An Open-label, Randomized, Multicenter Phase IIIb Study to Assess the Efficacy, Safety and Tolerance of BERIPLEX® P/N Compared With Plasma for Rapid Reversal of Coagulopathy Induced by Vitamin K Antagonists in Subjects Requiring an Urgent Surgical Procedure

Inclusion Criteria:

- Male and female subjects greater than or equal to 18 years,

- Subjects currently on oral VKA therapy,

- An urgent surgical procedure is required within 24 hours of the start of IMP,

- Due to the nature of the procedure, withdrawal of oral VKA therapy and infusion of
plasma are also indicated to reverse the VKA effect,

- INR greater than or equal to 2 within 3 hours before start of IMP,

- Informed consent has been obtained.

Exclusion Criteria:

- Subjects requiring urgent surgical procedures where according to the surgeon's
clinical judgment, an accurate estimate of blood loss is not possible (e.g., ruptured
aneurysm),

- Subjects for whom administration of intravenous vitamin K and vitamin K antagonists
withdrawal alone can adequately correct the subject's coagulopathy before initiation
of the urgent surgical procedure,

- Administration of intravenous vitamin K more than 3 hours or administration of oral
vitamin K more than 6 hours prior to infusion of IMP,

- Subjects in whom lowering INR within normal range may present an unacceptable risk
for a thromboembolic complication where the INR goal is to lower but not normalize
the INR because of risk of a procedure-associated stroke,

- Subjects, who despite medical management that includes close monitoring and
diuretics, may not, by investigator assessment, tolerate the total volume of IMP
required by the protocol,

- Expected need for additional non-study blood products before infusion of IMP (Note:
Administration of packed red blood cells is not an exclusion criterion),

- Expected need for platelet transfusions or desmopressin before Day 10,

- Acute trauma for which reversal of vitamin K antagonists alone would not be expected
to control or resolve an acute bleeding complication and/or control the acute
bleeding event,

- Unfractionated or low molecular weight heparin use within 24 hours before
randomization or potential need before completion of the procedure,

- History of thromboembolic event, myocardial infarction, unstable angina pectoris,
critical aortic stenosis, cerebral vascular accident, transient ischemic attack,
severe peripheral vascular disease, disseminated intravascular coagulation within 3
months of enrollment,

- Reversal of VKA therapy alone may not resolve the coagulopathy (eg, receiving a
potent anti-platelet agent, i.e., clopidogrel or prasugrel, or advanced liver
disease),

- Known history of antiphospholipid antibody syndrome or lupus anticoagulant
antibodies,

- Suspected or confirmed serious viral or bacterial infection, e.g., meningitis, or
sepsis at time of enrollment,

- Administration of whole blood, plasma, plasma fractions or platelets within 2 weeks
prior to inclusion into the study (Note: Administration of packed red blood cells is
not an exclusion criterion),

- Pre-existing progressive fatal disease with a life expectancy of less than 2 months,

- Known inhibitors to coagulation factors II, VII, IX, or X; or hereditary protein C or
protein S deficiency; or heparin-induced, type II thrombocytopenia,

- Treatment with any other investigational medicinal product within 30 days prior to
inclusion into the study,

- Presence or history of hypersensitivity to components of the study medication,

- Pregnant or breast-feeding women,

- Prior inclusion in this study or any other CSL Behring sponsored Beriplex study,

- For subjects with intracranial hemorrhage with:

- Glasgow Coma Score <10 (see Appendix 8)

- modified Rankin Score > 3 prior to ICH (see Appendix 9)

- Intracerebral hemorrhage

- Epidural hematomas

- Infratentorial hemorrhage

- Subarachnoid hemorrhage (SAH) subjects with a Hunt and Hess Scale >2

- Subdural hematomas that:

- are judged to be an acute subdural hematoma (based on neurosurgeon review)

- have a concurrent SAH or parenchymal contusion