This is the current release of the guideline.

This guideline updates a previous version: Warkentin TE, Greinacher A. Heparin-induced thrombocytopenia: recognition, treatment, and prevention: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004 Sep;126(3 Suppl):311S-37S.

The grades of recommendation (1A, 1B, 1C, 2A, 2B, 2C) are defined at the end of the "Major Recommendations" field.

Recognition of Heparin-Induced Thrombocytopenia (HIT)

Platelet Count Monitoring for HIT

For patients receiving heparin in whom the clinician considers the risk of heparin-induced thrombocytopenia (HIT) to be > 1.0%, the guideline developers recommend platelet count monitoring over no platelet count monitoring (Grade 1C). For patients receiving heparin who have an estimated risk of HIT of 0.1 to 1.0%, the guideline developers suggest platelet count monitoring over no platelet count monitoring (Grade 2C).

Platelet Count Monitoring of Patients Recently Treated With Heparin

For patients who are starting unfractionated heparin (UFH) or low molecular weight heparin (LMWH) treatment and who have received UFH within the past 100 days, or those patients in whom exposure history is uncertain, the guideline developers recommend obtaining a baseline platelet count and then a repeat platelet count within 24 hours of starting heparin over not obtaining a repeat platelet count (Grade 1C).

Anaphylactoid Reactions After IV UFH Bolus

For patients in whom acute inflammatory, cardiorespiratory, neurologic, or other unusual symptoms and signs develop within 30 minutes following an intravenous (IV) UFH bolus, the guideline developers recommend performing an immediate platelet count measurement, and comparing this value to recent prior platelet counts, over not performing a platelet count (Grade 1C).

Platelet Count Monitoring in Patients Receiving Therapeutic-Dose UFH

For patients who are receiving therapeutic-dose UFH, the guideline developers suggest platelet count monitoring at least every 2 or 3 days from day 4 to day 14 (or until heparin is stopped, whichever occurs first) over less frequent platelet count monitoring (Grade 2C).

Platelet Count Monitoring in Postoperative Patients Receiving UFH Antithrombotic Prophylaxis (Highest Risk Group for HIT)

For patients who are receiving postoperative antithrombotic prophylaxis with UFH (i.e., the patient population at highest risk for HIT [HIT risk > 1%]), the guideline developers suggest at least every-other-day platelet count monitoring between postoperative days 4 to 14 (or until UFH is stopped, whichever occurs first) over less frequent platelet count monitoring (Grade 2C).

Platelet Count Monitoring in Patients in Whom HIT Is Infrequent (0.1 to 1%)

For medical/obstetrical patients who are receiving prophylactic-dose UFH, postoperative patients receiving prophylactic-dose LMWH, postoperative patients receiving intravascular catheter UFH "flushes," or medical/obstetrical patients receiving LMWH after first receiving UFH (estimated HIT risk, 0.1 to 1%), the guideline developers suggest platelet count monitoring at least every 2 or 3 days from day 4 to day 14 (or until heparin is stopped, whichever occurs first), when practical, over less frequent platelet count monitoring (Grade 2C).

Platelet Count Monitoring When HIT Is Rare (< 0.1%): UFH and LMWH

For medical/obstetrical patients who are receiving only LMWH, or medical patients who are receiving only intravascular catheter UFH flushes (HIT risk < 0.1%), the guideline developers suggest clinicians do not use routine platelet count monitoring (Grade 2C).

Platelet Count Monitoring When HIT Is Rare (< 0.1%): Fondaparinux

For patients who are receiving fondaparinux thromboprophylaxis or treatment, the guideline developers recommend that clinicians do not use routine platelet count monitoring (Grade 1C).

Management of Patients in Whom Platelet Counts Are Not Monitored

In outpatients who will receive heparin prophylaxis or treatment, informed consent should include HIT and its typical sequelae (new thrombosis, skin lesions), and the patient should be advised to seek medical advice if these events occur (Grade 2C).

Screening for Subclinical HIT Antibody Seroconversion

In patients who receive heparin, or in whom heparin treatment is planned (e.g., for cardiac or vascular surgery), the guideline developers recommend against routine HIT antibody testing in the absence of thrombocytopenia, thrombosis, heparin-induced skin lesions, or other signs pointing to a potential diagnosis of HIT (Grade 1C).

When Should HIT Be Suspected?

For patients who are receiving heparin or have received heparin within the previous 2 weeks, the guideline developers recommend investigating for a diagnosis of HIT if the platelet count falls by >50%, and/or a thrombotic event occurs, between days 5 and 14 (inclusive) following initiation of heparin, even if the patient is no longer receiving heparin therapy when thrombosis or thrombocytopenia has occurred (Grade 1C).

Special Situation: Anticoagulant Prophylaxis and Platelet Count Monitoring After Cardiac Surgery

For postoperative cardiac surgery patients, the guideline developers recommend investigating for HIT antibodies if the platelet count falls by >50%, and/or a thrombotic event occurs, between postoperative days 5 and 14 (inclusive; day of cardiac surgery = day 0) (Grade 1C).

Treatment of HIT

Nonheparin Anticoagulants for Treating HIT (With or Without Thrombosis)

1. For patients with strongly suspected (or confirmed) HIT, whether or not complicated by thrombosis, the guideline developers recommend use of an alternative, nonheparin anticoagulant (danaparoid [Grade 1B], lepirudin [Grade 1C], argatroban [Grade 1C], fondaparinux [Grade 2C], bivalirudin [Grade 2C] over the further use of UFH or LMWH therapy or initiation/continuation of a VKA (Grade 1B).
2. For patients receiving lepirudin, the initial lepirudin infusion rate should be no higher than 0.10 mg/kg/h (patients with creatinine < 90 microgram-mol/L), with lower infusion rates for patients with higher serum creatinine levels (creatinine, 90 to 140 microgram-mol/L: starting infusion rate, 0.05 mg/kg/h; creatinine, 140 to 400 microgram-mol/L: starting infusion rate, 0.01 mg/kg/h; creatinine > 400 microgram-mol/L: starting infusion rate, 0.005 mg/kg/h) (Grade 1C). Furthermore, the guideline developers recommend that the initial IV bolus either be omitted or, in case of perceived life- or limb-threatening thrombosis, be given at a reduced dose (0.2 mg/kg) (Grade 1C). Further, the guideline developers recommend that APTT monitoring be performed at 4-hour intervals until it is apparent that steady state within the normal range (1.5 to 2.0 times patient baseline [or mean laboratory] APTT) is achieved (Grade 1C).
3. When argatroban is used to treat patients who have heart failure, multiple organ system failure, or severe anasarca, or who are postcardiac surgery, the guideline developers suggest beginning the initial infusion at a rate between 0.5 and 1.2 micrograms/kg/minute with subsequent adjustments using the APTT, over the usual recommended starting dose of 2.0 micrograms/kg/min (Grade 2C).
4. When danaparoid is used to treat patients with strongly suspected (or confirmed) HIT, the guideline developers recommend a therapeutic-dose regimen (see text) administered (at least initially) by the IV route over prophylactic-dose regimens or initial subcutaneous (SC) administration (Grade 1B).
5. For patients with strongly suspected or confirmed HIT, whether or not there is clinical evidence of lower-limb deep vein thrombosis (DVT), the guideline developers recommend routine ultrasonography of the lower-limb veins for investigation of DVT over not performing routine ultrasonography (Grade 1C)
.

Vitamin K Antagonists (VKAs)

Management of Direct Thrombin Inhibitor-VKA Overlap

For patients with strongly suspected or confirmed HIT, the guideline developers recommend against the use of VKA (coumarin) therapy until after the platelet count has substantially recovered (i.e., usually to at least 150 x 10⁹/L) over starting VKA therapy at a lower platelet count (Grade 1B); that VKA therapy be started only with low, maintenance doses (maximum, 5 mg of warfarin or 6 mg of phenprocoumon) rather than with higher initial doses (Grade 1B); and that the nonheparin anticoagulant (e.g., lepirudin, argatroban, danaparoid) be continued until the platelet count has reached a stable plateau, the international normalized ration (INR) has reached the intended target range, and after a minimum overlap of at least 5 days between nonheparin anticoagulation and VKA therapy rather than a shorter overlap (Grade 1B).

Reversal of VKA Anticoagulation

For patients receiving a VKA at the time of diagnosis of HIT, the guideline developers recommend use of vitamin K (10 mg by mouth [po] or 5 to 10 mg IV) (Grade 1C).

LMWH for HIT

For patients with strongly suspected HIT, whether or not complicated by thrombosis, the guideline developers recommend against use of LMWH (Grade 1B).

Prophylactic Platelet Transfusions for HIT

For patients with strongly suspected or confirmed HIT who do not have active bleeding, the guideline developers suggest that prophylactic platelet transfusions should not be given (Grade 2C).

Special Patient Populations

Patients With Previous HIT Undergoing Cardiac or Vascular Surgery

1. For patients with a history of HIT who are HIT antibody negative and require cardiac surgery, the guideline developers recommend the use of UFH over a nonheparin anticoagulant (Grade 1B).
2. For patients with a history of HIT who are antibody positive by platelet factor 4 (PF4)-dependent enzyme immunoassay (EIA) but antibody negative by washed platelet activation assay, the guideline developers recommend the use of UFH over a nonheparin anticoagulant (Grade 2C).

Remark: Preoperative and postoperative anticoagulation, if indicated, should be given with a nonheparin anticoagulant.

Patients With Acute or Subacute HIT Undergoing Cardiac Surgery

1. For patients with acute HIT (thrombocytopenic, HIT antibody positive) who require cardiac surgery, the guideline developers recommend one of the following alternative anticoagulant approaches (in descending order of preference): delaying surgery (if possible) until HIT has resolved and antibodies are negative or weakly positive (See the "Patients With Previous HIT Undergoing Cardiac or Vascular Surgery" recommendations above) (Grade 1B); using bivalirudin for intraoperative anticoagulation during cardiopulmonary bypass (if techniques of cardiac surgery and anesthesiology have been adapted to the unique features of bivalirudin pharmacology) (Grade 1B) or during "off-pump" cardiac surgery (Grade 1B); using lepirudin for intraoperative anticoagulation (if ECT is available and patient has normal renal function and is judged to be at low risk for postcardiac surgery renal dysfunction) (Grade 2C); using UFH plus the antiplatelet agent epoprostenol (if ECT monitoring is not available or renal insufficiency precludes lepirudin use) (Grade 2C); using UFH plus the antiplatelet agent, tirofiban (Grade 2C); or using danaparoid for intraoperative anticoagulation for off-pump coronary artery bypass surgery (Grade 2C) over performing the surgery with UFH when platelet-activating anti-PF4/heparin antibodies are known to be present in a patient with acute or recent HIT.
2. For patients with subacute HIT (platelet count recovery, but continuing HIT antibody positive), the guideline developers recommend delaying surgery (if possible) until HIT antibodies (washed platelet activation assay) are negative, then using heparin (See the "Patients With Previous HIT Undergoing Cardiac or Vascular Surgery" recommendation above) over using a nonheparin anticoagulant (Grade 1C). If surgery cannot be delayed, the guideline developers suggest the use of a nonheparin anticoagulant (See the recommendation above) over the use of UFH (Grade 2C).

Percutaneous Coronary Intervention (PCI)

1. For patients with strongly suspected (or confirmed) acute HIT who require cardiac catheterization or PCI, we recommend a nonheparin anticoagulant (bivalirudin [Grade 1B], argatroban [Grade 1C], lepirudin [Grade 1C] or danaparoid [Grade 1C]), over UFH or LMWH (Grade 1B).
2. For patients with previous HIT (who are antibody negative) who require cardiac catheterization or PCI, the guideline developers suggest use of a nonheparin anticoagulant (See the recommendation above) over UFH or LMWH (Grade 2C).

Definitions:

*The guideline developers use the wording recommend for strong (Grade 1) recommendations and suggest for weak (Grade 2) recommendations.

None provided

The type of supporting evidence is identified and graded for each recommendation (see "Major Recommendations").

Not applicable: The guideline was not adapted from another source.

2004 Sep (revised 2008 Jun)

American College of Chest Physicians - Medical Specialty Society

American College of Chest Physicians

American College of Chest Physicians (ACCP) Expert Panel on Antithrombotic and Thrombolytic Therapy

Primary Authors: Theodore E. Warkentin, MD; Andreas Greinacher, MD; Andreas Koster, MD; A. Michael Lincoff, MD

Committee Co-Chairs: Jack Hirsh, MD, FCCP (Chair); Gordon H. Guyatt, MD, FCCP; Gregory W. Albers, MD; Robert A. Harrington, MD, FCCP; Holger J. Schünemann, MD, PhD, FCCP

Participants: Giancarlo Agnelli, MD; Pierre Amarenco, MD; Jack E. Ansell, MD; Collin Baigent; Shannon M. Bates, MD; Kenneth A. Bauer, MD; Richard C. Becker, MD; Peter B. Berger, MD; David Bergqvist, MD, PhD; Rebecca J. Beyth, MD; Christopher P. Cannon, MD; Elizabeth A. Chalmers, MB, ChB, MD; Anthony K.C. Chan, MBBS; Clifford W. Colwell, Jr., MD; Anthony J. Comerota, MD; Deborah Cook, MD; Mark A. Crowther, MD; James E. Dalen, MD; Gabrielle deVeber, MD, MHSc; Maria Benedetta Donati, MD, PhD; James D. Douketis, MD; Andrew Dunn, MD; J. Donald Easton, MD; Michael Ezekowitz, MD; Margaret Fang; William H. Geerts, MD, FCCP; Alan S. Go, MD; Samuel Z. Goldhaber, MD, FCCP; Shaun D. Goodman, MD; Michael Gould, MD, FCCP; Ian A. Greer, MD; Andreas Greinacher, MD; David Gutterman, MD, FCCP, HSP; Jonathan L. Halperin, MD; John A. Heit, MD; Elaine M. Hylek, MD; Alan Jacobson, MD; Roman Jaeschke, MD, PhD; Amir K. Jaffer, MD; Susan Kahn; Clive Kearon, MBBCh, PhD; Fenella Kirkham, MBBC; Andreas Koster, MD, PhD; Michael R. Lassen, MD; Mark N. Levine, MD, MSc; Sandra Zelman Lewis, PhD; A. Michael Lincoff, MD; Gregory YH Lip, MD; Christopher Madias, MD; Warren J. Manning, MD; Daniel B. Mark, MD; M. Patricia Massicotte, MD, MSc; David Matchar, MD; Thomas W. Meade, DM, FCCP; Venu Menon, MD; Tracy Minichiello, MD; Paul Monagle, MBBS, MSc, MD, FCCP; Christopher M. O'Connor, MD; Patrick O'Gara, MD; E. Magnus Ohman, MD; Ingrid Pabinger, MD; Gualtiero Palareti, MD; Carlo Patrono, MD; Stephen G. Pauker, MD; Graham F. Pineo, MD; Jeffrey J. Popma, MD; Gary Raskob, PhD; Gerald Roth, MD; Ralph L. Sacco, MD; Deeb N. Salem, MD, FCCP; Charles-Marc Samama, MD, FCCP; Meyer Michel Samama, MD; Sam Schulman, MD, PhD; Daniel Singer, MD; Michael Sobel, MD; Shoshanna Sofaer, DrPH; Alex C. Spyropoulos, MD FCCP; Ph. Gabriel Steg, MD; Philip Teal, MD; Raymond Verhaeghe, MD; David A. Vorchheimer, MD; Theodore E. Warkentin, MD; Jeffrey Weitz, MD

Dr. Warkentin discloses that he has received grant monies from the Heart & Stroke Foundation of Ontario, as well as industry-related sources of Organon and GlaxoSmithKline. Dr. Warkentin also received consultant fees from Organon, GlaxoSmithKline, and GTI, Inc, and has served on the speakers bureaus of Organon, GlaxoSmithKline, Sanofi-Aventis.

Professor Greinacher discloses that he has received grant monies from projects funded by Graduiertenkolleg, BMBF, Krupp-Kolleg, and EFRE, and has been involved with industry projects such as the development of danaparoid (Orgaran) in heparin-induced thrombocytopenia and performed product evaluations of the PIFA Heparin/PF4 Rapid Assay.

Dr. Lincoff discloses that he has received grant monies from The Medicines Company, Sanofi, Lilly, Pfizer, Schering-Plough, and AstraZeneca. He is also on advisory committees for Sanofi, The Medicines Company, and Pfizer.

Professor Koster discloses that he has received consultant fees from The Medicines Company, and that he is on the speakers bureaus for the Medicines Company and Mitsubishi Pharma Europe. Professor Koster also has received fees from The Medicines Company.

American College of Clinical Pharmacy - Medical Specialty Society
American Society of Health-System Pharmacists - Professional Association

This is the current release of the guideline.

This guideline updates a previous version: Warkentin TE, Greinacher A. Heparin-induced thrombocytopenia: recognition, treatment, and prevention: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004 Sep;126(3 Suppl):311S-37S.

None available

This NGC summary was completed by ECRI on November 19, 2004. The information was verified by the guideline developer on January 12, 2005. This summary was updated by ECRI on March 6, 2007 following the U.S. Food and Drug Administration (FDA) advisory on Coumadin (warfarin sodium). This summary was updated by ECRI Institute on June 22, 2007 following the U.S. Food and Drug Administration (FDA) advisory on heparin sodium injection. This summary was updated by ECRI Institute on September 7, 2007 following the revised U.S. Food and Drug Administration (FDA) advisory on Coumadin (warfarin). This summary was updated by ECRI Institute on March 14, 2008 following the updated FDA advisory on heparin sodium injection. This NGC summary was updated by ECRI Institute on November 24, 2008. The updated information was verified by the guideline developer on January 7, 2009.

This NGC summary is based on the original guideline, which is subject to the guideline developer's copyright restrictions.