Heparin-Induced Thrombocytopenia (HIT)

Heparin Exposure and Prevalence

  • Over 12 Million Patients Receive Heparin Annually: 600k new HIT cases each year
  • HIT Occurs in Up to 5% of Patients Exposed to Heparin for >4 Days

Risk Factors

Dose/Route of Heparin Exposure

  • HIT Can Occur with Any Heparin Dose, Schedule, or Route of Administration (Subcutaneous or Intravenous)
  • Therapeutic Heparin Dosing Has a Higher Risk of HIT (0.76% of Cases), as Compared to Prophylactic Heparin Dosing (<0.1% of Cases) (Chest, 2007) [MEDLINE]
  • However, HIT Can Occur with Any Dose of Heparin: cases of HIT have been reported in patients with heparin-coated catheters
  • Very High Doses of Heparin May Be Associated with Lower Risk of HIT (As Occurs During Cardiopulmonary Bypass), as Compared to Therapeutic Heparin Dosing

Type of Heparin Exposure

  • HIT Can Occur with Any Heparin Dose, Schedule, or Route of Administration (Subcutaneous or Intravenous)
    • Patients treated with low molecular weight heparin can develop HIT with prior exposure to either unfractionated or low molecular weight heparin: frequency of HIT was higher in those previously exposed to heparins of any type (Blood, 2005) [MEDLINE]
  • Heparins
    • Heparin (Unfractionated) (see Heparin, [[Heparin]])
    • Dalteparin (Fragmin) (see Dalteparin, [[Dalteparin]])
    • Enoxaparin (Lovenox) (see Enoxaparin, [[Enoxaparin]])
    • Fondaparinux (Arixtra) (see Fondaparinux, [[Fondaparinux]])
    • Tinzaparin (Innohep) (see Tinzaparin, [[Tinzaparin]])
  • Risk of HIT is Less with Low Molecular Weight Heparins in the Surgical Patient Population (But Not in the Medical Patient Population)
    • HIT occurs in 2.6% % of unfractionated heparin-treated surgical patients [MEDLINE]
    • HIT occurs in 0.2% of low molecular weight heparin-treated surgical patients [MEDLINE]
    • Fondaparinux: HIT is less common with Fondaparinux (as a matter of fact, some cases of HIT have been treated with Fondaparinux)
    • Meta-analyses suggest that the relative risks of HIT with unfractionated vs low molecular weight heparins are comparable in medical patients (Chest, 2007) [MEDLINE]


  • Female Sex Carries a 2.37x-Fold Increased Risk of HIT (Blood, 2006) [MEDLINE]: unclear reasons
    • Female Predominance of HIT is Observed Only in Those Receiving Unfractionated Heparin (as Opposed to low Molecular Weight Heparin): with the highest risk observed in female surgical patients


  • Unclear if Older Age is a Risk fFactor for HIT: studies are currently lacking
  • HIT is Very Rare in Children

Specific Patient Populations

  • Impact of Surgery: risk of HIT is higher in surgical patients (likely related to vascular trauma), as compared to medical patients [MEDLINE]
  • Highest Risk Patient Populations: these patients may have multiple exposures to heparin, receive high heparin doses, and/or receive heparin for prolonged period of time
    • Cardiology/Interventional Cardiology
    • Post-Operative Orthopedic Surgery
    • Vascular Surgery
  • Study Examining Impact of Patient Population on Risk for HIT (Blood, 2000) [MEDLINE]
    • Cardiopulmonary Bypass Patients Treated with Unfractionated Heparin (see Cardiopulmonary Bypass, [[Cardiopulmonary Bypass]]): HIT occurs in 1% of cases
    • Orthopedic Patients Treated with Unfractionated Heparin: HIT occurs in 4.9% of cases
    • Orthopedic Patients Treated with Low Molecular Weight Heparin: HIT occurs in 0.9% of cases

Presence of Inherited Hypercoagulable States

  • Risk of HIT is Not Higher in Patients with Inherited Hypercoagulability (Such as Factor V Leiden and Prothrombin Gene Mutation)


Formation of Heparin-Dependent IgG Antibodies to Platelet Factor 4 Complexed with Heparin

  • Latency of Antibody Formation: formation of heparin-induced antibodies is believed to take at least 4 days of exposure to heparin
    • However, there are rare cases where the antibodies can form in the absence of heparin exposure: in these cases, an inflammatory stimulus or exposure to non-heparin polyanions may be involved
    • While heparin-induced IgM and IgA antibodies can also develop, IgG is thought to be the only pathogenic antibody (since the platelet surface Fc receptor only recognizes IgG)
    • Interestingly, naturally-occurring antibodies against platelet factor 4 complexed to heparin exist in 3-8% of the general population without HIT: these may develop when platelet factor 4 binds to negatively-charged polysaccharides on bacteria, creating an antigen in platelet factor 4 that mimics platelet factor 4 complexed to heparin (and this may explain why some patients have rapid development of heparin-induced antibodies following heparin exposure)
  • Necessity of Presence of Heparin for Heparin-Induced Antibody Binding: it is believed that the binding of heparin (or other polyanions) induce a conformational change in platelet factor 4 protein, resulting in a neoantigen, to which the heparin-induced antibodies bind
    • Therefore, heparin-induced antibodies only cause clinical symptoms when heparin is present
  • Heparin-Induced Antibody Binding to Platelet Factor 4-Heparin Complexes on the Platelet Surface
    • Fc region of the antibody is captured by the Fc receptor on the surface of the same or adjacent platelets -> platelet activation -> further platelet factor released from platelet alpha granules

Clinical Variability Based Upon Molecular Parameters

  • Optimal 1:1 Molar Ratio of Platelet Factor 4 Tetramer/Heparin Molecules: results in the formation of more ultralarge complexes (and is more imunogenic) and is related to the severity of clinical sequelae
    • This may explain why patients treated with high doses of heparin (as are used during cardiopulmonary bypass) are less likely to develop HIT than those exposed to standard doses of heparin
  • Type of Heparin: heparins vary in their ability to produce the optimal 1:1 ratio of platelet factor 4 tetamer/heparin molecules (this ratio results in formation of more ultralarge complexes)
    • HIT occurs in 2.6% of unfractionated heparin-treated patients (ultralarge complexes form most efficiently with unfractionated heparin) [MEDLINE]
    • HIT occurs in 0.2% of low molecular weight heparin-treated patients (ultralarge complex formation is 10x less efficient with low molecular weight heparin, as compared to unfractionated heparin) [MEDLINE]
    • Fondaparinux (Arixtra) (see Fondaparinux, [[Fondaparinux]]): HIT is less common with fondaparinux (ultralarge complex formation is negligible with fondaparinux, as it has no affinity for platelet factor 4)
  • Patients with Larger Amounts of Circulating or Platelet Surface-Bound Platelet Factor 4: have a higher risk and severity of HIT
  • Titer of Heparin-Induced Antibody: high titer antibodies that react with platelet factor 4 bound to non-heparin glycosaminoglycans (such as chondroitin sulfate) may explain the occurrence of HIT in patients who have never been exposed to heparin or in those who develop delayed-onset HIT after heparin withdrawal

Mechanisms of Thrombocytopenia

  • Removal of IgG-Coated Platelets by Reticuloendothelial System Macrophages in Spleen/Liver/Bone Marrow: similar to other types of drug-induced thrombocytopenia
  • Platelet Consumption in Thrombi

Mechanisms of Arterial and Venous Thrombosis

  • Endothelial Cell Activation
  • Endothelial Cell Injury Due to Binding of HIT Antibodies to Endothelial Heparan Sulfate: leads to increased tissue factor and thrombin generation
  • Endothelial Cell Release of Adhesion Molecules: such as IL-6 and vWF
  • Heparin-Induced Antibody Activation of Monocytes
  • Heparin-Induced Antibody Alteration of Other Aspects of the Coagulation Cascade: such as deceased activated protein C generation, etc
  • Platelet Activation
  • Release of Platelet Microparticles (Fragments from Platelet Membrane): these catalyze clot formation
  • Release of Procoagulant Substances from Activated Platelets

Formation of Heparin-Induced Antibodies (Detectable by Laboratory Assays) Without Clinical Thrombocytopenia and HIT (Blood, 2000) [MEDLINE]

  • Heparin-Induced Antibodies May Occur with Heparin Exposure
    • Cardiopulmonary Bypass Patients Treated with Unfractionated Heparin (see Cardiopulmonary Bypass, [[Cardiopulmonary Bypass]])
      • Days of Treatment: 5.1 +/- 2.2 days
      • Frequency of Heparin-Induced Antibodies: 20% (by activation assay) or 50% (by antigen assay)
      • Frequency of Clinical HIT: 1% of cases
    • Orthopedic Patients Treated with Unfractionated Heparin
      • Days of Treatment: 9.2 +/- 2.2 days
      • Frequency of Heparin-Induced Antibodies: 9.3% (by activation assay) or 14.1% (by antigen assay)
      • Frequency of Clinical HIT: 4.9% of cases
    • Orthopedic Patients Treated with Low Molecular Weight Heparin
      • Days of Treatment: 9.5 +/- 3.0 days
      • Frequency of Heparin-Induced Antibodies: 3.2% (by activation assay) or 7.5% (by antigen assay)
      • Frequency of Clinical HIT: 0.9% of cases
  • Heparin-Induced Antibodies May Occur Without Heparin Exposure



General Comments

  • Principle: ELISA assay used to detect the presence of heparin-induced anti-platelet factor 4 antibody in patient’s serum

Solid-Phase ELISA

  • Most Commonly Used Test for HIT
  • Principle of Assay: detects presence of anti-platelet factor 4 antibodies in serum
  • Accuracy
    • Sensitivity: 91 to >97%
    • Specificity: low
      • False-Positive Test Results (Usually with Lower OD Values) Can Occur in the Setting of Anti-Phospholipid Antibody Syndrome and Systemic Lupus Erythematosus (SLE)
  • ELISA Assay Cut-Off Values and Corresponding Serotonin Release Assay Result (J Thromb Haemost, 2008) [MEDLINE]
    • OD <0.40: SRA positive in 0.0 to 0.1% of cases
    • OD 0.40 to <1.00: SRA positive in 1-5% of cases
    • OD 1.00 to <1.40: SRA positive in 18-30% of cases
    • OD 1.40 to <2.00: SRA positive in 19-46% of cases
    • OD >2.00: SRA positive in 89-100% of cases
  • Impact of Renal Failure on Immunoassays
    • Heparin-Induced Antibodies are More Frequently Detected in the Setting of Renal Failure: they are found in 20% of patients during the first 90 days after hemodialysis (and by 6 mo, 9% of patiets of patients on hemodialysis or peritoneal dialysis have positive heparin-induced antibodies)

Functional Assays

General Comments

  • Principle of Assay: assay designed to measure the ability of heparin-induced antibody from patient’s serum to activate test platelets

Serotonin Release Assay (SRA)

  • Considered the Gold Standard Test
  • Principle: measures platelet activation by detecting the release of serotonin from test platelets in the presence of patient’s serum and heparin
  • Interpretation: <20% release -> negative
  • Accuracy
    • Positive-Predictive Value: 100%
    • Negative-Predictive Value: 80%

Heparin-Induced Platelet Aggregation (HIPA)

  • Principle of Assay: platelets or platelet-rich plasma from healthy donors is added to serum or platelet-poor plasma from a patient with suspected HIT -> platelet aggregation is measured in the absence of heparin and in the presence of low and high heparin concentrations
  • Criteria for Positive HIPA: minimal platelet aggregation in the absence of heparin and in the presence of high heparin concentrations (10 to 100 units/mL) and strong aggregation in the presence of low heparin concentrations (0.1 to 0.3 units/mL)
  • Accuracy
    • Sensitivity: low
    • Specificity: >90%

Clinical Subtypes of Heparin-Induced Thrombocytopenia (HIT)

Heparin-Induced Thrombocytopenia-Type I

  • Epidemiology: occurs in 10-20% of patients
  • Mechanism: non-antibody-mediated, non-immune type of HIT (due to platelet activation and sequestration)
  • Latency: thrombocytopenia occurs 1-4 days after starting heparin
  • Clinical Severity: less severe (platelet count rarely falls <100k)
    • One should consider the diagnosis of HIT in any patient with a decrease in platelet count >50% from baseline
    • Thromboembolic Events: absent
    • Hemorrhagic Events: absent
  • Treatment: observation (without discontinuation of heparin)
  • Prognosis: self-limited -> platelet counts generally recover, despite continuation of heparin

Heparin-Induced Thrombocytopenia-Type II (aka Heparin-Induced Thrombocytopenia and Thrombosis, HITT)

  • Epidemiology: occurs in 1-3% of patients
    • Reaction is idiosyncratic, not dose-dependent
  • Mechanism: antibody-mediated, immune type of HIT (due to antibody against platelet factor 4 complexed to heparin)
  • Latency: thrombocytopenia usually occurs around 4-7 days after starting heparin (may appear sooner in cases where patient has been exposed to heparin within the last 3 mo)
  • Clinical Severity: more severe (platelet counts may fall to around 60k)
    • One should consider the diagnosis of HIT in any patient with a decrease in platelet count >50% from baseline
    • Thromboembolic Events: 30-80% of cases
      • Arterial Thrombosis
      • Venous Thrombosis
    • Hemorrhagic events: rare
  • Treatment: cessation of heparin and use of alternative anticoagulation agent (see below)

Clinical Scoring Systems

4 T’s Scoring System (Am J Hematol, 2008) [MEDLINE]

Scoring System

  • General Comments
    • 4 T’s: thrombocytopenia, timing of platelet fall, thrombosis, and the absence of oTher causes of thrombocytopenia
    • 4 T’s Scoring System Has Been Clinically Validated with Unfractionated Heparin: although it has not been validated with low molecular weight heparin, it can also be used for these patients
  • Thrombocytopenia
    • Platelet Count fall <30% or Nadir <10k: 0 points
    • Platelet Count fall 30-50% or Nadir 10-19k: 1 points
    • Platelet Count fall >50% and Nadir ≥20k: 2 points
  • Timing of Platelet Count Fall
    • Platelet Count Fall at <4 days Without Recent Exposure: 0 points
    • Consistent with Fall at 5-10 Days but Unclear (eg: Missing Platelet Counts), Onset After Day 10, or Fall ≤1 Day with Prior Heparin Exposure Within 30-100 Days: 1 point
    • Clear Onset Between Days 5-10 or Platelet Count fFall at ≤1 day if Prior Heparin Exposure Within the last 30 Days: 2 points
  • Thrombosis or Other Sequelae
    • None: 0 points
    • Progressive or Recurrent Thrombosis, Non-Necrotizing (Erythematous) Skin Lesions, or Suspected Thrombosis That Has Not Been Proven: 1 point
    • Confirmed New Thrombosis, Skin Necrosis, or Acute Systemic Reaction After Intravenous Unfractionated Heparin Bolus: 2 points
  • OTher Causes for Thrombocytopenia
    • Definite: 0 points
    • Possible: 1 point
    • None Apparent: 2 points
  • Interpretation
    • Low Probability: 0-3 pts
    • Intermediate Probability: 4-5 pts
    • High Probability: 6-8 pts

Clinical Efficacy

  • Evaluation of 4T’s Scoring for Heparin-Induced Trombocytopenia (J Oncol Pharm Pract, 2010) [MEDLINE]
    • Using the 4T’s Scoring System, Patients at Low Risk Were More Likely to Receive Initial Inappropriate Therapy and Were More Likely to Have a Negative ELISA Test Result

Lillo-Le Louet Model

  • Used exclusively for assessment of thrombocytopenia in the post-cardiopulmonary bypass setting (has not been clinically validated)

HIT Expert Probability (HEP) Score

  • Scoring system based on broad expert opinion (has not been clinically validated)

Clinical Manifestations

Hematologic Manifestations

Thrombocytopenia (see Thrombocytopenia, [[Thrombocytopenia]])

  • Epidemiology: most common manifestation (occurs in 85-90% of cases)
  • Severity of Thrombocytopenia
    • Decrease in Platelet Count of >50% From Baseline: common
      • Approximately 5% of Cases Lack True Thrombocytopenia (with Platelet Count Remaining >150k), But Demonstrate a 30-50% Decrease in the Platelet Count from Baseline (Chest, 2012) [MEDLINE]
    • Mean Nadir in Platelet Count: 60k
    • Platelet Count <20k: rare
      • Therefore, Bleeding is Rare
  • Latency of Onset of Thrombocytopenia
    • Typical Onset of Thrombocytopenia: 5-10 days after heparin initiation (heparin antibodies usually develop between 5-8 days after heparin exposure, rarely develop later)
    • Early Onset of Thrombocytopenia: may occur within 24 hrs (mean: 10.5 hrs after initiation) in patients previously exposed to heparin in the prior 100 days (and have circulating heparin-induced antibodies)
    • Delayed Onset of Thrombocytopenia Following Heparin Withdrawal: incidence is unknown
      • Onset of HIT may occur as long as 40 days after stopping heparin (Ann Intern Med, 2002) [MEDLINE]
      • In one study, patients had high-titer heparin-induced antibodies (which manifested increased heparin-dependent as well as heparin-independent platelet activation) [MEDLINE]: may explain why HIT occurred in the absence of heparin
  • Timing of Thrombocytopenia in Relation to Thrombotic Events: thrombocytopenia often precedes onset of thrombotic events

Other Manifestations


  • General Comments
    • Thrombosis occurs in 50% of HIT cases
    • Thrombosis is the presenting finding in 25% of HIT cases
  • Venous Thrombosis: 20-50% of HIT cases manifest venous thrombosis
    • Adrenal Hemorrhage (see Adrenal Hemorrhage, [[Adrenal Hemorrhage]]): due to adrenal vein involvement
    • Cardiac Vein Thrombosis: due to cardiac vein involvement
    • Deep Venous Thrombosis (DVT) (see Deep Venous Thrombosis, [[Deep Venous Thrombosis]]): due to lower extremity vein involvement
    • Limb Ischemia/Gangrene with Associated Skin Necrosis (see Limb Ischemia, [[Limb Ischemia]]): reported with coumadin monotherapy of HIT-related DVT [MEDLINE]
    • Skin Necrosis (see Heparin, [[Heparin]]): due to involvement of skin veins
      • Clinical Progression: erythema -> purpura/hemorrhage -> necrosis
      • May occur at heparin injection sites: this is particularly characteristic of HIT
      • Common occurs in fatty areas, such as the abdomen (althugh may occur in distal extremities and the nose)
      • May appear similar to lesions of coumadin skin necrosis (although patients are not deficient in protein C, protein S, or antithrombin)
    • Upper Extremity Deep Venous Thrombosis (DVT): usually only occur in patients with a central venous catheter in place (and always at the catheter site)
  • Arterial Thrombosis: 3-10% of HIT cases manifest arterial thrombosis (which may be manifested by platelet-rich, “white thrombi”)
    • Acute Mesenteric Ischemia/Infarction (see Acute Mesenteric Ischemia, [[Acute Mesenteric Ischemia]]): due to involvement of mesenteric arteries
    • Ischemic Cerebrovascular Accident (CVA) (see Ischemic Cerebrovascular Accident, [[Ischemic Cerebrovascular Accident]]): due to involvement of central nervous system arteries
    • Limb Ischemia/Gangrene (due to Limb Ischemia, [[Limb Ischemia]]): due to limb artery involvement
    • Myocardial infarction (MI) (see Coronary Artery Disease, [[Coronary Artery Disease]]): due to coronary artery involvement
    • Renal Infarction: due to involvement of renal artery
    • Transient Global Amnesia: due to cerebral ischemia

Anaphylaxis (see Anaphylaxis, [[Anaphylaxis]])

  • Epidemiology: cases of anaphylaxis associated with HIT have been described
  • Clinical: manifested after heparin bolus
  • Prognosis: may be fatal

Clinical: Spontaneous HIT (Autoimmune HIT)

  • Definition: HIT-like, transient prothrombotic thrombocytopenic disorder without proximate heparin exposure -> considered controversial
  • Epidemiology: most cases had preceding infectious or inflammatory event (gram-negative bacteremia, orthopedic surgery)
  • Diagnosis: serologically indistinguishable from HIT
    • Cases described manifested tested strongly positive for anti-platelet factor 4/heparin immunoglobulin IgG in 2 different immunoassays and in the serotonin-release assay [MEDLINE]
    • Sera from the two cases also caused strong (>80%) serotonin release in the absence of heparin, a serologic feature characteristic of delayed-onset HIT (where heparin use precedes HIT but is not required for subsequent development or worsening of the thrombocytopenia) [MEDLINE]


HIT Type I

Cessation and Avoidance of Heparins + Use of Non-Heparin Anticoagulation

  • Chest 2012 Antithrombotic Therapy and Prevention of Thrombosis Guidelines (9th ed) [MEDLINE]: stop heparin and use non-heparin anticoagulant, as described below (grade 1C)

HIT Type II (aka Heparin-Induced Thrombocytopenia and Thrombosis, HITT)

Cessation and Avoidance of Heparins For Life

  • Cross-Reactivity of Low Molecular Weight Heparin with Unfractionated Heparin: 80-90% cross-reactivity
  • Heparin Cessation Alone is Insufficient
    • Anticoagulation with a non-heparin anticoagulant is recommended
    • Without appropriate treatment, HIT patients have a 52.8% risk of developing new thrombosis within 30 days after stopping heparin [MEDLINE]
    • Risk of thrombosis is 5-10% per day within the first week following discontinuation of heparin [MEDLINE]
    • Additionally, the risk of thrombosis persists even after platelet count returns to normal


  • Factor Xa Inhibitors (see Factor Xa Inhibitors, [[Factor Xa Inhibitors]])
    • Danaparoid (Orgaran) (see Danaparoid, [[Danaparoid]])
      • Chest 2012 Antithrombotic Therapy and Prevention of Thrombosis Guidelines (9th ed) [MEDLINE]: one of the recommended agents for HIT (although it is not FDA approved for HIT)
      • Metabolism: renal
    • Fondaparinux (Arixtra) (see Fondaparinux, [[Fondaparinux]])
      • Although fondaparinux has been used to treat HIT, there are case reports of it both causing HIT and exacerbating HIT
  • Thrombin Inhibitors (see Factor IIa Inhibitors, [[Factor IIa Inhibitors]])
    • Argatroban (Acova) (see Argatroban, [[Argatroban]]): most commonly used agent
      • Chest 2012 Antithrombotic Therapy and Prevention of Thrombosis Guidelines (9th ed) [MEDLINE]: one of the recommended agents for HIT
      • Metabolism: hepatic -> per Chest 2012 guidelines, this is the preferred agent in the setting of renal insufficiency (grade 2C) [MEDLINE]
      • Dose: 2 µg/kg/min IV -> check PTT 2 hrs later, titrate to PTT 1.5-3x baseline (max dose: 10 µg/kg/min)
    • Lepirudin (Refludan) (see Lepirudin, [[Lepirudin]])
      • Chest 2012 Antithrombotic Therapy and Prevention of Thrombosis Guidelines (9th ed) [MEDLINE]: one of the recommended agents for HIT
      • Metabolism: renal -> use with caution in renal insufficiency
      • Anti-Hirudin Antibodies: develop in 44% of cases (need to monitor PTT)
    • Desirudin (Iprivask, Revasc) (see Desirudin, [[Desirudin]]): subcutaneous administration
    • Bivalirudin (Angiomax, Angiox) (see Bivalirudin, [[Bivalirudin]])
  • Coumadin (see Coumadin, [[Coumadin]]): per Chest 2012 Antithrombotic Therapy and Prevention of Thrombosis Guidelines (9th ed) [MEDLINE]
    • Avoid coumadin monotherapy in HIT, as it may precipitate skin necrosis or venous gangrene of limbs (grade 1C)
    • After anticoagulation with non-heparin anticoagulant is therapeutic, start coumadin (at low dose, max: 5 mg) only after after the platelet count recovers to >150k (grade 1C)
    • If coumadin is present at time of HIT diagnosis, vitamin K should be given (grade 2C)
    • Overlap between non-heparin anticoagulant and coumadin should be at least 5 days and until INR is within the target range (grade 1C)
      • Additionally, INR should be rechecked after non-heparin anticoagulant has been discontinued: this is due to the fact that 21% of patients with INR >3 while on argatroban + coumadin had a subtherapeutic INR 4 hrs after stopping argatroban
      • An alternative strategy: once platelets have recovered to >150k, switch argatroban to fondaparinux, then start transition to coumadin (as fondaparinux does not influence the INR or PTT)

Use of Platelet Transfusions in Heparin-Induced Thrombocytopenia

  • Chest 2012 Antithrombotic Therapy and Prevention of Thrombosis Guidelines (9th ed) [MEDLINE]: platelet transfusion is only recommended to treat active bleeding or to facilitate an invasive procedure with a high-risk of bleeding (grade 2C)

Resolution of Thrombocytopenia and Heparin-Induced Antibodies

  • Platelet count usually recovers within 7 days after stopping heparin
    • However, heparin-induced antibodies may persist for 2-3 mo

Special Clinical Situations (per Chest 2012 Antithrombotic Therapy and Prevention of Thrombosis Guidelines (9th ed) [MEDLINE])

Need for Cardiac Surgery or Percutaneous Coronary Intervention

  • Acute HIT (Thrombocytopenic + Heparin Antibody-Positive)/Subacute HIT (Not Thrombocytopenic, But Heparin Antibody-Positive) with Urgent Need for Cardiac Surgery: use bivalirudin (grade 2C)
  • Acute HIT (Thrombocytopenic + Heparin Antibody-Positive) with Non-Urgent Need for Cardiac Surgery: delay surgery until HIT has resolved and heparin antibodies are negative (grade 2C)
  • History of HIT (with Negative Heparin Antibodies) with Need for Cardiac Surgery: use heparin (short-term only), as heparin-induced antibodies are short-lived and do not frequently result in anamnestic responses when the patient is subsequently re-challenged
  • History of HIT (with Positive Heparin Antibodies) with Need for Cardiac Surgery: use non-heparin anticoagulant
  • Acute HIT (Thrombocytopenic + Heparin Antibody-Positive)/Subacute HIT (Not Thrombocytopenic, But Still Heparin Antibody-Positive)/History of HIT with Need for Percutaneous Coronary Intervention: use bivalirudin or argatroban (grade 2C)

Other Clinical Scenarios

  • Acute HIT (Thrombocytopenic + Heparin Antibody-Positive)/Subacute HIT (Not Thrombocytopenic, But Still Heparin Antibody-Positive) with Need for Continuous Veno-Venous Hemodiaylsis (Continuous Renal Replacement Therapy, CRRT): use danaparoid or argatroban (grade 2C)
  • History of HIT with Acute Thrombosis (Not Related to HIT) and Normal Renal Function: use fondaparinux until transition to coumadin can be achieved (grade 2C)


  • Acute HIT (Thrombocytopenic + Heparin Antibody-Positive)/Subacute HIT (Not Thrombocytopenic, But Still Heparin Antibody-Positive) during Pregnancy: use danaparoid (grade 2C)
    • Alternative agents (either may be used if danaparoid is not available): lepirudin or fondaparinux


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