Page 2632 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 162 Resources for the Hematologist e13

Natural Anticoagulants (Antithrombin, Protein C, Protein S, Tissue Factor Pathway Inhibitor)
Summary points • Severe deficiency associated with severe thrombotic complications or lethality
• Acquired deficiencies more common than inherited
• Therapeutic repletion may be indicated in some deficiency states
Methodology Chromogenic (functional) or immunoassay (antigenic)
Specimen requirements Citrate
Indications Assessment of thrombotic risk, diagnosis of severe anticoagulant deficiency states, anticoagulant therapy monitoring
(antithrombin status with heparin therapy), assessment of repletion need with concentrate (AT, PC)
Reference range Tables 162.31 and 162.32
Interpretation • Levels lower in early infancy and may be reduced in acute thrombosis, consumptive coagulopathy, liver disease
• Estrogen, heparin, and asparaginase therapy, nephrotic syndrome associated with decreased AT
• PC, PS vitamin K dependent—levels reduced with deficiency and vitamin K antagonist exposure
• PS decreased in setting of inflammation, coexisting activated PC resistance (factor V Leiden), pregnancy, estrogen
therapy, sickle cell anemia, nephrotic syndrome
• No definitive threshold for what levels constitute adequate levels protective against thrombosis, but levels below
approximately 70% often considered abnormal
Related tests Thrombophilia evaluation, anticoagulation monitoring tests
Interfering substances Hemolyzed sample or lipemia

AT, Antithrombin; PC, protein C; PS, protein S.

D-Dimer
Summary points • Fibrin degradation byproduct of fibrinolytic process after cross-linking by FXIII
• Used as biomarker in thrombosis, disseminated intravascular coagulation
• Varied assay methods without clear standardization—reference values specific to method and population critical
to interpretation
Methodology Immunoassay
Specimen requirements Citrate or EDTA
Indications Assessment of possible venous thromboembolism, risk stratification for recurrent thrombosis, evaluation of
disseminated intravascular coagulation
Reference range Table 162.33
Interpretation • Elevated with recent fibrin formation and subsequent fibrinolysis (assuming normal fibrinolytic function)
• Elevated with inflammation, malignancy, surgery, recent trauma, bleeding, liver disease, pregnancy
• Varied assay methods without clear standardization—reference values specific to method and population critical
to interpretation
Related tests Thrombophilia evaluation, anticoagulation monitoring tests
Interfering substances Hemolyzed sample or lipemia
Reference Adam SS, Key NS, Greenberg CS: D-dimer antigen: Current concepts and future prospects, Blood 113:2878, 2009.

EDTA, Ethylenediaminetetraacetic acid; FXIII, factor XIII.

PFA-100
Summary points • Widely available method measuring time to platelet plug formation under high shear and in presence of platelet
agonists (epinephrine and ADP)
• Suboptimal sensitivity and specificity for platelet function disorders and von Willebrand disease
Methodology Automated aspiration of whole blood
Specimen requirements Citrate
Indications Assessment of primary hemostasis
Reference range Table 162.34
Interpretation • Determination of site-specific reference ranges recommended—longer closure times have been reported
• Prolonged closure times with more severe von Willebrand disease and platelet dysfunction but also with anemia,
thrombocytopenia, and antiplatelet therapy
• Specimen agitation and delayed time to assay may give spurious results
Related tests Platelet aggregometry, von Willebrand disease testing
Interfering substances Antiplatelet therapy and other drugs

ADP, Adenosine diphosphate.