Treatment of heparin-induced thrombocytopenia
For presumed heparin-induced thrombocytopenia (HIT) (an intermediate or high probability 4Ts score) or confirmed HIT (clinical features and positive laboratory test), immediately stop heparin (unfractionated or low molecular weight). An alternative anticoagulant must be started because HIT induces marked hypercoagulability with a high risk of arterial or venous thrombosis, despite the thrombocytopenia. Thrombocytopenia typically resolves within 7 days of stopping heparin.
In presumed or confirmed HIT the following treatment cautions apply:
- Do not give low molecular weight heparin (LMWH) as an alternative anticoagulant for patients with unfractionated heparin (UFH)-induced HIT (LMWH can cross-react with the HIT antibodies).
- Do not give UFH as an alternative anticoagulant for patients with LMWH-induced HIT (UFH can cross-react with the HIT antibodies).
- Do not use devices containing heparin (eg heparin-containing syringes and catheters).
- Do not use warfarin alone as the initial anticoagulant (warfarin can cause skin necrosis).
- Do not start warfarin until the platelet count is within the normal range.
To treat hypercoagulability caused by HIT, consider using full therapeutic doses of danaparoid, fondaparinux, bivalirudin, argatroban or a direct-acting oral anticoagulant (DOAC); choice depends on the local availability and patient-specific factors (eg kidney function). At the time of writing, there are no anticoagulants approved on the Pharmaceutical Benefits Scheme (PBS) for the treatment of HIT and argatroban is only available via the Special Access Scheme. Seek specialist haematologist advice regarding locally available drugs.
A suitable danaparoid regimen to treat HIT is:
danaparoid danaparoid danaparoid danaparoid
less than 60 kg: 1500 units intravenously, for the first dose
60 to less than 75 kg: 2250 units intravenously, for the first dose
75 to 90 kg: 3000 units intravenously, for the first dose
more than 90 kg: 3750 units intravenously, for the first dose
FOLLOWED BY
danaparoid 400 units/hour by intravenous infusion for 4 hours, then 300 units/hour for 4 hours, then 150 to 200 units/hour, adjusted according to anti-Xa level.
Check the anticoagulant effect of danaparoid daily with anti-Xa assays. Adjust the dose to achieve anti-Xa levels in the range of 0.5 to 0.8 units/mL; seek specialist haematologist advice. Danaparoid has a long half-life and is excreted via the kidneys; avoid its use if the patient’s creatine clearance (CrCl) is less than 30 mL/min. No specific antidote is available.
A suitable fondaparinux regimen to treat HIT is:
fondaparinux fondaparinux fondaparinux fondaparinux
less than 50 kg: 5 mg subcutaneously, once daily
50 to 100 kg: 7.5 mg subcutaneously, once daily
more than 100 kg: 10 mg subcutaneously, once daily.
Fondaparinux has a long half-life and is excreted via the kidneys; if it is required for a patient with a CrCl less than 50 mL/min seek advice from a specialist. No specific antidote is available.
In small case series bivalirudin has been effective for patients who developed HITTsu, 2012. A suitable regimen is:
Bivalirudin bivalirudin bivalirudin bivalirudin
CrCl more than 60 mL/min: initially 0.15 mg/kg/hour by intravenous infusion, adjusted according to APTT
CrCl 30 to 60 mL/min: initially 0.08 mg/kg/hour by intravenous infusion, adjusted according to APTT.
Consult a local protocol for activated partial thromboplastin time (APTT) values or seek specialist haematologist advice. There is no evidence for the safety and efficacy of bivalirudin for patients with a CrCl less than 30 mL/min.
Argatroban has limited availability, but it is preferred for patients with a CrCl less than 30 mL/min; seek specialist haematologist advice. A suitable argatroban regimen to treat HIT for non–critically unwell patients isJoseph, 2019:
argatroban argatroban argatroban argatroban
normal liver function: 2 micrograms/kg/minute by intravenous infusion, adjusted according to APTT
liver impairment: 0.5 micrograms/kg/minute by intravenous infusion, adjusted according to APTT.
A suitable argatroban regimen to treat HIT for critically unwell patients isJoseph, 2019:
argatroban argatroban argatroban argatroban
life-threatening thromboembolism: 2 micrograms/kg/minute by intravenous infusion, adjusted according to APTT
non–life-threatening thromboembolism: 1 microgram/kg/minute by intravenous infusion, adjusted according to APTT
liver impairment or no thrombosis: 0.5 micrograms/kg/min by intravenous infusion, adjusted according to APTT.
Consult a local protocol for APTT values or seek specialist haematologist advice.
At the time of writing, studies are underway to evaluate the use of DOACs as the initial treatment for HIT. DOACs can be used instead of warfarin after patients who have developed HIT have responded to parenteral anticoagulation and their platelet count has recoveredJoseph, 2019. For suggested DOAC dosages in low-risk, stable patients, see the American Society of Hematology pocket guide.
In a patient who has developed HIT, start warfarin when therapeutic anticoagulation with one of the above parenteral anticoagulants is established and the platelet count has risen, usually to more than 150 × 109/LLinkins, 2012. After starting warfarin, stop parenteral anticoagulant therapy once the international normalised ratio (INR) has been 2 or more on 2 consecutive days. Continue warfarin therapy for at least 1 month. In patients who have developed arterial or venous thrombosis, continue warfarin therapy for at least 3 months.
Give patients with a history of HIT who require parenteral anticoagulation (eg during perioperative periods) one of the above anticoagulants, to avoid re-exposure to heparin (UFH or LMWH). Seek specialist haematologist advice regarding locally available drugs and protocols.