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Assessment of the underlying causes of the immune thrombocytopenia: Ten years experience.

Byline: Mehmet Sinan Dal, Abdullah Karakus, Tuba Dal, Berrin Balik Aydin, Elif Hattapoglu, Mehmet Onder Ekmen, Turgay Ulas and Orhan Ayyildiz


Objective: Immune thrombocytopenia (ITP) is an immune haematologic disorder causing platelet destruction mediated by anti-platelet antibodies. In this study we aimed to evaluate the clinical and laboratory variables of ITP patients in southeast of Turkey.

Methods: In this retrospective study 167 ITP patients between 2005 and 2015 were evaluated. All patients were screened for immunological parameters including ANA (antinuclear antibodies), anti dsDNA (anti-double-stranded-DNA), ACA(anti-cardiolipin) IgM and IgG, LA (lupus anticoagulants). All patients were screened for Helicobacter pylori, HBsAg (Hepatitis B surface antigen), anti-HCV (hepatitis C virus antibody), and anti-HIV 1/2 (HIV antibody) and brucellosis.

Results: Among the patients, 50 (29.9%) patients were male, 117 (70.1%) were female. The age range of patients was 18-86 (mean 38.16+-14). In 56 patients (33.5%) splenectomy was performed. 36 patients (21.6%) were positive for ANA, 5 (3%) were positive for anti dsDNA, 14 (8.4%) for ACA Ig G, and 14 (8.4%) patients for ACA IgM. LA was tested in 165 patients and 30 (18%) patients were positive for LA. Microbiologic evaluation was as follows: 16 patients (9.6%) were positive for HbsAg, 109 (65.3%) positive for Anti-HBs, 5 positive for anti-HCV (3%), 56 (33.5%) patients were positive for Helicobacter pylori antigen, 5 (2.9%) for Brucella and one patient was positive for anti-HIV 1/2.

Conclusion: Immune thrombocytopenia patients have to be evaluated according to their demographic characteristics and laboratory results. Secondary causes of ITP were HIV, HCV, Helicobacter pylori, brucellosis, tuberculosis, and autoimmune diseases in our region. Management of ITP patients can change in different regions.

Keywords: Immune thrombocytopenia, Helicobacter pylori, Hepatitis C virus, Brucella, Antiphospholipid antibodies. (JPMA 67: 1004; 2017)


Immune thrombocytopenia (ITP) is an acquired autoimmune haematologic disorder characterized by immune-mediated platelet destruction, impairment of platelet production, and a variable bleeding tendency. ITP is defined as isolated thrombocytopenia with a platelet count 50 x109/L are asymptomatic and frequently diagnosed fortuitously; platelet counts between 20 and 50 x109/L are related to excessive bruising with minor trauma; petechiae or ecchymoses develop spontaneously when counts are between 10 and 20 x 109/L and spontaneous bleeding may occur. Patients with platelet counts below 10 x 109/L are at risk for severe bleeding, such as intracranial haemorrhage or other internal bleeding.

The risk of serious bleeding has been conjectural to increase with increasing patient age and among patients with platelet counts persistently 1/160 or at least a four-fold increase in this titer by the standard tube agglutination (STA) test in a two or three-week interval. All analyses were performed in accordance with the principles of the Declaration of Helsinki. This study was approved by Dicle University, Faculty of Medicine Institutional Review Board. Descriptive statistics for continuous variables were given as mean, standard deviation, minimum, maximum and median values. Data were analyzed using Statistical Package for the Social Scienses (SPSS) software, version 19.0 (SPSS Inc., Chicago, IL, USA).


Among the patients, 50 (29.9%) patients were male, 117 (70.1%) were female. The mean age of patients was 38.16+-14 with a range of 18-86 years. The mean number of children of female patients was 3.07+-3.12 (range 0-10). According to the IWG bleeding scale, 7% of the patients were assessed in grade 0, 51% in grade 1, 30% grade 2, 10% were in grade 3 and 2% in grade 4. Out of the patients 68% were from rural area. A total of 48 (28.7%) patients were smokers. In 56 patients (33.5%) splenectomy had been performed. Thirty six patients (21.6%) were positive for ANA, 5 (3%) patients were positive for dsDNA, 14 (8.4%) for ACA IgG, 14 (8.4%) patients for ACA IgM. Lupus Anticoagulant was tested in 165 patients and 30 (18%) patients were positive for LA (Table-1).

Table-1: Immunological parameters of the patients.

Immulogical parameters###Number of the patients

ANA*###36 (21.6%)

ds DNA*###5 (3%)

ACA IgG*###14 (8.4%)

ACA IgM*###10 (6%)

LA*###30 (18%)

Microbiologic evaluation was as follows: 16 patients (9.6%) were positive for HbsAg, 109 (65.3%) positive for anti-HBs, 5 positive for anti-HCV (3%), 56 (33.5%) patients were positive for Helicobacter pylori antigen, 5 (2.9%) for Brucellosis and one patient was positive for anti-HIV 1/2 (Table-2).

Table-2: Microbiologic evaluation of the patients.

Microbiological parameters###Number of the patients (%)

HbsAg*###16 (9.6%)

Anti HBS*###109 (65.3%)

Anti HCV*###5 (3%)

Anti HIV 1/2*###1 (0.59%)

H.pylori antigen###56 (33.5%)

Brucella###5 (2.9%)

Mycobacterium tuberculosis###1 (0.59%)

One patient was diagnosed as splenic tuberculosis. Mean laboratory levels results were as follow: white blood cell counts 8 x109/L, haemoglobin 13.12 gm/dl, platelet counts 46 x109/L, LDH 220 IU, total bilurubin 0.5 mg/dl, ALT 25 IU, AST 23 IU (Table-3).

Table-3: Biochemical laboratory results of the patients.

Biochemical laboratory results###Mean levels

WBC (x109/L)*###8

Hb (gm/dl)*###13.12

Platelet count (x109/L)###46

LDH (IU)*###220

Total bilirubin (mg/dl)###0.5

AST (IU)*###23

ALT (IU)*###25

APS developed in three patients (2 female, 1 male). We did not detect a significant difference between smokers and non smokers in platelet numbers and grade of bleeding (p>0.05).


ITP is an acquired immune disorder characterized by thrombocytopenia and mucocutaneous bleeding and it is commonly assumed that ITP results from autoantibodies causing accelerated platelet destruction. Autoantibodies may also inhibit platelet production.6 ITP is more common in women than in men between the ages of 30 and 60 years.5 In a Pakistani study with 86 chronic ITP patients, 64% of the patients were female, with a mean age at the time of diagnosis of 25.5 years (range: 2-65 years).12 Elezovic et al. reported that 136 out of 167 patients with chronic ITP were women (81.4%) and median age of their patients was 35 years.13 In an Irani study on 90 patients with chronic ITP, mean+-SD age at diagnosis was 36.7+-14.2 years and 77.8% were women.14 In a recent study of Payandeh et all. on patients with acute ITP, the mean+-SD age of the patients was 39.1+-13.3 years and 62.3% were women.15 In our study median age was 38 years and the big majority of the patients were female, similar to other studies.

The females are generally more frequently affected than males for many autoimmune diseases. The studies suggested that gender differences were related to the T cell and antibody responses that occur in autoimmune diseases. Females have increased immune reactivity, differences in the number or responsiveness of cells that constitute the immune response. Hormonal changes during pubertal maturation, pregnancy, and menopause may alter susceptibility to autoimmunity. Genetic factors and differential exposure to environmental factors including sunlight, can influence the prevalence of an autoimmune disease.16 In spite of these data, further studies are needed for determination of relationship between sex and ITP.

Smoking can cause significant increase in the platelet aggregability in ITP patients. The increase in platelet aggregability can be explained on the basis of increased platelet aggregating agents such as epinephrine and nor-epinephrine and injury to the endothelium or direct effect on platelets. Some studies reported that an increase in the epinephrine levels could cause release of platelets in circulation. However, in many studies, no significant change was found in the platelet counts in smokers.17 In our study 28,7% of the patients were smokers and we did not detect a significant difference between smokers and non smokers in platelet numbers and the grade of bleeding. We concluded that clinical findings including large scale studies were necessary on platelet numbers and platelet activity with bleeding risk.

Bleeding manifestations in patients with ITP range from mild skin bruises to life-threatening intracranial haemorrhage. Severe bleeding occurs when the platelet count falls 80%) in general population.22 We suggested that the group of ITP patients with symptoms or those from highly endemic regions should be considered for H. pylor) detection testing and therapy.

Many haematological abnormalities, such as pancytopenia, anaemia, and leukocytosis, can be associated with tuberculosis (TB). However ITP is an extremely rare event in TB. In Turkey ITP was reported in a 46-year-old male patient with pulmonary tuberculosis.23 We also presented a female case with 58-year-old with splenic tuberculosis and ITP in Diyarbakir.24 We thought that in the endemic regions for TB, tuberculosis should be considered as a secondary reason of ITP.

The pathogenetic role and the clinical importance of the presence of antiphospholipid antibodies (APAs) in patients with immune ITP are not clear. In a Turkey study the prevalence and clinical significance of APAs were investigated in patients with ITP. Eighty-two newly diagnosed ITP patients were prospectively studied. Thirty-one patients (37.8%) were APA positive at diagnosis. In addition, LA was an important risk marker for the development of thrombosis in ITP patients. After a median follow-up of 38 months, 14 ITP patients (45%) who had APA positivity developed clinical features (thrombosis or foetal losses) of antiphospholipid syndrome (APS). The positivity rate for LA was significantly higher in those patients with ITP who developed APS.25 In our study 14 (8.4%) patients for ACA IgM, 10 (6%) patients for ACA IgG. Lupus Anticoagulant was tested in 165 patients and 30 (18%) patients were positive for LA.

In our study APS developed in three patients. According to the data we suggested that in patients with ITP, the persistent presence of APAs was an important risk factor for the development of APS.

Hepatitis C virus has been reported to be associated with the occurrence of autoimmune disorders, including ITP. A study with 150 subjects reported that the prevalence of severe thrombocytopenia was significantly higher in ITP patients compared with that in chronic HCV patients.26 In our study 3% of the patients were HCV positive and we suggested that ITP patients should be screened for HCV antibody.

Brucellosis constitutes a major health problem in many parts of the world, particularly in the Mediterranean and the Middle East. Severe thrombocytopenia is a rare haematologic manifestation of brucellosis. Prompt recognition of this brucellosis complication and aggressive therapy is vital because the mortality rate associated with bleeding into the central nervous system is high. Altuntas et al. reported a case of brucellosis who was admitted with a severe thrombocytopenic purpura. The patient responded well to intravenous gamma globulin (IVIg) treatment with platelet recovery within 2-3 days.27 In cases of brucella induced immune thrombocytopenia, corticosteroid treatment might be useful for the prevention of bleeding complications.28,29

Thrombocytopenia is a common feature among HIV positive patients. However, there are few reports about this subject after highly active antiretroviral therapy (HAART). In a trial conducted in 55 HIV positive outpatients with thrombocytopenia in Brazil, in 63.6% patients, the cause of thrombocytopenia was classified as ITP and non immune in 25.5%.30 Various studies indicated that about 5% to 10% of HIV infected patients develop thrombocytopenia during the course of the disease, and ITP may be the sole clinical manifestation of HIV infection. Steroids, IVIGs, and antiretroviral therapy (ART) have all been tried with varied results but have been associated with fall in platelet count on withdrawal of therapy. Shah I. et al. reported a case of a 13-year-old girl who presented with thrombocytopenic purpura and had no response to ART but had normalization of platelet count while on steroids, which immediately fell below the normal range on withdrawing the steroids.31

In our study we detected anti HIV 1/2 positivity in one patient. Our result and literature data presented that thrombocytopenia remained a problem among HIV patients and a diagnostic approach related to the haematological consequences of HIV infection is needed for a better therapy option for this population.

In conclusion ITP was more common in females than in males. Gender differences may be related to the T cell and antibody responses, increased immune reactivity, differences in the number or responsiveness of cells that constitute the immune response, hormonal changes during pubertal maturation, pregnancy, and menopause. In our study we did not detect a significant difference between smokers and non smokers in platelet numbers. In presented study H. pylori prevalence was 33.5% in ITP patients. H. pylori should be detected and eradicated in ITP patients. HIV, HCV, brucellosis, tuberculosis, and autoimmune diseases including APS and SLE may be the other secondary cause of ITP so detection and treatment of secondary causes of ITP may contribute to the management of ITP patients.

Disclaimer: None.

Conflict of Interest: All authors declare that there is no conflict of interest or financial support.

Funding Sources: None.


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Publication:Journal of Pakistan Medical Association
Article Type:Report
Date:Jul 31, 2017
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