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Table 3 Main advantages and limitations of APTT and anti-Xa activity for UFH treatment laboratory monitoring

From: Management of the thrombotic risk associated with COVID-19: guidance for the hemostasis laboratory

 

Advantages

Limits

APTT

- largely available, low cost

- sensitive to clinically relevant changes of coagulation (coagulation proteins increases or deficiencies)

- numerous interferences; optical methods can be unreliable in case of DIC

- heparin sensitivity is highly reagent dependent

- APTT prolongation target needs to be established for each new batch of reagents

- APTT before UFH needed

- clinically irrelevant changes, or of dubious clinical relevance

APTT prolonged with:

• presence of antiphospholipid antibodies (viral infections)

• high CRP (depending on the reagent)

• high plasma levels in FDPs

• preanalytical (e.g., heparin/EDTA contamination, under-filling, delayed centrifugation, hypertriglyceridemia, hyperbilirubinemia)

APTT shortened with:

• preanalytical (e.g., prolonged venous stasis, vigorous mixing, coagulation of the sample, PF4)

• high factor VIII levels

Anti-Xa activity

- less vulnerable to biological interferences

- no requirement for measurement before UFH administration

- preanalytical interferences: PF4*; free hemoglobin and bilirubin if significant elevation

- insensitive to fluctuations in the underlying coagulation state (i.e., coagulation factor increases or defects), of potential clinical relevance

- AT deficiency (e.g. in sepsis): risk of heparin underdosing with kits containing exogenous AT; sensitivity to endogenous AT not evaluated with kits that do not contain exogenous AT

- variability in reagents composition (AT, dextran…)

- therapeutic range poorly defined

- not validated in hyperinflammatory states

- less available, more expensive

  1. *PF4 released by activated platelets during poor sampling technique will neutralize UFH, leading to an underestimation of its activity
  2. AT antithrombin, APTT activated partial thromboplastin time, UFH unfractionated heparin, PF4 platelet factor 4; CRP C-reactive protein, DIC disseminated intravascular coagulation, FDP fibrinogen and fibrin degradation products; FVIII factor VIII.