levels are associated with thrombosis. 7 CLINICAL SYNDROMES AND SUGGESTED DIAGNOSTIC TESTS BLEEDING DISORDERS Bleeding disorders may be due to abnormalities of the coagulation, platelet, vascular or fibrinolytic systems. Hereditary disorders are usually due to an abnormality of a single system, whereas acquired abnormalities may involve two or all of the systems listed above. Clinical laboratory tests are available to evaluate platelets, coagulation and fibrinolysis. EVALUATION OF A BLEEDING DISORDER The Coagulation Screen includes PT, APTT, Thrombin time, and Clauss Fibrinogen assays. The DIC panel includes these same tests plus a quantitative D-Dimer and platelet count. If heparin is discovered in either of these testing packages it will be removed and the APTT result will be reported for the sample containing heparin as well as for the sample after heparin removal. The APTT on the sample after heparin removal is a separate test that will be automatically added on in the event heparin is detected in the sample. Mixing studies may be ordered to determine if bleeding disorders are factor deficiency- or inhibitor- based. Appropriate factor assays, as indicated by screening test results and/or clinical history of the patient, are also available. COAGULATION DISORDERS Bleeding associated with coagulation abnormalities is characterized by the formation of large hematomas, hemarthrosis, large single ecchymosis (either spontaneous or following minor trauma) or delayed bleeding following trauma, surgical or dental procedures. Petechiae and mucosal hemorrhage are rare unless there is an associated platelet disorder. Coagulation disorders may be congenital or acquired. Congenital bleeding disorders are often associated with a positive family history. A moderate to severe deficiency usually presents in early infancy through adolescence. A mild deficiency may not be detected until the patient is challenged with surgery or trauma. The most common of the congenital disorders is von Willebrand disease. It is a platelet-like bleeding disorder with a quantitative and/or qualitative defect of von Willebrand factor and a borderline to decreased factor VIII activity. Von Willebrand disease is further described on page 9. Hemophilia A (VIII deficiency) is the next most common, followed by hemophilia B (IX deficiency). Both are inherited as sex-linked recessive disorders. Hemophilia C (XI deficiency) is inherited as an autosomal recessive trait. Factor XII deficiency is not associated with a bleeding disorder. Von Willebrand Disease type I may present with a mild to marked prolongation of the APTT but other testing more specific for defining the disease is available as the von Willebrand Disease Panel. All of the Hemophilias and the Factor XII deficiency will present with a mild to marked prolongation of the APTT with all other screening procedures normal. The other congenital coagulation factor deficiencies (II, V, VII, and X) are extremely rare. Factor II, V, or X deficiency will have a moderate to marked prolongation of the prothrombin time and mild to moderate prolongation of the APTT. An isolated Factor VII deficiency has a prolonged prothrombin time with all other screen assays normal. 8 Acquired bleeding disorders are more common in hospitalized patients and can be life threatening. Acquired disorders are associated with acute and chronic disseminated intravascular coagulation (DIC), liver disease, vitamin K deficiency (dietary, wide spectrum antibiotic therapy, and/or oral anticoagulant therapy), heparin therapy and the use of fluid for volume replacement as in trauma patients or dilutional as in massive blood transfusion. The patients may have multiple abnormalities including variable prolongation of the prothrombin time, APTT, thrombin time and decreased fibrinogen and platelets. Bleeding can be associated with acquired factor inhibitors. Inhibitors have been described for all coagulation proteins. Although inhibitors are rare, the most common have been described against factor VIII and factor V. A prolonged APTT which does not correct in a 1:1 mix and where the 1:1 mix APTT increases as the mix sits in a 37°C water bath is suggestive of a factor VIII inhibitor in a bleeding patient. A patient previously