Cold agglutinin disease: 2026 so far

Routine-care data added detail on benefits, while symptom and safety signals also appeared.

In the months covered, routine-care studies and small series described how sutimlimab was used outside clinical trials. Hemoglobin and hemolysis markers often improved quickly. In follow-up, they could stay stable, and some reports described using sutimlimab as a bridge (a temporary treatment while another therapy is starting). At the same time, cold-triggered circulation symptoms in the hands and feet often continued even when blood counts improved. One small report raised concern that cyanosis/acrocyanosis (bluish or purple discoloration from reduced blood flow) could worsen in some people, along with lab evidence of increased red-cell agglutination (red blood cells clumping together). Infections were reported during sutimlimab use. Severe infections were mostly seen in people who had previously received rituximab, and these reports did not prove sutimlimab caused the infections. This combination of findings suggests that improvement in anemia and day-to-day cold symptoms may not happen at the same pace, and that uncommon safety issues are still uncertain in small real-world datasets.

Research covered in: April 2026, May 2026, July 2026, August 2026, September 2026

Small cohorts and case reports described hemolysis responses and important side effects.

So far in 2026, a small real-world retrospective cohort (a look back at past medical records) reported that rituximab-based chemoimmunotherapy was followed by improvement in cold agglutinin-related hemolysis for many patients. This included people with primary CAD and Waldenstrom macroglobulinemia-associated disease. Case reports and small series also described rituximab as part of B-cell-directed plans (treatments aimed at the immune cells making the antibody) when a clonal B-cell disorder or mixed/complex autoimmune hemolysis was involved, with different outcomes from person to person. In the cohort, low white blood cell counts were common, including grade 3 to 4 neutropenia (a severe drop in infection-fighting white blood cells). Some infections were reported. No overt thrombotic events (blood clots) were observed in the cold agglutinin hemolysis groups during follow-up, noting the small sample. Taken together, these reports describe one observed path to improving hemolysis, while also showing why infection-related monitoring can be a concern when white blood cell counts drop.

Research covered in: January 2026, February 2026, March 2026, April 2026, June 2026, August 2026, September 2026

Case reports described how teams stabilized crises while immune treatments began to work.

In the months covered, several single-patient reports described crisis-level cold-antibody hemolysis managed with strict warming and warmed transfusions. Some reports also described temporary organ support, including dialysis (a machine that filters the blood when kidneys are not working) in one report. In rare, very severe situations, teams used blood-based procedures as bridges while other treatments were started. These included repeated whole-blood exchange in a child with mixed autoimmune hemolytic anemia and refractory cold agglutinin syndrome, and therapeutic plasma exchange (filtering the liquid part of blood to remove harmful proteins) in a Mycoplasma-associated case. The reports also highlighted that cold agglutinin problems can appear alongside infections or other immune illnesses, with improvement as the broader trigger was treated. These examples show what emergency stabilization can look like in extreme situations, while still leaving open how often these measures are needed or which approach works best.

Research covered in: January 2026, February 2026, March 2026, May 2026, June 2026

Consensus guidance and deeper testing showed why some cases get re-categorized.

In the months covered, expert consensus statements described a shared lab approach to confirm CAD. They emphasized a typical pattern, including a C3d-positive DAT (direct antiglobulin test, a blood test that checks for antibodies or complement on red blood cells) and serum cold agglutinins (antibodies that can clump red blood cells in the cold). They also stressed warm sample handling (keeping blood samples warm during collection and processing) to avoid misleading results. Retrospective cohorts and small series also showed that deeper bone marrow and molecular evaluation (testing for genetic and cell-level features) can change how cases are categorized. This included reclassifying some patients as having overt B-cell malignancies causing cold agglutinin syndrome, and it highlighted mismatches between lymphoma-like marrow appearance and CAD-like genetic/antibody-gene features in a small series. A guideline also reinforced DAT-based classification of cold versus warm autoimmune hemolytic anemia and summarized commonly used drug options, without adding new outcome data. Overall, these reports suggest that diagnosis can involve several layers of testing, and the label used may depend on how thoroughly possible underlying B-cell processes are evaluated.

Research covered in: April 2026, May 2026, June 2026, July 2026

One center reported long-term outcomes and clot-related observations.

So far in 2026, one single-center retrospective review reported longer-term outcomes in cold-type autoimmune hemolytic anemia (AIHA, where the immune system attacks red blood cells), including CAD/CAS. In that cohort, the report described lower 10-year survival than warm-type autoimmune hemolytic anemia. The same report noted thromboembolic events in some patients across the overall autoimmune hemolytic anemia cohort. It also reported antiphospholipid antibodies (immune proteins linked with clotting risk) more often in cold-type disease than warm-type disease. Because this was a small, single-center look back at routine care, it cannot show which treatments improve survival or prevent clots. Even so, it adds to the picture that real-world CAD/CAS follow-up continues to include long-term outcomes and clot-related complications.

Research covered in: June 2026