Common variable immunodeficiency (CVID) is the most common primary immune defect, resulting in hypogammaglobulinemia as well as deficits in cell-mediated immunity. Although it mainly manifests in immunodeficiency and related infection, CVID can also be associated with autoimmune phenomena such as immune thrombocytopenic purpura, hemolytic anemia, rheumatoid arthritis, lupus, primary biliary cirrhosis, and autoimmune hepatitis (AIH). AIH is a less common but serious complication of CVID, which can result in early cirrhosis, ascites, and even hepatocellular carcinoma. Here, we discuss a recent case of transplantation for cirrhosis secondary to AIH in the context of CVID. Although the patient's surgery occurred without complication, he rapidly developed fulminant alveolar hemorrhage and seizures, and died secondary to disseminated neuroaspergillosis.

Immune-mediated thrombocytopenic purpura (ITP) is recognized as a cell-specific autoimmune disorder, yet, multifactorial in origin. The development of thrombocytopenia is well proven to be mediated by both humoral (anti-platelet antibodies) and cellular (T-cell) mediated mechanisms. In some cases other autoantibodies are also induced, eg, antinuclear antibody (ANA), anti-dsDNA, and anti-cardiolipin, in addition to anti-platelet antibodies. The persistance of these autoantibodies during the course of ITP could herald future development of another autoimmune disease, eg, systemic lupus erythematosus (SLE) or anti-phospholipid syndrome (APS). Due to the better understanding of the pathophysiology of ITP, new novel therapies were introduced aiming to achieve long-lasting remissions. In this review we will focus on the autoimmune nature of the disease and on some of the mechanisms of action of these new therapies.

BACKGROUND AND OBJECTIVES:

Idiopathic thrombotic thrombocytopenic purpura (TTP) is a rare, clinically diagnosed disorder characterized by widespread intravascular platelet thrombosis. The pathophysiology involves acquired deficiency of ADAMTS13 (A disintegrin and metalloprotease with thrombospondin type 1 repeats), the enzyme responsible for cleavage of high molecular weight vonWillebrand factor multimers. Disease mortality is high, although prompt treatment with plasma exchange is generally effective. A readily available and highly reliable method of identifying ADAMTS13-deficient patients for appropriate plasma exchange is therefore of interest.

MATERIALS AND METHODS:

Our initial study involved the assessment of multiple clinical and laboratory variables in patients with clinically suspected TTP for whom ADAMTS13 assay was performed. Five variables were found to be of significant predictive power. This enabled the development of a point-based scoring system to efficiently determine the likelihood of TTP and response to plasma exchange in a given patient. This current study involved a separate validation cohort of patients with clinically suspected TTP who underwent ADAMTS13 testing within two large healthcare systems in Utah between 2009 and 2011. The previously derived score was applied to this cohort and its performance was analysed. Additionally, the original and validation cohorts were combined to revisit the predictive power of individual variables and the five-variable prediction score.

RESULTS:

A total of 84 (11 paediatric cases excluded) patients comprised the validation population. The percentage of TTP diagnoses in this group (10%) was identical to that in the initial cohort. Using an ADAMTS13 activity of <10% of normal, our original score correctly predicted or excluded severe ADAMTS13 deficiency in all patients in the second cohort when data for all variables was available. Individual variables retained predictive power and the performance of a three-variable parsimonious model, as well as the ultimate diagnoses for patients in the second cohort are described.

CONCLUSION:

This work confirms the predictive power of a simple point-based score to exclude TTP as evidenced by severe ADAMTS13 deficiency in appropriately selected patients. It may enable clinicians to rapidly begin plasma exchange or to pursue an alternative cause of thrombotic microangiopathy.

Background:

Thrombocytopenia (platelet counts less than 150,000/μl) is commonly encountered in various hematological disorders including myelodysplastic syndromes as well as various non-myelodysplastic hematological conditions.

Aim:

The present study was undertaken to calculate the prevalence of various conditions associated with thrombocytopenia and to record the megakaryocytic alterations in various cases of thrombocytopenia. Apart from this by means of statistical analysis it was tried to analyze whether a significant difference existed in megakaryocytic alteration noted in myelodysplastic versus non- myelodysplastic conditions. Materials and

Methods:

A prospective series of 60 bone marrow aspirations along with concomitant bone marrow biopsies was conducted in a tertiary care centre catering to both urban as well as rural population in north India. Statistical Analysis: The distribution of morphological changes in cases of non myelodysplastic conditions and myelodysplastic were compared using Chi-Square test. A p-value less than 0.05 was considered significant.

Results:

The commonest cause of thrombocytopenia for which bone marrow examination was sought was dimorphic anaemia (18 cases, 30%), followed by myelodysplastic syndrome (06 cases, 10%) which was followed equally by acute lymphocytic leukemia and blast crisis of chronic myeloid leukemia (CML). Of all the non-MDS conditions apart from dimorphic anaemia, idiopathic thrombocytopenic purpura and chronic myeloid leukemia (blast crisis); megakaryocytic dysplastic forms were not noted in any other condition. In cases of myelodysplasia; dysplastic forms, bare megakaryocytic nuclei, hypogranular forms and micromegakaryocytes were seen. Comparison between frequencies of normal, high and low number of nuclear lobes among MDS (n=9) and non MDS (n=68) conditions were found to be statistically significant.

Conclusion:

Further studies on the evaluation of megakaryocytic alteration and their contribution to thrombocytopenia can provide growing knowledge to the pathogenesis of numerous hematopoietic disorders that may identify broader clinical applications of the newer strategies to regulate platelet count and functioning.

The treatment of refractory idiopathic thrombocytopenia in adult is a challenge. Here we report successful treatment of an adult ITP patient with immunoadsorption using tryptophan column who were refractory to steroids, splenectomy, eltrombopag and various immunosuppressive medications.

This study was aimed to investigate the clinic significance of helicobacter pylori (HP) in children with idiopathic thrombocytopenic purpura (ITP). The infection of HP in 92 ITP children was determined by (13) C-Urea Breath Test, the same test was also performed on 66 healthy children. The 68 children infected with HP were randomly divided into 2 groups: single drug group treated only with corticosteroid and; combined drug group treated with corticosteroid and anti-helicobacter pylori treatment. The results showed that 68 patients infected with HP were found in 92 ITP children (74.7%), 26 patients infected with HP were observed in 66 healthy children (39.4%), which was lower than that in ITP children (74.7%, P < 0.05). After anti-helicobacter pylori therapy, the total effective rate and cure rate of ITP patients increased respectively from 73.5% to 94.1%, and the total recurrence rate (17.0%) was much lower than single drug group (47.1%, P < 0.05). Otherwise, after therapy the platelet count in both two groups increased continuously, and at the same time point, the platelet count in anti-helicobacterium pylori group was higher than that in the single drug group (P < 0.05). It is concluded that the ITP children have a higher infection rate of HP, which may be involved in the pathogenesis of ITP. Anti-helicobacterium pylori therapy would help to improve the therapeutic efficacy and reduce the recurrence of ITP children.

History and admission findings: We report on the case of a young women presenting with macrohaematuria, petechiae and strong headaches. Investigations: Laboratory showed a thrombotic microangiopathy with helmet cells, increased LDH levels (>600 U/l), and thrombocytopenia (<40 000/μl).Diagnosis, treatment and course: Due to strong haemolytic activity and headache with blurred vision, immediate plasma separation with fresh frozen plasma was commenced. Markedly decreased ADAMTS13 activity and detection of anti-ADAMTS13 antibodies were consistent with the diagnosis of idiopathic thrombotic thrombocytopenic purpura. In total, 11 plasma separations were required to stop disease activity. In parallel, immunosuppressive therapy using glucocorticoids was initiated. The patient was discharged from the hospital in a good general condition and with normalized laboratory findings 26 days after hospitalization.

Conclusions:

All patients with anemia and thrombocytopenia should be tested for haemolysis and helmet cells. An early diagnosis and initiation of necessary therapy are determining for the clinical outcome.

To investigate the expression of homeobox gene HOXA9 in the bone marrow mononuclear cells of children with acute leukemia (AL) and its clinical significance.Forty-six children with AL were divided into acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) groups. Fifteen children with idiopathic thrombocytopenic purpura were selected as a control group. The mRNA expression of HOXA9 was measured by reverse transcription polymerase chain reaction (RT-PCR).HOXA9 expression was detected in 63% of the 52 bone marrow samples from 46 AL children. The positive HOXA9 expression rate in the AML group was significantly higher than in the ALL and control groups (86% vs 35% and 13%; P<0.05). The mRNA expression of HOXA9 in the AML group was significantly higher than in the ALL and control groups (P<0.05). Among the children with AML, those with M5 AML had the highest HOXA9 mRNA level, followed by children with M4 AML and children with M1 and/or M2 AML, but HOXA9 expression was not detected in children with M3 AML. The high-risk subgroup of AML children had relatively high levels of HOXA9 expression. In the children with AML, the initial treatment subgroup had significantly higher positive HOXA9 expression rate and HOXA9 mRNA levels than in the remission subgroup and control group (P<0.05), but there were no significant differences between the latter two groups (P>0.05). The non-remission subgroup had significantly higher HOXA9 expression than the remission subgroup and control group (P<0.05). CONCLISONS: High expression of HOXA9 is associated with the occurrence of AL, and its expression level is significantly higher in children with AML than in those with ALL. There is a positive correlation between the expression level of HOXA9 and the risk of childhood leukemia, and high expression of HOXA9 suggests poor prognosis. Therefore, HOXA9 can be used as one of the indices in the diagnosis, treatment and prognosis prediction of childhood AL.

We report on 21 patients with idiopathic thrombotic thrombocytopenic purpura (TTP) whose courses of disease have been followed from the respective diagnosis until now. They had a documented ADAMTS13 activity below 5%, a high autoantibody titer and detectable ultralarge von Willebrand factor (VWF) multimers during their episodes. The initial diagnosis was based on clinical symptoms and on laboratory parameters: thrombocytopenia, haemolytic anaemia, schistocytes and an increased LDH level. 103 acute clinical episodes of 21 TTP-patients during a time period of 30 years are described. Case histories, comorbidities and sequelae were retrospectively documented. Results, conclusion: Although patients are consistently in a prothrombotic status, clinical acute manifestations only occur after triggering. Most common trigger factors are gastrointestinal infections and pregnancy. The relapse risk per month is 0.026; men have a higher risk for relapses (0.044) than women (0.021). Patients recover physically well, except for renal insufficiency in four cases. Nevertheless, major portion of patients suffers persistently from depression, anxiety disorders and persistent neurocognitive impairments.