Perioperative Antiplatelet and Anticoagulant Management Flashcards
Rivaroxiban is special among the anticoagulants, as. . .
. . . its halflife is related to creatinine clearance
In patients with normal renal function who are undergoing procedures at high risk for bleeding, the last dose of rivaroxaban should occur 48 to 72 hours prior to surgery. If the patient’s creatinine clearance is 30 to 49 mL/ min, the recommended last dose of rivaroxaban is 72 hours prior to surgery.
Anticoagulants and epidurals
Epidural catheters are a significant risk for severe bleeds. Anticoagulants need to be stopped prior to insertion and the subsequent dose delayed until ~24 hours after the catheter is in place. There should also be a shorter interval of anticoagulant holding when the catheter is removed.
Decision of whether or not to maintain anticoagulation in a patient with atrial fibrillation
The decision to initiate bridging anticoagulation therapy in this patient will ultimately be determined on the basis of the CHAD2 score. If the score puts them into the high-risk group, bridging therapy with an unfractionated heparin drip should be strongly considered during the perioperative period.
Bridging a warfarinized patient to surgery with LMWH
- Stop warfarin
- Switch to LMWH (aka dalteparin) in 2 days
-
Discontinue 24h prior to surgery
- If unfractionated heparin, discontinue 4-5 hours prior to surgery
- Begin LMWH bridge to warfarinization post-operatively
Relevance of CHADS-VASc to decision of whether or not to bridge anticoagulation
In someone on anticoagulation for atrial fribrillation as an indication, the decision of whether or not to do an anticoagulant bridge or to simply stop and resume in the perioperative period depends on their CHADS-VASc.
High-risk patients: Bridge w/ unfractionated heparin drip
Low risk: No need
Surgery in a patient with recent coronary stent placement on DAPT
- Elective surgeries should be deferred (at least 6 weeks for bare metal, at least 6 months for drug-eluting)
- Emergent surgeries may proceed with continuation of the DAPT
CHADS-VASc
- In terms of surgery:
- Low risk: 0-2
- Medium risk: 3-4
- High risk: 5-9
Perioperative warfarin management
- Stop 5 days before
- Resume 12-14 hours after
-
Bridging:
- For: Patient with a mechanical valves, at high risk for VTE, or atrial fibrillation with high stroke risk, and those undergoing low-bleeding-risk surgical procedures
- Unfractionated heparin drip or sub-cu LMWH
High thromboembolic risk mechanical valves
- Any mitral proethesis
- Caged-ball or tilting-disc aortic valve
- Recent (< 6 mo) stroke or TIA with valve
High risk for VTE
- < 3 months since prior VTE
- Thrombophilia:
- Protein C def
- Protein S def
- Antithrombin def
- APLS
- (Other thrombophilias and cancer are moderate risk)
Approved clinical applications for NOACs
- Prevention of strokes and embolic complications associated with atrial fibrillation
- The treatment of deep vein thrombosis (DVT) and pulmonary embolism
- Secondary prevention of DVT
- DVT prevention following knee or hip replacements
Dabigatran
- NOAC
- Plasma halflife 12-17 hr
-
Contraindicated in:
- Severe renal dysfunction
- Lab changes: Prolong PT and aPTT
- If necessary, hemodialysis may be performed to speed up clearance
Rivaroxiban
- aka Xeralto
- NOAC
- Half life:
- Good Cr clearance: 5-9 hrs
- Poor Cr clearance: 11-13 hrs
-
Contraindications:
- Severe renal dysfunction
- Pregnant
- Breastfeeding
- Liver affects metabolism – may be prolonged in liver disease
- Interacts w/ rifampin, antifungals, protease inhibitors
- Lab changes: Prolonged PT
- Can reverse w/ activated prothrombin complex concentrate or prothrombin complex concentrate
Apixaban
- aka Eloquis
- Plasma halflife: 8-15 hrs
-
Contraindications:
- Severe renal dysfunction (slightly higher threshhold than other NOACs in this regard)
- Pregnant
- Breastfeeding
- Anticoagulant effects may be meaured by anti-Xa antibody levels
- Can reverse with PCC and aPCC if necessary
General approach to perioperative anticoagulant or antiplatelet measurement
- Start by risk stratifying patient’s thrombosis risk
- Then, risk stratify operation’s bleeding risk
- Patients at high risk for thrombosis will require bridging of some sort
- Patients with moderate risk thrombosis is less clear, and here the bleeding risk must be strongly considered
- Low risk for thrombosis can certainly stop anticoagulants perioperatively
Irreversible platelet inhibitors
- Aspirin
- Clopidogrel
- Ticlopidine
- Prasugrel
Reversible platelet inhibitors
- NSAIDs
- dipyradimole
- cilostazol
Rule of thumb for NOACs and Cr clearance
- ClCr < 30 mL/min
- Dabigatran and Rivaroxiban contraindicated
- ClCr < 25 mL/min
- Apixaban contraindicated
Management of ITP
- In children:
- Very good prognosis generally with spontaneous recovery, only treat with corticosteroids in severe cases
- In adults:
- Treat if severe (recurrent manifestations other than petechiae, purpura) or < 30,000 plt
- Options:
- High dose dexamethasone
- RhoGam (if Rh+)
- IVIG
Reversing warfarinization for surgery
Give vitamin K AND FFP
Quick differentiation of the qualitative platelet defects
-
Bleeding time:
- Prolonged in all
-
Platelets:
- Typically normal in all, may be low in Bernard-Soulier
-
Coags:
- Prolonged PTT = Vw disease
- Normal PTT: BSS or GT
Non-immune heparin associated thrombocytopenia
A mild, transient drop in platelet count that can occur within 5 days of heparin exposure.
Mediated by heparin-induced platelet aggregation.
Not associated with thrombosis, unlike heparin-induced thrombocytopenia (the immune-mediated consumptive coagulation)
Despite that __ is involved in the pathophysiology of ITP, __ is not a finding of ITP and should in fact warrant concern for alternative diagnoses.
Despite that the spleen is involved in the pathophysiology of ITP, splenomegaly is not a finding of ITP and should in fact warrant concern for alternative diagnoses.
The diagnosis of ITP requires demonstration of ___
The diagnosis of ITP requires demonstration of normal to elevated levels of megakaryoctes in the bone marrow
When to treat ITP
- Bleeding complications are present
- OR platelet count < 30,000 / microliter
Treatment of ITP
- Initial treatment is with trial of steroids
- Produces good respose in most, but only 20-30% have sustained response and long-term corticosteroids should be avoided due to complications
- Second line is IVIG
- Third line is immunosuppression, rituximab, or TPO antagonist
- If refractory to medical therapy, splenectomy is indicated
- Plasmapheresis holds the role of a “rescue” modality for rectractory disease with bleeding
Criteria for splenectomy in ITP
-
Medically refractory disease
- Failure to increase platelets above 30,000 per microliter after 6 months of treatment
- Steroid-sparing option for patients who otherwise require chronic corticosteroid therapy
Outcomes with splenectomy in ITP
- Initially produces clinically significant response in 80-90% of patients
- However, only 60% have lasting responses
- Must give appropriate splenectomy prophylaxis:
- PPSV13, PPSV23, H. flu, N. meningitides vaccine
Humoral factors produced in the spleen
- Large quantity of IgM
- Opsonins
- Tuftsin: Tetrapeptide located in the Fc portion of IgG heavy chain. Facilitates phagocytosis, acts as neutrophil chemotactic agent, enhances cytotoxicity and ROS production, stimulates antigen processing
- Properdin: Positive regulator of complement. Stabilizes alternative complement pathway convertases. Stabilizes association of C3b and factor B. Necessary for Neisseria species immunity.
Properdin deficiency
Rare x-linked disease
Lack of properdin predisposes to severe Neisseria species infections
Splenectomy in inherited RBC membrane defect syndromes
For patients with hereditary spherocytosis, elliptocytosis, and ovalocytosis, splenectomy is sometimes recommended for those with Hgb < 6 g/dL
Splenectomy is contraindicated for patients with stomatocytosis, as studies have shown increased thromboembolic complications following splenectomy.
Types of RBC membrane defect
Overwhelming Postsplenectomy Sepsis (OPSS)
- Rare but potentially fatal condition that may develop in asplenic patients
- Vaccination against encapsulated organisms helps to prevent this (S. pneumoniae, H. infleunzae, N. meingitidis)
Post-splenectomy leukocytosis
It is not uncommon to develop WBC elevation to ~10,000-15,000
However, when WBC count exceeds 15,000, postoperative infection should be entertained
Sinistral portal hypertension
- Caused by splenic vein thrombosis
- Presents with splenomegaly and splenic vein hypertension in the absence of hepatomegaly/cirrhosis and generalized portal hypertension
- Short gastric veins also become dilated, producing gastric varices.
- GI bleeding secondary to gastric varices is an indication for splenectomy.
Symptomatic splenomegaly
- May develop in the context of a myeloproliferative disorder (PCV, Myelofirosis, CML, etc)
- Enlarged spleen in this context is due to extramedullary hematopoiesis
- If the spleen becomes too big, it may cause obstructive symptoms
- This is an indication for splenectomy,however this is a palliative measure that does not address the underlying disease.
Splenectomy in hairy cell leukemia
- Patients with hairy cell leukemia commonly develop splenomegaly and secondary thrombocytopenia
- First-line therapy is cladribine and pentostatin to address the route disease
- If the above fails, second-line is splenectomy as a palliative measure
Patients with ITP who respond well to ___ are also likely to respond well to splenectomy long-term.
Patients with ITP who respond well to corticosteroids are also likely to respond well to splenectomy long-term.
Primary hemostasis chain of events
Thrombogenesis diagram
Ticlopidine
Like clopidogrel, irreversibly binds the P2Y12 receptor and blocks ADP signaling and downstream platelet aggregation
Neutropenia is a potential side effect. Generally reserved for those who cannot tolerate aspirin or clopidogrel.
Dipyridamole
Coronary vasodilator given in combination with aspirin to prophylax against angina pectoris
Inhibits cAMP production within platelets to prevent platelet activation and vasoconstriction.
