INTRODUCTION — Heparin-induced thrombocytopenia (HIT) is a life-threatening complication of exposure to heparin (ie, unfractionated heparin, low molecular weight [LMW] heparin) that occurs in up to 5 percent of patients exposed, regardless of the dose, schedule, or route of administration. HIT results from an autoantibody directed against platelet factor 4 (PF4) in complex with heparin (referred to as a HIT antibody). HIT antibodies activate platelets and can cause catastrophic arterial and venous thrombosis, with a mortality rate as high as 20 percent, although with improved recognition and early intervention, mortality rates below 2 percent have been reported.
Here we discuss the prevention and management of HIT. Separate topic reviews discuss:
●Diagnosis of HIT – (See "Clinical presentation and diagnosis of heparin-induced thrombocytopenia".)
●Diagnosis and management of COVID-19 vaccine-induced immune thrombotic thrombocytopenia (VITT) – (See "COVID-19: Vaccine-induced immune thrombotic thrombocytopenia (VITT)".)
IMMEDIATE ACTIONS
Overview of initial management — HIT requires immediate treatment to reduce the risk of potentially life-threatening thrombosis (algorithm 1). In most cases, treatment must be initiated based on a strong clinical suspicion of HIT, even before confirmatory laboratory test results are available. For individuals with a strong clinical suspicion of HIT (eg, based on an intermediate or high probability 4 Ts score), therapy (discontinuation of all heparin, reversal of warfarin, initiation of a non-heparin anticoagulant) should not be delayed while awaiting laboratory testing.
There are two major goals of the initial treatment [1]:
●To halt platelet activation as rapidly as possible.
•In most cases, platelet activation only occurs in the presence of both heparin and HIT antibodies, and elimination of all heparin exposure is the best way to halt platelet activation. (See 'Stop heparin for a presumptive diagnosis of HIT' below.)
•There is increasing awareness of rare forms of HIT (eg, autoimmune HIT, which includes delayed-onset HIT, persisting or refractory HIT, and spontaneous HIT), characterized by platelet activation in the absence of heparin. Additional interventions to halt platelet activation may be needed in these cases. (See 'Autoimmune HIT' below.)
●To provide therapeutic-dose anticoagulation with a non-heparin-anticoagulant until the thrombosis risk has returned to baseline.
•The risk of thrombosis is high enough that therapeutic-dose anticoagulation is needed regardless of whether a thrombotic event has occurred [2-4]. A potential exception is an individual who has clinically significant bleeding or for whom the risk of bleeding is determined to be very high. Significant thrombocytopenia alone is not a contraindication to full-dose anticoagulation. (See 'Rationale for anticoagulation' below and 'HIT with bleeding' below.)
•There are several options among the non-heparin anticoagulants (table 1). The choice of non-heparin anticoagulant must consider the urgency for therapeutic anticoagulation (based on severity of clinical findings), the potential need for rapid reversal (ie, whether a reversal agent is available), the patient's renal and hepatic function (which affects drug metabolism), cost, and other factors. (See 'Choice and dose of non-heparin anticoagulant' below.)
•The duration of anticoagulation is generally longer for people who have had a thrombotic event than for those who have not. (See 'Duration of anticoagulation' below.)
Warfarin can be used for anticoagulation once stable anticoagulation with another non-heparin agent has been established and an adequate platelet count has been attained (eg, >150,000/microL). However, warfarin should not be used before anticoagulation with a non-heparin agent has been established or before platelet count recovery due to the potential risk of precipitating skin necrosis and venous limb gangrene resulting from rapid depletion of protein C in the first days of warfarin administration. If the patient is receiving warfarin when HIT with thrombosis or venous limb gangrene develops, warfarin should be reversed with vitamin K. In the absence of thrombosis or limb gangrene, discontinuation is sufficient, although administration of low-dose oral vitamin K may be considered given its low cost, safety, and potential to mitigate the risk of thrombosis. (See 'Hold or reverse warfarin' below and 'Transition to warfarin or other outpatient anticoagulant' below.)
Increasingly, long-term primary or secondary prophylaxis of thrombosis in patients with HIT and a normal and stable platelet count is provided with a therapeutic dose of a direct oral anticoagulant (DOAC). Although data are limited, preliminary evidence suggests this strategy to be both safe and effective. In patients who cannot take an oral medication, long-term subcutaneous fondaparinux can also be used. (See 'Direct oral anticoagulants' below.)
Although thrombocytopenia generally raises concerns about bleeding, especially when administering an anticoagulant, HIT-associated thrombocytopenia is not a contraindication to anticoagulation.
All individuals with suspected HIT should have ongoing evaluation including continuous assessment for other possible causes of thrombocytopenia, serial monitoring for bleeding and thrombotic complications, and serial measurement of platelet counts and other laboratory parameters as clinically indicated. The rationale and timing are summarized in the figure (figure 1). Any change in clinical findings (eg, development of a new thrombosis, further drop in platelet count) should prompt a recalculation of the 4 Ts score. (See "Clinical presentation and diagnosis of heparin-induced thrombocytopenia", section on 'Differential diagnosis' and "Diagnostic approach to the adult with unexplained thrombocytopenia" and "Causes of thrombocytopenia in children".)
Once results of HIT antibody testing are available (including a definitive result from an immunoassay and/or the result of a functional assay), further planning can be made regarding the need for ongoing anticoagulation and whether or not the individual can receive heparin in the future. (See 'Incorporating results of HIT antibody testing' below.)
Our approach is generally similar to that of others:
●A 2018 guideline from the American Society of Hematology (ASH) [5]
●A 2015 expert review and case discussion of HIT management [1]
●A 2012 guideline from the American College of Chest Physicians (ACCP) [6]
Similar to the 2018 ASH guideline, we include DOACs among possible non-heparin anticoagulants that may be used [5]. The above guidelines differ somewhat on the recommended duration of anticoagulation, as discussed below. (See 'Duration of anticoagulation' below.)
Stop heparin for a presumptive diagnosis of HIT — Individuals with a presumptive diagnosis of HIT should have immediate discontinuation of all heparin exposure (algorithm 1). There should be no exposure to unfractionated heparin, low molecular weight (LMW) heparin, heparin flushes, heparin-bonded catheters, or heparin-containing medications (eg, some prothrombin complex concentrates, some total parenteral nutrition preparations and others (table 2)). The need to avoid all forms of heparin exposure should be immediately conveyed to all personnel caring for the patient, along with a notation in the patient's medical record and signs posted at the bedside or attached to all intravenous delivery devices. Electronic medical records should build in fail-safe mechanisms to prevent ordering of heparin-containing medications in patients with either active or prior HIT.
The diagnosis of HIT must take into consideration both clinical and laboratory evidence, and, often, definitive laboratory data (ie, strongly positive immunoassay and/or positive functional assay for HIT antibodies) are not immediately available. Thus, a presumptive diagnosis of HIT must often be based on clinical findings and limited laboratory data that include serial platelet counts, other findings from the complete blood count (CBC), and coagulation testing.
Errors in either direction (making a presumptive diagnosis of HIT when HIT is unlikely or failing to make a presumptive diagnosis of HIT when HIT is likely) can have serious consequences for the patient. Thus, clinicians should closely review the patient's clinical findings and involve the consulting hematologist (if available) as early as possible.
●Diagnosing HIT when HIT is absent exposes the patient to unnecessary bleeding risks associated with the use of anticoagulants, cancellation of needed procedures, and/or future avoidance of heparin when heparin might be clinically indicated [7]. As an example, the risk of bleeding with argatroban may be as high as 20 percent [8]. The use of a parenteral anticoagulant typically necessitates a more prolonged hospital stay. The costs of anticoagulant administration, management of complications, and extended hospitalization are substantial [9].
●Failing to diagnose HIT when HIT is likely exposes the patient to a high risk of potentially avoidable thrombosis (arterial or venous). The risk of thrombosis with HIT in the absence of anticoagulation is as high as 30 to 50 percent, as discussed below. (See 'Rationale for anticoagulation' below.)
The 4 Ts score (calculator 1) is an extremely helpful and easy-to-use score that quantifies the clinical findings associated with HIT based on four parameters (degree of thrombocytopenia, timing, thrombotic events or sequelae, alternative causes of thrombocytopenia) (table 3). The 4 Ts score requires vigilance to document heparin exposure and its timing relative to a decrease in platelet count, as well as judgment related to the likelihood of alternative explanations for thrombocytopenia. It risk-stratifies patients into low, intermediate, or high probability of HIT. The score should be used as an initial guide for clinicians but should not substitute for clinical judgment [10].
●If the 4 Ts score is intermediate or high probability, we make a presumptive diagnosis of HIT because an intermediate or high probability 4 Ts score will capture >95 percent of patients with a reasonable likelihood of HIT regardless of whether they have had a thrombotic event. The score is highly sensitive, but many individuals with intermediate or high probability scores will not have HIT. Thus, the urgency of obtaining supportive laboratory testing should be emphasized.
●If the 4 Ts score is low probability, we do not make a presumptive diagnosis of HIT because the risk of HIT is exceedingly low (0 to 3 percent). However, in rare or complex cases, a clinician may suspect HIT despite a low probability 4 Ts score, and a presumptive clinical diagnosis of HIT may be made prior to laboratory testing.
The clinical evaluation for suspected HIT is discussed in more detail separately. (See "Clinical presentation and diagnosis of heparin-induced thrombocytopenia", section on 'Overview of our approach to evaluation'.)
Individuals with a presumptive diagnosis of HIT should receive full-dose anticoagulation until the diagnosis is confirmed (or refuted) by laboratory testing, at which time additional decisions about the duration of anticoagulation and follow-up can be made. (See 'Incorporating results of HIT antibody testing' below.)
Hold or reverse warfarin — Warfarin is a reasonable choice for anticoagulation in HIT, but it must not be started until after the individual is stably anticoagulated for an appropriate duration with a non-heparin anticoagulant and the platelet count has recovered [6]. The rationale is that during the initial phase of warfarin administration (first one to two days), there is a transient hypercoagulable state caused by depletion of functional protein C, which has a short half-life compared with the half-life of coagulation factors II and X. Functional protein S is also depleted. This rapid depletion of anticoagulant proteins may increase the risk of thrombosis, including venous limb gangrene in patients with thrombosis [11,12]. This has been observed in individuals with underlying protein C deficiency but is also possible in other individuals. (See "Protein C deficiency", section on 'Warfarin-induced skin necrosis' and "Warfarin and other VKAs: Dosing and adverse effects", section on 'Skin necrosis'.)
Patients who develop HIT while receiving warfarin should have their warfarin held, reversed with vitamin K (typically given intravenously), and an alternate, non-heparin anticoagulant started. The exact timing of vitamin K administration should attempt to minimize the chance of precipitating or exacerbating thrombosis due to HIT in the setting of the initial procoagulant effect of warfarin. Thus, for a patient starting on argatroban who has received one or two doses of warfarin, it may be appropriate to establish stable anticoagulation with argatroban before giving vitamin K. However, it is important not to under-dose the argatroban based on a prolonged aPTT that will occur if the patient has significant residual warfarin effect. For a patient starting fondaparinux or other medications that rapidly reach a predictable peak anticoagulant effect, it may be reasonable to give vitamin K at the same time the non-heparin anticoagulant is initiated.
These patients may transition back to warfarin (or perhaps a DOAC) after an appropriate duration of anticoagulation with the non-heparin anticoagulant and once the platelet count has normalized. (See 'Transition to warfarin or other outpatient anticoagulant' below.)
Start full-dose therapeutic anticoagulation with a non-heparin anticoagulant — For patients with a presumptive clinical diagnosis of HIT (and/or a confirmed diagnosis of HIT based on HIT antibody testing), we recommend immediate anticoagulation with a non-heparin anticoagulant rather than discontinuation of heparin alone, unless there is a strong contraindication (eg, bleeding, high bleeding risk). This applies to all patients, regardless of the initial indication for, and dose of, heparin (eg, full-dose anticoagulation, heparin flushes). The rationale for this practice and considerations regarding the choice of anticoagulant are discussed in the following sections. (See 'Anticoagulation' below.)
ANTICOAGULATION
Rationale for anticoagulation — Patients who develop HIT will have an ongoing need for anticoagulation due to the risk of thrombosis (arterial or venous thromboembolism [VTE]) associated with HIT, and possibly also for the condition for which heparin was administered originally (algorithm 1). Heparin cessation alone is not sufficient since patients with HIT remain at risk for subsequent thrombosis, especially during the period when the HIT antibody continues to activate platelets [2-4].
The persistent risk of thrombosis is illustrated by the following examples:
●A retrospective series of 127 patients with HIT, in which half were only diagnosed after they had a complicating thrombotic event [2]. Patients were treated with heparin cessation, with or without warfarin; they did not receive a parenteral non-heparin anticoagulant. Of the 62 patients who presented with HIT without thrombosis, subsequent 30-day thrombosis risk was 53 percent.
●Another study evaluated 113 patients with HIT in whom heparin was stopped early (mean 0.7 days) or late (mean five days) after the onset of thrombocytopenia [3]. The overall incidence of thrombosis was 45 and 34 percent in the early and late groups, respectively, with 61 and 40 percent of the thrombotic events occurring more than 24 hours after cessation of heparin.
Choice and dose of non-heparin anticoagulant — There are a number of non-heparin anticoagulants that can be used in a patient with HIT (table 1). These include parenteral direct thrombin inhibitors (eg, argatroban, bivalirudin), danaparoid (not available in the United States), fondaparinux, or direct oral anticoagulants (DOACs) such as apixaban, edoxaban, rivaroxaban, or dabigatran [13,14].
Our approach to the choice of anticoagulant considers the urgency of anticoagulation, possible need for urgent reversal, renal and hepatic function, and other considerations:
●Urgency of anticoagulation – For individuals with an acute thrombosis, a parenteral agent is typically used first, in order to have full-dose, therapeutic anticoagulation as rapidly as possible. Options include argatroban, bivalirudin, danaparoid, or fondaparinux. However, it may be appropriate to use a rapidly acting DOAC in certain cases.
●Possible need for urgent reversal – For individuals who may require an invasive procedure (eg, cardiac surgery) or those who have an especially high risk of bleeding, it may be prudent to use an anticoagulant that can be reversed rapidly. As examples, argatroban and bivalirudin have short half-lives, and their effects will be gone within approximately one hour following discontinuation (longer for argatroban with severe hepatic dysfunction and for bivalirudin with severe renal dysfunction). Reversal agents for the DOACs are discussed separately. (See "Management of bleeding in patients receiving direct oral anticoagulants".)
●Chronic kidney disease – For individuals with chronic kidney disease, we use argatroban at therapeutic doses. Once the individual has been stably anticoagulated, warfarin can be used, with close monitoring of the prothrombin time/international normalized ratio (PT/INR). Direct oral factor Xa inhibitors may be used in individuals with creatinine clearance >15 mL/minute; rivaroxaban and apixaban can be used in individuals with end-stage kidney disease and atrial fibrillation. Product information for the specific agent should be reviewed.
●Liver disease – For individuals with significant hepatic impairment, we use danaparoid (if available), fondaparinux, or bivalirudin at therapeutic doses. The direct oral factor Xa inhibitors can be used in with care in patients with mild hepatic insufficiency but generally should not be used in moderate to severe hepatic impairment unless drug levels are monitored. Product information for the specific agent should be reviewed.
●Kidney and liver impairment – For individuals with combined kidney and liver impairment, argatroban or bivalirudin can be used at reduced doses. Once the individual has been stably anticoagulated, warfarin can be used, with close monitoring of the prothrombin time/international normalized ratio (PT/INR). Direct Factor Xa inhibitors, particularly apixaban, are being used with increasing frequency in patients with chronic kidney disease, and these agents may be appropriate in selected patients with HIT, particularly after the acute phase of the disease has passed and thrombocytopenia has resolved.
●Other considerations in anticoagulant choice – Other considerations may include local availability, institutional and/or clinician preference, and cost. For individuals who cannot receive an intravenous agent, fondaparinux or one of the DOACs may be used. For those who cannot receive an oral agent, fondaparinux or one of the parenteral direct thrombin inhibitors may be used.
●Dosing – We use therapeutic rather than prophylactic dosing, except for patients with combined kidney and liver impairment. Specific dosing of each agent is described in the sections below.
Evidence for the similar efficacy of these anticoagulants in HIT consists of observational studies; randomized trials comparing different non-heparin anticoagulants in individuals with HIT are limited to two small trials. Efficacy and toxicity of various non-heparin anticoagulants was evaluated in a 2021 systematic review and meta-analysis that incorporated data from 92 studies involving 4698 patients [15]. This showed similar efficacy (platelet count recovery, reduction of thrombosis) of parenteral anticoagulants (argatroban, danaparoid, hirudins, fondaparinux) as well as DOACs. Safety (bleeding risk) was also similar, with a trend towards lower bleeding risk with DOACs that did not reach statistical significance. This analysis supports the use of fondaparinux or a DOAC in individuals who do not require an intravenous anticoagulant for acute thrombosis or who may require rapid reversal.
Specific agents
Argatroban — Argatroban is a parenteral small molecule direct thrombin inhibitor with a half-life of 24 minutes [16]. Its effect is monitored by the activated partial thromboplastin time (aPTT), although dose-dependent increases also occur in the prothrombin time [17]. Steady-state anticoagulation is reached one to three hours after intravenous administration; after discontinuation, the aPTT returns to normal within two hours. (See "Direct oral anticoagulants (DOACs) and parenteral direct-acting anticoagulants: Dosing and adverse effects", section on 'Argatroban'.)
In patients with normal hepatic function, the standard starting dose is 1 to 2 mcg/kg per minute by continuous intravenous infusion, adjusted to maintain the aPTT at 1.5 to 3 times baseline, not to exceed 100 seconds, although local infusion standards may differ.
Since argatroban is mostly hepatically metabolized, dose adjustment is required in the presence of hepatic dysfunction. A conservative lower starting dose (eg, 0.5 to 1.2 mcg/kg per minute) is appropriate in patients with total serum bilirubin >1.5 mg/dL (25.5 micromol/L), as well as in those with combined hepatic/renal dysfunction, heart failure, severe anasarca, or who are post-cardiac surgery [18]. In such patients, it is prudent to check the aPTT at four-hour intervals after drug initiation or dose change. Dose adjustment is not required in the presence of isolated renal impairment [19].
A small study of 24 patients suggested that an even lower starting dose of argatroban (0.2 mcg/kg per minute) may be appropriate in critically ill patients with multiple organ dysfunction syndrome and HIT [20]. We generally initiate dosing at 0.5 mcg/kg per minute in these patients.
Since both warfarin and argatroban elevate the PT/INR, institutional guidelines should specify the appropriate INR target during the transition to warfarin in order to achieve an INR in the range of 2 to 3 when argatroban is discontinued. This target will differ according to the reagents used to determine the PT/INR in each particular institution. (See 'Transition to warfarin or other outpatient anticoagulant' below.)
Three prospective trials of the use of argatroban for the treatment of HIT in 1419 patients have been published [21-23]. These studies showed superior efficacy of argatroban compared with historic controls in reducing subsequent thrombotic events and death due to thrombosis, with no difference in bleeding risk.
Bivalirudin — Bivalirudin (Angiomax, previously called Hirulog), a parenteral direct thrombin inhibitor and hirudin analog, has been successfully used in patients with HIT, with reduced doses safely used in patients with renal failure and patients with combined hepatic and renal failure [6,24,25]. Its effect is monitored by the aPTT. (See "Direct oral anticoagulants (DOACs) and parenteral direct-acting anticoagulants: Dosing and adverse effects", section on 'Bivalirudin'.)
The recommended initial dose of bivalirudin for HIT is approximately 0.15 mg/kg per hour, adjusted to achieve an aPTT 1.5 to 2.5 times baseline, or as per institutional guidelines. Doses of 0.14 mg/kg per hour in patients with hepatic dysfunction, 0.03 to 0.05 mg/kg per hour in patients with renal or combined hepatic and renal dysfunction, and 0.04±0.03 mg/kg per hour in those receiving continuous renal replacement therapy have been used successfully [26]. Bivalirudin can be removed by hemodialysis.
Danaparoid — Danaparoid (Orgaran) is a heparinoid (heparan derivative) that consists predominantly of dermatan sulfate and low-sulfated heparan sulfate; it is not available in the United States but is available elsewhere. There is extensive experience using danaparoid in patients with HIT, including those with acute HIT and those with a history of HIT who require cardiopulmonary bypass surgery [27,28]. Danaparoid is administered subcutaneously or intravenously.
The recommended therapeutic dose of danaparoid in HIT is an initial intravenous (IV) bolus of 2250 units, modified according to body weight, followed by an IV infusion at the rate of 400 units/hour for four hours, 300 units/hour for the next four hours, and 200 units/hour thereafter. (See "Heparin and LMW heparin: Dosing and adverse effects", section on 'Danaparoid'.)
Danaparoid is monitored by anti-factor Xa activity. Doses are adjusted to achieve anti-factor Xa levels of 0.5 to 0.8 anti-Xa units/mL [6].
Potential disadvantages of danaparoid are the need to measure anti-factor Xa levels, which are less readily available in some settings; its long half-life (25±10 hours); its renal elimination; and the absence of a reversal agent [29].
In some centers, danaparoid may be administered subcutaneously rather than intravenously, particularly when being used to prevent, rather than treat, HIT-associated thrombosis. The package insert should be consulted in such cases to determine the recommended dose.
Fondaparinux — Fondaparinux is a chemically synthesized version of the active pentasaccharide subunit of heparin that does not interact with platelet factor 4 (PF4) and therefore has a theoretical role in treatment and/or prevention of HIT. The 2018 American Society of Hematology guidelines suggest the use of fondaparinux for suspected or confirmed HIT in appropriate patients [5]. The recommendation was conditional, based on a very low certainty of evidence. (See 'Choice and dose of non-heparin anticoagulant' above.)
Therapeutic dosing of fondaparinux is 5 to 10 mg per day (weight based); it is administered subcutaneously. Monitoring is not used in routine practice, although drug levels can be measured. Patients taking fondaparinux for prolonged periods should have periodic monitoring of renal function. (See "Fondaparinux: Dosing and adverse effects", section on 'Monitoring'.)
The safety of fondaparinux in HIT is supported by data from a retrospective review of the Matisse trial, which randomized patients with deep vein thrombosis to treatment with fondaparinux versus low molecular weight (LMW) heparin [30]. A retrospective review of patients with pre-existing HIT antibodies found that fondaparinux did not cause HIT in any of 10 such patients, whereas LMW heparin caused HIT in each of four such patients. Fondaparinux is widely used in the management of patients with confirmed HIT [31-33].
The long half-life of fondaparinux (17 hours), its renal elimination, and the lack of an antidote are potential concerns [34].
Fondaparinux can be given during pregnancy, as described in case reports and other publications [35,36].
Direct oral anticoagulants — Accumulating evidence from observational studies suggests that direct oral anticoagulants (DOACs; oral anticoagulants that directly target thrombin [dabigatran] or factor Xa [eg, apixaban, edoxaban, rivaroxaban]) may be effective in reducing thrombosis risk in HIT, without stimulating HIT antibodies. These agents may be a good option for individuals with HIT, either in the acute setting or for prolonged therapy.
Observational data have identified individuals with HIT who were treated with a DOAC [14,37]. The greatest experience was with rivaroxaban. In some cases, the DOAC was given as initial therapy, and, in some, it was preceded by a parenteral agent. In one of the reviews, there was one thrombotic complication (extension of a catheter-associated thrombus), three cases of clinically relevant bleeding, and no deaths [37]. In the other, there was only one thrombosis and no major bleeding episodes [14]. A subsequent review of 12 patients treated with DOACs in the setting of HIT also reported no new thromboses or major bleeding after starting the DOAC [38]. In vitro studies using patient plasma have not demonstrated any adverse effects of DOACs on HIT antibodies (ie, they did not promote HIT antibody binding to platelets or platelet aggregation) [39,40].
Dosing of DOACs in HIT has not been well-established based on clinical trials; we would use the following approach based on mechanistic understanding and placing a high value on avoiding thromboembolism:
●If a DOAC is started as the initial non-heparin anticoagulant, we would follow the dosing recommended for patients with acute VTE (table 4) and would continue that dosing for a minimum of the standard VTE treatment period or until the platelet count is normal, whichever is longer. Thus, if apixaban is chosen, the dose would be 10 mg twice daily for a minimum of seven days, followed by 5 mg twice daily for the remainder of the course. If the platelet count takes longer than seven days to normalize, we would wait to switch to the 5 mg twice daily dose until the platelet count is ≥150,000/microL. This recommendation is based on personal preference and is not supported by data or significant real-world experience. Use of a DOAC without an initial course of a parenteral anticoagulant should be viewed as highly experimental and should only be used after the patient provides appropriate consent.
●If a DOAC is started after a period of parenteral anticoagulation, we would use the usual dose approved for initial VTE therapy; we would not use the reduced doses that have been tested for extended secondary prevention beyond three to six months of therapy. Thus, the dose for rivaroxaban would be 20 mg once daily and the dose for apixaban would be 5 mg twice daily. If the initial parenteral anticoagulant is used for less than seven days and a switch to apixaban is planned, the initial apixaban dose should be 10 mg twice daily until a total of seven days of combined therapy has passed; for rivaroxaban, the initial dose should be 15 mg twice daily until a total of 21 days of combined therapy has passed. This recommendation is based on personal preference and is not supported by data or significant real-world experience. We prefer apixaban over rivaroxaban in patients with HIT due to the more stable drug levels likely to be achieved with twice-daily dosing compared with once-daily dosing.
A slightly different approach to dosing of the DOACs is suggested in the 2018 American Society of Hematology (ASH) guideline, also based on theoretical considerations rather than evidence from clinical trials [5]. However, the underlying principle of maintaining therapeutic levels of DOAC-based anticoagulation are the same. Online tools are provided on the ASH website [41].
Data on the use of DOACs during pregnancy and breastfeeding are extremely limited, and, as a result, these agents are avoided in pregnancy. (See "Use of anticoagulants during pregnancy and postpartum".)
Other agents — Use of intravenous immune globulin (IVIG) for autoimmune HIT is discussed below. (See 'Autoimmune HIT' below.)
Other approaches, including fibrinogen-depleting agents (eg, ancrod), thrombolysis, plasmapheresis, or dextran, are either not effective, are unproven, or should be used only in unusual circumstances under the supervision of very experienced clinicians.
INCORPORATING RESULTS OF HIT ANTIBODY TESTING — The final diagnosis of HIT is typically confirmed (or excluded) once data from HIT antibody testing are available. (See "Clinical presentation and diagnosis of heparin-induced thrombocytopenia", section on 'Diagnosis'.)
In some cases, the quantitative result of an immunoassay (eg, enzyme-linked immunosorbent assay [ELISA]) for anti-platelet factor 4 (PF4) antibodies is sufficiently low (optical density [OD] <0.40) to exclude HIT or sufficiently high (OD >2.00 for individuals with an intermediate probability 4 Ts score; >1.5 for those with a high probability 4 Ts score) to confirm the diagnosis of HIT. If the results of an immunoassay are indeterminant, a functional assay (eg, serotonin-release assay [SRA] or heparin-induced platelet aggregation [HIPA]) is typically required to confirm or exclude the diagnosis of HIT. These interpretations are summarized in the table (table 5) and discussed in more detail separately. (See "Clinical presentation and diagnosis of heparin-induced thrombocytopenia", section on 'HIT antibody testing'.)
If a diagnosis of HIT is confirmed, the patient should continue on a non-heparin anticoagulant; the duration of anticoagulation depends on the presence or absence of thrombosis (see 'Duration of anticoagulation' below). The importance of the HIT diagnosis and its implications should be emphasized to the patient and all individuals caring for the patient and recorded in the medical record. Sources of heparin include unfractionated heparin, low molecular weight (LMW) heparin, heparin flushes, heparin-bonded catheters, and certain heparin-containing medications and blood products (eg, some prothrombin complex concentrates [PCCs], hematopoietic stem cells, some forms of total parenteral nutrition (table 2)). (See 'Lifelong heparin avoidance (list of sources)' below.)
If a diagnosis of HIT is excluded based on pretest probability and/or HIT antibody testing, the individual can resume heparin therapy (if the original indication persists) and can receive heparin in the future. Alternative causes for thrombocytopenia should be sought, the medical record should clearly state that the patient does not have HIT, and the patient should be educated about the findings and their implications, including the future use of heparin. (See "Clinical presentation and diagnosis of heparin-induced thrombocytopenia", section on 'Differential diagnosis' and "Diagnostic approach to the adult with unexplained thrombocytopenia" and "Causes of thrombocytopenia in children".)
SUBSEQUENT MANAGEMENT
Evaluation for thrombosis — The presence of a venous or arterial thrombosis has implications for the duration of anticoagulation, as discussed below. (See 'Duration of anticoagulation' below.)
All individuals with HIT and signs or symptoms of thrombosis or thromboembolism should have appropriate evaluations to document the location and extent of the thrombus.
We maintain a high index of suspicion for arterial and venous thrombotic events.
In addition, we screen all individuals diagnosed with HIT for lower extremity deep vein thrombosis (DVT), even if asymptomatic; in our experience there is a high frequency of DVT, even in individuals without symptoms. This is consistent with recommendations from the 2018 American Society of Hematology guideline on HIT [5].
Documenting thrombosis, if present, allows more targeted care. It also impacts the duration of non-heparin anticoagulation, which is longer for those with thrombosis than for those without. (See 'Duration of anticoagulation' below.)
Transition to warfarin or other outpatient anticoagulant — As noted above, warfarin should not be used as the initial anticoagulant in patients with HIT, and, if the patient is receiving warfarin at the time HIT is diagnosed, the warfarin should be discontinued and its effects reversed with vitamin K (see 'Hold or reverse warfarin' above). However, once alternative anticoagulation has been started, warfarin can be used for subsequent oral anticoagulation. (See 'Duration of anticoagulation' below.)
Warfarin should be started in a patient with HIT only when both of the following have been accomplished [3,6,11]:
●The patient has been stably anticoagulated with an alternative anticoagulant, and
●The platelet count has increased to at least 150,000/microL
There should be a minimum of five days of overlapping therapy and the international normalized ratio (INR) should be in the target range before the alternative anticoagulant is discontinued [6].
The starting dose of warfarin should be a low maintenance dose of ≤5 mg/day (or phenprocoumon ≤6 mg/day), rather than a high initial or loading dose (eg, ≥10 mg/day), to minimize the transient hypercoagulable state induced by the rapid decline in protein C and S levels [6,42]. (See "Warfarin and other VKAs: Dosing and adverse effects", section on 'Initial dosing' and "Warfarin and other VKAs: Dosing and adverse effects", section on 'Establishing a maintenance dose'.)
Warfarin must be monitored by the prothrombin time (PT) with INR. The target range for anticoagulation should be an INR in the range of 2 to 3. If the patient is being transitioned from argatroban to warfarin, guidelines regarding the appropriate INR target should be followed because both warfarin and argatroban elevate the INR. (See 'Argatroban' above.)
Another option is to transition to (or continue) a direct oral anticoagulant (DOAC) in the outpatient setting, such as the thrombin inhibitor dabigatran or one of the factor Xa inhibitors (apixaban, edoxaban, or rivaroxaban) (table 1). These agents do not require routine monitoring, and, thus, their use avoids the monitoring challenge of transitioning to warfarin in a patient on argatroban. Compared with warfarin, the DOACs also have a shorter functional half-life, fewer drug interactions, do not require ongoing laboratory monitoring, and generally have a lower bleeding risk.
Prior to switching to dabigatran or edoxaban, a minimum of five days of parenteral anticoagulant therapy should be administered, regardless of whether a thrombosis has occurred; although there is no evidence for this strategy, it is extrapolated from their use for the acute treatment of venous thromboembolism (VTE). Apixaban and rivaroxaban do not require an initial period of parenteral anticoagulant. (See "Direct oral anticoagulants (DOACs) and parenteral direct-acting anticoagulants: Dosing and adverse effects".)
The DOACs are contraindicated in individuals with a mechanical heart valve or during pregnancy or breastfeeding.
●Warfarin is used in the outpatient setting for an individual with a mechanical valve. (See "Antithrombotic therapy for mechanical heart valves".)
●Fondaparinux given subcutaneously is an option for outpatient therapy during pregnancy. (See "Fondaparinux: Dosing and adverse effects".)
Duration of anticoagulation — The length of treatment with warfarin or other anticoagulants following an episode of HIT has not been defined in any prospective study. In view of the high risk of thrombosis following the diagnosis of HIT, we suggest that patients with HIT continue anticoagulation with a non-heparin anticoagulant for at least four weeks and for at least three months if a thrombotic event has occurred.
This is consistent with the 2012 American College of Chest Physicians (ACCP) Guidelines and the 2018 American Society of Hematology (ASH) Guideline, although the ASH guideline also allows for shorter duration of anticoagulation (until platelet count normalization) in individuals who have not had a thrombosis, and for some individuals, the appropriate duration of anticoagulation may be longer [5,6].
Expected resolution — The resolution of thrombocytopenia following withdrawal of heparin typically occurs within seven days, often sooner. A minority of patients may have more prolonged thrombocytopenia (persisting HIT) after heparin is discontinued. Clinicians should maintain a high suspicion for continued heparin exposure or other potential causes of thrombocytopenia for patients who do not show a trend toward improving platelet count within three to four days of heparin withdrawal. Other possible diagnoses and evaluations are described separately. (See "Clinical presentation and diagnosis of heparin-induced thrombocytopenia", section on 'Differential diagnosis' and "Diagnostic approach to the adult with unexplained thrombocytopenia" and "Drug-induced immune thrombocytopenia" and "Drug-induced thrombotic microangiopathy (DITMA)" and "Warfarin and other VKAs: Dosing and adverse effects", section on 'Skin necrosis'.)
Despite the rapid normalization of platelet counts and resolution of clinical HIT, HIT antibodies can persist for an extended period of time (and may exceed three months) [43]. (See 'Duration of anticoagulation' above.)
Lifelong heparin avoidance (list of sources) — Patients diagnosed with HIT based on clinical and laboratory data should scrupulously avoid all sources of heparin (including low molecular weight [LMW] heparin and heparin flushes) for life (except in very selected circumstances discussed below). This information should be conveyed to the patient, family members, and all individuals caring for the patient; and emphasized in the medical record, through the inclusion of "heparin allergy."
Sources of heparin include the following (table 2):
●LMW heparins (eg, enoxaparin, dalteparin, nadroparin, tinzaparin)
●Heparin flushes (eg, for arterial lines or heparin locks)
●Heparin-bonded catheters
●Heparin-containing medications (eg, some forms of prothrombin complex concentrates [PCCs])
●Some hematopoietic stem cell (HSC) products
●Some formulations of intravenous medications
●Some total parenteral nutrition preparations
If an individual with a history of HIT requires extended duration anticoagulation in the future, the best alternative(s) to heparin depend on the clinical setting. Approaches to anticoagulant selection are discussed in separate topic reviews on the specific indication.
A rare exception to lifelong heparin avoidance may be an individual who requires a very brief course of heparin (eg, for cardiac surgery). Case reports of aggressive plasmapheresis until the HIT antibody is no longer detectable, followed immediately by surgery, suggest this strategy could be used in expert centers for exceptional cases [44,45]. Cardiopulmonary bypass in patients with active or remote HIT is discussed separately. (See "Management of heparin-induced thrombocytopenia (HIT) during cardiac or vascular surgery".)
PREVENTION — The best way to prevent HIT is to limit heparin exposure. Discussions of strategies to limit the duration of heparin exposure and the lower risk of HIT with low molecular weight (LMW) rather than unfractionated heparin in different clinical scenarios are presented separately. (See "Heparin and LMW heparin: Dosing and adverse effects" and "Clinical presentation and diagnosis of heparin-induced thrombocytopenia", section on 'Incidence and risk factors'.)
A hospital-wide program in which LMW heparin was substituted for unfractionated heparin resulted in a decrease in cases of documented HIT (from 16.5 to 6.1 per 10,000 admissions); HIT with thrombosis was also decreased (from 4.6 to 0.4 per 10,000 admissions) [46]. Hospital expenses related to HIT were also substantially decreased.
A baseline platelet count and periodic platelet count monitoring are used in most patients receiving heparin for more than four days. For patients receiving heparin who are estimated to have a risk of HIT >1 percent, the 2012 American College of Chest Physicians (ACCP) Guidelines suggest platelet count monitoring every two or three days from day 4 to 14 or until heparin is stopped [6]. This and additional details of heparin monitoring are discussed separately. (See "Heparin and LMW heparin: Dosing and adverse effects", section on 'Platelet count monitoring'.)
SPECIAL SCENARIOS
Cardiopulmonary bypass — Patients undergoing cardiac surgery, vascular surgery, or surgeries that require cardiopulmonary bypass (CPB) following or during an episode of HIT are challenging to manage due to the need for intraoperative anticoagulation. Our approach to the management of procedures requiring anticoagulation in individuals with suspected, current, or prior HIT is discussed in detail separately. (See "Management of heparin-induced thrombocytopenia (HIT) during cardiac or vascular surgery".)
Hemodialysis — The use of a non-heparin anticoagulant for prophylaxis or treatment of thromboembolic complications of HIT is similar to the general population. Hemodialysis can be performed using the "no heparin" method (also used for individuals at high risk for bleeding) or using an alternative non-heparin anticoagulant. (See "Anticoagulation for the hemodialysis procedure", section on 'Patients at high risk for bleeding'.)
Autoimmune HIT
Types of HIT variants (delayed onset, refractory, spontaneous) — There are several variants of HIT in which HIT may be present in the absence of heparin (table 6). These syndromes are sometimes referred to as autoimmune HIT:
●Delayed-onset HIT is defined by clinical HIT with thrombocytopenia and/or thrombosis five or more days after heparin has been withdrawn.
●Refractory HIT (also called persistent HIT) refers to HIT with persistent thrombocytopenia and/or thrombosis that lasts for weeks after stopping heparin. This term is only used to refer to ongoing thrombocytopenia or thrombosis due to HIT antibodies; the antibodies alone do not indicate a persistent HIT syndrome.
●Spontaneous HIT refers to HIT that occurs in the absence of recent heparin exposure.
These variants are also referred to collectively as autoimmune HIT [47]. These variants, their pathogenesis, and studies describing their presentation and investigation are discussed separately. (See "Clinical presentation and diagnosis of heparin-induced thrombocytopenia", section on 'Terminology and HIT variants'.)
Management of these variants can be challenging because these patients continue to have clinical HIT in the absence of heparin exposure. Patients with these variants should be treated as if they have HIT (ie, avoid all heparin exposure, hold and reverse warfarin if present, and treat with a non-heparin anticoagulant) [47]. It may be preferable to use a non-heparin anticoagulant that is not monitored with the activated partial thromboplastin time (aPTT) due to the possible interference of HIT-associated disseminated intravascular coagulation (DIC) in some individuals, although there are many considerations that affect the choice of non-heparin anticoagulant. (See 'Choice and dose of non-heparin anticoagulant' above.)
For all these variants it is crucial to confirm that the patient is not experiencing any ongoing or new exposure to heparin that might be responsible for apparent refractoriness to treatment. Sources of heparin are listed above. (See 'Lifelong heparin avoidance (list of sources)' above.)
VITT (COVID-19 vaccine-induced immune thrombotic thrombocytopenia) — COVID-19 vaccine-induced thrombotic thrombocytopenia (VITT) is an incompletely understood syndrome that is emerging as an extremely rare complication in recipients of certain adenovirus-based COVID-19 vaccines.
This syndrome presents with thrombosis and/or thrombocytopenia within 5 to 30 days after receipt of certain COVID-19 vaccines. Diagnosis uses platelet factor 4 (PF4) antibody testing with an enzyme-linked immunosorbent assay (ELISA) and/or a functional test. Management is similar to autoimmune HIT, with therapeutic anticoagulation using a non-heparin anticoagulant and administration of high-dose intravenous immune globulin (IVIG). Epidemiology, evaluation, and management are discussed in detail separately. (See "COVID-19: Vaccine-induced immune thrombotic thrombocytopenia (VITT)".)
Guidance has also been published by the American Society of Hematology (frequently asked questions) and British Society Haematology (expert panel guidance) [48,49].
Role of IVIG — Individuals with platelet activation and thrombocytopenia from HIT-like antibodies in the absence of heparin exposure may need additional interventions to block platelet activation such as intravenous immune globulin (IVIG) [47]. Several reports have described the successful use of IVIG in patients with refractory HIT.
●A 2017 report described three patients with HIT who had extensive thrombosis and protracted thrombocytopenia for two to three weeks after heparin discontinuation, for whom subsequent treatment with intravenous immune globulin (IVIG; dose, 1 g/kg per day for two days) resulted in rapid improvement in their platelet counts [50]. Analysis of their serum, as well as the serum of an additional five patients with similar presentations, documented that IVIG blocked HIT antibody-induced platelet activation in an in vitro assay.
●Other reports have described similar cases with similar responses to IVIG at doses including 400 mg/kg per day or 1 g/kg per day for two to four days [51-54].
Based on these considerations, we would limit consideration of IVIG to patients in whom continued heparin exposure has been ruled out, and in whom there is persistent thrombocytopenia and/or recurrent or refractory thrombosis.
IVIG can be administered at a dose of 1 g/kg once daily for two days or 0.4 g/kg daily for four or five days [50-53]; evidence comparing different regimens in individuals with HIT is not available. The regimen of 0.4 g/kg for four or five days may be preferred, given that a treatment response may be seen prior to the last dose(s), potentially allowing the remaining doses to be deferred.
If IVIG is used, it is used in combination with therapeutic-dose anticoagulation with a non-heparin agent [47]. Although IVIG may reduce platelet activation, anticoagulation is required to reduce the risk of thrombosis (ie, both interventions are required). (See 'Overview of initial management' above.)
HIT with bleeding — Bleeding is rare in patients with HIT. However, if bleeding occurs and the platelet count is <50,000/microL (<100,000/microL for central nervous system bleeding), platelet transfusion should be considered. Platelet transfusions may also be appropriate for some patients who require an invasive procedure. This decision is individualized based on the patient's clinical status, platelet count, and expected bleeding risk. Further information regarding platelet transfusions is presented separately. (See "Platelet transfusion: Indications, ordering, and associated risks", section on 'Indications for platelet transfusion' and "Platelet transfusion: Indications, ordering, and associated risks", section on 'TTP or HIT'.)
Additional interventions for bleeding include the use of a reversal agent, if the patient is still anticoagulated, and correction of surgical/anatomic defects. (See "Heparin and LMW heparin: Dosing and adverse effects", section on 'Bleeding'.)
In contrast to the treatment of bleeding, platelet transfusions and reversal agents are generally not used prophylactically (ie, for the routine prevention of bleeding) in patients with HIT, due to the low risk of bleeding in this syndrome and the possibility, although small, that additional platelets might precipitate thrombotic events (ie, "add fuel to the fire").
Support for the use of platelet transfusions in patients with bleeding in the setting of HIT comes from two reports (41 patients in total) that showed appropriate 24-hour post-transfusion platelet count increments in the majority, with cessation of bleeding in two-thirds of the bleeding patients [55,56].
Our approach is supported by a large retrospective review that included 6332 patients with HIT, approximately 7 percent of whom received a platelet transfusion [57]. There was a slight increase in the rate of arterial thrombosis in patients with HIT who received platelets compared with those who did not (6.9 versus 3.1 percent; absolute increase, 3.8 percent; adjusted odds ratio [OR], 3.4; 95% CI 1.2-9.5). The rate of venous thrombosis was not different in those who received platelets and those who did not (adjusted OR 0.8; 95% CI 0.4-1.7). An earlier review of the literature revealed no case of a complication clearly attributable to platelet transfusion [55].
Our approach is consistent with the 2012 American College of Chest Physician (ACCP) Guidelines, which concluded that platelet transfusions can be considered in patients with HIT and overt bleeding or during the performance of an invasive procedure with a high bleeding risk, particularly if heparin has been stopped for at least several hours [6].
HIT during pregnancy — HIT during pregnancy is extremely rare. (See "Clinical presentation and diagnosis of heparin-induced thrombocytopenia", section on 'Incidence and risk factors'.)
If a pregnant woman develops HIT, or if a woman receiving anticoagulation for HIT becomes pregnant, it is important to use an anticoagulant that causes the least risk to the developing embryo/fetus. Options include fondaparinux or danaparoid, or, for a woman with a mechanical heart valve, warfarin. These subjects are discussed in more detail separately. (See "Use of anticoagulants during pregnancy and postpartum", section on 'HIT during or immediately preceding pregnancy' and "Management of antithrombotic therapy for a prosthetic heart valve during pregnancy", section on 'Vitamin K antagonist'.)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Anticoagulation" and "Society guideline links: Heparin-induced thrombocytopenia (HIT)".)
SUMMARY AND RECOMMENDATIONS
●Presumptive diagnosis is sufficient for treatment – We make a presumptive diagnosis of heparin-induced thrombocytopenia (HIT) based on clinical findings and immediately available laboratory data. The 4 Ts score (calculator 1) is an easy-to-use score that quantifies the clinical findings associated with HIT (eg, degree of thrombocytopenia, timing, thrombotic events or sequelae, alternative causes of thrombocytopenia) (table 3). This score should be used as a guide but should not substitute for clinical judgment. (See "Clinical presentation and diagnosis of heparin-induced thrombocytopenia", section on '4 Ts score'.)
●Immediate treatment – Individuals with a presumptive diagnosis of HIT should be treated as if they have HIT until definitive laboratory testing is available (algorithm 1). The two main goals of treatment are to stop platelet activation by removing all sources of heparin and to provide anticoagulation until the risk of thrombosis has returned to baseline. (See 'Immediate actions' above.)
•All sources of heparin should be discontinued.
•If the patient is receiving warfarin, this should be stopped and reversed with vitamin K until anticoagulation with another non-heparin anticoagulant has been established.
•We recommend full-dose therapeutic anticoagulation with a non-heparin anticoagulant rather than discontinuing heparin alone or discontinuing heparin and providing a lower (eg, prophylactic) dose of a non-heparin anticoagulant (Grade 1B).
●Choice of anticoagulant – There are several non-heparin anticoagulants that can be used in a patient with HIT. These include parenteral direct thrombin inhibitors (eg, argatroban, bivalirudin), danaparoid (not available in the United States), fondaparinux, or direct oral anticoagulants (DOACs) such as apixaban, edoxaban, rivaroxaban, or dabigatran. Our approach to the choice of anticoagulant takes into account the urgency of anticoagulation, possible need for urgent reversal, renal and hepatic function, and other considerations such as route of administration (table 1). (See 'Anticoagulation' above.)
●Diagnostic confirmation – Once definitive laboratory testing is available, we confirm or exclude the diagnosis of HIT. We consider the diagnosis confirmed if there is a high probability 4 Ts score and an enzyme-linked immunosorbent assay (ELISA) with optical density (OD) >1.50, an intermediate probability 4 Ts score and ELISA OD >2.00, or a positive functional assay (serotonin release assay [SRA], heparin-induced platelet aggregation [HIPA]) (table 5). We consider the diagnosis excluded if the 4Ts score is low probability, if there is an ELISA with OD <0.40, or if there is a negative functional assay. Individuals for whom HIT is excluded can continue on heparin-based anticoagulation, if indicated. An alternative explanation for thrombocytopenia should be sought. (See 'Incorporating results of HIT antibody testing' above and "Clinical presentation and diagnosis of heparin-induced thrombocytopenia", section on 'Diagnosis' and "Clinical presentation and diagnosis of heparin-induced thrombocytopenia", section on 'Differential diagnosis'.)
●Further evaluations and transition to oral anticoagulation – For patients with confirmed HIT, non-heparin anticoagulation is continued. We have a low threshold for evaluating symptoms of thrombosis, and we perform lower extremity ultrasound in all individuals who are asymptomatic to detect clinically silent deep vein thrombosis (DVT). Warfarin can be started once the patient has been stably anticoagulated with a non-heparin anticoagulant and the platelet count has recovered to ≥150,000/microL. Low initial warfarin doses, rather than higher "loading" doses, should be used, and the non-heparin anticoagulant should be continued for at least five days along with warfarin and until the international normalized ratio (INR) has reached the target range of 2 to 3. Other options for outpatient treatment include fondaparinux or a DOAC (table 1). (See 'Evaluation for thrombosis' above and 'Transition to warfarin or other outpatient anticoagulant' above.)
●Duration of anticoagulation – The duration of anticoagulation with a non-heparin agent depends on whether a thrombotic event has occurred (see 'Duration of anticoagulation' above):
•For individuals who have not had a thrombosis, we suggest anticoagulation for at least four weeks (Grade 2C).
•For individuals who have had a thrombosis, we suggest anticoagulation for at least three months (Grade 2C).
The importance of lifetime avoidance of heparin should be conveyed to the patient, family members, and all clinicians caring for the patient and should be emphasized in the medical record through the inclusion of "heparin allergy" (table 2). (See 'Lifelong heparin avoidance (list of sources)' above.)
●IVIG for HIT variants – Rare variants of HIT including delayed-onset HIT, refractory (persistent) HIT, or spontaneous HIT, collectively referred to as autoimmune HIT (table 6), are characterized by HIT antibodies that activate platelets in the absence of heparin. These conditions should be treated similarly to other forms of HIT; in addition, refractory HIT may respond to intravenous immune globulin (IVIG). (See 'Autoimmune HIT' above.)
●COVID-19 vaccine and VITT – Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a very rare complication associated with certain COVID-19 vaccines. Management is similar to autoimmune HIT, with anticoagulation using a non-heparin anticoagulant and administration of intravenous immune globulin (IVIG), as discussed in detail separately. (See 'VITT (COVID-19 vaccine-induced immune thrombotic thrombocytopenia)' above.)
●Bleeding – Bleeding is rare with HIT, and we suggest not giving prophylactic platelet transfusions in the absence of bleeding (Grade 2B). However, platelet transfusions should be given if there is clinically important bleeding and a platelet count <50,000/microL (<100,000/microL for central nervous system bleeding). Anticoagulant reversal may also be indicated in selected cases of serious bleeding; this decision requires input from the treating clinician and/or consultants with expertise in HIT. (See 'HIT with bleeding' above.)
●Cardiac or vascular surgery patients – The management of suspected, current, or prior HIT in individuals undergoing cardiac or vascular surgery that requires intraoperative anticoagulation is discussed in detail separately. (See "Management of heparin-induced thrombocytopenia (HIT) during cardiac or vascular surgery".)
●Pregnancy – HIT is rare in pregnancy. If HIT develops during pregnancy or if an individual receiving anticoagulation for HIT becomes pregnant, it is important to use an anticoagulant that causes the least risk to the developing embryo/fetus. Options include fondaparinux or danaparoid, or, if a mechanical heart valve is present, warfarin. These subjects are discussed in more detail separately. (See "Use of anticoagulants during pregnancy and postpartum", section on 'HIT during or immediately preceding pregnancy' and "Management of antithrombotic therapy for a prosthetic heart valve during pregnancy", section on 'Vitamin K antagonist'.)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Steven Coutre, MD (deceased), who contributed to an earlier version of this topic review.
