|Year : 2023 | Volume
| Issue : 2 | Page : 146-156
Do we need local guidelines for the diagnosis and management of immune thrombocytopenia in Iraq?
Ahmed Mjali1, Bassam Francis Matti2, Nareen Tawfeeq Abbas3, Hassan Ali Abood Nassrullah4, Alaadin Sahham Naji5, Alaa Fadhil Alwan6, Waseem Fadhil Al-Tameemi7, Haider Hasan Jaleel Al-Shammari8, Tareq Abdullah Saleh2, Mohammed Kamil Al Qayyim2, Amer Shareef Mohammed9
1 Department of Hematology/Oncology, Al-Hussein Medical City, Karbala, Iraq
2 Department of Hematology, Baghdad Teaching Hospital, Medical City, Baghdad, Iraq
3 Department of Hematology, Hiwa Hematology/Oncology Hospital, Sulaymaniyah, Iraq
4 Department of Internal Medicine, College of Medicine, University of Al-Ameed, Karbala, Iraq
5 Department of Hematology, Baghdad Medical College, Baghdad University, Baghdad, Iraq
6 Department of Clinical Hematology, The National Center of Hematology, Mustansiriyah University, Baghdad, Iraq
7 Department of Medicine, Hematology Unit, College of Medicine, Al Nahrain University, Baghdad, Iraq
8 Department of Pathology, Baghdad University College of Medicine, Baghdad, Iraq
9 Department of Internal Medicine, Thi.Qar Medical College, Thi-Qar University, Nasiriyah, Iraq
|Date of Submission||17-Feb-2023|
|Date of Decision||06-Jun-2023|
|Date of Acceptance||09-Jun-2023|
|Date of Web Publication||27-Jul-2023|
Dr. Ahmed Mjali
Department of Hematology/Oncology, Al- Hussein Medical City, Karbala
Source of Support: None, Conflict of Interest: None
AIMS: Immune thrombocytopenia (ITP), also known as immune thrombocytopenic purpura, is an autoimmune disorder characterized by a low platelet count in the blood. This study aimed to assess the health infrastructure in Iraq regarding the diagnosis and management of patients with immune thrombocytopenia (ITP), with a focus on the use of guidelines in ITP management.
SETTINGS AND DESIGN: This was a cross-sectional study carried out between October and November 2022 to assess ITP diagnosis, management, and the use of guidelines in 18 governorates in Iraq.
MATERIALS AND METHODS: Invited to this study were 79 hematologists who were registered in the Iraqi Society of Hematology and who practiced in the 18 governorates. Out of the 79 hematologists, 65 participated in this survey. Data were collected using a questionnaire.
STATISTICAL ANALYSIS USED: IBM SPSS 28 for Windows was used for the analysis and Microsoft Excel was used for creating the graphs. Descriptive statistics were presented in the form of numbers and percentages as all variables were categorical.
RESULTS: The most requested routine tests were manual assessment of platelet count (83.1%), blood film (98.5%), virology screen (90.9%), connective tissue screen (85.9%), and prothrombin time and partial thromboplastin time (78.5%). More than 80% of the hematologists request bone marrow aspiration for the patients who have no response to the first-line treatment. Only the genetic test and the quantitative immunoglobulin level testing were available in the private sector both by (100%), while the other tests were available in both sectors. More than 85% treat the patients as outpatients. Active bleeding, not platelet count, was the indication for hospitalization for 60% of the hematologists. Corticosteroids were chosen as the first choice as initial treatment by (93.8%), intravenous immunoglobulin the second choice by (6.2%). In the second-line treatment, rituximab was chosen as the first choice by (75.3%), and eltrombopag as the second choice (65%). Only 83% of the hematologists referred to a guideline, and the American Society of Hematology guideline was the most referred to.
CONCLUSIONS: These results showed the need to establish national guidelines for the Diagnosis and Management of Immune Thrombocytopenia in Iraq to be able to effectively treat the laboratory findings and physical symptoms of ITP in addition to address the patient's emotional and mental health needs.
Keywords: Guidelines, immune thrombocytopenia, platelets, splenectomy, steroids
|How to cite this article:|
Mjali A, Matti BF, Abbas NT, Abood Nassrullah HA, Naji AS, Alwan AF, Al-Tameemi WF, Jaleel Al-Shammari HH, Saleh TA, Al Qayyim MK, Mohammed AS. Do we need local guidelines for the diagnosis and management of immune thrombocytopenia in Iraq?. J Appl Hematol 2023;14:146-56
|How to cite this URL:|
Mjali A, Matti BF, Abbas NT, Abood Nassrullah HA, Naji AS, Alwan AF, Al-Tameemi WF, Jaleel Al-Shammari HH, Saleh TA, Al Qayyim MK, Mohammed AS. Do we need local guidelines for the diagnosis and management of immune thrombocytopenia in Iraq?. J Appl Hematol [serial online] 2023 [cited 2023 Sep 27];14:146-56. Available from: https://www.jahjournal.org/text.asp?2023/14/2/146/383050
| Introduction|| |
Immune thrombocytopenia (ITP), also called idiopathic thrombocytopenic purpura, immune thrombocytopenic purpura) is an acquired thrombocytopenia caused by autoantibodies against platelet antigens. When adults are generally asymptomatic, it is one of the most frequent causes of thrombocytopenia.,, Adults with ITP often have a chronic course, but 80%–90% of children with ITP experience spontaneous remission within weeks to months of disease onset. Signs and symptoms often start appearing with platelet counts <100 × 109/L, but bleeding is uncommon until platelet counts drop below 30 × 109/L, and the most serious complication of ITP is cerebral hemorrhage.
After ruling out any underlying and/or initiating causes of the thrombocytopenia, ITP remains a diagnosis of exclusion because there is no definite diagnostic test for it. The difficulties in identifying ITP are due to the absence of a sensitive or precise diagnostic test and the abundance of additional probable causes of thrombocytopenia.
Initial treatment of newly diagnosed ITP is recommended at a platelet count <20–30 × 109/L in adult patients without symptoms.,,, In addition, experts advise that each patient's treatment should be unique and focused on preventing bleeding as well as reducing toxicity and improving the quality of life.
Oral corticosteroids are the suggested first-line treatment for patients with chronic ITP. In addition, intravenous immunoglobulin (IVIG), with or without corticosteroids, has been a common first-line anti-ITP therapy. IVIG therapy is advised for use in patients who require a rapid increase in platelet count due to severe bleeding since it is usually believed to have a more rapid platelet response than corticosteroids., Another way for treating ITP is using anti-D for patients with an intact spleen who are Rh-positive.
The majority of ITP patients respond to primary therapy, such as glucocorticoids or IVIG, but a good number of patients eventually need secondary therapy because it is challenging to maintain long-term responses. Such patients may think about undergoing surgery (splenectomy) or receiving medication treatment Thrombopoietin receptor agonists (TPO-RAs), rituximab. In patients with newly diagnosed ITP, rituximab has been investigated in combination with dexamethasone versus dexamethasone alone. As for TPO-RA, the total response rate is anticipated to be between 60% and 90%, although it is not typically believed to be curative because roughly 25%–40% of patients have reported long-term remission following treatment.,,
Guidelines for the diagnosis and management of patients with ITP are required to help practitioners make decisions about inpatient versus outpatient management, thresholds for when to begin treatment, and options for second-line treatment in adults. Unfortunately, currently, there are no local guidelines in Iraq for the diagnosis and management of patients with ITP. In 1996 and 2011, the American Society of Hematology (ASH) supported efforts to create guidelines for the diagnosis and management of patients with ITP. These guidelines used different approaches to arrive at recommendations for testing and treatment.
International guidelines cannot be applied in all countries. Access to new high-cost therapies is impossible in developing countries like Iraq. These countries need to have their own guidelines based on the availability of therapies and also on the financial situation for that country. The objective of this study was to assess the health infrastructure in Iraq regarding the diagnosis and management of patients with ITP, with a focus on the use of guidelines in ITP management.
| Materials and Methods|| |
Study design and participants
This was a cross-sectional study carried out between October and November 2022 to assess ITP diagnosis, management, and the use of guidelines in 18 governorates in Iraq. Immune thrombocytopenia (ITP) guidelines refer to a set of recommendations and best practices developed by medical experts and professional organizations for the diagnosis, management, and treatment of immune thrombocytopenia. These guidelines aim to provide healthcare providers with evidence-based guidance on how to approach patients with ITP, ensuring optimal care and improving patient outcomes. Invited to this study were all the 79 adult hematologists who were registered in the Iraqi Society of Hematology and who practiced in the 18 governorates. Out of the 79 hematologists, 65 participated in this survey. Adult patients' age in Iraq is 18 years and older.
Included in the study were all the physicians who were certified as clinical hematologists, registered in the Iraqi Society of Hematology and practicing in Iraq. Excluded from the study were those who were not practicing in Iraq.
Data were collected using an online questionnaire. The questionnaire was developed in the English language based on the objectives of the study and through a review of the literature. It underwent content validity testing by a hematologist faculty member with expertise in biostatistics and questionnaire development. Several modifications were made to the first draft of the questionnaire through an iterative process. The pre-final version of the questionnaire was uploaded and designed on Google Forms®, which is an electronic tool for developing online surveys. The questionnaire was then piloted with a small group of hematologists to test its clarity and comprehension, and minor modifications were made to produce the final valid version.
The questionnaire was developed using a Google Forms link and provided in the English language. The questionnaire invitations were E-mailed to all the physicians listed as hematologists at the Iraqi Society of Hematology. A consent form was included in the questionnaire to inform participants about the study's aims, assurance about the confidentiality of the replies submitted, and willingness to participate. The questionnaire comprised 10 questions about demographic information of the participating hematologists, the investigations for ITP (routine tests requested), diagnosis (bone marrow aspiration and biopsy), availability of investigations (government sector, private sector, both sectors), general treatment, initial treatment (drugs of choice), second-line treatment (drugs of choice), availability of drugs (government sector, private sector, both sectors), as well as guideline-related questions.
Ethical approval was obtained from the Ethics Committee of Iraqi Society of Hematology under the number (SEPT-22-2937548).
Statistical Package for the Social Sciences (SPSS) Version 28 was used for the analysis and Microsoft Excel was used for creating the graphs. Descriptive statistics were presented in the form of numbers and percentages as all variables were categorical.
| Results|| |
Demographic information of the participating hematologists is presented in [Table 1]. Out of 79 hematologists registered in the Iraqi Society of Hematology and practicing in Iraq, 65 (82%) responded to the questionnaire. They were distributed over 15 governorates. There were no hematologists fromAl-Anbar, Diyala, and Maysan governorates. Regarding the different sectors, the hematologists were distributed as follows: private sector 2 (3%), governmental sector 11 (17%), and both sectors 52 (80%).
|Table 1: Demographic information of the participating hematologists (n=65)|
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Investigations of the hematologists' routine requests for ITP are presented in [Table 2]. When investigating ITP, 83.1% of the hematologists routinely request a manual assessment of platelet count, 98.5% routinely request blood film, 60.0% routinely request Helicobacter pylori test, stool antigen or breath test, 90.9% routinely request virology screen, 85.9% routinely request connective tissue screen (antinuclear antibody test), 35.4% routinely request anti-phospholipid antibodies, 33.9% routinely request thyroid function test, 78.5% routinely request prothrombin time (PT), partial thromboplastin time (PTT) and serum fibrinogen, 15.4% routinely request chest X-ray (CXR), 87.7% routinely request abdominal ultrasound, 36.9% routinely request a direct anti-globulin test, 1.6% routinely request quantitative immunoglobulin (Ig) level testing, 31.3% routinely request bone marrow aspiration and biopsy. Moreover, 4.6% of the hematologists prefer that patients with typical features of ITP should have bone marrow aspiration and biopsy at initial diagnosis, 83.1% of hematologists prefer that patients who have no response to the first-line treatment should have bone marrow aspiration and biopsy, and 93.9% of hematologists prefer that bone marrow examination should include bone marrow aspiration and biopsy.
|Table 2: Investigations of the hematologist's routine requests for immune thrombocytopenia (n=65)|
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Regarding platelet function tests, 13.9% of the hematologists routinely request platelet function tests. Of these hematologists, 6.3% request the platelet function tests after corticosteroid failure, 6.3% request them after excessive bleeding and bruising, 12.6% request them with the presence of family history, 56.2% request them after poor response to treatment, 6.3% request them in refractory disease, 6.3% request them before second-line treatment, and 6.3% request them before splenectomy.
Hematologists' answers to the availability of investigations in different sectors are presented in [Table 3]. A manual assessment of platelet count was available in both sectors by 73.8%. Blood film was available in both sectors by 76.9%. H. pylori test was available in the private sector by 57.8%. The urea breath test was available in private sector by 85.9%. Stool antigen was available in private sector by 62.5%. Virology screen (routine serologic evaluation for human immunodeficiency viruses (HIV) and hepatitis C virus (HCV) and hepatitis B virus (HBV) was available in both sectors by 70.8%. Bone marrow aspiration and biopsy were available in government sector by 35.4%, in private sector by 16.9% and in both sectors by 47.7%. Connective tissue screen was available in private sector by 65.6%. The antiphospholipid screen was available in private sector by 73.4%. Thyroid function test was available in both sectors by 55.3%. Epstein–Barr virus (EBV) test was available in private sector by 84.1%. Cytomegalovirus (CMV) test was available in private sector by 82.5%. PT, PTT, Bleeding time, and serum fibrinogen tests were available in both sectors by 61.5%. A genetic test (Diepoxybutane test to exclude Fanconi anemia) was available in private sector by 100%. CXR was available in both sectors by 76.6%. Abdominal US was available in both sectors by 76.9%. Platelet function tests were available in private sector by 87.3%. Direct anti-globulin test was available in both sectors by 58.4%. Quantitative Ig level testing was available in private sector by 100%; and finally, screening for Gaucher disease was available in the private sector by 63.5%.
|Table 3: Hematologist's answers to the availability of investigations in different sectors|
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Hematologists' answers to general treatment questions are presented in [Table 4]. Hematologists treating inpatients were 14.1%, while 85.9% of the hematologists treat outpatients. Hematologists who thought that the platelet count should be a consideration in treatment decisions for patients with ITP were 80.0%.
Answers of the hematologists to initial treatment questions are presented in [Table 5]. Regarding initial treatment, 93.8% of the hematologists considered corticosteroids as their initial treatment, 6.2% of the hematologists considered IVIG as their initial treatment, and none of them considered anti-D as their initial treatment. For steroids, 81.5% of the hematologists considered prednisolone as their initial treatment, only 3.1% of the hematologists consider methylprednisolone as their initial treatment, and 15.0% of the hematologists consider dexamethasone as their initial treatment. Regarding antifibrinolytic use, 35.4% of the hematologists used it routinely.
Drugs as first, second, and third choice in second-line treatment are presented in [Table 6]. Rituximab was chosen by 75.3% of the hematologists as a first choice in second-line treatment. Eltrombopag was chosen by 65% of the hematologists as a second choice in second-line treatment whereas romiplostim was chosen by 65.3% of the hematologists as a third choice in second-line treatment.
|Table 6: Drugs as first, second, and third choice in second line treatment|
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Hematologists' answers to the availability of drugs in different sectors are presented in [Table 7]. Prednisolone was available in both sectors by 69.2%. Dexamethasone was available in both sectors by 78.5%. Methylprednisolone was available in private sector by 56.9%. IVIG was available in both sectors by 46.9%. Anti-D was available in government sector by 43.6%. Rituximab was available in government sector by 61.5%. Eltrombopag was available in private sector by 100.0%. Romiplostim was available in government sector by 68.8%. Danazol was available in private sector by 81.3%. Azathioprine was available in both sectors by 50.0%. Cyclosporin A was available in both sectors by 58.7%. Cyclophosphamide was available in both sectors by 64.1%. Dapsone was available in private sector by 81.3%. Mycophenolate mofetil was available in both sectors by 46.8%. Vinca alkaloids were available in both sectors by 50.7%. And finally, All-trans retinoic acid was available in private sector by 44.4%.
|Table 7: Hematologist's answers to the availability of drugs in different sectors|
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Hematologists' answers to guidelines-related questions are presented in [Table 8]. As shown in this table, 83.0% of the hematologists referred to a certain guideline when investigating, diagnosing, and treating ITP. Most of the hematologists (72.7%) referred to ASH guidelines.
| Discussion|| |
ITP is an autoimmune disease affecting platelet count that causes thrombocytopenia and an increased risk of bleeding. ITP management varies worldwide. It ranges from observation, medical treatment depending on bleeding symptoms, acceptable platelet counts, and availability of hospitalization or outpatient treatment. We carried out this study to assess ITP diagnosis, management, and the use of guidelines all over 18 governorates in Iraq.
Regarding the investigations for ITP, the most requested routine tests by our responding hematologists were manual assessment of platelet count, blood film, virology screen (including HIV, EBV, CMV, HBV, and HCV), connective tissue screen, PT, PTT, serum fibrinogen, abdominal ultrasound. More than half of the hematologists do not request anti-phospholipid antibodies, thyroid function test, CXR, direct anti-globulin test, quantitative Ig level testing, screening for Gaucher disease, and bone marrow aspiration and biopsy.
Regarding the bone marrow aspiration and biopsy, more than 80% of the responding hematologists request bone marrow aspiration for the patients who have no response to the first-line treatment, and they agree that the bone marrow examination should include bone marrow aspiration and bone marrow biopsy. On the other hand, more than 85% of the responding hematologists think that patients with the typical feature of ITP should not have a bone marrow aspirate at the initial diagnosis. According to the evidence currently available, when there is isolated thrombocytopenia and no abnormal features present on physical examination or examination of the blood smear, a bone marrow examination is not required in the initial diagnosis (Grade B recommendation), whether or not treatment is recommended. In Iraq, a large number of patients undergo bone marrow aspiration and biopsy, which may not be necessary for typical ITP patients.
Regarding platelet function tests, more than 85% of the hematologists do not request these, and those who request these tests, they request them when there is a poor response to the treatment. In fact, platelet function tests are performed only if the platelet count seems to be adequate yet there is excessive bleeding or bruising.
The current ASH guideline for the management of patients with immune thrombocytopenic purpura (ITP) is an update to the 2011 guidelines. For the initial diagnosis of ITP, recommendations from 2011 ASH that are not addressed in the 2019 ASH guideline request testing patients for HCV and HIV. If there are abnormalities in the blood count or smear (apart from thrombocytopenia and potentially signs of iron deficiency), they advise further investigations. In addition, patients presenting with typical ITP do not require a bone marrow examination, regardless of age.
An International Consensus Report (ICR) on the investigation and management of ITP was issued in 2010 by a global group of experts. These recommendations were supported by evidence, and they also pointed out any areas where further information was needed. The 2010 consensus report included suggestions based on the investigators' professional judgment to provide a useful perspective. The ICR recommendations state that at the time of initial diagnosis, a thorough history, physical examination, complete blood count, and an analysis of the peripheral blood film should all be considered. According to the information that is now available, a bone marrow examination is not necessary for the initial diagnosis, whether or not therapy is advised when there is isolated thrombocytopenia and no abnormal characteristics visible on physical examination or examination of the blood smear. In the relevant regions, the initial work-up should include a stool antigen test or urea breath test for the identification of H. pylori infection.
In Iraq, 60.0% of hematologists routinely request H. pylori test, stool antigen or breath test. The detection of H. pylori infection with the urea breath test or the stool antigen test should be considered in adults with typical ITP, in those with digestive symptoms, and those from areas of high prevalence; the evidence does not support routine testing in ITP patients outside of these areas since it does not help us much (evidence level IIa).
Before receiving IVIg therapy or to rule out an immune deficiency syndrome (evidence level IV; Grade C recommendation), quantitative Ig level testing is indicated. If a patient is relapsing after being in remission, is not responding to their initial treatments, is considering splenectomy, or if other abnormalities are found in their blood count or morphology, a bone marrow examination may be necessary.
Regarding the availability of investigations in different sectors, our responding hematologists reported that only the genetic test and the quantitative Ig level testing were available in the private sector only. The other tests were available in both sectors. Still, there is no diagnostic test for ITP and it remains a diagnosis of exclusion. We still have to exclude all other causes of low platelet count. This has a major impact on the patients, and poses a great challenge to the health system, especially in our limited resources country where not all investigations are available.
Regarding the general treatment of ITP, more than 85% of our hematologists treat the patients as outpatients. About 14.1% of our patients treated as inpatients, which is quite a large percentage are treating patients as inpatients.
In the case of hospitalized patients, active bleeding, not platelet count, was the indication for hospitalization for 60% of our hematologists. Platelet count was a major consideration for the treatment decisions for patients with ITP in 80% of the responding hematologists, and the most common threshold to start the treatment was below 30 × 109/L with or without bleeding, and above 30 × 109/L with bleeding.
In adults with an established diagnosis of ITP and a platelet count of <20 × 109/L who have minor mucocutaneous bleeding or who are asymptomatic, they suggest outpatient management rather than hospital admission.
Relevant factors that contribute to management decisions include: Pertinent factors that influence management decisions include: comorbidities predisposing to bleeding, complications of specific therapies, the extent of bleeding, potential interventions that may cause bleeding, patient need for non-ITP medications that may create a bleeding risk, tolerance of side effects, activity and lifestyle, accessibility of care and patient worry or anxiety about disease burden. Moreover, The ASH guideline also suggests hospital admission for individuals who are resistant to therapy, have social issues, have doubts about their diagnosis, have substantial comorbidities that increase their risk of bleeding, or have more significant mucosal bleeding. Patients who are not being admitted to the hospital need to be educated and given quick access to a hematologist. The need for admission is also variable across the range of platelet counts represented here (0–20 × 109/L).
According to the ICR, therapy for ITP can often be administered as an outpatient procedure, unless there is active bleeding or other medical factors (anticoagulant therapy), the patient needs close monitoring, or it is the initial presentation for thrombocytopenia and platelets are ≤20 × 109/L. Although hemorrhagic death is a major concern, analysis of data from 17 adult case studies estimated the rate of fatal hemorrhage to be 0.0162–0.0389 cases per adult patient-year at risk.
An increased risk of bleeding exists in patients over the age of 60 and in those who have experienced prior bleeding. Both bleeding and infection increase mortality. Treatment is rarely indicated in patients with platelet counts above 50 × 109/L in the absence of the following: clearly identified comorbidities for bleeding, bleeding due to platelet dysfunction or another hemostatic defect, mandated anticoagulation therapy, in persons whose profession or lifestyle predisposes them to trauma, or surgery. When discussing therapy choices, patient preferences must also be taken into account.
The evidence-based guidelines of the Korean Society of Hematology Aplastic Anemia Working Party (KSHAAWP) discuss the management approaches for ITP in Korea based on evidence and expert opinions. In adult patients with newly diagnosed ITP and a platelet count <20 × 109/L without symptoms or with minor mucocutaneous bleeding, corticosteroids are recommended rather than observation, while if the platelet count is ≥20 × 109/L they recommend observation rather than corticosteroids.
Regarding the drugs of choice as initial treatment according to their practice, more than 90% of our responding hematologists chose corticosteroids as the first choice, IVIG as the second choice, and anti-D as the third choice. Regarding initial treatment options, drug choices look fairly typical and similar to international practice.
Moreover, among their corticosteroid choices, prednisone was their first choice, dexamethasone was the second, and methylprednisolone was the third. Moreover, more than 60% of the responders do not use antifibrinolytics routinely.
In adults with newly diagnosed ITP and a platelet count of <30 × 109/L who are asymptomatic or have minor mucocutaneous bleeding, the ASH guideline panel suggests corticosteroids rather than management with observation. In adults with newly diagnosed ITP and a platelet count of ≥30 × 109/L who are asymptomatic or have minor mucocutaneous bleeding, they recommend against corticosteroids and in favor of management with observation. Regarding the duration and type of corticosteroid, in adults with newly diagnosed ITP, the ASH guideline recommends against a prolonged course (>6 weeks including treatment and taper) of prednisone and in favor of a short course (≤6 weeks). They suggest either prednisone (0.5–2.0 mg/kg per day) or dexamethasone (40 mg per day for 4 days) as the type of corticosteroid for initial therapy.
As per the ICR guidelines, corticosteroids are the standard initial treatment for adults with ITP who need treatment and do not have a relative contradiction: Prednisolone at 1 mg/kg (maximum dose 80 mg, even in patients weighing >80 kg) for 2 weeks, to a maximum of 3 weeks, or dexamethasone 40 mg/d for 4 days, repeated up to 3 times. Use of IVIg (1 g/kg on 1 or 2 consecutive days or 0.4 g/kg per day for 5 days), or IV anti-D (50–75 mg/kg once) where available, may be appropriate in patients with bleeding, at high risk for bleeding, who require a surgical procedure, or who are unresponsive to prednisolone. TPO-RAs and rituximab are not considered initial therapies.
As per the KSHAAWP guidelines, in adult patients with newly diagnosed ITP, they recommend either prednisone (0.5–2.0 mg/kg/day) or dexamethasone (40 mg/day for 4 days) as the type of initial corticosteroid treatment.
In second-line treatment of ITP, our responding hematologists chose rituximab as the first choice, eltrombopag as the second choice, and romiplostim as the third choice. Regarding the second-line option, rituximab is obviously still very popular in our country in the contrary to Europe where hematologists are using a great deal of TPO-RAs.
Rituximab is safe as second-line treatment in ITP but there is always a worry about vaccination especially COVID-19 vaccination because patients who have rituximab will not respond to the vaccine for at least 6 months.
On the other hand, mycophenolate is cheap and safe second-line therapy. However, we have avoided mycophenolate during the pandemic because of the risk of increasing the chances of COVID-19 infection or making COVID-19 more severe.
For second-line therapies, ASH guideline compares splenectomy, TPO-RA, and rituximab, one against the other. In adults with ITP lasting ≥3 months who are corticosteroid-dependent or have no response to corticosteroids, they suggest either TPO-RA or rituximab rather than splenectomy, and TPO-RA rather than rituximab. These recommendations are the outcome of dichotomous assessment of treatments that are often taken into consideration simultaneously. Each of these second-line treatments has the potential to be an effective therapy and therefore the selection of therapy should be based on the patient's values and preferences, ITP duration, frequency of bleeding episodes requiring hospitalization or rescue medication, comorbidities, age, medication compliance, social and medical support networks, cost, and availability.
As per the ICR guidelines, subsequent treatment recommends medical therapies with robust evidence such as rituximab, TPO-RAs (eltrombopag, avatrombopag, and romiplostim), and fostamatinib.
As per the KSHAAWP guidelines, in adult patients with corticosteroid-dependent or refractory ITP for more than 3 months, they recommend a TPO-RA, either eltrombopag or romiplostim. In adult patients with ITP lasting ≥3 months who are corticosteroid-dependent or unresponsive to corticosteroids, they recommend TPO-RA rather than splenectomy. Splenectomy should be postponed for at least 12 months after diagnosis because of the possibility of spontaneous remission in the first year. Moreover, in adults with ITP who fail to respond to TPO-RA or experience relapse after discontinuing TPO-RA, they recommend rituximab as a third-line therapy.
In the end, COVID-19 made us rethink ITP management, the pandemic has meant that we have been able to avoid immune-suppressing therapies and use a lot of TPO-RAs as second-line treatment. This is a major paradigm shift for the management of ITP.
Regarding drug availability, only eltrombopag was found fully in the private sector and not found in the government sector. All other drugs were found at different percentages in both sectors. Thus, prescribing drugs and the treatment pathways depend highly on the financial situation and the type of care provided. In Iraq, the health system is mixture of private and governmental with fluctuation of romiplostim availability and supplying chain as a second line therapy. Moreover, a study carried out by Wasekar et al. showed that a response may be achieved with immunosuppressive agents like mycophenolate mofetil.
Regarding the use of guidelines, only 83% of our responding doctors referred to a guideline, and the ASH guideline was the most referred to by more than 70% of our responding doctors. In Iraq, the ICR which provides consensus recommendations on the diagnosis and management of ITP in adults is not popular. That report can be an applicable guideline in resources-limited countries in the middle east. Moreover, ASH guidelines were started much earlier than ICR and they were published before COVID-19. Both guidelines need to be updated.
This study can be evaluated in light of its strengths and limitations. The recall bias that hampered the interpretation of the survey data, the comparison of individual physician practice to center-wide practice, and the fact that hematologists are typically only consulted after another clinician has decided to admit a patient are all intrinsic limitations of this study. In addition, this survey does not go into specifics about special populations such as children and pregnant women, instead concentrating on the general clinical and management features of ITP. Another drawback of this survey is that it does not include all potential clinical outcomes for each instance. The strength of this survey lies in the fact that it is the first survey carried out by the Iraqi Society of Hematology which includes all the registered hematologists and evaluates the ITP management practice in all Iraqi governorates.
These data give a snapshot of practice in Iraq, which hopefully can be used to shape our guidelines. This paper tested the water and it will be followed by national guidelines for Iraq providing recommendations on the diagnosis and management of Iraqi ITP patients that are suitable to our health infrastructures and resources.
| Conclusions|| |
By identifying individuals who are more likely to benefit from treatment, we should work to create a treatment paradigm that minimizes exposure to unnecessary medications. Based on the clinical course and expected or actual bleeding severity, individualized treatment regimens should be created. In addition, a validated screening tool that can be used in routine clinical practice to identify clinically important patient-reported outcomes would be beneficial for both patients and hematologists in terms of properly monitoring a patient's quality of life. Only then will we be able to effectively treat the laboratory findings and physical symptoms of ITP in addition to address the patient's emotional and mental health needs. Finally, these findings demonstrated the necessity for us to create our own local regulations that are appropriate for our resources and infrastructure.
Name: Dr. Drew Provan from Barts and The London School of Medicine and Dentistry, Queen Mary University of London. Role: Without his help and limitless support, this study could not have been carried out. He helped in guiding the whole study design, in reviewing the questionnaire, and in reviewing the final draft of the manuscript.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Platelet Disorder Support Association. ITP & Genetics. Available from: https://pdsa.org/genetics
. [Last accessed on 2022 Jul 11].
Moulis G, Germain J, Comont T, Brun N, Dingremont C, Castel B, et al.
Newly diagnosed immune thrombocytopenia adults: Clinical epidemiology, exposure to treatments, and evolution. Results of the CARMEN multicenter prospective cohort. Am J Hematol 2017;92:493-500.
Heitink-Pollé KM, Uiterwaal CS, Porcelijn L, Tamminga RY, Smiers FJ, van Woerden NL, et al.
Intravenous immunoglobulin versus observation in childhood immune thrombocytopenia: A randomized controlled trial. Blood 2018;132:883-91.
Mithoowani S, Cervi A, Shah N, Ejaz R, Sirotich E, Barty R, et al.
Management of major bleeds in patients with immune thrombocytopenia. J Thromb Haemost 2020;18:1783-90.
Provan D, Arnold DM, Bussel JB, Chong BH, Cooper N, Gernsheimer T, et al.
Updated international consensus report on the investigation and management of primary immune thrombocytopenia. Blood Adv 2019;3:3780-817.
LeVine DN, Brooks MB. Immune thrombocytopenia (ITP): Pathophysiology update and diagnostic dilemmas. Vet Clin Pathol 2019;48 Suppl 1:17-28.
Neunert C, Terrell DR, Arnold DM, Buchanan G, Cines DB, Cooper N, et al.
American society of hematology 2019 guidelines for immune thrombocytopenia. Blood Adv 2019;3:3829-66.
Park YH, Kim DY, Kim S, Choi YB, Shin DY, Kim JS, et al.
Management of immune thrombocytopenia: 2022 update of Korean experts recommendations. Blood Res 2022;57:20-8.
Choi PY, Merriman E, Bennett A, Enjeti AK, Tan CW, Goncalves I, et al.
Consensus guidelines for the management of adult immune thrombocytopenia in Australia and New Zealand. Med J Aust 2022;216:43-52.
Mishra K, Kumar S, Singh K, Jandial A, Sandal R, Sahu KK, et al.
Real-world experience of anti-D immunoglobulin in immune thrombocytopenia. Ann Hematol 2022;101:1173-9.
Bussel JB, Garcia CA. Diagnosis of immune thrombocytopenia, including secondary forms, and selection of second-line treatment. Haematologica 2022;107:2018-36.
Birocchi S, Podda GM, Manzoni M, Casazza G, Cattaneo M. Thrombopoietin receptor agonists for the treatment of primary immune thrombocytopenia: A meta-analysis and systematic review. Platelets 2021;32:216-26.
González-López TJ, Pascual C, Álvarez-Román MT, Fernández-Fuertes F, Sánchez-González B, Caparrós I, et al.
Successful discontinuation of eltrombopag after complete remission in patients with primary immune thrombocytopenia. Am J Hematol 2015;90:E40-3.
Lucchini E, Palandri F, Volpetti S, Vianelli N, Auteri G, Rossi E, et al.
Eltrombopag second-line therapy in adult patients with primary immune thrombocytopenia in an attempt to achieve sustained remission off-treatment: Results of a phase II, multicentre, prospective study. Br J Haematol 2021;193:386-96.
Zaja F, Carpenedo M, Baratè C, Borchiellini A, Chiurazzi F, Finazzi G, et al.
Tapering and discontinuation of thrombopoietin receptor agonists in immune thrombocytopenia: Real-world recommendations. Blood Rev 2020;41:100647.
DeSouza S, Angelini D. Updated guidelines for immune thrombocytopenic purpura: Expanded management options. Cleve Clin J Med 2021;88:664-8.
Elalfy MS. Three decades of experience in managing immune thrombocytopenia in children in Arab countries. Semin Hematol 2013;50 Suppl 1:S22-5.
Paniccia R, Priora R, Liotta AA, Abbate R. Platelet function tests: A comparative review. Vasc Health Risk Manag 2015;11:133-48.
Kistangari G, McCrae KR. Immune thrombocytopenia. Hematol Oncol Clin North Am 2013;27:495-520.
Pulanić D, Bátorová A, Bodó I, Červinek L, Ionita I, Lissitchkov T, et al.
Use of thrombopoietin receptor agonists in adults with immune thrombocytopenia: A systematic review and central European expert consensus. Ann Hematol 2023;102:715-27.
Spiera R, Jinich S, Jannat-Khah D. Rituximab, but not other antirheumatic therapies, is associated with impaired serological response to SARS- CoV-2 vaccination in patients with rheumatic diseases. Ann Rheum Dis 2021;80:1357-9.
Provan D, Semple JW. Recent advances in the mechanisms and treatment of immune thrombocytopenia. EBioMedicine 2022;76:103820.
Jumaa AK, Saleh TA, Khalaf AA, Abbas MS. Efficacy and safety of romiplostim in adult Iraqi patients with refractory immune thrombocytopenia. Iraqi J Hematol 2020. 9:92-6.
Wasekar N, Badarkhe G, Pandit S, Ramesh YV, Nagarkar R. Therapeutic efficacy and clinical effectiveness of mycophenolate mofetil and dexamethasone for immune thrombocytopenia: A retrospective observational study. Iraqi J Hematol 2021; 10:28-33. [Full text]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8]