Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Prospective, Randomized, Cross-over Study of an Activated Prothrombin Complex Concentrate for Secondary Prophylaxis in Patients With Hemophilia A and Inhibitors
Brief Summary: The objective of this study is to assess whether prophylactic therapy with an activated prothrombin complex concentrate (FEIBA)will result in a significant reduction in the number of bleeds in patients with hemophilia and persistent high responding inhibitors.


Options:
A: Inclusion Criteria:

* age ≥ 12 years and ≤ 55 years
* severe haemophilia A (FVIII \< 1%)
* absence of inhibitors (Bethesda titre \< 0.6 BU/ml)
* Previous Treated Patients (prior exposure days \> 200)
* Kogenate Bayer administered 20-30 IU/kg -3 times a week, for the prophylaxis group
* ≥ 6 joint bleeds requiring treatment with FVIII concentrates in the previous 6 months before enrollment, for on-demand group
* written informed consent

Exclusion Criteria:

* concomitant severe and chronic diseases or congenital skeletal malformation
* unreliability of patient or likelihood of follow-up failure
* presence of inhibitors or history of inhibitors (in the previous 2 years)
* currently on immune tolerance treatment
* hepatic cirrhosis or liver disease in rapid progression
* AIDS
* platelet count \< 75,000/mm3
* presence of conditions that influence negatively patient´s compliance
* participation in another study
B: Inclusion Criteria:

* Male patients with moderately severe or severe congenital haemophilia B with a factor IX activity of 2% or below according to medical records
* History of at least 150 exposure days to other factor IX products
* Patients currently treated on-demand with at least 6 bleeding episodes during the last 12 months or at least 3 bleeding episodes during the last 6 months, or patients currently on prophylaxis

Exclusion Criteria:

* Known history of factor IX inhibitors based on existing medical records, laboratory report reviews and patient and legally acceptable representative (LAR) interviews
* HIV (Human immunodeficiency virus) positive, with a viral load equal to or above 400,000 copies/mL and/or CD4+ lymphocyte count equal to or below 200/microL
* Congenital or acquired coagulation disorders other than haemophilia B
* Previous arterial thrombotic events (e.g. myocardial infarction and intracranial thrombosis) or previous deep venous thrombosis or pulmonary embolism (as defined by available medical records)
* Immune modulating or chemotherapeutic medication
C: Inclusion Criteria:

* Documented history of moderately severe or severe hemophilia B (FIX:C less than or equal to 2%)
* Male subjects, aged 6 years to 65 years.
* Subjects with a minimum of 12 bleeding episodes, 6 of which must be joint bleeds, in the 12 months before screening.

Exclusion Criteria:

* Subjects currently utilizing FIX primary prophylaxis.
* Subjects with HIV+ who have a CD4 count less than 200
* Subjects with hepatic or renal impairment.
* Prothrombin time or International Normalized Ration more than 1.5 times the upper limit of normal.
* Major surgery or an orthopedic surgical procedure within the past 3 months or is planned within the duration of participation in this study.
* Past history of, or current FIX inhibitor.
* Hypersensitivity to any FIX product or hamster protein.
* Exposure to any investigational drug, except for rFIX-R, or device within 30 days of providing consent/assent (as appropriate) for this study.
* Bleeding disorders other than hemophilia B.
* Concurrent inflammatory disease that in the investigator's judgment could confound the study results.
D: Inclusion Criteria:

* hemophilia A, any severity, with documented history of high-titer inhibitor (\>5BU); current use of bypassing agents (PCCs, aPCCs or rFVIIa) for treatment of bleeds; \>/= 6 bleeds requiring bypassing therapy in the previous 6 months

Exclusion Criteria:

* concomitant immune tolerance therapy; clinically symptomatic liver disease, platelet count less than 100,000

Answer: D