Thrombosis prophylaxis for factor V.sup.LEIDEN carriers

• US 5,977,057 A
• Filed: 05/08/1996
• Issued: 11/02/1999
• Est. Priority Date: 05/08/1996
• Status: Expired due to Fees

• Current Assignee: University of Vermont & State Agricultural College
• Original Assignee: University of Vermont & State Agricultural College
• Inventors: Van't Veer, Cornelis, Kalafatis, Michael, Mann, Kenneth G.
• Primary Examiner(s): Achutamurthy, Ponnathapura
• Assistant Examiner(s): Saidha, Tekchand
• Application Number:
  US08/707,782
• Time in Patent Office: 1,273 Days
• Field of Search: 514/2, 514/8, 514/12, 530/300, 530/350, 435/13
• US Class Current: 514/14.9
• CPC Class Codes: A61K 38/57 from animals; from humans A61K38/553, A61K38/556 take precedence
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors

Abstract

Persons having the Factor V^LEIDEN mutation and a lower than average plasma level of TFPI have been found to be at elevated risk of thrombosis. Prophylactic methods for reducing the risk of thrombosis employ the administration of TFPI to achieve higher levels in the plasma.

Claims

1. A method of reducing the risk of thrombosis in a person who carries a Factor V^LEIDEN allele, the method comprising the step of:

administering to the person an amount of Tissue Factor Pathway Inhibitor (TFPI) or active fragment thereof sufficient to achieve plasma levels of TFPI which are higher than 89 ng/ml.

2. The method of claim 1 wherein the TFPI or active fragment thereof is administered by infusion pump.

3. The method of claim 1 wherein the TFPI or active fragment thereof is self-administered.

4. The method of claim 1 wherein the TFPI or active fragment thereof is administered orally.

5. The method of claim 1 wherein said TFPI or active fragment thereof comprises a first Kunitz-domain consisting of amino acids 47-117.

6. The method of claim 1 wherein said TFPI or active fragment thereof comprises a second Kunitz domain consisting of amino acids 118-188.

7. The method of claim 1 wherein said TFPI or active fragment thereof comprises a first and a second Kunitz domain consisting of amino acids 47-188.

8. The method of claim 1 wherein said TFPI or active fragment thereof lacks a third domain.

9. The method of claim 1 wherein said TFPI or active fragment thereof is administered in a total daily dose of 4-20 mg/kg.

10. The method of claim 1 wherein said TFPI or active fragment thereof is administered in a total daily dose of 6-10 mg/kg.

11. The method of claim 1 wherein said TFPI or active fragment thereof is administered in a total daily dose of 2-50 mg/kg.

12. The method of claim 1 wherein said TFPI or active fragment thereof is administered at a dose of 1 ug to 20 ug per kg.

13. The method of claim 1 wherein said TFPI or active fragment thereof is administered at a dose of 20 ug to 10 mg per kg.

14. The method of claim 1 wherein said TFPI or active fragment thereof is administered at a dose of 1 mg to 7 mg per kg.