Hemodialysis-related-heparin-induced thrombocytopenia (HD-HIT) is a drug-induced, immunoglobulin- mediated disorder that it is suspected in dialysis patients with an unexpected fall in the platelet count, and/or unexplained thrombotic events, particularly visible clotting in the circuit under an adequate heparin dose, that begins between 5 and 10 days (nadir between 7 and 30 days, mostly by the third to fifth session) after heparin initiation. Although a positive result for anti-PF4/heparin complex antibodies (HIT antibodies) is presumably detected by sensitive ELISA, the diagnosis should be confirmed, whenever possible, using a functional assay. Immediately after the clinical suspicion of HIT, all sources of heparin should be discontinued including heparin used to flush or lock catheters. Alternative non-heparin anticoagulants, preferentially a direct thrombin inhibitor, should be restarted for dialysis. Early treatment is important as thrombus formation including a clotting circuit may complicate at a high rate within 30 days after the cessation of heparin. Argatroban, a synthetic direct thrombin inhibitor, as an alternative to heparin, must contribute to the rapid recovery of the platelet count and disappearance of visible circuit clotting. A steady decreasing of the ELISA titers can be expected after heparin discontinuation. A negative seroconversion of HIT antibodies is usually observed by ~30 to more than 100 days after discontinuation. Re-exposure to heparin can be selected at the same dose of heparin as used before the onset of HIT. A small peak of HIT antibodies may often appear after exposure, but a follow-up of the antibody titers shows that they not reach a threshold to induce the recurrence of HIT. When HD-HIT patients exhibit a high index of thrombotic formation or worsening thrombosis, the same alternative anticoagulant therapy may be needed on non-session days.