Tehran University Medical Journal

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This study was carried out to examine the comorbidity of depression and anxiety disorders.
Materials and Methods: 261 depressed (n=153) and anxious (n=108) patients were psychiatrically interviewed, and then tested by two scales, BAI and BD1 261 healthy subjects (matched with depressed and anxious patients) completed BAT and BDl as well.
Results: The results showed that %55.6 of depressed and %58.3 of anxious patients had respectively a comorbid anxiety and depression disorders.
Conclusion: The detection of symptoms overlap revealed that depressed patients experienced most of the anxiety symptoms, and anxious patients reported most of the depression symptoms. The prevalence of depression and anxiety symptoms among healthy subjects will be discussed.

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Background: Major platelet adhesive receptors that contribute significantly to thrombus formation include platelet receptor glycoprotein Ibα (GPIbα) of the GPIb-IX-V complex and platelet glycoprotein VI (GPVI). GPIbα plays a crucial role in platelet tethering to sub-endothelial matrix, which initiates thrombus formation at arterial shear rates, whereas GPVI is critically involved in platelets firm adhesion to the site of injury regardless of shear condition. During storage, platelets experience some changes that deleteriously affect the expression levels of platelet receptors, which in turn can alter platelet functional behaviors. Considering the important roles of GPIbα and GPVI in platelet adhesion, it seems that any dramatic changes in the expression levels of these receptors can influence adhesive function of transfused platelets. Thereby examining GPIbα and GPVI expression during the storage of platelet concentrates may provide some useful information about the functional quality of these products after transfusion.

Methods: In our experimental study, 5 PRP-platelet concentrates were randomly obtained from Iranian Blood Transfusion Organization (IBTO). All the platelet products met the standard quality assessment based on AABB (American Association of Blood Banks) guidelines. Washed platelets were subjected to flowcytometry analysis for the evaluation of GPIbα and GPVI receptor expression in day 1, 3 and 5 after storage. Data were presented as mean fluorescence intensity (MFI) and analyzed by Kruskal-Wallis test with Dunn’s multiple comparison test.

Results: The GPIbα expression on first day (MFI=86±5.9) was reduced three days after storage (MFI= 69±6.9). The expression levels continued to reduce until day 5 in which GPIbα expression was markedly decreased to (MFI= 61±7.7) (P= 0.0094). GPVI expression on the days 1, 3 and 5 after storage were 20.6±3.3, 24±2.5 and 14±4.9, respectively. The results showed a significant decrease of expression on day 5, compared to that in day 3 after storage (P= 0.0213).

Conclusion: Our study showed significant decreases in the expression of platelet receptors GPIbα and GPVI after 5 days storage, suggesting a major defect in adhesive function of platelets during this term.

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Background: Platelet adhesion typically occurs by the critical role of GPIb-V-IX in capturing free-flowing platelets to the injured vessel wall where its rapid binding kinetics enables platelet tethering even under conditions of high shear through the interaction of the major ligand-binding subunit of GPIb-V-IX, GPIbα with subendothelial-bound vWF. During storage, platelet undesired activation may lead to platelet storage lesion (PSL) which changes the expression levels of platelet functional receptors including GPIbα. This study investigates the levels of expression and ectodomain shedding of platelet adhesive receptor GPIbα during the storage of platelet rich plasma (PRP) concentrates (PRP- PCs).

Methods: Five PRP-platelet concentrates were obtained from Iranian Blood Transfusion Organization (IBTO). The GPIbα expressions of platelets were analyzed on day 1, 3 and 5 after storage using flowcytometry. To examine the ectodomain shedding of this receptor the microparticle free supernatants obtained from stored platelets were subjected to western blot analysis. For control study, blood specimens was drawn from healthy consenting individuals and resting platelets were isolated while resuspended in Tyrode buffer.

Results: Our results indicated a continuous decrease of GPIbα expression during storage where the expression from fist day (Mean fluorescence intensity=86±5.9) was significantly reduced compared to that of fifth day (mean fluorescence intensity=61±7.7) after storage (P=0.0094). Conversely, shed GPIbα (Glycocalicin) demonstrated continuous elevation during five-day storage (P=0.0098). According to the results the shedding levels for the first day were increased from 0.31± 0.3 to 1.5± 0.4 by the day 5 after storage.  

Conclusion: Our study has demonstrated significant loss of platelet GPIbα during storage mostly due to receptor ectodomain shedding that leads to significant increase of soluble GPIbα in stored platelets. Considering the high levels of shed GPIbα in long stored platelets whether the transfusion of such products might be associated with defective adhesive function of platelets or possible proinflammatory effects could be of interests for future investigation.

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Background: Human leukocyte antigen E is a member of non-classical HLA class I. Interaction between HLA-E molecule on the target cells and inhibitory CD94/NKG2A receptor on the cell surface of natural killer (NK) cells has an important role in the regulation of immune system against pathogens; therefore different cell surface expression of HLA-E molecule plays an important role in host resistance against viral infections as well as host response to treatment. Considering this fact, we analyzed the frequency of different HLA-E genotypes (HLA-E*01010101, HLA-E*01030103, HLA-E*01010103) in major thalassemic patients who underwent frequent transfusion therapy and are thus more susceptible to infectious diseases.

Methods: This study was a cross-sectional study of 104 major thalassemic patients who referred to Tehran Thalassemia Clinic between the years 2015 to 2016. Blood DNA was extracted and proliferated by sequence-specific primer polymerase chain reaction (SSP PCR). The PCR product was subjected to electrophoresis on 1.5 percent agarose gel then DNA fragment bands on the gel were detected by exposing to UV light. Furthermore, PCR products were also subjected to sequencing analysis for further confirmation.

Results: From 104 patients in this study, 49 (47.1%) were man and 55 (52.9%) were women. These patients were in the age range of 16 to 43 years (mean+SD; 31.03±4.7 year). The frequency of HLA-E*01010103 genotype (64.4 percent) was significantly (P= 0.001) higher than the genotypes of HLA-E*01010101 (15.4%) and HLA-E*01030103 (20.2%) whereas there was no difference between the frequency of HLA-E*0103 allele (52.4%) and HLA-E*0101 (47.6%).

Conclusion: This is the first study that examined the HLA-E polymorphisms in Iranian thalassemic patients referred to Tehran Thalassemia Clinic. This study has shown that the frequency of HLA-E*01010103 genotype was significantly higher than other genotypes of HLA-E whereas there was no difference between the frequency of HLA-E*0103 allele and HLA-E*0101 allele. Whether different frequencies of HLA-E genotype may affect thalassemic patients’ susceptibility to blood-borne infections will be of interest for future studies.

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Background: Platelet storage is complicated by deleterious changes that cause progressive structural and functional damages, so-called platelet storage lesion (PSL). PSL is commonly manifested by augmented platelet activation which is also associated with the increased levels of reactive oxygen species (ROS). Whether ROS generation increases during the storage of platelet concentrates and whether it will be correlated with P-selectin expression as a valid marker of platelet activation was investigated in this study. Methods: In our experimental study, six PRP-platelet concentrates were randomly obtained from Iranian Blood Transfusion Organization (IBTO). All the platelet products met the standard quality assessment based on AABB guidelines. Washed platelets were subjected to flow cytometry analysis for the evaluation of P-selectin expression and intracellular ROS production using DHR 123 in day 0, 1, 3 and 5 after storage. Statistical data were analyzed by Kruskal-Wallis test with Dunn’s multiple comparison test. For correlations, linear regression analysis was applied. P values of less than 0.05 were considered to be significant. Results: Platelets ROS generation significantly increased from day 0 to day 5 of storage (P= 0.0002). This observed gradual increase was also directly correlated with the increasing levels of P-selectin expression during platelet storage (r= 0.72, P= 0.0001). Conclusion: Our study showed significant increases in ROS generation during the storage of platelet concentrates correlated with the increments of P-selectin expression as an important marker of platelet activation. This finding suggests that the analysis of ROS generation can also be considered a marker of platelet activation during storage. However, whether ROS generation first induces platelet activation or platelet activation during storage triggers ROS generation is still remain to be determined.

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Blood transfusion is commonly implemented to manage life and health-threatening conditions on a rapid and short-term basis. Over the years, ongoing technical advances have dramatically improved transfusion medicine to provide more safety and effectiveness. However, transfusion is still complicated with different adverse events that mainly induced by the presence of allogeneic leukocytes in the blood products. Several lines of evidence have shown that leukocytes in blood components are involved in the induction of febrile nonhemolytic transfusion reactions (FNHTRs), HLA alloimmunization and platelet refractoriness as well as the increased risk of the infectious diseases transmitted by leukotropic viruses including cytomegalovirus (CMV), human T-lymphotropic virus (HTLV)-I/II and Epstein-Barr virus (EBV). During current decades, introducing various leuko-reduction techniques have shown to be associated with less transfusion related adverse events and improved clinical outcomes. The lower incidence and severity of febrile transfusion reactions; reduced risk of transfusion related transmission of CMV or other leukocyte-associated infections, lowered incidence of alloimmune platelet refractoriness in addition to reducing risk of mortality and morbidity in patients are considered as clinical benefits of leuko-reduced products. Currently, by the use of 3^rd and 4^th generation of filters, the highest levels of leukoreduction in blood components have been achieved. Filtration techniques have also the advantages of being performed shortly after preparation of components (pre-storage) or post-storage even at the patient’s bedside. However, it seems that pre-storage depletion of leukocytes provides better protection than post-storage techniques due to the elimination of leukocyte-derived cytokines effects which are increasingly released during storage. Particularly in platelet products, the earlier depletion of leukocyte also favors less platelet-induced leukocyte activation which may be triggered by the interaction between either activated platelets or their released chemokines and residual leukocytes during storage. Despite the benefits attributed to leukoreduction of blood components, the global use of leukoreduced products is commonly hampered by its high cost especially in developing countries in which leukoreduction of blood components is usually limited to some patients with special conditions. In this review, after briefly introducing of some transfusion adverse events that are attributed to allogeneic leukocytes existed in blood products, the effects of leukoreduction process in the attenuation of these events will be discussed.