Interventional procedures: New guidelines on safe coagulation status. Poster No.:

C-2515

Congress:

ECR 2013

Type:

Educational Exhibit

Authors:

C. O Brien , S. Leong , H. K. Kok , J. Mc Hugh , W. Torreggiani ;

1

1

2

1

1

1

2

Dublin/IE, Cork/IE

Keywords:

Outcomes, Hematologic diseases, Education and training, Venous access, Biopsy, Arterial access, Percutaneous, MR-Angiography, Interventional vascular, Interventional non-vascular, Hematologic

DOI:

10.1594/ecr2013/C-2515

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Learning objectives • •

•

To discuss current guidelines regarding safe coagulation parameters under which a range of interventional procedures can be performed. We review and discuss new data regarding coagulation studies including threshold levels of international normalised ratio (INR), activated partial thromboplastin time (APTT), prothrombin time (PT) and platelet counts. Specific contemporary guidelines for the following procedures will be included: Peripherally inserted central catheter (PICC) insertion, percutaneous transhepatic biliary drainage, percutaneous nephrostomy, percutaneous abscess drainage, paracentesis, arterial access and intervention, embolisation, lung biopsy, thyroid biopsy (fine needle aspiration) and liver biopsy (core).

Background The minimally invasive nature of Interventional Radiology (IR) procedures have revolutionised the management of patients ranging from central venous access for parenteral therapy to complex transcatheter embolisation procedures. Specific preprocedure work up including coagulation status have largely been derived and extrapolated from open surgical practice and guidelines such as the empirical use of INR cut-off values of 1.4 for performing interventional procedures. Despite this, there is significant variation in practice between IR operators and indeed between different institutions which can lead to unnecessary delay or cancellation of procedures. Recently, the Society of Interventional Radiology (SIR) and Cardiovascular and Interventional Radiology Society of Europe (CIRSE) published a comprehensive set of consensus 1

guidelines specific to coagulation status and haemostasis specific to IR practice. We review the recommendations of the SIR/CIRSE and similar guidelines, discuss new anticoagulants and antiplatelet agents that Interventional Radiologists should be familiar with and present a list of acceptable coagulation parameters for commonly performed procedures based on these data. Prior to undergoing an IR procedure, most patients will have a full blood count and coagulation study performed. The parameters measured generally include the haemoglobin level, platelet count, INR, PT and APTT as described in Table 1. Patients with abnormal coagulation status may have an underlying clotting disorder or be on anticoagulant medications. The coagulation cascade describes the mechanism of clotting; both coagluation disorders and anticoagulation medications affect this cascade at different levels and result in specific alterations in coagulation paremeters as shown in Figure 1. Newer direct thrombin inhibitors (DTI) are also increasingly used in clinical

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practice and radiologists should be familiar with their mechanism of action (Figure 2). Commonly used DTI include dabigatran, recombinant hirudins, bivalirudin, argatroban 2

and ximelagatran.

Table 1. Coagulation parameters

1,3,5.

INR

International normalised ratio which is a measure of the time it takes for blood to clot against a predetermined average.

PT

Prothrombin time, a test that evaluates the extrinsic and common pathways of the coagulation cascade to determine a patients potential to bleed.

APTT

Activated partial thromboplastin time, a test that evaluates the intrinsic and common pathways of the coagulation cascade. The time to clot formation is measured.

Platelet Count

Platelets are involved in haemostasis and the platelet count is a measure of the volume of circulating platelets. This does not measure the qualitative function of platelets which can be altered in disease states.

Figure 1. Coagulation cascade with sites of action of various anticoagulants and antiplatelet agents indicated. Reproduced from O'Connor SD et al, AJR Am J Roentgenol 3, 4

2009; 193:1656-64 and Selwyn AP, Am J Cardiol 2003; 91:3H-11H.

Figure 2. Mechanism of action of newer direct thrombin inhibitors (DTI) in comparison to 2

heparin. Reproduced from Di Nisio et al, New Engl J Med 2005; 353:1028-40.

In addition to anticoagulants, haematological and systemic diseases affecting the coagulation system are also important determinants of a patient's coagulation status. These disorders may arise secondary to a quantitative or qualitative defect in the coagulation cascade, typically involving coagulation factors or platelets. Common coagulation disorders and their corresponding effects on coagulation parameters are summarised in Table 2. In particular, patients with hepatobiliary disease and patients

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receiving chronic antibiotics are prevalent in IR practice and radiologists need to be aware of the increased bleeding risk in this group secondary to vitamin K depletion. Table 2. Common coagulation disorders and affected coagulation factors and 1, 6

parameters. Disorder

Clotting factor affected

Measurement

Haemophillia

Factor VIII and XII

PT, INR and APTT

Von Willebrand's Disease

Factor VIII

PT, INR and APTT

Disseminated intravascular Activation of the fibrinolytic PT, INR and APTT coagulation system Liver disease

Vitamin K deficiency

PT, INR and APTT

Bile duct obstruction

Loss of vitamin K secondary PT, INR and APTT to decreased fat absorbtion

Thrombocytopenia

Low platelet count

Platelet count

Anti-phospholipid syndrome

Lupus anti coagulant

PT, INR and APTT

Images for this section:

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Fig. 1: Figure 1. Coagulation cascade with sites of action of various anticoagulants and antiplatelet agents indicated. Reproduced from O'Connor SD et al, AJR Am J Roentgenol 2009; 193:1656-64 and Selwyn AP, Am J Cardiol 2003; 91:3H-11H.3, 4

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Fig. 2: NEJM Review article Direct thrombin inhibitors Marcello Di Nisio, M.D., Saskia Middeldorp, M.D., and Harry R. Büller, M.D. Mechanism of Action of Direct Thrombin Inhibitors as Compared with Heparin

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Imaging findings OR Procedure details Management of coagulation status prior to IR procedures In patients with an abnormal coagulation status, specific management steps will be required prior to intervention to minimise the risk of bleeding complications. Treatment with haemostatic agents such as fresh frozen plasma (FFP), platelets, vitamin K, desmopressin and cryoprecipiate may be required in patients with impaired homeostasis. 1.

2.

1, 3

FFP is prepared from pooled units of whole blood and contains plasma proteins which include clotting factors and 500mg of fibrinogen. As this is a blood product, the use of FFP should follow local blood product transfusion guidelines. Platelets are often transfused when the count is less than 50,000/uL 3

3.

4.

although evidence to support this threshold is weak. The qualitative function of platelets can be altered significantly in uraemic states and operators should not be falsely reassured by a normal platelet count. Platelets are also a fractionated blood product and should also follow local blood product transfusion guidelines. Vitamin K is a fat-soluble vitamin and is used to reverse the effects of warfarin and in vitamin K depleted states such as in hepatobiliary disease and chronic antibiotic therapy. This can be administered orally, intravenously or subcutaneously depending on the bleeding risk and INR level. Desmopressin is a synthetic analogue of antidiuretic hormone (ADH) and is used to elevate levels of factor VIII and von Willebrand factor in patients with 1

5.

haemophilia or von Willebrand disease. Cryoprecipitate is used for patients who have deficiencies of fibrinogen, usually in the setting of disseminated intravascular coagulation (DIC).

Many patients undergoing IR procedures will be on anticoagulant medications which affect different pathways in the coagulation cascade. Some of these agents will have short term effects (hours) whilst some persist for days. The mechanism of action, duration and management recommendations for these agents are summarised in Table 2.

Table 2. Common anticoagulants, mechanism of action and recommendations prior to 3

IR procedures. Medication

Mechanism action

of Duration of action

Recommendation

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Aspirin

Irreversible 7 to 10 days inhibition of platelets by inhibiting cyclooxygenase

Do not stop

Non steroidal anti Reversible inhition 24 hrs to 2 days inflammatory drugs of platelets (NSAIDS)

Do not stop

Clopidogrel (Plavix) Irreversibly inhibits 7 to 10 days plalelets by inhibiting an adenosine diphosphate chemoreceptor

Stop 3-5 days prior to procedure. Consult prescribing physician first. Restart immediately +/- loading dose

Warfarin

Inhibits the 3 to 5 days production of the vitamin K dependant extrinsic clotting factors: II, VII, IX, X and Protein S and C

Stop 3-5 days before, reduce dose to get INR less than 2 then restart immediately or stop for 3-5 days and bridge with heparin

Heparin

Inhibits factor Xa via 6 to 8 hours antithrombin III

Stop 6 hours before procedure and restart 12 hours later

Low molecular Inhibits factor Xa weight heparin (LMWH)

Up to 24 hours

Stop 12 hours before and restart 12 hours after the procedure

Figure 3. Large right retroperitoneal haematoma displacing the right kidney anteriorly (white arrow) in a patient who underwent emergency embolisation for uncontrolled lower gastrointestinal bleeding from angiodysplasia. The patient was on dual antiplatlet therapy with aspirin and clopidogrel and was on a therapeutic dose of low molecular weight heparin following recent percutaneous coronary intervention for an ST elevation myocardial infarct.

Coagulation status guidelines for ten common IR procedures

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Coagulation values for ten common interventional procedures, as compiled from a 1, 3

literature review of recent IR guidelines are summarised in Table 3. These coagulation parameters should be considered as part of the overall assessment of an individual patient. Safe coagulation thresholds will vary depending on the presence of co-existing medical conditions such as DIC in critically-ill patients or uraemia in patients with chronic kidney disease. Equally important are procedural skills and techniques in minimising the bleeding risk such as the use of small percutaneous access needles (22 gauge), small incisions to create a seal around percutaneous drains / sheaths and small French size sheaths and catheters. Percutaneous vascular or visceral access should also be obtained using real-time imaging guidance with ultrasound where possible to further minimise the complication risk. 1, 3

Table 3. Coagulation values for ten common interventional procedures. Procedure

INR

Platelet count (µL)

PICC

25,000

Percutaneous transhepatic 50,000

Percutaneous nephrostomy 50,000

Percutaneous drainage

abscess 25,000

Paracentesis

25,000

Arterial intervention

50,000

Embolisation

50,000

Lung biopsy

25,000

Thyroid biopsy (FNA)

N/A

N/A

Liver biopsy (percutaneous, 50,000

Contemporary anticoagulation agents New anticoagulant agents are being used in clinical practice such as dabigatran, fondaparinux, prasugrel and ticagrelor and IR operators need to be familiar with their mechanism of action and management. Dabigatran (Pradaxa) is an oral DTI and is increasingly used as an alternative to warfarin. Dabigatran does not require monitoring of INR levels and is renally excreted. There is no specific reversal agent for dabigatran, therefore the administration of plasma

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clotting factors should be reserved for patients with life threatening haemorrhage where 7

supportive measures and control of the bleed site have failed . Fondaparinux (Arixtra) is an indirect selective inhibitor of factor Xa. It is used in a similar 1

way to LMWH and is renally excreted . It does not interact with platelets or platelet factor 4 and for this reason it does not induce thrombocytopenia as compared to heparin-based agents. There is no specific reversal agent for fondaparinux, however high doses of recombinant factor VIIa may partially normalise a prolonged APTT. Monitoring can be achieved by anti-factor Xa assays calibrated for fondaparinux. Guidelines for elective surgery suggest discontinuation for 2 to 4 days prior to the procedure in patients with 8

normal renal function . Prasugrel (Effient) is a new generation anti-platelet agent and works in a similar fashion to clopidogrel by inhibiting adenosine diphosphate activation of glycoprotein IIb and IIIA receptor complex. As platelet aggregation is inhibited for the life of the platelet, platelet aggregation returns to normal 5 to 9 days post-discontinuation. It is possible to restore haemostasis by administering exogenous platelets 6 to 8 hours after the last 1

dose . Ticagrelor (Brilinta) is a similar new anti-platelet agent which reversibly blocks the adenosine diphosphate receptors at the P2T12 receptor on the platelet surface, reducing 9

platelet aggregation . If discontinued platelet aggregation will resume within 12 hours, 10

this will minimise bleeding in patients who need to have invasive interventions. Images for this section:

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Fig. 3: Figure 3. Large right retroperitoneal haematoma displacing the right kidney anteriorly (white arrow) in a patient who underwent emergency embolisation for uncontrolled lower gastrointestinal bleeding from angiodysplasia. The patient was on dual antiplatlet therapy with aspirin and clopidogrel and was on a therapeutic dose of low molecular weight heparin following recent percutaneous coronary intervention for an ST elevation myocardial infarct.

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Conclusion

Table to summarise contemporary and widely used anticoagulants, their mode of action, duration of action and recommendation for stopping prior to an invasive 1,7,8,11

procedure.

Anticoagulation

Mode of action

Duration of action

Recommendation

Aspirin

Irreversible 7 to 10 days inhibition of platelets by inhibiting cyclooxygenase

Do not stop

Clopidogrel (Plavix)

Irreversibly 7 to 10 days inhibits plalelets by inhibiting an adenosine diphosphate chemoreceptor

Stop 3-5 days prior to procedure. Consult prescribing physician first. Restart immediately +/loading dose

Prasugrel (Effient) Reduces platelet 5 to 9 days aggregation and activation by irreversibly blocking the P2Y12 of the ADP receptor on the platelet

Stop at least 7 days prior to procedure.

Dabigatran (Pradaxa)

Stop 1 to 2 days if the creatinine clearence is 50ml/min

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XI, XIII. Also inhibits platelet aggregation. Warfarin

Inhibits the 3 to 5 days production of the vitamin K dependant extrinsic clotting factors: II, VII, IX, X and Protein S and C

Stop 3-5 days before, reduce dose to get INR less than 2 then restart immediately or stop for 3-5 days and bridge with heparin

Heparin

Inhibits factor Xa 6 to 8 hours via antithrombin III

Stop 6 hours before procedure and restart 12 hours later

Fondaparinux

Indirect selective inhibitor of factor Xa

1 to 2 days.

Stop 2 to 4 days prior to procedure

Up to 24 hours

Stop 12 hours before and restart 12 hours after the procedure

Low Molecular Inhibits factor Xa Weight Heparin (LMWH)

References

1.

2. 3. 4. 5.

Patel IJ, Davidson JC, Nikolic B, et al. Consensus guidelines for periprocedural management of coagulation status and hemostasis risk in percutaneous image-guided interventions. J Vasc Interv Radiol. 23(6): 727-36. Di Nisio M, Middeldorp S, Buller HR. Direct thrombin inhibitors. N Engl J Med, 2005. 353(10): 1028-40. O'Connor SD, Taylor AJ, Williams EC, Winter TC. Coagulation concepts update. AJR Am J Roentgenol, 2009. 193(6): 1656-64. Selwyn AP. Prothrombotic and antithrombotic pathways in acute coronary syndromes. Am J Cardiol, 2003. 91(12A): 3H-11H. Y.l.Chee, J.C.Crawford, H.G.Watson, M. Greaves. Guidelines on the assessment of bleeding risk prior to surgery or invasive procedures. British Journal of Haematology, 2008. 140 (5):496-504.

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6.

Philip A Kalra, editor. Essential revision notes for the MRCP. Pastest, edition 3

7.

Lexicomp Dabigatran: Drug information. 2012 Up To Date. Topic 8926 Version 43.0 Kenneth A Bauer, Lawerence LK Leung, Jennifer s Tirnauer. Therapeutic use of Fondaparinux. Up To Date 2012. Topic 1319 Version 10.0.

8. 9.

c.

c

Lexicomp . Ticagrelor: Drug information. 2013 Up To Date. Topic 16784 Version 24.0 10. Harvey D. White, Oral Antiplatelet Therapy for Atherothrombotic Disease. American heart Journal, 2011. 161(3):450-461 11. Lexicompc. Prasugrel: Drug information. 2013. Up To Date. Topic 9533 Version 43.0

Personal Information

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