A male 52-year-old patient (body mass index 43 U) undergoing antithrombotic therapy with Enoxaparin (Lovenox®) after hip surgery presented with ongoing pain, a swollen leg and isolated necrotic spots on day eight after surgery. Medical history revealed previous uneventful administration of Enoxaparin 2 years ago. Despite from normal platelet count (286G/l) at the beginning of LMWH therapy, standard laboratory parameters now showed a new onset of thrombocytopenia (33 G/l). Clinical state, results of ultrasound of the lower limb and a CT-angiography supplied evidence of a major thromboembolic event within the right arteria femoralis superficialis and concomitant compartment syndrome. Administration of Enoxaparin was stopped immediately and treatment with Argatroban (Argatra®) was initiated. According to the 4T’s score (8 points) and the detection of PF4-heparin antibodies via an ELISA immunoassay, HIT diagnosis was likely and finally confirmed with heparin-induced platelet aggregation assay (HIPAA). Despite interventional thrombectomy and fasciotomy, amputation of the left leg had to be performed 2 days later. On day 15 after hip surgery, thrombosis of the right vena poplitea and vena femoralis superficialis required interventional thrombectomy and fasciotomy. However, this did not prevent from amputation because of ongoing necrosis of the right lower limb. Acral necrotic spots indicated microembolism. Due to septic shock the patient developed acute kidney failure and citrate-dialysis had to be performed. Furthermore, it took dilatative tracheotomy in order to facilitate respiratory weaning. Throughout a 30-days stay at the intensive care unit, hemodynamic and respiratory parameters stabilised and the patient regained renal function. Moreover, platelet count normalized. Due to essential repetitive surgical interventions, administration of Argatroban had to be continued for at least 38 days because of—compared to vitamin k inhibitor—better perioperative controllability. Therapy with Argatroban was switched to Phenprocoumon (Marcoumar®) afterwards according to current bridging guidelines. The patient could be transferred to the normal ward and further rehabilitation.