Table 1 Etiologies of antithrombin-III (AT-III) mediated and non-AT-III mediated heparin resistance and diagnostic workup

Low ATIII-level

 Reduced ATIII synthesis

  Hereditary ATIII deficiency

Evaluate family history, previous thrombotic events?

  Hepatic dysfunction

Evaluate ALT, AST, GT, AF, bilirubin, albumin, Factor V

 Increased ATIII clearance

  Nephrotic syndrome (loss of ATIII in the kidney)

Creatinin, albumin, urine protein/creatinine ratio

 Accelerated consumption

  Use of heparin or low molecular weight heparin

Evaluate heparin use

  Upregulated hemostatic system, e.g. disseminated intravascular coagulation, endocarditis, venous thromboembolism, major surgery or trauma in past few days

Evaluate PT, APTT, fibrinogen, d-dimer, C-reactive protein. Signs of thrombosis?

  Mechanical

Cardiopulmonary bypass, ventricular assist device, intra-aortic balloon pump, extracorporeal membrane oxygenation

  Medication (asparaginase, oral contraceptives, estrogen therapy)

Evaluate medication

  Pregnancy especially in case of pre-eclampsia

Pregnancy test in premenopausal women

Normal ATIII-level

 Increased heparin-binding

  Proteins

  Chemokines

  Extracellular matrix proteins

  Growth factors

  Enzymes

  Other: FVIII, von Willebrand factor, Fibrinogen, Lactoferrin, Histidine-rich glycoprotein, lipoproteins/albumin, AL amyloid

FVIII, von Willebrand factor antigen and activity, Fibrinogen, M-protein, free light chains, bone marrow examination on indication

  Platelets

Complete blood count

  Thrombophilia

  Platelet activation/release

Evaluation of medication

  Medication (Nitroglycerin)

  Variable non-specific binding