Coag Part 2 Flashcards
CKD patients display a baseline anemia due to:
-lack of erythropoietin
-platelet dysfunction (due to uremic environment)
What 2 things are shown to shorten bleeding times in CKD?
-dialysis
-correction of anemia
Treatment of platelet dysfunction in CKD:
-Cryoprecipitate (rich vWF)
-DDAVP
-Conjugated estrogen given pre-operatively for 5 days
What is DIC?
-disseminated intravascular coagulation
-pathological hemostatic response to tissue factor/7a complex causing excessive antagonism of the extrinsic pathway-which overwhelms the anticoagulant mechanism-generates intravascular thrombin
What 2 things become depleted during widespread microvascular thrombotic activity, causing multi=organ dysfunction?
-coagulation factors
-platelets
What can precipitate DIC?
-trauma
-amniotic fluid embolus
-malignancy
-sepsis
-incompatible blood transfusion
What lab finding are found with DIC:
-decreased platelets
-prolonged PT/PTT/Thrombin time
-increased soluble fibrin and fibrin degradation products
Management of DIC:
correct underlying condition and administer appropriate blood products
What is trauma-induced coagulopathy?
What is a common cause of trauma-related death?
Why causes coagulopathies to occur?
-uncontrolled hemorrhage
-acidosis, hypothermia, and/or hemodilution
What is Trauma-induced coagulopathy?
-independent acute coagulopathy seen in trauma patients-thought to be related to activated protein C decreasing thrombin generation
What is the driving force for protein C activition?
Hypo-perfusion
What happens to endothelial glycocalyx, which contains proteoglycans?
It degrades due to the protein C activation
What does proteoglycan-shedding result in?
Auto-heparinization
What does platelet dysfunction contribute to?
increased bleeding
The most common inherited prothrombotic diseases are caused by a mutation in _______ or ____
-factor V
-PT
What does factor V leidin mutation lead to ?
-leads to activated protein C resistance
-present in 5% caucasian population
What does prothrombin mutation cause?
Increased PT concentration-leading to hypercoagulation
What is thrombophilia?
-inherited or acquired predisposition for thrombotic events
-manifests as venous thrombosis
-highly susceptible to virchow’s triad
What is virchows triad again?
-blood stasis
-endothelial injury
-hypercoagulability
What is antiphospholipid syndrome?
autoimmune disorder with antibodies against the phospholipid-binding proteins in the coagulation system
What is antiphospholipid syndome characterized by?
What do people with this syndrome often require?
-characterized by recurrent thrombosis and pregnancy loss
-often require life-long anticoagulants
What factors greatly increase the risk of thrombosis in people with antiphospholipid syndrome?
-oral contraceptives
-pregnancy
-immobility
-infection
-surgery
-trauma
Heparin-Induced Thrombocytopenia:
-mild to moderate thrombocytopenia associated with heparin
-occurs 5-14 days after heparin treatment
-it’s an autoimmune response occurring in up to 5% of pts receiving heparin
What does HIT result in?
platelet count reduction as well as activation of the remaining platelets and potential thrombosis
If a patient has received a prior heparin dose, thrombocytopenia or thrombosis may occur within __ day(s) of subsequent dose.
1 day of subsequent dose
Risk factors for HIT:
-women
-pts receiving high heparin doses such as with cardiopulmonary bypass
-increased risk with unfractionated heparin compared to LMWH
What to do if HIT is susprected:
-D/C heparin
-convert to an alt. anticoagulant
-warfarin is CONTRAINDICATED b/c it decreases protein C and S synthesis
What is the HIT diagnosis confirmed with?
-HIT antibody testing
-antibodies are typically cleared from circulation in 3 months
PT info:
-prothrombin time: plasma is mixed with tissue factor and the number of seconds is measured until a clot forms
-assess integrity of extrinsic and common pathways
-used to monitor vit K antagonists like warfarin
What factor deficiencies does PT reflect?
Factor 1, 2, 5, 7, 10
What factors are vit K dependent?
Factors 2, 7, and 10
aPTT info:
-activated partial thromboplastin time
-measures seconds until clot forms after mixing plasma with phospholipid, Ca++, and an activator of the intrinsic pathway
-assess integrity of intrinsic and common pathways
-may be used to measure effect of heparin
What specific deficiencies is the aPTT test more sensitive towards?
Factor 8 and 9
Anti-factor Xa activity assay:
-aka “Factor Xa inhibition test” plasma combined with Xa and an artificial substrate that releases a colorimetric signal after factor Xa is cleaved
-provides assessment of heparin’s anticoagulant effect
-also used to assess effect of LMWH, fondaparinux, and factor Xa inhibitors
Platelet Count:
-standard component of coagulation testing
-normal= >100,000 platelets/microliter
-POC testing available
ACT:
-activated clotting time: variation of whole blood clotting time w/ addition of a clotting activator to accelerate clotting time
-addresses intrinsic and common pathways
-used to measure responsiveness to heparin
-normal: 107 +/- 13 seconds
-POC analyzers available
Heparin Concentration Measurement:
-protamine-concentration is the MOST popular POC method to determine perioperative heparin concentration
-1 mg protamine will inhibit 1 mg heparin
-this test estimates plasma heparin concentration
What happens as amount of protamine in heparin blood increases?
-as increasing amts of protamine are added to heparinized blood, time to clot DECREASES until protamine concentration > heparin concentration
Viscoelastic Coagulation Tests:
-measures all aspects of clot formation from early fibrin generation to clot retraction and fibrinolysis-coag diagrams generated
-allows for more precise blood product administration
Diagrams generated from viscoelastic coag tests:
-TEG: thromboelastogram
-ROTEM: rotational thromboelastometry
TEG Diagram Image:
R time:
-time to start forming clot
-5-10 min= normal
-prob with coag factors
-Tx: FFP
K time:
-time until clot reaches a fixed strength
-1-3 min= normal
-fibrinogen prob
-Tx: cryo
Alpha angle:
-speed of fibrin accumulation
-53-72 seconds= normal
-prob with fibrinogen
-tx: cryo
Maximum amplitude (MA):
-highest vertical amplitude of the TEG
-50-70 min= normal
-prob with platelets
-Tx: platelets and/or DDAVP
Lysis at 30 minutes: (LY30)
-% of amplitude reduction 30 min after maximum amplitude
-0-8%= normal
-prob with excess fibrinlysis
-Tx: TXA or aminocaproic acid
What do platelet inhibitors do and what are the 3 main classes?
inhibit platelet aggregation and/or adhesion
-COX inhibitors
-P2Y12 receptor antagonists
-Platelet GIIb/IIa R antagonists
COX inhibitors:
-block Cox 1 from forming TXA2-which is important in platelet aggregation
-ASA: anti-platelet effects x7-10 days after d/c
-NSAIDs: anti-plt effect x3 days
P2Y12 receptor antagonists:
-inhibit P2Y12-R-preventing GIIb/IIIa expression
-plavix: anti-plt effects x7 days after d/c
-ticlopidine: anti plt effects x14-21 days after d/c
-ticagrelor and cangrelor: short acting, <24 hr activity
Platelet GIIb/IIIa R antagonists:
-prevent vWF and fibrinogen from binding to GIIb/IIIa-R
-abciximab, eptifibatide, tirofiban
Vitamin K antagonists:
-inhibit synthesis of vit-K dependent factors (2, 7, 9, 10, protein C and S)
Warfarin:
-most common vit K antagonists
-DOC for valvular Afib and valve-replacements
-long halflife:40 hrs-can take 3-4 days to reach therapeutic INR of 2-3
-usually requires heparin until therapeutic effected achieved
-monitor PT/INR freq.
-reversible with Vit K
How does heparin work?
It binds to antithrombin which DIRECTLY inhibits soluble thrombin and Xa
Unfractionated Heparin:
-short half life, given IV
-fully reversible with protamine
-close monitoring required
LMWH:
-longer halflife, dosed BID SQ
-no coag testing needed
-protamine only partially effective
Fondaparinux:
-much longer halflife (17-21 hr), dosed once/day
-protamine not effective
How do direct thrombin inhibitors work?
They bind and block thrombin in both soluble and fibrin-bound states
-hirudin, argatroban, bivalirudin, and dabigatran
What’s random about hirudin?
naturally found in leeches lol
Argatroban:
-synthetic, reversible binds to thrombin-HL 45 min
-monitored intraop with PTT or ACT
Bivalirudin:
-synthetic, shortest HL of direct thrombin inhibitors
-DOC for renal or liver impairment
Dabigatran (Pradaxa):
-1st direct oral anticoagulant
-direct thrombin inhibitor approved for CVA prevention and non-valvular A-fib
Direct oral anticoagulants (DOACs):
-newer class, introduced in past 10 yrs
-have more predictable PK/PD
-fewer drug interactions and fewer embolic events, intracranial hemorrhages, and lower mortality than warfarin
-dosed daily w/o lab monitoring
-efficacy similar to warfarin-not much shorter HL
What are examples of Xa inhibitors?
-Rivaroxaban (Xarelto)
-Apixaban (Eliquis)
-Edoxaban (Savaysa)
Thrombolytics:
-used to dissolve blood clots
-may be given IV or directly into site of blockage
What are most thrombolytics?
-Most are serin proteases that convert plasminogen to plasmin-breaks down fibrinogen to fibrin
The 2 categories of thrombolytics:
-fibrin-specific: altepase (tPA), Reteplase, and Tenecteplase
-non-fibrin-specific: Streptokinase **not widely used d/t allergic reactions
Surgery is CONTRAINDICATED within ___ day(s) of thrombolytic treatment.
-10 days
List of Absolute and Relative Contraindications for Thrombolytics
-absolute: vascular lesions, severe-uncontrolled HTN, recent cranial surgery or trauma, brain tumor, ischemic stroke < 3 months, and active bleeding
-relative: ischemic stroke >3 months, active peptic ulcer, current use of anticoagulant drugs, pregnancy, prolonged/traumatic CPR <3 weeks prior, major surgery < 3 weeks prior
What are procoagulants?
-used to mitigate blood loss
-2 classes: antifibrinolytics and factor replacements
Antifibrinolytics:
2 subclasses: lysine analogues and a SERPIN
-lysine analogues: epsilon-aminocaproic acid (EACA) and TXA: binds and inhibits plasminogen from binding to fibrin-impairing fibrinolysis
-SERPIN: aprotinin (removed from market d/t renal and cardio toxicity)
Factor Replacements:
-Recombinant VIIa (RfVIIa): increase thrombin generation via intrinsic and extrinsic paths
-Prothrombin complex concentrate (PCC): contain vit K factors
-fibrinogen concentrate: derived from pooled plasma, standard concentration
-cryo and FFP: cheaper and contain more coag factors, but less specific composition
Preop guidelines for warfarin:
-low risk pts should d/c 5 days prior to surgery and restart 12-24 hrs postop
-high risk pts should stop 5 days prior and bridge w/ UFH or LMWH
Preop guidelines for heparin:
-UFH d/c’d 4-6 hr prior to surgery and resumed (NO bolus) > 12 hr postop
-LMWH d/c’d 24 hour prior to surgery and resumed 24 hr postop
Preop guidelines for Aspirin:
not as defined
-moderate/high risk pts: current recc is to continue ASA
-low risk pts: stop 7-10 days prior to surgery
Preop guidelines for pts post-coronary stent placement:
-bare metal stents: delay elective surgery 6 wks after placement
-drug-eluding stents: delay elective surgery 6 months after placement
Graph for neuraxial anesthesia on anti-coags:
-no restrictions for NSAID and Heparin SQ BID
What may be required for excessive bleeding or emergent surgery?
Warfarin reversal
Prothrombin complex concentrates for the DOC for what?
emergent coumadin reversal (though HL is short)
Concurrent ____ __ is required to restore carboxylation of vit K dependent factors by the liver for more sustained correction
Concurrent vitamin K
Do reversal agents exist for direct thrombin inhibitors?
No reversal for most, but not a horrible thing b/c HL is relatively short
-exception: DOAC Dabigatran (Pradaxa) does have an antidote-Idarucizumab
What can DOAC factor Xa inhibitors by reversed by?
Andexanet-a derivative of factor Xa
Master List of Common Anticogulants:
