Haematology CE/CME ACCREDITED Watch Time: 25 mins

touchEXPERT OPINIONS Getting personal: Individualizing therapy for cold agglutinin disease

Watch two experts give their perspectives on the recommended workup for a timely and accurate diagnosis, as well as the evolving treatment landscape, and the importance of individualizing therapy for patients with cold agglutinin disease.

Now Playing:
Up Next:
Dr Catherine M Broome
MedStar Georgetown University Hospital, Washington DC, USA
Optimizing the diagnostic workup for CAD: Clinical presentations and differential diagnoses

Dr Catherine M Broome considers when to suspect CAD, and the steps needed to confirm a diagnosis, the impact of poor sample handling and delays to diagnosis, as well as the importance of real-world data in informing ongoing management of CAD.

1/2 Next Interview
Take CE/CME Test

In this interview, Dr Catherine M Broome answers the following questions:

  • What signs and symptoms should increase your clinical suspicion of cold agglutinin disease?
  • What tests, and in what order, are recommended to diagnose primary cold agglutinin disease?
  • How important is timing of tests and proper sample handling in obtaining accurate results?
  • How do diagnostic delays impact treatment decisions and outcomes?
  • Will longitudinal real-world data help to inform our understanding of the natural history of cold agglutinin disease?

Catherine M Broome, MD, is board certified in internal medicine, haematology and medical oncology. She has been on the staff at the MedStar Georgetown University Hospital’s Lombardi Comprehensive Cancer Center for 13 years. read more

A fascination with the science of haematology, and the opportunity to develop a strong relationship with patients and their families led Dr Broome to specialize in haematology and medical oncology. Dr Broome focuses on developing a partnership with her patients, providing them the most up-to-­date information and treatment options. They work together to develop a treatment plan that fits medically, while also taking into account all aspects of the patient’s life.

In addition to patient care, Dr Broome is an associate professor in the Lombardi Cancer Center’s Department of Medicine. She also serves on the hospital’s safety committee.

Dr Catherine M Broome discloses Advisory board/panel fees from Alexion, Annexon Biosciences, Argenx, Incyte and Sanofi. Consultancy fees from Star Therapeutics.

Dr Ilene Ceil Weitz
Keck-USC School of Medicine, Los Angeles, USA
Current and emerging treatment options for CAD: Importance of individualizing therapy

Dr Ilene Weitz outlines the role of complement inhibitors as an alternative treatment option in the evolving treatment landscape of CAD, and how to use specific markers to tailor treatment for individual patients.

2/2 Take CE/CME Test
Take CE/CME Test

In this interview, Dr Ilene Ceil Weitz answers the following questions:

  • How are complement inhibitors changing the current treatment paradigm for cold agglutinin disease?
  • In terms of the evolving treatment landscape for cold agglutinin disease, when should clinicians consider the use of rituximab or sutimlimab?
  • Are there any biomarkers or other factors to help tailor treatment to the individual patient?
  • What indicators can be used to measure treatment response, and how can we measure the impact of cold agglutinin disease from a patient perspective?

Dr Weitz, MD, is a professor of clinical medicine in the Division of Hematology at Keck-USC School of Medicine. read more

Dr Weitz attended the Medical College of Pennsylvania, and did her internal medicine training at Cedars Sinai Medical Center in Los Angeles. She completed her haematology fellowship at Scripps Clinic and Research Foundation.  

Dr Weitz’s research and clinical interests include: haemostasis thrombosis, complement disorders (including paroxysmal nocturnal haemoglobinuria, atypical haemolytic uremic syndrome and cold agglutinin disease), aplastic anaemia, iron metabolism, haemoglobinopathies (sickle cell and thalassaemia), mega platelet syndromes, and immune-mediated blood disorders.   

She has published multiple original articles, reviews and chapters. Dr Weitz received the faculty teaching award from the University of Southern California, as well as Cedars Sinai Medical Center in the USA. She was honoured with the Morris Press Humanism award from Cedars Sinai Medical Center.

Dr Ilene Ceil Weitz discloses Advisory board/panel fees from Alexion, Apellis, Novartis and Sanofi. Speaker’s bureau fees from Alexion.

Take CE/CME Test
Overview & Learning Objectives

In this activity, US-based experts discuss best practice for diagnosing cold agglutinin disease (CAD) and how real-world data can inform our understanding of the natural history of the disease, as well as the current and emerging treatment options, and how we can use specific markers to tailor therapy and measure outcomes in patients with CAD.

This activity is jointly provided by USF Health and touchIME. read more

Target Audience

This activity has been designed to meet the educational needs of haematologists and haematologist-oncologists involved in the management of patients with cold agglutinin disease.


USF Health adheres to the Standards for Integrity and Independence in Accredited Continuing Education. All individuals in a position to influence content have disclosed to USF Health any financial relationship with an ineligible organization. USF Health has reviewed and mitigated all relevant financial relationships related to the content of the activity. The relevant financial relationships are listed below. All individuals not listed have no relevant financial relationships.


Dr Catherine M Broome discloses: Advisory board/panel fees from Alexion, Annexon Biosciences, Argenx, Incyte and Sanofi. Consultancy fees from Star Therapeutics.

Dr Ilene Ceil Weitz discloses: Advisory board/panel fees from Alexion, Apellis, Novartis and Sanofi. Speaker’s bureau fees from Alexion.

Content reviewer

Caitlin Papa, APRN has no relevant financial relationships to disclose.

Touch Medical Directors

Kathy Day and Sadaf Kazi have no financial interests/relationships or affiliations in relation to this activity.

USF Health Office of Continuing Professional Development and touchIME staff have no financial interests/relationships or affiliations in relation to this activity.

Requirements for Successful Completion

In order to receive credit for this activity, participants must review the content and complete the post-test and evaluation form. Statements of credit are awarded upon successful completion of the post-test and evaluation form.

If you have questions regarding credit please contact cpdsupport@usf.edu.



This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through a joint providership of USF Health and touchIME. USF Health is accredited by the ACCME to provide continuing medical education for physicians.

USF Health designates this enduring material for a maximum of 0.75 AMA PRA Category 1 CreditTM.  Physicians should claim only the credit commensurate with the extent of their participation in the activity.

The European Union of Medical Specialists (UEMS) – European Accreditation Council for Continuing Medical Education (EACCME) has an agreement of mutual recognition of continuing medical education (CME) credit with the American Medical Association (AMA). European physicians interested in converting AMA PRA Category 1 CreditTM into European CME credit (ECMEC) should contact the UEMS (www.uems.eu).

Advanced Practice Providers

Physician Assistants may claim a maximum of 0.75 Category 1 credits for completing this activity. NCCPA accepts AMA PRA Category 1 CreditTM from organizations accredited by ACCME or a recognized state medical society.

The AANPCP accepts certificates of participation for educational activities approved for AMA PRA Category 1 CreditTM by ACCME-accredited providers. APRNs who participate will receive a certificate of completion commensurate with the extent of their participation.

Date of original release: 10 October 2022. Date credits expire: 10 October 2023.

If you have any questions regarding credit please contact cpdsupport@usf.edu.

Learning Objectives

After watching this activity, participants should be better able to:

  • Outline strategies for the accurate diagnosis of cold agglutinin disease
  • Evaluate the current and emerging treatment options for patients with cold agglutinin disease using the latest data
  • Assess potential strategies for individualizing the treatment for patients with cold agglutinin disease

View and download resources from this activity to support your learning and share with colleagues

Register to touchONCOLOGY for FREE
  • Peer-reviewed journals and expert opinions
  • Interactive CME and e-learning modules
  • Video conference highlights
Register For Free Now

This content is intended for healthcare professionals only. Please confirm that you are a healthcare professional.

Accept Decline
CE/CME Test (0.75 Points) Close

To obtain the CME credit(s), please complete this post-test. Please complete and click to see your results and continue.

Question 1/5
What tests and in what order would you recommend to your colleagues to confirm a suspected case of CAD?

CAD, cold agglutinin disease; DAT, direct antiglobulin test; LDH, lactate dehydrogenase.

For a patient suspected of having CAD, the first step is to check for signs of haemolysis, such as increased LDH and bilirubin levels, and assess for increased reticulocytes, although in some cases reticulocytes may appear normal or low. If haemolysis is present, an autoimmune aetiology can be confirmed with a DAT. A monospecific DAT positive for C3d, and a cold agglutinin titre ≥64 suggests either CAD or CAS. If there is no other underlying pathology, then a diagnosis of CAD can be made.


C, serum complement protein; CAD, cold agglutinin disease; CAS, cold agglutinin syndrome; DAT, direct antiglobulin test; LDH, lactate dehydrogenase.


Berentsen S, Barcellini W. N Engl J Med. 2021;385:1407–19.

Question 2/5
A 68-year-old woman has presented with severe anaemia and cold-induced circulatory symptoms resulting in lesions on two fingers. After deciding she is in need of prompt treatment to quickly improve her condition, what treatment would you recommend?

Rituximab, with or without chemotherapy, can support patients with CAD; however, average time to response can be approximately 2 months.1 Sutimlimab has been shown in phase III clinical trials to give rapid improvements in haemoglobin and bilirubin levels within 1–3 weeks, and improved fatigue over the longer term.2,3 Corticosteroids are not considered effective in CAD, and eculizumab is recommended as an acute treatment, possibly as a bridge to more long-term treatment.1


CAD, cold agglutinin disease.


  1. Jäger U, et al. Blood Rev. 2020;41:100648.
  2. Röth A, et al. Blood. 2022;140:980–91.
  3. Röth A, et al. N Engl J Med. 2021;384:1323–34.
Question 3/5
What does retrospective data tell us about the risks associated with CAD and the use of conventional treatment approaches?

CAD, cold agglutinin disease.

Even after diagnosis and treatment, patients continue to experience symptoms and complications. Retrospective data over a 10-year period showed that patients with CAD have a 1.9 times higher risk of thromboembolic events compared to patients without CAD.1 Another large scale retrospective trial found that 72% of patients with CAD experienced severe anaemia within 1-year of follow-up.2 


CAD, cold agglutinin disease.


  1. Broome C, et al. Res Pract Thromb Haemost. 2020;4:628–35.
  2. Mullins M, et al. Blood Adv. 2017;1:839–48.
Question 4/5
What indicators should you use to monitor your patient with CAD to reliably assess their response to treatment?

CAD, cold agglutinin disease; LDH, lactate dehydrogenase.

Monitoring for signs of haemolysis is central to assessing the response to treatment in patients with CAD. Haemoglobin is the most direct marker of disease severity and is reduced in moderate and severe forms of haemolytic anaemia. Reticulocytes are usually increased in haemolysis; however, reticulocytopenia may also be seen in some cases. LDH and bilirubin both rise with haemolysis. A complete response to therapy can be defined as haemoglobin levels >12 g/dL and other haemolytic marker normalization. A partial response is classed as haemoglobin levels >10g/dL or a 2 g/dL increase and reduction of haemolytic markers with no transfusion need. 


CAD, cold agglutinin disease; LDH, lactate dehydrogenase.


Barcellini W, Fattizzo B. Dis Markers. 2015;2015:635670.

Question 5/5
Your patient is experiencing disabling cold-induced circulatory symptoms and has asked to be considered for sutimlimab therapy. What would you advise this patient about the effect of sutimlimab on cold-induced circulatory symptoms?

Cold-induced circulatory symptoms are seen in up to 90% of patients.1 These symptoms, such as Raynaud’s phenomenon or acrocyanosis, are due to red blood cell agglutination following cold agglutinin binding prior to complement activation.2 Sutimlimab, as a C1s inhibitor, acts downstream of the cold agglutinin binding,1 and has not been demonstrated to improve cold-induced circulatory symptoms in clinical trials.3 


C1s, complement component 1s; CAD, cold agglutinin disease.


  1. Berentsen S, et al. J Blood Med. 2019;10:93–103.
  2. Berentsen S. Front Immunol. 2020;11:590.
  3. Röth A, et al. Blood. 2022;140:980–91.
Post Test Feedback Close
Step 1: Post CE/CME Test Feedback

Please note this feedback form is compulsory to complete your CE/CME evaluation

* = Mandatory Field

Please complete this short online feedback form.
Please indicate how well each statement met your expectations.

Accreditation Close

Please provide your details so that we can send you your certificate, which will be emailed to the address provided. All fields are required.

* = Mandatory Field
Your Accreditation Close
Copied to clipboard!
accredited arrow-down-editablearrow-downarrow_leftarrow-right-bluearrow-right-dark-bluearrow-right-greenarrow-right-greyarrow-right-orangearrow-right-whitearrow-right-bluearrow-up-orangeavatarcalendarchevron-down consultant-pathologist-nurseconsultant-pathologistcrosscrossdownloademailexclaimationfeedbackfiltergraph-arrowinterviewslinkmdt_iconmenumore_dots nurse-consultantpadlock patient-advocate-pathologistpatient-consultantpatientperson pharmacist-nurseplay_buttonplay-colour-tmcplay-colourAsset 1podcastprinter scenerysearch share single-doctor social_facebooksocial_googleplussocial_instagramsocial_linkedin_altsocial_linkedin_altsocial_pinterestlogo-twitter-glyph-32social_youtubeshape-star (1)tick-bluetick-orangetick-red tick-whiteticktimetranscriptup-arrowwebinar Sponsored Department Location NEW TMM Corporate Services Icons-07NEW TMM Corporate Services Icons-08NEW TMM Corporate Services Icons-09NEW TMM Corporate Services Icons-10NEW TMM Corporate Services Icons-11NEW TMM Corporate Services Icons-12Salary £ TMM-Corp-Site-Icons-01TMM-Corp-Site-Icons-02TMM-Corp-Site-Icons-03TMM-Corp-Site-Icons-04TMM-Corp-Site-Icons-05TMM-Corp-Site-Icons-06TMM-Corp-Site-Icons-07TMM-Corp-Site-Icons-08TMM-Corp-Site-Icons-09TMM-Corp-Site-Icons-10TMM-Corp-Site-Icons-11TMM-Corp-Site-Icons-12TMM-Corp-Site-Icons-13TMM-Corp-Site-Icons-14TMM-Corp-Site-Icons-15TMM-Corp-Site-Icons-16TMM-Corp-Site-Icons-17TMM-Corp-Site-Icons-18TMM-Corp-Site-Icons-19TMM-Corp-Site-Icons-20TMM-Corp-Site-Icons-21TMM-Corp-Site-Icons-22TMM-Corp-Site-Icons-23TMM-Corp-Site-Icons-24TMM-Corp-Site-Icons-25TMM-Corp-Site-Icons-26TMM-Corp-Site-Icons-27TMM-Corp-Site-Icons-28TMM-Corp-Site-Icons-29TMM-Corp-Site-Icons-30TMM-Corp-Site-Icons-31TMM-Corp-Site-Icons-32TMM-Corp-Site-Icons-33TMM-Corp-Site-Icons-34TMM-Corp-Site-Icons-35TMM-Corp-Site-Icons-36TMM-Corp-Site-Icons-37TMM-Corp-Site-Icons-38TMM-Corp-Site-Icons-39TMM-Corp-Site-Icons-40TMM-Corp-Site-Icons-41TMM-Corp-Site-Icons-42TMM-Corp-Site-Icons-43TMM-Corp-Site-Icons-44TMM-Corp-Site-Icons-45TMM-Corp-Site-Icons-46TMM-Corp-Site-Icons-47TMM-Corp-Site-Icons-48TMM-Corp-Site-Icons-49TMM-Corp-Site-Icons-50TMM-Corp-Site-Icons-51TMM-Corp-Site-Icons-52TMM-Corp-Site-Icons-53TMM-Corp-Site-Icons-54TMM-Corp-Site-Icons-55TMM-Corp-Site-Icons-56TMM-Corp-Site-Icons-57TMM-Corp-Site-Icons-58TMM-Corp-Site-Icons-59TMM-Corp-Site-Icons-60TMM-Corp-Site-Icons-61TMM-Corp-Site-Icons-62TMM-Corp-Site-Icons-63TMM-Corp-Site-Icons-64TMM-Corp-Site-Icons-65TMM-Corp-Site-Icons-66TMM-Corp-Site-Icons-67TMM-Corp-Site-Icons-68TMM-Corp-Site-Icons-69TMM-Corp-Site-Icons-70TMM-Corp-Site-Icons-71TMM-Corp-Site-Icons-72