Table 2.

Mechanisms of Heparin Resistance

Antithrombin Deficiency

1. Congenital 2. Acquired •Decreased synthesis (eg, liver disease, malnutrition) •Increased clearance (eg, nephrotic syndrome) •Increased consumption (eg, heparin therapy) •Upregulated hemostatic system (eg, sepsis, infective endocarditis, DIVC, DVT, PE) •Mechanical support devices (eg, ECMO, IABP, CPB) •Medications (eg, asparaginase)

Non-Antithrombin Mediated

1. Increased heparin binding to other proteins, cells and non-endothelial surfaces •Plasma proteins (eg, albumin, cell adhesion proteins, glycoproteins, lipoproteins, nuclear; proteins, microbial proteins, viral proteins) •Extracellular matrix proteins (eg, laminin, collagens, thrombospondin, fibronectin, vitronectin) •Chemokines (eg, PF4, interleukins, macrophage proteins, monocyte proteins) •Cells (eg, endothelial cells, macrophages, platelets) •Miscellaneous (eg, von Willebrand factor, factor VIII, fibrinogen) •Nonendothelial surfaces (eg, intravenous tubings, ECMO circuits) 2. High platelet count ≥300,000 cells/mm3 (due to the activation of PF4, a strong inhibitor of heparin) 3. Low albumin concentrations ≤35 g/dL (albumin exhibits heparin-like action) 4. Preoperative relative hypovolemia (dehydration leading to increased concentration of other compatible molecules binding to heparin) 5. Medications (eg, andexanet alfa)

Abbreviations: CPB, cardiopulmonary bypass; DIVC, disseminated intravascular coagulopathy; DVT, deep vein thrombosis; ECMO, extracorporeal membrane oxygenation; IABP, intra-aortic balloon pump; PE, pulmonary embolism; PF4, platelet factor 4.