Strategies for choosing perisurgery anticoagulation in patients with a recent history of heparin-induced thrombocytopenia awaiting heart transplantation
| EIA result . | Functional assay result* . | Strategy . | Grade of recommendation† . |
|---|---|---|---|
| negative | negative | Use heparin.12 | 1B |
| positive | positive | Postpone surgery and retest by functional assay every 3 days. If functional assay becomes negative use heparin during surgery and alternative anticoagulants post surgery. | 1B |
| positive | positive | In high urgency situation, use alternative anticoagulants bivalirudin > lepirudin > heparin + epoprostenol = heparin + tirofiban, if transplant team is trained to handle the alternative anticoagulants during and after surgery. | bivalirudin, 1C; lepirudin, 2C; heparin + epoprostenol, 2C; heparin + tirofiban, 2C |
| positive | negative | In high urgency situation, use heparin. | 2C |
| positive | not available within acceptable time | Repeat EIA with conjugate specific for IgG. If negative, use heparin during surgery and alternative anticoagulants after surgery, as IgM and IgA antibodies are very unlikely to cause clinical HIT.19 | 2C |
| positive | not available within acceptable time | Repeat EIA and add to a second well 100 IU/mL heparin. If there is not a decrease > 50% in OD in the presence of high heparin, the antibody is likely not PF4/heparin complex–specific, and heparin can be used during surgery.20 | 2C |
| positive | not available within acceptable time | PF4/heparin EIA IgG positive and inhibited by high heparin: perform the EIA in duplicate. If both tests give an OD < 1.0, use heparin.14 In this case, it is a feasible backup safety measure to have epoprostenol or tirofiban on hand during surgery in case clotting starts to manifest during surgery due to HIT antibodies. Both substances will immediately block platelet activation or aggregation, respectively. If the PF4/heparin EIA gives an OD > 1.0 the patient may have both, heparin dependent and heparin independent, platelet activating antibodies and heparin should not be given.21 | 2C |
| EIA result . | Functional assay result* . | Strategy . | Grade of recommendation† . |
|---|---|---|---|
| negative | negative | Use heparin.12 | 1B |
| positive | positive | Postpone surgery and retest by functional assay every 3 days. If functional assay becomes negative use heparin during surgery and alternative anticoagulants post surgery. | 1B |
| positive | positive | In high urgency situation, use alternative anticoagulants bivalirudin > lepirudin > heparin + epoprostenol = heparin + tirofiban, if transplant team is trained to handle the alternative anticoagulants during and after surgery. | bivalirudin, 1C; lepirudin, 2C; heparin + epoprostenol, 2C; heparin + tirofiban, 2C |
| positive | negative | In high urgency situation, use heparin. | 2C |
| positive | not available within acceptable time | Repeat EIA with conjugate specific for IgG. If negative, use heparin during surgery and alternative anticoagulants after surgery, as IgM and IgA antibodies are very unlikely to cause clinical HIT.19 | 2C |
| positive | not available within acceptable time | Repeat EIA and add to a second well 100 IU/mL heparin. If there is not a decrease > 50% in OD in the presence of high heparin, the antibody is likely not PF4/heparin complex–specific, and heparin can be used during surgery.20 | 2C |
| positive | not available within acceptable time | PF4/heparin EIA IgG positive and inhibited by high heparin: perform the EIA in duplicate. If both tests give an OD < 1.0, use heparin.14 In this case, it is a feasible backup safety measure to have epoprostenol or tirofiban on hand during surgery in case clotting starts to manifest during surgery due to HIT antibodies. Both substances will immediately block platelet activation or aggregation, respectively. If the PF4/heparin EIA gives an OD > 1.0 the patient may have both, heparin dependent and heparin independent, platelet activating antibodies and heparin should not be given.21 | 2C |
Washed platelet assays for excluding clinically relevant HIT antibodies such as the serotonin release test (requiring radioactivity16 ) or the heparin-induced platelet activation (HIPA) test (does not require radioactivity16 ) are not commercially available and require specialized laboratories. Access to functional assays varies between medical systems. In some countries a network of trained laboratories offers the HIPA test with a turnaround time of 48 hours or less, while in other countries it is a major problem to get samples tested within a reasonable time for clinical decision processes. In these settings, there is increasing evidence that some maneuvers may support the use the PF4/heparin enzyme immunoassay (EIA) alone for deciding on the strategy of anticoagulation during cardiac surgery or heart transplantation. These maneuvers are not optimal, but, given the consequences of taking a patient off the heart transplant list, they might be acceptable.
OD indicates optical density; and Ig, immunoglobulin.
Requirements for relying on a functional assay: (1) use either platelets of 2 known sensitive donors or a panel of 4 donors. Do not pool donor platelets, but test the patient serum with each donor's platelets separately; (2) use a known negative and a known weak positive control serum which must give the expected results; (3) use low (0.2 IU/mL) and high (100 IU/mL) heparin concentrations to show that the high heparin concentrations inhibit the reaction; (4) use the monoclonal antibody IV.3 to show that platelet activation is Fc-RIIa–dependent; (5) use apyrase in the washing buffer during platelet activation to exclude desensitization of platelets by adenosindiphosphate; and (6) heat-inactivate patient serum at 56°C for 30 minutes and add hirudin 5 IU/mL (final concentration) to exclude complement- and thrombin-dependent platelet activation.
Grades of recommendation were applied according to the system of the American College of Chest Physicians (ACCP) Evidence-Based Clinical Practice Guidelines (2008).2