Decline In Platelet Count Research Articles

Chronological Analysis of Acute Hematological Outcomes after Proton and Photon Beam Craniospinal Irradiation in Pediatric Brain Tumors.

PurposeThis study aimed to compare the early hematological dynamics and acute toxicities between proton beam craniospinal irradiation (PrCSI) and photon beam craniospinal irradiation (PhCSI) for pediatric brain tumors.Materials and MethodsWe retrospectively reviewed patients with pediatric brain tumors who received craniospinal irradiation (CSI). The average change in hemoglobin levels (ΔHbavg), absolute lymphocyte counts (ΔALCavg), and platelet counts (ΔPLTavg) from baseline values was evaluated and compared between the PrCSI and PhCSI groups at 1 and 2 weeks after the initiation of CSI, 1 week before and at the end of radiotherapy, and 3–4 weeks after the completion of radiotherapy using t-test and mixed-model analysis.ResultsThe PrCSI and PhCSI groups consisted of 36 and 30 patients, respectively. There were no significant differences in ΔHbavg between the two groups at any timepoint. However, ΔALCavg and ΔPLTavg were significantly lower in the PhCSI group than in PrCSI group at every timepoint, demonstrating that PrCSI resulted in a significantly lower rate of decline and better recovery of absolute lymphocyte and platelet counts. The rate of grade 3 acute anemia was significantly lower in the PrCSI group than in in the PhCSI group.ConclusionPrCSI showed a lower rate of decline and better recovery of absolute lymphocyte and platelet counts than PhCSI in the CSI for pediatric brain tumors. Grade 3 acute anemia was significantly less frequent in the PrCSI group than in the PhCSI group. Further large-scale studies are warranted to confirm these results.

SARS-CoV-2 vaccination and ITP in patients with de novo or preexisting ITP

AbstractCases of de novo immune thrombocytopenia (ITP), including a fatality, following SARS-CoV-2 vaccination in previously healthy recipients led to studying its impact in preexisting ITP. In this study, 4 data sources were analyzed: the Vaccine Adverse Events Reporting System (VAERS) for cases of de novo ITP; a 10-center retrospective study of adults with preexisting ITP receiving SARS-CoV-2 vaccination; and surveys distributed by the Platelet Disorder Support Association (PDSA) and the United Kingdom (UK) ITP Support Association. Seventy-seven de novo ITP cases were identified in VAERS, presenting with median platelet count of 3 [1-9] ×109/L approximately 1 week postvaccination. Of 28 patients with available data, 26 responded to treatment with corticosteroids and/or intravenous immunoglobulin (IVIG), and/or platelet transfusions. Among 117 patients with preexisting ITP who received a SARS-CoV-2 vaccine, 19 experienced an ITP exacerbation (any of: ≥50% decline in platelet count, nadir platelet count <30 × 109/L with >20% decrease from baseline, and/or use of rescue therapy) following the first dose and 14 of 70 after a second dose. Splenectomized persons and those who received 5 or more prior lines of therapy were at highest risk of ITP exacerbation. Fifteen patients received and responded to rescue treatment. In surveys of both 57 PDSA and 43 UK patients with ITP, prior splenectomy was associated with worsened thrombocytopenia. ITP may worsen in preexisting ITP or be identified de novo post–SARS-CoV2 vaccination; both situations responded well to treatment. Proactive monitoring of patients with known ITP, especially those postsplenectomy and with more refractory disease, is indicated.

Vancomycin-related thrombocytopenia in neonates

Background With the improvement of neonatal care in the country and survival of the preterm infants and sick neonates, many arising problems are being observed. One of these is the significant presence of neonatal thrombocytopenia and the need for lots of platelet transfusions per an infant. Many neonatal factors can cause thrombocytopenia, but we observed severe, prolonged thrombocytopenia in infants who received specifically vancomycin for sepsis or other medical/surgical conditions. Literature search revealed that vancomycin can cause immune thrombocytopenia by inducing platelet antibodies, though this is scarcely described in neonates. Participants and methods This is a hospital-based longitudinal study held in NICU during February 2017 to February 2019. All admitted neonates (term and preterm) who received vancomycin were involved, but those with maternal thrombocytopenia, systemic lupus erythematosus (SLE), maternal eclampsia/HELLP (Haemolysis, Elevated Liver enzymes, Low Platelets) syndrome, and Intr Uterine Growth Rrestriction (IUGR) were excluded. Results Of 117 infants admitted in this period, 68 infants fulfilled the inclusion criteria. The severe decline in platelet count observed on the second to third day of vancomycin treatment continued throughout the treatment and started to rise 2–3 days after discontinuation. During treatment with vancomycin, platelet transfusion 2–3 times a day was observed not to raise platelet level significantly, but it prevented serious bleeding. Conclusion Vancomycin-induced thrombocytopenia in neonate is a rising new problem in NICUs. The authors may need to add adjunctive intravenous immunoglobulins or methylprednisolone or change the dosing system to smaller frequent doses, given over longer time, to overcome this serious problem.

ACUTE HEPARIN-INDUCED THROMBOCYTOPENIA WITH DELAYED IN-STENT SUBACUTE THROMBOSIS OF DRUG ELUTING STENTS, INTRACARDIAC THROMBOSIS, BIVENTRICULAR HEART FAILURE, AND HYPOXIA

TOPIC: Cardiovascular Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: Heparin-induced thrombocytopenia (HIT) is a fatal complication in patients with an average exposure of one to two weeks or can be rapid (< 24hrs) on re-exposure. In susceptible patients, antibodies directed against platelet factor 4 and heparin complexes cause HIT with thrombosis (HITTS). An average incidence of HIT is 0.1%-5% in patients on heparin therapy [1] CASE PRESENTATION: A 73-year-old female with a history of coronary disease, hypertension, and hyperlipidemia came to an outside hospital with a persistent cough, dyspnea, and acute hypoxia. She was treated for acute heart failure exacerbation and non-ST segment elevation myocardial infarction (NSTEMI) based on workup. An echocardiogram (ECHO) revealed an ejection fraction (EF) of 50%. She underwent staged percutaneous coronary intervention (PCI) and placement of an everolimus-based stent in the left anterior descending artery (LAD) followed by another stent in the left circumflex artery (LCX) after three days. Following stent placements, she went into pulmonary edema and was placed on noninvasive ventilation and was transferred to our institute to further manage acute hypoxic respiratory failure. Her hypoxia worsened, requiring endotracheal intubation, vasopressor support. She was treated for heart failure exacerbation and pneumonia. A repeat ECHO revealed two right ventricular thrombi with a severe decline in biventricular EF (Figure A). Anticoagulation with heparin was started, followed by a decline in platelet count > 50% due to HIT on day two, and was switched to argatroban (Figure B). Blood work showed NSTEMI, and a coronary angiogram revealed in-stent thrombosis of both stents (Figure C). Repeat successful PCI to LAD, and LCX with thrombus aspiration was completed. The patient had a complicated clinical course and never recovered DISCUSSION: As age increases, the risk of HIT gets higher [1]. HIT increases early mortality by 50% and embolic events by 20%-50%[2,3]. An increased HIT risk in females with cardiopulmonary bypass, hemodialysis, and vascular surgery was observed [4]. Venous thrombosis may be associated with surgery and arterial thrombosis with cardiovascular disease [5]. HIT antibody rate in patients with ACS is high and can induce symptoms in the absence of thrombocytopenia [6]. The odds of early stent thrombosis are < 1%[7]. The occurrence of thrombosis during therapeutic heparin anticoagulation is a concern for HITTS regardless of platelet counts and duration of therapy. Acute NSTEMI due to in-stent and intracardiac thrombosis due to HITTS is rare CONCLUSIONS: HITTS should be suspected in coronary thrombosis of unknown origin. Immediate heparin discontinuation and alternate anticoagulation are a must in HITTS, which can present with normal platelet counts REFERENCE #1: Hogan M, Berger JS. Heparin-induced thrombocytopenia (HIT): Review of incidence, diagnosis, and management. Vasc Med. 2020;25(2):160-73 REFERENCE #2: Solanki J, Shenoy S, Downs E, Palkimas S, Goldman S, Sharma AM. Heparin-Induced Thrombocytopenia and Cardiac Surgery. Semin Thorac Cardiovasc Surg. 2019;31(3):335-44 REFERENCE #3: Warkentin TE. Think of HIT. Hematology Am Soc Hematol Educ Program. 2006;408-414. doi:10.1182/asheducation-2006.1.408 DISCLOSURES: No relevant relationships by Tarang Patel, source=Web Response No relevant relationships by SACHIN PATIL, source=Web Response No relevant relationships by Shyam Shankar, source=Web Response No relevant relationships by Tushar Tarun, source=Web Response No relevant relationships by Ritika Verma, source=Web Response

Data-driven analysis of the kinetics of the JAK2V617F allele burden and blood cell counts during hydroxyurea treatment of patients with polycythemia vera, essential thrombocythemia, and primary myelofibrosis.

Hydroxyurea (HU) treatment of patients with essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF) (MPNs) normalizes elevated blood cell counts within weeks in the large majority of patients. Studies on the impact of HU upon the kinetics of the JAK2V617F allele burden, leukocyte, and platelet counts over time are scarce. Using data-driven analysis as a novel tool to model the kinetics of the JAK2V617F allele burden and blood cell counts over time during treatment with HU. Using serial measurements of JAK2V617F and correlation analysis of routine hematological values (the Hb-concentration, leukocyte count, platelet count, and lactic dehydrogenase), we present a detailed description and analysis of the kinetics of the JAK2V617F, leukocyte, and platelet counts and lactic dehydrogenase in 27 patients (PV=18; ET=7; PMF=2), who were followed in the Danish randomized trial (DALIAH). To further analyze the JAK2V617F kinetics, we use a machine learning clustering algorithm to group the response patterns. Response patterns were highly heterogeneous, with clustering resulting in 3 groups and 3 outliers. In the large majority of patients, HU treatment was initially associated with a modest decline in the JAK2V617F allele burden in concert with a decline in leukocyte and platelet counts. However, HU did not induce a sustained and continuous decrease in the JAK2V617F allele burden. Using data-driven analysis of the JAK2V617F allele burden, leukocyte, and platelet kinetics during treatment with HU, we have shown that HU does not induce a sustained decrease in the JAK2V617F allele burden and neither induces sustained normalization of elevated cell counts in MPN patients. Our results may explain why MPN patients during treatment with HU still have a substantially increased risk of thrombosis.

Spleen Size and Thrombocytopenia After Transcatheter Aortic Valve Implantation

The pathophysiology of thrombocytopenia after transcatheter aortic valve implantation (TAVI) thrombocytopenia is still poorly understood. We assessed the association of spleen size with acquired thrombocytopenia in patients undergoing TAVI. We included 732 patients who underwent TAVI with new generation transcatheter heart valves (THVs) at our center from February 2016 to July 2019. We measured splenic volume index in consecutive patients derived from multidetector row computed tomographic datasets. Patients were stratified according to post-TAVI thrombocytopenia, which was defined as a decline in platelet count (DPC) ≥50% at nadir, and evaluated regarding baseline characteristics and outcome parameters. After the procedure, platelet counts declined from 212.9 ± 67.4×109/L at baseline to 138.8 ± 49.8×109/L at nadir after a median of 2 days (interquartile range [IQR] 2 to 3). Of all patients, 10.1% showed a DPC ≥50%. Compared with patients with DPC <50%, patients with DPC ≥50% had significantly lower splenic volume index (95.5 ml/m2 [IQR 78.0 to 123.7] vs 85.8 ml/m2 [IQR 71.4 to 102.6], p=0.008). A multivariable analysis revealed that the splenic volume index was negatively associated with a DPC ≥50% (OR 0.89, 95% CI 0.82 to 0.97, p=0.005), independent of the type of THV (balloon-expandable THV: OR 2.06, 95% CI 1.13 to 3.76, p=0.02), major bleeding (OR 13.40, 95% CI 3.58 to 50.40, p <0.001), blood transfusion (OR 3.63, 95% CI 1.54 to 8.56, p=0.003), or postprocedural paravalvular leakage ≥moderate (OR 5.48, 95% CI 1.23 to 24.40, p=0.03). Furthermore, DPC ≥50% was independently associated with 1-year mortality (HR 3.36, 95% CI 1.66 to 6.81, p <0.001). In conclusion, acquired thrombocytopenia remains prevalent in modern TAVI patients. Spleen size appears to be associated with the occurrence of thrombocytopenia after TAVI, which is independently correlated with 1-year mortality.

Crimean-Congo Hemorrhagic Fever Mimicking Multisystem Inflammatory Syndrome in Children Associated With COVID-19: A Diagnostic Challenge

To the Editors: Crimean-Congo hemorrhagic fever (CCHF), which is endemic in our country, is a zoonotic disease characterized by fever and hemorrhage that may be severe and even fatal. The primary transmission route to humans is tick bite; however, other forms of transmission are also reported including direct contact with blood or other bodily fluids of infected animals, nosocomial and vertical transmission.1 The clinical diagnosis of CCHF is difficult to establish because symptoms are nonspecific in the prehemorrhagic phase of the disease and laboratory findings are similar to other childhood infectious diseases.1,2 Here, we report two cases with fever, elevated inflammatory markers, and multisystem organ involvement initially considered as multisystem inflammatory syndrome in children (MIS-C), but subsequently diagnosed with CCHF—highlighting the diagnostic challenge in distinguishing MIS-C from other infectious diseases. To our knowledge, no CCHF cases misdiagnosed as MIS-C have been reported to date. Case 1 A 9-year-old boy was referred to our clinic with a preliminary diagnosis of MIS-C because of persisting fever, abdominal pain, conjunctivitis and increasing levels of acute phase reactants despite intravenous antibiotic treatment. His mother had been diagnosed with coronavirus disease-2019 (COVID-19) 2 months prior to admission. On admission, he had tachycardia (130 beats/min), conjunctivitis and maculopapular rash. His laboratory examination revealed lymphocytopenia, thrombocytopenia and elevated levels of liver function tests, troponin, pro-brain natriuretic peptide (pro-BNP) and inflammatory markers including procalcitonin (Table 1). Although all MIS-C criteria were met, CCHF diagnosis was also suspected, despite lack of tick bite, since the patient had progressively decreasing platelet count, and had a history of living in an endemic area and his family was engaged in animal husbandry. Polymerase chain reaction (PCR) test for CCHF was positive, and the patient was treated and discharged without any complications. TABLE 1. - Clinical and Laboratory Findings of Patients Case 1 Case 2 Demographics Age, years 9 15 Gender Male Male Presenting symptoms Fever (duration) Yes (4 days) Yes (3 days) Abdominal pain Yes Yes Vomiting Yes Yes Diarrhea Yes Yes Headache No Yes Nonpurulent conjunctivitis Yes Yes Rash Maculopapular rash Malar rash Admission laboratory findings White blood cell count (×103/µL) 3.49 2.33 Absolute lymphocyte count (/µL) 730 460 Absolute neutrophil count (/µL) 2630 1410 Hemoglobin (g/dL) 14.3 15 Platelet count (/μL) 43,000 130,000 Ferritin (normal range: 6–40 ng/mL) 20,880 1940 D-dimer (normal range: 0–550 ng/mL) 18,100 2150 CRP (normal range: 0–4 mg/L) 78 37 LDH (normal range:140–260 IU/L) 787 455 Albumin level (g/dL) 2.9 4.6 AST/ALT (U/L) 120/115 98/68 Procalcitonin (< 0.5 ng/mL) 8 Not performed Troponin (< 0.05 ng/mL) 0.08 0.03 Pro-BNP (< 71 pg/mL) 160 Not performed Imaging results Abdominal ultrasound Normal Hepatosplenomegaly Echocardiogram Mitral regurgitation Normal Organ system involvement Cardiovascular ✓ No Respiratory No No Gastrointestinal ✓ ✓ Hematologic ✓ ✓ Renal No No Neurologic No No Dermatologic ✓ ✓ SARS-CoV-2 RT-PCR Negative Negative SARS-CoV-2 antibody Negative Negative History of COVID-19 exposure Yes Yes CCHF-related characteristics History of tick bite No No History of close contact with animals Yes Yes CCHF PCR Positive Positive Treatment Ribavirin Ribavirin ALT indicates alanine aminotransferase; AST, aspartate aminotransferase; BNP, brain natriuretic peptide; CCHF, Crimean-Congo hemorrhagic fever; COVID-19, coronavirus disease 19; CRP, C-reactive protein; LDH, lactate dehydrogenase; MIS-C, multisystem inflammatory syndrome; RT-PCR, reverse transcriptase polymerase chain reaction; SARS-CoV-2, severe acute respiratory system coronavirus 2. Case 2 A 15-year-old boy was referred to our hospital with a preliminary diagnosis of MIS-C because of having fever, conjunctivitis, gastrointestinal symptoms, elevated inflammatory markers and history of exposure to his father who had documented COVID-19 infection three months ago. On admission, he had fever, bilateral conjunctivitis, and malar rash. Laboratory analysis revealed lymphocytopenia and thrombocytopenia in addition to elevated inflammatory markers (Table 1). Detailed questioning revealed that he had a history of close contact with animals; however, history of tick bite was not present. On the following days, his fever persisted and platelet count continued to decrease. CCHF PCR was positive and he was treated successfully. To conclude, similar to MIS-C, clinical manifestations of CCHF include fever, headache, myalgia, rash, conjunctivitis, abdominal pain, nausea, vomiting and diarrhea.1,3 Detailed patient history and differential diagnosis are important to avoid unnecessary treatment and protect healthcare providers since infection control measures are essential in CCHF. Our two cases highlight that CCHF should be ruled out when evaluating possible MIS-C, even in the absence of tick bite history, especially in patients with progressive decline in platelet count, those living in endemic areas, and those with a history of close contact with animals.

Incidence and Clinical Outcomes of Thrombocytopenia after Transcatheter Aortic Valve Replacement in Thai Patients

Background: Post-transcatheter aortic valve replacement (TAVR) thrombocytopenia has been reported to be a predictor of higher mortality and worse clinical outcomes in published studies mostly from Western countries; however, data from Asian countries are generally limited, while data from Thai population are lacking. Objective: To evaluate the incidence and outcomes of Thai patients who developed thrombocytopenia after TAVR. Materials and Methods: The present research was a retrospective observational study. The authors collected data from patients underwent TAVR at Siriraj Hospital between 2009 and 2019. The patients were stratified into four groups according to nadir platelet count, no thrombocytopenia with platelet of 150,000/uL or more, mild with platelet of 100,000 to 149,999/uL, moderate at 50,000 to 99,999/uL and severe at less than 50,000/uL. In addition, the patients with moderate to severe thrombocytopenia were stratified into two groups according to the percentage decline in platelet count (DPC) post procedure as DPC of less than 50% or DPC of 50% or more from the baseline platelet count. Results: Eighty-three patients were reviewed. One patient who died intraoperatively was excluded. Thrombocytopenia occurred in 62 patients (75.6%), in which 36.6% (n=30) of the cases were classed as moderate, and 8.5% (n=7) as severe thrombocytopenia. The platelet count returned to baseline before discharge or during the follow-up period in 83.8% (n=52) of patients. The incidence of in-hospital mortality was significantly higher in patients with severe thrombocytopenia than those with mild thrombocytopenia at 28.6% versus 4% (p=0.011). The duration of admission, length of stay in the CCU, incidence of life-threatening bleeding, clopidogrel discontinuation, platelet transfusion, rate of infection, shock, and acute kidney injury were also significantly higher in patients with moderate to severe thrombocytopenia. Conclusion: Acquired thrombocytopenia after TAVR is a common phenomenon in Thai patients (75%) but usually transient with a nadir platelet count greater than 50,000/uL. Most patients had spontaneous platelet recovery. The presence of severe thrombocytopenia with a nadir platelet count of less than 50,000 is a red flag sign for concomitant infection. The severity of thrombocytopenia is significantly associated with higher mortality and post-procedural adverse events. Keywords: Thrombocytopenia; Transcatheter aortic valve replacement (TAVR)

Usefulness of Thrombopoietin Receptor Agonists for Thrombocytopenia after Allogeneic Stem Cell Transplantation. An Eight-Year Single Center Experience

IntroductionProlonged isolated thrombocytopenia (PT) and secondary failure of platelet recovery (SFPR) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) are well known complications that could lead to a potentially lethal bleeding. To date, there are not specific guidelines for the treatment of post allo-HSCT thrombocytopenia, being platelet transfusion the mainstay of the management. Thrombopoietin receptor agonists (TRA), e.g. Eltrombopag (ETP) and Romiplostim have been approved for the treatment of primary immune thrombocytopenia and thrombocytopenia in other conditions (e.g. aplastic anemia) but information on their role in the allo-HSCT is scarce. The aims of our study were a) to analyze the effectiveness, in terms of platelet recovery and length of the response, and b) the safety profile of TRA for the treatment of thrombocytopenia after allo-HSCT in our Institution.MethodsWe performed a retrospective study on 467 patients who underwent to allo-HSCT from 2010 to 2017 in our center, of which a total of 17 patients were treated with TRA as compassionate use for thrombocytopenia after peripheral blood allo-HSCT. In order to be subsidiary to receive a TRA, patients had to be in complete remission with complete chimerism. Patients with thrombocytopenia related to cytomegalovirus and/or thrombotic microangiopathy were excluded. PT was defined as the engraftment of all peripheral blood cell lines but with a platelet (PLT) count <20,000/μL or dependence on PLT transfusions for more than 60 days after allo-HSCT. SFPR was defined as a decline in PLT count <20,000/μL for 7 consecutive days, or requirement of transfusion support after achievement of sustained PLT count ≥50,000/μL without transfusions for 7 consecutive days post-HSCT. The effectiveness or response consisted on achieving platelet recovery (≥20,000/μL) and transfusion independence of at least 7 days.ResultsPatient characteristics are detailed in table 1. One patient was excluded due to short course of treatment that was not evaluable. Platelet recovery and transfusion independence was achieved in 9 out of 16 patients (56%) with a median of 71 days (range: 8-176 days). Three of these responder-patients (R-patients) were switched to an alternative TRA in order to achieve response. Most of the R-patients had SFPR (n=7; 78%). Four patients (44%) were previously treated with mesenchymal stromal cells (MSC; n=2), immunoglobulins (n=3) and/or rituximab (n=1). The median of treatment duration was 181 days (21-350) and all R-patients (n=9) discontinued TRA. At the last follow-up, with a median of 282 days (67-1617), 7 out 9 patients (78%) maintained the response [P=152,000/μL (11,000-358,000)] and 6 (67%) are alive.Among NR-patients (n=7; 43.7%), the median duration of TRA treatment was 14 days (8-82) and 3 patients (43%) were previously treated (MSC and/or immunoglobulins). The main characteristics of NR-patients related to poor response were: active acute graft-versus host disease (GVHD) (n=2; p=0,038), active chronic GVHD (n=1; p=0,025), decreased number of bone marrow megakaryocytes (<++) (n=6; p>0,05), 5 (71%) required platelet transfusion frequency >2 times per week (p>0,05) and all NR-patients received packed red blood cell transfusions (p=0,09). In this group, at the last follow-up, with a median of 86 days (9-144), all except one patient died due to infection (n=5; 83%) or relapse disease (n=1). Finally, no adverse events were related to TRA.ConclusionsTreatment of thrombocytopenia after allo-HSCT with TRA is feasible. Further prospective studies are necessary to determine if these treatments may be considered as a potentially therapeutic alternative. [Display omitted] DisclosuresSanchez-Guijo:Pfizer: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding.

Copper Deficiency

BACKGROUND: Acquired copper deficiency in the pediatric population is a rare event but given the hematologic and potentially irreversible neurologic consequences, prompt recognition and treatment is important. Copper is an essential cofactor in enzymatic reactions essential to proper hematologic, skeletal, neurologic and vascular function. Copper is found in a variety of foods including meats, nuts, legumes, and whole grains while lacking in highly processed foods. Copper requirements in children over the age of 4 is 15 mg/day, which is readily acquired in a typical diet. Copper deficiency is known to occur in patients with the rare X-linked mutation in the ATP7A copper transport protein, known as Menkes Syndrome, and in older individuals with gastrointestinal bypass surgery who lose the ability to absorb copper through the duodenum and proximal jejunum, however, it is rarely reported in other conditions. Pediatric patients with autism spectrum disorders or developmental delay with a limited dietary repertoire are at risk for copper deficiency thus a high index of suspicion must exist in order to diagnose the disorder.CASE PRESENTATION: A 15 y/o boy with a prior diagnosis of global developmental delay and oral aversion presented with parental concerns for worsening fatigue, weakness and gait instability. Symptoms had been slowly progressive and accompanied by weight loss. His longstanding feeding difficulties had been refractory to intensive feeding programs yet he continued to feed orally (with no prior attempts at enteral/parenteral nutrition). A daily diet consisted only of 50-60 oz of milk and 25-30 individual servings of butterscotch pudding (1680-1880 calories/day, 0.7mg iron/day).Upon presentation he was afebrile with global muscle weakness. Growth parameters were at the 25th and 2nd percentiles for height and weight, respectively. Initial complete blood count demonstrated white blood cell count of 3.3, absolute neutrophil count of 760, hemoglobin of 4.4 with MCV of <50, reticulocyte count of 0.5, platelet count of 392. Review of his peripheral blood smear revealed microcytic, hypochromic red cells without marked fragmentation, anisopoikilocytosis or ringed sideroblasts; there were no morphologic abnormalities of his leukocytes or platelets. Iron studies demonstrated ferritin of 45, total iron binding capacity of 514, and 2% iron saturation. He had no evidence of B12 or folate deficiency. Stool guaiac was negative for occult blood loss. He was hospitalized to receive transfusion of red blood cells and begin IV iron therapy due to his inability to tolerate oral repletion.Over the the next 2 months he demonstrated some improvement in his anemia but had worsening leukopenia, neutropenia and a declining platelet count. He had worsening neurologic function with increasing need for assistance in his activities of daily living. Due to lack response to IV iron and worsening cytopenias, additional evaluation was performed which revealed a serum copper level of 6 (range 60-190), and cerulosplasmin of 2.1 (range 22-58).Once a diagnosis of copper deficiency was made, the patient promptly began a course of parenteral copper repletion. He received IV copper 35mcg/kg/day x 3 days then weekly intravenous infusions. Given his malnutrition, a G-tube was placed to begin oral copper repletion and enteral nutrition. Within 3 weeks his copper level improved as well as his blood counts. Unfortunately, although his blood counts and copper levels normalized, his neurologic status remains below his old baseline although he has made gains in his gross and fine motor abilities.DISCUSSION: Children with limited dietary repertoires are at risk for otherwise rare nutritional deficiencies such as copper deficiency. It is not uncommon that nutritional deficiencies may become more prominent when children reach puberty and have increased dietary requirements not only of calories, but also of micronutrients and trace elements. This patient's clinical course demonstrates the need to have a high index of suspicion of concomitant nutritional deficiencies other than those routinely evaluated such as iron, B12 and folate given his finding of both iron and copper deficiency. Review of his blood smear at presentation was consistent with iron deficiency and did not demonstrate typical hallmarks of copper deficiency such as ringed sideroblasts. DisclosuresMalec:Bioverativ: Consultancy, Other: Research funding; Shire: Consultancy, Other: Research funding.

Exacerbation of immune thrombocytopenia following COVID-19 vaccination.

SummaryThere is concern that COVID‐19 vaccination may adversely affect immune thrombocytopenia (ITP) patients. Fifty‐two consecutive chronic ITP patients were prospectively followed after COVID‐19 vaccination. Fifteen percent had no worsening of clinical symptoms but no post‐vaccination platelet count; 73% had no new symptoms and no significant platelet count decline. However, 12% had a median platelet count drop of 96% within 2–5 days post vaccination with new bleeding symptoms; after rescue therapy with corticosteroids +/− intravenous immunoglobulin (IVIG), platelets recovered to >30 × 109/l a median three days later. ITP exacerbation occurred independently of remission status, concurrent ITP treatment, or vaccine type. Safety of a second vaccine dose needs careful assessment.

Chronic Hepatitis Is Common and Often Untreated Among Children with Hepatitis B Infection in the United States and Canada

To determine the outcomes of chronic hepatitis B virus (HBV) infection in a large, prospectively studied cohort of children in the US and Canada. This was a prospective, observational study of children with chronic HBV enrolled in 7 clinical centers and evaluated at baseline, weeks 24 and 48, and annually thereafter, with analysis of demographic, clinical, physical examination, and blood test data. Among 362 children followed for a median of 4.2years, elevated alanine aminotransferase (ALT) levels (>1 upper limit of normal) were present in 72% at last evaluation, including in 60% of children with loss of hepatitis B e antigen during follow-up and 70% of those who were hepatitis B e antigen negative at baseline. Significant ALT flares (male patients ≥400 U/L, female patients ≥350 U/L) occurred in 13 children. Of 129 children who fulfilled the American Association for the Study of Liver Diseases treatment criteria during follow-up, anti-HBV treatment was initiated in only 25. One child died (unrelated to liver disease), 1 developed cirrhosis, but no episodes of cirrhotic decompensation or hepatocellular carcinoma were observed. Decline in platelet count was inversely associated with ALT elevations. In a cohort of children with chronic HBV infection in the US and Canada, many children remained at risk of progressive liver disease due to active hepatitis, but major clinical outcomes such as cirrhosis, cancer, and death were rare. Many children who met criteria for treatment remained untreated.

Platelet count patterns and patient outcomes in sepsis at a tertiary care center: Beyond the APACHE score.

Acute physiology and chronic health evaluation II (APACHE-II) scoring system is used to classify disease severity of patients in the intensive care unit. However, several limitations render the scoring system inadequate in identifying risk factors associated with outcomes. Little is known about the association of platelet count patterns, and the timing of platelet count and other hematologic parameters in predicting mortality in patients with sepsis.This retrospective observational study included 205 septic shock patients, with an overall mortality of 47.8%, enrolled at a tertiary care hospital in Riyadh, Kingdom of Saudi Arabia between 2018 and 2020. Bivariate and multivariate regression analyses were used to identify hematologic risk factors associated with mortality. We used the bivariate Pearson Correlation test to determine correlations between the tested variables and APACHE-II score.Two platelet count patterns emerged: patients with a decline in platelet count after admission (group A pattern, 93.7%) and those with their lowest platelet count at admission (group B pattern, 6.3%). The lowest mean platelet count was significantly lower in nonsurvivors (105.62 ± 10.67 × 103/μL) than in survivors (185.52 ± 10.81 × 103/μL), P < .001. Bivariate Pearson correlation revealed that the lowest platelet count and platelet count decline were significantly correlated with APACHE-II score (r = −0.250, P < .01), (r = 0.326, P < .001), respectively. In multiple logistic regression analysis, the independent mortality risk factors were degree of platelet count decline in group A (odds ratio, 1.028 [95% confidence interval: 1.012–1.045], P = .001) and platelet pattern in group B (odds ratio, 6.901 [95% confidence interval: 1.446–32.932], P = .015). The patterns, values, subsets, and ratios of white blood cell count were not significantly associated with mortality.Nadir platelet count and timing, and degree of platelet count decline are useful markers to predict mortality in early septic shock. Therefore, platelet count patterns might enhance the performance of severity scoring systems in the intensive care unit.

Vancomycin Induced Thrombocytopenia Complicating Permanent Pacemaker Placement: A Case Report

Introduction: Vancomycin is widely used in patients with methicillin resistant staphylococcus aureus (MRSA) infections or with other infections unresponsive to other antibiotics. Vancomycin-related adverse effects, including nephrotoxicity, ototoxicity, red-man syndrome, and neutropenia have been reported. Vancomycin induced thrombocytopenia is a rare complication of vancomycin that many physicians are unaware of. When an acute decline in platelet count or bleeding occur in patients on vancomycin, vancomycin- induced thrombocytopenia should be considered. Case: We present a case of acute severe thrombocytopenia that occurred within 12 hours after vancomycin infusion in a patient that received permanent pacemaker placement. Vancomycin was discontinued and patient’s platelets returned to baseline five days after vancomycin was discontinued. Conclusion: This case report highlights the importance of physicians being aware of vancomycin induced thrombocytopenia, a rare but reversible complication of vancomycin, which if diagnosed early will lead to early discontinuation of vancomycin, early resolution of thrombocytopenia and reduced hospital stay.

Analysis of high-risk factors and clinical characteristics of sepsis-related liver injury

To analyze the risk factors and clinical characteristics of liver injury in patients with sepsis and to provide a reference for early recognition, early diagnosis, early intervention, and improve the survival rate of patients. The clinical data of sepsis patients admitted to the department of general intensive care unit (ICU) of the Second Affiliated Hospital of Zhejiang University School of Medicine from July 2014 to October 2020 were retrospectively analyzed. According to the occurrence of acute liver injury, patients with sepsis were divided into the liver injury group and the non-liver injury group, and the differences of demographic data, history, history of primary diseases, laboratory indicators on the first time of admission, treatments, the severity of the disease and other indicators were compared and analyzed. Logistic regression was used to analyze the risk factors for sepsis-related liver injury. A total of 527 patients with sepsis were enrolled, and 129 patients with acute liver injury, accounting for 24.48%. Compared with the non-liver injury group, acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA), pro-brain natriuretic peptide (pro-BNP), serum MB isoenzyme of creatine kinase (CK-MB), total bile acid (TBA), serum creatinine (SCr), blood urea nitrogen (BUN), lactic acid (Lac), lactate dehydrogenase (LDH), C-reactive protein (CRP), procalcitonin (PCT) in liver injury group were significantly increased [APACHE II score: 23.00±10.40 vs. 16.10±8.10, SOFA score: 9.17±4.29 vs. 5.90±3.12, pro-BNP (ng/L): 5 500.0 (1 166.0, 16 865.0) vs. 1 377.2 (448.8, 6 136.5), CK-MB (U/L): 23.0 (13.0, 55.0) vs. 18.0 (13.0, 31.0), TBA (μmol/L): 5.0 (2.4, 12.9) vs. 2.6 (1.4, 4.9), SCr (μmol/L): 146.0 (75.0, 222.0) vs. 71.0 (52.0, 125.8), BUN (mmol/L): 13.4 (8.8, 20.2) vs. 7.9 (4.9, 11.6), Lac (mmol/L): 2.0 (1.4, 4.4) vs. 1.4 (1.0, 2.2), LDH (μmol×s-1×L-1): 6.43 (3.76, 11.99) vs. 4.55 (3.38, 6.63), CRP (mg/L): 113.0 (61.8, 201.0) vs. 95.0 (37.3, 170.1), PCT (μg/L): 3.8 (1.0, 23.3) vs. 0.8 (0.2, 6.4)], prothrombin time (PT), international standard ratio (INR) and activated partial thrombin time (APTT) were significantly longer [PT (s): 19.4±7.6 vs. 16.0±4.0, INR: 1.7±1.0 vs. 1.3±0.5, APTT (s): 54.0±25.8 vs. 44.1±15.1], plasma fibrinogen (FIB), platelet count (PLT), albumin (ALB), and cholesterol (CHOL) were decreased [FIB (g/L): 4.2±2.3 vs. 4.9±1.8, PLT (×109/L): 116.3±74.3 vs. 182.7±108.6, ALB (g/L): 25.4±5.5 vs. 27.6±5.5, CHOL (mmol/L): 2.5±1.2 vs. 3.2±1.3], the probability of shock was significantly increased (91.47% vs. 59.19%), and the duration of shock was prolonged [days: 5.0 (2.0, 9.0) vs. 1.0 (0.0, 3.0)], positive rate of microbial culture (81.40% vs. 71.11%), probability of occurrence of drug-resistant bacteria (67.44% vs. 47.99%) were significantly higher, mechanical ventilation time [days: 6.0 (2.0, 12.7) vs. 2.4 (0.0, 6.9)], continuous renal replacement therapy (CRRT) time [days: 1.2 (0.0, 5.0) vs. 0.0 (0.0, 0.0)], the length of intensive care unit (ICU) stay [days: 9.0 (5.0, 18.0) vs. 7.0 (3.0, 13.0)] were significantly longer, 28-day mortality was significantly higher (80.62% vs. 28.89%), and the differences were statistically significant (all P < 0.05). Further Logistic regression analysis showed that PLT decline, PT prolongation, CRRT duration, shock duration and 28-day mortality were correlated with sepsis-related liver injury [odds ratios (OR) and 95% confidence interval (95%CI) were 0.992 (0.987-0.998), 3.103 (1.507-6.387), 1.198 (1.074-1.336), 1.196 (1.049-1.362), and 0.213 (0.072-0.633), respectively, all P < 0.05]. Prolonged PT and decreased PLT are independent risk factors for sepsis complicated with liver injury. The long duration of CRRT, long duration of shock, and high mortality are independent clinical characteristics of patients with sepsis-related liver injury.

Outcomes With Heparin-Induced Thrombocytopenia After Cardiac Surgery

Heparin-induced thrombocytopenia (HIT) is an immune-mediated reaction to heparin that provokes a prothrombotic state and causes a decline in platelet count. Data describing outcomes of HIT after cardiac surgeryare limited. This study sought to determine theimpact of HIT on short-term outcomes after cardiac surgery. This was an observational study of cardiac surgeries from 2010 to 2018. Patients with HIT were matched against patients without HIT using 2:1 nearest-neighbor propensity matching. Matching was performed to assess the impact of HIT on operative mortality (The Society of Thoracic Surgeons definition) and thromboembolic events (including deep vein thrombosis, pulmonary embolism, stroke, and/or acute limb ischemia), which were the primary outcomes of interest. Of 11,820 patients undergoing a Society of Thoracic Surgeons indexed cardiac surgery, 131 (1.1%) developed HIT after their index operation. After matching operative mortality was 21.8% in HIT patients compared with 5.3% in non-HIT patients. Thromboembolic events occurred in 29.1% of HIT patients compared with 2.9% in non-HIT patients. On subanalysis operative mortality was significantly higher for the HIT group without thromboembolic events (16.7%) and the HIT group with thromboembolic events (34.4%) compared with the non-HIT group (5.3%). However operative mortality was not significantly higher in the HIT group with thromboembolic events compared with the HIT group without thromboembolic events, after Bonferroni correction. Although uncommon, HIT is a highly morbid and potentially lethal complication, which should reinforce the importance of timely recognition and treatment of this adverse outcome.

Longitudinal decrease in platelet counts as a surrogate marker of liver fibrosis.

BACKGROUNDLiver cirrhosis is a significant source of morbidity and mortality worldwide. The disease is usually indolent and asymptomatic early in its course while many cirrhotic patients are diagnosed late when severe complications occur. A major challenge is to diagnose advanced fibrosis as early as possible, using simple and non-invasive diagnostics tools. Thrombocytopenia represents advanced fibrosis and portal hypertension (HTN) and most non-invasive scores that predict liver fibrosis incorporate platelets as a strong risk factor. However, little is known about the association between longitudinal changes in platelet counts (PTC), when still within the normal range, and the risk of cirrhosis.AIMTo explore whether platelet counts trajectories over time, can predict advanced liver fibrosis across the different etiologies of liver diseases.METHODSA nested case-control study utilizing a large computerized database. Cirrhosis cases (n = 5258) were compared to controls (n = 15744) matched for age and sex at a ratio of 1:3. All participants had multiple laboratory measurements prior to enrollment. We calculated the trends of PTC, liver enzymes, bilirubin, international normalized ratio, albumin and fibrosis scores (fibrosis-4 and aspartate transaminase-to-platelet ratio index) throughout the preceding 20 years prior to cirrhosis diagnosis compared to healthy controls. The association between PTC, cirrhosis complications and fibrosis scores prior to cirrhosis diagnosis was investigated.RESULTSThe mean age in both groups was 56 (SD 15.8). Cirrhotic patients were more likely to be smokers, diabetic with chronic kidney disease and had a higher prevalence of HTN. The leading cirrhosis etiologies were viral, alcoholic and fatty liver disease. The mean PTC decreased from 240000/μL to 190000/μL up to 15 years prior to cirrhosis diagnosis compared to controls who’s PTC remained stable around the values of 240000/μL. This trend was consistent regardless of sex, cirrhosis etiology and was more pronounced in patients who developed varices and ascites. Compared to controls whose values remained in the normal range, in the cirrhosis group aspartate aminotransferase and alanine aminotransferase, increased from 40 U/L to 75 U/L and FIB-4 increased gradually from 1.3 to 3 prior to cirrhosis diagnosis. In multivariable regression analysis, a decrease of 50 units in PTC was associated with 1.3 times odds of cirrhosis (95%CI 1.25-1.35).CONCLUSIONIn the preceding years before the diagnosis of cirrhosis, there is a progressive decline in PTC, within the normal range, matched to a gradual increase in fibrosis scores.

Phototherapy in full term neonates suffering from unconjugated hyperbilirubinemia; Does it affect platelet count?

Objectives: Investigating the hazardous effect of Phototherapy on Platelet counts in healthy neonates with Neonatal hyperbilirubinemia (NH). Study Design: Cross Sectional study. Setting: Department of Paediatrics, SMBB Medical College Layari General Hospital, Karachi, Sindh. Period: January 2018 to May 2019. Material &amp; Methods: A sample of 313 neonates suffering from NH was selected according to the inclusion and exclusion criteria. Blood Platelets were counted at baseline, and 24, 48 and 72 hours of phototherapy. Statistical software SPSS 21.0 (IBM, Incorp, USA) was used for data analysis using paired t-test and Pearson`s Chi- square test at P≤0.05. Results: Platelet counts at 24, 48 and 72 hours of phototherapy were found 2.97±0.45×109/L, 3.38±0.48×109/L and 3.52± 0.47×109/L respectively. Platelet counts at 24, 48 and 72 hours showed statistically significant difference compared to baseline counts (P&lt;0.05). A statistically insignificant decline in total population platelet count after phototherapy was noted (P&gt;0.05). However, thrombocytopenia was noted in 9 (2.87%) cases; comprising mild and moderate in 7 (2.23%) and 2 (0.64%) cases respectively. Conclusion: The present study observed thrombocytopenia in 9 (2.87%) of total cases; of which mild and moderate thrombocytopenia occurred in 7 (2.23%) and 2 (0.64%) cases respectively.

A comparison between leukocyte reduced low titer whole blood vs non-leukocyte reduced low titer whole blood for massive transfusion activation.

Hemorrhagic shock is the leading cause of survivable death in trauma patients and recent literature has focused on resuscitation strategies including transfusing low-titer group O whole blood (LTOWB). Debate remains regarding whether leukocyte reduced (LR) whole blood is of clinical benefit or detriment to patients requiring massive transfusion. This study compares survival outcomes between LR-LTOWB and non-LR LTOWB. The objective of this prospective, observational study was to detect any difference in 24-hour survival between patients receiving LR-LTOWB and non-LR LTOWB during their massive transfusion activation. Secondary objectives were to report any difference in ICU LOS, ventilation days, in-hospital survival, and hospital LOS. Data collected included patient sex, age, mechanism of injury, Injury Severity Score (ISS), Trauma Injury Severity Score (TRISS), cause of death, and number of LTOWB transfused. A total of 167 patients received 271 LTOWB transfusions. There were 97 patients that received 168 units of LR-LTOWB while 70 patients received 103 units of non-LR LTOWB. The two study groups were comparable in terms of age, sex, ISS, TRISS, and the number of LTOWB transfused. The use of LR LTOWB during the initial massive transfusion activation in traumatically injured patients was not associated with increased 24-hour survival compared to when using non-LR LTOWB. No transfusion associated adverse events were reported. The administration of either LR or non-LR LTOWB was not associated with >24 hours survival in patients presenting with massive hemorrhage. The high cost and the rapid decline in platelet count of LR whole blood may be a consideration.

Low-Normal Platelets and Decreasing Platelets Are Risk Factors for Hearing Impairment Development.

Identification of undefined risk factors will be crucial for the development of therapeutic strategies in hearing impairment. Platelets are likely to affect the development of sudden sensorineural hearing loss, which is a primary risk factor for permanent hearing impairment. This implies that abnormal platelets might contribute to long-term hearing loss. This study investigated the role of platelets in the development of hearing impairment over a 5-year period. This study was a retrospective cohort study and consisted of a population-based survey, which was performed for 1,897 participants in 2014 to 2019. To evaluate the effect of platelet level on hearing ability, the subjects were divided into two groups: a high-normal platelet group (25 ∼ 40 × 104 cells/μL) and a low-normal platelet group (15 ∼ 25 × 104 cells/μL). Subjects were defined as having hearing impairment when pure tone audiometry was over 25 dB HL in either ear (tested in 2017 and 2019). Incidence of hearing impairment was analyzed. Incidence of hearing impairment at low frequencies was significantly higher in the low-normal platelet group than in the high-normal group year over year. Low-normal platelet count associated with low-frequency hearing impairment (LFHI) incidence (odds ratio [OR], 2.34; 95% confidence interval [CI], 1.15-4.76). In the low-normal platelet group, subjects whose counts declined from baseline developed more LFHI than those whose counts increased over time. Further, decreasing platelets appeared to be an independent risk factor contributing to the incidence of LFHI (OR, 2.10; 95%CI, 1.09-4.06) in the low-normal platelet group. Both a low-normal platelet and a declining platelet count were independently associated with the incidence of LFHI. 3 Laryngoscope, 131:E1287-E1295, 2021.