If factitious use of heparin or thrombin inhibitors is suspected, thrombin time (TT) and reptilase time help determine if heparin or direct thrombin inhibitor is present. TT is prolonged by both heparin and thrombin inhibitors, but reptilase time is not affected by either of the drugs.
Lupus anticoagulant should be tested if there is no history of treatment with unfractionated heparin or direct thrombin inhibitors such as lepirudin and argatroban. However, antiphospholipid antibodies are estimated to have a prevalence of 1.0% to 5.6% in healthy populations.7 Moreover, lupus anticoagulant is transient in most cases and is most often of no clinical significance. It is therefore important to interpret the lupus anticoagulant in the context of the illness.
If the inhibitor is still a mystery, you will need to test for specific factor inhibitors like factor VIII inhibitor (acquired hemophilia). Inhibitors are alloantibodies, which develop, for example, in patients with hemophilia who are treated with blood products such as fresh frozen plasma (FFP), cryoprecipitate, or factor VIII concentrate.
When an elevated number doesn't mean what you think
There are certain limitations of APTT in identifying the deficient factors because the sensitivity of APTT to identify deficient common pathway factors is low.8 (There may be deficiency of a common pathway factor but a normal APTT). Composition of the partial thromboplastin reagent can result in marked differences in the sensitivity of the test to coagulation factor deficiencies.
In addition, factor VIII levels may give false-negative results in pregnancy and in response to physical stress and trauma, as factor VIII rises markedly in both cases. Thus, it may mask a mild deficiency.
Deficiencies of factor XII, HMWK, or PK do not result in a bleeding disorder despite prolonging the APTT markedly. This is important since factor XII deficiency has been found to be among the most common causes of unexpected prolongation of APTT.9
CASE You exclude an acquired bleeding disorder based on Mr. K’s history, physical exam, and normal results on his liver panel and a complete blood count. However, a repeat APTT is prolonged and a mixing study with normal plasma corrects the APTT. Further testing demonstrates normal factors IX and XI, but his level of factor VIII is only 10% of the reference range, confirming a diagnosis of hemophilia A.
You advise Mr. K to get vaccinated against hepatitis A and B. You also discuss available treatment options and their indications. Recombinant factor VIII is the treatment of choice for bleeding episodes. Prophylactic treatment is given before surgical procedures or activities that carry a high risk of provoking a bleed.
Factor VIII infusion 3 times a week to prevent hemarthrosis in severely affected patients is gaining acceptance. Desmopressin acetate (DDAVP) is the drug of choice for treatment of patients with mild hemophilia (factor VIII activity >5%).10 Antifibrinolytic agents like ε-aminocaproic acid and tranexamic acid can be used for mucosal oral or dental bleeds. You also make sure Mr. K obtains a medical alert bracelet.