Prevalence of Thrombocytopenia Among Iron Deficiency Anemia in Arab Population in Qatar

Abstract Prevalence of Thrombocytopenia among Iron Deficiency Anemia in Arab population in Qatar INTRODUCTION / BACKGROUND Iron deficiency anemia is a common cause of anemia, and account for almost half of the causes of all anemias. It is well known and common that iron deficiency anemia can be with thrombocytosis, A study reviewed 450 patients with a diagnosis of anemia between 2002 and 2006 was performed in which 143 of them were having IDA found that 31% of them were having associated thrombocytosis (4). A retrospective study conducted in Turkey found that Iron deficiency anemia and thrombocytopenia found in 13 from 615 patients (2.1%) (5). IDA and thrombocytopenia are found in certain ethnicity where we don t have data from studies about Arab Population. Materials and Methods We retrospectively reviewed the electronic medical records of patients attended hematology/ IV iron room clinics with the diagnosis of IDA over 2 years from the period between December 2017 to December 2019 in Hamad Medical Corporation, Qatar. Complete blood count and iron parameters were collected and analyzed. Thrombocytopenia was defined as Platelet count of less than 150 × 109/L. Statistical analysis was done using mean and SD and paired t test to compare variables after versus before treatment. Depending on previous studies available in the literature, the prevalence of IDA and thrombocytopenia reported from the study done in Turkey (2.1%), based on this we expect the prevalence estimates in Arab population is 3% (with margin of error +/- %) and confidence level 95%, the required sample size needed would be a total of 1744 participants +- 0.8. The adequate sample size was determined using the following statistical equation: Inclusion Criteria: Arab Female who is diagnosed with iron deficiency anemia or iron depleted and receive iron therapy. Exclusion criteria: Extreme age less than 18 and above 65Any chronic organ dysfunction or failurePrevious bariatric surgery or gastrostomyMalignancy (Known or discovered at any time during study follow up) Results: Out of 1752 cases of IDA, 39 cases had thrombocytopenia, (2.2 %) (table 1) with mean age of 41.38. The mean Platelet count was 108 x 10^9 in patients with thrombocytopenia while it was 325 x 10^9 in non-thrombocytopenia patients. Platelets count mean increased to 179 x 10^9 after iron replacement (p < 0.05). Analysis of thrombocytopenia according to nationalities was obtained which showed 28 cases among Qatari's (2.2%), 4.1 % in Egyptians, 3.8% in Yemenis, 3.1% Sudanese, 2.9%,2.7% in Jordanian and Syrian respectively and 1.1% in other nationalities (table 2). Discussion: Qatar is multinational country with large number of expatriates working in it. In our study thrombocytopenia occurred in 39 cases out of 1752 cases included in the study which represent 2.2% of them. Most of our patients were of Qatari nationality 1327 in which 28 cases of thrombocytopenia were found, with 3.8 % in Egyptian the 2nd most common Arab residents in Qatar. Further analysis according to nationalities revealed 3.1%, 2.9%, 2.7% in Yemenis, Sudanese and Jordanian patients, with 1.1% in other patients from other Arab nationalities. Comparison of blood parameters including platelet count before and after iv iron therapy were obtained which showed mean platelet count was 108 x 10^9 which increased to 179 x 10^9 after iron therapy, The mechanisms for the thrombocytopenia associated with IDA are not well established, although iron plays a critical role both in the synthesis of platelets and in the regulation of thrombopoiesis. Other blood parameters including WBC, ANC, Lymphocyte count showed decremental responses after iron therapy with WBC dropped from 6.3 to 6.1, ANC from 3.5 to 2.7 and lymphocyte count from 1.9 to 1.8 in thrombocytopenic patients. Conclusion: The prevalence of thrombocytopenia among IDA in Qatar was 2.2%, which normalized after iv iron therapy. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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Iron Therapy Induced Leukopenia

Blood ◽

10.1182/blood-2020-135951 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 39-40

Author(s):

Hussam A Almasri ◽

Ashraf Tawfiq Soliman ◽

Vincenzo Desanctis ◽

Arwa E Alsaud ◽

Ruoa Alhashimy ◽

...

Keyword(s):

Bone Marrow ◽

Iron Deficiency ◽

Tract Infection ◽

Iron Deficiency Anemia ◽

Side Effect ◽

Iron Therapy ◽

Deficiency Anemia ◽

Ferric Carboxymaltose ◽

Iv Iron ◽

Iron Replacement

Introduction Iron deficiency anemia (IDA) is the most common cause of anemia in both developed and developing countries, particularly affecting females in the child bearing age and children. The treatment of IDA is a major health goal, it consists of treating the underlying cause and iron supplements. Iron replacement comes in form of oral or intravenous, there are certain side effects of this therapy including constipation and allergy. Leukopenia as a side effect of iron therapy is under reported in the literature as only sporadic cases were prescribed. We conducted a study to clarify this issue and to check for its clinical significance. Objective: To assess the relationship between iron therapy (intravenous) and leukopenia, neutropenia or lymphocytopenia, and its impact on patient's clinical settings. Materials and Methods We retrospectively reviewed the electronic medical records of patients attended Haematology clinic for iron deficiency anemia and treated with intravenous iron (ferric carboxymaltose or iron saccharide) over 2 years in Hamad Medical Corporation, Doha/Qatar. Adult female patients with IDA cases who received IV iron were included. anemia due to other nutrients deficienciesa nd conditions (including other medications) that may alter WBCs count were excluded.Age, Ethnicity, BMI, Complete blood count and iron studies data were collected before and after treatment with IV iron therapy. Infection occurrence at the time of IDA and leukopenia, the use of antibiotics and infection related complications were also collected. Leukopenia was defined as WBCs count to be less than 4000/microlitre, Neutropenia as ANC less than 1500/microlitre and lymphocytopenia as lymphocytes less than 1000/mocrolitre. Statistical analysis was done using mean , SD and t test. Results After iron therapy, out of 1567 case of iron deficiency anemia, 30 cases (1.914%) have leukopenia,15 cases (0.957%) have neutropenia and 12 cases (0.765%) have lymphocytopenia. All had normal readings before treatment. 2 patients (6.66%) had infection, 1 had upper respiratory tract infection and 1 urinary tract infection, the latter was treated with antibiotics, none reported infection related complications Discussion Leukocytopenia is defined as low WBCs circulating in the blood and this can be caused by low neutrophils count, low lymphocytes count, other WBCs components or combined. Some previous reported cases generated the idea of a possible connection between iron supplement therapy and leukopenia, Brito-Babapulle et al reported a case of fatal bone marrow suppression linked to ferric carboxymaltose therapy in a patient with IDA. The pathophysiology is not well understood but thought to be a toxic effect of iron on bone marrow and it can affect all cell lineages. Our findings suggest possible iron replacement side effect as there was significant drop of the WBCs count after treating IDA patients with IV iron, however this association was not common. There was no life threatening or serious infections in the affected patients, which can suggest that most of these cases are mild and transient. More studies are needed to address this issue, particularly on larger scales. Patient education also may be appreciated before treatment with IV iron. Conclusions: Leukopenia in form of neutropenia or lymphocytopenia maybe a side effect of IV iron therapy. Clinical significance is limited in view of current literature further studies needed to elaborate more in this important adverse event. Disclosures No relevant conflicts of interest to declare.

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The Prevalence of Lymphocytopenia Among Arab Population with Iron Deficiency Anemia an Experience from Qatar

Blood ◽

10.1182/blood-2020-135911 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 15-16

Author(s):

Hussam A Almasri ◽

Ashraf Tawfiq Soliman ◽

Vincenzo Desanctis ◽

Rita Wafik Ahmad ◽

Mustafa A Al-Tikrity ◽

...

Keyword(s):

Iron Deficiency ◽

Iron Deficiency Anemia ◽

Lymphocyte Count ◽

Iron Therapy ◽

Deficiency Anemia ◽

Upper Respiratory Tract ◽

Cell Counts ◽

The Mean ◽

Tract Infections ◽

Iron Replacement

Introduction Iron deficiency anaemia (IDA) is one of the most common health problems worldwide, its prevalence is up to 1 in 5 of the general population. The diagnosis of absolute iron deficiency is easy unless the condition is masked by inflammatory conditions. All cases of iron deficiency should be assessed for treatment and underlying cause.In developing countries, iron deficiency anemia is nutritional, resulting from reduced intake of bioavailable iron , and often associated with infections causing hemorrhages, such as hookworm infestation . In Western societies, other than in individuals at risk, iron depletion results from chronic bleeding and/or reduced iron absorption, disorders that may be more relevant than anemia itself.The association between IDA and lymphocytopenia is poorly addressed in the literature. Objective: To assess the prevalence of lymphocytopenia in a large cohort with IDA and to study the effect of iron replacement on lymphocytes count. Materials and Methods We retrospectively reviewed the electronic medical records of patients attended haematology clinic with the diagnosis of IDA over 2 years in Hamad Medical Corporation, Qatar. Patients with other forms of anemia were excluded as those with chronic or systemic diseases. Complete blood count and iron parameters were collected and analysed. Lymphocytopenia was defined as lymphocyte count less than 1000/microlitre. Statistical analysis was done using mean and SD and paired t test to compare variables after versus before treatment. Results The mean age of our IDA patients was 37.95 years with a mean BMI = 31.82. Out of 1567 case of IDA, 20 had lymphocytopenia, (1.276%). The mean lymphocytes count mean increased from 0.73 +/- 0.15 x 10^9 before iron replacement, to 1.79 +/- 0.74 x 10^9 after iron treatment (p < 0.05) (iron dose of 1000 mg of IV iron saccharate or ferric carboxymaltose) . Four out of the 20 patients with lymphopenia had mild infections (2 upper respiratory tract infections, 1 urinary tract infection and one gastroenteritis) with no serious complications. These findings suggested that the lymphopenia associated with IDA is correctable and does not increase infection risk in these patients. Discussion Our study showed a possible negative impact of IDA on lymphocytes count in a small number of patients that was corrected with the correction of anemia with iron therapy. Animal studies showed that iron deficiency may lead to impaired T lymphoid differentiation and may negatively affect all cell lineage in haematopoiesis not only on erythroid line. A case control study by Das et al. found significantly lower levels of CD4+ T-cell counts and CD4:CD8 ratios in iron deficient children, however there was no significant effect on immunoglobulin levels. Conclusions: Lymphopenia may occur in a small percentage of patients with IDA. Significant increase in the lymphocyte count occur with iron therapy and correction of the anemia. Lymphopenia was not associated with serious infections. Disclosures No relevant conflicts of interest to declare.

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The Prevalence of Reactive Thrombocytosis and Thromboembolic Events in Arab Population with Iron Deficiency Anemia (a retrospective study)

Blood ◽

10.1182/blood-2020-135923 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 16-17

Author(s):

Rita Wafik Ahmad ◽

Ashraf Tawfiq Soliman ◽

Vincenzo Desanctis ◽

Lina A Okar ◽

Mustafa A Al-Tikrity ◽

...

Keyword(s):

Platelet Count ◽

Iron Deficiency ◽

Carotid Artery ◽

Iron Deficiency Anemia ◽

Case Reports ◽

Deficiency Anemia ◽

Thromboembolic Events ◽

Arab Population ◽

Reactive Thrombocytosis ◽

Thrombocyte Count

INTRODUCTION Iron deficiency is the most prevalent nutritional deficiency worldwide. Iron deficiency anemia (IDA) is the most common type of anemia, its prevalence is 1 out of 5 of the population. IDA is a well-known cause of reactive thrombocytosis which is mostly asymptomatic. Only few observational studies and case reports have described thromboembolic events in the context of this reactive thrombocytosis in the absence of other hypercoagulable states OBJECTIVES To assess the frequency of thromboembolic events in Arab patients with reactive thrombocytosis secondary to iron deficiency anemia (IDA). METHODS We retrospectively reviewed thromboembolic events in iron-deficient patients with reactive thrombocytosis. Our study sample included female patients who received iron replacement for IDA between April 2018 and March 2020 at Hamad Medical Corporation, Doha, Qatar. We excluded pregnant, non-Arab patients and patients under 18 or over 65 years of age. Reactive thrombocytosis was defined as thrombocyte count of more than or equal to 450 x 109 /L in the presence of iron deficiency anemia and ferritin level less than 30µg/l. RESULTS Out of 1567 patients (mean age =50 +/- 8.66 years) with the diagnosis of IDA, 292 (18.63%) had thrombocytosis. They had a mean platelet count = 534 +/- 121 x 109 /L). None of them had any symptom or sign of thromboembolic events. Discussion Thrombocytosis can be categorized into primary causes such as primary bone marrow disorders and myeloproliferative neoplasms, and secondary causes including infection, inflammation or drug-induced. Iron deficiency anemia leads to reactive thrombocytosis in a mechanism that is yet to be fully understood. The clinical impact of increased platelet counts is not well recognized in literature, and it has not been studied in the Arab population. Although reactive thrombocytosis has been generally considered benign, few case reports described thromboembolic events in patients with IDA reactive thrombocytosis. Few cases in the literature described thromboembolic events in reactive thrombocytosis with IDA. H. Z. Batur Caglayan et al published a case report of a 41-year-old Turkish female patient who presented with transient ischemic attack (TIA) due to intraluminal carotid artery thrombus, which was attributed to IDA-associated thrombocytosis. Another case series by P T Akins et al described three women with severe IDA and thrombocytosis secondary to menorrhagia who developed carotid artery thrombi. The mechanism by which low iron can affect thrombocyte count is still unknown. One study in mice and humans demonstrated that iron deficiency caused reduced megakaryocyte proliferation but increased ploidy independent of thrombopoietin. However, another study failed to identify the exact mechanism by which iron deficiency leads to increased platelet count. CONCLUSION Our study did not find any thromboembolic incident in a large number of patients with reactive thrombocytosis secondary to IDA diagnosed over two years in our Arab population. Disclosures No relevant conflicts of interest to declare.

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Potential New Treatment Option for Iron Deficiency Anemia Patients with a History of Unsatisfactory Oral Iron Therapy- Results of a Phase III, Randomized, Open-Label, Active-Controlled Trial of Ferumoxytol.

Blood ◽

10.1182/blood.v120.21.2099.2099 ◽

2012 ◽

Vol 120 (21) ◽

pp. 2099-2099 ◽

Cited By ~ 1

Author(s):

David Hetzel ◽

Audrone Urboniene ◽

Kristine Bernard ◽

William Strauss ◽

Michael Cressman ◽

...

Keyword(s):

Iron Deficiency ◽

Iron Deficiency Anemia ◽

Controlled Trial ◽

Treatment Options ◽

Oral Iron ◽

Iron Therapy ◽

Deficiency Anemia ◽

Oral Iron Therapy ◽

History Of ◽

Iv Iron

Abstract Abstract 2099 Background: While oral iron is the preferred first-line treatment for patients with iron deficiency anemia (IDA), there are patients who cannot take oral iron, do not tolerate it or do not adequately respond to oral iron. In the US and Canada, the only approved treatment options for these patients are the iron dextrans, which have boxed safety warnings and inconvenient dosing regimens. Therefore, many of these anemic patients do not receive IV iron, and remain inadequately treated and symptomatic. In the EU, several IV irons, including iron sucrose (IS), are approved for second line use. Few studies have evaluated the IV irons in head-to-head studies. Ferumoxytol (FER) is a new IV iron approved for the treatment of IDA in patients with chronic kidney disease (CKD) that is formulated to allow for bolus IV injection. This randomized, controlled trial was designed to investigate the efficacy and safety of FER compared to IS for the treatment of IDA in patients with a history of unsatisfactory oral iron therapy or in whom oral iron could not be used. Methods: The study was designed to demonstrate non-inferiority and consisted of a 14 day screening period, treatment and a 5 week follow-up period. Key inclusion criteria included a Baseline hemoglobin (Hgb) less than 10 g/dL and >7 g/dL, and transferrin saturation (TSAT) < 20%. Patients were randomized 2:1 to receive either FER, administered as 2 injections of 510 mg 5±3 days apart, or IS, administered as 5 infusions or injections of 200 mg on 5 non-consecutive days over a 14 day period. Results: A total of 605 subjects were randomized to the 2 treatment arms (FER, n= 406; IS, n=199). FER demonstrated non-inferiority to IS in the proportion of subjects with a >2.0 g/dL increase in Hgb at any time from Baseline to Week 5 (the primary efficacy endpoint), compared to those treated with IS, (FER, 84%; IS 81%) with the lower bound of the 95% CI [-3.89%] above the predefined non inferiority margin [-15%]. In addition at each post-treatment time point, a higher percentage of FER-treated subjects achieved a >2.0 g/dL increase in Hgb compared to those treated with IS. FER also achieved non-inferiority to IS in the mean change in Hgb from Baseline to Week 5 with a robust 2.7g/dL increase in Hgb compared to 2.4g/dL with IS (the lower bound of the 95% CI [0.06g/dL] was above the predefined non-inferiority margin [-0.5g/dL]); this treatment difference (0.3 g/dL) was statistically significant (p=0.0124), and FER actually achieved superiority over IS. The overall rates of adverse events (AEs) and related AEs were lower in the FER group compared to IS-treated subjects. The serious adverse event (SAE) rate was higher in FER-treated subjects (FER, 4.2%; IS, 2.5%), but no pattern or safety trend was observed to suggest a specific safety signal; treatment-related SAEs were reported in 2 (0.5%) FER-treated subjects (1 anaphylactoid reaction and 1 hypertension). Protocol-defined AEs of Special Interest (signs/symptoms of hypotension or hypersensitivity associated with IV iron use) were reported at a higher rate in IS-treated subjects compared to the FER treatment group (IS, 5.0%; FER, 2.7%). Cardiovascular AE rates were comparable in the 2 treatment groups (1.0%). Overall, the safety profile of FER was comparable to that of IS and no new safety signals were identified. Conclusion: In this randomized, controlled trial, the efficacy and safety of 2 doses of FER were shown to be comparable to IS in treating IDA patients with a history of unsatisfactory oral iron therapy or in whom oral iron could not be used. For this IDA patient population, which has limited treatment options in the US and Canada, FER may offer an important, new treatment option with a convenient 2 dose regimen. Disclosures: Off Label Use: Feraheme (ferumoxytol) injection. For treatment of iron deficiency anemia in non-CKD patients. Bernard:AMAG Pharmaceuticals, Inc.: Employment. Strauss:AMAG Pharmaceuticals, Inc.: Employment. Cressman:AMAG Pharmaceuticals, Inc.: Employment. Li:AMAG Pharmaceuticals, Inc.: Employment. Allen:AMAG Pharmaceuticals, Inc.: Employment.

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Economic, Transfusion, and Efficacy Outcomes with the Addition of IV Iron Sucrose to Oral Iron Therapy in Pregnancy Associated Iron Deficiency Anemia

Blood ◽

10.1182/blood.v128.22.4737.4737 ◽

2016 ◽

Vol 128 (22) ◽

pp. 4737-4737

Author(s):

Nilupa Gaspe Mudiyanselage ◽

Tarek Elrafei ◽

Beth Lewis ◽

Mary King ◽

Marianna Strakhan ◽

...

Keyword(s):

Iron Deficiency ◽

Pregnant Women ◽

Iron Deficiency Anemia ◽

Oral Iron ◽

Iron Sucrose ◽

Iron Therapy ◽

Deficiency Anemia ◽

Iron Group ◽

Iv Iron ◽

Iron Replacement

Abstract Background: Prior studies have indicated that transfusion is unusual (2%) in pregnant women with iron deficiency anemia. Nonetheless, compliance with oral iron replacement can be an issue and physicians may wish to use IV iron therapy in markedly anemic pregnant women. Objectives: to evaluate the effectiveness of adding intravenous iron sucrose concentrate (ISC) to pregnant patients already taking oral iron in terms of effect on hemoglobin, effect on ferritin levels, rates of transfusion, and cost. Methods: We analyzed all referrals from Obstetrics to Hematology clinic and Obstetrics consultation (Internal medicine) clinic from January 2014 to June 2016. Of the 176 pregnant patients, 98 were referred for anemia, including 81 patients with Hgb < 12 g/dl and ferritin < 20 ug/L. All had previously been given oral ferrous sulfate prescriptions. Patients with hemoglobinopathy were excluded. All 81 patients were advised to continue on the oral iron, and 40 were given IV iron sucrose (ISC group). Results: The average cumulative dose of iron sucrose was 700 mg, a mean of 5.575 doses (initiated in the third trimester in 38 of 40 patients). The lowest antepartum Hgb was 8.18 g/dl in the ISC group and 9.58 in the oral only group; there was an average Hgb increase of 2.17 vs 1.76 g/dl respectively (p=.107 NS and the 0.41 g/dl difference was considered to be of no clinical consequence). 89% in the ISC group vs 30% in the oral achieved a ferritin >20 (p=0.000015). No adverse events in the IV iron group were reported. There was 1 transfusion in the oral iron group attributable to iron deficiency (2.4%) vs none in the IV iron group (p = 0.107 NS). Two patients were transfused in the antenatal period before IV iron was started and 1 transfused because of post-partum hemorrhage. The total cost of the IV iron therapy would add an average of $1,500 per patient. Thus, and additional cost of $60,000 in IV iron would be required to prevent 1 transfusion [40:1]. Conclusions: ISC corrects ferritin in more patients than oral iron replacement, but did not significantly increase Hgb levels or have a meaningful impact on the transfusion rate. The additional cost and lack of clinically improved outcomes with IV iron argue against its use and in favor of strategies to ensure compliance with oral iron. Disclosures No relevant conflicts of interest to declare.

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Intravenous Iron Therapy in Patients with Iron Deficiency Anemia: Dosing Considerations

Anemia ◽

10.1155/2015/763576 ◽

2015 ◽

Vol 2015 ◽

pp. 1-10 ◽

Cited By ~ 30

Author(s):

Todd A. Koch ◽

Jennifer Myers ◽

Lawrence Tim Goodnough

Keyword(s):

Iron Deficiency ◽

Iron Deficiency Anemia ◽

Cumulative Dose ◽

Clinical Studies ◽

Intravenous Iron ◽

Iron Therapy ◽

Deficiency Anemia ◽

Ferric Carboxymaltose ◽

Iv Iron ◽

Iron Deficit

Objective.To provide clinicians with evidence-based guidance for iron therapy dosing in patients with iron deficiency anemia (IDA), we conducted a study examining the benefits of a higher cumulative dose of intravenous (IV) iron than what is typically administered.Methods.We first individually analyzed 5 clinical studies, averaging the total iron deficit across all patients utilizing a modified Ganzoni formula; we then similarly analyzed 2 larger clinical studies. For the second of the larger studies (Study 7), we also compared the efficacy and retreatment requirements of a cumulative dose of 1500 mg ferric carboxymaltose (FCM) to 1000 mg iron sucrose (IS).Results.The average iron deficit was calculated to be 1531 mg for patients in Studies 1–5 and 1392 mg for patients in Studies 6-7. The percentage of patients who wereretreatedwith IV iron between Days 56 and 90 was significantly (p<0.001) lower (5.6%) in the 1500 mg group, compared to the 1000 mg group (11.1%).Conclusions.Our data suggests that a total cumulative dose of 1000 mg of IV iron may be insufficient for iron repletion in a majority of patients with IDA and a dose of 1500 mg is closer to the actual iron deficit in these patients.

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Ferumoxytol Treatment Results in Robust Hemoglobin Increases in Iron Deficiency Anemia Patients with a History of Unsatisfactory Oral Iron Therapy in a Phase III, Randomized, Placebo-Controlled Trial.

Blood ◽

10.1182/blood.v120.21.2098.2098 ◽

2012 ◽

Vol 120 (21) ◽

pp. 2098-2098

Author(s):

Saroj Vadhan Raj ◽

Michael Cressman ◽

David Ford ◽

William Strauss ◽

Gerri Poss ◽

...

Keyword(s):

Iron Deficiency ◽

Iron Deficiency Anemia ◽

Group Treatment ◽

Oral Iron ◽

Phase Iii ◽

Iron Therapy ◽

Deficiency Anemia ◽

Oral Iron Therapy ◽

History Of ◽

Iv Iron

Abstract Abstract 2098 Background: Although oral iron therapy is often the initial approach to the treatment of iron deficiency anemia (IDA), many patients fail to adequately respond or do not tolerate oral iron. Unfortunately for these patients, approved treatment options are limited in the US and Canada to only the IV iron dextrans, which have boxed safety warnings and inconvenient dosing regimens. Many of these patients, therefore, do not get IV iron, and remain inadequately treated and symptomatic. Ferumoxytol (FER), a new IV iron approved for the treatment of IDA in patients with chronic kidney disease (CKD), is being investigated to treat IDA patients without CKD who have a history of unsatisfactory oral iron therapy or in whom oral iron cannot be used. This randomized, placebo-controlled, double blind trial was designed to assess the efficacy and safety of FER for the treatment of these IDA patients. Methods: Key inclusion criteria included a Baseline hemoglobin (Hgb) less than 10 g/dL and >7 g/dL, and transferrin saturation (TSAT) <20%. Subjects were randomized 3:1 to receive 2 injections of either FER (510 mg, 5±3 days apart) or placebo (IV normal saline). Efficacy assessments included comparisons of the change in Hgb, TSAT and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) score in the 2 treatment groups between Baseline and Week 5. Results: A total of 808 subjects were randomized to the 2 treatment arms (FER, n=608; placebo, n=200). FER demonstrated superiority to placebo with 81.1% of subjects achieving an increase in Hgb of >2.0 g/dL from Baseline to Week 5 compared to only 5.5% in the placebo group (treatment difference: 75.6%, p<0.0001). At each post-FER treatment time point, a larger percentage of FER-treated subjects had a >2.0 g/dL increase in Hgb compared with those treated with placebo. The superiority of FER was also demonstrated for the mean change in Hgb from Baseline to Week 5 with a robust 2.7 g/dL increase compared to only 0.1 g/dL in the placebo group (treatment difference: 2.54 g/dL, p<0.0001). An increase in TSAT from Baseline to Week 5 was only observed in FER-treated subjects (mean change: FER, 11.0%; placebo −0.1%). In addition, a statistically significant improvement in fatigue from Baseline to Week 5, as measured by the FACIT-Fatigue, was shown for FER-treated subjects compared to placebo (p<0.0001). The rates of adverse events (AEs) and related AEs were higher in the FER group, although no pattern or safety trend was observed to suggest a specific safety signal. The overall rate of serious adverse events (SAEs) was comparable between the 2 treatment groups (FER, 2.6%; placebo, 3.0%), and treatment-related SAEs associated with the class of IV iron products were reported in 4 (0.7%) FER-treated subjects. As expected, protocol-defined AEs of Special Interest (signs/symptoms of hypotension or hypersensitivity associated with IV iron use) were noted at a higher rate in FER-treated subjects (FER, 3.6%; placebo, 1.0%). All cardiovascular AEs were considered unrelated by the investigators. Overall, FER was well tolerated and no new safety signals were identified. Conclusion: In this randomized, placebo-controlled Phase III trial, 2 doses of FER were shown to be highly effective in raising hemoglobin and iron parameters in non-CKD patients with IDA who had a history of unsatisfactory oral iron therapy. FER also significantly reduced fatigue, and was generally well tolerated with no new safety signals being identified. Therefore, FER could provide an important, new treatment option for IDA patients with a history of unsatisfactory oral iron therapy or in whom oral iron could not be used. Disclosures: Vadhan Raj: AMAG Pharmaceuticals, Inc.: Research Funding. Off Label Use: Feraheme (ferumoxytol) injection. For treatment of iron deficiency anemia in non-CKD patients. Cressman:AMAG Pharmaceuticals, Inc.: Employment. Strauss:AMAG Pharmaceuticals, Inc.: Employment. Bernard:AMAG Pharmaceuticals, Inc.: Employment. Li:AMAG Pharmaceuticals, Inc.: Employment. Allen:AMAG Pharmaceuticals, Inc.: Employment.

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Intravenous Iron Induced Cytopenias(Leukopenia,Neutropenia,Lymphocytopenia) Among Arab Population with Iron Deficiency Anemia

Blood ◽

10.1182/blood-2020-136283 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 18-19

Author(s):

Hussam A Almasri ◽

Ashraf Tawfiq Soliman ◽

Vincenzo Desanctis ◽

Rita Wafik Ahmad ◽

Mustafa A Al-Tikrity ◽

...

Keyword(s):

Bone Marrow ◽

Iron Deficiency ◽

Iron Deficiency Anemia ◽

Side Effect ◽

Intravenous Iron ◽

Iron Therapy ◽

Deficiency Anemia ◽

Ferric Carboxymaltose ◽

Iv Iron ◽

Iron Replacement

Introduction Iron deficiency anemia (IDA) is the most common cause of anemia in both developed and developing countries, particularly affecting females in the child bearing age and children. The treatment of IDA is a major health goal, it consists of treating the underlying cause and iron supplements. Iron replacement comes in form of oral or intravenous, there are certain side effects of this therapy including constipation and allergy. Leukopenia as a side effect of iron therapy is under reported in the literature as only sporadic cases were prescribed. We conducted a study to clarify this issue and to check for its clinical significance. Objective: To assess the relationship between iron therapy (intravenous) and leukopenia, neutropenia or lymphocytopenia, and its impact on patient's clinical settings. Materials and Methods We retrospectively reviewed the electronic medical records of patients attended Haematology clinic for iron deficiency anemia and treated with intravenous iron (ferric carboxymaltose or iron saccharide) over 2 years in Hamad Medical Corporation, Doha/Qatar. Adult female patients with IDA cases who received IV iron were included. anemia due to other nutrients deficienciesa nd conditions (including other medications) that may alter WBCs count were excluded.Age, Ethnicity, BMI, Complete blood count and iron studies data were collected before and after treatment with IV iron therapy. Infection occurrence at the time of IDA and leukopenia, the use of antibiotics and infection related complications were also collected. Leukopenia was defined as WBCs count to be less than 4000/microlitre, Neutropenia as ANC less than 1500/microlitre and lymphocytopenia as lymphocytes less than 1000/mocrolitre. Statistical analysis was done using mean , SD and t test. Results After iron therapy, out of 1567 case of iron deficiency anemia, 30 cases (1.914%) have leukopenia,15 cases (0.957%) have neutropenia and 12 cases (0.765%) have lymphocytopenia. All had normal readings before treatment. 2 patients (6.66%) had infection, 1 had upper respiratory tract infection and 1 urinary tract infection, the latter was treated with antibiotics, none reported infection related complications Discussion Leukocytopenia is defined as low WBCs circulating in the blood and this can be caused by low neutrophils count, low lymphocytes count, other WBCs components or combined. Some previous reported cases generated the idea of a possible connection between iron supplement therapy and leukopenia, Brito-Babapulle et al reported a case of fatal bone marrow suppression linked to ferric carboxymaltose therapy in a patient with IDA. The pathophysiology is not well understood but thought to be a toxic effect of iron on bone marrow and it can affect all cell lineages. Our findings suggest possible iron replacement side effect as there was significant drop of the WBCs count after treating IDA patients with IV iron, however this association was not common. There was no life threatening or serious infections in the affected patients, which can suggest that most of these cases are mild and transient. More studies are needed to address this issue, particularly on larger scales. Patient education also may be appreciated before treatment with IV iron. Conclusions: Leukopenia in form of neutropenia or lymphocytopenia maybe a side effect of IV iron therapy. Clinical significance is limited in view of current literature further studies needed to elaborate more in this important adverse event. Figure Disclosures No relevant conflicts of interest to declare.

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