Setting: office
CC: “My surgeon told me to see about my bleeding risk before surgery.”
HPI: A 50-year-old woman comes to see you about an elevated aPTT that her surgeon found prior to a planned lumpectomy for breast cancer. She had her screening mammogram at age 50 years and a small abnormality was found. Needle biopsy showed infiltrating ductal carcinoma. Bleeding was not excessive at the time of the biopsy. The patient is perimenopausal now and her menstrual periods have always been modest in intensity, lasting 3 to 4 days.
PMHX: normal vaginal delivery for children; no additional bleeding
Medications: none
PE: normal
Initial Orders:
CBC
PT, aPTT, INR
LFTs
Hemophilia is not expressed in women.
Hemophilia does not present at this age without abnormal bleeding.
Move the clock forward 1 week to get test results. This is a preoperative clearance case and is not an emergency. In preoperative clearance cases, never write the phrase “cleared for surgery.” If there is nothing to do, write “Medically optimal for procedure. No further medical management needed prior to procedure.”
Laboratory Test Results:
CBC and LFTs: normal
PT and INR: normal
aPTT: prolonged to 65 seconds
Order a mixing study first when evaluating clotting factor deficiencies. Any clotting factor deficiency will correct to a normal aPTT when mixed 50:50 with normal plasma. This is because the clotting factor level has to be decreased by 70% to 80% before the aPTT will even begin to elevate. Often, the coagulation test will not be abnormal until the clotting factor deficiency is as much as 85% to 90%.
If the aPTT does not correct or attain a normal level when mixed with normal plasma, it likely means the presence of a clotting factor inhibitor. Acquired inhibitors of factor VIII and IX can occur with aging and may not have serious pathologic significance. However, factor inhibitors can be caused by cancer.
Deficiencies correct aPTT to normal.
Inhibitors do not correct to normal.
The mixing study shows a normalization of aPTT. Order a hematology consultation to show that you “know when to get help,” but remember that consultants will never tell you concretely what to do.
Because this is a clotting factor deficiency, you should order specific clotting factor levels. The patient’s gender and age eliminate the possibility of hemophilia.
Orders:
Factor XI level
Factor XII level
Factor XII deficiency is never associated with bleeding and never needs treatment.
Factor XIII deficiency does cause bleeding, but it is not in the clotting cascade, so aPTT is normal.
Factor XIII is “clot stabilizing factor” and may make fibrin permanently resistant to the effects of plasmin.
Reports:
Factor XI 15% of normal level
Factor XII 90% of normal level
Because the patient does not bleed under normal activity, there is no regular therapy to use. With a lumpectomy, the patient is about to undergo a serious operative procedure. You should tell the surgeon to give her fresh frozen plasma (FFP) an hour prior to the procedure. Factor XI replacement is not available in the United States. The value of aminocaproic acid and tranexamic acid for surgical procedures with factor XI deficiency is not clear. Both agents inhibit plasmin and prevent the breakdown of fibrin. The basic science mechanism question is clear. Whether to use them before operative procedures in factor XI deficiency is not clear.
Give FFP before operative procedures to patients with factor XI deficiency.
FFP has all clotting factors except:
• Factor VIII
• vWF