PCC > FFP PCC
- Recommend against rFVII
What are the recommendations of DOAC reversal?
Acute ingestion: activated charcoal
Factor Xa inhibitors: PCC and ANdexxa
Dabigatran: Indarucizumab, 4F-PCC, Hemodialysis (last resort)
T/F: Reversal of Xa inhibitors and DTIs are guided by lab parameters?
FALSE guided by bleeding
When only use Praxbind in neurocritical care if: Alternatives?
- Dose administered within 3-5 half-lives
OR - 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
Describe the algorithm of reversal DOAC treatment?
