A case of lower limb ulcer caused by hydroxyurea in treating primary thrombocytosis.

Hydroxyuria is a common medication for treating blood system diseases, but ulcers in the lower limbs caused by this medication are often rare and not often suspected. We reported an elderly patient with lower limb ulcers caused by hydroxyurea treatment for primary thrombocytosis. When hydroxide is used, close observation of skin lesions and prompt handling of any skin disruption should prevent ulcers.

[Role and mechanism of platelet-derived growth factor BB in thrombocytosis in Kawasaki disease]. / è¡€å°æ¿è¡ç”Ÿç”Ÿé•¿å› å­BBåœ¨å·å´Žç— è¡€å°æ¿å¢žå¤šä¸­çš„ä½œç”¨åŠæœºåˆ¶ç ”ç©¶.

OBJECTIVES: To study the role and mechanism of platelet-derived growth factor BB (PDGF-BB) on platelet production in Kawasaki disease (KD) mice and human megakaryocytic Dami cells through in vitro and invivo experiments. METHODS: ELISA was used to measure the expression of PDGF in the serum of 40 children with KD and 40 healthy children. C57BL/6 mice were used to establish a model of KD and were then randomly divided into a normal group, a KD group, and an imatinib group (30 mice in each group). Routine blood test was performed for each group, and the expression of PDGF-BB, megakaryocyte colony forming unit (CFU-MK), and the megakaryocyte marker CD41 were measured. CCK-8, flow cytometry, quantitative real-time PCR, and Western blot were used to analyze the role and mechanism of PDGF-BB in platelet production in Dami cells. RESULTS: PDGF-BB was highly expressed in the serum of KD children (P<0.001). The KD group had a higher expression level of PDGF-BB in serum (P<0.05) and significant increases in the expression of CFU-MK and CD41 (P<0.001), and the imatinib group had significant reductions in the expression of CFU-MK and CD41 (P<0.001). In vitro experiments showed that PDGF-BB promoted Dami cell proliferation, platelet production, mRNA expression of PDGFR-ß, and protein expression of p-Akt (P<0.05). Compared with the PDGF-BB group, the combination group (PDGF-BB 25 ng/mL + imatinib 20 µmol/L) had significantly lower levels of platelet production, mRNA expression of PDGFR-ß, and protein expression of p-Akt (P<0.05). CONCLUSIONS: PDGF-BB may promote megakaryocyte proliferation, differentiation, and platelet production by binding to PDGFR-ß and activating the PI3K/Akt pathway, and the PDGFR-ß inhibitor imatinib can reduce platelet production, which provides a new strategy for the treatment of thrombocytosis in KD.

Mean platelet volume, thrombocytosis, and survival in non-small cell lung cancer patients treated with first-line pembrolizumab alone or with chemotherapy.

INTRODUCTION: Patients treated with immune checkpoint inhibitors (ICIs) may not response to treatment and are at risk for immune-related adverse events (irAEs). Platelet function has been linked to both oncogenesis and immune evasion. We studied the association between the change in mean platelet volume (MPV), platelet count, survival, and the risk of developing irAEs in patients with metastatic non-small cell lung cancer (NSCLC) who have received first-line ICI. METHODS: In this retrospective study, delta (∆) MPV was defined as the difference between cycle 2 and baseline MPV. Patient data were collected via chart review, and Cox proportional hazard and Kaplan-Meier method were used to assess the risk and estimate median overall survival. RESULTS: We identified 188 patients treated with first-line pembrolizumab, with or without concurrent chemotherapy. There were 80 (42.6%) patients received pembrolizumab monotherapy, and 108 (57.4%) received pembrolizumab in combination with platinum-based chemotherapy. Patients whose MPV (∆MPV ≤ 0) decreased had hazard ratio (HR) = 0.64 (95% CI 0.43-0.94) for death with p = 0.023. Patients with ∆MPV ≤ - 0.2 fL (median), there was a 58% increase in the risk of developing irAE (HR = 1.58, 95% CI 1.04-2.40, p = 0.031). Thrombocytosis at baseline and cycle 2 was associated with shorter OS with p = 0.014 and 0.039, respectively. CONCLUSION: Change in MPV after 1 cycle of pembrolizumab-based treatment was significantly associated with overall survival as well as the occurrence of irAEs in patients with metastatic NSCLC in the first-line setting. In addition, thrombocytosis was associated with poor survival.

Aberrant Platelet Aggregation as Initial Presentation of Essential Thrombocythemia: Failure of Entero-Coated Aspirin to Reduce Platelet Hyperactivation.

Essential thrombocythemia (ET) is a myeloproliferative neoplasm variant characterized by excessive production of platelets. Since the most common cause of mortality and morbidity in ET patients is thrombosis, the excessive production of platelets may cause thrombotic events. However, little is known about the function of platelets in ET. We report a female patient who presented as asymptomatic, without a remarkable medical history, and ET was diagnosed after an incidental finding of moderate thrombocytosis. Notably, together with thrombocytosis, an abnormal platelet phenotype was found for the presence of a massive, rapid and spontaneous formation of aggregates and platelet hypersensitivity to subthreshold concentrations of aggregating agonists. Bone marrow histopathological examination and genetic analysis with the JAK2 (V617F) gene mutation findings confirmed the initial suspicion of ET. Although the ET patient was placed on aspirin, the persistence of the platelet hyperactivation and hyperaggregability prompted a switch in antiplatelet medication from entero-coated (EC) to plain aspirin. As result, platelet hypersensitivity to agonists and spontaneous aggregation were no longer found. Collectively, our study demonstrates that platelet function analysis could be a reliable predictor of ET and that plain aspirin should be preferred over EC aspirin to attenuate platelet hyperreactivity.

Long-Term Molecular Remission after Treatment with Imatinib in a Chronic Myeloid Leukemia Patient with Extreme Thrombocytosis Harboring Rare e14a3 (b3a3) BCR::ABL1 Transcript: A Case Report.

An atypical BCR::ABL1 fusion gene transcript in chronic myeloid leukemia (CML) patients, even those with variant Philadelphia (Ph) chromosome translocation, is very rare. In the present study, we report a case of CML (41 years, female) with extreme thrombocytosis at onset, with the variant Ph chromosome and rare e14a3 (b3a3) BCR::ABL1 transcript. The patient was prescribed imatinib as a first-line therapy and subsequently achieved complete hematologic remission within 2 months and major molecular response (MMR) within 3 months, and the transcript was undetectable within half a year. During up to nine years of follow-up, the quantification of this rare fusion gene was consistently negative with no BCR::ABL1 kinase domain mutations. Furthermore, we collected previously reported CML cases with the e14a3 (b3a3) transcript that indicated that the e14a3 (b3a3) transcripts appeared to have a larger number of thrombocytosis and variant Ph translocations than CML in general. This subgroup of CML might have better responses and outcomes to imatinib than patients with common transcripts.

Effect of iron supplementation on platelet count in adult patients with iron deficiency anemia.

Iron deficiency anemia (IDA) affects more than 1.2 billion individuals globally. In addition to anemia, reactive thrombocytosis is also a common clinical hematological condition in patients with IDA. However, some case reports have described the thrombotic complications in association with IDA-induced thrombocytosis. Patients with a high risk of thrombosis need prompt identification and effective treatment to prevent thrombotic complications. While iron replacement treatment has been shown to decrease platelet count in this context, there is limited published evidence on how iron supplementation affects the thrombocytosis caused by IDA. We retrospectively examined the clinical records of 440 patients with IDA from an RCT completed from 1 January 2016, to 30 December 2017, and data obtained from this study was used for post hoc analysis to examine the effect of iron on platelet count in IDA-induced thrombocytosis.The mean ± standard deviation (SD) platelet counts of the 440 patients with IDA was 310.23 ± 98.72 × 109/L. With baseline platelet counts>450 × 109 /L as the cutoff for thrombocytosis, patients were divided into 2 groups: 36 (8.1%) in the IDA with thrombocytosis group (mean ± SD platelet count, 521.67 ± 73.85 × 109/L) and the remaining 404 in the IDA without thrombocytosis group (mean ± SD platelet count, 291.39 ± 76.11 × 109/L).Differences were found in baseline characteristics including white blood cell (WBC) count, hemoglobin (Hb) level, mean corpuscular volume (MCV), transferrin saturation (TSAT), serum iron (SI) level, and total iron-binding capacity (TIBC) between the two groups (P < .05). From baseline to 8 weeks of continuous iron supplementation treatment, the mean platelet counts in both groups were decreased at 2-week treatment intervals. And in the IDA with thrombocytosis group, half of the patients resolved thrombocytosis after 2 weeks of iron supplementation, and the counts of all patients with thrombocytosis decreased below 450 × 109 /L within 6 weeks.In conclusion, the rate of reactive thrombocytosis in patients with IDA was 8.1%. IDA patients with thrombocytosis showed more severe anemia, lower ferritin, and more advanced iron deficiency than those without thrombocytosis. Platelet counts of half of the patients with thrombocytosis reduced below cut off of 450 × 109/L for thrombocytosis after 2 weeks of treatment, and all patients resolved thrombocytosis after 6 weeks. Our study provided clinical evidence for more effective and individualized iron management in the future. IDA patients with thrombocytosis should take active iron treatment and increase follow-up frequency to prevent thrombotic events. For patients with persistent thrombocytosis, a concomitant clonal process should be considered.

Treatment outcomes for patients with myelodysplastic syndrome/myeloproliferative neoplasms with ring sideroblasts and thrombocytosis.

Myelodysplastic syndrome/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T) is characterized by anemia, ring sideroblast erythroid precursors, and persistent thrombocytosis. Case reports suggest lenalidomide may be effective in treating MDS/MPN-RS-T. We evaluated a large series of patients with MDS/MPN-RS-T to compare hematological improvement (HI) response rates among different drug therapies including lenalidomide. We identified 167 patients with MDS/MPN-RS-T. Among the patients tested, 84% had SF3B1 mutations and 43% had JAK2 V617F mutations. The median OS for the cohort was 81 months. Overall, 76 patients (46%) received erythropoiesis-stimulating agents (ESAs), 47 patients (28%) received lenalidomide, and 45 patients (27%) received hypomethylating agents (HMAs). The HI rates were 58%, 53%, and 24%, respectively. The median duration of treatment was 11 months for lenalidomide compared to 6 months for HMAs. Rates of HI improvement were higher in patients with MDS/MPN-RS-T treated with ESAs or lenalidomide, in comparison to those treated with HMAs.

[Efficacy of venetoclax combined azacitidine in newly diagnosed acute myeloid leukemia unfit for standard chemotherapy: a single center experience].

Objective: To investigate the effectiveness and safety of the VA regimen, which combines venetoclax with azacitidine in the treatment of patients with newly diagnosed acute myeloid leukemia (AML) who are not suitable candidates for conventional chemotherapy. Methods: In the Department of Hematology at the Second Hospital of Hebei Medical University, 66 AML patients who received venetoclax and azacitidine treatment from May 2020 to March 2022 were the subject of a retrospective study. The complete remission (CR) rate, cCR rate, ORR rate, MRD negative rate, the incidence of adverse events,1-year EFS, and OS were retrospectively analyzed. Patients subgroups with varying ages, ECOG scores, primary and secondary, risk stratifications, and gene mutation were compared for differences in efficacy and survival. Results: The median follow-up was 4.25 (0.9-19.9) months, and the median number of treatment courses was 2 (1-8) cycles. After the first cycle, the cCR rate was 78.8% , and the MRD negative rate was 51.9% . After prolonged treatment, the cCR rate was 81.8% and MRD negative rate was 66.7% . The median EFS and OS, respectively, were13.2 and 15.3 months. Secondary AML showed inferior efficacy and prognosis. IDH1/2 or NPM1 mutation groups had a significantly higher rate of CR than the control group (P<0.05) . The CR rate and MRD negative rate of patients with rebound thrombocytosis were significantly higher than those without rebound thrombocytosis (P<0.05) . Those who had epigenetic modification mutations (DNMT3, ASXL1, TET2) were more likely to benefit from ongoing therapy. The most common grade 3 and 4 adverse reactions were neutropenia, thrombocytopenia, and anemia. Conclusions: In real-world patients with newly diagnosed AML who are not candidates for standard chemotherapy, the VA regimen produces rapid deep remission. Primary AML patients, rebound thrombocytosis, IDH1/2, and NPM1 gene mutations are favorable factors for treatment benefit, and adverse reactions were tolerable.

The Effect of TLR4 Blockade on Some Indicators of Systemic Inflammatory Response to Proteus mirabilis LPS in Rats.

The effects of TLR4 blocker on blood cell morphology, concentrations proinflammatory cytokines, and functional state of the liver and kidneys were studied in outbred male rats (n=60) after intravenous injection of 20 mg/kg LPS isolated from opportunistic Proteus mirabilis strain ATCC 51393. TLR4 blocker TLR4-IN-C34 was injected intravenously in a dose of 1 mg/kg/day over 3 days. Systemic inflammatory reaction induced by LPS was characterized by elevation of serum TNFα, IL-1ß, IL-6, erythrocyte sedimentation rate, leukocytosis, and thrombocytosis. Increased activity of hepatocyte enzymes (ALT, alkaline phosphatase, and lactate dehydrogenase), retention of nitrogen metabolites (urea and creatinine), elevated content of protein oxidation products, and enhanced protein catabolism were also observed. Administration of TLR4 blocker reduced parameters of inflammatory reaction and prevented the development of hypercatabolic syndrome; endotoxicosis and kidney function indicators approached the normal levels.

A Young Woman with Thrombocytosis.

The diagnostic approach to thrombocytosis involves consideration of reactive, hereditary, and neoplastic causes. Once reactive causes of thrombocytosis, such as iron deficiency, infections, solid tumors, and other obvious causes such as post-splenectomy thrombocytosis, have been ruled out, the focus shifts to myeloid malignancies, such as chronic myeloid leukemia (CML), the classic Philadelphia chromosome-negative (Ph-) myeloproliferative neoplasms (MPNs), essential thrombocythemia (ET), primary myelofibrosis (PMF), polycythemia vera (PV), myelodysplastic syndrome (MDS) with isolated deletion 5q and the rare MDS/MPN "overlap" syndrome, MDS/MPN with ring sideroblasts, and thrombocytosis (MDS/MPN-RS-T).

Clinical analysis and literature review of a case with the myelodysplastic syndrome/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis.

Objective: Myelodysplastic syndrome/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T) is a new disease entity in the 2016 WHO classification, characterized by anemia, thrombocytosis and bone marrow ring sideroblasts. We herein reported a case of MDS/MPN-RS-T and discuss its clinical characteristics. Methods: A 69-year-old woman presented to our hospital with recurrent dizziness and fatigue. Hematologic investigations, bone marrow analysis and genomic DNA sequencing studies were performed. Results: Peripheral blood testing showed normocytes anemia and thrombocytosis, and bone marrow analysis revealed hypercellular with clusters of megakaryocytes and 95% ring sideroblasts (RS). She had a normal karyotype and was found to have SF3B1 mutations. Decitabine therapy produced a clinical response and disease remission in this patient. Conclusions: Our report provides a definite conceptual framework for a better understanding of the characteristics of MDS/MPN-RS-T.

COVID-19 in Neonates and Infants: Progression and Recovery.

Between March 10, 2020 and April 17, 2020, of 8/70 (11.4%) SARS-CoV-2 positive infants that presented, 5/8 (63%) developed fever, 4/8 (50%) had lower respiratory tract involvement, 2/8 (25%) had neutropenia and thrombocytosis, and 4/8 infants (50%) were treated for suspected sepsis with broad-spectrum antibiotics. Only 1/8 (13%) required pediatric intensive care. All patients were eventually discharged home well.

An unusual case of extreme thrombocytosis caused by iron deficiency.

Iron deficiency is a common cause of reactive thrombocytosis resulting in usually mild to moderately increased but sometimes even in extreme thrombocytosis (ie, >1000×109/L). We report a case of a 34-year-old woman who developed an increased platelet count of 1953×109/L. Upon admission, cytoreductive therapy was initiated until an underlying chronic myeloproliferative neoplasia was ruled out. The patient had undergone bariatric surgery 5 years previously, and surprisingly, a diagnosis of reactive thrombocytosis due to iron deficiency secondary to iron malabsorption was made. It is concluded that the degree of extreme thrombocytosis may be even fourfold to fivefold increased in patients with severe iron deficiency. Our finding emphasises the importance of regular control of possible need for iron supplementation following bariatric surgery.

Secondary severe thrombocytosis in a patient who underwent splenectomy due to hereditary spherocytosis and its treatment using hydroxyurea.

Thrombocytosis is a frequently seen condition during childhood. While it usually develops secondarily due to reasons such as infection or anemia, it may rarely develop due to clonal causes. Thrombocytosis becomes a life-threatening condition by causing severe complications such as hemorrhage and thrombosis development. Treatment is not recommended in patients who are asymptomatic and with a platelet count below 1,500,000/mm3, however, treatment is required in cases who are symptomatic and with a platelet count above 1,500,000/mm3 in conditions such as primary thrombocytosis. This article present the outcomes of a patient who was treated using low-dose hydroxyurea when he developed severe thrombocytosis after splenectomy.