Study finds inherited thrombophilia screening not needed in AIHA
Acquired clotting risk factors appear more important in predicting thrombosis risk
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Routine screening for inherited thrombophilia, genetic risk factors linked to excessive blood clotting, is not needed for people with autoimmune hemolytic anemia (AIHA), including cold agglutinin disease (CAD), according to a study.
Although people with AIHA are known to face a higher risk of blood clots, inherited thrombophilia risk factors were uncommon in the study. Only eight of the 92 evaluated patients (8.7%) had inherited thrombophilia abnormalities, and these were not clearly associated with clotting events in the cohort.
Acquired clotting risk factors linked to thrombotic events
In contrast, patients who tested positive for certain acquired clotting risk factors — particularly anti-phospholipid antibodies, which mistakenly target components of cell membranes — experienced multiple clotting events.
“Our findings support the decision to avoid the screening for inherited thrombophilia in AIHA patients, while testing for acquired risk factors, particularly anti-phospholipid antibodies, is advised,” the researchers wrote. “We would suggest to screen all patients at diagnosis, and then to reevaluate those positive.”
The study, “Thrombophilia screening in patients with autoimmune hemolytic anemia: a single-center analysis,” was published in Haematologica.
AIHA is a group of rare autoimmune disorders in which the immune system produces antibodies that attack red blood cells, leading to their destruction — a process known as hemolysis. When red blood cells are destroyed, the body cannot deliver enough oxygen to tissues, causing symptoms of anemia.
CAD is a form of AIHA in which antibodies bind to red blood cells at cold temperatures. In warm AIHA, the immune attack occurs at warmer temperatures, while mixed AIHA involves both cold- and warm-temperature antibodies.
Previous research has shown that people with AIHA face a higher risk of developing blood clots. Risk factors for these events include severe anemia at diagnosis, signs of active hemolysis on blood tests, previous spleen removal, and Evans syndrome, a related condition in which the immune system destroys red blood cells and platelets.
However, it remains unclear whether people with AIHA should routinely be screened for thrombophilia, inherited or acquired conditions that increase the likelihood of developing blood clots.
Study evaluated thrombophilia screening in AIHA patients
To address this question, researchers in Italy analyzed 92 adults with AIHA (59% women) enrolled in the observational CYTOPAN study (NCT05931718). The median age at the first AIHA episode was about 60, with most patients between 45 and 72 years old. More than half (about 58%) had warm AIHA while 31% had CAD, and the remaining patients had rarer mixed and atypical forms.
All participants underwent thrombophilia screening. This included reviewing clinical records, evaluating personal and family histories of clotting events, and testing blood samples for clotting-related risk factors. During follow-up, patients experienced a median of two hemolytic episodes, or periods when red blood cell destruction increases.
A personal history of blood clots in veins or arteries was documented in four patients (4.3%), while more than half (54.3%) reported a family history of clotting events.
Blood test results showed that about one in five patients (22%) had abnormalities associated with thrombophilia. Those included inherited deficiencies in natural blood-clotting regulatory proteins (8.7%). Another 11% of patients tested positive for anti-phospholipid antibodies — immune proteins that mistakenly target components of cell membranes and are known to increase the risk of blood clots.
Other acquired clotting risk factors also common
In addition to these antibodies, several other acquired clotting risk factors were common. These included recent surgery or trauma (54%), oral contraceptive use among women (48%), cardiovascular disease risk factors (43%), other autoimmune conditions (23%), and a history of cancer (15%).
Some participants also had other medical conditions linked to a higher risk of clotting. These included Evans syndrome, paroxysmal nocturnal hemoglobinuria, and thrombocythemia — a condition marked by very high platelet counts.
“Notably, thrombophilia screening was performed after a median of 4 years … post AIHA diagnosis, thus limiting the reliability of the acquired risk factors in this analysis,” the team wrote.
Overall, the researchers recorded 29 clotting events in 20 patients (22%). Eleven occurred at the time of AIHA diagnosis and 18 occurred afterward. Most vein-related clotting events happened during AIHA relapses.
The overall rate of clotting events was lower among patients with thrombophilia than among those without it (6.7 vs. 10.6 events per 100 patient-years), although the values varied widely. Patient-years refer to the combined amount of time all participants were followed in the study.
Inherited thrombophilia not tied to clotting events
When researchers compared patients who had blood clots with those who did not, many traditional clotting risk factors were similarly distributed between the two groups. However, only one of the eight patients with inherited thrombophilia experienced a clotting event.
About one in five patients (21.7%) received preventive treatment to reduce clotting risk, including vitamin K blockers, antiplatelet therapy, or both. All seven patients who tested positive for two or three types of anti-phospholipid antibodies experienced multiple clotting events despite receiving blood-thinning medications.
Overall, while the total number of clotting events was higher among patients who did not receive preventive therapy, the rate of clots per patient-year appeared higher among those who did receive such treatment. The researchers suggested this likely reflects the higher baseline risk and shorter observation period among patients placed on preventive therapy.
“Routine [inherited] thrombophilia screening is not warranted in AIHA, while the evaluation of acquired and modifiable risk factors, particularly testing for anti-phospholipid antibodies, is advisable,” the researchers concluded. “AIHA remains the major risk factor for [blood clots], warranting [preventive therapy] during haemolytic events.”
