Approach
Treatment of suspected HIT is premised upon 4Ts score:
≥4 indicating a high or intermediate clinical probability of HIT, or
≤3 indicating a low probability of HIT.
[Figure caption and citation for the preceding image starts]: Diagnostic algorithm for heparin-induced thrombocytopeniaCreated by the BMJ Knowledge Centre [Citation ends].
Suspected HIT with 4Ts score ≥4, or confirmed acute HIT
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) and a blood sample 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.
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]
A non-heparin anticoagulant should be initiated before the result of the HIT assay 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]
Choice of non-heparin anticoagulant
The choice of non-heparin anticoagulant depends on clinical factors such as whether cardiac surgery or percutaneous coronary intervention (PCI) is necessary, the presence of renal impairment, and pregnancy. It may also depend on other factors such as cost, availability, and the ability to monitor the anticoagulant effect.
Non-heparin anticoagulant options include argatroban, fondaparinux, bivalirudin, danaparoid, and the direct oral anticoagulants (DOACs) rivaroxaban and apixaban.[38] Fondaparinux and DOACs are not licensed for the treatment of HIT. However, fondaparinux is known to be a safe anticoagulant for prophylaxis (in patients without HIT or with remote 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 been reported in a single case study for treatment of HIT, so it cannot be recommended for use for this indication.[62] However, edoxaban is known to be a safe anticoagulant for prophylaxis (in patients without HIT or with remote HIT).
Cardiac surgery or PCI[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, fondaparinux, or a DOAC (rivaroxaban, apixaban, or dabigatran).[38]
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.
In those requiring urgent cardiac surgery, bivalirudin is indicated. Use is generally limited to the procedure with other non-heparin alternatives used peri-operatively.
Patients requiring PCI should be treated with bivalirudin, or, alternatively, argatroban as a second-line option.
Renal impairment[38]
Argatroban is the preferred non-heparin anticoagulant in patients with renal insufficiency. Bivalirudin is an alternative option (a dose reduction may be required).
Argatroban can also be used in patients who require renal replacement therapy. Danaparoid or bivalirudin are alternative options (dose reduction may be required). Haemodialysis with regional citrate anticoagulation or saline flushes may be used instead of non-heparin anticoagulants once platelets have normalised.
Pregnant or breastfeeding women[43][44][63]
None of the non-heparin anticoagulants are 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.
Suspected HIT with 4Ts score ≤3
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 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:[38][45]
there is uncertainty about the score (e.g., multiple missing platelet counts, history of recent heparin exposure is unclear, concurrent potential causes of thrombocytopenia).
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 patients requiring ongoing anticoagulation. 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.
Platelet recovery
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 non-heparin 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 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 taken 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.
Remote HIT
Patients with a prior history of HIT may require thromboprophylaxis during medical admissions or following surgery. ASH guidelines recommend using a non-heparin anticoagulant (e.g., DOAC or fondaparinux) over unfractionated heparin or LMWH.[38]
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