Perioperative Antiplatelet and Anticoagulant Management

Question 1

Rivaroxiban is special among the anticoagulants, as. . .

Answer 1

. . . 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.

Question 2

Anticoagulants and epidurals

Answer 2

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.

Question 3

Decision of whether or not to maintain anticoagulation in a patient with atrial fibrillation

Answer 3

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.

Question 4

Bridging a warfarinized patient to surgery with LMWH

Answer 4

• 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

Question 5

Relevance of CHADS-VASc to decision of whether or not to bridge anticoagulation

Answer 5

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

Question 6

Surgery in a patient with recent coronary stent placement on DAPT

Answer 6

• 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

Question 7

CHADS-VASc

Answer 7

• In terms of surgery:
  
  • Low risk: 0-2
  • Medium risk: 3-4
  • High risk: 5-9

Question 8

Perioperative warfarin management

Answer 8

• 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

Question 9

High thromboembolic risk mechanical valves

Answer 9

• Any mitral proethesis
• Caged-ball or tilting-disc aortic valve
• Recent (< 6 mo) stroke or TIA with valve

Question 10

High risk for VTE

Answer 10

• < 3 months since prior VTE
• Thrombophilia:
  
  • Protein C def
  • Protein S def
  • Antithrombin def
  • APLS
  • (Other thrombophilias and cancer are moderate risk)

Question 11

Approved clinical applications for NOACs

Answer 11

1. Prevention of strokes and embolic complications associated with atrial fibrillation
2. The treatment of deep vein thrombosis (DVT) and pulmonary embolism
3. Secondary prevention of DVT
4. DVT prevention following knee or hip replacements

Question 12

Dabigatran

Answer 12

• 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

Question 13

Rivaroxiban

Answer 13

• 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

Question 14

Apixaban

Answer 14

• 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

Question 15

General approach to perioperative anticoagulant or antiplatelet measurement

Answer 15

• 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

Question 16

Irreversible platelet inhibitors

Answer 16

• Aspirin
• Clopidogrel
• Ticlopidine
• Prasugrel

Question 17

Reversible platelet inhibitors

Answer 17

• NSAIDs
• dipyradimole
• cilostazol

Question 18

Rule of thumb for NOACs and Cr clearance

Answer 18

• ClCr < 30 mL/min
  
  • Dabigatran and Rivaroxiban contraindicated
• ClCr < 25 mL/min
  
  • Apixaban contraindicated

Question 19

Management of ITP

Answer 19

• 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

Question 20

Reversing warfarinization for surgery

Answer 20

Give vitamin K AND FFP

Question 21

Quick differentiation of the qualitative platelet defects

Answer 21

• 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

Question 22

Non-immune heparin associated thrombocytopenia

Answer 22

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)

Question 23

Despite that __ is involved in the pathophysiology of ITP, __ is not a finding of ITP and should in fact warrant concern for alternative diagnoses.

Answer 23

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.

Question 24

The diagnosis of ITP requires demonstration of ___

Answer 24

The diagnosis of ITP requires demonstration of normal to elevated levels of megakaryoctes in the bone marrow

Question 25

When to treat ITP

Answer 25

• Bleeding complications are present
• OR platelet count < 30,000 / microliter

Question 26

Treatment of ITP

Answer 26

• 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

Question 27

Criteria for splenectomy in ITP

Answer 27

• 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

Question 28

Outcomes with splenectomy in ITP

Answer 28

• 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

Question 29

Humoral factors produced in the spleen

Answer 29

• 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.

Question 30

Properdin deficiency

Answer 30

Rare x-linked disease

Lack of properdin predisposes to severe Neisseria species infections

Question 31

Splenectomy in inherited RBC membrane defect syndromes

Answer 31

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.

Question 32

Types of RBC membrane defect

Answer 32

Question 33

Overwhelming Postsplenectomy Sepsis (OPSS)

Answer 33

• 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)

Question 34

Post-splenectomy leukocytosis

Answer 34

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

Question 35

Sinistral portal hypertension

Answer 35

• 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.

Question 36

Symptomatic splenomegaly

Answer 36

• 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.

Question 37

Splenectomy in hairy cell leukemia

Answer 37

• 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

Question 38

Patients with ITP who respond well to ___ are also likely to respond well to splenectomy long-term.

Answer 38

Patients with ITP who respond well to corticosteroids are also likely to respond well to splenectomy long-term.

Question 39

Primary hemostasis chain of events

Answer 39

Question 40

Thrombogenesis diagram

Answer 40

Question 41

Ticlopidine

Answer 41

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.

Question 42

Dipyridamole

Answer 42

Coronary vasodilator given in combination with aspirin to prophylax against angina pectoris

Inhibits cAMP production within platelets to prevent platelet activation and vasoconstriction.