GUIDELINES for the DIAGNOSIS and MANAGEMENT of
HEPARIN-INDUCED THROMBOCYTOPENIA (HIT) with or
without THROMBOSIS
Amendments
Date
Page(s)
Comments
20/04/12 6
Updated at consultant request to include
(section warning on marking requests for anti-Xa
6)
levels with ‘danaparoid’ to allow
accurate lab testing.
Updated to refer to haematology for
advice on adjusting rate of infusion.
20/04/12 Cover
Comments on document amended to
read Mike Barker, Pharmacist due to
post holder change.
Approved by
Drugs & Therapeutics
Committee, May 2012
Drugs & Therapeutics
Committee, May 2012
Compiled by:
Ingrid Sparla, Pharmacist
In Consultation with:
Dr. Tanya Bernard, Consultant Haematologist
Ratified by:
Drugs & Therapeutics Committee
Date ratified:
November 2011
Date issued:
December 2011
Review date:
November 2014
Target audience:
All clinical staff
Impact Assessment
carried out by:
Ingrid Sparla, Pharmacist
Comments on this document to:
Mike Barker, Pharmacist
Volume 1
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INTRODUCTION
Heparin induced thrombocytopenia (HIT) is an important complication of the use of heparins. HIT is
an antibody-mediated adverse effect of heparin and associated with a prothrombotic state which
presents with either asymptomatic thrombocytopenia, with venous or arterial thrombosis, skin
lesions or rarely with a generalised systemic reaction which can be severe or even fatal. It is
therefore important that HIT is recognised as early as possible and managed appropriately.
PURPOSE
These guidelines have been developed to assist clinical and nursing staff in the diagnosis and
management of heparin induced thrombocytopenia (HIT).
RESPONSIBILITIES
The clinical team looking after a patient is responsible for ensuring that in consultation with the
haematologists heparin-induced thrombocytopenia is diagnosed and managed appropriately and
that they are familiar with these guidelines.
Staff involved in the prescribing, preparation, storage and administration of danaparoid for the
treatment of HIT are responsible for ensuring that they are familiar with these guidelines.
In particular:
- The clinical team is responsible for ensuring that no contraindications to danaparoid apply, that a
valid and correct prescription for danaparoid is available for the duration of treatment, that a
baseline coagulation screen and a full blood count have been sent prior to commencing
danaparoid, and that plasma anti-Xa activity is monitored and the dose of danaparoid adjusted
accordingly as outlined in these guidelines.
- The nursing staff looking after a patient prescribed danaparoid is responsible for ensuring that
danaparoid is ordered from pharmacy as soon as possible to avoid delay in treatment, and that
loading dose and maintenance dose are prepared and administered as outlined in these
guidelines.
- Pharmacy is responsible for ensuring that danaparoid is made available to the patient as soon as
possible to avoid delay in treatment.
DISSEMINATION AND IMPLEMENTATION
The guidelines are available on the trust intranet.
PROCESS FOR MONITORING COMPLIANCE WITH THE EFFECTIVENESS OF POLICIES
Through observation and audit
CORE EQUALITY IMPACT ASSESSMENT
See Appendix 1
ARCHIVING ARRANGEMENTS
This is a trust-wide document and archiving arrangements are managed by Quality Department
who can be contacted to request master/archived copies.
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INCIDENCE OF HEPARIN-INDUCED THROMBOCYTOPENIA
HIT may occur in any patient who is receiving Unfractionated Heparin (UFH) or Low Molecular
Weight Heparin (LMWH). LMWH are associated with a lower incidence of HIT than UFH.
The incidence of HIT is higher in surgical patients than it is in medical patients and obstetric
patients. The highest incidence is in patients who have undergone major lower limb orthopaedic
surgery and cardiac surgery.
The highest risk of HIT is in days 5-10 of exposure. Occasionally, the onset can occur after more
than 10 days of heparin exposure but it is rare after 15 days. Recently exposed patients (within
previous 100 days) may develop HIT within the first 24 hours of re-exposure because of preexisting antibodies.
50% of patients who develop HIT will have associated thrombosis. However, in those presenting
without thrombosis (isolated HIT) there is a high risk of subsequent thrombosis if heparin is not
stopped and an alternative anticoagulant given.
MONITORING OF PLATELET COUNT
The following recommendations apply:






All patients who are to receive heparin of any sort should have a platelet count on the day
of starting treatment.
For patients who have been exposed to heparin in the last 100 days, a baseline platelet
count and a platelet count 24 hours after starting heparin should be obtained.
For all patients receiving UFH, alternate day platelet counts should be performed from days
4 to 14.
For surgical and medical patients receiving LMWH platelet counts should be performed
every 2–4 days from days 4 to 14.
Obstetric patients receiving treatment doses of LMWH should have platelet counts
performed every 2–4 days from days 4 to 14.
Obstetric patients receiving prophylactic LMWH are at low risk and do not need routine
platelet monitoring.
DIAGNOSIS OF HEPARIN-INDUCED THROMBOCYTOPENIA
The diagnosis of HIT is based on the presence of a combination of clinical and laboratory features.
If the platelet count falls by 50% or more, or falls below the laboratory normal range and/or the
patient develops new thrombosis or skin allergy between days 4 and 14 of heparin administration
HIT should be considered and a clinical assessment made to estimate the pretest probability of
HIT using the scoring system below.
Points (0,1 or 2 for each categories: maximum possible score = 8)
‘The 4T’s’
2
Thrombocytopenia
(NB: severe thrombocytopenia
(platelet <15x109/l) is unusual
in HIT)
Timing of platelet count fall
or other sequelae (first day of
heparin exposure considered
day 0)
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Section 1
1
>50% fall or
platelet nadir
20-100x109/l
Clear onset between
days 5 and 10; or less
than 1 day if heparin
exposure within past
100 days
First ratified
Nov 2011
0
30-50% fall or
platelet nadir 10-19x109/l
Consistent with immunisation
but not clear (e.g. missing
platelet counts) or onset of
thrombocytopenia after day 10
Reviewed
Issue 2
<30% fall or
platelet nadir <10x109/l
Platelet count fall too
early (without recent
heparin exposure)
Page 3 of 10
Thrombosis or other
sequelae (e.g. skin lesions)
Other causes for
thrombocytopenia not
evident
New thrombosis; skin
necrosis; post heparin
bolus acute systemic
reaction
No other cause for
platelet count fall
evident
Progressive or recurrent
thrombosis; erythematous skin
lesions, suspected thrombosis
not yet proven
None
Possible other cause is evident
Definite other cause is
present
Pretest probability score: 6-8 = high probability of HIT
4-5 = intermediate probability of HIT
0-3 = low probability of HIT
If the pretest probability of HIT is intermediate or high, heparin should be stopped and an
alternative anticoagulant started at therapeutic dosage (unless there are significant
contraindications) while laboratory tests to detect the anti-heparin/anti-platelet factor 4 (PF4)
antibodies are performed.
Documentation of the occurrence of HIT in clinical records is essential and the diagnosis of
HIT should be marked as a serious allergy.
TREATMENT OF HEPARIN-INDUCED THROMBOCYTOPENIA
In patients with HIT, alternative anticoagulation should be provided irrespective of whether or not
there is evidence of a new thrombotic event unless the risk of haemorrhage is deemed excessive.
For patients with strongly suspected or confirmed HIT, heparin should be stopped and full-dose
anticoagulation with danaparoid (Orgaran®) commenced (in the absence of a significant
contraindication).
Platelet transfusion should generally be avoided in HIT as this can drive the thrombotic process
and precipitate or exacerbate arteriovenous thromboemboli. Discuss with haematologist on call if
severe/life-threatening bleeding occurs.
IV DANAPAROID INFUSION REGIMEN
1. General aspects
Danaparoid is given by intravenous injection followed by an intravenous infusion.
Ensure that a valid IV danaparoid infusion prescription (loading and maintenance dose) is available
for the duration of treatment.
Ensure that a baseline coagulation screen and a full blood count have been sent prior to
commencing IV danaparoid.
Danaparoid is available in ampoules containing danaparoid 750 units in 0.6ml.
2. Contraindications to danaparoid

As with heparins, in patients receiving danaparoid for treatment rather than for prophylaxis,
spinal or epidural anaesthesia in elective surgical procedures is contra-indicated

severe haemorrhagic diathesis, e.g. haemophilia and idiopathic thrombocytopenic purpura,
unless the patient also has HIT and no alternative anti-thrombotic treatment is available

haemorrhagic stroke in the acute phase

uncontrollable active bleeding state
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
severe hypertension

active gastroduodenal ulcer, unless it is the reason for operation

diabetic retinopathy (relative contraindication)

acute bacterial endocarditis

hypersensitivity to danaparoid

hypersensitivity to sulphite
3. Warnings and Precautions
Danaparoid has been shown to have a low incidence (<10%) of (platelet) cross-reactivity with
plasma from patients sensitised by heparin. Although the risk of antibody-induced
thrombocytopenia is very small, it is advisable to check the number of platelets regularly. If
antibody-induced thrombocytopenia occurs, one should stop the use of danaparoid and consider
alternative treatment dependant on availability.
For further or more detailed information please refer to the SPC of danaparoid (Orgaran®),
www.medicines.org
4. Preparation of danaparoid IV bolus injection and IV infusion
IV bolus injection (loading dose)
The dose can be given neat or may be diluted with sodium chloride 0.9%, give over 15-30
seconds.
IV infusion (maintenance dose)
Make up a syringe with 4500 units (3.6ml) danaparoid (= six ampoules of 750 units/0.6ml) plus
41.4 ml of normal saline 0.9% or dextrose 5% to a total volume of 45ml.
The final concentration is 100 units/ml.
The syringe must be changed every 24 hours and infusion set every 72 hours.
5. Dosage and Administration
Danaparoid is given by intravenous injection (loading dose) followed by an intravenous infusion
(maintenance dose) as per table below:
Renal function
Normal to mildly
impaired (CrCl 2050 ml/min) renal
function
Moderately (CrCl
10-20 ml/min) and
severely impaired
(CrCl <10 ml/min)
renal function
Volume 1
Loading dose
(IV bolus over 15-30 sec)
< 55kg: 1250 units (1ml)
55- 90kg: 2500 units (2ml)
> 90kg: 3750 units (3ml)
< 55kg: 1250 units (1ml)
55- 90kg: 2500 units (2ml)
> 90kg: 3750 units (3ml)
Section 1
First ratified
Nov 2011
Maintenance dose
(IV infusion)
400 units/hr for 2 hrs,
then 300 units/hr for 2 hrs,
followed by an initial
maintenance infusion of
200 units/hr
400 units/hr for 2 hrs,
then 300 units/hr for 2 hrs,
followed by an initial
maintenance infusion of
150 units/hr
Reviewed
Issue 2
Monitoring
Monitoring of plasma
anti-Xa activity not
necessary unless
patients are > 90kg
Monitoring of plasma
anti-Xa activity is
advised for all
patients, adjust
maintenance dose
according to anti-Xa
levels (target level:
0.5-0.8 units/ml)
Page 5 of 10
Patients on CVVH
(Intensive Care
Unit only)
< 55kg: 2000 units (1.6ml)
400 units/hr for 4 hrs
followed by a maintenance
infusion of 150-400 units/hr
to maintain plasma anti-Xa
levels of 0.5-1.0 units/ml
 55kg: 2500 units (2ml)
600 units/hr for 4 hrs,
then 400 units/hr for 4 hrs,
followed by a maintenance
infusion of 200-600units/hr
to maintain plasma anti-Xa
levels of 0.5-1.0 units/ml
Monitoring of plasma
anti-Xa activity is
advised for all
patients, adjust
maintenance dose
according to anti-Xa
levels
6. Monitoring of anti-Xa levels
Anti-Xa levels should be monitored in the following patient groups:



patients weighing > 90kg
patients with moderate (CrCl 10-20ml/min) to severe (CrCl <10ml/min) renal impairment
patients receiving continuous venous-venous haemofiltration (CVVH)
However, lack of availability of anti-Xa monitoring is NOT a contraindication to use of
danaparoid.
NOTE: Anti-Xa levels for patients on danaparoid are measured in a different way to those
corresponding to low-molecular weight heparins.
*The request form MUST be marked ‘danaparoid anti-Xa’ for the laboratory to process the
samples correctly*
If it is unclear whether levels have been correctly ordered please confirm with the
haematology laboratory (3038) before interpretation.
Anti-Xa factor levels should be initially measured soon after completion of the accelerated infusion
protocol, thereafter every 24 hours.
Target plasma anti-Xa levels during the maintenance infusion are 0.5-0.8 units/ml.
In patients on CVVH (Intensive Care Unit only) target plasma anti-Xa levels are 0.5-1.0 units/ml.
Plasma anti-Xa levels are linearly related to the dose of danaparoid given, contact haematology
for advice on adjusting the infusion rate if out of range.
7. Duration of danaparoid therapy and initiation of warfarin
The duration of danaparoid therapy and the subsequent use of oral anticoagulants depend on
whether the patient has had a thrombotic event. For patients with isolated thrombocytopenia,
therapeutic doses of danaparoid are recommended until the platelet counts recover to a stable
plateau, if not to baseline values.
Warfarin can increase the risk of microvascular thrombosis in HIT and its introduction should be
delayed until there has been substantial resolution of the thrombocytopenia. It should then be
introduced at low dose and with overlap of danaparoid until the INR is therapeutic for two
consecutive days.
Please discuss with haematologist duration of therapy and potential initiation of oral
anticoagulants.
Volume 1
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REFERENCES
1. David Keeling, Simon Davidson and Henry Watson, on behalf of the Haemostasis and Thrombosis
Task Force of the British Committee for Standards in Haematolgy: The management of heparininduced thrombocytopenia. British Society for Haematology, 133, 259–269, 2006
2. Warkentin TE, Greinacher A, Koster A, Lincoff AM. Treatment and prevention of heparin-induced
thrombocytopenia: American College of Chest Physicians Evidence-Based Clinical Practice
Guidelines (8th Edition). Chest 2008 Jun;133 (6 Suppl): 340S-80S.
3. SIGN: Prevention and management of venous thromboembolism, Clinical guideline No 122,
December 2010
4. JPJ Wester, on behalf of the NVIC Committee Nephrology and Intensive Care Medicine: Guidelines
for anticoagulation with danaparoid sodium and lepirudin in continuous venovenus hemofiltration.
Neth J Crit Care. 2001: 8(4): 293-301
5. Y. Sakr. Heparin-induced thrombocytopenia in the ICU: an overview. Critical Care 2011, 15:211
6. G. M. Arepally and T. L. Ortel. Heparin-Induced Thrombocytopenia. NEJM 2006; 355 (8): 809-819
7. BNF 62, September 2011
8. New Zealand data sheet of Orgaran, http://www.medsafe.govt.nz/profs/datasheet/o/Orgaraninj.pdf
(accessed 11/10/11)
9. SPC of Orgaran, www.medicines.org.uk (accessed 12/10/11)
10. Medusa Injectable Medicines Guide, http://medusa.wales.nhs.uk/ (accessed 12/10/11)
APPENDICES
APPENDIX 1
Equality Impact Assessment Summary
Name of author: Ingrid Sparla
Policy/Service: Guidelines for the diagnosis and management of heparin-induced
thrombocytopenia (HIT) with or without thrombosis
Background
 Description of the aims of the policy
 Context in which the policy operates
 Who was involved in the Equality Impact Assessment
The aim of these guidelines is to support and guide clinical staff (doctors, nurses and pharmacists)
in the diagnosis and treatment of HIT in adult inpatients. They are intended to be used on
advice/after discussion with the consultant haematologists.
These guidelines should be accessible for clinical staff at any time on the intranet.
This equality impact assessment has been carried out by me.
Methodology
 A brief account of how the likely effects of the policy was assessed (to include race and
ethnic origin, disability, gender, culture, religion or belief, sexual orientation, age)
 The data sources and any other information used
 The consultation that was carried out (who, why and how?)
These guidelines are not discriminatory in any way but are for patients with heparin-induced
thrombocytopenia irrelevant of race / gender / belief /age etc.
The data sources are from national and international guidelines, medical journals and websites
related to medicines (see references)
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Consultation was carried out with Consultant Haematologist Tanya Bernard via email and in
meetings.
Key Findings
 Describe the results of the assessment
 Identify if there is adverse or a potentially adverse impacts for any equalities groups
I do not feel that these guidelines have any discriminatory factors or potentially adverse outcomes
for any equalities groups.
Conclusion
 Provide a summary of the overall conclusions
These guidelines are aimed at supplying summarised guidance to clinical staff involved in the
management of patients with heparin-induced thrombocytopenia.
No equality groups are adversely impacted as a result of these guidelines.
Recommendations
 State recommended changes to the proposed policy as a result of the impact assessment
 Where it has not been possible to amend the policy, provide the detail of any actions that
have been identified
 Describe the plans for reviewing the assessment
No changes to guidelines required
Guidance on Equalities Groups
Race and Ethnic origin (includes gypsies and
travellers) (consider communication, access to
information on services and employment, and
ease of access to services and employment)
Religion or belief (include dress, individual
care needs, family relationships, dietary
requirements and spiritual needs for
consideration)
Disability (consider communication issues,
access to employment and services, whether
individual care needs are being met and
whether the policy promotes the involvement of
disabled people)
Sexual orientation including lesbian, gay
and bisexual people (consider whether the
policy/service promotes a culture of openness
and takes account of individual needs
Gender (consider care needs and employment
issues, identify and remove or justify terms
which are gender specific)
Age (consider any barriers to accessing
services or employment, identify and remove or
justify terms which could be ageist, for example,
using titles of senior or junior)
Social class (consider ability to access services
and information, for example, is information
provided in plain English?)
Culture (consider dietary requirements, family
relationships and individual care needs)
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APPENDIX 2
PROFORMA FOR RATIFICATION OF POLICIES PROCEDURES and GUIDELINES BY
RATIFYING COMMITTEE
Name of Person completing form:
Date:
Guidelines for the diagnosis and management of
heparin-induced thrombocytopenia (HIT) with or without
thrombosis
Ingrid Sparla
12/11/2011
Author(s) (Principle contact)
Ingrid Sparla
Name of author or sponsor to attend ratifying
committee when policy/guideline is discussed
Ingrid Sparla and Tanya Bernard
Date of final draft
13/11/2011
Policy/Guidelines Name:
Has this policy/guideline been thoroughly proofread to check for errors in spelling, typing,
grammar and consistency?
(delete as necessary)
By whom:
Is this a new or revised policy/guideline?
(delete as necessary)
Describe the development process used to
generate this policy/guideline.
Who was involved, which groups met, how often
etc.?
Who is the policy/guideline primarily for?
Is this policy/guideline relevant across the Trust or
in limited areas?
How will the information be disseminated and how
will you ensure that relevant staff are aware of this
policy/guideline?
Describe the process by which adherence to this
policy/guideline will be monitored.
(This needs to be explicit and documented for
example audit, survey, questionnaire)
Is there a NICE or other national guideline
relevant to this topic? If so, which one and how
does it relate to this policy/guideline?
Has the policy been checked against minimum
requirements for NHS LA Standards (if applicable)
What (other) information sources have been used
to produce this policy/guideline?
Has the policy/guideline been impact assessed
with regard to disability, race, gender, age,
religion, sexual orientation?
Other than the authors, which other groups or
individuals have been given a draft for
comment?(e.g. staff, unions, human resources,
finance dept., external stakeholders and service
users)
Which groups or individuals submitted written or
verbal comments on earlier drafts?
Who considered those comments and to what
extent have they been incorporated into the final
draft?
Have financial implications been considered?
Proposed review date
Volume 1
Section 1
First ratified
Nov 2011
Yes
Ingrid Sparla, Tanya Bernard
New
Peer discussion via UKCPA with pharmacists at other
NHS Hospitals
Local discussion with Consultant Haematologist Tanya
Bernard.
All clinical staff
In all adult areas across the trust
The guidelines will be available on the Intranet
An announcement via Aspire will ensure that relevant
staff are aware of them
The haematologists will direct doctors to these
guidelines when a HIT case is discussed.
Through audit
See reference 1. The national guidelines were used as
a reference to compile these local guidelines
N/A
See ‘references’ for information sources used, also
communication with pharmacists at other trusts
Yes – see core EIA
Consultant Haematologists
Consultant Haematologist Tanya Bernard
The author considered all previous comments, they all
have been incorporated into the final draft
Yes
3 years from ratification
Reviewed
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Volume 1
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First ratified
Nov 2011
Reviewed
Issue 2
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