In this cross-sectional study, we have established the prevalence of immune hemolytic anemia among our patients with lymphoid malignancies: specifically CLL, MM and lymphomas.
5.1 Prevalence of immune hemolytic anemia among lymphoid malignancy
The prevalence of immune hemolytic anemia among lymphoid malignancies was 10%. Almost the same percentage was reported in the study done in India by Ghosh et al where the prevalence was 10.6% (28). Thus, patients with lymphoid malignancy must be regarded as being at a higher risk of developing IHA, as from a review article on causes of anemia in cancer by Balana Louis Gaspar et al (27). A study done in south Nigeria by Kaladada et al showed a prevalence of AIHA of about 6% (2/35) among B cell neoplasm; this lower might be explained by the fact that most of their participants were already on chemotherapy, and all those with positive DAT were not on chemotherapy(7). In our study, we observed 4 out of 9 patients with positive DAT had never been transfused in life and one had been transfused in more than 120 days ago; That means the prevalence of AIHA in our study can be estimated to be 6% (5/86) that is almost the same in the study of south Nigeria(7).
5.2 Frequency of IHA among different types of B cell neoplasms
The prevalence of IHA among CLL/SLL, Multiple myeloma, NHL and HL was 13% (3/23), 7% (2/29), 13.8% (4/29) and 14% (1/7) respectively. Almost the same prevalence among CLL/SLL was reported in the study done in Egypt by Basma et al that showed the prevalence of AIHA in CLL to be 11.9% (10). Some studies reported prognostic implication of lymphoid malignancies when presented with IHA (11)(12)(13).
We have low prevalence of IHA among multiple myeloma compared to other few published studies. The study done by Rajesh et al in India showed a slightly higher prevalence of 10.6% (14) that is different from ours that is 7%; this difference can be explained by the fact that most of our participants were already on chemotherapy containing steroids that may have reduced the frequency of IHA.
So far, there are very few studies done showing prevalence of IHA in lymphomas. A study done by Ji Cheng in China showed a prevalence of AIHA among NHL of 0.91%, which is significantly lower than the present study that showed a prevalence of 14% (1/7). Similarly, the present study reports prevalence of 14% for HL but other studies reported that IHA is rare among HL. However, our sample size for lymphomas was small and also our patients present at late stage of the disease which is a risk factor of developing AIHA in hematological malignancy as explained by Ji Cheng et al (15). The same as others wherever these conditions develop AIHA, the prognosis is poor (16)(17) but our study did not assess the survival rate as it was cross sectional study.
5.3 Association between IHA and treatment offered to patients with chronic lymphoid malignancies.
The prevalence of IHA among participants who had never been exposed to chemotherapy or steroids was 23% (7/31). Among 9 participants with positive DAT, 78% (7/9) had never been on steroids whereas 22% (2/9) had been on the latter: this difference was statistically significant with P value of 0.012 and this showed that steroids may be protective to develop IHA. The observed odds ratio was 8.2 that means the risk of developing IHA while not on steroids is 8.2 times more if you are on steroids. This can be explained by the fact that first line and most effective treatment of IHA is steroids and almost all chemotherapy regimen for lymphoid malignancies include steroids, so there is much chance that if the participant had IHA but was on steroids, the disease will clear out and hence negative DAT (18).
4 out 9 positive DAT meaning 44% (4/9) had been transfused in less than 120 days that is the life span of red cells; this means that they may have allo-immune hemolytic anemia or AIHA.
5.4 Status of different hemolytic markers
DAT is the gold standard for the diagnosis of AIHA; but other parameters help to assess the severity of hemolysis. These includes reticulocytes count, indirect bilirubin and LDH (19)(20) (21)(22); they may suggest AIHA even in the rare cases (estimated 5%) when DAT is negative (23). They are also very important in non-immune hemolytic anemia where they will raise whereas DAT is negative
In our study the median absolute reticulocytes count among IHA and non IHA was 80700/L and 41600/L: a considerable difference, though not statistically significant. The highest reticulocyte count that was reported among IHA patients was 557480/L was and lowest was 1380/L. Three out of nine participants had reticulocytes count below the low limit of reference range and two had the one higher than the upper limit of reference range, four remaining had the one within the limits of normal range that is 50,000-100,000/L. Therefore, reticulocytopenia with IHA was found in 33.3% (3/9). This findings is similar in other studies where cases of AIHA with reticulocytopenia have been reported like Lockard et al reported four cases of AIHA and reticulocytopenia with erythroid hyperplasia in the bone marrow (24); the same findings were reported by William et al who assessed 55 cases of AIHA and he found 14 (25.5%) of them had reticulocytopenia and they had poor prognosis compared to those with normal or higher reticulocytes count(25).
In our study, we have found that total, conjugated, unconjugated bilirubins were higher in IHA group compared to non IHA and the difference was statistically significant. These findings may suggest that total and indirect bilirubin can be a good marker of IHA for treatment in case DAT is not available, however, more studies are required to confirm this concept. Jorge et al reported a case of high indirect bilirubin in hemolysis (26).
LDH was high in both IHA and non IHA groups but higher in IHA with a median of 516 and 293 respectively and a P value of 0.0062. LDH usually rises in case of malignancies (27) and it has been used for long time as treatment response monitoring for lymphomas, the lower value observed in the non IHA group should be due to the fact that most of them were on chemotherapy for long period of time. LDH has been used for long time as a marker of hemolysis especially intravascular hemolysis (28) and our study can show how it is even relevant in extravascular hemolysis.