BALANCING THROMBOTIC AND BLEEDING RISKS

Dr Syed RazaMD, MRCP(UK),Dip Card(UK),CCT(UK),FCCP

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

• 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.

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.

WARFARIN

Newer Anticoagulants

– Direct Thrombin Inhibitors:• hirudin, lepirudin, desirudin, bivalirudin, • ximelagatran, Dabigatran

– Xa inhibitors:• fondaparinux, idraparinux• Rivaroxaban, Apixaban

– Heparinoids:• Danaparoid (discontinued)

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.

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.

Case Scenario

• 80 Yrs male• Hypertensive• Congestive Cardiac Failure• Atrial Fibrillation

CHADS2 : 3 CHA2DS2-VAS : 4

Assessment of Bleeding Risk

• Age• Hypertension• Renal Failure• Hepatic impairment• Significant anemia/ suspected leukemia

HAS – BLED : 4 >3 : Increased bleeding risk

How about the thrombo prophylaxis for DVT?

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?

Baseline Risk of VTE

Baseline Risk of VTE

Bahl et al. Ann Surg. 2010;251:344-350.

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.

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

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’

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

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.

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

THROMBOTIC AND BLEEDING RISK ASSESSMENT IN ACUTE CORONARY SYNDROME

Antiplatelet agents

Aspirin– “No doctor, I am on no medication…” – Commonest cause of post op wound oozing– Ticlopidine– Dipyridamole– Clopidogrel– Prasugrel– Ticagrelor

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

Bleeding Risk Score: CRUSADE

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

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

Does bleeding influence the prognosis of ACS patients ?

Bleeding in ACS

Question to be answered:Question to be answered:

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

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

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%

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

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

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.

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

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

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

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

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