heparin induced thrombocytopenia adult inpatient clinical ... · the following guideline is...

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Heparin Induced Thrombocytopenia – Adult – Inpatient

Clinical Practice Guideline

Note: Active Table of Contents – Click to follow link

EXECUTIVE SUMMARY ........................................................................................ 3

SCOPE ................................................................................................................. 4

METHODOLOGY .................................................................................................. 4

DEFINITIONS1 ...................................................................................................... 5

INTRODUCTION .................................................................................................. 5

RECOMMENDATIONS ......................................................................................... 6

UW HEALTH IMPLEMENTATION ........................................................................ 13

APPENDIX A. EVIDENCE GRADING SCHEME(S) ................................................... 14

APPENDIX B. DECISION TO TREAT HIT BASED ON 4T SCORE AND LAB TEST INTERPRETATION – HEPARIN INDUCED THROMBOCYTOPENIA – ADULT – CPG . 15

APPENDIX C. SELECTION OF NON-HEPARIN ANTICOAGULANT – HEPARIN INDUCED THROMBOCYTOPENIA – ADULT – CPG ............................................... 16

REFERENCES ...................................................................................................... 17

Copyright © 2017 University of Wisconsin Hospitals and Clinics AuthorityContact: Lee Vermeulen, [email protected] Last Revised: 05/[email protected]

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Contact for Content: Name: Anne Rose, PharmD - Pharmacy; Anticoagulation Stewardship Phone Number: (608) 263-9738 Email Address: [email protected] Contact for Changes: Name: Philip Trapskin, PharmD, BCPS – Drug Policy Program Phone Number: (608) 263-1328 Email Address: [email protected] Guideline Author(s): Anne Rose, PharmD – Pharmacy: Anticoagulation Stewardship Coordinating Team Members: John Sheehan, MD – Hematology Eliot Williams, MD – Hematology Review Individuals/Bodies: David Yang, MD – Clinical Lab Committee Approvals/Dates: Inpatient Anticoagulation Committee Pharmacy & Therapeutics Committee (Last Periodic Review: 05/2017) Release Date: May 2017 | Next Review Date: May 2019

Copyright © 2017 University of Wisconsin Hospitals and Clinics AuthorityContact: Lee Vermeulen, [email protected] Last Revised:

05/[email protected]

mailto:[email protected]

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Executive Summary

Guideline Overview The following guideline is intended to guide the diagnosis and management of heparin induced thrombocytopenia. Key Practice Recommendations 1. Diagnosis of HIT is based on both clinical (thrombocytopenia or new thrombosis) and

laboratory findings. (UW Health moderate quality of evidence, strong recommendation)

2. The heparin induced platelet Ab (ELISA) can be performed in the clinical lab and should be utilized first if laboratory diagnosis is needed. (UW Health low quality of evidence, strong recommendation)

2.1 A strongly positive ELISA (OD > 1) with a high suspicion for HIT can reliably confirm the diagnosis of HIT (UW Health moderate quality of evidence, strong recommendation)

2.2 A negative ELISA reliably rules out HIT (UW Health moderate quality of evidence, strong recommendation)

3. A heparin dependant Ab (SRA) may be considered if uncertainty exists in the diagnosis of

HIT based on the ELISA results and 4T score. (UW Health moderate quality of evidence, strong recommendation)

4. For all patients with suspected or confirmed HIT: discontinue all heparin (including flushes) and/or low molecular weight heparin orders by any route (UW Health low quality of evidence, strong recommendation)

5. Start a non-heparin anticoagulant immediately upon ELISA confirmation or if awaiting results

of the SRA. (UW Health low quality of evidence, strong recommendation)

6. Treatment options 6.1 Nonsurgical: Fondaparinux or direct oral anticoagulants (DOAC) 6.2 Surgical: Argatroban 6.3 Cardiac surgery: Bivalirudin

7. Length of treatment

7.1 Isolated HIT (HIT without thrombosis): anticoagulation should be continued for 4 weeks

7.2 HITT: anticoagulation should be continued for at least 3 months and then assess the risk versus benefit of discontinuing therapy.

Companion Documents 1. Appendix B. Decision to treat HIT based on 4T score and lab test interpretation – Heparin

Induced Thrombocytopenia – Adult – CPG 2. Appendix C. Selection of non-heparin anticoagulant – Heparin Induced Thrombocytopenia –

Adult – CPG



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Scope

Disease/Condition(s): Heparin Induced Thrombocytopenia Intended Users:

Physicians

Advanced Practice Providers

Pharmacists

Registered Nurses Objective(s): This clinical practice guideline is intended to provide recommendations for the diagnosis and treatment of HIT. Target Population: Adult inpatients with suspicion or diagnosis of HIT Interventions and Practices Considered:

Assistance with diagnosis of HIT based on clinical presentation and laboratory confirmation

Assistance with treatment of HIT including parenteral and oral options and patients with a history of HIT requiring cardiac surgery

Major Outcomes Considered: Frequency of HIT laboratory testing Time to platelet count recovery Thrombotic event rate Drug costs

Methodology

Methods Used to Collect/Select the Evidence: Electronic database searches (e.g., PUBMED) were conducted by the guideline author(s) and workgroup members to collect evidence for review. Expert opinion and clinical experience were also considered during discussions of the evidence. Methods Used to Formulate the Recommendations: The workgroup members agreed to adopt recommendations developed by external organizations and/or arrived at a consensus through discussion of the literature and expert experience. All recommendations endorsed or developed by the guideline workgroup were reviewed and approved by other stakeholders or committees (as appropriate). Methods Used to Assess the Quality of the Evidence/Strength of the Recommendations: Recommendations developed by external organizations maintained the evidence grade assigned within the original source document and were adopted for use at UW Health. Internally developed recommendations, or those adopted from external sources without an assigned evidence grade, were evaluated by the guideline workgroup using an algorithm adapted from the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology (see Figure 1 in Appendix A).

Rating Scheme for the Strength of the Evidence/Recommendations: See Appendix A for the rating scheme(s) used within this document.



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Cost Analysis: Medication Price per dose/vial ($) Price per day ($)

Argatroban 50 mL vial 149.48 per vial Varies based on bags per day

Apixaban 5 mg 9.14 per dose 18.28

Bivalirudin 250 mg/5 mL 380.98 per vial Varies based on bags per day

Dabigatran 150 mg 5.23 per dose 10.46

Fondaparinux (5 mg, 7.5 mg or 10 mg) 33.43 per dose 33.43

Rivaroxaban 15 mg 8.46 per dose 16.92

Recognition of Potential Health Care Disparities: Patients with HIT or HITT requiring at least 30 days of anticoagulant therapy it is important to consider both drug and monitoring costs to the patient. While warfarin is the least expensive medication, the cost for monitoring the INR should be considered. Additionally, the availability of INR monitoring and access, including transportation, to clinic facilities should be considered. Direct oral anticoagulants and fondaparinux may have medication assistance programs for patients who qualify and require minimal monitoring.

Definitions1

1. Heparin induced thrombocytopenia (HIT): immune mediated drug reaction resulting in platelet activation, increased thrombin production and increased risk for venous and arterial thrombosis.

2. Isolated HIT: HIT without thrombosis 3. HITT: HIT with thrombosis 4. Acute HIT: thrombocytopenia with a positive HIT antibody 5. Sub-acute HIT: recovered platelets with a positive HIT antibody

Introduction

HIT is an immune associated thrombocytopenia occurring in 1 to 3% of patients receiving unfractionated heparin (UFH) and 0.8% of patients receiving low molecular weight heparin (LMWH).2 See Table 2. HIT is an immunologic reaction to heparin with a typical onset of five to fourteen days after the initiation of heparin. HIT can also present within minutes to hours in patients who have been previously exposed to heparin within the past 100 days.1-3 An estimated 17-55% of patients with HIT develop venous thrombosis complications. If left untreated the event can be life or limb-threatening.1

Due to HIT being an immune reaction, it can develop from any source of heparin: intravenous, subcutaneous, heparin flushes, or heparin-coated vascular catheters.1-3 HIT is more common with intravenous administration, larger doses, and longer duration of treatment. 1-3 Risk for developing HIT is influenced by the duration and type of exposure, the dose and specific patient populations.1



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Table 2: Incidence of HIT1 Patient Population (after 4 days exposure) Incidence of HIT

Surgical (post-operative)

Heparin – Prophylactic or Therapeutic Heparin – Flush LMWH – Prophylactic or Therapeutic Cardiac surgery Orthopedic surgery

1-5% 0.1-1% 0.1-1% 1-3% 1-5%

Medical

Heparin – Prophylactic or Therapeutic LMWH – Prophylactic or Therapeutic ICU Cancer

0.1-1% 0.6% 0.4% 1%

Recommendations

Screening for HIT

1. Clinical assessment can assist in the diagnosis of HIT and clinical prediction tools have been developed to determine the probability of HIT1-3 (UW Health moderate quality of evidence, strong recommendation) 1.1 The most validated has been the 4T score (Table 3)4-6 (UW Health moderate quality of

evidence, strong recommendation) 1.1.2 The 4T score has less specificity in critically ill patients but can still be utilized

to assist with diagnosis. Other causes of thrombocytopenia should be investigated in this patient population7,8

(UW Health low quality of evidence, weak/conditional recommendation)

1.2 Low 4T scores have a low probability of HIT: 0-3%1,4-8 1.2.1 If a low 4T score is calculated then no further diagnostic testing is

recommended. Other causes of thrombocytopenia should be investigated. (UW Health moderate quality of evidence, strong recommendation)

1.2.2 Table 4 lists medications that may cause thrombocytopenia 1.3 An intermediate or high 4T score requires laboratory confirmation for diagnosis1,4-8 (UW

Health moderate quality of evidence, strong recommendation)



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Table 3. 4T Score – Scoring is based on the summation of all categories1

4T 2 Points 1 Point 0 Points

Thrombocytopenia PLT fall > 50% AND nadir > 20 AND no surgery within previous 3 days

PLT fall > 50% but surgery within previous 3 days

PLT fall 30-50% or nadir 10-19K

PLT fall < 30%

Any PLT fall with nadir <10K

Timing of PLT count

fall Fall 5-10 days after heparin

Fall within 1 day after heparin and exposed to heparin within past 5-30 days

Fall 5-10 days after heparin but unclear (e.g. missing PLT)

Fall in 1 day after heparin with exposure in past 31-100 days

Fall after 10 days

Fall < 4 days without recent heparin exposure

Thrombosis or other

sequelae Confirmed new thrombosis

Skin necrosis at injection site

Anaphylactoid reaction to IV heparin bolus

Adrenal hemorrhage

Recurrent VTE while on therapeutic anticoagulants

Suspected thrombosis

Erythematous skin lesions at heparin injection sites

Thrombosis suspected

Other causes of

Thrombocytopenia No alternative explanation for

platelet fall Sepsis without proven source

Thrombocytopenia associated with initiation of ventilator

Other

Within 72 hrs of surgery

Confirmed bacteremia or fungemia

Chemo/radiation within 20 days

DIC due to non-HIT cause

Post-transfusion purpura

Drug induced thrombocytopenia

Other

Clinical Suspicion Scoring: 0-3 = Low, 4-5 = Intermediate, 6-8 = High

Table 4. Drugs associated with thrombocytopenia1

Causative Drug

Relatively common

Glycoprotein IIb/IIIa antagonists (abciximab, eptifibatide, tirofiban) Quinine Quinidine Sulfa Antibiotics

Carbamazepine Vancomycin

Less Common

Amitriptyline Amoxicillin Piperacillin Nafcillin Cephalosporins Celecoxib Ciprofloxacin Fentanyl

Furosemide Metronidazole Naproxen Phenytoin Propranolol Ranitidine Rifampin

Confirming Diagnosis of HIT

2. Diagnosis of HIT is based on both clinical (thrombocytopenia or new thrombosis) and laboratory findings.1-3 (UW Health moderate quality of evidence, strong recommendation)

2.1 Routine laboratory screening without signs or symptoms of HIT is not recommended (UW Health moderate quality of evidence, strong recommendation)

2.2 The heparin induced platelet Ab (ELISA) can be performed in the clinical lab and should be utilized first if laboratory diagnosis is needed. (UW Health low quality of evidence, strong recommendation)



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2.3 After reviewing clinical and laboratory data if diagnosis remains uncertain consider a hematology or vascular surgery consult (UW Health low quality of evidence, weak/conditional recommendation)

Table 5. Laboratory Tests for Diagnosing HIT1,9,10

Test Lab Test Name Performed at UW Lab

Turn Around Time

Sensitivity Specificity

ELISA Enzyme Linked Immunosorbent Assay

Heparin Induced Platelet Ab

YES 3 hours (STAT) *if after 4pm call lab to arrange for

STAT testing

> 95% 50-89%

SRA Serotonin Release Assay

Heparin Dependant Ab – Serotonin Release Assay

NO 48 hours > 90% > 90%

3. A heparin induced platelet Ab (ELISA) should be ordered for intermediate or high

suspicion of HIT (as scored by 4T)1. (UW Health low quality of evidence, strong recommendation) 3.1 The optical density (OD) of the ELISA can identify the probability of HIT1

(UW Health low quality of evidence, strong recommendation)

3.1.1 An OD < 1: weak positive; more likely to be HIT negative 3.1.2 An OD > 1: strong positive; more likely to be HIT positive 3.2 A strongly positive ELISA (OD > 1) with a high suspicion for HIT can reliably confirm

the diagnosis of HIT1,9,10 (UW Health moderate quality of evidence, strong recommendation)

3.3 The ELISA method can be associated with false positive results.1 An SRA may be needed to confirm diagnosis – see Section 4.

3.4 A negative ELISA reliably rules out HIT9,10 (UW Health moderate quality of evidence, strong recommendation)

4. A heparin dependant Ab (SRA) may be considered if uncertainty exists in the diagnosis of

HIT based on the ELISA results and 4T score.1,9,10 (UW Health moderate quality of evidence, strong recommendation) 4.1 In a weakly positive ELISA with an intermediate/high suspicion for HIT (based on 4T

score) consider sending a SRA for confirmation. (UW Health low quality of evidence, strong recommendation)

4.2 A positive SRA reliably confirms the diagnosis of HIT, 1,9,10 (UW Health moderate quality of evidence, strong recommendation)

4.3 A negative SRA reliably rules out HIT9,10 (UW Health moderate quality of evidence, strong recommendation)

5. The following steps should be done for all patients with suspected or confirmed HIT

5.1 Discontinue all heparin (including flushes) and/or low molecular weight heparin orders by any route (UW Health low quality of evidence, strong recommendation)

5.2 Discontinue and reverse warfarin with phytonadione1 (UW Health low quality of evidence, strong recommendation)

5.2.1 If started less than 7 days when HIT diagnosed 5.2.2 Resume warfarin when platelet count has recovered to 100-150 x109/L 5.3 Obtain bilateral lower extremity ultrasonography to evaluate for deep vein

thrombosis, even if clinical findings are absent (UW Health low quality of evidence, weak/conditional recommendation)



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5.3.1 Consider bilateral upper extremity ultrasonography if central infusion lines are present (UW Health low quality of evidence, weak/conditional recommendation)

5.4 Start a non-heparin anticoagulant immediately upon ELISA confirmation or if awaiting results of the SRA.1 (UW Health low quality of evidence, strong recommendation)

Anticoagulant Treatment Options for HIT 6. Fondaparinux

Fondaparinux is a synthetic pentasaccaride that selectively binds to antithrombin III which results in an indirect inhibition of factor Xa. When given subcutaneously, fondaparinux has a half-life of 17-21 hours. It is eliminated by renal excretion with 80% excreted unchanged11. While fondaparinux has demonstrated similar efficacy and safety outcomes compared to traditional treatment in small studies and case reports, its use has not been completely established for treatment of HIT.11-14 6.1 Therapeutic dosing should be based on renal function and total body weight

(TBW)11– In patients with CrCl > 80 mL/min see Table 6 (UW Health low quality of evidence, weak/conditional recommendation)

6.1.1 For CrCl < 80 mL/min refer to UW Health Renal Dosing Guidelines

Table 6. Therapeutic Fondaparinux Dosing11-14

CrCl > 80 mL/min Total Body Weight (kg)

Dose

< 50 5 mg subcutaneous daily

50 - 100 7.5 mg subcutaneous daily

> 100 10 mg subcutaneous daily

6.2 Prophylactic dosing of fondaparinux for suspected or confirmed HIT may also be

considered at a dose of 2.5 mg daily if there is not an indication for therapeutic anticoagulation15 (UW Health low quality of evidence, weak/conditional recommendation)

6.3 Should not be used in patients with bacterial endocarditis or scheduled neuraxial anesthesia or spinal puncture11

(UW Health low quality of evidence, strong recommendation)

7. Argatroban Argatroban directly inhibits thrombin. When given intravenously the half-life is dependent

on hepatic function. In patients with normal hepatic function the expected half-life is 40 minutes. In patients with impaired hepatic function the half-life is prolonged to 180 minutes.16

7.1 Dosing is based on TBW16

(UW Health low quality of evidence, strong recommendation) 7.2 No initial bolus is needed. Infusion rates should be initiated and adjusted based on

recommendations in table 8 and 9. (UW Health low quality of evidence, strong recommendation)

7.3 The maximum infusion rate is 10 mcg/kg/min (UW Health low quality of evidence, strong recommendation)



https://uconnect.wisc.edu/servlet/Satellite?cid=1126675845032&pagename=B_EXTRANET_UWH_HOME%2FFlexMemberFile%2FLoad_File&c=FlexMemberFile

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Table 8. Argatroban Initial Infusion Rate16,17

Indication for dose adjustment Initial Infusion rate Based on total body weight

Normal hepatic function 2 mcg/kg/min

Moderate hepatic function 0.5 mcg/kg/min

Heart Failure, Multiple organ system failure, severe anascara, cardiac surgery

0.5-1.2 mcg/kg/min

Table 9. Argatroban Dose Adjustments16,17

Hepatic function PTT Adjustment

Normal hepatic function

< 1.5 x baseline PTT Increase by 0.5 mcg/kg/min

Goal 1.5 - 3.0 x baseline PTT (*Maximum 100 seconds)

Continue same rate

> 3 x baseline PTT Decrease by 0.5 mcg/kg/min

Moderate hepatic function

< 1.5 x baseline PTT Increase by 0.25 mcg/kg/min

Goal 1.5 - 3.0 x baseline PTT (*Maximum 100 seconds)

Continue same rate

> 3 x baseline PTT Decrease by 0.25 mcg/kg/min

7.4 PTT should be measured every 2 hours after initiation or any rate adjustment (UW Health low quality of evidence, strong recommendation)

7.5 Once 2 consecutive PTTs are in target range then PTT may be checked daily (UW Health low quality of evidence, strong recommendation)

8. Direct Oral Anticoagulants (DOACs) The use of DOACs (i.e. dabigatran, rivaroxaban, apixaban) has recently been reported as

possible alternative treatment options for HIT. Case reports and small case series are the only data currently available as large randomized, controlled trials are unlikely to occur due to the low prevalence of HIT. To date each of these agents have shown promising outcomes regarding platelet recovery and preventing thrombotic events with no major bleeding events.18-25 They offer an easier alternative for treatment as they have standardized dosing, minimal monitoring and oral administration.18 Between the 3 DOAC options rivaroxaban has the most case reports and case series data.21-25

8.1 When selecting a DOAC for treatment of HIT it is important to consider patient risk

factors. DOAC should be avoided in patients with: (UW Health low quality of evidence, weak/conditional recommendation)

8.1.1 Creatinine clearance < 30 mL/min or hemodialysis26,27 8.1.2 Weight: < 50 kg, > 120 kg or BMI > 35 kg/m2 28,29 8.1.3 The potential for procedure or surgery in 24 hours26,27 8.1.4 Critical illness 8.2 Rivaroxaban 15 mg by mouth twice daily until platelet count recovers then decrease

dose to 20 mg daily21-25 (UW Health low quality of evidence, weak/conditional recommendation)

8.2.1 Platelet count recovery defined as > 150 x 109/L or to previous baseline 8.2.2 If thrombosis confirmed continue 15 mg twice daily for 21 days then decrease

to 20 mg daily27



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8.3 Dabigatran 150 mg by mouth twice daily19,20 (UW Health low quality of evidence,

weak/conditional recommendation) 8.4 Apixaban 5 mg by mouth twice daily30 (UW Health low quality of evidence,

weak/conditional recommendation) 8.5 For duration of therapy see Section 10.

9. Special Populations

9.1 Urgent cardiac surgery with acute or sub-acute HIT or cardiac catheterization or

percutaneous coronary intervention1 9.1.1 Bivalirudin is recommended (UW Health low quality of evidence, weak/conditional

recommendation) 9.1.2 Dosing is based on TBW to a max of 150 kg (UW Health low quality of evidence,

strong recommendation) 9.1.3 No initial bolus is needed. Infusion rates should be initiated and adjusted

based on recommendations in tables 10 and 11. (UW Health low quality of evidence, strong recommendation)

Table 10. Initial Bivalirudin Infusion Rate31-35

Estimated Creatinine Clearance (mL/min)

Initial Bivalirudin Infusion Rate (mg/kg/hr)

> 60 0.15

30 – 60 0.08

< 30 / Renal Replacement Therapy 0.05

Table 11. Bivalirudin Dose Adjustments36-40

PTT (seconds)

Dose Adjustment

Monitoring Recommendation

< 1.5 x baseline Increase infusion by 20% Recheck PTT 2 hrs after rate change

1.5 to 2.5 x baseline Continue current rate Recheck PTT in 2 hrs; if within therapeutic range 2 consecutive times, check PTT every 12 hours.

>2.5 - 3 x baseline Decrease infusion by 20% Recheck PTT 2 hrs after rate change

>3 x baseline Hold for 1 hour, then restart at 50% lower rate

Recheck PTT 2 hrs after rate change

9.2 Urgent cardiac surgery with a history of HIT and a negative HIT antibody1 9.2.1 Recommend unfractionated heparin during the procedure (UW Health low

quality of evidence, weak/conditional recommendation) 9.2.2 Recommend a non-heparin anticoagulant post operatively (UW Health low

quality of evidence, weak/conditional recommendation)



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10. Transitioning Therapies Transitioning from a parenteral anticoagulant to oral anticoagulant should occur only in a

stable patient and after platelet recovery to at least 150 K/uL or upon return to usual baseline1. (UW Health low quality of evidence, strong recommendation)

10.1 Fondaparinux to warfarin1,11

10.1.1 Once platelet count normalizes start warfarin 5 mg daily (UW Health low quality of evidence, strong recommendation)

10.1.2 Dose adjust warfarin until the INR is > 2. When INR is within a therapeutic range for two consecutive results and after a minimum of 5 days, discontinue fondaparinux. (UW Health low quality of evidence, strong recommendation)

10.2 Argatroban to warfarin1,16,36 10.2.1 Adjust infusion rate to achieve a PTT level just above 1.5x normal before

starting warfarin at 5 mg daily. (UW Health low quality of evidence, strong

recommendation) 10.2.2 The combination of argatroban and warfarin creates a laboratory discrepancy

which falsely elevates INR values. During the combination target an INR of > 4.

10.2.3 Once the INR is > 4 and after a minimum of 5 days on dual anticoagulant therapy, argatroban can be held and the INR repeated in 4-6 hours. (UW Health low quality of evidence, strong recommendation)

10.2.4 If the repeat INR off of argatroban is sub-therapeutic the infusion should be resumed at the previous rate and the procedure repeated daily until the INR on warfarin alone is therapeutic. When this occurs argatroban can be discontinued. (UW Health low quality of evidence, strong recommendation)

10.3 Parenteral to DOAC11,16,20,26,27,41 10.3.1 Stop fondaparinux and start DOAC at the time of next scheduled

fondaparinux dose. (UW Health low quality of evidence, strong recommendation) 10.3.2 Stop argatroban infusion and start DOAC at the same time. (UW

Health low quality of evidence, strong recommendation) 11. Duration of Anticoagulation

11.1 Isolated HIT (HIT without thrombosis): anticoagulation should be continued for 4 weeks1

11.2 HITT: anticoagulation should be continued for at least 3 months and then assess the risk versus benefit of discontinuing therapy.2

12. Laboratory Monitoring1,11,16,26,27

(UW Health low quality of evidence, strong recommendation) 12.1 Platelets should be monitored daily for recovery. Once they have normalized (100-

150 x 109/L) they may be monitored less often. 12.2 CBC should be monitored every 48 hours while hospitalized and on an

anticoagulant. 12.3 Creatinine should be monitored as clinically indicated.



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UW Health Implementation

Potential Benefits:

Standardized approach to diagnosis of HIT

Selection of optimal treatment based on patient specific factors

Potential Harms:

Hemorrhagic complications

Thrombotic complications

Qualifying Statements: Neither fondaparinux nor the DOACs are FDA approved for the treatment of HIT. Current existing data is from case reports and/or case series. There are no randomized, controlled trials using these medications for the treatment of HIT. The workgroup agreed that case reports and case series will likely be the only available data as HIT is a rare occurrence which makes large randomized trials a challenge for this disease state. The workgroup reviewed the available data and felt the benefit to using these agents (as described in the guideline) outweighed the lack of strong clinical data. Recommendations were graded to reflect the lack of controlled clinical data. Pertinent UW Health Policies & Procedures 1. None identified Guideline Metrics 1. VTE Performance Measure – VTE 4 – UFH with dosage and platelet monitored by protocol 2. Frequency for HIT laboratory testing and false positive ELISA HIT results 3. Time to platelet count recovery 4. Thrombotic event rate

Implementation Plan/Clinical Tools 1. Guideline will be posted on uConnect in a dedicated location for Clinical Practice Guidelines. 2. Guideline will be posted on the uwhealth.org/anticoagulation webpage. 3. Release of the guideline will be advertised in the Physician/APP Briefing newsletter. 4. Content and hyperlinks within clinical tools, documents, or Health Link related to the

guideline recommendations (such as the following) will be reviewed for consistency and modified as appropriate.

Order Sets & Smart Sets IP – HIT (Heparin Induced Thrombocytopenia) Adult – Supplemental – Order Set [3596] Disclaimer Clinical practice guidelines assist clinicians by providing a framework for the evaluation and treatment of patients. This guideline outlines the preferred approach for most patients. It is not intended to replace a clinician’s judgment or to establish a protocol for all patients. It is understood that some patients will not fit the clinical condition contemplated by a guideline and that a guideline will rarely establish the only appropriate approach to a problem.



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Appendix A. Evidence Grading Scheme(s)

Figure 1. GRADE Methodology adapted by UW Health

GRADE Ranking of Evidence

High We are confident that the effect in the study reflects the actual effect.

Moderate We are quite confident that the effect in the study is close to the true effect, but it is also possible it is substantially different.

Low The true effect may differ significantly from the estimate.

Very Low The true effect is likely to be substantially different from the estimated effect.

GRADE Ratings for Recommendations For or Against Practice

Strong The net benefit of the treatment is clear, patient values and circumstances are unlikely to affect the decision.

Weak/conditional Recommendation may be conditional upon patient values and preferences, the resources available, or the setting in which the intervention will be implemented.



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Appendix B. Decision to treat HIT based on 4T score and lab test interpretation – Heparin Induced Thrombocytopenia – Adult – CPG

HIT Suspicion

4T Score

Low Intermediate / High

Continue Heparin Product & Consider Other Causes

Stop All Heparin Products & Obtain STAT ELISA

Negative ELISA

Positive ELISA (OD >1) AND High 4T Score

Obtain a SRA AND Start non-heparin anticoagulant while waiting for SRA to result and HIT to be diagnosed

Positive ELISA (OD < 1) AND Intermediate 4T Score OR Diagnostic uncertainty OR HIT diagnosis would impact future therapy (CAD patient who may need a CABG)

HIT Diagnosed Start non-heparin anticoagulant Negative

SRA

Positive SRA HIT Diagnosed Continue non-heparin anticoagulant

CPG Contact for Changes: Name: Philip J Trapskin, PharmD, BCPS Phone Number: 263-1328 Email Address: [email protected] Revised: 2/2017



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Appendix C. Selection of non-heparin anticoagulant – Heparin Induced Thrombocytopenia – Adult – CPG

CPG Contact for Changes: Name: Philip J Trapskin, PharmD, BCPS Phone Number: 263-1328 Email Address: [email protected] Revised: 2/2017



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References

1. Linkins LA, Dans AL, Moores LK, et al. Treatment and prevention of heparin-induced thrombocytopenia: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e495S-530S.

2. Shantsila E, Lip GY, Chong BH. Heparin-induced thrombocytopenia. A contemporary clinical approach to diagnosis and management. Chest. 2009;135(6):1651-1664.

3. Hassell K. Heparin-induced thrombocytopenia: diagnosis and management. Thromb Res. 2008;123 Suppl 1:S16-21.

4. Bryant A, Low J, Austin S, Joseph JE. Timely diagnosis and management of heparin-induced thrombocytopenia in a frequent request, low incidence single centre using clinical 4T's score and particle gel immunoassay. Br J Haematol. 2008;143(5):721-726.

5. Denys B, Stove V, Philippé J, Devreese K. A clinical-laboratory approach contributing to a rapid and reliable diagnosis of heparin-induced thrombocytopenia. Thromb Res. 2008;123(1):137-145.

6. Warkentin TE, Linkins LA. Non-necrotizing heparin-induced skin lesions and the 4T's score. J Thromb Haemost. 2010;8(7):1483-1485.

7. Lo GK, Juhl D, Warkentin TE, Sigouin CS, Eichler P, Greinacher A. Evaluation of pretest clinical score (4 T’s) for the diagnosis of heparin-induced thrombocytopenia in two clinical settings. J Thromb Haemost. 2006; 4:759-65.

8. Crowther MA, Cook DJ, Albert M, et al. The 4Ts scoring system for heparin-induced thrombocytopenia in medical-surgical intensive care unit patients. J Crit Care. 2010; 25(2):287-93.

9. Bakchoul T, Giptner A, Najaoui A, Bein G, Santoso S, Sachs UJ. Prospective evaluation of PF4/heparin immunoassays for the diagnosis of heparin-induced thrombocytopenia. J Thromb Haemost. 2009;7(8):1260-1265.

10. Harenberg J, Huhle G, Giese C, et al. Determination of serotonin release from platelets by enzyme immunoassay in the diagnosis of heparin-induced thrombocytopenia. Br J Haematol. 2000;109(1):182-186.

11. Product information: Arixtra® subcutaneous injection, fondaparinux sodium subcutaneous injection. GlaxoSmithKline, Research Triangle Park, NC, 2008.

12. Grouzi E, Kyriakou E, Panagou I, Spiliotopoulou I. Fondaparinux for the treatment of acute heparin-induced thrombocytopenia: a single-center experience. Clin Appl Thromb Hemost. 2010;16(6):663-667.

13. Lobo B, Finch C, Howard A, Minhas S. Fondaparinux for the treatment of patients with acute heparin-induced thrombocytopenia. Thromb Haemost. 2008;99(1):208-214.

14. Snodgrass MN, Shields J, Rai H. Efficacy and safety of fondaparinux in patients with suspected heparin-induced thrombocytopenia. Clin Appl Thromb Hemost. 2016; 22(8): 712-17

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16. Product information: argatroban IV injection. Encysive Pharmaceuticals Inc. Houston, TX. 2008.

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