The objective of this study was to investigate the therapeutic effectiveness and safety profile of Eltrombopag, a thrombopoietin receptor agonist, as prolonged therapy in refractory CTD-ITP patients.

We conducted a pilot observational study of Eltrombopag in CTD-ITP patients who were unresponsive to or intolerant of conventional medications. Eltrombopag was administered orally at 25-75 mg/qd and adjusted on the basis of tolerance and efficacy until a minimum dosage of 25 mg/qd was reached. Clinical and laboratory data were collected and analysed monthly. The therapeutic response, relapse, and adverse events during the follow-up were also reviewed and evaluated.

Fifty-two patients were enrolled and followed monthly for a median of 6 months. Thirty-six (90%) patients achieved durable overall remission. The remission rates were 67.5% at month 1, 87.5% at month 2, 97.5% at month 3, and 95% at month 6. The platelet count of the patients improved significantly, with the median reaching 50 × 109/L within 2 weeks (p = 0.003). Disease activity indices were reduced in SLE and pSS patients (p = 0.016), allowing glucocorticoid tapering (p = 0.004). One patient had no response, four relapsed, and fifteen (28.8%) experienced clinically relevant adverse events. In the analyses, protopathy, comorbidity, and prior treatment were associated with efficacy.

For refractory CTD-ITP patients, Eltrombopag demonstrated significant clinical improvement, safety, and a steroid-sparing effect with prolonged use. Patient characteristics at baseline may affect treatment efficacy.

The latest WHO report determined the increasing diversity within the CoV-2 omicron and its descendent lineages. Some heavily mutated offshoots of BA.5 and BA.2, such as BA.4.6, BF.7, BQ.1.1, and BA.2.75, are responsible for about 20% of infections and are spreading rapidly in multiple countries. It is a sign that Omicron subvariants are now developing a capacity to be more immune escaping and may contribute to a new wave of COVID-19. Covid-19 infections often induce many alterations in human physiological defense and the natural control systems, with exacerbated activation of the inflammatory and homeostatic response, as for any infectious diseases. Severe activation of the early phase of hemostatic components, often occurs, leading to thrombotic complications and often contributing to a lethal outcome selectively in certain populations. Development of autoimmune complications increases the disease burden and lowers its prognosis. While the true mechanism still remains unclear, it is believed to mainly be related to the host autoimmune responses as demonstrated, only in some patients suffering from the presence of autoantibodies that worsens the disease evolution. In fact in some studies the development of autoantibodies to angiotensin converting enzyme 2 (ACE2) was identified, and in other studies autoantibodies, thought to be targeting interferon or binding to annexin A1, or autoantibodies to phospholipids were seen. Moreover, the occurrence of autoimmune heparin induced thrombocytopenia has also been described in infected patients treated with heparin for controlling thrombogenicity. This commentary focuses on the presence of various autoantibodies reported so far in Covid-19 diseases, exploring their association with the disease course and the durability of some related symptoms. Attempts are also made to further analyze the potential mechanism of actions and link the presence of antibodies with pathological complications.

Perioperative management of orthopaedic patients with a hematologic disorder is a complex endeavor that requires a multidisciplinary team-based approach. A team composed of an experienced orthopaedic surgeon, an anesthesiologist, and a hematologist is necessary to achieve optimal outcomes. Patients with hemophilia and other complex hematologic disorders should be managed at, or in consultation with a hematologist at, a comprehensive hemophilia center. Bleeding disorders and inherited thrombophilia present unique challenges for the perioperative management of orthopaedic surgery. Comprehensive preoperative planning and familiarity with treatment guidelines can help to minimize these risks. Knowledge of the disease processes outlined in this article will provide orthopaedic surgeons with the requisite background knowledge that is needed to initiate safe and effective treatment strategies involving this high-risk patient population.

Oral transmission of Trypanosoma cruzi, the etiologic agent of Chagas disease, is presently the most important route of infection in Brazilian Amazon. Other South American countries have also reported outbreaks of acute Chagas disease associated with food consumption. A conspicuous feature of this route of transmission is presenting symptoms such as facial and lower limbs edema, in some cases bleeding manifestations and risk of thromboembolism are evident. Notwithstanding, studies that address this route of infection are largely lacking regarding its pathogenesis and, more specifically, the crosstalk between immune and hemostatic systems. Here, BALB/c mice were orally infected with metacyclic trypomastigotes of T. cruzi Tulahuén strain and used to evaluate the cytokine response, primary and secondary hemostasis during acute T. cruzi infection. When compared with control uninfected animals, orally infected mice presented higher pro-inflammatory cytokine (TNF-α, IFN-γ, and IL-6) serum levels. The highest concentrations were obtained concomitantly to the increase of parasitemia, between 14 and 28 days post-infection (dpi). Blood counts in the oral infected group revealed concomitant leukocytosis and thrombocytopenia, the latter resulting in increased bleeding at 21 dpi. Hematological changes paralleled with prolonged activated partial thromboplastin time, Factor VIII consumption and increased D-dimer levels, suggest that oral T. cruzi infection relies on disseminated intravascular coagulation. Remarkably, blockade of the IL-6 receptor blunted hematological abnormalities, revealing a critical role of IL-6 in the course of oral infection. These results unravel that acute T. cruzi oral infection results in significant alterations in the hemostatic system and indicates the relevance of the crosstalk between inflammation and hemostasis in this parasitic disease.

Patients with autoimmune hepatitis (AIH) may sometimes have concomitant idiopathic thrombocytopenic purpura (ITP). Severe thrombocytopenia in ITP interferes with percutaneous liver biopsy for pathological diagnosis of AIH. Here, we report a case of AIH with ITP in a 63-year-old woman. The patient presented to our hospital with liver dysfunction and thrombocytopenia. For histological examination, transjugular liver biopsy (TJLB) was performed, leading to a diagnosis of AIH. Corticosteroids treatment led to an improvement in her liver enzyme levels and platelet count. In conclusion, patients with AIH may sometimes have concomitant ITP. TJLB was effective for making the diagnosis of AIH with severe thrombocytopenia due to ITP.

The natural history and its modulation by treatments administered for immune thrombocytopenia (ITP) in the clinical practice remains unknown. In addition, little information is available on the characteristics and management of ITP in Spain.

We conducted an observational, multicenter, registry in 70 Hematology Services from Spain between 2009 and 2011, which included children from 2 months of age and adults with primary ITP or another ITP diagnosed within the last 6 months (platelet count [PC] < 100 × 10⁹/l). Patients were followed-up at 6 and 12 months.

484 patients were included (median [Q1, Q3] age 52 [29,74] years, 87.6% adults), 56% women, 10.5% with secondary ITP. Median (Q1, Q3) PC at diagnosis was 12 × 10⁹/l (4, 32); 72% of patients had bleeding symptoms (62% cutaneous bleeding, 29% oral cavity bleeding, 18% epistaxis). 81% of patients with primary ITP received first-line treatment, mainly with corticosteroids (>6 weeks in 59% of cases), either alone (41%) or associated with intravenous immunoglobulin (33%). The response (≥30 × 10⁹/L) to first-line treatment was 92%. A total of 19% of patients received second-line treatment and 6% additional treatments. At 12 months, 74% of primary ITP patients maintained a PC ≥ 100 × 10⁹/L in absence of treatment (10% still had hemorrhagic manifestations).

Characteristics of Spanish ITP patients are comparable to those from other countries. Although a high response rate to first-line treatments is observed, at 1 year, the disease persists in around one quarter of patients. Overall therapeutic management in Spain conforms to current recommendations, except for an excessive duration of corticosteroids therapy.

To assess safety and efficacy of a 10% intravenous immunoglobulin in patients with primary immune thrombocytopenic purpura (ITP).

ITP patients in two multicenter studies (Trials A/B) were treated with 2 g/kg Flebogamma® 10% DIF (over 2-5 days) and were followed up to 1-3 months.

18 patients in Trial A and 58 in Trial B were enrolled (12 children in Trial B). The response rate (platelet count ≥50 × 109/l) was 72.2% (Trial A) and 76.1/100% (adults/children; Trial B). Most patients improved bleedings (83.3% Trial A; 88.9% Trial B). Potential treatment-related adverse events were reported by 38.9% (Trial A) and 30.4/83.3% (adults/children; Trial B) of patients. All serious adverse events (five patients) resolved without sequelae.

Flebogamma 10% DIF was effective and safe in patients with primary ITP.

The neurotrophin family is comprised of the structurally related secreted proteins nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophine-4 (NT-4). They bind and activate the tyrosine kinase receptors Trk A, B, and C in a ligand-specific manner and additionally bind a shared p75NTR receptor. The neurotrophins were originally defined by their ability to support the survival and maturation of embryonic neurons. However, they also control important physiological functions of the adult nervous system including learning and memory, sensation, and energy homeostasis. For example, NGF/trkA signaling is critical for normal and pathological sensation of pain. Likewise, the BDNF/trkB pathway controls feeding and metabolism, and its dysfunction leads to severe obesity. Antibodies can modulate neurotrophin signaling. Thus, NGF blocking agents can attenuate pain in several animal models, and a recombinant humanized NGF blocking antibody (Tanezumab) has shown promising results in human clinical trials for osteoarthritic pain. On the other hand trkB agonist antibodies can modulate food intake and body weight in rodents and nonhuman primates. The power of monoclonal antibodies to modulate neurotrophin signaling promises to turn the rich biological insights into novel human medicines.

This Phase III study examined the efficacy and safety of Rhophylac (CSL Behring AG, Bern, Switzerland), a highly pure, liquid-stable anti-D preparation, in chronic immune thrombocytopenic purpura (ITP).

Ninety-eight patients (96 adults, two adolescents) with chronic ITP and platelet counts < 30 x 10(9)/l received a single intravenous injection of 50 microg/kg bodyweight Rhophylac.

A response (defined as an increase in platelet count by >or= 20 x 10(9)/l to >or= 30 x 10(9)/l in the first 15 days after treatment) was seen in 66% of patients. Mean time to response was 3.1 +/- 3.0 days, and mean duration of response was 19.2 +/- 1.1 days for responders. The most frequent drug-related adverse events were chills, pyrexia, an increase in bilirubin, and headache; events were mainly mild or moderate. there was no severe hemolysis or renal failure.

rhophylac is well tolerated and efficacious in chronic itp.

Autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) associated with Evans syndrome; combination of autoimmune hemolytic anemia (AIHA) and immune thrombocytopenic purpura (ITP) has rarely been reported. We report the case of a 53-year-old patient who presented with weakness, myalgia, arthralgia, shortness of breath and purpura. Initial laboratory investigations revealed liver dysfunction, anemia and thrombocytopenia. Anti-nuclear (ANA) and antimitochondrial M2 (AMA M2) antibodies were positive. Diagnose of PBC-AIH overlap was made by clinical, serological and histological investigations. AIHA and ITP was identified with clinical-laboratory findings and bone marrow puncture. She was treated with IVIG followed by prednisolone and ursodeoxycholic acid. Hemoglobin-thrombocytes increased rapidly and transaminases improved at day 8. We have reported the first case in the literature with AIH-PBC overlap syndrome concurrent by ITP and AIHA which suggest the presence of shared genetic susceptibility factors in multiple autoimmune conditions including AIH, PBC, ITP and AIHA.

The goal of this study is to develop a flow cytometric immunobead array (FCIA) assay to detect platelet autoantibodies commonly present in bleeding patients with immune thrombocytopenic purpura (ITP).

Polystyrene microbeads coated with antibodies against human platelet glycoproteins (GPs) IX (SZ1), Ib (SZ2), IIIa (SZ21), IIb (SZ22), and P-selectin (SZ51) were incubated with platelet lysate from 50 ITP patients and 86 controls. The platelet antigen-autoantibody complexes were detected by flow cytometry using an FITC-labeled antibody. The results were compared with that of a monoclonal antibody immobilization of platelet antigen (MAIPA) assay.

By FCIA, platelet autoantibodies against GPIb, GPIIb, GPIIIa, GPIX and P-selectin were detected in ITP patients. Mean fluorescent intensity values with antibodies SZ1, SZ2, SZ21, SZ22 and SZ51 were all higher in ITP patients than controls (p values<0.01). In ROC analysis, values of the area under the curve were 0.89, 0.82, 0.93, 0.94 and 0.95, respectively. In ITP diagnosis, the FCIA assay with these five antibodies had better sensitivity and accuracy than the MAIPA assay (96% vs. 44% in sensitivity; 80.9% vs. 64.7% in accuracy, p<0.01).

FCIA assays with multiple antibodies against platelet GPs may be used to improve the diagnosis of ITP in hospitals.

Splenectomy is considered the second-line of treatment in patients with chronic primary immune thrombocytopenia (ITP) in whom glucocorticoids have failed. Some patients do not respond to splenectomy or they have postoperative complications. Based on our previous experience using kinetic and scintigraphic parameters, we did a retrospective study with the aim of comparing all these parameters as a means of predicting the success of splenectomy in persistent and chronic primary ITP. Forty-one consecutive patients with chronic primary ITP refractory to prednisone, who had been splenectomized, were included in the study. The response to splenectomy was assessed by evaluating bleeding and platelet counts before and at different times after surgery. A complete platelet kinetic study was performed before the splenectomy using autologous (111) In-labeled platelets. The scintigraphic parameters measured included different indices between spleen/heart, liver/hearth, and spleen/liver. Thirty-six patients gave a complete response after splenectomy and five patients did not respond. A statistically significant difference between both groups was found with initial platelet recovery and with some scintigraphic indices which also showed a variable prediction value for the success of splenectomy. Among these indices, the spleen/liver at 30 minutes demonstrated a predictive value with a 100% of sensitivity and a 100% of specificity.

some platelet kinetic parameters and scintigraphic indices, in particular the spleen/liver at 30 minutes, were useful to predict the outcome of splenectomy in persistent and chronic primary ITP and, therefore, they should be taken into account when deciding whether or not to perform a splenectomy.

Autoimmune hematological disorders encompass a broad group of hematological conditions characterized by the loss of self-tolerance to a variety of antigens. Despite good response to first-line therapy in the majority of patients, relapses are common, necessitating new and safe therapeutic options. The anti-CD20 monoclonal antibody rituximab has led to substantial improvement in the treatment of malignant and immune-mediated disorders involving B cells. Although experience with rituximab in immune-mediated hematological disorders is rarely supported by randomized trials, there is now substantial experience with rituximab suggesting that anti-CD20 therapy is an effective and well-tolerated alternative to immunosuppressive therapy in these disorders. However, caution is needed based on recent reports describing-sometimes severe-rituximab-related complications.

Immune thrombocytopenic purpura (ITP) is an immunomediated disease characterized by a decrease in platelet count and, in its more severe forms, by bleeding symptoms. Many drugs have been implicated in the pathogenesis of drug-induced thrombocytopenia in adults; only limited data on drug-related ITP in children have been published. Our study was set up to evaluate the consistency of the association between drug and vaccine use and ITP in children. This study is part of an Italian multicentre study on adverse drug reactions in children, coordinated by the Italian National Institute of Health, which was started in November 1999 and is ongoing. The study was conducted by enrolling all children aged more than 1 month who were hospitalized through the paediatric emergency department for the following conditions: thrombocytopenia (platelet count <100 x 103/L); acute neurological disorders; non-infectious mucocutaneous diseases and vasculitis; and endoscopically confirmed gastroduodenal lesions and/or clinically defined haematemesis and melaena. Children with chronic pathologies or concomitant diagnoses of cancer or immunodeficiency were not included in our study. During hospital admission, a physician interviewed parents using a structured questionnaire. The main aim of the interview was to collect information on drug exposure in a time period of 3 weeks and vaccine exposure in a period of 6 weeks preceding hospitalization. Using a case-control study design, exposure of children with thrombocytopenia (cases) to drugs and vaccines was compared with similar exposure of children with gastroduodenal lesions and neurological disorders (controls); this allowed us to estimate the odds ratios (ORs) of the occurrence of thrombocytopenia associated with the use of drugs or vaccines. Up to December 2007, the study population included 387 cases of thrombocytopenia and 1924 controls. Despite the low platelet count, ITP was generally a mild disease, without serious bleeding in the majority of cases and associated with a short length of hospital stay. After adjusting for concurrent use of other drugs, use of the antibacterials was associated with a more than 2-fold increase in the risk of developing ITP (OR 2.4; 95% CI 1.8, 3.1). Mucolytics and NSAIDs were associated with an OR of 1.9; 95% CI 1.2, 2.9 and 1.5; 95% CI 1.0, 2.1 respectively, while paracetamol (acetaminophen) was associated with an OR of 1.5; 95% CI 1.2, 2.0. MMR vaccination was associated with an increased risk of developing ITP (OR 2.4; 95% CI 1.2, 4.7). The results of this study provide evidence for an association between ITP and exposure to selected antibacterials, NSAIDs, paracetamol, mucolytics and MMR vaccination.

Inflammatory reactions of the spleen occur in the context of two pathophysiological settings. First, lymphoid hyperplasia of the spleen can be the result of a principally physiological production of immune effector cells e.g. due to systemic viral infections, autoimmune diseases and acquired or inherited immunodeficiencies. Second, the spleen itself may be the target of a pathological inflammatory reaction; this setting is exemplified by abscess formation due to septicopyemic spread of bacteria and by granulomatous inflammations, e.g. due to tuberculosis or sarcoidosis. Differential diagnostic considerations have to include splenic inflammatory pseudotumors, mycobacterial spindle cell tumors and lymphomas with granulomatous or histiocyte-rich reactive changes.

A 58-year-old Japanese woman presented with chronic fluctuating liver dysfunction with purpura. Raynaud's phenomenon had been diagnosed 4 years previously. At the initial examination, skin biopsy showed limited cutaneous systemic sclerosis (SSc). Laboratory investigations revealed liver dysfunction. Anti-nuclear antibodies, anti-mitochondria M2 antibody, anti-thyroglobulin antibody, and platelet-associated IgG were positive. Primary biliary cirrhosis (PBC) and autoimmune hepatitis (AIH) were diagnosed serologically, clinically and histologically. Immune thrombocytopenic purpura (ITP) was diagnosed by bone marrow puncture, clinical and laboratory findings, and Helicobacter pylori IgG was positive. She was treated with prednisolone 30 mg/day, ursodeoxycholic acid 600 mg/day, and a 7-day course of lansoprazole plus amoxicillin and clarithromycin. Thrombocytes increased rapidly and transaminase improved at day 7. We report a rare case of PBC-AIH overlap syndrome with concurrent ITP and SSc which suggest the presence of shared genetic susceptibility factors in multiple autoimmune conditions including PBC, AIH, ITP and SSc.

In recent years, there has been a tremendous increase in the number of clinical studies with monoclonal antibodies and small molecules in the treatment of hematological malignancies. Clinical observations have shown that some of these molecules may also aid in the treatment of immune-mediated hematological disorders. Moreover, immunotherapy has become an important treatment cornerstone in other, non-hematological, auto-immune diseases. This paper reviews the current state of the use of these new molecules in the treatment of the most frequently encountered immune-mediated hematological disorders: auto-immune hemolytic anemia (AIHA), idiopathic thrombocytopenic purpura (ITP), and thrombotic thrombocytopenic purpura (TTP).

Transplantation-mediated alloimmune thrombocytopenia (TMAT) is donor-derived thrombocytopenia following solid-organ transplantation. To date, no clear consensus on the appropriateness of organ utilization from cadaver donors with a history of idiopathic thrombocytopenia purpura (ITP) has emerged. Herein is reported a devastating case of TMAT following liver transplantation utilizing an allograft from a donor with ITP that resulted in allograft failure. The literature is reviewed in this context to propose preliminary guidelines regarding utilization of allografts from cadaver donors with a history of ITP.

Rituximab, a monoclonal chimeric antibody to the CD20 antigen, is an effective treatment for non-Hodgkin lymphomas. Moreover, rituximab has also shown efficacy in various autoimmune disorders. In this review, we will focus on the use of rituximab in childhood disorders of hemostasis associated with inhibitor formation. Although the results presented suggest that rituximab can be useful in the treatment of this subset of pediatric patients, most of the data come from isolated case reports or descriptions of small, uncontrolled series. Therefore, large, prospective, and randomized trials are needed to confirm the positive, preliminary results.

To evaluate the efficacy and safety of treatment with rituximab in patients presenting autoimmune thrombocytopenic purpura and haemolytic anaemia.

A check was carried out of the medical records of the patients starting treatment with rituximab for compassionate use in 2004 at doses of 375 mg/m2 per week for 4 weeks. The rate of patients achieving full response in accordance with the best criteria found in the bibliography was assessed. All adverse reactions described in the medical records were gathered.

Six patients with thrombocytopenic purpura were candidates for treatment. Five began treatment, four of them completed treatment, and three of these patients achieved full response. This response was achieved at different times and was sustained for at least six months. Two patients with autoimmune haemolytic anaemia were treated and both achieved full response again at different times and in this case, it was sustained for at least 8 months. One patient suffered mild adverse reactions to treatment.

Rituximab is a new perspective for the treatment of refractory autoimmune cytopenias, and has a good safety profile.

To search for novel mechanisms that contribute to the pathophysiology of idiopathic thrombocytopenic purpura (ITP), we determined the whole blood gene expression profile in five ITP patients and five control samples. Using DNA microarrays that contained 24,473 unique putative genes, we found 176 cDNAs that were strongly correlated with ITP. These included a cluster of interferon-regulated genes and TLR7, as well many less-well characterized genes which are candidates for further study. We believe this approach is likely to yield new insights into our understanding of the molecular pathophysiology of ITP.

Autoimmune thrombocytopenia is a disorder characterized by antibody-mediated accelerated platelet destruction. Despite its clinical importance, the diagnosis of which is one of exclusion, thus inevitably associated with potential difficulties. Current methods used to determine antigen-specific antibodies including MAIPA and the radioactive immunobead assay, are not routinely used due to methodological and practical limitations. To facilitate diagnosis, flow cytometric methods have been developed, suitable for testing a single or multiple samples. The feasible flow cytometric methods with their high sensitivity and specificity should facilitate the routine use of diagnostic methods for autoimmune thrombocytopenia and permit follow-up to determine immune remission.

We proposed diagnostic criteria for immune thrombocytopenic purpura (ITP) by modifying the existing guidelines for diagnosis of ITP and by incorporating laboratory tests found useful for predicting its diagnosis, for example erythrocyte count, leukocyte count, anti-GPIIb/IIIa antibody-producing B cells, platelet-associated anti-GPIIb/IIIa antibodies, percentage of reticulated platelets, and plasma thrombopoietin.

To validate our criteria, we conducted a multi-center prospective study involving 112 patients with thrombocytopenia and a morphologically normal peripheral blood film at the first visit. Each patient underwent a physical examination, routine laboratory tests, and specialized tests for the anti-GPIIb/IIIa antibody response and platelet turnover.

Ninety-one patients (81%) satisfied the proposed criteria at first visit. Clinical diagnosis was made by skilled hematologists > 6 months after the first visit; ITP was diagnosed in 88 patients and non-ITP disorders in 24. The proposed criteria had 98% sensitivity, 79% specificity, a 95% positive predictive value, and a 90% negative predictive value. A relatively low specificity appears to be attributed to a few patients who had both ITP and aplastic anemia or myelodysplastic syndrome.

Our preliminary diagnostic criteria based on ITP-associated laboratory findings were useful for the differential diagnosis of ITP, but additional evaluations and modifications will be necessary to develop criteria that can be used routinely.

In immune thrombocytopenic purpura (ITP), thrombocytopenia is a result of both increased platelet destruction and insufficient platelet production. In adults, the course is commonly chronic, but most patients never experience serious bleeding even with severe thrombocytopenia. In case series of consecutive adult patients identified at the time of diagnosis, the frequency of death from bleeding is low, < 1%. The goal of treatment is only to prevent bleeding, not to correct the platelet count to normal. All current treatments are designed to diminish the increased platelet destruction, either by immunosuppression or splenectomy. The frequency of death from complications of treatment is similar to the frequency of death from bleeding. Perhaps because of increasing recognition of both the infrequent occurrence of serious bleeding and the risks of immunosuppressive treatment and splenectomy, data from case series across the past 30 years suggest a trend toward less therapy and fewer splenectomies among patients with ITP. However treatment is necessary for patients with severe and symptomatic thrombocytopenia. Splenectomy remains the most effective treatment for ITP, with two-thirds of patients achieving durable complete remissions. Immunosuppressive agents, including rituximab and combinations of agents, may be less effective than splenectomy in achieving complete remissions and the remissions may also be less durable. New agents for patients with ITP are currently in development that enhance platelet production, rather than diminish platelet destruction. In preliminary reports, these agents have been effective in maintaining safe platelet counts in patients with chronic ITP that was refractory to splenectomy and other treatments.

Thrombocytopenia is common among liver transplant candidates and recipients. The aim of our study was to determine the incidence and outcome of new-onset immune-mediated thrombocytopenic purpura (ITP) following liver transplantation at a single center. Among the 256 liver transplant recipients with an International Classification of Diseases, Ninth Edition code for thrombocytopenia, 8 cases of new-onset ITP were identified, leading to an overall incidence of 0.7% in 1,105 consecutive liver transplant recipients over a 15-year period. All 8 patients were Caucasian, 5 (63%) were male, and the median age at ITP onset was 54 years (range, 15-63). The median platelet count at presentation was 3,500 cells/mL (range, 1,000-12,000) and liver disease was due to hepatitis C (38%), primary sclerosing cholangitis (38%), and cryptogenic cirrhosis (25%). The median time from transplant to ITP onset was 53.5 months (range, 1.9-173). Three of the 6 patients tested (50%) had cell-bound antiplatelet antibodies, 1 patient had an underlying hematological malignancy, and none of the organ donors had a history of ITP. Corticosteroids and/or immunoglobulin infusions were effective in 4 patients. However, serial rituximab infusions were required in 4 patients with persistent thrombocytopenia, and 3 of them eventually required splenectomy to induce disease remission. At a median follow-up of 19.7 months, 7 long-term survivors remain in remission with a median platelet count of 267,000 cells/mL. In conclusion, new-onset ITP is an infrequent but important cause of severe thrombocytopenia in liver transplant recipients. Corticosteroids and immunoglobulin infusions were effective in 50% while the remainder of patients required rituximab infusions or eventual splenectomy for long-term disease remission.

Laparoscopic splenectomy has become widely accepted as the approach of choice for the surgical treatment of benign and malignant hematologic diseases. Advances in technology have led to better outcomes for the procedure, and have allowed surgeons to apply the technique to disease processes that were at one time felt to be contraindications to laparoscopic splenectomy. However, challenges still remain. There is a steep learning curve associated with the procedure. The development of cost-effective laparoscopic simulators to target the skills required for laparoscopic splenectomy and other laparoscopic procedures is essential. The advent of devices which isolate and seal the large blood vessels that surround the spleen have reduced intra-operative bleeding and minimized conversions to open splenectomy. Improvements in optics and instrumentation, as well as robotic technology, will continue to define the frontier of minimally invasive surgery, and further facilitate the acceptance of laparoscopic splenectomy for the treatment of benign and malignant hematologic diseases.