Immunologic Thrombocytopenia Research Articles

Macrophage modulation in activation process induced immune thrombocytopenia

The immune system operates like an orchestra that harmoniously maintains the homeostasis balance while protecting from external or internal pathogens attack. Inflammation is one of the key critical immune defenses to eradicate pathogens and encourage tissue repair and recovery by activating the host’s immune and non-immune cells. As a part of the immune response during inflammation, blood platelets serve various functions; however, their activation and involvement in inflammation can also contribute to pathological conditions, such as thrombosis, which results in myocardial infarction, stroke, and venous thromboembolism. Activated platelets can mobilize and release intracellular granules (alpha and dense granules), which include secondary mediators like chemokine PF4/CXCL4. In contrast to most other chemokines, PF4 participates in several long-term regulatory processes, such as cell differentiation, survival, and proliferation. However, recent findings suggest that PF4 is also responsible for modulating macrophage polarization, which can substantially impact the development of induced immune thrombotic thrombocytopenia. This review aims to explain how PF4 induced vascular problems by modulation of macrophage development during immunological thrombocytopenia. A literature search using the keywords PF4, CXCL4, macrophage M4, platelet macrophage M4, and induced immune thrombocytopenia was done using the following databases: Google Scholar, ProQuest, ScienceDirect, and Scopus for articles published from 2000 to 2023. The literature study was done to find the connection between platelet activation, macrophage modulation, and vascular problems such as atherosclerosis and thromboembolism in induced immune thrombotic thrombocytopenia. Several recent studies on PF4, macrophage modulation, and vaccine-induced thrombotic thrombocytopenia were carefully reviewed. This review concludes that macrophage polarization modulation is promising in managing vascular problems in patients with induced immune thrombotic thrombocytopenia.

Evans Syndrome: A Rare Case of Concurrent Autoimmune Haemolytic Anaemia and Immune Thrombocytopenia

Immunological thrombocytopenia (ITP), immune neutropenia, and/or autoimmune haemolytic anaemia (AIHA) can develop concurrently or sequentially in Evans syndrome (ES), an uncommon illness. Frequent relapses, a heavy therapeutic load, and an elevated risk of infection and thrombosis are its hallmarks, all of which have a substantial impact on survival. Several illnesses, including as lymphoproliferative disorders, other systemic autoimmune diseases, and primary immunodeficiencies, can be categorized as primary or secondary to ES. The syndrome has a major influence on survival and quality of life and is frequently severe and sometimes fatal. Effective management of ES requires prompt therapy, including anti-infectious and anti-thrombotic prophylaxis.

Clinicopathological and flowcytometric analysis of platelet function in patients presenting with thrombocytopenia

Platelet function disorders are highly heterogeneous; those may be inherited/ acquired. Patients with these may have inadequate platelet count with impaired function, but may also have both. Early detection of platelet dysfunction also helps in better patient management and improve outcome. Prospective study done in 50 cases, Patient’s details history of thrombocytopenia. Complete blood count with peripheral smear is done and various parameters are analysed with respect to the platelet count, PDW, P-LCR. On EDTA preserved blood sample four monoclonal antibodies CD41, CD42b, CD61 and CD62p are applied and analysed by flow cytometer. In 50 thrombocytopenia cases out of which 06(12%) were immunological thrombocytopenia & 44 (88%) were non-immunological thrombocytopenia.

Les erreurs diagnostiques de la maladie de Gaucher dans la vraie vie : étude rétrospective du Registre français de la Maladie de Gaucher

IntroductionGaucher disease is an autosomal recessive genetic disorder. It is caused by a deficiency of the lysosomal enzyme, glucocerebrosidase which leads to an accumulation of glucosylceramide in the macrophages. Splenomegaly, hepatomegaly, cytopenias (anemia, thrombocytopenia) and bone disorders are the main symptoms. The diagnosis is often delayed, leading to unnecessary investigations and treatments, and delaying the specific treatment. The primary objective of our study was to establish, in patients who had a diagnostic delay of more than one year, the reported misdiagnoses before the final diagnosis. The secondary objectives were to investigate the risk factors associated with error and delayed diagnosis. MethodsRetrospective study including patients with Gaucher disease from the French Gaucher Disease Registry. Collection of data by a single investigator from a standardized form. ResultsAmong 83 patients with a known diagnostic delay, 13 patients (15 %) had one or two misdiagnoses. These included osteo-articular diagnoses (osteomyelitis, osteoarthritis, arthritis, osteochondritis, rheumatic fever, n=8), haematological diagnoses (gestational thrombocytopenia, immunological thrombocytopenia, n=4), infectious diagnoses (visceral leishmaniasis, mononucleosis, n=2) and hemochromatosis. The osteo-articular and infectious diagnoses concerned the child and the adolescent while the haematological diagnoses and the hemochromatosis concerned the adult. No factors were found associated with misdiagnoses. Patients with a diagnostic delay greater than one year were less likely to have hepatosplenomegaly as the first symptom. ConclusionThere is a risk of diagnostic error related to phenotypic heterogeneity and lack of specificity of Gaucher disease symptoms. This study helps to better identify the misdiagnoses associated with Gaucher disease.

Epidemiological, Biological and Etiological Profile of Thrombocytopenia Diagnosed at the Hematology Laboratory of the Arrazi Hospital of the University Hospital Center Mohammed Vi-Marrakesh- Prospective Study (March 2021-August 2021)

Study objectives: This study attempts to describe the epidemiological and biological profiles as well as the common etiologies of thrombocytopenia in patients admitted to University Hospital center Mohammed VI in Marrakesh, Morocco, over a period of six months between March 2021 and August 2021. Patients and methods: This is a prospective study of 673 patients hospitalized in the University Hospital center -Mohammed VI-Marrakesh between March and August 2021 whose admission blood tests show thrombocytopenia. Results: Thrombocytopenia was found in 673 patients, mainly from the intensive care unit (28%) and the department of hematology & oncology (16%), the sex ratio was 1.3 with a male predominance of 58%, the average age of our patients was 37.1 years. On biological plan, prothrombin (PT) and CRP were the two most noticed disturbed biological markers in our series, at 50% and 79% respectively, the etiological profile of our patients demonstrated a predominance of peripheral thrombocytopenia at 83.2%, The most frequent causes were infectious (43%), bacterial, viral or parasitic, followed by anomaly of distribution of platets (12%) and immunological thrombocytopenia (9%). Conclusion: Our study shows that thrombocytopenia is a frequent biological anomaly that can affect both sexes, of any age, it is most often multifactorial, but the main cause is infection, requiring a correlation of epidemiological, clinical and biological profiles in order to adapt the treatment.

An Unusual Case of Severe Vaccine Induced Immunologic Thrombocytopenia Purpura from Moderna SARS-CoV-2 Vaccination in an Immunocompromised Patient

An Unusual Case of Severe Vaccine Induced Immunologic Thrombocytopenia Purpura from Moderna SARS-CoV-2 Vaccination in an Immunocompromised Patient

Association between Immunological Thrombocytopenia and Thrombosis, Is It an Exotic Phenomenon?—A Case Report

Immunologic thrombocytopenia (ITP) is an autoimmune disease associated with the production of autoantibodies against specific platelet membrane glycoproteins. A thrombotic event as an unusual occurrence during ITP is becoming more and more frequent. In fact, several recent studies have shown an increased thrombotic risk in this situation. The case presented here is that of a fifty-one-year-old woman with extensive cerebral venous thrombosis 2 years after her ITP diagnosis. During IT, thrombosis may be triggered by the release of pro-thrombotic platelet micro-particles and by platelet activation due to the interaction between autoantibodies and platelet glycoproteins. Immunosuppressive therapy has also been linked in several studies to the thrombotic phenomenon. Increased thromboembolic risk should be taken into account in all ITP patients.

L’axe CD40-CD40L : implications actuelles et futures en immunologie clinique

The CD40-CD40 ligand (CD40L) pathway is a backbone of communication between cells of the immune system. It makes it possible to generate a proinflammatory signal and thus participates in the pathogenesis of dysimmune diseases, transplant rejection and atherosclerosis. Because of this therapeutic target of choice, several generations of anti-CD40L monoclonal antibodies have emerged since the 1990s. The first generation of antibodies was responsible for thromboembolic toxicity for which the mechanisms are starting to be defined. New generations of antibodies were designed to overcome this toxicity and are still being developed in lupus, rheumatoid arthritis, Sjogren's syndrome or immunologic thrombocytopenia. In addition to these targeted therapies, there are data suggesting the impact of several drugs among molecules used in cardiology and clinical immunology on the level of CD40L. The objective of this review is to recall the clinical issues related to the CD40-CD40L axis and to present current or future treatments that block CD40L which would allow clinicians to diversify their options for managing dysimmune diseases.

Phage display identification of immunodominant epitopes and autoantibodies in autoimmune diseases

Phage display represents an invaluable tool to study autoimmune diseases. The side effects of immunosuppressive drugs for the treatment of autoimmune diseases raise awareness of the need to explore alternative therapeutic approaches such as antibodies and peptides. Therefore, phage display is an important technique for generating such molecules, so the purpose of this review is to determine the potential advantages of this technique in the research of autoimmune diseases. Many studies have also demonstrated the efficacy of phage display in identifying immunodominant epitopes of autoimmune diseases such as Goodpasture disease, immunologic thrombocytopenia, and systemic lupus erythematosus. Phage display peptide libraries have been screened with immunopurified autoantibodies from patients with autoimmune diseases. This makes it possible to more precisely locate the autoantibody binding sites, reveal a possible epitope sharing between the host and microbe, and identify a motif that mimics an antigenic structure such as that of dsDNA. Several studies have been conducted that have investigated the effectiveness of phage display in isolating autoantibody repertoires of autoantibodies against human epitopes. This allows the identification and design of antibody fragments (e.g., Fab, scFv, sdAb) that could block the binding of autoantibodies such as the deposition of IgG in the kidney and reduce the clinical signs of disease. In conclusion, phage display helps identify common epitopes and hotspot residues that can be potential therapeutic targets for the treatment of autoimmune diseases. This leads to a better understanding of the immunopathogenesis of autoimmune diseases and the development of more specific therapeutic strategies.

Eltrombopag inhibits Type I interferon-mediated antiviral signaling by decreasing cellular iron

Thrombocytopenia is common among patients with viral hepatitis, limiting the use of antiviral therapy. Eltrombopag (EP) is a thrombopoietin receptor (TPO-R) agonist that has been approved for treatment of immune thrombocytopenia patients with hepatitis virus infection. Interferon-α (IFN-α) plays a crucial role in the antiviral response, and is recommended as the first-line agent for chronic hepatitis B patients. Here, we investigated whether EP inhibits the production of IFN-stimulated genes (ISGs) induced by IFN-α through the TPO-R-independent pathway by mediating reactive oxygen species production by iron chelation. Our results assessed the inhibitory effect of EP on IFN-α signaling, which contributes to the downregulation of ISGs produced by monocytes and sheds light on the underlying mechanisms using iron chelation to treat patients with hepatitis-related immunological thrombocytopenia.

儿童免疫性血小板减少症相关机制研究进展及药物评价

儿童免疫性血小板减少症相关机制研究进展及药物评价

Clinical Significance of Platelet Membrane Glycoprotein GPIIb/IIIa in Diagnosis and Treatment of Immune Thrombocytopenia

To explore the clinical significance of platelet membrane glycoprotein (GPIIb/IIIa) detection by flow cytometry (FCM) combined with enzyme-linked immunosorbent assay (ELISA) in diagnosis and treatment of immune thrombocytopenia(ITP). Fifty-two patients with immunological thrombocytopenia admitted to the Department of Hematology in our hospital during October 2014-October 2018 were enrolled in ITP group. Thirty healthy people from the physical examination center were enrolled in control group. The positive expression rate of platelet membrane glycoprotein was measured by FCM, and the peripheral platelet count was detected by automatic analyzer, and the plasma membrane glycoprotein level was measured by ELISA. The difference between the two groups was compared. The platelet membrane glycoprotein levels in ITP patients before and after treatment were compared. The positive expression rate of GPIIb/IIIa (i,e CD41+/CD61+) and plasma GPIIb/IIIa levels in ITP patients were significantly lower than those in the healthy controls. The increased expression of platelet GPIIb/IIIa was associated with the response to therapy. The positive expression rate and level of GPIIb/IIIa postively correlated with its platelet count. The sensitivity of platelet GPIIb/IIIa combined with platelet count for diagnosis of ITP was 90.38%, the specificity was 93.33%, the positive likelihood ratio was 13.57, and the positive predictive value was 95.92%. The platelet membrane glycoprotein detection as a preliminary screening method used for diagnosis of immune thrombocytopenia is simple, convenient, sensitive and rapid, thus may be considered as a new method for clinical diagnosis.

Aberrant Expression of a Proliferation-Inducing Ligand Underlies Autoimmune Mechanisms in Immune Thrombocytopenia

Background: Immunological thrombocytopenia (ITP) is an antibody-mediated autoimmune disease characterized by accelerated platelet destruction and suboptimal platelet production. The proliferation-inducing ligand (APRIL or TNFSF13), a member of the TNF superfamily, is structurally and functionally related to the TNF family of B cell activating factors (BAFF, TNFSF13b) and has been shown to regulate lymphocyte survival by interacting with its receptors. And activation. Transmembrane activators and calcium regulate cyclophilin ligand interactors (TACI) and B cell mature antigens (BCMA). APRIL is secreted by various cells as soluble factors, including inactive B cells, T cells, monocytes, neutrophils, macrophages and dendritic cells, as well as epithelial cells, osteoclasts and megakaryocytes. Recent studies have shown that APRIL not only participates in normal immune responses, but also plays an important role in the establishment and/or maintenance of autoimmune and inflammatory diseases.Aims: Based on the relationship between APRIL, which promotes proliferation and regulates immunity, and the development of autoimmunity, we hypothesize that APRIL may play a role in the pathogenesis of ITP.Methods:1. The EDTA anticoagulated whole blood was collected, and peripheral blood mononuclear cells (PBMC) were separated by Ficoll density gradient centrifugation. The APRIL levels on the surface of T cells, B cells, DC cells and platelets were detected by flow cytometry.Detection of plasma APRIL levels in patients with ITP by ELISA.Real time quantitative PCR were used for detecting the level of APRIL and its receptors BCMA and TACI from PBMC of healthy controls and ITP patients.Use soluble APRIL or BLyS protein and APRIL inhibitors to examine the effect of APRIL inhibition on IL-10 secretion by B cells. Flow cytometry and intracellular staining were used to evaluate B10 cells.Resoult: 1. The APRIL on the platelet surface of patients with ITP was significantly lower than that of the normal control group (p<0.01). In the ITP patients of 10 patients with complete remission, the content of APRIL on the platelet surface was significantly increased after treatment (p=0.02), and there was no significant change in the treatment-ineffective group. .The levels of APRIL and its receptors BCMA and TACI on B cells and DC cells in ITP patients were higher than those in normal controls, and the difference was statistically significant. APRIL is not expressed on CD4 + T cells, CD8 + T cells.The expression of APRIL mRNA in PBMNCs was significantly higher in ITP patients than in the normal control group (p <0.01). There was no difference in BCMA and TACI expression in PBMNC of ITP patients compared to normal controls.Plasma APRIL levels were significantly higher in ITP patients than in the normal control group, p = 0.04, and negatively correlated with platelet count, p = 0.029.In 10 patients with ITP, the percentage of CD19 + B cells remained similar between patients, and the results showed that the amount of B10 cells in the medium supplemented with APRIL was greater than that of B10 cells containing BLyS and control medium (p<0.01; p= 0.01), and the use of APRIL inhibitors resulted in a decrease in B10 cells.Conclusion: Our study shows that aberrant expression of APRIL is involved in the autoimmune response of ITP, and the effect of treatment can be assessed by measuring changes in the level of APRIL on the platelet surface. We also speculate that APRIL inhibits, rather than promotes, an immune-mediated inflammatory response in the pathogenesis of ITP. Our current observations support that the immunomodulatory effects of APRIL may be due, at least in part, to stimulation of IL-10 producing B cells. DisclosuresNo relevant conflicts of interest to declare.

Clinical characteristics and thrombosis outcomes of paediatric antiphospholipid syndrome: analysis of 58 patients.

The study aims to analyse the clinical and immunological manifestations of paediatric antiphospholipid syndrome (APS) in patients, based on the 2006 revised classification criteria of definite APS. Fifty-eight paediatric patients with APS were enrolled and analysed retrospectively. A total of 37 female and 21 male patients with a mean age of 14±3years at disease onset were included. Fourteen (24%) cases were primary APS, and 40 (69%) cases were secondary to systemic lupus erythaematosus (SLE). Anti-nuclear antibody (ANA) positivity and hypocomplementemia were more common in secondary APS than in primary APS. The most common manifestations of thrombosis were deep vein thrombosis of the lower extremities (25 cases, 37%). Non-thrombotic manifestations were mainly immunologic thrombocytopenia, autoimmune haemolytic anaemia, skin lesions, arthritis, pulmonary hypertension, heart valve vegetations and spontaneous abortion. LA, ACL and anti-β2GPI were positive in 42 (95%), 28 (64%) and 34 (77%) cases, respectively. Over half (23 cases, 52%) of the patients were triple-positive for antiphospholipid (aPL) antibodies. Among patients with single-positive LA and anti-β2GPI, the proportion with venous thrombosis was 100% (5 cases) and 0% (0 cases), respectively. The arterial thrombosis proportions were 22% (5 cases), 21% (3 cases) and 14% (1 case) in the triple-, double- and single-aPL-positive groups, respectively (P>0.05). Fifty-three (91%) cases were followed up for 3 to 140months, with a median time of 32months. Seven (13%) cases had recurrences or appearances of thrombosis during follow-up, all of which were double- or triple-aPL positive. APS in the paediatric patients is mostly secondary to SLE. ANA positivity and hypocomplementemia are more common in secondary APS, but there are no differences in the other clinical manifestations between the primary and secondary APS groups. Deep vein thrombosis is the most common thrombotic event. Positive LA may increase the risk of venous thrombosis. Multiple-aPL positivity does not increase the proportion of thrombosis. Long-term anticoagulant or antiplatelet therapy is needed to prevent thrombosis recurrence in double- or triple-positive aPL cases.

CHRONIC LYMPHOCYTIC LEUKEMIA INVOLVEMENT OF CENTRAL NERVOUS SYSTEM: A SINGLE CENTRE EXPERIENCE

Introduction: Chronic lymphocytic leukemia (CLL) involvement of central nervous system (CNS) is reported to be rare, mainly due to only occasional appear of predominantly non-specific neurological symptoms. Neurologic complications arising from direct leukemic involvement of CNS is stated in only 1% of patients (pts) with CLL. There is no treatment consensus with similar results of intrathecal chemotherapy or whole-brain irradiation, but some more recent studies reported more encouraging data with application of immunochemotherapy or tyrosine kinase inhibitor, ibrutinib. CLL with CNS involvement is related with poorer outcome, especially for pts with unfavorable cytogenetic (17p deletion). Methods: We presented a small series of four pts that were diagnosed and treated in our Institution. All pts met the International Workshop on CLL diagnostic criteria (2008). Diagnosis of CNS involvement was established via neuroimaging methods such as MRI, as well as cerebrospinal fluid (CSF) cytology, and CSF multiparameter flow cytometry immynophenotyping method (CSF FCM). Results: All pts were men with average age of 55.25 years (yrs). On CNS onset, all had disseminated disease and 17p deletion was registered in one case. Average latency period from CLL to CNS onset was 2.91 yrs. We registered heterogeneous neurological symptoms on CNS onset, including bradypsyhia, headaches, nausea, vomiting, dysphasia, repeated unconsciousness, urinary incontinence, dyslexia, lack of fine motor control, diplopia and bilateral eyelid swelling. Diagnostics included positive CSF cytology in three cases, CSF FCM was performed in all of our cases. MRI scan was performed in all cases and was conclusive in three (75%) cases. On CLL onset, two pts were treated with systemic chemotherapy, FC (fludarabine, cyclophosphamide) in one case and CHOP (cyclophosphamide, doxorubicine, vincristine, prednisolone) in other, third was initially treated with corticosteroid therapy due to immunological thrombocytopenia and fourth was on “watch and wait” policy, due to comorbidities. Two of our pts were treatment naïve on CNS onset. When CLL in CNS was diagnosed, systemic chemotherapy was applied in all cases. First patient received high-dose methotrexate with intrathecal therapies, second R(rituximab)-FC, and two received DHAP regimen (dexametasone, high-dose cytarabine, cisplatin) in two cases. Average and median OS from CNS onset was 4 and 3.5 months, respectively, with lethal outcome in 75% of cases in our follow-up. Conclusions: CLL in CNS is still rarely diagnosed, primarily due to the presence of heterogeneous, non-specific neurological symptoms, or their absence. The most effective diagnostics includes MRI, CSF-FCM, and if it is possible PCR detection of CLL cells in CSF. Our results confirm the poor therapeutic outcome and short survival in our group of pts. Keywords: chronic lymphocytic leukemia (CLL); flow cytometry; immunochemotherapy.

Autoimmune cytopenias associated with inflammatory bowel diseases: Insights from a multicenter retrospective cohort

IntroductionAutoimmune cytopenias (AIC) including autoimmune hemolytic anemia (AIHA) and immunologic thrombocytopenia (ITP) are rare immunologic disorders, scarcely reported in inflammatory bowel diseases (IBD). We conducted a multicentric retrospective study, including a case-control analysis, that aimed to describe the characteristics and outcomes of patients affected by AIC and IBD. MethodForty cases were recruited from 4 IBD centers and 2 AIC tertiary centers. Controls were recruited from the MICISTA registry. ResultsFrom the MICISTA registry, incidences were estimated at 4.1/100,000 patient-years and 12.5/100,000 patient-years after IBD diagnosis for AIHA and ITP, respectively. All AIHA patients (n=14) had colonic involvement (13/14 with UC), whereas CD (52%) and UC (48%) diagnoses were evenly distributed among ITP patients. Compared to control IBD patients, cases were characterized by a higher frequency of extra-intestinal manifestations (37.5% vs 17%, p<0.001) and by the presence of IBD severity’s hallmark. AIHA and IBD ran mainly in parallel, and 12 out of 14 AIHA were warm AIHA. In isolated cases, rituximab and infliximab were efficient to treat IBD and AIC, respectively. IBD surgery may induce AIC remission in some cases. ConclusionAlthough low, incidence of AIC appears higher in IBD patients compared to the general population. The association seems to be mainly non-fortuitous, especially for colitis-associated AIHA.

High dose of dexamethasone combined with recombinant human thrombopoietin in treatment of severe immunologic thrombocytopenia

Objective To compare the clinical effects of high-dose dexamethasone only and high-dose dexamethasone combined with recombinant human thrombocytopenia(rhTPO) in treatment of severe immunologic thrombocytopenia(ITP). Methods From January 2013 to March 2015, a total of 75 patients with severe ITP were included in the study. They were randomly divided into research group (n=38) and control group (n=37). There were no significant differences in general condition such as age, gender ratio between two groups (P>0.05). Combination therapy of high-dose dexamethasone (40 mg/time×1 time/d×4 d) and rhTPO (15 000 U/time×1 time/d×14 d) were given to ITP patients in research group. Meanwhile high-dose dexamethasone (40 mg/time×1 time/d×4 d) only was given to ITP patients in control group. And the adjuvant therapy was the same in both groups. The clinical effects and incidence of adverse reactions were compared between two groups by statistical methods. The study protocol was approved by the Ethical Review Board of Investigation in Human Being of First People′s Hospital of Jining city.Informed consent was obtained from each participants. Results There were significant differences in objective response rate(77.3% vs 47.8%), effective time [(6.9±1.4) d vs (10.2±2.1) d] and increased platelet amounts[ (155.2±101.2) ×109/L vs (55.7±33.3) ×109/L] between two groups(χ2=5.01, U=2.46, 3.15; P 0.05). Conclusions The high-dose dexamethasone combined with rhTPO in the treatment of severe ITP is better than high-dose dexamethasone only, with shorter median time and higher increased platelet amounts. Key words: Thrombopoietin; Dexamethasone; Thrombocytopenia

Effects of the interleukin-21 expression in patients with immune thrombocytopenia and its regulation by high-dose dexamethasone

To investigate the correlation of immunologic thrombocytopenia(ITP) pathogenesis with the abnormal expression of IL-21, and to explore the association of high-dose dexamethasone (HD-DEX) treatment with the IL-21 expression. 26 newly diagnosed ITP patients and 24 healthy controls were enrolled in this study. The mononuclear cells and serum were obtain from density gradient centrifugation in the newly diagnosed ITP patients before HD-DXM treatment, and the samples of healthy controls were also used for assays. The protein and mRNA expression of IL-21 on peripheral blood mononuclear cells(MNC) were determined by flow cytometry and real-time reverse-transcription polymerase chain reaction. Plasma levels of IL-21, IFN-γ and IL-4 were determined by enzyme-linked immunoabsorbent assay (ELISA). IL-21 expression on mononuclear cells was significantly higher in ITP patients (13.07%) than that in normal controls (8.2%), the ratio of IL-21/GAPDH mRNA expression on MNC was significantly higher in ITP patients (9.524±0.97) than that in normal controls (3.701±0.60, P<0.01). After HD-DXM therapy, the ratio of IL-21/GAPDH mRNA decreased significantly (5.87±1.21) as compared with the level before treatment. Significantly high levels of serum IL-21, IFN-γ and lower IL-4 were found in ITP patients, as compared with healthy controls. Serum IL-21 and IFN-γ levels in ITP patients decreased significantly after HD-DXM administration (P<0.01), while post-treatment levels of IL-4 were increased significantly, compared with the levels before treatment (P<0.01). Therapeutic effect of DXM on ITP associates with down-regalation of IL-21 expression. The increased expression of IL-21 involves in the pathogenesis of ITP.

Refractory Immunological Thrombocytopenia Purpura and Splenectomy in Pregnancy.

Thrombocytopenia is defined as a platelet count of less than 100,000 platelets per microlitre (mcL). Thrombocytopenia develops in approximately 6-7% of women during pregnancy and at least 3% of these cases are caused by immunological platelet destruction. Herein, we present a pregnant woman who develops at the first trimester autoimmune thrombocytopenia purpura associated with positive antiphospholipid antibodies. The disease was refractory to pharmacological treatments but had a favourable response to splenectomy. The patient carried the pregnancy to term without complication and gave birth to a healthy baby girl.

Heparin-Induced Thrombocytopenia During Extracorporeal Membrane Oxygenation

HEPARIN-INDUCED THROMBOCYTOPENIA (HIT) is an immune-mediated adverse effect of heparin therapy. Two clinical entities of HIT can be distinguished: HIT I and HIT II. HIT I is a harmless pharmacologic phenomenon associated with decreased platelet count within 24–48 h after initiation of heparinization. Unlike HIT II, it is not associated with thrombosis and does not necessitate discontinuation of heparin. In contrast, HIT II can cause both bleeding and thrombotic complications. It is the most important and most frequent drug-induced immunologic thrombocytopenia. Besides orthopedic and vascular surgery patients, patients after cardiac surgery are at highest risk of developing HIT II (1–5%). Its clinical importance is based on its strong association with venous and arterial thrombosis and thromboembolism (heparin-induced thrombocytopenia with associated thrombosis, HITT). HIT is caused by the development of an IgG antibody that recognizes multimolecular complexes of platelet factor 4 (PF4) and heparin. This so-called heparin-PF4-IgG complex leads to platelet activation and release of additional PF4 from alpha granules in platelets when bound to the platelet Fc receptor. Note that heparin forms a necessary part of the complex leading the further PF4 release. PF4 released in excess binds to heparin-like molecules on the surface of endothelial cells leading to immunemediated endothelial cell injury and heightening the risk for HITT and disseminated intravascular coagulation (DIC). The mainstay of therapy in HIT/HITT is the avoidance of further exposure to heparin in any form, avoidance of platelet transfusions and deferral of vitamin-K-antagonists until platelet recovery. Early use of alternative anticoagulants is inevitable when the indication for anticoagulation persists or in individuals with HITT. Extracorporeal membrane oxygenation (ECMO) remains a last line life-saving therapeutic option in patients suffering from