Immune-related Thrombocytopenia Research Articles

A single-arm phase II study of platinum doublet induction chemotherapy combined with toripalimab for driver gene-negative advanced NSCLC.

e20565 Background: PD-1/PD-L1 inhibitors combined with platinum doublet chemotherapy have become the standard first-line treatment for driver gene-negative advanced non-small cell lung cancer (NSCLC). However, not all patients can benefit from this treatment. Previous studies have shown that induction chemotherapy can reduce tumor burden, induce tumor immunogenic cell death, and improve the tumor immune microenvironment. Therefore, effective induction chemotherapy may enhance the efficacy of PD-1/PD-L1 immunotherapy. This single-arm, phase II clinical trial aims to evaluate the efficacy and safety of induction chemotherapy followed by immunotherapy (Toripalimab: PD-1 inhibitor) in treatment of driver gene-negative advanced NSCLC. Methods: Eligible patients received platinum doublet chemotherapy for 2-4 cycles (pemetrexed + platinum for adenocarcinoma; paclitaxel or gemcitabine + platinum for squamous cell carcinoma). patients who achieved tumor response (CR/PR/SD) received Toripalimab (240mg Q3W) for 2 years or until disease progression or intolerable toxicity. The primary endpoint was progression-free survival (PFS), which was defined as the duration from the initiation of induced chemotherapy to either tumor progression or death from any cause,and the secondary endpoints were toxicity, overall survival (OS), and clinical tumor response including objective response (defined as complete [CR] or partial response [PR]) and disease control (defined as CR, PR, or stable disease [SD]) during the course of combination treatment with Toripalimab following induction chemotherapy. Results: During the period from February 2020 through October 2023, a total of 19 qualified patients were enrolled in the study. As of December 31. 2023,the median follow-up was 22,9 months (range,15.9 to 30 months).11 patients (57.9%) experienced PFS events and 7 (36.8%) died, mOS were not reached. mPFS was 7.9 mo (95% CI,4.8-15.0months).12-month and 18-month PFS rate were 43% and 35%, respectively. One patient has not received tumor response assessment. Among the remaining 18 pts, 10 patients had a PR,5 patients had SD, and 3 patients had PD. The ORR and DCR were 55.6% and 83.3% respectively.42.1% (8/19) pts experienced immune-related adverse events(irAEs), included immune-related pneumonia (21.1%), rash (10.5%), hypothyroidism (10.5%). 2 pts experienced ≥3 grade irAEs, including grade 3 rash and grade 4 immune-related thrombocytopenia. Conclusions: Induction chemotherapy combined with Toripalimab achieved impressive 12-month and 18-month PFS rates in pts with driver gene-negative advanced NSCLC, along with manageable toxicities. These findings demonstrate the potential of induction chemotherapy could enhance the efficacy of immunotherapy. Clinical trial information: NCT04613804 .

Effect of reducing the number of neoadjuvant chemoimmunotherapy cycles on clinical efficacy in locally advanced PD-L1 positive gastric cancer: A single center phase 2 study.

e16074 Background: The standard therapeutic recommendation is neoadjuvant chemotherapy with FLOT regimen following radical resection in patients with locally advanced gastric cancer. It is not clear whether neoadjuvant anti-PD-1 antibody plus FLOT regimen could improve the pathological complete response (pCR) rate and how to combine anti-PD-1 antibody and FLOT regimen. We conduct this phase II study to explore this problem (NCT 04891016). Methods: This study is a prospective clinical study, patients are randomly enrolled into the experiment group and the control group according to the random number method. The patients in the experiment group receive standard dose of FLOT regimen plus toripalimab every three weeks, toripalimab is administered on third day in each cycle, after three cycles operation is performed. The patients in the control group receive standard dose of FLOT regimen plus toripalimab every two weeks, toripalimab is administered on the first day in each cycle, after four cycles operation is performed. The primary endpoint is pCR and the secondary endpoint is recurrence-free survival. Results: From June 2021 until present, 57 patients with locally advanced gastric cancer were enrolled in this study, including 28 patients in the experiment group and 29 in the control group. Three patients in the experiment group and two in the control group withdrew from the study as to the influence of COVID-19’s epidemic or personal reason. One patient in the experiment group postponed operation due to immune-related thrombocytopenia. The remaining 51 patients completed the prescribed chemotherapy plus toripalimab and operation, and all the operations were R0 resection. Among these 51 patients, pCR was got in 16 patients and the pCR rate was 31.4%, MPR rate was 66.7%. Further analysis according to the expression of PD-L1 is shown. The overall incidence of adverse events was 93%. The incidence and severity of myelosuppression in the experiment group were lower than those in the control group. Among all the patients received R0 resection, 6 patients experienced recurrence and the remaining are still kept in recurrence-free status. The recurrence-free survival is not available at present. Conclusions: 1) Neoadjuvant therapy with FLOT plus toripalimab is safe and effective in locally advanced gastric cancer. 2) Postponing the use of toripalimab when combined with FLOT as neoadjuvant regimen in locally advanced gastric cancer patients with PD-L1 CPS ≥1 could reduce the number of chemotherapy cycles and thus reduce the adverse events of chemotherapeutic drugs, while the dose intensity of chemotherapy is import in patients with PD-L1 CPS ＜1. Clinical trial information: NCT04891016 .[Table: see text]

Case report: combination of immune-related thrombocytopenia and myocarditis in а patient treated with immune checkpoint inhibitors for non‑small cell lung cancer

Immune-related adverse events (irAE) present a unique challenge in modern oncology. In patient treated with immune checkpoint inhibitors (anti-PD-1, anti-CTLA-4, anti-PD-L1) for solid tumors irAEs rate ranges from 60 to 85 % [1]. irAEs lead to complete treatment discontinuation in approximately 40 % of patients [2]. The most common irAEs are endocrinopathies (up to 10 %), pneumonitis (5 to 10 %), autoimmune hepatitis (up to 20 %), colitis (up to 30 %), and skin toxicity (up to 50 %) [3]. Other forms of adverse events, such as hematologic and cardiovascular toxicities, are very rarely reported. We present a clinical case of two rare adverse events in a patient treated with pembrolizumab for PD-L1‑positive advanced non-small cell lung cancer.

Selection of Automated Platelet Counting Methods Based on Mean Platelet Volume (MPV).

Impedance-based detection and optic detection with fluorescence are common platelet counting methods used by modern hematology analyzers. There are few studies to compare the accuracy of platelet counts using these methods in case of increased MPV. Sixty patients with immune-related thrombocytopenia (IRTP) and 60 healthy controls were included. Platelet counts were obtained by BC-6900 analyzer using impedance detection (PLT-I) and optic detection with fluorescence (PLT-O). Flow cytometry was used as the reference (FCM-ref). The platelet counts in patients using PLT-I were significantly lower than those using PLT-O or FCM-ref by an average of 13.3%. The platelet counts by PLT-O compared to FCM-ref were not statistically significant. MPV inversely affected the platelet counts. When MPV was < 13 fL, platelet counts by all three methods were not statistically different. When MPV was ≥ 13 fL, platelet counts by PLT-I were significantly lower (-15.8%) than those by PLT-O or FCM-ref. Furthermore, when MPV was ≥ 15 fL, platelet counts using PLT-I were further decreased (-23.6%) compared to the counts obtained by PLT-O or FCM-ref. The platelet counts by PLT-O in patients with IRTP is as accurate as by FCM-ref. When MPV is < 13 fL, platelet counts by all three methods are comparable. However, when MPV is ≥ 13 fL, platelet counts by PLT-I can erroneously decrease by as many as 23.6%. Therefore, in case of IRTP, or any cases when MPV ≥ 13 fL, platelet counts obtained by PLT-I method should be carefully checked by other methods, such as PLT-O to ensure a more accurate platelet count.

Immune checkpoint inhibitor-related thrombocytopenia: incidence, risk factors and effect on survival

IntroductionImmune checkpoint inhibitors (ICI) are associated with unique immune-related adverse events (irAEs). Immune-related thrombocytopenia (irTCP) is an understudied and poorly understood toxicity; little data are available regarding either risk of irTCP or the effect of irTCP on clinical outcomes of patients treated with ICI.MethodsWe conducted a retrospective review of sequential cancer patients treated with ICI between 2011 and 2017 at our institution. All patients who received ICI alone or in combination with other systemic therapy in any line of treatment were included; those with thrombocytopenia ≥ grade 3 at baseline were excluded. We calculated the incidence of ≥ grade 3 irTCP and overall survival (OS). Patient factors associated with irTCP were assessed.ResultsWe identified 1,038 patients that met eligibility criteria. Overall, 89 (8.6%) patients developed grade ≥ 3 thrombocytopenia; eighteen were attributed to ICI (1.73% overall). Patients who developed grade ≥ 3 irTCP had worse overall survival compared to those whose thrombocytopenia was unrelated to ICI (4.17 vs. 10.8 month; HR. 1.94, 95% CI 1.13, 3.33; log-rank p = 0.0164). Patients with grade ≥ 3 irTCP also had worse survival compared to those without thrombocytopenia (4.17 vs. 13.31 months; HR 2.22, 95% CI 1.36, 3.62; log-rank p = 0.001). The incidence of irTCP appeared lowest among those treated with PD-1/L1 monotherapy (p = 0.059) and was not associated with cancer type, smoking status, age, gender, race, or line of therapy.ConclusionsUnlike other irAEs, we found that irTCP was associated with worse overall survival. The incidence of irTCP appeared lowest among those treated with PD-1/L1 monotherapy.

Immune checkpoint inhibitor-related thrombocytopenia: Incidence, risk factors, and effect on overall survival.

e14549 Background: Immune checkpoint inhibitors (ICI) are a standard of care therapy for patients with many different cancers. ICI are generally well tolerated but are associated with unique immune-related adverse events (irAEs). Immune-related thrombocytopenia (irTCP) is an understudied and poorly understood toxicity and risk factors for irTCP are unknown. Although other irAE have been associated with clinical benefit, little data is available regarding either risk of irTCP or the effect of irTCP on clinical outcomes of patients treated with ICI. Methods: We conducted a retrospective review of sequential patients with any solid or hematologic cancer treated with ICI between 2011 and 2017 at The Ohio State University Comprehensive Cancer Center. All patients who received ICI alone or in combination with other systemic therapy in any line of treatment were included; those with thrombocytopenia ≥ grade 3 at baseline were excluded. Thrombocytopenia grading was performed utilizing the Common Terminology Criteria for Adverse Events version 5.0. Attribution to ICI was defined as timing after ICI initiation, lack of alternative causes, and improvement with either holding treatment or use of immune suppressive therapy. Overall survival (OS) was calculated from the date of initiation of ICI to death from any cause or date of the last follow-up examination. Cox proportional hazard models were used to examine the associations between platelet categories with OS. Median OS was estimated using Kaplan-Meier method with 95% CI. Results: We identified 1,038 patients treated with ICI therapy after excluding patients with baseline thrombocytopenia. The median age was 61.4; 613 (59.1%) were male and 613 (59.1%) had history of smoking. The most common cancer types were melanoma (n = 337, 32.5%), lung (n = 213, 20.5%), and renal cell carcinoma (n = 114, 11%). The most common ICI were PD1/L1 (n = 729, 70.2%) and CTLA4 (n = 191, 18.4%). Overall, 89 (8.6%) patients developed grade ≥3 thrombocytopenia; twenty were attributed to ICI (1.93% overall). Patients who developed ≥3 irTCP had worse overall survival compared to those whose thrombocytopenia was unrelated to ICI (5.45 vs 11.3 months; HR. 2.077, 95% CI 1.231, 3.503; log-rank p = 0.005). Patients with ≥3 irTCP also had shorter survival compared to those without thrombocytopenia of any etiology (5.45 vs 13.3 months; HR 2.247, 95% CI: 1.414, 3.571; p &lt; 0.001). irTCP was more common among those treated with PD1/L1 (p = 0.03) but was not associated with cancer type, smoking status, age, gender, race, or line of therapy. Conclusions: Type of immunotherapy is related to irTCP, whereas cancer type and line of therapy are not. Unlike other irAEs, we found that irTCP was associated with shorter overall survival. These findings provide important insight into a poorly understood and rare toxicity. irTCP should be evaluated in more extensive studies to better inform clinical decision making.

Nivolumab-related severe thrombocytopenia in a patient with relapsed lung adenocarcinoma: a case report and review of the literature

BackgroundImmune checkpoint inhibitor therapy has changed the standard drug therapy for relapsed or advanced non-small cell lung cancer; its efficacy is well-recognized by pulmonary physicians, oncologists, and thoracic surgeons. Nivolumab, one of the anti-programmed cell death 1 antibodies, was the first immune checkpoint inhibitor to be approved and is used as a standard second-line regimen for patients with non-small cell lung cancer irrespective of the expression of programmed cell death ligand 1. Programmed cell death 1 antibodies have been generally confirmed to be less toxic than conventional cytotoxic chemotherapy, although unusual immune-related adverse events such as type I diabetes mellitus, adrenal failure, and myasthenia gravis may occur with a very low incidence. A case of severe grade V immune-related thrombocytopenia after two courses of nivolumab as second-line therapy for relapsed non-small cell lung cancer is reported.Case presentationAn 82-year-old Japanese woman with relapsed lung adenocarcinoma was treated with nivolumab as second-line systemic therapy at our institute. Her laboratory data indicated thrombocytopenia suspected to be an immune-related adverse event following two courses of nivolumab. Subsequently, she developed a massive pulmonary hemorrhage and left cerebral infarction despite intensive treatment including systemic steroid therapy. Although there have been a few reports of thrombocytopenia caused by nivolumab, this is the first report of grade V thrombocytopenia following administration of nivolumab for relapsed non-small cell lung cancer.ConclusionA very difficult case of grade V immune-related thrombocytopenia after the administration of nivolumab as second-line therapy for relapsed lung adenocarcinoma was described. Immune-related thrombocytopenia is a rare adverse event, but it must be considered a possible complication because it may become critical once it has occurred.

Clinical usage of intravenous immunoglobulin in neonates in a tertiary care centre: a retrospective observational study

Background: Intravenous Immunoglobulin (IVIG) is a blood product manufactured from pooled plasma. With increasing availability, an increased usage in neonates is being noted, though its utilisation has not been audited thoroughly. The objectives of this study are to describe the usage pattern and indications of IVIG and its outcome in a state-run tertiary care NICU.Methods: This retrospective observational study was carried out at the inborn unit of Department of Neonatology, Madras Medical College, Chennai on a cohort of neonates who received IVIG over 3.5 years from January 2016 to June 2019. Data was collected from drug register, neonatal case records, exchange transfusion register and death register.Results: Our study cohort had 55 neonates who received IVIG over 3.5 years. Indications for IVIG usage were Rh-alloimmunisation (23), ABO-alloimmunisation (7), prophylaxis of perinatal varicella (20), and other immune thrombocytopenia (5). Among 30 neonates with ABO-/Rh-incompatibility, 11 required exchange transfusion (ET). ET rates have shown a decreasing trend during this period. 2 babies with Rh-immunisation and Hydrops expired. None of the babies given prophylaxis for perinatal varicella manifested the disease. Neonates treated for immune thrombocytopenia were successfully discharged.Conclusions: This study shows the IVIG usage pattern in a tertiary care neonatal unit. In neonates with Hemolytic disease due to Rh-/ABO-alloimmunisation treated with IVIG, a reduction in rates of exchange transfusion has been noted. IVIG is being used increasingly for prophylaxis of perinatal varicella and immune related thrombocytopenia with promising benefits. It is prudent to have SOPs for IVIG administration with standardised issue and transfusion forms for documentation to regulate its judicious use.

A single-center investigational study of CD36 antigen deficiency and platelet alloantibody distribution in different populations in Northern China as well as platelet alloantibodies effect on pregnancy

BackgroundPlatelet antibodies can lead to clinical diseases such as platelet transfusion refractoriness (PTR), fetal/neonatal alloimmune thrombocytopenia (FNAIT), etc. This study is aimed at understanding CD36 expression, platelet alloantibody distribution in different populations in Northern China, and effects of platelet alloantibodies on pregnancy. Study design and methodsWhole blood samples of 612 subjects including hematological patients, pregnant women, and blood donors were collected at a single center, then CD36 expressions were determined, followed by platelet antibody screening and characterization of platelet antibody specificity. A retrospective analysis was performed in 1552 pregnant women admitted to Department of Obstetrics, in order to investigate FNAIT occurrence. ResultsRate of CD36 deficiency expression was 2.12% (13/612), all cases exhibited type II deficiency without type I deficiency being detected, and such rate is lower than that in Southern China (3.43%), Japanese (4.87%) and in the black people (4.18%), and higher than that in the White people (0.09%). Positive rates of platelet antibody screening in hematological patient group (6.86%, 14/204) and in pregnant women group (6.31%, 13/206) are higher than that in blood donor group (0.49%, 1/202), P < .01. Out of 1552 pregnant women, there were not children with FNAIT. ConclusionThe frequency of CD36 deficiency in northern China was low, all of them were type II deficiency, and no CD36 antibody was detected. It is speculated that the risk of immune-related thrombocytopenia caused by CD36 deficiency in this population is very low. Platelet antibodies should be monitored early in patients with hematological and multiple miscarriages pregnant.

Hematological Side Effects of Immune Checkpoint Inhibitors: The Example of Immune-Related Thrombocytopenia.

Immune-related hematological adverse events are amongst the rare but potentially life-threatening complications of immune checkpoint inhibitors. The spectrum of these toxicities is broadening as the number of patients exposed to these agents is increasing. Yet, they are still relatively unknown to many clinicians, possibly due to a lack of specific diagnostic criteria, which poses a challenge for their recognition and proper reporting, and partly due to their low incidence, often too low to be noted in most clinical trial publications. Since early detection and prompt intervention are crucial to prevent fatal consequences, it is of outmost importance that medical staff and patients be aware of these potential toxicities and learn to recognize and treat them adequately. This publication outlines strategies and offers guidance on the detection, diagnosis, risk assessment, monitoring and management of immune-related thrombocytopenia, a relatively common example of immune-related hematological toxicity of immune checkpoint inhibitors.

Integrin GPIIIa49-57 is the pivotal switch controlling platelet fragmentation

Unique autologous antibodies (Abs) against platelet integrin GPIIIa49-66 (CAPESIEFPVSEARVLED) have been detected in patients with HIV-1 immune-related thrombocytopenia (HIV-1-ITP), which is capable of inducing complement-independent platelet fragmentation through reactive oxygen species (ROS) release. However, the efficiency of inducing platelet fragmentation is inconsistent among the different patient Abs or similar rabbit polyclonal Abs against the region and the reason remains unclear. In this study, we developed a batch of murine monoclonal antibodies (mAbs) against different locus of GPIIIa49-66 region by hybridoma technology. All these mAbs are capable of binding to human platelets. Among these mAbs, clones 1E7 and 5A10 were identified to target the epitope of GPIIIa49-57 (CAPESIEFP, named P1); clones 1C1 and 1E5 target GPIIIa57-64 (PVSEARVL, named P2), and clones 4D5 and 5F8 target GPIIIa59-66 (SEARVLED, named P3). By incubation of human platelets with these mAbs, the platelet fragmentation induced by mAbs against P1 was 5–6 folds higher than that by the control mAb (6-fold for 5A10 and 5.6-fold for 1E7). However, platelet fragmentation induced by mAbs against P2 (1C1) and P3 (5F8) was only 1.9- and 1.1-fold higher than that by the control mAb, respectively. Thus, our data demonstrate that platelet integrin GPIIIa49-57 is the pivotal switch controlling platelet fragmentation.

A Humanized Single-Chain Variable Fragment Antibody Against Beta3 Integrin in Escherichia coli

Patients with HIV-1 immune-related thrombocytopenia (HIV-1-ITP) have a unique antibody (Ab) against platelet GPIIIa49-66, which is capable of inducing oxidative platelet fragmentation in the absence of complement activation. By screening a human phage antibody library with the GPIIIa49-66 peptide as bait, we have developed several humanized phage Abs, which act similarly to the parental Ab. However, the presence of a stop codon in the heavy chain of the obtained phage clones limits their expression in soluble recombinant form. To circumvent this problem, we mutated the stop codon inside clone 11 that exhibits the highest binding activity to platelet GPIIIa49-66, resulting in a soluble scFv format (named A11) in Escherichia coli Rosseta. In in vitro binding assay, A11 exhibited similar binding specificity to parental Ab at various concentrations. Moreover, A11 is able to induce oxidative platelet fragmentation by preferentially binding to activated versus resting platelets. These findings provide a proof-of-principle for the development of a novel approach to inhibit arterial thrombosis by generating a selective scFv for the lysis of platelet-rich thrombi.

Dissolution of arterial platelet thrombi in vivo with a bifunctional platelet GPIIIa49-66 ligand which specifically targets the platelet thrombus

AbstractPatients with HIV-1 immune-related thrombocytopenia have a unique antibody (Ab) against integrin GPIIIa49-66 capable of inducing oxidative platelet fragmentation via Ab activation of platelet nicotinamide adenine dinucleotide phosphate oxidase and 12-lipoxygenase releasing reactive oxygen species. Using a phage display single-chain antibody (scFv) library, we developed a novel human monoclonal scFv Ab against GPIIIa49-66 (named A11) capable of inducing fragmentation of activated platelets. In this study, we investigated the in vivo use of A11. We show that A11 does not induce significant thrombocytopenia or inhibit platelet function. A11 can prevent the cessation of carotid artery flow produced by induced artery injury and dissolve the induced thrombus 2 hours after cessation of blood flow. In addition, A11 can prevent, as well as ameliorate, murine middle cerebral artery stroke, without thrombocytopenia or brain hemorrhage. To further optimize the antithrombotic activity of A11, we produced a bifunctional A11-plasminogen first kringle agent (SLK), which homes to newly deposited fibrin strands within and surrounding the platelet thrombus, reducing effects on nonactivated circulating platelets. Indeed, SLK is able to completely reopen occluded carotid vessels 4 hours after cessation of blood flow, whereas A11 had no effect at 4 hours. Thus, a new antithrombotic agent was developed for platelet thrombus clearance.

The pathology of bone marrow failure

An important indication for bone marrow investigation is the presence of bone marrow failure, which manifests itself as (pan)cytopenia. The causes of cytopenia are varied and differ considerably between childhood and adulthood. In the paediatric age group inherited bone marrow failure syndromes are important causes of bone marrow failure, but they play only a minor role in later life. This review gives a comprehensive overview of bone marrow failure disorders in children and adults. We classified the causes of bone marrow failure according to the main presenting haematological abnormality, i.e. anaemia, neutropenia, thrombocytopenia or pancytopenia. The following red cell disorders are discussed: red cell aplasia, sideroblastic anaemia, congenital dyserythropoietic anaemia, haemolytic anaemia, paroxysmal nocturnal haemoglobinuria, iron deficiency anaemia, anaemia of chronic disease and megaloblastic anaemia. The neutropenias occur in the context of Shwachman-Diamond syndrome (SDS), severe congenital neutropenia, cyclic neutropenia, immune-related neutropenia and non-immune neutropenia. In addition, the following causes of thrombocytopenia are discussed: congenital amegakaryocytic thrombocytopenia, thrombocytopenia with absent radii, immune-related thrombocytopenia and non-immune thrombocytopenia. Finally, we pay attention to the following pancytopenic disorders: Fanconi anaemia, dyskeratosis congenita, aplastic anaemia, myelodysplastic syndromes and human immunodeficiency virus (HIV) infection.

Role of molecular mimicry of hepatitis C virus protein with platelet GPIIIa in hepatitis C–related immunologic thrombocytopenia

AbstractPatients with HIV-1 immune-related thrombocytopenia (HIV-1–ITP) have a unique Ab against platelet GPIIIa49-66 capable of inducing oxidative platelet fragmentation in the absence of complement. HIV-1–seropositive drug abusers are more prone to develop immune thrombocytopenia than non–drug abusers and have a higher coinfection with hepatitis C virus (HCV) than non–drug abusers (90% vs 30%). Molecular mimicry was sought by screening a phage peptide library with anti–GPIIIa49-66 antibody as bait for peptides sharing homology sequences with HCV. Several phage peptide clones had 70% homology with HCV protein. Sera from dually infected thrombocytopenic patients with HCV and HIV-ITP reacted strongly with 4 nonconserved peptides from HCV core envelope 1. Reactivity correlated inversely with platelet count (r2 = 0.7, P < .01). Ab raised against peptide PHC09 in GPIIIa−/− mice induced thrombocytopenia in wild-type mice. Affinity-purified IgG against PHC09 induced oxidative platelet fragmentation in vitro. Drug abusers dually infected with HCV and HIV-1 had a greater incidence and severity of thrombocytopenia as well as titer of anti–GPIIIa49-66/PHC09 Ab. NZB/W F1 mice injected with recombinant core envelope 1 developed Ab versus PHC09 and significantly decreased their platelet count (P < .001). Thus, HCV core envelope 1 can induce thrombocytopenia by molecular mimicry with GPIIIa49-66.

Thrombotic Thrombocytopenic Purpura in HIV-Infected Patients

Thrombocytopenia is one of the most common hematologic abnormalities seen in patients infected with the human immunodeficiency virus (HIV). Because HIV-infected patients have a higher incidence of immune-related thrombocytopenia, the laboratory and clinical features of thrombotic thrombocytopenic purpura (TTP) may be overlooked and the diagnosis never considered. The clinical course and treatment of these entities are distinctly different. Early diagnosis and appropriate therapy with plasma exchange therapy may be lifesaving. Outcome and survival with TTP may be related to the stage of HIV infection and the severity of immunosuppression at the time of the diagnosis. The effect that highly active antiretroviral therapy (HAART) will have on the incidence of TTP remains to be seen. Reviewed are 7 episodes of TTP that occurred in 5 patients we cared for along with the literature pertaining to this topic.

Clinical and hematological characteristics of hepatosplenic T gamma/delta lymphoma with isochromosome for long arm of chromosome 7.

Hepatosplenic T gamma/delta lymphoma is a rare entity of peripheral T cell lymphoma. Three of 386 patients with non-Hodgkin's lymphoma in our institute were found to have this subtype of lymphoma. All had chromosomal abnormalities of isochromosome 7q and trisomy 8. The clinical and hematological features of these three patients are reported. All were males with ages ranging from 23 to 29 years. Initial presentation comprised purpura and variable degree of hepatosplenomegaly. None had superficial lymphadenopathy. Hematologically, they showed pictures resembling immune related thrombocytopenia and/or hemolytic anemia. Examination of the bone marrows revealed hypercellularity with increased number of megakaryocytes and erythroid cells and various degrees of abnormal lymphoid cell infiltration. The histopathologic section of the spleen from one patient who underwent splenectomy revealed abnormal cell infiltration in the sinusoids of the red pulp. Lymphoma cells showed T gamma/delta lymphoid immunophenotype (CD3+ CD2+ CD4- CD8-, TCR delta-1+, and beta F1-). The platelet counts were elevated transiently after initial treatment with corticosteroids, but the condition soon deteriorated. All died of refractory lymphoma five to nine months after diagnosis. Review of the literature, showed that only four other cases have been reported until now and although no cytogenetic data were available for these patients, they had very similar clinical pictures as those in this series. It is suggested that hepatosplenic T gamma/delta lymphoma represents a rare, but distinct, clinicopathological and cytogenetic entity.