Final Diagnosis:

This is Coumadin induced Vitamin K deficiency and excessive utilization of blood products.

Discussion

Immediate intervention by the pathologist in Case #2 prevented excessive administration of FFP thus decreasing the fluid and viral exposure risks to the patient

Blood utilization and review has historically been assigned to the laboratory pathologist for appropriateness.  The guidelines for blood administration are established and approved by the medical staff in each hospital and may be slightly different for each institution.  These guidelines are based on previous history, patient population and experience.  Some institutions, for non adherence recommend a verbal conference with the physician asking why he/she deviated from policy.  Other institutions send a letter to the physician requiring a written response explaining the cause of the deviation.  Any deviation from the guidelines requires intervention by the Pathologist.  If continuous deviation by a single physician is identified, disciplinary action may be necessary and a letter is placed in the physician’s personnel file at the hospital.  The letter is signed by the Administrator, Pathologist and Physician involved.  In larger institutions, more signatures may be required.

The above patients demonstrate both deviations from the guidelines because of  lack of immediate intervention  and adherence to the guidelines due to immediate intervention by the pathologist.  These cases demonstrate the importance of history and a basic knowledge by the pathologist of coagulation abnormalities.

These cases demonstrate the presence of warfarin resulting in prolongation of the PT/INR without prolongation of the PTT.  This occurs because of the interference with terminal gamma glycosylation of the Vitamin K dependent factors, Factors II, VII, IX and X.  The PT is preferentially prolonged over the PTT since the half-life of Factor VII is the shortest of all factors identified.  Interference does occur with Factors II, IX, and X but is not manifested until much later in time.  Factor assays for these four factors would demonstrate the effect on all factors but would show a marked effect on Factor VII as opposed to the others.  Factor assays in the above cases would not be appropriate because of the time required to perform the tests.  Vitamin K is the preferred antidote for warfarin therapy; however, it does require a finite period of time to act.  FFP contains the clotting factors and administration of FFP will replace the vitamin K dependent factors but should be accompanied by administration of Vitamin K.  This allows for immediate replacement and administration of the antidote.  In addition, it is known that warfarin can persist in the system for a maximum of two weeks, although most cases only last 7-10 days.  Vitamin K must be administered at least every 12 hours due to its short half-life.  Therefore, one must remember that continuous administration of Vitamin K is necessary for the effects to persist.

References

1. Beutler E, Lichtman MA, Coller BS, Kipps TJ and Seligsohn U.  William Hematology 6th ed. MCGraw-Hill, 2001;1777-1792.

2. Colman RW, Hirsh J, Marder VJ, Clowes AW and George JN. Hemostasis and Thrombosis 4th ed.Lippincott Williams Wilkins, 2001; 1505-1509.

3. Goodnight JR and Hathaway WE. Disorders of Hemostasis and Thrombosis 2nd ed. McGraw-Hill, 2001; 557-566.

4. Kroll MH. Manual of Coagulation Disorders. Blackwell Science, 2001; 51-57.

5. Petrides M and Stack G. Practical Guide to Transfusion Medicine. AABB Press, 2001; 156-7,160.