Study of OCTAPLEX in Patients With Acute Major Bleeding on DOAC Therapy With Factor Xa Inhibitor

Inclusion Criteria:

1. Patients on oral factor Xa inhibitor therapy and with known or suspected baselineanti-factor Xa activity of at least 100 ng/mL:

• Patients who received or who are believed by the investigator to have received adose of oral factor Xa inhibitor and who have a baseline anti- factor Xa activity ofat least 100 ng/mL according to the locally available test (e.g., chromogenic assay)performed outside of the study as part of standard of care OR

• Patients who received or who are believed by the investigator to have receivedtheir latest dose of oral factor Xa inhibitor (e.g., rivaroxaban ≥10 mg,apixaban ≥2.5 mg, edoxaban ≥30 mg) ≤8 hours prior to enrolment OR

-Patients who received or who are believed by the investigator to have receivedtheir latest dose of oral factor Xa inhibitor (e.g., rivaroxaban ≥10 mg, apixaban ≥2.5 mg, edoxaban ≥30 mg) >8 hours prior to enrolment or at an unknown time, but forwhom the investigator suspects a baseline anti- factor Xa activity of at least 100ng/mL and assesses that the administration of OCTAPLEX is clinically indicated

2. Aged ≥18 years

3. Patients who have given written informed consent or for whom written informedconsent has been obtained from the patient's legally authorised representative ontheir behalf -Wherever possible, prospective written informed consent will beobtained before enrolment from the patient or, if they are incapable of providingit, from their legally authorised representative

-If prospective written informed consent is not possible, deferred consentprocedures will be permitted outside the US if approved by the local ethicscommittee or otherwise permitted under local regulations

-When deferred consent procedures are used outside the US, written informed consentshould be obtained from the patient as soon as they recover the capacity to provideit, or otherwise from their legally authorised representative

4. Patients who have acute major bleeding defined as follows:

• Bleeding that is life-threatening or uncontrolled, e.g., with signs or symptomsof haemodynamic compromise, such as severe hypotension, poor skin perfusion, orlow cardiac output that cannot be otherwise explained

OR

• Symptomatic bleeding in critical organs (intracranial, intraspinal, intraocular, gastrointestinal, retroperitoneal, intra-articular, pericardial, or intramuscular with compartment syndrome)

OR

• Acute overt bleeding associated with a fall in haemoglobin (Hgb) level of ≥2 g/dL, OR a Hgb level ≤8 g/dL if no baseline Hgb level is available, OR in the opinion of the investigator that the patient's Hgb level will fall to ≤8 g/dL with resuscitation

Exclusion Criteria:

1. Patients with 'Do not resuscitate' (DNR) orders

2. Patients with acute trauma for which reversal of DOAC therapy with factor Xainhibitor alone would not be expected to control the bleeding event

3. Hgb decrease without accompanying evidence of source of bleeding

4. Acute coronary syndrome, ischaemic stroke or venous thromboembolism (VTE) within thepreceding 3 months

5. Patients with a history, within the last 3 months, of disseminated intravascularcoagulation (DIC) or hyperfibrinolysis

6. Patients with a known congenital bleeding disorder

7. Known inhibitors to coagulation factors II, VII, IX, or X; heparin-induced, type IIthrombocytopenia; or immunoglobulin A (IgA) deficiency with known antibodies againstIgA

8. Known hypersensitivity to plasma-derived products or heparin

9. Patients who received haemostatic agents, including plasma, platelets, PCC,activated PCC (aPCC), recombinant factor VIIa, or recombinant factor Xainactivated-zhzo (andexanet alfa), for the current bleeding event prior to enrolment (antifibrinolytic drugs and local haemostatic agents are allowed)

10. Patients who received ticlopidine within 14 days, prasugrel within 7 days,ticagrelor within 5 days, dipyridamole within 1 day or cangrelor within 1 hourpreceding the bleeding event

11. Patients on enoxaparin therapy for thromboembolic prophylaxis

12. A score of less than 7 on the Glasgow Coma Scale in non-intubated patients or anestimated intracerebral haematoma volume of more than 60 mL. (Patients intubated orsedated at the time of screening may be enrolled if intubation or sedation were donefor non-neurologic reasons)

13. Patients with expected survival of less than 24 hours, in the opinion of theinvestigator (in collaboration with other medical experts as appropriate per usuallocal practice)

14. Patients scheduled to undergo surgery in less than 12 hours, with the exception ofminor surgeries and invasive procedures which are allowed for diagnostic ortherapeutic reasons or if intended to address a second (non-index) bleeding event

15. Patients who are pregnant or breastfeeding at the time of enrollment

16. Patients previously enrolled in this study

17. Patients participating in another interventional clinical treatment study currentlyor during the past 1 month prior to study inclusion