BALANCING THROMBOSIS AND BLEEDING RISKS
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BALANCING THROMBOTIC AND BLEEDING RISKS
Dr Syed RazaMD, MRCP(UK),Dip Card(UK),CCT(UK),FCCP
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OBJECTIVES
1. Burden of thrombosis and anti thrombotic related bleeding complications
2. Assessment of thrombotic and bleeding risks3. How best to maintain a balance4. How to manage common anti thrombotic
related bleeding complications
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• Due to increasing number of elderly population, prevalence of thrombosis related complications and bleeding associated with anti thrombotic treatment is constantly rising.
• There are various tools to assess thrombotic risk but assessment of bleeding risk is often ignored.
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Antithrombotic therapy has revolutionized the medical management of patients.
Over the past 20 years, the development of new
antithrombotic medications and strategies has reduced ischemic events very significantly.
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WARFARIN
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Newer Anticoagulants
– Direct Thrombin Inhibitors:• hirudin, lepirudin, desirudin, bivalirudin, • ximelagatran, Dabigatran
– Xa inhibitors:• fondaparinux, idraparinux• Rivaroxaban, Apixaban
– Heparinoids:• Danaparoid (discontinued)
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YING - YANG PRINCIPLE
• With every approach to reduce thrombosis, however, there is an accompanying risk of increasing bleeding complications .
• Conversely, reducing bleeding complications may increase thrombotic (ischemic) events.
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Thrombosis vs Bleeding
• They both increase morbidity and mortality
• Balancing both ends of the spectrum is essential, and an individualized approach to therapy is advocated.
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Case Scenario
• 80 Yrs male• Hypertensive• Congestive Cardiac Failure• Atrial Fibrillation
CHADS2 : 3 CHA2DS2-VAS : 4
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Assessment of Bleeding Risk
• Age• Hypertension• Renal Failure• Hepatic impairment• Significant anemia/ suspected leukemia
HAS – BLED : 4 >3 : Increased bleeding risk
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How about the thrombo prophylaxis for DVT?
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Case Scenario
• 50-year-old woman scheduled to undergo elective laparoscopic cholecystectomy– PMH : COPD– No personal or family history of VTE– Medications: Spiriva®, albuterol– Stopped smoking 1 year ago
• What should we recommend for perioperative VTE prophylaxis in this patient?
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Baseline Risk of VTE
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Baseline Risk of VTE
Bahl et al. Ann Surg. 2010;251:344-350.
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The Antithrombotic Therapy and Prevention of Thrombosis. ACCP Feb.2012
• significantly impacted the more than 600 recommendations for the prevention, diagnosis, and treatment of thrombosis
• DVT prophylaxis not for everybody• Risk stratification for VTE is recommended
(many may receive unnecessarily) • Bleeding risk is to be assessed.
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If the patient develops hemorrhagic stroke but high
thrombotic risk Will you …..
• 1.Stop all anticoagulant• 2.Use only prophylactic dose anticoagulant.• 3.IVC Filter• 4.Continue Oral anticoagulant maintaining low
level INR
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FACTORS INFLUENCING DECISION ON RE/COMMENCING AFTER ICH
• Size of expanding haematoma• Time from onset of haemorrhage• Degree of INR rise• Radiological finding – ‘Spot Sign’
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The “spot sign” (arrow), contrast extravasation after contrast-enhanced computed tomography, is associated with a high risk of hematoma expansion.
GOLDSTEIN J N , GREENBERG S M Cleveland Clinic Journal of Medicine 2010;77:791-799
©2010 by Cleveland Clinic
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What do the guidelines say ?
Initiation of anticoagulant after ICH – only if risk of thrombosis outweighs risk of bleeding.
The European Stroke Initiative : 10-14 days American College of Cardiology : 7-10 days American College of Chest Physicians : LMWH
next day. No clear guidelines on Oral anticoagulant.
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Bleeding Risk Assessment Tools
• 1.ACS – CRUSADE• 2. AF – HAS – BLED• 3.DVT/PE – Out Patient Bleeding Risk Index• 4.DVT- PE – IMPROVE• 5. DVT/PE – HEMORR2HAGES
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THROMBOTIC AND BLEEDING RISK ASSESSMENT IN ACUTE CORONARY SYNDROME
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Antiplatelet agents
Aspirin– “No doctor, I am on no medication…” – Commonest cause of post op wound oozing– Ticlopidine– Dipyridamole– Clopidogrel– Prasugrel– Ticagrelor
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Ischemic Complications
Ischemic Complications Hemorrhage
HITHemorrhage
HIT
► Angina
► MI
► Angina
► MI
► Major Bleeding
► Minor Bleeding
► Thrombocytopenia
► Major Bleeding
► Minor Bleeding
► Thrombocytopenia
Composite Adverse Event EndpointsComposite Adverse Event Endpoints
Evolving Paradigm for Evaluating ACS Management Strategies
Evolving Paradigm for Evaluating ACS Management Strategies
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Bleeding Risk Score: CRUSADE
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Independent Independent Predictors of Predictors of Major Bleeding Major Bleeding in Marker Positive in Marker Positive Acute Coronary Acute Coronary SyndromesSyndromes
Moscucci, GRACE Registry, Moscucci, GRACE Registry, Eur Heart JEur Heart J. 2003 Oct;24(20):1815-23. . 2003 Oct;24(20):1815-23.
Predictors of Major Bleeding in ACS
• Older Age• Female Gender• Renal Failure• History of Bleeding• Right Heart Catheterization• GPIIb-IIIa antagonists• Dual anti platelet• Use of anticoagulant• NSAIDS and COX2 Inhibitors
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Risk of events
Risk of bleeding
ThrombosisHemostasis
Two sides of the same coin
Degree of Anticoagulation
Ris
k
Balancing Events and BleedingBalancing Events and BleedingBalancing Events and BleedingBalancing Events and Bleeding
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Does bleeding influence the prognosis of ACS patients ?
Bleeding in ACS
Question to be answered:Question to be answered:
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Moscucci M et al. Moscucci M et al. Eur Heart JEur Heart J 2003;24:1815-23. 2003;24:1815-23.
P<0.001
5.13.0
5.37.0
18.616.1 15.3
22.8
0.0
10.0
20.0
30.0
40.0
No Bleed
Bleed
Overall Unstable NSTEMI STEMIOverall Unstable NSTEMI STEMI ACS AnginaACS Angina
Pat
ien
ts (
%)
Pat
ien
ts (
%)
Major Bleeding Predicts Mortality in ACSMajor Bleeding Predicts Mortality in ACSMajor Bleeding Predicts Mortality in ACSMajor Bleeding Predicts Mortality in ACS
24,045 ACS patients in the GRACE registry, in-hospital death24,045 ACS patients in the GRACE registry, in-hospital death24,045 ACS patients in the GRACE registry, in-hospital death24,045 ACS patients in the GRACE registry, in-hospital death
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Warfarin therapy and Bleeding
• Most serious complication of Warfarin• Common cause for litigation
• Most common sites of serious bleeding:– Epistaxis and gum bleed– Soft tissue including wounds
• Serious but less common sites of bleeding: _ Intracranial GIT
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Incidence of Bleeding in Warfarin therapy
Fatal bleeding(Bleeding is cause of death)
0.1-1%
Major bleeding
(GIT, retroperitoneal, intracranial or intra occular bleedingor any bleeding from an orifice + shock / needing transfusion or invasive procedure)
0.5-6.5%
Minor bleeding 6.2 - 21.8%
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Management of Overanticoagulated patient on Warfarin:
Serious or life-threatening Bleeding
• Admit to Hospital (ICU) – urgent referral• Stop Warfarin temporarily• Local control of bleeding• Reversal of INR
• Monitor INR 6 hrly and repeat Rx
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Reversal of Anticoagulation
• 1.Vitamin K (Several hours) – 5-10 mg I/V• 2.Fresh Frozen Plasma (few hours) 10-50 U/Kg• 3.Prothrombin Protein Complex ( minutes) –
10- 50 U/Kg• 4.Recombinant factor VII a (minutes) – 40-80
microgram/Kg
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PERIOPERATIVE MANAGEMENT
• Perioperative management of patients on warfarin or antiplatelet therapy involves assessing and balancing individual risks for thromboembolism and bleeding.
• Discontinuing anticoagulant and antiplatelet therapy is usually necessary for major surgery but increases the risk of thrombotic events.
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Managing Peri-operative anticoagulant therapy : 3 Options
• 1. Continue oral anticoagulant • 2. Stop therapy before surgery and re-start after
surgery (eg. Low risk AF)• 3. Bridge therapy (eg. MVR, High risk AF, Recent
VTE) Bridge therapy, is an effective means of reducing
the risk of thromboembolism but may increase the risk of bleeding
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How do I bridge ?
• Bridging is use of heparin for a brief period (period between stopping and recommencing oral anti coagulant)
• 1. Unfractionated Heparin• 2.Low Molecular Weight Heparin
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Chronic anticoagulation and surgery –(Bridging) : Recommendations
Stop Warfarin at least 5 days beforeStart UF Heparin or LMWH once INR less that 1.2Stop Heparin 6-24 hrs before surgeryStart Warfarin soon after surgery Start Heparin after 24 hrs of surgery if no active bleedingStop Heparin once therapeutic INR is achieved
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Patient Education
• Why they have been prescribed anti platelet and anticoagulant.
• Duration of treatment.• Advise on compliance • Importance of monitoring• Interaction with drugs and diet• Side effects /bleeding : when to seek medical
attention
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Take Home Message
Anticoagulants are being under utilized due to fear of bleeding.
• Assessment of bleeding risk must be objective with the use of bleeding risk tools.
• Physicians must maintain a fine balance between thrombosis and bleeding
• Antithrombotic agents are double edged swored that the physicians must chose carefully
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