The development of a heparin-like anticoagulant (HLAC) in plasma cell neoplasia has previously been described in clinical literature. Testing of this HLAC, primarily in vitro, has demonstrated that neutralization may be achieved with protamine sulfate, owing to antithrombin III cofactor activity. We report a case in which intravenous protamine sulfate was administered to a patient with IgG-kappa monotypic multiple myeloma, which resulted in resolution of bleeding and coagulopathy, confirmed via objective laboratory data. Our case is intended to demonstrate that intravenous protamine sulfate should be considered in acute bleeding with plasma cell neoplasia. We review the literature to observe past experiences about this phenomenon. We postulate that chemotherapy, targeted therapies, and immunotherapies may also disrupt production of a HLAC. With further investigation, this strategy could be applicable in other hematological malignancies with bleeding diathesis, chiefly if the pathophysiology of the HLAC is precisely defined.