Difference between revisions of "Heparin-induced thrombocytopenia"
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− | + | {{#lst:Editorial board transclusions|heme}} | |
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− | |<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] | + | |<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} [[Tutorial#Regimens|regimens]] on this page</b></font></div> |
− | <div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] | + | <div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div> |
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{{TOC limit|limit=3}} | {{TOC limit|limit=3}} | ||
=Guidelines= | =Guidelines= | ||
+ | '''Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.''' | ||
==[https://www.hematology.org/ ASH]== | ==[https://www.hematology.org/ ASH]== | ||
− | + | *'''2018:''' Cuker et al. [https://doi.org/10.1182/bloodadvances.2018024489 American Society of Hematology 2018 guidelines for management of venous thromboembolism: heparin-induced thrombocytopenia] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6258919/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30482768 PubMed] | |
− | *'''2018:''' Cuker et al. [ | + | ==[https://b-s-h.org.uk/ BSH]== |
+ | *'''2023:''' Arachchillage et al. [https://doi.org/10.1111/bjh.19180 Diagnosis and management of heparin-induced thrombocytopenia: Third edition] [https://pubmed.ncbi.nlm.nih.gov/38153164/ PubMed] | ||
+ | **'''2012:''' Watson et al. [https://doi.org/10.1111/bjh.12059 Guidelines on the diagnosis and management of heparin-induced thrombocytopenia: second edition] [https://pubmed.ncbi.nlm.nih.gov/23043677/ PubMed] | ||
+ | **'''2006:''' Keeling et al. [https://doi.org/10.1111/j.1365-2141.2006.06018.x The management of heparin-induced thrombocytopenia] [https://pubmed.ncbi.nlm.nih.gov/16643427/ PubMed] | ||
+ | ==NCCN== | ||
+ | *[https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1423 NCCN Guidelines - Cancer-Associated Venous Thromboembolic Disease] | ||
=Anticoagulation, all lines of therapy= | =Anticoagulation, all lines of therapy= | ||
==Argatroban monotherapy== | ==Argatroban monotherapy== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen=== | ===Regimen=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
− | ! style="width: | + | !style="width: 20%"|Study |
− | ! style="width: | + | !style="width: 20%"|Dates of enrollment |
− | ! style="width: | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | ! style="width: | + | !style="width: 20%"|Comparator |
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1161/01.cir.103.14.1838 Lewis et al. 2001 (ARG-911)] |
+ | |Not reported | ||
| style="background-color:#91cf61" |Prospective, historical control | | style="background-color:#91cf61" |Prospective, historical control | ||
|Multiple | |Multiple | ||
|Reduced all-cause death, all-cause amputation, and new thrombosis | |Reduced all-cause death, all-cause amputation, and new thrombosis | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1001/archinte.163.15.1849 Lewis et al. 2003 (ARG-915)] |
+ | |1996-11-01 to 1998-08-31 | ||
| style="background-color:#91cf61" |Prospective, historical control | | style="background-color:#91cf61" |Prospective, historical control | ||
|Multiple | |Multiple | ||
Line 41: | Line 45: | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4234853/ Treschan et al. 2014 (ALicia)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4234853/ Treschan et al. 2014 (ALicia)] | ||
+ | |Not reported to 2012-03-31 | ||
| style="background-color:#1a9851" |Randomized, double-blind | | style="background-color:#1a9851" |Randomized, double-blind | ||
|Lepirudin | |Lepirudin | ||
|Suggests less bleeding in surgical patients with argatroban. | |Suggests less bleeding in surgical patients with argatroban. | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1182/blood-2014-09-599498 Kang et al. 2014] |
+ | |2005-02 to 2011-06 | ||
| style="background-color:#ffffbe" |Retrospective, propensity score-matched | | style="background-color:#ffffbe" |Retrospective, propensity score-matched | ||
|[[#Fondaparinux_monotherapy|Fondaparinux]] | |[[#Fondaparinux_monotherapy|Fondaparinux]] | ||
|Similar efficacy and safety to fondaparinux | |Similar efficacy and safety to fondaparinux | ||
|- | |- | ||
− | |[ | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc4641392/ Tardy-Poncet et al. 2015] |
+ | |2009-09-10 to 2011-02-02 | ||
| style="background-color:#91cf61" |Prospective | | style="background-color:#91cf61" |Prospective | ||
|None | |None | ||
Line 56: | Line 63: | ||
|} | |} | ||
''Note: In ALicia, only 15 patients (23%) in the study had confirmed HIT.'' | ''Note: In ALicia, only 15 patients (23%) in the study had confirmed HIT.'' | ||
− | |||
''Note: In the study by Tardy-Poncet et al. only 20 patients were enrolled, 16 with confirmed by as judged by an independent scientific committee. The majority (14, 70%) were in an intensive care unit, and six patients died due to their underlying medical condition.'' | ''Note: In the study by Tardy-Poncet et al. only 20 patients were enrolled, 16 with confirmed by as judged by an independent scientific committee. The majority (14, 70%) were in an intensive care unit, and six patients died due to their underlying medical condition.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Anticoagulation==== | ====Anticoagulation==== | ||
− | + | *[[Argatroban (Acova)]] by the following study-specific criteria: | |
− | * | + | **ARG-911 & ARG-915: 2 mcg/kg/min IV adjusted to maintain activated partial thromboplastin time 1.5 to 3 times baseline value. |
− | * | + | **ALicia, without liver dysfunction: 0.5 mcg/kg/min IV adjusted to maintain activated partial thromboplastin time 1.5 to 2 times baseline value. |
− | * | + | **ALicia, with severe liver dysfunction (bilirubin >4 mg/dL): 0.25 mcg/kg/min IV adjusted to maintain activated partial thromboplastin time 1.5 to 2 times baseline value. |
− | *Tardy-Poncet: Starting dose of 1 mcg/kg/min IV but those with hepatic impairment or at risk of decreased hepatic perfusion were recommended to start at 0.5 mcg/kg/min. Child-Pugh Class C patients were excluded. | + | **Tardy-Poncet: Starting dose of 1 mcg/kg/min IV but those with hepatic impairment or at risk of decreased hepatic perfusion were recommended to start at 0.5 mcg/kg/min. Child-Pugh Class C patients were excluded. |
+ | </div></div> | ||
===References=== | ===References=== | ||
− | + | #'''ARG-911:''' Lewis BE, Wallis DE, Berkowitz SD, Matthai WH, Fareed J, Walenga JM, Bartholomew J, Sham R, Lerner RG, Zeigler ZR, Rustagi PK, Jang IK, Rifkin SD, Moran J, Hursting MJ, Kelton JG; ARG-911 Study Investigators. Argatroban anticoagulant therapy in patients with heparin-induced thrombocytopenia. Circulation. 2001 Apr 10;103(14):1838-43. [https://doi.org/10.1161/01.cir.103.14.1838 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11294800/ PubMed] | |
− | #'''ARG-911:''' Lewis BE, Wallis DE, Berkowitz SD, Matthai WH, Fareed J, Walenga JM, Bartholomew J, Sham R, Lerner RG, Zeigler ZR, Rustagi PK, Jang IK, Rifkin SD, Moran J, Hursting MJ, Kelton JG; ARG-911 Study Investigators. Argatroban anticoagulant therapy in patients with heparin-induced thrombocytopenia. Circulation. 2001 Apr 10;103(14):1838-43. [https:// | + | #'''ARG-915:''' Lewis BE, Wallis DE, Leya F, Hursting MJ, Kelton JG; ARG-915 Study Investigators. Argatroban anticoagulation in patients with heparin-induced thrombocytopenia. Arch Intern Med. 2003;164:1849-1856. [https://doi.org/10.1001/archinte.163.15.1849 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12912723/ PubMed] |
− | #'''ARG-915:''' Lewis BE, Wallis DE, Leya F, Hursting MJ, Kelton JG; ARG-915 Study Investigators. Argatroban anticoagulation in patients with heparin-induced thrombocytopenia. Arch Intern Med. 2003;164:1849-1856. [https:// | + | #'''ALicia:''' Treschan TA, Schaefer MS, Geib J, Bahlmann A, Brezina T, Werner P, Golla E, Greinacher A, Pannen B, Kindgen-Milles D, Kienbaum P, Beiderlinden M. Argatroban versus lepirudin in critically ill patients (ALicia): a randomized controlled trial. Critical Care. 2014 Oct 25;18(5):588. [https://doi.org/10.1186/s13054-014-0588-8 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4234853/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25344113/ PubMed] [https://clinicaltrials.gov/study/NCT00798525 NCT00798525] |
− | #'''ALicia:''' Treschan TA, Schaefer MS, Geib J, Bahlmann A, Brezina T, Werner P, Golla E, Greinacher A, Pannen B, Kindgen-Milles D, Kienbaum P, Beiderlinden M. Argatroban versus lepirudin in critically ill patients (ALicia): a randomized controlled trial. Critical Care. 2014 Oct 25;18(5):588. [https:// | + | #'''Retrospective:''' Kang M, Alahmadi M, Sawh S, Kovacs MJ, Lazo-Langner A. Fondaparinux for the treatment of suspected heparin-induced thrombocytopenia: a propensity score-matched study. Blood. 2015 Feb 5;125(6):924-9. Epub 2014 Dec 16. [https://doi.org/10.1182/blood-2014-09-599498 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25515959/ PubMed] |
− | #'''Retrospective:''' Kang M, Alahmadi M, Sawh S, Kovacs MJ, Lazo-Langner A. Fondaparinux for the treatment of suspected heparin-induced thrombocytopenia: a propensity score-matched study. Blood. 2015 Feb 5;125(6):924-9. [ | + | #Tardy-Poncet B, Nguyen P, Thiranos JC, Morange PE, Biron-Andreani C, Gruel Y, Morel J, Wynckel A, Grunebaum L, Villacorta-Torres J, Grosjean S, de Maistre E. Argatroban in the management of heparin-induced thrombocytopenia: a multicenter clinical trial. Crit Care. 2015 Nov 11;19:396. [https://doi.org/10.1186/s13054-015-1109-0 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc4641392/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26556106/ PubMed] |
− | #Tardy-Poncet B, Nguyen P, Thiranos JC, Morange PE, Biron-Andreani C, Gruel Y, Morel J, Wynckel A, Grunebaum L, Villacorta-Torres J, Grosjean S, de Maistre E. Argatroban in the management of heparin-induced thrombocytopenia: a multicenter clinical trial. Crit Care. 2015 Nov 11;19:396. [https:// | ||
− | |||
==Danaparoid monotherapy== | ==Danaparoid monotherapy== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen=== | ===Regimen=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
− | ! style="width: | + | !style="width: 20%"|Study |
− | ! style="width: | + | !style="width: 20%"|Dates of enrollment |
− | ! style="width: | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | ! style="width: | + | !style="width: 20%"|Comparator |
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1055/s-0037-1616046 Chong et al. 2001] |
+ | |Not reported in abstract | ||
| style="background-color:#1a9851" |Phase 3 | | style="background-color:#1a9851" |Phase 3 | ||
|Dextran 70 | |Dextran 70 | ||
|Improved complete clinical recovery with danaparoid | |Improved complete clinical recovery with danaparoid | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1182/blood-2014-09-599498 Kang et al. 2014] |
+ | |2005-02 to 2011-06 | ||
| style="background-color:#ffffbe" |Retrospective, propensity score-matched | | style="background-color:#ffffbe" |Retrospective, propensity score-matched | ||
|[[#Fondaparinux_monotherapy|Fondaparinux]] | |[[#Fondaparinux_monotherapy|Fondaparinux]] | ||
|Similar efficacy and safety to fondaparinux | |Similar efficacy and safety to fondaparinux | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
====Anticoagulation==== | ====Anticoagulation==== | ||
− | |||
*[[Danaparoid (Orgaran)]] 2400 anti-Xa units IV bolus once on day 1, then 400 units/hr IV for 2 hours, then 300 units/hr IV for 2 hours, then 200 units/hr IV continuous infusion for 120 hours (total dose: 6200 units) | *[[Danaparoid (Orgaran)]] 2400 anti-Xa units IV bolus once on day 1, then 400 units/hr IV for 2 hours, then 300 units/hr IV for 2 hours, then 200 units/hr IV continuous infusion for 120 hours (total dose: 6200 units) | ||
− | |||
'''5-day course''' | '''5-day course''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | + | #Chong BH, Gallus AS, Cade JF, Magnani H, Manoharan A, Oldmeadow M, Arthur C, Rickard K, Gallo J, Lloyd J, Seshadri P, Chesterman CN; Australian HIT Study Group. Prospective randomised open-label comparison of danaparoid with dextran 70 in the treatment of heparin-induced thrombocytopaenia with thrombosis: a clinical outcome study. Thromb Haemost. 2001 Nov;86(5):1170-5. [https://doi.org/10.1055/s-0037-1616046 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11816702/ PubMed] | |
− | #Chong BH, Gallus AS, Cade JF, Magnani H, Manoharan A, Oldmeadow M, Arthur C, Rickard K, Gallo J, Lloyd J, Seshadri P, Chesterman CN; Australian HIT Study Group. Prospective randomised open-label comparison of danaparoid with dextran 70 in the treatment of heparin-induced thrombocytopaenia with thrombosis: a clinical outcome study. Thromb Haemost. 2001 Nov;86(5):1170-5. [https:// | + | #'''Retrospective:''' Kang M, Alahmadi M, Sawh S, Kovacs MJ, Lazo-Langner A. Fondaparinux for the treatment of suspected heparin-induced thrombocytopenia: a propensity score-matched study. Blood. 2015 Feb 5;125(6):924-9. Epub 2014 Dec 16. [https://doi.org/10.1182/blood-2014-09-599498 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25515959/ PubMed] |
− | #'''Retrospective:''' Kang M, Alahmadi M, Sawh S, Kovacs MJ, Lazo-Langner A. Fondaparinux for the treatment of suspected heparin-induced thrombocytopenia: a propensity score-matched study. Blood. 2015 Feb 5;125(6):924-9. [ | ||
− | |||
==Fondaparinux monotherapy== | ==Fondaparinux monotherapy== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen=== | ===Regimen=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
− | ! style="width: | + | !style="width: 20%"|Study |
− | ! style="width: | + | !style="width: 20%"|Dates of enrollment |
− | ! style="width: | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | ! style="width: | + | !style="width: 20%"|Comparator |
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1182/blood-2014-09-599498 Kang et al. 2014] |
+ | |2005-02 to 2011-06 | ||
| style="background-color:#ffffbe" |Retrospective, propensity score-matched | | style="background-color:#ffffbe" |Retrospective, propensity score-matched | ||
− | |1. [[#Argatroban_monotherapy|Argatroban]]<br> 2. [[#Danaparoid_monotherapy|Danaparoid]] | + | |1. [[#Argatroban_monotherapy|Argatroban]]<br>2. [[#Danaparoid_monotherapy|Danaparoid]] |
|Similar efficacy and safety to argatroban, danaparoid | |Similar efficacy and safety to argatroban, danaparoid | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
====Anticoagulation==== | ====Anticoagulation==== | ||
− | |||
*[[Fondaparinux (Arixtra)]] | *[[Fondaparinux (Arixtra)]] | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | + | #'''Retrospective:''' Kang M, Alahmadi M, Sawh S, Kovacs MJ, Lazo-Langner A. Fondaparinux for the treatment of suspected heparin-induced thrombocytopenia: a propensity score-matched study. Blood. 2015 Feb 5;125(6):924-9. Epub 2014 Dec 16. [https://doi.org/10.1182/blood-2014-09-599498 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25515959/ PubMed] | |
− | #'''Retrospective:''' Kang M, Alahmadi M, Sawh S, Kovacs MJ, Lazo-Langner A. Fondaparinux for the treatment of suspected heparin-induced thrombocytopenia: a propensity score-matched study. Blood. 2015 Feb 5;125(6):924-9. [ | ||
− | |||
==Lepirudin monotherapy== | ==Lepirudin monotherapy== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen=== | ===Regimen=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
− | ! style="width: | + | !style="width: 20%"|Study |
− | ! style="width: | + | !style="width: 20%"|Dates of enrollment |
− | ! style="width: | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | ! style="width: | + | !style="width: 20%"|Comparator |
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4234853/ Treschan et al. 2014 (ALicia)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4234853/ Treschan et al. 2014 (ALicia)] | ||
+ | |Not reported to 2012-03-31 | ||
| style="background-color:#1a9851" |Randomized, double-blind | | style="background-color:#1a9851" |Randomized, double-blind | ||
|[[#Argatroban_monotherapy|Argatroban]] | |[[#Argatroban_monotherapy|Argatroban]] | ||
Line 151: | Line 148: | ||
|} | |} | ||
''Note: Only 15 patients (23%) in the study had confirmed HIT.'' | ''Note: Only 15 patients (23%) in the study had confirmed HIT.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Anticoagulation==== | ====Anticoagulation==== | ||
− | + | *[[Lepirudin (Refludan)]] by the following renal function-based criteria: | |
− | *[[Lepirudin (Refludan)]] by the following criteria: | + | **Continuous renal replacement therapy: 5 mcg/kg/hr IV continuous infusion, adjusted to maintain activated partial thromboplastin time 1.5 to 2 times baseline value |
− | ** | + | **Creatinine 1.3 mg/dl or more: 10 mcg/kg/hr IV continuous infusion, adjusted to maintain activated partial thromboplastin time 1.5 to 2 times baseline value |
− | ** | + | **Creatinine less than 1.3 mg/dl: 50 mcg/kg/hr IV continuous infusion, adjusted to maintain activated partial thromboplastin time 1.5 to 2 times baseline value |
− | ** | + | </div></div> |
===References=== | ===References=== | ||
− | + | #'''ALicia:''' Treschan TA, Schaefer MS, Geib J, Bahlmann A, Brezina T, Werner P, Golla E, Greinacher A, Pannen B, Kindgen-Milles D, Kienbaum P, Beiderlinden M. Argatroban versus lepirudin in critically ill patients (ALicia): a randomized controlled trial. Critical Care. 2014 Oct 25;18(5):588. [https://doi.org/10.1186/s13054-014-0588-8 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4234853/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25344113/ PubMed] [https://clinicaltrials.gov/study/NCT00798525 NCT00798525] | |
− | #'''ALicia:''' Treschan TA, Schaefer MS, Geib J, Bahlmann A, Brezina T, Werner P, Golla E, Greinacher A, Pannen B, Kindgen-Milles D, Kienbaum P, Beiderlinden M. Argatroban versus lepirudin in critically ill patients (ALicia): a randomized controlled trial. Critical Care. 2014 Oct 25;18(5):588. [https:// | ||
− | |||
==Rivaroxaban monotherapy== | ==Rivaroxaban monotherapy== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen=== | ===Regimen=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
− | ! style="width: | + | !style="width: 20%"|Study |
− | ! style="width: | + | !style="width: 20%"|Dates of enrollment |
− | ! style="width: | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | ! style="width: | + | !style="width: 20%"|Comparator |
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1111/jth.13330 Linkins et al. 2016 (McMaster 2012-02-09)] |
+ | |2013-01 to 2015-07 | ||
| style="background-color:#91cf61" |Prospective cohort | | style="background-color:#91cf61" |Prospective cohort | ||
|None | |None | ||
Line 180: | Line 175: | ||
|} | |} | ||
''Note: In the first prospective study of DOACs in HIT by Linkins, 22 patients were enrolled with suspected HIT. The overall symptomatic recurrent VTE rate was 4.5% (1 patient out of 22), but only 12 of the patients were confirmed to have HIT. The thrombotic event rate among HIT-positive participants was 8.3%. The study was stopped early due to slow accrual but had enrolled the minimum required number of HIT patients.'' | ''Note: In the first prospective study of DOACs in HIT by Linkins, 22 patients were enrolled with suspected HIT. The overall symptomatic recurrent VTE rate was 4.5% (1 patient out of 22), but only 12 of the patients were confirmed to have HIT. The thrombotic event rate among HIT-positive participants was 8.3%. The study was stopped early due to slow accrual but had enrolled the minimum required number of HIT patients.'' | ||
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
====Anticoagulation==== | ====Anticoagulation==== | ||
− | |||
*[[Rivaroxaban (Xarelto)]]: 15 mg PO twice per day until platelet recovery (or until day 21 if acute thrombosis present at study entry), then 20 mg once per day until day 30 | *[[Rivaroxaban (Xarelto)]]: 15 mg PO twice per day until platelet recovery (or until day 21 if acute thrombosis present at study entry), then 20 mg once per day until day 30 | ||
− | + | '''30-day course''' | |
+ | </div></div> | ||
===References=== | ===References=== | ||
− | + | #'''McMaster 2012-02-09:''' Linkins LA, Warkentin TE, Pai M, Shivakumar S, Manji RA, Wells PS, Wu C, Nazi I, Crowther MA. Rivaroxaban for treatment of suspected or confirmed heparin-induced thrombocytopenia study. J Thromb Haemost. 2016 Jun;14(6):1206-10. Epub 2016 May 10. [https://doi.org/10.1111/jth.13330 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27061271/ PubMed] [https://clinicaltrials.gov/study/NCT01598168 NCT01598168] | |
− | #'''McMaster 2012-02-09:''' Linkins LA, Warkentin TE, Pai M, Shivakumar S, Manji RA, Wells PS, Wu C, Nazi I, Crowther MA. Rivaroxaban for treatment of suspected or confirmed heparin-induced thrombocytopenia study. J Thromb Haemost. 2016 Jun;14(6):1206-10. [https:// | + | ##'''Update:''' Warkentin TE, Pai M, Linkins LA. Direct oral anticoagulants for treatment of HIT: update of Hamilton experience and literature review. Blood. 2017 Aug 31; 130:1104-1113. Epub 2017 Jun 23. [https://doi.org/10.1182/blood-2017-04-778993 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28646118/ PubMed] |
− | ##'''Update:''' Warkentin TE, Pai M, Linkins LA. Direct oral anticoagulants for treatment of HIT: update of Hamilton experience and literature review. Blood. 2017; 130:1104-1113. [ | ||
=Other Treatments, all lines of therapy= | =Other Treatments, all lines of therapy= | ||
− | |||
==IVIG monotherapy== | ==IVIG monotherapy== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen=== | ===Regimen=== | ||
{| class="wikitable" style="width: 60%; text-align:center;" | {| class="wikitable" style="width: 60%; text-align:center;" | ||
Line 203: | Line 193: | ||
!style="width: 33%"|[[Levels_of_Evidence#Efficacy|Efficacy]] | !style="width: 33%"|[[Levels_of_Evidence#Efficacy|Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.7326/0003-4819-111-11-946 Frame et al. 1989] |
| style="background-color:#ffffbe" |First published report | | style="background-color:#ffffbe" |First published report | ||
|First report of IVIg use in HIT | |First report of IVIg use in HIT | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1023/a:1023238915316 Winder et al. 1998] |
| style="background-color:#ffffbe" |Case series | | style="background-color:#ffffbe" |Case series | ||
|Three additional cases in the literature | |Three additional cases in the literature | ||
Line 219: | Line 209: | ||
|Two additional cases | |Two additional cases | ||
|} | |} | ||
− | ''Note | + | ''Note: There is a growing interest in the use of intravenous immunoglobulin for difficult cases of heparin-induced thrombocytopenia. There are no prospective, randomized studies, but there is a growing body of scientific literature to support the rationale in certain select cases. Thus, IVIg is included on this page for reference.'' |
− | ====Supportive | + | <div class="toccolours" style="background-color:#b3e2cd"> |
+ | ====Supportive therapy==== | ||
*[[Intravenous immunoglobulin (IVIG)]] 1 g/kg IV once per day for two days (Winder et al., Padmanabhan et al., and Park et al.) | *[[Intravenous immunoglobulin (IVIG)]] 1 g/kg IV once per day for two days (Winder et al., Padmanabhan et al., and Park et al.) | ||
**The case reported from 1989 used 0.4 gm/kg/d for three days. | **The case reported from 1989 used 0.4 gm/kg/d for three days. | ||
− | + | </div></div> | |
− | + | ===References=== | |
− | + | #'''Case report:''' Frame JN, Mulvey KP, Phares JC, Anderson MJ. Correction of severe heparin-associated thrombocytopenia with intravenous immunoglobulin. Ann Intern Med. 1989 Dec 1;111(11):946-7. [https://doi.org/10.7326/0003-4819-111-11-946 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2510573/ PubMed] | |
− | #'''Case report:''' Frame JN, Mulvey KP, Phares JC, Anderson MJ. Correction of severe heparin-associated thrombocytopenia with intravenous immunoglobulin. Ann Intern Med. 1989 Dec 1;111(11):946-7. [https:// | + | #'''Case series:''' Winder A, Shoenfeld Y, Hochman R, Keren G, Levy Y, Eldor A. High-dose intravenous gamma-globulins for heparin-induced thrombocytopenia: a prompt response. J Clin Immunol. 1998 Sep;18(5):330-4. [https://doi.org/10.1023/a:1023238915316 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9793825/ PubMed] |
− | #'''Case series:''' Winder A, Shoenfeld Y, Hochman R, Keren G, Levy Y, Eldor A. High-dose intravenous gamma-globulins for heparin-induced thrombocytopenia: a prompt response. J Clin Immunol. 1998 Sep;18(5):330-4. | + | #'''Case series:''' Padmanabhan A, Jones CG, Pechauer SM, Curtis BR, Bougie DW, Irani MS, Bryant BJ, Alperin JB, Deloughery TG, Mulvey KP, Dhakal B, Wen R, Wang D, Aster RH. IVIg for Treatment of Severe Refractory Heparin-Induced Thrombocytopenia. Chest. 2017 Sep;152(3):478-485. Epub 2017 Apr 17. [https://doi.org/10.1016/j.chest.2017.03.050 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5812774/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28427966/ PubMed] |
− | #'''Case series:''' Padmanabhan A, Jones CG, Pechauer SM, Curtis BR, Bougie DW, Irani MS, Bryant BJ, Alperin JB, Deloughery TG, Mulvey KP, Dhakal B, Wen R, Wang D, Aster RH. IVIg for Treatment of Severe Refractory Heparin-Induced Thrombocytopenia. Chest. 2017 Sep;152(3):478-485. Epub 2017 Apr 17. [https://doi.org/10.1016/j.chest.2017.03.050 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5812774/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28427966 PubMed] | + | #'''Case series:''' Park BD, Kumar M, Nagalla S, De Simone N, Aster RH, Padmanabhan A, Sarode R, Rambally S. Intravenous immunoglobulin as an adjunct therapy in persisting heparin-induced thrombocytopenia. Transfus Apher Sci. 2018 Aug;57(4):561-565. Epub 2018 Jun 26. [https://doi.org/10.1016/j.transci.2018.06.007 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6482842/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30244713/ PubMed] |
− | #'''Case series:''' Park BD, Kumar M, Nagalla S, De Simone N, Aster RH, Padmanabhan A, Sarode R, Rambally S. Intravenous immunoglobulin as an adjunct therapy in persisting heparin-induced thrombocytopenia. Transfus Apher Sci. 2018 Aug;57(4):561-565. Epub 2018 Jun 26. | ||
− | |||
[[Category:Heparin-induced thrombocytopenia regimens]] | [[Category:Heparin-induced thrombocytopenia regimens]] | ||
[[Category:Disease-specific pages]] | [[Category:Disease-specific pages]] | ||
[[Category:Autoimmune hematologic conditions]] | [[Category:Autoimmune hematologic conditions]] | ||
[[Category:Thrombotic disorders]] | [[Category:Thrombotic disorders]] |
Latest revision as of 23:40, 6 July 2024
Section editor | |
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Benjamin Tillman, MD Vanderbilt University Nashville, TN, USA |
0 regimens on this page
0 variants on this page
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Guidelines
Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.
ASH
- 2018: Cuker et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: heparin-induced thrombocytopenia link to PMC article PubMed
BSH
- 2023: Arachchillage et al. Diagnosis and management of heparin-induced thrombocytopenia: Third edition PubMed
- 2012: Watson et al. Guidelines on the diagnosis and management of heparin-induced thrombocytopenia: second edition PubMed
- 2006: Keeling et al. The management of heparin-induced thrombocytopenia PubMed
NCCN
Anticoagulation, all lines of therapy
Argatroban monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Lewis et al. 2001 (ARG-911) | Not reported | Prospective, historical control | Multiple | Reduced all-cause death, all-cause amputation, and new thrombosis |
Lewis et al. 2003 (ARG-915) | 1996-11-01 to 1998-08-31 | Prospective, historical control | Multiple | Reduced all-cause death, all-cause amputation, or new thrombosis |
Treschan et al. 2014 (ALicia) | Not reported to 2012-03-31 | Randomized, double-blind | Lepirudin | Suggests less bleeding in surgical patients with argatroban. |
Kang et al. 2014 | 2005-02 to 2011-06 | Retrospective, propensity score-matched | Fondaparinux | Similar efficacy and safety to fondaparinux |
Tardy-Poncet et al. 2015 | 2009-09-10 to 2011-02-02 | Prospective | None | New or extended thrombosis in 25% of patients and major bleeding in 15%. |
Note: In ALicia, only 15 patients (23%) in the study had confirmed HIT. Note: In the study by Tardy-Poncet et al. only 20 patients were enrolled, 16 with confirmed by as judged by an independent scientific committee. The majority (14, 70%) were in an intensive care unit, and six patients died due to their underlying medical condition.
Anticoagulation
- Argatroban (Acova) by the following study-specific criteria:
- ARG-911 & ARG-915: 2 mcg/kg/min IV adjusted to maintain activated partial thromboplastin time 1.5 to 3 times baseline value.
- ALicia, without liver dysfunction: 0.5 mcg/kg/min IV adjusted to maintain activated partial thromboplastin time 1.5 to 2 times baseline value.
- ALicia, with severe liver dysfunction (bilirubin >4 mg/dL): 0.25 mcg/kg/min IV adjusted to maintain activated partial thromboplastin time 1.5 to 2 times baseline value.
- Tardy-Poncet: Starting dose of 1 mcg/kg/min IV but those with hepatic impairment or at risk of decreased hepatic perfusion were recommended to start at 0.5 mcg/kg/min. Child-Pugh Class C patients were excluded.
References
- ARG-911: Lewis BE, Wallis DE, Berkowitz SD, Matthai WH, Fareed J, Walenga JM, Bartholomew J, Sham R, Lerner RG, Zeigler ZR, Rustagi PK, Jang IK, Rifkin SD, Moran J, Hursting MJ, Kelton JG; ARG-911 Study Investigators. Argatroban anticoagulant therapy in patients with heparin-induced thrombocytopenia. Circulation. 2001 Apr 10;103(14):1838-43. link to original article PubMed
- ARG-915: Lewis BE, Wallis DE, Leya F, Hursting MJ, Kelton JG; ARG-915 Study Investigators. Argatroban anticoagulation in patients with heparin-induced thrombocytopenia. Arch Intern Med. 2003;164:1849-1856. link to original article PubMed
- ALicia: Treschan TA, Schaefer MS, Geib J, Bahlmann A, Brezina T, Werner P, Golla E, Greinacher A, Pannen B, Kindgen-Milles D, Kienbaum P, Beiderlinden M. Argatroban versus lepirudin in critically ill patients (ALicia): a randomized controlled trial. Critical Care. 2014 Oct 25;18(5):588. link to original article link to PMC article PubMed NCT00798525
- Retrospective: Kang M, Alahmadi M, Sawh S, Kovacs MJ, Lazo-Langner A. Fondaparinux for the treatment of suspected heparin-induced thrombocytopenia: a propensity score-matched study. Blood. 2015 Feb 5;125(6):924-9. Epub 2014 Dec 16. link to original article PubMed
- Tardy-Poncet B, Nguyen P, Thiranos JC, Morange PE, Biron-Andreani C, Gruel Y, Morel J, Wynckel A, Grunebaum L, Villacorta-Torres J, Grosjean S, de Maistre E. Argatroban in the management of heparin-induced thrombocytopenia: a multicenter clinical trial. Crit Care. 2015 Nov 11;19:396. link to original article link to PMC article PubMed
Danaparoid monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Chong et al. 2001 | Not reported in abstract | Phase 3 | Dextran 70 | Improved complete clinical recovery with danaparoid |
Kang et al. 2014 | 2005-02 to 2011-06 | Retrospective, propensity score-matched | Fondaparinux | Similar efficacy and safety to fondaparinux |
Anticoagulation
- Danaparoid (Orgaran) 2400 anti-Xa units IV bolus once on day 1, then 400 units/hr IV for 2 hours, then 300 units/hr IV for 2 hours, then 200 units/hr IV continuous infusion for 120 hours (total dose: 6200 units)
5-day course
References
- Chong BH, Gallus AS, Cade JF, Magnani H, Manoharan A, Oldmeadow M, Arthur C, Rickard K, Gallo J, Lloyd J, Seshadri P, Chesterman CN; Australian HIT Study Group. Prospective randomised open-label comparison of danaparoid with dextran 70 in the treatment of heparin-induced thrombocytopaenia with thrombosis: a clinical outcome study. Thromb Haemost. 2001 Nov;86(5):1170-5. link to original article PubMed
- Retrospective: Kang M, Alahmadi M, Sawh S, Kovacs MJ, Lazo-Langner A. Fondaparinux for the treatment of suspected heparin-induced thrombocytopenia: a propensity score-matched study. Blood. 2015 Feb 5;125(6):924-9. Epub 2014 Dec 16. link to original article PubMed
Fondaparinux monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Kang et al. 2014 | 2005-02 to 2011-06 | Retrospective, propensity score-matched | 1. Argatroban 2. Danaparoid |
Similar efficacy and safety to argatroban, danaparoid |
Anticoagulation
References
- Retrospective: Kang M, Alahmadi M, Sawh S, Kovacs MJ, Lazo-Langner A. Fondaparinux for the treatment of suspected heparin-induced thrombocytopenia: a propensity score-matched study. Blood. 2015 Feb 5;125(6):924-9. Epub 2014 Dec 16. link to original article PubMed
Lepirudin monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Treschan et al. 2014 (ALicia) | Not reported to 2012-03-31 | Randomized, double-blind | Argatroban | Suggests less bleeding in surgical patients with argatroban. |
Note: Only 15 patients (23%) in the study had confirmed HIT.
Anticoagulation
- Lepirudin (Refludan) by the following renal function-based criteria:
- Continuous renal replacement therapy: 5 mcg/kg/hr IV continuous infusion, adjusted to maintain activated partial thromboplastin time 1.5 to 2 times baseline value
- Creatinine 1.3 mg/dl or more: 10 mcg/kg/hr IV continuous infusion, adjusted to maintain activated partial thromboplastin time 1.5 to 2 times baseline value
- Creatinine less than 1.3 mg/dl: 50 mcg/kg/hr IV continuous infusion, adjusted to maintain activated partial thromboplastin time 1.5 to 2 times baseline value
References
- ALicia: Treschan TA, Schaefer MS, Geib J, Bahlmann A, Brezina T, Werner P, Golla E, Greinacher A, Pannen B, Kindgen-Milles D, Kienbaum P, Beiderlinden M. Argatroban versus lepirudin in critically ill patients (ALicia): a randomized controlled trial. Critical Care. 2014 Oct 25;18(5):588. link to original article link to PMC article PubMed NCT00798525
Rivaroxaban monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Linkins et al. 2016 (McMaster 2012-02-09) | 2013-01 to 2015-07 | Prospective cohort | None | New thrombosis in one of the HIT patients (8.3%) |
Note: In the first prospective study of DOACs in HIT by Linkins, 22 patients were enrolled with suspected HIT. The overall symptomatic recurrent VTE rate was 4.5% (1 patient out of 22), but only 12 of the patients were confirmed to have HIT. The thrombotic event rate among HIT-positive participants was 8.3%. The study was stopped early due to slow accrual but had enrolled the minimum required number of HIT patients.
Anticoagulation
- Rivaroxaban (Xarelto): 15 mg PO twice per day until platelet recovery (or until day 21 if acute thrombosis present at study entry), then 20 mg once per day until day 30
30-day course
References
- McMaster 2012-02-09: Linkins LA, Warkentin TE, Pai M, Shivakumar S, Manji RA, Wells PS, Wu C, Nazi I, Crowther MA. Rivaroxaban for treatment of suspected or confirmed heparin-induced thrombocytopenia study. J Thromb Haemost. 2016 Jun;14(6):1206-10. Epub 2016 May 10. link to original article PubMed NCT01598168
- Update: Warkentin TE, Pai M, Linkins LA. Direct oral anticoagulants for treatment of HIT: update of Hamilton experience and literature review. Blood. 2017 Aug 31; 130:1104-1113. Epub 2017 Jun 23. link to original article PubMed
Other Treatments, all lines of therapy
IVIG monotherapy
Regimen
Study | Evidence | Efficacy |
---|---|---|
Frame et al. 1989 | First published report | First report of IVIg use in HIT |
Winder et al. 1998 | Case series | Three additional cases in the literature |
Padmanabhan et al. 2017 | Case series | Three refractory cases with resolution of thrombocytopenia |
Park et al. 2018 | Case series | Two additional cases |
Note: There is a growing interest in the use of intravenous immunoglobulin for difficult cases of heparin-induced thrombocytopenia. There are no prospective, randomized studies, but there is a growing body of scientific literature to support the rationale in certain select cases. Thus, IVIg is included on this page for reference.
Supportive therapy
- Intravenous immunoglobulin (IVIG) 1 g/kg IV once per day for two days (Winder et al., Padmanabhan et al., and Park et al.)
- The case reported from 1989 used 0.4 gm/kg/d for three days.
References
- Case report: Frame JN, Mulvey KP, Phares JC, Anderson MJ. Correction of severe heparin-associated thrombocytopenia with intravenous immunoglobulin. Ann Intern Med. 1989 Dec 1;111(11):946-7. link to original article PubMed
- Case series: Winder A, Shoenfeld Y, Hochman R, Keren G, Levy Y, Eldor A. High-dose intravenous gamma-globulins for heparin-induced thrombocytopenia: a prompt response. J Clin Immunol. 1998 Sep;18(5):330-4. link to original article PubMed
- Case series: Padmanabhan A, Jones CG, Pechauer SM, Curtis BR, Bougie DW, Irani MS, Bryant BJ, Alperin JB, Deloughery TG, Mulvey KP, Dhakal B, Wen R, Wang D, Aster RH. IVIg for Treatment of Severe Refractory Heparin-Induced Thrombocytopenia. Chest. 2017 Sep;152(3):478-485. Epub 2017 Apr 17. link to original article link to PMC article PubMed
- Case series: Park BD, Kumar M, Nagalla S, De Simone N, Aster RH, Padmanabhan A, Sarode R, Rambally S. Intravenous immunoglobulin as an adjunct therapy in persisting heparin-induced thrombocytopenia. Transfus Apher Sci. 2018 Aug;57(4):561-565. Epub 2018 Jun 26. link to original article link to PMC article PubMed