Mild Thrombocytopenia Research Articles

Clear Cell Papillary Renal Cell Carcinoma: Case Series with Review of the Literature

Abstract Clear cell papillary renal cell carcinoma (CCPRCC) was included as a separate entity in the World Health Organisation classification of renal tumours in 2016. Immuno-histopathological and genetic characteristics are much known, but still, clinical features and long-term follow-up require more consolidated data. We report three cases of CCPRCC, detected in different clinical settings. The first case was co-incidentally diagnosed on routine imaging, in a follow-up case of open cystolithotripsy. The second case presented with haematuria under evaluation; and the third case presented with mild thrombocytopenia without anaemia or a positive Coombs test. All the cases revealed characteristic histopathological examination and immunohistochemistry. None of the patients showed tumour recurrence/metastases on follow-up. The study holds importance as it presents CCPRCC cases in different clinical scenarios, describes a rarely reported case of thrombocytopenia without associated anaemia/positive Coombs test, and emphasises the need to consider CCPRCC in relevant clinico-radiological settings and immuno-histopathological features, due to its indolent nature and consequently better prognosis.

CLINICO-INVESTIGATIVE PROFILE OF THROMBOCYTOPENIA IN THIRD TRIMESTER OF PREGNANCY

Background:Thrombocytopenia often occurs in pregnancy, ranking as the second most common hematologic abnormality following anemia. It affects approximately 6% to 10% of pregnant women.1 This research aimed to explore the factors linked to thrombocytopenia among rural Indian women in their third trimester of pregnancy. Methods:This prospective observational study was conducted at Dr.BalasahebVikhePatil Rural Medical College and Dr.VitthalraoVikhePatilsPravara Rural Hospital in India. The study specifically targeted rural Indian women in their third trimester of pregnancy with a platelet count below 150,000 per cubic millimeter. Results:In the present study, among the 86 cases examined, the largest proportion (44.2%) were diagnosed with Gestational Thrombocytopenia, followed by 27.9% diagnosed with hypertensive disorders of pregnancy and 16.3% with HELLP syndrome. Among the 39 cases of gestational thrombocytopenia, 41.01% were categorized as mild thrombocytopenia. Of the 38 cases of hypertensive disorders of pregnancy accompanied by thrombocytopenia, 63% were associated with pre-eclampsia and 36.8% with HELLP syndrome. Additionally, 61.6% of the babies were born with low birth weight, and 73.5% of these cases were linked to maternal platelet counts below 100,000 per cubic millimeter.. Conclusions:The research underscores gestational thrombocytopenia as the leading cause during the third trimester, followed by hypertensive disorders such as pre-eclampsia and HELLP syndrome. It emphasizes the need for careful monitoring, particularly for first-time mothers and those in their third trimester, due to increased risks. The link between maternal platelet count and neonatal outcomes, particularly low birth weight, highlights the complex relationship between maternal health and fetal well-being.

Serglycin controls megakaryocyte retention of platelet factor 4 and influences megakaryocyte fate in bone marrow

AbstractMegakaryocytes (MKs) produce platelets, and similar to other hematopoietic progenitors, they are involved in homeostatic aspects of their bone marrow niche. MKs release and endocytose various factors, such as platelet factor 4 (PF4)/CXCL4. Here, we show that the intra-α-granular proteoglycan, serglycin (SRGN), plays a key role in this process by retaining PF4, and perhaps other factors, during MK maturation. Immature, SRGN–/– MKs released ∼80% of their PF4, and conditioned media from these cells negatively affected wild-type MK differentiation in vitro. This was replicated in wild-type MKs by treatment with the polycation surfen, a known inhibitor of glycosaminoglycan (GAG)/protein interactions. In vivo, SRGN–/– mice had an interstitial accumulation of PF4, transforming growth factor β1, interleukin-1β, and tumor necrosis factor α in their bone marrow and increased numbers of immature MKs, consistent with their mild thrombocytopenia. SRGN–/– mice also had reduced numbers of hematopoietic stem cells and multipotent progenitors, reduced laminin, and increased collagen I deposition. These findings demonstrate that MKs depend on SRGN and its charged GAGs to balance the distribution of PF4 and perhaps other factors between their α-granules and their adjacent extracellular spaces. Disrupting this balance negatively affects MK development and bone marrow microenvironment homeostasis.

Thrombocytopenia and In-hospital outcomes in patients with acute ischemic stroke undergoing intravenous thrombolysis: Findings from a nationwide registry study in China

Background and ObjectiveOur study aimed to evaluate the associations between platelet count (PC) and in-hospital outcomes for patients with stroke after rt-PA intravenous thrombolysis. MethodsWe identified patients who had been hospitalized with a primary diagnosis of stroke and had received rt-PA intravenous thrombolysis from June 2015 to July 2019 at participating hospitals in the Chinese Stroke Center Alliance. PC measured before intravenous thrombolysis was categorized into the following four groups: severe thrombocytopenia (PC < 100 × 109/L), mild thrombocytopenia (100 ≤ PC < 150 × 109/L), normal PC (150 ≤ PC ≤ 450 × 109/L), and thrombocythemia (PC > 450 × 109/L). Outcomes were determined from clinical data collected during hospitalization. The primary clinical outcome was symptomatic intracranial hemorrhage (sICH). Secondary outcomes were mortality, bleeding events, gastrointestinal (GI) hemorrhage, and in-hospital stroke recurrence. We used multivariate logistic regression models to evaluate the associations between PC and outcomes. ResultsWe included 44,882 individuals with a median age of 66 years, of whom 34.7 % were female, 951 (2.1 %) had severe thrombocytopenia, 7218 (16.1 %) had mild thrombocytopenia, 36,522 (81.4 %) had a normal PC, and 191 (0.4 %) had thrombocythemia. Both severe and mild thrombocytopenia groups had higher risks of bleeding events (adjusted OR 1.30; 95 % CI,1.01-1.67; p = 0.045; adjusted OR 1.32; 95 % CI,1.19-1.46; p < 0.001) and sICH (adjusted OR 1.48;95 % CI,1.13-1.94; p = 0.005; adjusted OR 1.43;95 % CI,1.27-1.60; p < 0.001) than the normal PC group. Patients with 100 ≤ PC < 150 × 109/L also had a higher risk of in-hospital stroke recurrence (adjusted OR 1.12; 95 % CI,1.02-1.22; p = 0.02). ConclusionsIntravenous thrombolysis brings a high risk of sICH given PC < 150 × 109/L, especially PC < 100 × 109/L. It indicated that PC < 100 × 109/L is a reasonable contraindication to thrombolysis.

Thrombocytopenia developed in intensive care unit for congenital heart disease: incidence, risk factors, and outcomes

BackgroundThrombocytopenia is common for patients in the intensive care unit (ICU) and is associated with adverse outcomes. ICU thrombocytopenia in pediatric patients who underwent cardiac surgeries with cardiopulmonary bypass (CPB) is inadequately studied. ObjectivesWe aimed to investigate the incidence, risk factors, and prognostic role of ICU thrombocytopenia after congenital cardiac surgeries with CPB. MethodsA retrospective study involving 11 761 patients was conducted. Patients were categorized into 4 groups of thrombocytopenia based on platelet counts tested during ICU: non (>150 × 109/L), mild (100-150 × 109/L), moderate (50-100 × 109/L), and severe (<50 × 109/L). Logistic and Cox regression analyses were utilized to explore the risk factors of thrombocytopenia and the association of ICU thrombocytopenia with 30-day mortality. ResultsICU thrombocytopenia was observed in 4007 patients (34.1%), with mild, moderate, and severe thrombocytopenia occurring in 2773 (23.6%), 987 (8.4%), and 247 (2.1%) patients, respectively. Younger age, cyanotic congenital heart disease, CPB duration, and preoperative laboratory findings (red blood cell, thrombocytopenia, red cell distribution width, hematocrit, and coagulation disorder) were identified as independent risk factors of ICU thrombocytopenia. Patients with moderate (hazard ratio [95% CI]: 11.38 [3.02-42.87]; P < .001) and severe thrombocytopenia (hazard ratio [95% CI]: 49.54 [13.11-187.14]; P < .001) had a significantly higher risk of 30-day mortality. Furthermore, with the increase in the severity of ICU thrombocytopenia, there was an incremental increase in the incidence of postoperative critical bleeding and thrombosis, perioperative blood transfusions, length of ICU stays, and duration of mechanical ventilation. ConclusionICU thrombocytopenia occurred in one-third of children after congenital cardiac surgery with CPB, and it was associated with multiple adverse outcomes.

Thrombocytopenia 4 (THC4): Six novel families with mutations of the cytochrome c gene.

Thrombocytopenia 4 (THC4) is an autosomal-dominant thrombocytopenia caused by mutations in CYCS, the gene encoding cytochrome c (CYCS), a small haeme protein essential for electron transport in mitochondria and cell apoptosis. THC4 is considered an extremely rare condition since only a few patients have been reported so far. These subjects presented mild thrombocytopenia and no or mild bleeding tendency. In this study, we describe six Italian families with five different heterozygous missense CYCS variants: p.Gly42Ser and p.Tyr49His previously associated with THC4, and three novel variants (p.Ala52Thr, p.Arg92Gly, and p.Leu99Val), which have been classified as pathogenic by bioinformatics and segregation analyses. Moreover, we supported functional effects of p.Ala52Thr and p.Arg92Gly on oxidative growth and respiratory activity in a yeast model. The clinical characterization of the 22 affected individuals, the largest series of THC4 patients ever reported, showed that this disorder is characterized by mild-to-moderate thrombocytopenia, normal platelet size, and function, low risk of bleeding, and no additional clinical phenotypes associated with reduced platelet count. Finally, we describe a significant correlation between the region of CYCS affected by mutations and the extent of thrombocytopenia, which could reflect different degrees of impairment of CYCS functions caused by different pathogenetic variants.

Managing recurrent parvovirus B19-associated anemia after a pediatric kidney transplant

A 13-year-old girl who had a kidney transplant four weeks prior presented with a 10-day history of fatigue, paleness, and headache. On physical examination, tachycardia and paleness were noted. Laboratory testing was notable for severe anemia and mild leukopenia and thrombocytopenia. Polymerase chain reaction (PCR) test for Epstein-Barr virus (EBV) and cytomegalovirus (CMV) were negative and for parvovirus B19 (PVB19) was positive. Despite lower immunosuppression and administration of intravenous immunoglobulin (IVIG) it persisted for 15 months, and frequent red blood cell transfusions were needed. PVB19 is a less common but significant complication. The patient's clinical course demonstrates the importance of this complication and the challenges in its management. A notable void exists in the literature regarding standardized treatment protocols for PVB19-induced recurrent anemia after kidney transplant. This case indicates the need for further research and consensus to guide effective clinical interventions in similar cases.

L-plastin associated syndrome of immune deficiency and hematologic cytopenia

BackgroundLCP1 encodes L-plastin, an actin-bundling protein primarily expressed in hematopoietic cells. In mouse and fish models, LCP1 deficiency has been shown to result in hematological and immune defects. ObjectiveTo determine the nature of a human inborn error of immunity resulting from a novel genetic variant of LCP1. MethodsWe performed genetic, protein and cellular analysis of PBMCs from a kindred with apparent autosomal dominant immune deficiency. We identified a candidate causal mutation in LCP1, which we evaluated by engineering the orthologous mutation in mice and Jurkat cells. ResultsA splice-site variant in LCP1 segregated with lymphopenia, neutropenia, and thrombocytopenia. The splicing defect results in at least two aberrant transcripts, producing an in-frame deletion of 24 nucleotides, and a frameshifting deletion of exon 8. Cellular analysis of the kindred revealed a proportionate reduction of T and B cells, and a mild expansion of transitional B cells. Similarly, mice carrying the orthologous genetic variant exhibited the same in-frame aberrant transcript, reduced expression Lcp1 and gene dose-dependent leukopenia, mild thrombocytopenia, and lymphopenia, with a significant reduction of T cell populations. Functional analysis revealed that LCP1c740-1G>A confers a defect in platelet development and function with aberrant spreading on collagen. Immunological analysis revealed defective actin organisation in T cells, reduced migration of PBMCs from patients, splenocytes from mutant mice, and a mutant Jurkat cell line in response to CXCL12, impaired germinal centre B cell expansion after immunisation, and reduced cytokinesis during T cell proliferation. ConclusionWe describe a unique human hematopoietic defect affecting neutrophils, lymphocytes and platelets, arising from partial LCP1 deficiency.

Mild Thrombocytopenia, a Predictor of Outcomes After Laparoscopic Cholecystectomy: Assessment of Surgical Risk in Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease.

A common cause of mild thrombocytopenia is chronic liver disease, the most common etiology being metabolic dysfunction-associated steatotic liver disease (MASLD). Mild thrombocytopenia is a well-defined, independent marker of hepatic fibrosis in patients with chronic liver disease. Currently, there is a paucity of information available to characterize perioperative risk in patients with MASLD; therefore, the characterization of perioperative morbidity is paramount. We used a platelet threshold of 150×10 9 as a surrogate for fibrosis in patients undergoing laparoscopic cholecystectomy to study its effect on perioperative complications and mortality. We queried the American College of Surgeons National Surgical Quality Improvement Program database for laparoscopic cholecystectomies occurring from 2005 through 2018. Demographic differences between patients with and without thrombocytopenia were evaluated using the t test or the χ 2 test, whereas adjusted and unadjusted differences in outcome risk were evaluated using log-binomial regression models. We identified 437,630 laparoscopic cholecystectomies of which 6.9% included patients with thrombocytopenia. Patients with thrombocytopenia were more often males, older, and with chronic disease. Patients with thrombocytopenia and higher Aspartate Aminotransferase to Platelet Ratio Index scores had 30-day mortality rates risk ratio of 5.3 (95% CI: 4.8-5.9), with higher complication rates risk ratio of 2.4 (95% CI: 2.3-2.5). The most frequent complications included the need for transfusion, renal, respiratory, and cardiac. Perioperatively, patients with mild thrombocytopenia undergoing laparoscopic cholecystectomy had higher mortality rates and complications compared with patients with normal platelet counts. Thrombocytopenia may be a promising, cost-effective tool to identify patients with MASLD and estimate perioperative risk, especially if used in high-risk populations.

Feto-Maternal Outcome in Pregnancy With Thrombocytopenia and Abnormal Platelet Indices.

Platelet count and its associated indices like mean platelet volume (MPV) and platelet distribution width (PDW) are cost-effective biomarkers that are easily accessible and have a potent role in the diagnosis and management of thrombocytopenia.Since anaemia and thrombocytopenia often go together in pregnancy, it is advisable to utilise these indices for feto-maternal benefit. The study was conducted in the Department of Obstetrics and Gynaecology at a tertiary care centre in New Delhi from July 2022 to December 2023 whereinpregnant womenof age 18-40 years, period of gestation >28 weeks with thrombocytopenia or abnormal platelet indices were enrolled. Women with pancytopenia, bone marrow suppression or past or current SARS-CoV-2 positive status were excluded. A total of 150 women were enrolled in the study. The mean age of study population was 25.33 ± 2.90 (range 19-34) years. Subjects were divided into three groups - Group A (mild thrombocytopenia) 24.6%, Group B (moderate thrombocytopenia) 64.6% andGroup C (severe thrombocytopenia) 10.6% based on thrombocytopenia severity. Analysing the risk factors, Group C was found to have a significantly higher number of patients with anaemia (p=<0.001), fever (p=0.031), abnormal liquor volumes (p=0.004) and need for blood and platelet transfusion (p=0.077). On correlation of thrombocytopenia with abnormal platelet indices, it was observed that manual platelet count (MPC) and MPV were indirectly correlated (p=0.027). PDW wasfound to be directly associated with severe thrombocytopenia and indirectly associated with moderate thrombocytopenia. Conclusion: Thrombocytopenia in pregnancy is directly correlated to factors like maternal fever and anaemia, fetal growth restriction, abnormal liquor, blood products and platelet transfusions. It was also concluded that platelet indices like PDW and MPV play an important role in predicting the feto-maternal outcome and hence timely interventions can be done to improve the same.

Prevalence and risk factors of thrombocytopenia during the third trimester of pregnancy

Background and objective: Thrombocytopenia, described as a platelet count of less than 150,000 mm3, is a common diagnosis during the period of pregnancy, existing in 7–12% of pregnancies. Mild thrombocytopenia occurs if platelet counts are less than 100,000 mm3, while moderate thrombocytopenia is between 50,000 and 100,000 mm3, and severe thrombocytopenia occurs if platelet counts are less than 50,000 mm3. It could be connected to physiologic changes or pathological diseases; some of them have an impact on pregnancy and may offer a serious risk to both the mother and the unborn child. This study sought to estimate the proportions of the underlying causes as well as the prevalence of thrombocytopenia among pregnant women visiting the antenatal care center in Erbil. Methods: A cross-sectional study was performed in a maternity teaching hospital in Erbil city, Kurdistan region, Iraq. A convenience sample of 600 pregnant women was used from 28 weeks to 40 weeks of gestation. Over a period of 1 year, starting in January 2021 and ending in December 2021. Results: The prevalence of thrombocytopenia among the 600 cases was 24.8%, but the majority (75.2%) had a normal platelet count; the degrees of thrombocytopenia were severe in 1.8% of the cases, mild in 8.3%, and moderate in 14.7% of the cases. Conclusion: A statistically significant association between preeclampsia and HELLP syndrome has been reported as a serious condition that leads to thrombocytopenia. High serum albumin levels in pregnant women related to hypertension had a major impact on the number of platelet counts and should be considered a severe disease.

Profiles of Hematological Parameters in &lt;i&gt;Plasmodium vivax&lt;/i&gt; Malaria Patients attending Lady Reading Hospital, Peshawar

Background: Plasmodium is a type of parasite that causes malaria. Fiveknown species of Plasmodium can cause malaria in humans, Plasmodium falciparum, plasmodium vivax, Plasmodium ovale, Plasmodium malariae, and Plasmodium knowlesi. This study was designed to assess the effect of plasmodium vivax infection on malaria-associated hematological parameters. Material and Methods: This descriptive cross-sectional study was conducted at Lady Reading Hospital, Peshawar. The duration of the study was four (04) months from June to September 2023. A total of 384 samples possessed positive malarial parasite on peripheral smear both genders having different ages groups were included in the study. Variables such as age frequencies and percentage were reported for gender, hemoglobin, platelets, and white blood cells (WBC). This study was approved by the Ethical Committee of Ahmad Medical Institute, Peshawar. All collected data were analyzed through SPSS-22. Result: The study findings revealed that 196(51.0%) patients were males and 186(49%) were females. Out of 384 patients, 178 (46.4%) were between 10-30 years, 164(42.7%) were between 31-50 years, and 42(10.9%) were between 51-70 years age. Furthermore, out of 384, 11(2.9%) were normal, 69(18.0%) were anemic, 154(40.1%) were thrombocytopenia, 28(7.3%) were leukocytosis. Overall, distribution of thrombocytopenia, 120(31.3%) were no thrombocytopenia, 113 (29.4%) were mild thrombocytopenia, 104 (27.1%) were moderate thrombocytopenia, 47(12.4) were severe thrombocytopenia. Conclusion: Gaining further knowledge about these hematological indicators would enable their application in monitoring treatment response and early detection of malaria complications. The two most frequent hematological abnormalities results associated with malaria infection were thrombocytopenia and anemia.

Management of Thrombocytopenia with Partial Splenic Embolization in Liver Cirrhosis

Thrombocytopenia is a frequent complication in patients with cirrhosis. Thrombocytopenia is generally divided into mild, moderate, and severe thrombocytopenia. Thrombocytopenia in liver cirrhosis not only increases the risk of bleeding during surgery but can also have an impact on patient management, such as liver biopsy, administration of antiviral therapy, and postponement of elective surgery. The pathophysiology of thrombocytopenia in chronic liver disease can be caused by decreased platelet production, sequestration in the spleen, and increased platelet destruction. Partial splenic embolization (PSE) is one option for treating thrombocytopenia in chronic liver disease. PSE is an effective procedure in treating complications associated with hypersplenism and portal hypertension, such as esophageal varices, pancytopenia, portal hypertensive gastropathy and ascites.

Depression in the elderly and dementia with Lewy bodies: A case report of a challenging diagnosis

IntroductionDepression and dementia with Lewy bodies (DLB) are two fairly common pathologies in the elderly which can have similar presentations or be associated and therefore pose a diagnostic challenge.ObjectivesWe propose to illustrate, through our case, the diagnostic and therapeutic challenge of these two pathologies.MethodsWe present the case of Ms. S. BA aged 67, without organic or psychiatric history, admitted to the psychiatry department for massive anxiety and insomnia. The troubles date back to nineteen months when the patient isolated herself, remained bedridden, lost her appetite and no longer slept. The evolution quickly led to the appearance of an excessive agitation. The patient became distracted, talking and laughing to herself, and ran away from the house. She consulted several free-lance psychiatrists and received several antipsychotic medications without improvement. The admission interview revealed a very anxious patient with a difficult contact. Her speech was centred on well-detailed visual hallucinations with themes of death. The neurological examination was difficult at first. She was started on haloperidol and clonazepam. After 2 days, neurological examination showed a parkinsonian syndrome and a temporal disorientation. Other cognitive functions were difficult to assess. The two diagnoses evoked were DLB and a characterized depressive episode with psychotic features. Standard workup showed mild anaemia and thrombocytopenia. Brain MRI and electroencephalogram and immune tests were normal. However, PET imaging was not available in our hospital. Haloperidol was immediately stopped and the patient was treated with an anticholinergic corrector in combination with quetiapine at 200 mg. The evolution was characterized by a significant reduction in anxiety and visual hallucinations with a marked improvement of the parkinsonian syndrome. Depressive symptoms took the forefront of the clinical presentation; hence we associated sertraline with quetiapine. The subsequent evolution showed a clear improvement in the depressive symptoms with total resolution of the parkinsonian symptoms and a normal cognitive evaluation.ResultsIn our case, the clinical evolution constituted a key element in the diagnostic orientation. So far, it is unlikely that our patient has DLB and the diagnosis retained was a characterized depressive episode with psychotic and melancholic features. Depression in the elderly can have atypical presentations, and raise the possibly of other differential diagnoses. Diagnostic uncertainty should not delay the implementation of treatment.ConclusionsThe choice of molecules must take into account the associated somatic symptoms for a better tolerance. In the absence of a biological or iconographic examination with good sensitivity and specificity, the therapeutic test remains the only way to decide.Disclosure of InterestNone Declared

Prevalence of Hepatitis B Viral Infection in Pregnant Women at the Suhum Municipality, Ghana

Background. Global prevalence of chronic hepatitis B virus (HBV) infection was estimated between 257 and 291 million since 2020, posing a great public health challenge. In Africa, an estimated 60 million cases of HBV were reported in the same year. Pregnant women might be susceptible to HBV infection dependent on their level of awareness and knowledge about the causes, transmission, and prevention of HBV. The aim of the study was to assess the awareness and prevalence of HBV infection and prolonged bleeding risk among pregnant women at the Suhum Municipality of Ghana. Methods. The study was a cross-sectional design involving pregnant women who were sampled following their visit to the antenatal unit at the Suhum Government Hospital. Sociodemographics including history of HBV screening and vaccinations were obtained from consented individuals using pretested questionnaires. Also, venous blood samples were obtained for platelet count, whereas bleeding time assay was performed to assess functional platelet disorders. Results. Hepatitis B prevalence was 4.4%, with 14.1% prevalence of mild thrombocytopenia and 1.5% prevalence of prolonged bleeding time. Pregnant women who had tertiary education and previous screening were about 8 times (AOR=7.78, 95% CI: 1.50-40.50) and 14 times (AOR=13.66, 95% CI: 1.72-108.75) more likely to have knowledge of hepatitis B than those without tertiary education and previous screening, respectively. Conclusion. The prevalence of HBV was 4.4%. Education status and previous screening were associated with demonstration of knowledge about HBV; therefore, intensification of education and screening are recommended.

The Y49H cytochrome c variant enhances megakaryocytic maturation of K-562 cells

Five pathogenic variants in the gene encoding cytochrome c (CYCS) associated with mild autosomal dominant thrombocytopenia have been reported. Previous studies of peripheral blood CD34+ or CD45+ cells from subjects with the G42S CYCS variant showed an acceleration in megakaryopoiesis compared to wild-type (WT) cells. To determine whether this result reflects a common feature of the CYCS variants, the c.145T>C mutation (Y49H variant) was introduced into the endogenous CYCS locus in K-562 cells, which undergo megakaryocytic maturation in response to treatment with a phorbol ester. The c.145T>C (Y49H) variant enhanced the megakaryocyte maturation of the K-562 cells, and this effect was seen when the cells were cultured at both 18 % and 5 % oxygen. Thus, alteration of megakaryopoiesis is common to both the G42S and Y49H CYCS variants and may contribute to the low platelet phenotype. The Y49H CYCS variant has previously been reported to impair mitochondrial respiratory chain function in vitro, however using extracellular flux analysis the c.145T>C (Y49H) variant does not alter mitochondrial bioenergetics of the K-562 cells, consistent with the lack of a phenotype characteristic of mitochondrial diseases in CYCS variant families. The Y49H variant has also been reported to enhance the ability of cytochrome c to trigger caspase activation in the intrinsic apoptosis pathway. However, as seen in peripheral blood cells from G42S CYCS variant carriers, the presence of Y49H cytochrome c in K-562 cells did not significantly change their response to an apoptotic stimulus.

The Prevalence and Associated Risk Factors for Neonatal Thrombocytopenia Among Newborns Admitted to the Neonatal Intensive Care Unit.

Background Thrombocytopenia is the most prevalent hematological condition in neonates that develops in the neonatal intensive care unit (NICU). This set of illnesses is caused by either decreased platelet production due to placental insufficiency, increased platelet breakdown (consumption), or a combination of the two causes. Based on platelet count, it is defined as mild, moderate, or severe thrombocytopenia, with early and late onset. Purpose The purpose of this study is to determine the prevalence of thrombocytopenia and the factors that contribute to it in newborns hospitalized in the neonatal critical care unit at the Maternity and Children Hospital in Al Ahsa, Saudi Arabia. Methods This descriptive retrospective cross-sectional study was carried out at the NICU of the Maternity and Children Hospital in Al Ahsa, Saudi Arabia, over the span of one year (August 2022 to August 2023) among hospitalized neonates with thrombocytopenia. Thrombocytopenia is defined as a platelet count of 150,000 or less. These patients were monitored until they recovered or died. Results The inclusion criteria were met by a total of 242 newborns with thrombocytopenia. Half of the neonates (57%) were full-term, with Apgar scores greater than 5 at the first (84%) and fifth (93%) minutes, respectively. The great majority of individuals (84%) experienced early-onset thrombocytopenia of mild severity (62%) and were asymptomatic (93%). The majority of the cases resolved spontaneously, with only 21%requiring platelet transfusion. There was a significant relationship discovered between gestational age and the severity of thrombocytopenia, with very preterm infants having moderate to severe thrombocytopenia, as well as birth weight (p=0.001). Furthermore, neonates with severe thrombocytopenia had a considerably higher mortality rate (p=0.001). Conclusion The mortality and morbidity of newborns with perinatal risk for neonatal thrombocytopenia can be reduced with timely detection of the cause and development of thrombocytopenia, as well as adequate and early care.

Altered conformational dynamics contribute to species-specific effects of cytochrome c mutations on caspase activation

Variants in the gene encoding human cytochrome c (CYCS) cause mild autosomal dominant thrombocytopenia. Despite high sequence conservation between mouse and human cytochrome c, this phenotype is not recapitulated in mice for the sole mutant (G41S) that has been investigated. The effect of the G41S mutation on the in vitro activities of cytochrome c is also not conserved between human and mouse. Peroxidase activity is increased in both mouse and human G41S variants, whereas apoptosome activation is increased for human G41S cytochrome c but decreased for mouse G41S cytochrome c. These apoptotic activities of cytochrome c are regulated at least in part by conformational dynamics of the main chain. Here we use computational and in vitro approaches to understand why the impact of the G41S mutation differs between mouse and human cytochromes c. The G41S mutation increases the inherent entropy and main chain mobility of human but not mouse cytochrome c. Exclusively in human G41S cytochrome c this is accompanied by a decrease in occupancy of H-bonds between protein and heme during simulations. These data demonstrate that binding of cytochrome c to Apaf-1 to trigger apoptosome formation, but not the peroxidase activity of cytochrome c, is enhanced by increased mobility of the native protein conformation.

Abstract WP211: Mechanical Thrombectomy in Patients With Mild Thrombocytopenia is Safe and Effective; a Systematic Review and Meta-Analysis

Background: MT is a effective treatment for AIS patients with LVO, but MT on TP patients is risky due to lack of data and potential hemorrhage. Methods: Our review followed the PRISMA guidelines for systematic review and meta-analysis. We defined thrombocytopenia as platelet count ≤150х109/L, with further sub-classification into two groups: 1) Mild TP (Platelet count 100,000 - 149,000x109/L); 2) Moderate/severe TP (platelet count &lt;100х109/L). A favorable outcome was 90-day functional independence (mRS) ≤ 2). Unfavorable outcomes were mortality at 90 days and (sICH). Results: Compared to patients with normal platelets, patients with TP had no significant difference in outcomes (mRS &gt;2) at 90 days (RR 0.80 [95% CI: 0.69 - 0.94] p = 0.006). Further analysis based on sub-groups, the difference in mRS score was not statistically significant in patients with mild TP group (RR 0.84 [95% CI: 0.70 - 1.00] p = 0.05) and moderate/severe TP group (RR 0.71 [95% CI: 0.48 - 1.06] p = 0.09) when compared to patients with normal platelets. However Mortality was found to be higher in the TP group (RR 1.95 [95% CI: 1.62 - 2.36] p &lt; 0.00001), with similar trends of increased mortality in the mild and severe TP group (RR 1.88 [ 95% CI: 1.34 - 2.63] p = 0.0002 and RR 2.07 [95% CI: 1.46 - 2.92] p &lt; 0.0001). There was an overall slight increase in the incidence of sICH in the TP group (Relative Risk [RR] 2.47 [95% CI: 1.51 - 4.05], p = 0.0003) compared to patients with normal platelet counts, however subgroup demonstrated no significant higher risk in the mild thrombocytopenia group (RR 2.34 [95% CI: 1.24 - 4.40], p = 0.008) Conclusions: Mechanical thrombectomy for LVO in patients with mild thrombocytopenia is safe and does not increase the risk of sICH or worse outcomes. However, caution is advised in cases of moderate to severe thrombocytopenia, as there is a slightly higher risk of sICH and mortality. Nonetheless, we recommend thrombectomy for LVO patients with thrombocytopenia.

Anaplasma phagocytophilum infection associated with strong inflammatory response in 3 cats.

Anaplasmosis is a vector-borne disease caused by Anaplasma (A.) spp. which currently is still rarely diagnosed in cats. This article describes 3 independent cases of anaplasmosis in cats from different regions of Germany presented to veterinarians in 2021. All cats showed unspecific clinical signs, such as fever, reduced general condition, and decreased appetite. One cat additionally had generalized limb pain, another showed reluctance to move as well as vomiting. On complete blood cell count, only 1 of 3 cats showed mild thrombocytopenia. A. phagocytophilum was detected in blood samples of all 3 cats by polymerase chain reaction. Additionally, in 2 cats (in which blood smears were evaluated) morulae could be detected within neutrophilic granulocytes. Initially, all 3 cats had highly elevated serum amyloid A (SAA) concentrations. Treatment with doxycycline caused a rapid improvement of clinical signs, followed by a decrease of SAA concentrations to normal levels as well as negative PCR results after a treatment duration of at least 28 days. In cats with fever, otherwise unspecific clinical signs with only mild or no hematological changes, elevated SAA concentrations, and previous exposure to ticks, attending veterinarians should consider anaplasmosis as differential diagnosis.