the safety of anticoagulants foundation

The Safety of Anticoagulants Foundation

David Gerrett

Senior Pharmacist, Medication Safety Team NHS England /NHS Improvement

#PharmacyTogether2018

Declaration of Interest

Working for NHS Improvement on the response to the WHO Challenge


3 |3 |

The Third Challenge

Medication Without Harm: WHO's Third Global Patient Safety Challenge. 29 March 2017. http://www.who.int/patientsafety/medication-safety/en/

Medication Without Harm challenge WHO aims to “reduce severe avoidable medication related harm globally by 50% in the next 5 years”.

Many others will talk to this – the focus here is on one possible avenue of activity

4 |4 |

WHO Matrix

Presentation title

Domains

Priorities Patients and

the Public

Medicines Healthcare

professionals

Systems and

practices of

medication

High risk

situations

Polypharmacy

Transitions of

care

5 |5 |

What we need to do here!

Two simple (?) questions1.what are the errors

2.what might we do about them

6 |6 |

We had a look in the NRLS

Date: 13Oct17

Incidents reported as occurring between 1st July 2012 and 30th June 2017 (based on the date the incident was reported to have occurred)

(Exported to the NRLS on or before 12th October 2017)

Categorical: Incident category lvl1 equal to Medication

Free text filters: All terms searched in the following fields

IN07 Description of what happened

IN10 Action Preventing Reoccurrence

IN11 Apparent Causes

MD05 Approved name

MD06 Proprietary name

MD30 Approved name

MD31 Proprietary name

Free text search based on list of the following terms

Terms includes misspells:

Anticoagulant, low molecular weight heparin, LMW heparin, LMWH, heparin (not preceededby 'low molecular weight' or 'LMW'), NOAC, Dalteparin, Fragmin, Enoxaparin, Clexane, Tinzaparin, Innohep, Danaparoid, Orgaran, Argatroban, Exembol, Hirudin, Bivalirudin, Anglox, Epoprostenol, Flolan, Fondaparinux, Arixtra, Warfarin, Marevan, Acenocoumarol, Sinthrome, Phenindione, Dabigatran, Pradaxa, Apixaban, Eliquis, Rivaroxaban, Xarelto

7 |7 |

and….there are quite a few reported

Row Labels Death Severe Moderate Low No Harm

Patient

Group (blank) Grand Total

Warfarin 27 77 616 2966 21772 2 1 25461

Dalteparin 17 16 164 862 10168 11227

Clexane 7 19 209 1116 8805 10156

Enoxaparin 10 11 117 782 7826 8746

Tinzaparin 1 7 134 450 5763 6355

heparin 1 16 110 626 4560 5313

Rivaroxaban 10 16 140 503 4575 5244

Fragmin 4 3 55 468 4016 4546

Apixaban 6 16 62 272 2904 3260

Anticoagulant 2 3 28 74 1982 2089

Fondaparinux 1 3 17 151 1025 1197

Dabigatran 3 4 35 95 855 992

LMWH 1 3 70 21 97 192

Sinthrome 5 23 129 157

Epoprostenol 2 18 123 143

Acenocoumarol 1 14 111 126

Flolan 2 13 103 118

Argatroban 1 10 71 82

Xarelto 1 3 9 56 69

Innohep 1 3 57 61

Danaparoid 6 46 52

Eliquis 1 7 38 46

Pradaxa 1 2 4 37 44

NOAC 6 3 14 23

Bivalirudin 21 21

Phenindione 2 2 17 21

Arixtra 2 10 12

Orgaran 2 2

Marevan 1 1

Grand Total 91 195 1783 8500 75184 2 1 85756

8 |8 |

and….there are quite a few reported

Row Labels Death Severe Moderate Low No Harm

Patient

Group (blank) Grand Total

Warfarin 27 77 616 2966 21772 2 1 25461

Dalteparin 17 16 164 862 10168 11227

Clexane 7 19 209 1116 8805 10156

Enoxaparin 10 11 117 782 7826 8746

Tinzaparin 1 7 134 450 5763 6355

heparin 1 16 110 626 4560 5313

Rivaroxaban 10 16 140 503 4575 5244

Fragmin 4 3 55 468 4016 4546

Apixaban 6 16 62 272 2904 3260

Anticoagulant 2 3 28 74 1982 2089

Fondaparinux 1 3 17 151 1025 1197

Dabigatran 3 4 35 95 855 992

LMWH 1 3 70 21 97 192




Flolan 2 13 103 118


Xarelto 1 3 9 56 69

Innohep 1 3 57 61

Danaparoid 6 46 52

Eliquis 1 7 38 46

Pradaxa 1 2 4 37 44

NOAC 6 3 14 23

Bivalirudin 21 21


Arixtra 2 10 12

Orgaran 2 2

Marevan 1 1

Grand Total 91 195 1783 8500 75184 2 1 85756

9 |9 |

Row Labels Death Severe Moderate Low No HarmPatient Group (blank)

Grand Total subtotal

Warfarin 27 77 616 2966 21772 2 1 25461 25766

Marevan 1 1




Dalteparin 17 16 164 862 10168 11227 42546

Enoxaparin 10 11 117 782 7826 8746

Tinzaparin 1 7 134 450 5763 6355

Fragmin 4 3 55 468 4016 4546

Clexane 7 19 209 1116 8805 10156

Innohep 1 3 57 61

Fondaparinux 1 3 17 151 1025 1197

Arixtra 2 10 12

Danaparoid 6 46 52

Orgaran 2 2

LMWH 1 3 70 21 97 192

Rivaroxaban 10 16 140 503 4575 5244 9678

Apixaban 6 16 62 272 2904 3260

Dabigatran 3 4 35 95 855 992

Xarelto 1 3 9 56 69

Eliquis 1 7 38 46

Pradaxa 1 2 4 37 44

NOAC 6 3 14 23

heparin 1 16 110 626 4560 5313 5313


Flolan 2 13 103 118


Bivalirudin 21 21

Anticoagulant 2 3 28 74 1982 2089 2453

Grand Total 91 195 1783 8500 75184 2 1 85756 85756

10 |

The nature of error and the learning.

We have looked at the reported serious harm and the moderates plus a random selection of other harm.

The value of the NRLS reports is in identifying the ‘what happened’ with pointer to ‘why’

Now we will look at redacted examples for some of the themes we have identified.

11 |


Vit K antagonist+LMWH+interaction

Patient admitted on warfarin, co-prescribed [LMWH], INR 3.6 on admission but not checked regularly thereafter, on clarithromycin. Patient becomes unwell, INR [>] 10, bilateral subdural [haemorrhage] found 5 days later. Entered a phase of prolonged seizures and subsequently died. When bleed discovered, blood thinning stopped. Appropriate management after bleed detected. Reported outcome – Death

Speaks of1. Monitoring issues2. Combining warfarin with LMWH3. Interaction with antibiotic

12 |

The nature of guidance

13 |


Patient admitted on warfarin, co-prescribed [LMWH], INR 3.6 on admission but not checked regularly thereafter, on clarithromycin. Patient becomes unwell, INR [>] 10, bilateral subdural [haemorrhage] found 5 days later. Entered a phase of prolonged seizures and subsequently died. When bleed discovered, blood thinning stopped. Appropriate management after bleed detected. Reported outcome – Death

Speaks of1. Monitoring issues2. Combining warfarin with LMWH3. Interaction with antibiotic

2. Prescribing and administration of LMWH and warfarin at an inappropriate dose and/or duration was a frequent error. It was difficult to establish from some incident descriptions whether there was a prophylactic or therapeutic indication for anticoagulation.

14 |



Patient treated for PE [pulmonary embolism] with tinzaparin and warfarin, plan to stop warfarin when INR therapeutic. INR 2.3 on [date], therefore therapeutic -Tinzaparin not stopped. Seen on [date] - melaena reported, hypotensive, still on Tinzaparin and Warfarin, INR 9.3. Endoscopy diagnosed bleeding duodenal ulcer. Died [date]. Concerns - bleeding worse as on warfarin and tinzaparin. Possible delay in reporting of Melaena. Outcome – Death

Patient was on warfarin prior to admission. INR was 5.2 on [date, high]. Warfarin was stopped, but INR was not rechecked. Also, subsequently, LMWH was administered. INR on [date] was found to be 12.5. She was found to have bilateral subdural haematoma and transferred to another hospital. Outcome –Death

15 |



Patient treated for PE [pulmonary embolism] with tinzaparin and warfarin, plan to stop warfarin when INR therapeutic. INR 2.3 on

[date], therefore therapeutic - Tinzaparin not stopped. Seen on [date] - melaena reported, hypotensive, still on Tinzaparin and

Warfarin, INR 9.3. Endoscopy diagnosed bleeding duodenal ulcer. Died [date]. Concerns - bleeding worse as on warfarin and

tinzaparin. Possible delay in reporting of Melaena. Outcome – Death

Patient was on warfarin prior to admission. INR was 5.2 on [date, high]. Warfarin was stopped, but INR was not rechecked. Also,

subsequently, LMWH was administered. INR on [date] was found to be 12.5. She was found to have bilateral subdural haematoma

and transferred to another hospital. Outcome – Death

Speaks of

1. Monitoring issues

2. INR >>6, NPSA Alert 18, BSH guidance

3. Need for regular checks 3-5 days - average half-lives of the vitamin K-dependent

coagulation factors II, VII, IX, and X. X and II are the longest at 52 and 60 hours -

16 |

LMWH and antiplatelets, then Kit K antagonist, LMWH and antiplatelets

Patient had been prescribed aspirin (in addition to LMWH 20mg bd to cover withholding of warfarin) by cardiology while in CCU prior to transfer. Documented in med notes needs to be on antiplatelet and start warfarin later on possibly in 2 weeks’ time - then she can stop aspirin. Warfarin recommenced by GP visiting community hospital during the ward round. Patient still taking aspirin and LMWH 20mg bd. LMWH was supposed to be discontinued when INR >2 as documented on treatment sheet. TTO [outpatient To Take Out] written with warfarin, aspirin and LMWH 20mg bd until INR >2. Verified by pharmacist on [date]. Patient discharged without being seen again by pharmacist to review treatment. Patient re - admitted to hospital with epistaxis [nosebleed] documented as secondary to warfarin and aspirin taken together. Reported outcome – Severe

Speaks of1. communication issues, continuing care2. Common-sense (?) of combining warfarin, LMWH and aspirin

(Triple therapy for PCI [percutaneous coronary intervention=stents] OAT + aspirin + clopidogrel/dipyridamole)

3. Complexity of manipulating anticoagulants


17 |


Interactions

Patient admitted with haemoptysis and INR 9.5, on warfarin. Also been prescribed erythromycin by GP. This antibiotic can interact with warfarin to increase it effect which is probably reason for dangerously high INR. Outcome Moderate Harm

Speaks of

Surely this is a no-brainer?But

NICE https://bnf.nice.org.uk/interaction/warfarin.html#bnf_i1538443535555

18 |


Interactions

Patient admitted with haemoptysis and INR 9.5, on warfarin. Also been prescribed erythromycin by GP. This antibiotic can interact with warfarin to increase it effect which is probably reason for dangerously high INR. Outcome Moderate Harm

Speaks ofSurely this is a no-brainer?But Stockley’s on line 302 hits/monographs to the interaction

Coumarins + Antibacterials; Macrolides

(Latest modification: 31-Mar-2015)

Most controlled studies suggest that macrolides do not cause clinically relevant changes

in the pharmacokinetics or anticoagulant effects of warfarin.….the increased risk … with

…erythromycin … was not statistically significant…. and no increased risk of

bleeding…with erythromycin. [Yet there have been] a number of case reports describ[ing]

large increases in INRs and/or bleeding in patients taking coumarins and macrolides.

19 |

The perioperative period

These incidents described situations where anticoagulation, commonly warfarin, failed to be restarted post procedure/surgery. This often involved discharge of the patient without any specific advice regarding instructions to re-start at a specified time. There also appeared to be differing advice conveyed to patients from various practitioners. There were particular issues when patients had been advised to stop their anticoagulation and their elective procedure was cancelled but the patient was not advised to restart anticoagulation until the procedure was re-booked.


Patient was admitted for brachytherapy as part of cancer treatment. They had been on Warfarin for …..DVT. Patient was on SC heparin during the procedure. As they had significant haematuria heparin was stopped. Patient was discharged after haematuria stopped. However, no appointment with warfarin clinic was arranged and patient was without any anticoagulation. Patient subsequently developed pulmonary embolism and died at [name] Hospital …Reported Severe harm

20 |


These incidents described situations where anticoagulation is stopped in preparation for

procedure/surgery. There are local SOPs. Here are some, and there are many more


21 |


An elderly patient underwent a mastectomy on [date]. The patient was advised to stop their warfarin, which they were on for Atrial Fibrillation, 10 days prior to surgery. The patient was discharged on [date] without any explicit advice relating to re - starting warfarin. Warfarin was re - started 2 days after discharge. Patient suffered a stroke at home on [date] and subsequently died on [date]. Reported Severe harm

22 |

Patient was on warfarin with a history of atrial fibrillation and previous strokes . Patient was undergoing investigations and received an appointment for a sigmoidoscopy. It had been discussed at the patient last clinic appointment regarding whether warfarin should be stopped prior to this appointment and the doctor said that the risks and benefits would be considered at the time. When they received the appointment an appointment was booked at the patient local anti - coagulation clinic which they attended and a phone call was made to the Endoscopy Unit who advised that the patient should come off warfarin for 5 days prior to the procedure and restart after the procedure. The patient underwent the procedure and restarted their warfarin however they suffered a stroke the day after the sigmoidoscopy thought to be as a result of the warfarin being stopped.Reported Severe harm


You just can’t win!

23 |

Patient is on maintenance warfarin which was stopped for an ERCP. 4 days later they were admitted with a stroke/TIA. INR on admission was 1.1. As prophylactic anticoagulation was essential, they should have been on alternative treatment e.g. enoxaparin, the patient, underwent a revision of a right total knee replacement on [date]. Surgery was completed successfully and the patient made a good initial recovery from the procedure. On [date], the patient got up from bed unassisted and began to walk forward when she suddenly collapsed. CPR was commenced but despite all efforts, no cardiac output could be obtained and the patient was pronounced dead at [time]. Following a review of the case, it is understood that the patient did not receive the anti - coagulant post-surgery as requested by their consultant. The working diagnosis during this emergency situation was pulmonary embolism until INR was in therapeutic range again. Reported Severe harm

omitted and delayed


24 |

Patient admitted post Left CIA angioplasty via retrograde approach. Procedure uncomplicated with manual pressure to control haemorrhage. Sudden onset of large left groin haematoma with continued expansion despite manual pressure. Review of notes revealed patient on [NOAC/DOAC] and that this had not been stopped pre-procedure. Medication, including [NOAC/DOAC], recorded in pre -angioplasty check list. Patient taken to theatre for emergency Left CFA repair (suture) under GA. Found to be actively bleeding. Required blood transfusion and drain left in situ. Peri-operative cardiac event with Troponin rise. Prolonged hospital admission. Reported Severe harm


Not just warfarin

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From what we understand, great variation in guidance, communication issues, monitoring issues and ……sometimes you can’t win!


26 |26 |

https://www.sps.nhs.uk/wp-content/uploads/2011/08/Implementing-Patient-Safety-

Alert-18-anticoagulant-therapy-resource-May-2018.pdf current

Resources

27 |27 | Presentation title

https://onlinelibrary.wiley.com/doi/epdf/10.1111/bjh.14344 2016

Resources

28 |28 |

Resources on the way

29 |29 |

Summary

We have issues

when combining anticoagulants

Monitoring ‘across the board’

Interactions

The preoperative period

Heaps of guidance, NICE KTT BSH BNF local and it varies

From the audience,

anything we have missed?

30 |30 |

WHO Matrix

Domains

Priorities Patients and

the Public

Medicines Healthcare

professionals

Systems and

practices of

medication

High risk

situations

Polypharmacy

Transitions of

care

31 |31 |

What we might do?• A campaign of enlightenment about the nature of errors that can occur with anticoagulants

and [if we have the evidence] possible measures that have been shown to minimise the risk.

• The updating of NPSA Alert 18 and supporting resources with the addition of new OATs and specifically the inclusion of advice on preparation for the preoperative period and duel therapy with LMWH

• Harmonisation and dissemination of information to support risk reduction of DOACs dosing in renal impairment (specifically communicated to the NHS as a risk)

• From the WHO Evidence of impact from continuous monitoring of metrics for prescribing and anticoagulant related harm – link HES data on bleeds to primary care anticoagulant prescribing (and later with EPMA in secondary care)

Presentation title

1. Get the ‘experts’ together – show the evidence and prioritise

actions

2. Send a Programme Initiation Document (PID) to the WHO

Program Board

3. Keep everyone updated and ‘in the loop’

………do our best!

How do we start?

32 |32 |

Summary

We know the issues, medicines are complicated, the environments in which medicines are used are complicated. There is complex risk/benefit balance. The WHO Challenge is an opportunity to focus on this.

Any questions?

We value your opinion, so please don’t forget to fill in the evaluation

form!

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the safety of anticoagulants foundation

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