first indication of the development of this antibody is a rapid unexplained drop in the platelet count after the administration of heparin. Thrombocytosis (marked increase in platelet count) may be primary or secondary. Primary thrombocytosis is observed in myeloproliferative disorders such as polycythemia vera, essential thrombocythemia and chronic granulocytic leukemia. Polycythemia vera and essential thrombocythemia are associated with prolonged elevations of the platelet count and thrombosis due to abnormal platelet number and function. In secondary or reactive thrombocytosis the platelets have normal function and the elevated platelet count is usually transient. VON WILLEBRAND DISEASE Von Willebrand disease (vWD) is considered one of the most common inherited bleeding disorders. Most cases are inherited as a heterozygous autosomal dominant trait with a mild to moderate bleeding tendency. A rare form (A) which leads to elevated levels of prothrombin in plasma. Evaluation of the prothrombin gene requires DNA testing. The APCR defect is the most common genetic defect associated with thrombosis, occurring in approximately 5% of the normal population and in approximately 20-40% of patients with documented thrombophilia. The next most common defect is a persistent elevation of factor VIII activity. The incidence of elevated factor VIII activity is similar to that of APCR/Factor V Leiden. Approximately 2% of the normal population and 10% of thrombophilia patients have the prothrombin polymorphism. Together, hereditary protein S, protein C and anti-thrombin account for approximately 12-15% of documented cases of thrombophilia. Clinically, most of the inherited disorders present with venous thrombosis after puberty and may be associated with minor trauma, surgery or pregnancy. Approximately 50% of the patients with hereditary thrombophilia present with a thrombotic event before age 35. Recently, it has been recognized that many patients with thrombophilia have multiple genetic defects that combine to increase their thrombotic risk. Protein C, protein S, or antithrombin deficiency may be combined with each other but the most common combination is with the R506Q mutation of factor V, elevated factor VIII or the prothrombin mutation. While a single factor 15 deficiency may be associated with a 2-5 fold increased risk for thrombosis, a patient with a combined deficiency may have a ten-fold or greater increase in the risk of venous thrombosis. The finding of combined deficiencies has led to a reevaluation of laboratory tests used to screen for thrombophilia. It is no longer recommended to run a single test or a reflexive panel, instead a complete panel of thrombophilia assays should be run to evaluate the patient. One cause of acquired venous and arterial thrombosis is the antiphospholipid syndrome. This disorder is associated with persistently elevated anticardiolipin antibodies and/or lupus inhibitor (also known as lupus anticoagulant). A woman presenting with multiple spontaneous abortions should also be suspect for the antiphospholipid syndrome. Other acquired causes of venous thrombosis include trauma, nephrotic syndrome, liver disease, venous insufficiency and malignancy. When a venous thrombosis occurs in an unusual location such as a portal, axillary or intracranial vein, there is a high index of suspicion for an antiphospholipid syndrome, antithrombin deficiency or malignancy. 16 REFERENCE CHART OF DIAGNOSTIC TESTS/PANELS AVAILABLE For a more detailed description of tests, please see page 22. Please refer to page 4 for instructions on the collection, processing and storage of samples. TEST/PANEL SAMPLE REFERENCE FREQUENCY COMMENT RANGE OF TESTING Activated Partial 1 mL frozen plasma 22-35 sec Daily Thromboplastin Time (APTT) Anti-beta 2 1 mL frozen serum < 10 units T, F Part of antiphospholipid glycoprotein I panel. Anticardiolipin IgA 1 mL frozen serum < 12 APL T, F Part of antiphospholipid panel. Anticardiolipin IgG 1 mL frozen serum < 12 GPL T, F Part of antiphospholipid panel. Anticardiolipin IgM 1 mL frozen serum < 15 MPL T, F Part of antiphospholipid panel. Antiphospholipid 1 mL frozen serum see