Lab Values Relevant to the Radiologist - Nova Scotia ... Values Relevant to the Radiologist ......

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  • Lab Values Relevant to the

    RadiologistGillian Shiau

    Swiped from Jim Hensons Muppets

  • Disclosures

    Nothing to disclose

  • Outline1) Coagulation:

    High-level review of the clotting cascade

    Review of commonly encountered anticoagulants and antiplatelet agents and hemostatic agents

    Review of guidelines for percutaneous image-guided procedures

    2) Renal function:

    Review of creatinine and GFR calculations

    Classic teaching regarding contrast-induced nephropathy (CIN)

    Emerging evidence on CIN

    Management of renal functionhttp://www.arizonatransplantassociates.com/

    http://myhomegarden.xyz/

  • Recall the Coagulation Cascade

    Oral anticoagulants for Asian patients with atrial fibrillation Sabir I et al. Nature Reviews Cardiology 11, 290

    303 (2014) doi:10.1038/nrcardio.2014.22

    *Measured using PT/INR

    *Measured using PTT

  • Coagulopathy Workup

    INR: 0.9-1.1 Reflects the extrinsic pathway (I, II, V, VII, X)

    Elevated if on PO anticoagulant therapy;

    Liver dysfunction synthesis of Vitamin K dependent II, VII, IX, and X; also proteins C and S)

    Also elevated if: Vit K deficiency; lupus anticoagulants; DIC, bile duct obstruction, malabsorption, malnutrition)

    aPTT: 25-35s Reflects intrinsic pathway (VIII, IX, XI, XII)

    Elevated if on heparin (usu 1.5-2.5 times for therapeutic)

    Also elevated if: liver disease, DIC, Vit K deficiency, use of therapeutic anticoagulants (eg. hirudin, argatroban)

    CBC: Hgb: 135-170g/L (also can look at MCV: normal 83-98fL)

    Platelets: 150-450 x 109/L (beware HIT heparin induced thrombocytopenia)

    TT: < 20s

  • Commonly Used Anticoagulants Agent Half-Life Test Reversal Agent

    Warfarin 40 hours INR FFP

    Unfractionated

    heparin

    1.5 hrs aPTT Protamine (1mg/100IU)

    LMWH (Lovenox,

    Enoxaparin)

    4.5-7 hours Anti-Xa Incomplete. Protamine can

    repeat dose PRN

    LMWH (Dalteparin,

    Fragmin)

    2.5 hrs Anti-Xa Incomplete. Protamine can

    repeat dose PRN

    LMWH (Tinzaparin,

    INNOHEP)

    3-4 hrs Anti-Xa Incomplete. Protamine can

    repeat dose PRN

    Fondaparinux

    (Arixtra)

    17 hrs Anti-Xa None. Consider recombinant

    factor VIIa

    Bivalirudin

    (Angiomax)

    25 minutes aPTT None. Consider recombinant

    factor VIIa

    Argatroban 45 minutes aPTT None. Consider recombinant

    factor VIIa

    Cook. Anticoagulation Management. Semin Intervent Radiol. 2010 Dec; 27(4): 360367. doi: 10.1055/s-0030-1267849

  • Anticoagulants Warfarin

    Oral vitamin K antagonist

    MOA: affects clotting factors II, VII, IX, X and proteins C and S

    t1/2 of 37hrs but dependent on amount of circulating clotting factors II prothrombin is most important with t1/2 of 96hrs;

    VII has shortest t1/2 of 6 hrs

    Monitored using INR

    Indications: afib; DVT/PE; hypercoagulable states; mechanical heart valves

    Antithrombotic effect: delayed onset and transient HYPERcoagulability heparinization indicated when initiating treatment

    http://www.phassociation.uk.com/treatment_for_ph/warfarin.php

    St Jude Medical. http://www.mechanicalheartvalve.co.uk/

  • Anticoagulants WarfarinTime til procedure Reversal Management

    > 5 days Hold warfarin x 5 days

    1-5 days Hold warfarin; check INR 24hrs preprocedure

    1 day Hold warfarin, check INR

    - If INR > 1.9 2 mg vit K PO

    - If INR 1.5-1.9 1 mg vit K PO

    < 24hrs or emergent Hold warfarin; check INR

    - If INR > 3 FFP and consider factor concentrates

    - If INR 1.5-3 2 units of FFP and recheck INR

    Cook. Anticoagulation Management. Semin Intervent Radiol. 2010 Dec; 27(4): 360367. doi: 10.1055/s-0030-1267849

  • Anticoagulants Heparin (UFH)

    IV or subcutaneous medication of mixture of large and small heparin fractions

    MOA: forms complex with antithrombin (III) which inhibits activation of factors II and X

    t1/2 of 60-90minutes (nonlinear)

    Monitored using aPTT (full anticoagulation = 1.5-2.5x normal); can use ACT (activated clotting time, normal

  • Anticoagulants Heparin (LMWH)

    Multiple formulations (enoxaparin; tinzaparin; dalteparin; nadroparin) derived from UFH uniform size

    MOA forms complex with antithrombin (III) which inhibits activation of thrombin *reduced bridging of antithrombin

    inhibition of other factors is more important than with UFH (aPTTunderestimates the anticoagulation d/t LMWH)

    t1/2 is ~4x that of UFH (~4.5hrs)

    Reversal protamine (less effective and predictable than with UFH) can give an additional half dose PRN

    Complications: reduced incidence of HIT and osteopenia

    Enoxaparain training. Iyer BK.

  • Anticoagulants Direct Thrombin

    Inhibitors Aptly named directly inhibit thrombin

    Bivalent (Hirudin; bivalirudin; lepirudin) binds at active site and exosite 1

    Univalent (Argatroban) binds only at active site

    Does not require monitoring (only test could do would be a clotting time)

    Indication: contraindication to heparin (eg. HIT)

    Reversal: no specific agent factor concentrates and recombinant factors induce partial reversal

  • New Kid on the Block: Dabigatran Also known as Pradaxa

    MOA: directly inhibits both free and clot-bound thrombin; renally cleared

    Indications: VTE prevention; afib pts for prevention of stroke and systemic arterial thromboembolism

    Monitoring: INR and PTT relatively insensitive (often normal); thrombin time is quite sensitive

    Reversal: studies in progress. Early studies show that Idarucizumab complete rerversethe anticoagulant effects within minutes (in Clinical Trials)

  • New Kids on the Block: Direct Xa

    Inhibitors Rivaroxaban (Xarelto); Apixaban

    Rivaroxaban: ~50% hepatically cleared; and 66% excreted in urine

    Indications: VTE prevention in ortho pts; afib pts for prevention of stroke and systemic arterial thromboembolism; also approved for acute tx and secondary prevention of DVT and PE

    Apixaban: Metabolized by CYP3A4; partly eliminated by kidneys

    Reversal strategies: NO agent currently (some synthetic molecules in the works Andexanet alpha and aripazine) Laulicht2012.

  • Antiplatelet Aspirin

    MOA: inhibits platelet cyclooxygenase (enzyme that contributes to production of thromboxane A2), thereby inhibiting platelet aggregation and activation

    Platelet lifespan is 10days so withholding x 5 days 30-50% of platelets will have normal function

    Indication: coronary artery disease

    The Awkard Yeti

  • Antiplatelet Thienopyridines Multiple formulations: clopidogrel, ticlopidine,

    prasugrel

    MOA: inhibit adenosine diphosphate (ADP) dependent binding to platelet receptors inhibit activation of glycoprotein Iib/IIIa

    Duration of action lifespane of platelet (7-10days) but effective t1/2 is ~4 hours

    Reversal: partial restoration of hemostatic function if administer exogenous platelets 6-8 hours post last dose as newly transfused platelets do not undergo inhibition

  • Antiplatelets NSAIDs Nonsteroidal antiinflammatory

    drugs usually do not cause significant problems unless patient has underlying coagulopathy

    MOA: inhibit platelet aggregation

    Reversal: reversible decays with clearance from blood (specific NSAID dependent for duration)

    *Paradoxical: diminish antiplatelet effect of ASA if given concomitantly

    http://rccatalyst.com/?p=26277

  • Antiplatelets Glycoprotein IIb/IIIa

    Inhibitors Abciximab; eptifibatide; tirofiban

    MOA: antagonist to integrin complex glycoprotein IIb/IIIa found on platelets inhibiting platelet aggregation

    Reversal: specific formulation dependent

    Abciximab stop 24hrs preprocedure (at least 12 hrs)

    Tirofiban can stop at moment of incision without increased bleeding risk

  • Hemostatic Agents

    FFP contains plasma proteins (including coagulation factors) effects are variable d/t vitamin K

    dependent clotting factors (sometimes need to concomitantly use vitamin K)

    Platelets Fractionated blood product dose in increments of 4-6 units

    Protamine Rapid onsent within 10 minutes of administration with SHORT half life paradoxic repeat

    anticoagulation after protamine administration

    Side effects: bradycardia; hypotension; pulmonary arterial hypertension; decreased O2 consumption; anaphylactoid

    Vitamin K If stable, elective case, PO (5-10mg) administration preferred

    IV administration associated w/ risk of anaphylactoid reaction

    Cryoprecipitate Used if acquired or hereditary deficiency of fibrinogen

    Recombinant Factor VIIa Used in hemophilia patients + factor VIII inhibitors OR non-hemophilia patients with SEVERE

    bleeding and acute trauma

    Desmopressin Synthetic analogu of ADH unclear MOA to enhance plasma levels of factor VIII and vWF

    (dosed at 0.3g/k IV diluted in 100cc of NS in a 20-30 minute infusion)

    Side effects: mild hyponatremia; tachyphylaxis. Case reports: vascular thrombosis, MI

  • Guidelines for Anticoagulation Rx Pre-

    Procedure LOW RISK If LOW risk of bleeding that is EASILY DETECTED AND CONTROLLABLE:

    Vascular procedures: dialysis access; venography; central line removal; IVC filter placement; PICC line insertion

    Nonvascular procedures: Drainage catheters exchange (biliary, nephrostomy, abscess); thora-/paracentesis; superficial aspiration and

    bx (excluding intrathoracic/intraabdominal) such as thyroid, superficial L