Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

suspected HIT with 4Ts score of ≥4, or confirmed acute HIT

1st line – stop heparin (including LMWH) immediately and take blood sample

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ACUTE
|
suspected HIT with 4Ts score of ≥4, or confirmed acute HIT
1st line – 

stop heparin (including LMWH) immediately and take blood sample

If a patient has suspected HIT and an intermediate- or high-probability 4Ts score (i.e., ≥4), all sources of heparin (including low molecular weight heparin [LMWH]) must be discontinued immediately (including heparin used for flushing lines). A blood sample should be sent for laboratory confirmation of HIT.[38]

Some clinicians are unaware that LMWH is contraindicated in patients with suspected or confirmed HIT; therefore, it is important to reiterate that LMWH should not be continued or started in these patients.

Consider – discontinue vitamin K antagonist (if started) and administer vitamin K

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ACUTE
|
suspected HIT with 4Ts score of ≥4, or confirmed acute HIT
Consider – 

discontinue vitamin K antagonist (if started) and administer vitamin K

Additional treatment recommended for SOME patients in selected patient group

If a vitamin K antagonist (e.g., warfarin) has been started, oral or intravenous vitamin K should be administered and the vitamin K antagonist discontinued.

Vitamin K antagonists alone will not prevent the development of HIT-associated thrombosis. Furthermore, they increase the risk of venous gangrene if used without overlap with other non-heparin anticoagulants in patients with confirmed HIT who have not achieved platelet recovery.[57]

Primary options

phytomenadione: consult specialist for guidance on dose

Plus – argatroban, bivalirudin, danaparoid, fondaparinux, or a direct oral anticoagulant + delay non-urgent surgery

Back
ACUTE
|
suspected HIT with 4Ts score of ≥4, or confirmed acute HIT
|
non-pregnant normal renal function: requiring non-urgent cardiac surgery
Plus – 

argatroban, bivalirudin, danaparoid, fondaparinux, or a direct oral anticoagulant + delay non-urgent surgery

Treatment recommended for ALL patients in selected patient group

A non-heparin anticoagulant should be initiated before the HIT assay result is available (even if the patient does not currently have thrombosis).[38] Therapeutic doses of a non-heparin anticoagulant should be given to patients with a high-probability 4Ts score (≥6), and patients with an intermediate-probability 4Ts score (4 or 5) who are not at high risk of bleeding.[38] Therapeutic doses should be continued if HIT is confirmed. Patients with an intermediate-probability 4Ts score who are at high risk of bleeding can be given prophylactic doses of a non-heparin anticoagulant while awaiting results of the HIT assay.[38] However, once HIT is confirmed, the dose should be increased to therapeutic levels if possible.[38]

Non-urgent cardiac surgery should be delayed until the patient is HIT antibody negative (i.e., approximately 60-100 days depending on the type of HIT assay used).[38]

Options for these patients include argatroban, bivalirudin, danaparoid, fondaparinux, or a direct oral anticoagulant (DOAC; rivaroxaban, apixaban, or dabigatran).[38] Fondaparinux and DOACs are not licensed for the treatment of HIT.

Despite rare reports of fondaparinux-induced HIT, observational studies report the successful use of fondaparinux to treat HIT, and it is considered to be a non-heparin anticoagulant.[2][3] A history of fondaparinux-induced HIT should be ruled out before use.

Accumulated observational evidence suggests that the DOACs rivaroxaban, apixaban, and dabigatran may be safe and effective for the treatment of HIT.[58][59] Most published reports have been for rivaroxaban.[60][61] Edoxaban has only been reported in a single case study for treatment of HIT, so it cannot be recommended for use for this indication.[62]

Lead-in therapy with a parenteral anticoagulant before starting dabigatran is not required in patients with HIT.

Once scheduled, heparin can be used during cardiac surgery in patients with a previous history of HIT if HIT antibodies are negative, but exposure to heparin should be limited to the procedure with non-heparin anticoagulants used peri-operatively.

Primary options

argatroban: consult specialist for guidance on dose

Secondary options

bivalirudin: consult specialist for guidance on dose

OR

danaparoid sodium: consult specialist for guidance on dose

OR

fondaparinux: consult specialist for guidance on dose

OR

rivaroxaban: consult specialist for guidance on dose

OR

apixaban: consult specialist for guidance on dose

OR

dabigatran: consult specialist for guidance on dose

Plus – bivalirudin

Back
ACUTE
|
suspected HIT with 4Ts score of ≥4, or confirmed acute HIT
|
non-pregnant normal renal function: requiring urgent cardiac surgery
Plus – 

bivalirudin

Treatment recommended for ALL patients in selected patient group

A non-heparin anticoagulant should be initiated before the HIT assay result is available (even if the patient does not currently have thrombosis).[38] Therapeutic doses of a non-heparin anticoagulant should be given to patients with a high-probability 4Ts score (≥6), and patients with an intermediate-probability 4Ts score (4 or 5) who are not at high risk of bleeding.[38] Therapeutic doses should be continued if HIT is confirmed. Patients with an intermediate-probability 4Ts score who are at high risk of bleeding can be given prophylactic doses of a non-heparin anticoagulant while awaiting results of the HIT assay.[38] However, once HIT is confirmed, the dose should be increased to therapeutic levels if possible.[38]

Bivalirudin is the non-heparin anticoagulant of choice in patients who require urgent cardiac surgery.[38] Dose varies according to on-pump or off-pump procedures and requires special technical considerations to prevent intra-operative stasis of blood.[64] Use is generally limited to the procedure with other non-heparin alternatives used peri-operatively.

Primary options

bivalirudin: consult specialist for guidance on dose

Plus – bivalirudin or argatroban

Back
ACUTE
|
suspected HIT with 4Ts score of ≥4, or confirmed acute HIT
|
non-pregnant normal renal function: requiring PCI
Plus – 

bivalirudin or argatroban

Treatment recommended for ALL patients in selected patient group

A non-heparin anticoagulant should be initiated before the HIT assay result is available (even if the patient does not currently have thrombosis).[38] Therapeutic doses of a non-heparin anticoagulant should be given to patients with a high-probability 4Ts score (≥6), and patients with an intermediate-probability 4Ts score (4 or 5) who are not at high risk of bleeding.[38] Therapeutic doses should be continued if HIT is confirmed. Patients with an intermediate-probability 4Ts score who are at high risk of bleeding can be given prophylactic doses of a non-heparin anticoagulant while awaiting results of the HIT assay.[38] However, once HIT is confirmed, the dose should be increased to therapeutic levels if possible.[38]

Patients requiring percutaneous coronary intervention (PCI) should be treated with bivalirudin, or, alternatively, argatroban as a second-line option.[38]

High doses of argatroban are not recommended in PCI patients with clinically significant hepatic disease.

Primary options

bivalirudin: consult specialist for guidance on dose

Secondary options

argatroban: consult specialist for guidance on dose; dose depends on activated clotting time

Plus – argatroban or danaparoid or bivalirudin

Back
ACUTE
|
suspected HIT with 4Ts score of ≥4, or confirmed acute HIT
|
non-pregnant: requiring renal replacement therapy
Plus – 

argatroban or danaparoid or bivalirudin

Treatment recommended for ALL patients in selected patient group

A non-heparin anticoagulant should be initiated before the HIT assay result is available (even if the patient does not currently have thrombosis).[38] Therapeutic doses of a non-heparin anticoagulant should be given to patients with a high-probability 4Ts score (≥6), and patients with an intermediate-probability 4Ts score (4 or 5) who are not at high risk of bleeding.[38] Therapeutic doses should be continued if HIT is confirmed. Patients with an intermediate-probability 4Ts score who are at high risk of bleeding can be given prophylactic doses of a non-heparin anticoagulant while awaiting results of the HIT assay.[38] However, once HIT is confirmed, the dose should be increased to therapeutic levels if possible.[38]

Argatroban can be used in patients who require renal replacement therapy. Danaparoid or bivalirudin are alternative options (dose reduction may be required).[38]

Primary options

argatroban: consult specialist for guidance on dose; a dose adjustment may be necessary in dialysis patients

Secondary options

danaparoid sodium: consult specialist for guidance on dose

OR

bivalirudin: consult specialist for guidance on dose

Plus – argatroban or bivalirudin

Back
ACUTE
|
suspected HIT with 4Ts score of ≥4, or confirmed acute HIT
|
non-pregnant: renal insufficiency not requiring renal replacement therapy
Plus – 

argatroban or bivalirudin

Treatment recommended for ALL patients in selected patient group

A non-heparin anticoagulant should be initiated before the HIT assay result is available (even if the patient does not currently have thrombosis).[38] Therapeutic doses of a non-heparin anticoagulant should be given to patients with a high-probability 4Ts score (≥6), and patients with an intermediate-probability 4Ts score (4 or 5) who are not at high risk of bleeding.[38] Therapeutic doses should be continued if HIT is confirmed. Patients with an intermediate-probability 4Ts score who are at high risk of bleeding can be given prophylactic doses of a non-heparin anticoagulant while awaiting results of the HIT assay.[38] However, once HIT is confirmed, the dose should be increased to therapeutic levels if possible.[38]

Argatroban is the preferred non-heparin anticoagulant in these patients. Bivalirudin is an alternative option (a dose reduction may be required).[38]

Primary options

argatroban: consult specialist for guidance on dose

Secondary options

bivalirudin: consult specialist for guidance on dose

Plus – fondaparinux or danaparoid

Back
ACUTE
|
suspected HIT with 4Ts score of ≥4, or confirmed acute HIT
|
pregnant or breastfeeding
Plus – 

fondaparinux or danaparoid

Treatment recommended for ALL patients in selected patient group

A non-heparin anticoagulant should be initiated before the HIT assay result is available (even if the patient does not currently have thrombosis).[38] Therapeutic doses of a non-heparin anticoagulant should be given to patients with a high-probability 4Ts score (≥6), and patients with an intermediate-probability 4Ts score (4 or 5) who are not at high risk of bleeding.[38] Therapeutic doses should be continued if HIT is confirmed. Patients with an intermediate-probability 4Ts score who are at high risk of bleeding can be given prophylactic doses of a non-heparin anticoagulant while awaiting results of the HIT assay.[38] However, once HIT is confirmed, the dose should be increased to therapeutic levels if possible.[38]

Non-heparin anticoagulants are not approved for use in pregnant or breastfeeding women. Danaparoid and fondaparinux have been used in this setting; however, there are limited data available to support this practice.[43][44][63]

Despite rare reports of fondaparinux-induced HIT, observational studies report the successful use of fondaparinux to treat HIT, and it is considered to be a non-heparin anticoagulant.[2][3] A history of fondaparinux-induced HIT should be ruled out before use.

Fondaparinux is not licensed for the treatment of HIT.

Primary options

fondaparinux: consult specialist for guidance on dose

OR

danaparoid sodium: consult specialist for guidance on dose

suspected HIT with 4Ts score ≤3

1st line – continue heparin and do not test for HIT unless there is uncertainty about the score

Back
ACUTE
|
suspected HIT with 4Ts score ≤3
1st line – 

continue heparin and do not test for HIT unless there is uncertainty about the score

A low 4Ts score (i.e., ≤3) alone has high negative predictive value; guidelines recommend against laboratory testing in these patients.[38][43][44]

Heparin (including low molecular weight heparin [LMWH]) can be continued as needed if there is NO uncertainty about the 4Ts score, and/or the clinician decides that a HIT assay is not necessary.

Testing for HIT should be considered if there is uncertainty about the score (e.g., multiple missing platelet counts, history of recent heparin exposure is unclear, concurrent potential causes of thrombocytopenia).[38][45]

Heparin should be stopped immediately if clinical suspicion is sufficiently high to warrant the clinician ordering an assay.

While awaiting assay results, an alternative non-heparin anticoagulant can be started in those requiring ongoing anticoagulation. Direct oral anticoagulants (DOACs; rivaroxaban, apixaban, or dabigatran) and fondaparinux are preferred (depending on the indication) over argatroban or bivalirudin until HIT is confirmed, because they have a lower risk of bleeding and are less costly.

Fondaparinux and DOACs are not licensed for the treatment of HIT.

Despite rare reports of fondaparinux-induced HIT, observational studies report the successful use of fondaparinux to treat HIT, and it is considered to be a non-heparin anticoagulant.[2][3] A history of fondaparinux-induced HIT should be ruled out before use.

Accumulated observational evidence suggests that the DOACs rivaroxaban, apixaban, and dabigatran may be safe and effective for the treatment of HIT.[58][59] Most published reports have been for rivaroxaban.[60][61] Edoxaban has only been reported in a single case study for treatment of HIT, so it cannot be recommended for use for this indication.[62]

Lead-in therapy with a parenteral anticoagulant before starting dabigatran is not required in patients with HIT.

Primary options

fondaparinux: consult specialist for guidance on dose

OR

rivaroxaban: consult specialist for guidance on dose

OR

apixaban: consult specialist for guidance on dose

OR

dabigatran: consult specialist for guidance on dose

ONGOING

platelet recovery (subacute HIT A)

1st line – continue initial anticoagulant and transition to warfarin or fondaparinux, or continue fondaparinux or direct oral anticoagulant

Back
ONGOING
|
platelet recovery (subacute HIT A)
1st line – 

continue initial anticoagulant and transition to warfarin or fondaparinux, or continue fondaparinux or direct oral anticoagulant

Platelet recovery is generally said to have occurred when platelet levels have returned to >150 × 10⁹/L (>150 × 10³/microlitre), or to the patient’s previous baseline platelet count if it was <150 × 10⁹/L (<150 × 10³/microlitre).

The duration of treatment for confirmed HIT is controversial. In patients with HIT-provoked thrombosis, 3 months of anticoagulant therapy is reasonable. In patients without thrombosis, non-heparin anticoagulant therapy should continue at least until platelet recovery.[38][44]

Platelet recovery indicates that ongoing thrombin generation has been halted. The American Society of Hematology (ASH) refers to the state after platelet recovery, but prior to the functional assay becoming negative, as subacute HIT A.[38] Treatment options for subacute HIT A in non-pregnant patients include direct oral anticoagulants (DOACs; rivaroxaban, apixaban, dabigatran); vitamin K antagonists (e.g., warfarin) are an alternative.[38]

Warfarin is considered safe to use during breastfeeding. DOACs should not be used during breastfeeding because of uncertainty about transfer into breast milk. Warfarin should be started at a low dose only after platelet recovery and overlapped with argatroban, danaparoid, bivalirudin, or fondaparinux for a minimum of 5 days until the international normalised ratio (INR) is therapeutic. Argatroban prolongs the INR; therefore, a specialist should be consulted for guidance on switching to warfarin. Overlap is not required when switching from DOACs to warfarin; however, switching between oral anticoagulants should be done under specialist guidance and take individual patient circumstances into account.

Fondaparinux is another option for ongoing treatment; however, it requires subcutaneous injections. It is preferred over warfarin in pregnant women, but data on its safety are limited. A specialist should be consulted for guidance on overlapping with fondaparinux because the time course will differ depending on the initial anticoagulant.

Fondaparinux is not licensed for the treatment of HIT.

Primary options

warfarin: consult specialist for guidance on dose and switching from initial anticoagulant

Secondary options

fondaparinux: consult specialist for guidance on dose and switching from initial anticoagulant

OR

rivaroxaban: consult specialist for guidance on dose and switching from initial anticoagulant

OR

apixaban: consult specialist for guidance on dose and switching from initial anticoagulant

OR

dabigatran: consult specialist for guidance on dose and switching from initial anticoagulant

Plus – haemodialysis with regional citrate anticoagulation or saline flushes

Back
ONGOING
|
platelet recovery (subacute HIT A)
|
requiring renal replacement therapy
Plus – 

haemodialysis with regional citrate anticoagulation or saline flushes

Treatment recommended for ALL patients in selected patient group

If platelets have normalised, haemodialysis with regional citrate anticoagulation or saline flushes may be used instead of non-heparin anticoagulants.

remote HIT

1st line – thromboprophylaxis

Back
ONGOING
|
remote HIT
1st line – 

thromboprophylaxis

Patients with a prior history of HIT may require thromboprophylaxis during medical admissions or following surgery. American Society of Hematology guidelines recommend using a non-heparin anticoagulant (e.g., direct oral anticoagulant or fondaparinux) over unfractionated heparin or low molecular weight heparin.[38]

Primary options

rivaroxaban: consult specialist for guidance on dose

OR

apixaban: consult specialist for guidance on dose

OR

dabigatran: consult specialist for guidance on dose

OR

edoxaban: consult specialist for guidance on dose

OR

fondaparinux: consult specialist for guidance on dose

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Choose a patient group to see our recommendations

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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