Thrombotic thrombocytopenic purpura (TTP) is a rare pregnancy complication characterized by microangiopathic hemolytic anemia and consumption thrombocytopenia. We herein describe the case report of a 32-year-old woman who was six weeks pregnant with twins and developed thrombotic thrombocytic purpura (TTP). The patient had a history of sickle cell trait, migraines, and preeclampsia. She presented with complaints of nausea, fatigue, sore throat, and cough and was found to be anemic with a hemoglobin of 7 g/dl and thrombocytopenic with a platelet count of 8 x 10/μL. The patient was promptly initiated on steroids and plasmapheresis with an excellent initial response. However, after three days, she developed a sudden onset headache and shortness of breath, and repeat labs showed worsening anemia (7.3 g/dl) and thrombocytopenia (8 x 10/μL). ADAMTS13 activity was significantly low at 2%. Plasmapheresis was continued, and caplacizumab and rituximab treatment was initiated. The fetal ultrasound showed no cardiac activity in the fetal poles, and the patient had a dilation and curettage(D&C) for a missed abortion. She was discharged with a prednisone taper, daily caplacizumab, and weekly rituximab. This case report underscores the criticality of the prompt identification of TTP in its early stages, and appropriate management strategies for patients with refractory TTP (rTTP), including plasmapheresis, caplacizumab, and rituximab.