Shared decision making, thrombotic thrombocytopenic purpura, and caplacizumab
Authors: Senthil Sukumar, James N. George, Spero R. Cataland
Journal: American Journal of Hematology (2020)

Shared decision-making between physicians and patients is a concept developed from a long history of advocating for patient-centered care. Patient-centered care has been defined as care that is respectful of and responsive to individual patient preferences and needs. Patient-centered care ensures that patient values guide all clinical decisions.1 Although the importance of shared decision-making is universally accepted, the integration of shared decision-making into a busy clinical practice rarely occurs.2 As new treatments for critical illnesses become available, the importance of shared decision-making becomes greater. When a decision is shared between the physician and his/her patient then, with the patient's encouragement, the physician may take a step beyond current standard care. To illustrate how shared decision-making can fundamentally change and improve patient care, we describe our experience with a patient whom we know well. Our patient is a 56 year-old woman with a 10-year history of relapsing thrombotic thrombocytopenic purpura (TTP). When she came to our clinic for a scheduled 3 month follow-up evaluation, she reported generalized fatigue, abdominal pain, and nausea for the previous 4 days. Examination was normal except for lower extremity purpura. Her platelet count was 86,000/μL; 3 months previously it had been 243,000/μL. Her hemoglobin was 12.7 gm/dL and lactate dehydrogenase was 270 U/L. The blood smear had many schistocytes. Relapsed TTP was assumed and treatment would be required. This is when our conversation began. She asked if hospitalization, central venous catheter placement, plasma exchange, and glucocorticoids could be avoided. She was well enough to remain at home. Her adult children would ensure that she was safe at home. She had multiple previous and difficult experiences with all of these conventional components of TTP treatment. Our experience supported her concerns that complications caused by central venous catheters and plasma exchange are frequent,3 and that side-effects of corticosteroids can be intolerable. We discussed the potential limitations and risks of not being hospitalized and not being treated with plasma exchange and corticosteroids. On the following morning our laboratory would eventually report that the ADAMTS13 activity was undetectable (<2.5%), confirming the diagnosis of relapsed TTP. Then we discussed alternative management. We described the recent availability of caplacizumab, a humanized immunoglobulin which targets the A1 domain of von Willebrand Factor (vWF) and inhibits platelet binding. We described the recent clinical trials that had documented prompt platelet count recovery in patients with TTP who received caplacizumab, plasma exchange, and immunosuppression.4 We described how caplacizumab prevents the formation of microvascular thrombi and resultant tissue ischemia. We described how caplacizumab had been effective for treatment of a Jehovah's Witness patient, who refused all blood products.5 We told her that caplacizumab can stop the symptoms of TTP but that immunosuppressive treatment was required to allow recovery of ADAMTS13. We suggested that rituximab could provide immunosuppression and that corticosteroids may not be required. Then we reached a shared decision. We would not admit her to the hospital and would not begin plasma exchange or treatment with corticosteroids. Caplacizumab, 10 mg intravenously, was started that day in our clinic. She returned to clinic each day for the next 2 days to receive caplacizumab (10 mg subcutaneously) and to learn how to administer caplacizumab to herself daily, subcutaneously (Figure 1). Her symptoms rapidly resolved as her platelet count recovered within 48 hours. Rituximab was begun on day 6, when her platelet count was 321,000/μL. Then rituximab was continued weekly for the following 3 weeks (375 mg/m2). The ADAMTS13 activity recovered to 31% day 44; then caplacizumab was discontinued. Now, 2 months later, she is asymptomatic and doing well. This is the first report of treatment for TTP with only caplacizumab and rituximab. Management of our patient's relapse without the currently accepted treatment with plasma exchange and corticosteroids would not have been considered without our patient's requests, and would not have been possible without our patient's intelligence, understanding and agreement. We could confidently manage her as an outpatient because she was reliable, she lived near to the medical center, and her family could help with her management and guarantee her safety. Also, we would not have considered this treatment if her thrombocytopenia had been severe or if she had any neurologic symptoms. But with all of these supportive circumstances, we were able to manage our patient successfully. Our experience illustrates the ability of caplacizumab and rituximab, without hospitalization, to achieve a remission in patients with TTP. More importantly, our experience illustrates the value of integrating shared decision-making into clinical practice and exemplifies how shared decision-making can facilitate changes of medical practice, including utilization of new treatments. None. There was no outside support for this project. Spero R. Cataland has received research support and consulting fees from Sanofi/Ablynx.