hemophilia B. Factor IX inhibitors are not time or temperature dependent. Spontaneous factor IX antibodies are very rare and are usually associated with an autoimmune disorder. FIBRINOGEN Method: Clot based Clauss or Kinetic method. Acquired abnormalities of fibrinogen can be quantitative or qualitative and may be associated with a bleeding problem or with thrombosis. Decreased quantities of fibrinogen are noted in liver disease, renal disease, ascites, acute DIC and asparaginase therapy. Acquired dysfunctional fibrinogen is observed in nephrotic syndrome and DIC. Fibrinogen is an acute phase reactant protein. It is markedly increased in inflammation and infection. During pregnancy the fibrinogen level rises rapidly with a two to three fold increase noted by the end of the third trimester. An elevated fibrinogen is an indication that an acute phase response is occurring that may lead to increased levels of factor VIII, von Willebrand factor and PAI-1. Recent studies suggest that chronically increased fibrinogen levels are associated with an increased risk of arterial thrombosis including stroke and myocardial infarction. Inherited abnormalities may be due to a lack of fibrinogen (afibrinogenemia, autosomal recessive), deficiency of fibrinogen (hypofibrinogenemia, autosomal dominant or recessive) or a dysfunctional fibrinogen molecule (dysfibrinogenemia, autosomal dominant). All of the mentioned conditions are rare. Dysfunctional fibrinogens are the most common and may be asymptomatic or associated with an increased risk of bleeding or thrombosis depending on the specific defect. The prothrombin time has a slight to moderate prolongation; the APTT has a normal to slight prolongation; the thrombin time is moderately prolonged. On a 1:1 mix the thrombin time may show partial correction. The diagnosis of a dysfunctional fibrinogen can be confirmed with an antigenic fibrinogen or total clottable fibrinogen determination. Typically the kinetic fibrinogen will be lower than the antigenic or total clottable method fibrinogen. To specifically classify the type of dysfunctional fibrinogen it is necessary to perform specific research assays to identify the abnormality in the protein. Direct thrombin inhibitors, such as argatroban and lepirudin, will falsely prolong clotting times and falsely decrease the fibrinogen concentration. HEPARIN ACTIVITY (UNFRACTIONATED AND LOW MOLECULAR WEIGHT) Method: Chromogenic, anti-Xa activity assay. This assay is calibrated using a hybrid unfractionated and low molecular weight heparin curve. Generally patients on unfractionated heparin therapy are monitored with the aPTT. Conditions other than heparin may be present that alter the APTT making the test ineffective as a heparin-monitoring tool. The most common cause of interference is the presence of a lupus anticoagulant. Lupus inhibitors do not interfere with the heparin activity assay. The aPTT cannot be used to monitor low molecular weight heparin therapy. Low molecular weight heparin inhibits factor Xa more potently than thrombin. The Heparin Activity assay is the assay of choice to monitor patients on Low Molecular Weight Heparin. 29 LUPUS INHIBITOR (ANTICOAGULANT) Method: Hexagonal (II) phase phospholipid clotting assay It is very important that all the platelets are removed from the sample prior to freezing, as residual platelets will adversely affect the test results. Freezing will rupture the platelet membrane resulting in neutralization of some of the antiphospholipid antibody, which may cause a false negative result in the assay. A mixture of patient plasma, normal plasma pool and a buffer are added to a modified aPTT reagent that is very sensitive to lupus inhibitors. If the modified aPTT is prolonged, phospholipid is substituted for buffer and the aPTT repeated. If the phospholipid corrects the aPTT then a lupus inhibitor is present. Patients are reported as negative, borderline positive, moderate positive or strong positive. A patient with a borderline positive result may have a transient lupus inhibitor associated with infection or reaction to some drugs. Direct thrombin inhibitors, such as argatroban and lepirudin, will falsely prolong clotting time and invalidate this assay. Lupus inhibitors (antiphospholipid