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e12    Part XIII  Consultative Hematology


         Coagulation Screening Tests (PT, aPTT, Fibrinogen)
          Summary points        •  PT, aPTT used to screen for coagulation factor deficiency and monitor anticoagulation; fibrinogen detects
                                 hypofibrinogenemia, dysfibrinogenemia
                                •  PT elevated with deficiencies of extrinsic and common pathway factors (PT expressed as INR when used to
                                 monitor oral anticoagulant therapy)
                                •  aPTT elevated with deficiencies of intrinsic and common pathway factors and inhibitors (heparin, lupus
                                 anticoagulant, specific factor inhibitors)
          Methodology           Clot detection
          Specimen requirements  Citrate
          Indications           Suspected coagulation factor deficiency, monitor anticoagulation
          Reference range       Table 162.30
          Interpretation        •  Reference ranges dependent on reagents and instrumentation, requiring laboratory-specific and population-
                                 specific ascertainment (e.g., aPTT is normally prolonged during neonatal period)
                                •  PT and aPTT vary in their sensitivity to deficiency of individual coagulation factors—PT tends to be least sensitive
                                 to FII, aPTT to FIX
                                •  Normal aPTT does not exclude mild but clinically significant factor deficiency (especially hemophilia B and von
                                 Willebrand disease)
                                •  Prolonged PT suggests deficiency of one or more factors (fibrinogen, II, V, VII, X) or presence of a coagulation
                                 inhibitor
                                •  Prolonged aPTT suggests deficiency of one or more factors (fibrinogen, II, V, VIII, IX, X, XI, or other contact
                                 pathway factors) or presence of inhibitor such as lupus anticoagulant or heparin (consider heparin contamination
                                 in specimen drawn from a heparinized line)
                                •  Prolonged PT and aPTT suggests vitamin K deficiency, liver disease, disseminated intravascular coagulation,
                                 common pathway factor deficiency
                                •  Isolated prolonged PT (normal aPTT) suggests FVII deficiency
                                •  Shortening of aPTT may reflect elevated FVIII level (caused by inflammation)
                                •  Spurious prolongation of tests with polycythemia, partially filled collection tube, prolonged storage or warming,
                                 clotted specimen
          Related tests         Coagulation factor levels (fibrinogen, factors II, V, VII, VIII, IX, X, XI, other contact pathway factors), lupus
                                 anticoagulant, mixing studies
          aPTT, Activated partial thromboplastin time; FII, factor II; FIX, factor IX; FVII, factor VII; FVIII, factor VIII; INR, international normalized ratio; PT, prothrombin time.





         Coagulation Factor Levels (Fibrinogen, II, V, VII, VIII, von Willebrand Factor, IX, X, XI, Contact Pathway Factors)
          Summary points        •  Choice of which specific factor(s) to measure driven by clinical scenario and screening test results (e.g., isolated
                                 prolonged PT suggests FVII deficiency, isolated preoperative aPTT suggests measurement of at least FVIII, FIX,
                                 and FXI, to assess bleeding risk)
                                •  Low von Willebrand factor may not result in abnormal screening test results
          Methodology           Clot detection
          Specimen requirements  Citrate
          Indications           Suspected coagulation factor deficiency, especially as suggested by prolonged coagulation screening test and
                                 subsequent mixing study that corrects, assessment of risk factors for thrombosis (e.g., high FVIII), monitoring of
                                 factor-replacement therapy in patients with coagulopathy
          Reference range       Tables 162.30 and 162.32
          Interpretation        •  No definitive threshold for what constitutes hemostatically adequate factor level, but criteria for diagnosing mild
                                 factor deficiency often set at 40%–50%
                                •  Fibrinogen, FVIII, and von Willebrand factor are acute-phase reactants
                                •  Factor deficiency may be due to reduced production (hereditary factor deficiency, liver disease, vitamin K
                                 deficiency), increased consumption (disseminated intravascular coagulation), or specific inhibitor (FVIII)
                                •  Acquired deficiency of multiple factors occurs with liver disease, vitamin K deficiency (including vitamin
                                 K–antagonist therapy or toxicity), disseminated intravascular coagulation—FV, FVII, and FVIII may aid in
                                 distinguishing between these
                                •  Rare inherited combined factor deficiencies exist (combined FV/FVIII, vitamin K–dependent factors)
                                •  With exception of FXI, contact factor deficiencies (FXII, high-molecular-weight kininogen, prekallikrein) may cause
                                 prolonged aPTT but are not associated with increased bleeding risk
                                •  Vitamin K–dependent and contact factors are physiologically low in early infancy
                                •  FV and FVIII are particularly labile, with potential for spuriously low levels—carefully consider abnormally low
                                 levels in clinical and laboratory context and assess need for repeat/confirmatory testing
          Related tests         Specific factor inhibitor testing, lupus anticoagulant, mixing studies
          aPTT, Activated partial thromboplastin time; FIX, factor IX; FV, factor V; FVII, factor VII; FVIII, factor VIII; FXI, factor XI; FXII, factor XII; PT, prothrombin time.
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