Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (410 page)

   Lipid profile

   Homocysteine

   Second-tier tests:

   Comprehensive investigation of possible underlying neoplasm or a myeloproliferative disorder, including JAK-2 mutation.

   To be considered as risk factors.

   Pregnancy.

   Paroxysmal nocturnal hemoglobinuria (PNH)–flow cytometry.

   Drugs: chemotherapy, thalidomide, lenalidomide, tamoxifen, contraceptive, and hormone replacement therapy.

   If TTP is strongly suspected, start therapy and order ADAMTS 13 assay.

   Chronic renal disease and the nephrotic syndrome

   If promyelocytic leukemia is suspected, order diagnostic tests (FISH, karyotype, flow cytometry) on bone marrow aspirate and start therapy promptly.

Suggested Readings

Dahlback B. Advances in understanding pathogenic mechanisms of thrombophilic disorders.
Blood.
2008;112:19–27.

Huisman MV, Klok FA. How I diagnose acute pulmonary embolism.
Blood.
2013;121:4443–4448.

Middeldorp S. Is thrombophilia testing useful?
Hematology Am Soc Hematol Educ Program.
2011;2011:150–155.

ANTIPHOSPHOLIPID ANTIBODY SYNDROME (APS)

   Definition

APS is an autoimmune prothrombotic disorder that can affect both the venous and arterial circulation. The other major clinical manifestations are obstetrical. The laboratory criteria are the presence of a
lupus anticoagulant (LA)
(see below), β
2 glycoprotein 1
ELISA and
anticardiolipin
antibodies of the IgG or IgM isotype (see pp. 806–807). The diagnosis of APS requires both clinical features and laboratory confirmation with the persistence of antibodies for at least 12 weeks. Lupus anticoagulants are more commonly associated with thrombotic events than are the anticardiolipin antibodies (ACA). Antiphospholipid antibodies (APLA) are directed against phospholipid-binding plasma proteins. APLA comprise a heterogeneous family of auto- and alloantibodies (IgG and IgM subclasses) directed against specific plasma proteins with
affinity
for phospholipid surfaces. The antigenic targets are β2 glycoprotein 1, factor II (prothrombin), and possibly protein C, protein S, kininogens, complement factor H, and annexin V. The most commonly detected subgroups of APLA include ACLA, antiprothrombin antibodies, and anti-β2 glycoprotein I antibodies (anti-β2 GP 1).