From the Guidelines
Patients who are heparin non-responders should be switched to a non-heparin anticoagulant, such as argatroban, bivalirudin, danaparoid, fondaparinux, or a direct oral anticoagulant (DOAC), as recommended by the American Society of Hematology guidelines. The choice of agent may be influenced by drug factors, patient factors, and experience of the clinician 1. In patients with critical illness, increased bleeding risk, or increased potential need for urgent procedures, argatroban or bivalirudin may be preferred due to their shorter duration of effect. Some key considerations for management options include:
- Argatroban, with an initial dose and adjustment to target aPTT 1.5-3 times baseline, is a suitable alternative for heparin non-responders
- Bivalirudin, with a dose of 0.15-0.2 mg/kg/hr, is another option for patients who do not respond to heparin
- Fondaparinux, administered subcutaneously at a dose of 5-10 mg daily based on weight, can also be used to bypass the antithrombin-dependent mechanism of heparin
- For patients with antithrombin deficiency, supplementation with antithrombin concentrate while continuing heparin therapy may restore anticoagulant effect, as suggested by the guidelines 1. Regular monitoring with anti-Xa levels rather than aPTT provides more accurate assessment of anticoagulation in these challenging cases. The choice between these options depends on the patient's renal function, bleeding risk, and the specific clinical scenario requiring anticoagulation, as outlined in the American Society of Hematology guidelines 1.
From the FDA Drug Label
If the coagulation test is unduly prolonged or if hemorrhage occurs, discontinue heparin promptly Resistance to heparin is frequently encountered in fever, thrombosis, thrombophlebitis, infections with thrombosing tendencies, myocardial infarction, cancer, in postsurgical patients, and patients with antithrombin III deficiency. Close monitoring of coagulation tests is recommended in these cases. Adjustment of heparin doses based on anti-Factor Xa levels may be warranted.
The management options for patients who are heparin non-responders include:
- Close monitoring of coagulation tests
- Adjustment of heparin doses based on anti-Factor Xa levels
- Consideration of alternative anticoagulants if necessary, as in the case of heparin-induced thrombocytopenia (HIT) or heparin-induced thrombotic thrombocytopenia (HITT) 2
From the Research
Management Options for Heparin Non-Responders
Heparin non-responders, also known as heparin resistance, can be defined as the requirement of high doses of unfractionated heparin (UFH) to achieve therapeutic anticoagulation levels or the inability to do so 3. The management of these patients can be challenging and requires alternative anticoagulation strategies.
Alternative Anticoagulants
Several alternative anticoagulants have been studied for the management of heparin non-responders, including:
- Direct thrombin inhibitors (DTIs) such as lepirudin and argatroban 4
- Direct factor Xa inhibitors such as rivaroxaban 4, 5, 6
- Fondaparinux, a synthetic pentasaccharide anticoagulant 7
- Danaparoid, a low-molecular-weight heparinoid 4, 7
Efficacy and Safety of Alternative Anticoagulants
Studies have shown that these alternative anticoagulants can be effective and safe in managing heparin non-responders:
- Rivaroxaban has been shown to be effective in treating patients with heparin-induced thrombocytopenia (HIT) 5, 6
- Fondaparinux has been shown to have similar effectiveness and safety as argatroban and danaparoid in patients with suspected HIT 7
- Direct thrombin inhibitors such as lepirudin and argatroban are approved for the treatment of HIT 4
Considerations for Management
When managing heparin non-responders, the following considerations should be taken into account:
- The underlying cause of heparin resistance should be identified and addressed if possible 3
- The choice of alternative anticoagulant should be based on the patient's clinical condition and the availability of the medication
- Close monitoring of the patient's anticoagulation status and platelet count is essential to prevent thrombotic or bleeding complications 4, 7, 5, 6