Methods for treating intracranial hemorrhage and assessing efficacy
Compositions and methods useful for assessing the hemostatic efficacy in a patient having suffered from intracranial hemorrhage while undergoing an anticoagulation treatment with a factor Xa (fXa) inhibitor are described. The method can include administering to the patient a fXa derivative that has reduced catalytic activity as compared to the wild-type fXa protein, is capable of binding to the factor Xa inhibitor and cannot assemble into a prothrombinase complex; obtaining a blood sample from the patient following the administration; and measuring an anti-fXa activity in the sample, wherein the anti-fXa activity reflects the hemostatic efficacy in the patient. Once the assessment is made, suitable medical interventions can be implemented.
1 . A method for treating intracranial hemorrhage, comprising:
administering andexanet alfa to a patient undergoing an anticoagulation treatment with a factor Xa (fXa) inhibitor who has suffered intracranial hemorrhage;
obtaining a blood sample from the patient following the administration;
measuring an anti-fXa activity in the sample; and
administering to the patient a second dose of the andexanet alfa if the anti-fXa activity is above a predetermined anti-fXa activity threshold,
wherein the method does not comprise measuring hemostatic efficacy in the patient.
2 . The method of claim 1 , wherein the predetermined anti-fXa activity threshold is from 30 to 50 ng/ml when the fXa inhibitor is apixaban, rivaroxaban, betrixaban or edoxaban, or from 0.25 to 0.5 IU/ml when the fXa inhibitor is enoxaparin.
3 . The method of claim 1 , further comprising measuring the anti-fXa activity in a sample obtained from the patient prior to the administration of the andexanet alfa.
4 . The method of claim 1 , wherein the administration comprises a bolus injection of the andexanet alfa.
5 . The method of claim 4 , wherein the administration further comprises an infusion of the andexanet alfa after the bolus injection.
6 . The method of claim 5 , wherein the blood sample is obtained at 10 minutes to 4 hours following the administration.
7 . The method of claim 1 , wherein the anti-fXa activity is measured with a chromogenic assay.