Nadir Platelet Count Research Articles

Assessment of Platelet Count in Pediatric Patients with Dengue Fever Admitted in A Tertiary Care Hospital of Bangladesh

Background: Dengue is a major vector-borne disease that is prevalent in tropical and sub-tropical countries. A hallmark of dengue fever is thrombocytopenia. This study was conducted to evaluate the platelet count in relation to severity and outcome of dengue infection in a cohort of hospitalized children during 2019 dengue outbreak in Bangladesh.
 Materials and methods: This observational study was carried out in the Department of Pediatrics of Chittagong Medical College Hospital, Chattogram, Bangladesh. One hundred and ninety two consecutive serologically positive dengue cases (Age £ 12 years) admitted from July 2019 to December 2019 were enrolled in the study. Platelet count was done daily from day 3 to 7 days of illness.
 Results: Overall the mean age was 7.04 (±3.23) years with male preponderance (59.4%). As per the nadir platelet count 53 (27.7%) patients had counts >150,000, 66 patients (34.3%) had count between 100,000 and 150,000, 36 patients (18.7) had count between 50,000 and 1, 00,000, 13 patients (15.1%) had count between 20,000 and 50,000 while the remaining 6 patients (3.1%) had profound thrombocytopenia. Children with profound thrombocytopenia were likely to had dengue shock syndrome and prolonged hospitalization. There was no fatality in this series.
 Conclusion: Though thrombocytopenia was common profound thrombocytopenia was not frequent in the hospitalized pediatric patients with dengue infection.
 IAHS Medical Journal Vol 4(2), June 2021; 13-16

Managing argatroban in heparin-induced thrombocytopenia: Aretrospective analysis of 729 treatment days in 32 patients with confirmed heparin-induced thrombocytopenia.

Managing argatroban in heparin-induced thrombocytopenia: Aretrospective analysis of 729 treatment days in 32 patients with confirmed heparin-induced thrombocytopenia.

Pre- and postpregnancy platelet counts: evaluating accuracy of gestational thrombocytopenia and immune thrombocytopenia purpura diagnoses

Given the overlapping clinical indicators and lack of diagnostic testing, misdiagnosis of immune thrombocytopenic purpura and gestational thrombocytopenia in pregnancy may be common. Current recommendations suggest utilizing platelet nadir during pregnancy to guide diagnosis. This study aimed to assess the accuracy of gestational thrombocytopenia and immune thrombocytopenic purpura diagnoses using pre- and postpregnancy platelet counts. This was a retrospective cohort study of patients diagnosed with gestational thrombocytopenia and immune thrombocytopenic purpura from January 2017 to December 2019. Platelet counts were extracted from charts and evaluated at several time periods, namely prepregnancy (within 5 years), during pregnancy, and postpartum (>6 weeks to 5 years). A diagnosis of gestational thrombocytopenia was considered inaccurate if platelet counts were <150,000/µL pre- or postpregnancy with no other apparent causes or if the platelet nadir dropped below 100,000/µL during pregnancy. A diagnosis of immune thrombocytopenic purpura was deemed inaccurate if pre- or postpregnancy platelet counts were >150,000/µL. The primary outcome was accuracy of gestational thrombocytopenia and immune thrombocytopenic purpura diagnoses in patients. Secondary outcomes included mean platelet counts during pregnancy and difference in mean platelet counts for patients with an accurate vs inaccurate diagnosis of gestational thrombocytopenia. Outcomes were summarized with descriptive statistics and compared using Student t tests. A total of 116 patients met the inclusion criteria of which 111 (96%) and 5 (4%) had gestational thrombocytopenia and immune thrombocytopenic purpura diagnoses, respectively. Platelet counts outside of pregnancy were available for 91 (82%) of the patients, and 66 (57%) had prepregnancy platelet counts available. Of the 91 patients, the diagnosis was considered accurate in 61 (67%) and 5 (100%) patients with gestational thrombocytopenia and immune thrombocytopenic purpura, respectively. Conversely, 30 of 35 (86%) patients with immune thrombocytopenic purpura were found to be inaccurately diagnosed with gestational thrombocytopenia after application of platelet thresholds. Among these 30 patients, 10 had a prepregnancy platelet count <150,000/µL, 12 had a postpartum platelet count <150,000/µL, 3 had a platelet count nadir <100,000/µL during pregnancy, and 7 met more than 1 criterion. Pre- and postpregnancy platelet counts and platelet count nadir differed significantly for patients with an accurate vs inaccurate diagnosis of gestational thrombocytopenia (P<.001). When pre- and postpregnancy platelet counts were checked, one-third of cases of gestational thrombocytopenia met the criteria for immune thrombocytopenic purpura and were thus incorrectly diagnosed during pregnancy. Prepregnancy platelet counts, available for most patients, should be considered when diagnosing gestational thrombocytopenia vs immune thrombocytopenic purpura.

Incidence of bleeding and thromboembolism and impact on overall survival in adult patients with hemophagocytic lymphohistiocytosis: A 20‐year provincial retrospective cohort study

BackgroundHemophagocytic lymphohistiocytosis (HLH) is a rare syndrome characterized by uncontrolled immune activation and high risk of death. There is scarce data on the incidence of bleeding and thromboembolism in HLH. ObjectivesTo determine the cumulative incidence of bleeding and thromboembolism and impact on survival in adults with HLH. Patients/MethodsWe conducted a multicenter retrospective cohort study of adults with HLH in Alberta, Canada (1999–2019). The cumulative incidence of bleeding and thromboembolism were calculated, accounting for competing risks. Cox proportional hazards models were used to assess the impact of bleeding and thromboembolism on overall survival (OS). ResultsWe identified 97 adults with HLH (median age 46 years). Venous thromboembolism (VTE) occurred in 11 (11%) patients at a median of 9 days from admission. ISTH major bleeding and clinically relevant non‐major bleeding occurred in 39 (40%) patients, at a median of 16 days after admission. Nadir platelet count (adjusted odds ratio [aOR] 1.8 per log decrease, 95% confidence interval [CI] 1.2–2.8) and mechanical ventilation (aOR 4.9, 95% CI 1.8–14.8) were independent predictors of bleeding on multivariable analysis. Adjusting for competing risks, the 90‐day cumulative incidences of bleeding and thromboembolism were 39% and 13%, respectively. The median OS was 18.8 months. VTE, but not bleeding, was significantly associated with adverse OS (adjusted hazard ratio 2.5, 95% CI 1.1–5.7). ConclusionsIn adults with HLH, VTE appears more common than previously described and is a predictor of mortality, although this may be due to unadjusted confounding. VTE prevention and treatment are challenging due to high bleeding rates.

Platelet Transfusion and In-Hospital Mortality in Veno-Arterial Extracorporeal Membrane Oxygenation Patients.

Thrombocytopenia is common during extracorporeal membrane oxygenation (ECMO), and platelets are sometimes transfused to meet arbitrary goals. We performed a retrospective cohort study of veno-arterial (VA) ECMO patients from a single academic medical center and explored the relationship between platelet transfusion and in-hospital mortality using multivariable logistic regression. One hundred eighty-eight VA ECMO patients were included in the study. Ninety-one patients (48.4%) were transfused platelets during ECMO. Patients who received platelet transfusion had more coronary artery disease, lower platelet counts at cannulation, higher predicted mortality, lower nadir platelet counts, more ECMO days, and more red blood cell (RBC) and plasma transfusion. Mortality was 19.6% for patients who received no platelets, 40.8% for patients who received 1-3 platelets, and 78.6% for patients who received 4 or more platelets ( P &lt; 0.001). After controlling for confounding variables including baseline severity of illness, central cannulation, postcardiotomy status, RBC and plasma transfusion, major bleeding, and total ECMO days, transfusion of 4 or more platelets remained associated with in-hospital mortality; OR = 4.68 (95% CI = 1.18-27.28), P = 0.03. Our findings highlight the need for randomized controlled trials that compare different platelet transfusion triggers, so that providers can better understand when platelet transfusion is indicated in VA ECMO patients.

COVID-19 vaccination in patients with immune thrombocytopenia

AbstractImmune thrombocytopenia (ITP) is an acquired autoimmune disorder that is characterized by low platelet count and increased bleeding risk. COVID-19 vaccination has been described as a risk factor for de novo ITP, but the effects of COVID-19 vaccination in patients with ITP are unknown. We aimed to investigate the effects of COVID-19 vaccination in patients with ITP on platelet count, bleeding complications, and ITP exacerbation (≥50% decline in platelet count, or nadir platelet count < 30 × 109/L with a >20% decrease from baseline, or use of rescue therapy). Platelet counts in patients with ITP and healthy controls were collected immediately before and 1 and 4 weeks after the first and second vaccinations. Linear mixed-effects modeling was applied to analyze platelet counts over time. We included 218 patients with ITP (50.9% female; mean age, 55 years; and median platelet count, 106 × 109/L) and 200 healthy controls (60.0% female; mean age, 58 years; median platelet count, 256 × 109/L). Platelet counts decreased by 6.3% after vaccination. We did not observe any difference in decrease between the groups. Thirty patients with ITP (13.8%; 95% confidence interval [CI], 9.5-19.1) had an exacerbation and 5 (2.2%; 95% CI, 0.7-5.3) suffered from a bleeding event. Risk factors for ITP exacerbation were platelet count < 50 × 109/L (odds ratio [OR], 5.3; 95% CI, 2.1-13.7), ITP treatment at time of vaccination (OR, 3.4; 95% CI, 1.5-8.0), and age (OR, 0.96 per year; 95% CI, 0.94-0.99). Our study highlights the safety of COVID-19 vaccination in patients with ITP and the importance of the close monitoring of platelet counts in a subgroup of patients with ITP. Patients with ITP with exacerbation responded well on therapy.

442 Thrombocytopenia following transcatheter aortic valve implantation in portico and Evolute recipients

Abstract Aims Thrombocytopenia (TP) following transcatheter aortic valve implantation (TAVI) is a common phenomenon and is associated with mortality and complications. The underlying mechanisms are still unclear. Few data exist on differential risk of thrombocytopenia between different types of transcatheter valves. Methods and results This retrospective study aimed to evaluate the different behaviour of platelet count in Portico or Evolut recipients. Patients underwent TAVI between Feb 2017 to Aug 2021 at Gemelli Molise Hospital were enrolled and were divided in two groups: Portico (n = 90) and Evolut recipients (n = 64). Blood samples and platelets count were collected at admission (T1), implantation day (T2), second post TAVI day (T3), third post TAVI day (T4) and at discharge (T5). Drop platelets count (DPC) was calculated in this way: 100% × (baseline platelet count–nadir platelet count)/(baseline platelet count). CT and echo data were collected. The overall analysis consisted of a total of 154 patients who underwent TAVI. Among these patients, 90 patients (58%) were implanted with Portico valve, and 64 patients (42%) with an Evolut valve. We observed no differences among baseline characteristic between two groups. Interestingly, patients implanted with Portico valve, showed a high degree of thrombocytopenia at time T3, T4 and T5 (respectively, 122 ± 42 vs. 143 ± 43, P 0.004; 111 ± 39 vs. 137 ± 43, P 0.000; 136 ± 56 vs. 173 ± 69, P 0.001). DPC was greater in Portico valve (44 ± 16 vs. 31 ± 15, P = 0.000). No differences were found among inflammation variables (neutrophil lymphocyte ratio, CRP), implantation depth, degree of calcification evaluated with CT (FACTS score) and PVL. Balloon post dilatation (BPD) was performed in 33% of Portico recipients vs. 18% of Evolut recipients (P 0.044). No correlations were found between DPC and BPD in Portico patients (r = 0.035, P = 0.744) and Evolut recipients (r = 0.074, P = 0.569). Conclusions Our study suggests a more thrombocytopenia in Portico recipients, irrespective inflammation, valve calcification, perivalvular leak, implantation factors. Larger studies are needed to confirm these data.

Critical peptic ulcer bleeding requiring massive blood transfusion: outcomes of 270 cases.

Critical peptic ulcer bleeding requiring massive transfusion is a gastroenterological emergency. Few data exist on management and outcomes. The Australian and New Zealand Massive Transfusion Registry collects comprehensive data on adult patients receiving massive transfusion across all bleeding contexts. To evaluate clinical factors, management (procedural interventions, transfusions) and outcomes after massive transfusion for critical peptic ulcer bleeding. Demographics, diagnosis, procedures and mortality data were available for 5482 massive transfusion cases from 23 hospitals. International Classification of Diseases 10th Edition, Australian Modification codes were used to determine peptic ulcer bleeding and the Australian Classification of Health Intervention for interventions (i.e. endoscopic, radiological, surgical). Peptic ulcer bleeding accounted for 270 (4.9%) of all in-hospital massive transfusion cases; 70% were male. Median number of red blood cell (RBC) units transfused was 7 (interquartile range, 6-10). Thirty-day mortality was 19.6%. Age (75 vs 67 years; P = 0.009) and Charlson Comorbidity Index (3 vs 1; P < 0.001) were higher in those who died. Highest 24-h international normalised ratio (1.5 vs 1.4; P < 0.001) and creatinine (118 μmol/L vs 96 μmol/L; P = 0.03) and nadir platelet count (86 × 109 /L vs 118 × 109 /L; P = 0.01) were also associated with 30-day mortality. There were no differences in mortality according to number of RBC, platelets or plasma units transfused, gastroscopy (with or without intervention), interventional radiology or surgery. One in five patients with critical peptic ulcer bleeding requiring massive transfusion died by 30 days. Mortality was associated with patient characteristics rather than clinical interventions (e.g. procedures, blood product transfusion).

Clinical manifestations, laboratory profile and outcomes of dengue virus infection in hospitalised older patients.

Due to an ageing population, dengue among older patients is encountered more frequently in many countries. Our study aimed to explore the clinico-laboratory parameters and outcomes among dengue-infected older patients in comparison with younger patients. This retrospective chart review involved dengue patients with dengue non-structural protein 1 (NS1) antigen positivity admitted to a tertiary hospital in Malaysia from January to July 2015. A comparison was made between older people (aged ≥60 y) and others. Among 406 dengue patients, 43 (10.6%) were older people. Older dengue patients were less likely to present with persistent vomiting (adjusted OR [AOR] 0.247, 95% CI 0.093 to 0.656, p=0.005), while restlessness and confusion were more common at presentation (AOR 3.356, 95% CI 1.024 to 11.003, p=0.046). Older patients had significantly lower albumin upon admission (38 vs 40 g/L, p=0.036) and during hospital stay (35 vs 37 g/L, p=0.015). Compared with younger patients, older patients were more likely to have experienced nadir platelet counts of <50×109/L (AOR 2.897, 95% CI to 1.176 to 7.137, p=0.021). They were also more likely to require an extended hospital stay (AOR 3.547, 95% CI 1.575 to 7.986, p=0.002). Diagnosis of dengue in older people may be challenging because of atypical presentations. Increased vigilance is necessary as there is an increased tendency to develop severe thrombocytopenia, hypoalbuminemia and prolonged hospitalisation in older people.

Clinical Characteristics of Severe Acute Chest Syndrome in Children with Sickle Cell Disease

Background: Acute chest syndrome (ACS) is a form of acute lung injury that is a leading cause of morbidity and mortality in children and adults with sickle cell disease (SCD). Despite advances in health maintenance and disease-modifying therapies for SCD, ACS remains a common and often severe complication. There is still limited understanding of why some patients suffer more severe ACS episodes. Few studies have specifically investigated clinical parameters associated with severe ACS in the pediatric population. The purpose of this study is to determine the association between hematologic and radiologic clinical findings and severe ACS in children and adolescents with SCD.Methods: We conducted a single-institution retrospective chart review of 120 pediatric patients with HbSS or HbSβ 0 thalassemia and at least one documented episode of ACS, and then further classified patients by their most severe ACS event. We extracted laboratory and radiologic data to compare clinical findings. Infections reported in patient encounters were verified by documented viral PCR and blood cultures. Continuous variables were analyzed using Welch's t-test; categorical variables were analyzed using Fisher's exact test.Results: Eighty patients in the moderate ACS group were excluded for this analysis. Twenty patients (median age 5.6 years, SD 4.20) had mild ACS defined by no supplemental oxygen requirement, only one segmental or lobar infiltrate on chest radiography, and transfusion of less than 3 units (or 15 cc/kg) of red blood cells. Twenty patients (median age 7.6 years, SD 4.01) had severe ACS characterized by acute respiratory failure requiring mechanical (invasive or non-invasive) ventilation and/or exchange transfusion. Median length of stay for patients with severe ACS was longer than for the mild cohort (mean: 8 days vs 2 days, p <0.001). The median absolute neutrophil count (ANC) was significantly higher in the severe ACS cohort (19.8 x 10 3µL vs. 9.4 x 10 3 µL, p = 0.004). The median platelet count nadir was significantly lower in the severe ACS group compared to the mild group (165 x 10 3 µL vs. 309 x 10 3 µL, p <0.001). Review of radiologic data showed that the median number of lobes affected in the severe ACS group were 3, compared to 1 lobe in the mild group (p <0.001). Approximately 65% of patients with mild ACS had left-sided disease (p = 0.18), while 85% of patients with severe ACS had bilateral disease (p = 0.002). The risk of pleural effusions was also significantly increased with severe ACS [OR 76.00 (95% CI 9.235-825.6), p <0.001]. When we analyzed infection at time of ACS, the proportion of laboratory-confirmed viral infections were twice as high in the mild ACS cohort (41.2%), compared to the severe ACS cohort (20.0%, p = 0.279). There were no bloodstream bacterial infections found in either cohort.Conclusion: Severe ACS in children is a clinically distinct phenotype associated with longer length of stay, higher ANC and lower platelet nadir counts during active ACS, increased involvement of 3 or more lung lobes, and presence of pleural effusions. A lower proportion of confirmed viral infections were found in the severe ACS cohort compared to mild ACS patients, although did not reach statistical significance. Future prospective studies investigating the utility of these specific laboratory and radiographic parameters as components of an ACS severity prediction score are warranted. DisclosuresTubman: Forma Pharmaceuticals: Consultancy; Novartis Pharmaceuticals: Honoraria, Research Funding; Global Blood Therapeutics: Consultancy, Research Funding; Perkin Elmer: Honoraria. Fasipe: Emmaus: Consultancy; Bluebird Bio: Consultancy; Global Blood Therapeutics: Consultancy, Other: Grant Review Committee ; Novartis: Consultancy; Pfizer: Research Funding.

Bendamustine Is a Safe and Effective Regimen for Lymphodepletion before Tisagenlecleucel in Patients with Large B-Cell Lymphomas

Bendamustine Is a Safe and Effective Regimen for Lymphodepletion before Tisagenlecleucel in Patients with Large B-Cell Lymphomas

Dabigatran as first-line treatment for heparin-induced thrombocytopenia in the intensive cardiac care setting

Abstract Introduction Heparin-induced thrombocytopenia (HIT) is a rare immune-mediated disorder related to the use of unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) which is associated with increased risk of vascular thrombosis. HIT constitute a relevant and not so uncommon clinical issue in the intensive cardiac care unit setting. Parenteral non-heparin anticoagulants are recommended for the treatment of HIT. The efficacy of dabigatran, direct oral anticoagulant, is poorly documented in this indication. In laboratory-confirmed HIT only few cases with short-term use and early conversion to and from another anticoagulant were reported. Purpose The purpose of our study was to evaluate the efficacy and safety of dabigatran as a first-line and the only one anticoagulant used in the treatment of HIT. Methods We prospectively enrolled 5 patients with the diagnosis of HIT who were hospitalized in our intensive cardiac care unit in 2017–2021. Heparin was stopped immediately on the suspicion of HIT and off-label dabigatran therapy was initiated the same day. There were no conversion to another non-heparin anticoagulant – dabigatran was used continuously from suspicion of HIT for at least 3 months. In all patients we used latex immunoassay to confirm the diagnosis of HIT. Lower-extremity compression ultrasonography was performed to exclude thrombosis. We distinguished HIT with thrombosis (HITT) and isolated HIT (HIT without thrombosis). The minimal follow-up period on dabigatran treatment was 3 months and the maximal 4 years. Results All the patients were male with the median age of 73 years (interquartile range, 52–78 years) and all were exposed to both, UFH and LMWH. The median platelet (PLT) count before exposition to heparin was 182000/μl (interquartile range, 171000/μl–321000/μl). Platelet count fall &amp;gt;50% was observed after a median time of 9 days (interquartile range, 7–11 days) after exposition to heparin and a median PLT count nadir was 87000 μl/l (interquartile range, 25000/μl–103000/μl). Two patients had intermediate and three high probability of HIT. HITT was diagnosed in one patient. The manifestation of HITT was upper-extremity arterial thrombosis and pulmonary embolism. Four patients were diagnosed with isolated HIT. PLT count recovery &amp;gt;15ehab724.2982/μl was observed after a median time of 3 days on dabigatran treatment (interquartile range, 2–7 days). In the patient with HITT, a complete resolution of upper-limb arterial thrombosis was observed. At the minimal observation period end point (3 months) all the patients survived without bleeding or new thrombotic event. Moreover, neither bleeding nor recurrence of HIT occurred during the total follow-up period. Conclusion Dabigatran is safe and efficient as first-line treatment for HIT and can be used as the only one anticoagulant in this challenging, clinical scenario. Funding Acknowledgement Type of funding sources: None.

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.

Thrombocytopenia and platelet count recovery in patients with sepsis-3: a retrospective observational study

Thrombocytopenia is common in critical illness. But there are no studies that focus on thrombocytopenia and platelet recovery in Sepsis-3 patients. We employed a large database to identify sepsis based on Sepsis-3 criteria. Patients were grouped by nadir platelet count during ICU, propensity score matching was used to eliminate covariates imbalance, multivariable cox proportional hazard model was used for evaluating mortality. A total of 9709 patients were enrolled based on Sepsis-3, 1794 (18%) patients developed thrombocytopenia, with 858 (8.8%) exhibiting thrombocytopenia at ICU admission (prevalent), 891 (9.2%) developed thrombocytopenia during ICU stay (incident). In the incident thrombocytopenia group, survivors exhibited higher nadir platelet count, higher rate in platelet count recovery and shorter time to platelet recovery compared to non-survivors. Platelet recovery was not observed until 1 days (IQR, 1–2) after weaning of mechanical ventilation and 1 days (IQR, 1–3) after discontinuation of vasopressor in survivors of incident thrombocytopenia. Furthermore, thrombocytopenia was associated with longer duration of ICU length of stay, longer duration of mechanical ventilation and vasopressor use compared to no thrombocytopenia. Moderate (20–50 × 109/L) and severe (<20 × 109/L) thrombocytopenia group showed increased 28 days mortality compared to no thrombocytopenia, while the mortality rate between mild (51–100 × 109/L) and no thrombocytopenia group (≥100 × 109/L) showed no significant difference. Taken together these data revealed that thrombocytopenia occurred in 18% Sepsis-3 patients; platelet recovery occurred more frequent and earlier in survivors; platelet recovery was not observed until clinical improvement. Thrombocytopenia in Sepsis-3 demonstrated increased disease severity, and patients with platelet count <50 × 109/L showed increased 28 days mortality.

Are HPA-5b antibodies a significant cause of FNAIT and associated bleeding or merely an incidental finding?

Are HPA-5b antibodies a significant cause of FNAIT and associated bleeding or merely an incidental finding?

Oseltamivir Improved Thrombocytopenia During Veno-Arterial Extracorporeal Membrane Oxygenation in Adults With Refractory Cardiac Failure: A Single-Center Retrospective Real-World Study.

Background: Severe thrombocytopenia is a common complication of extracorporeal membrane oxygenation (ECMO). Oseltamivir can be used to treat infection-associated thrombocytopenia.Objective: To evaluate the effect of oseltamivir on attenuating severe thrombocytopenia during ECMO.Methods: This was a single-center real-world study in critically ill patients supported with venous-arterial extracorporeal membrane oxygenation (VA-ECMO). Patients suspected or confirmed with influenza received oseltamivir according to the Chinese guidelines. Thrombocytopenia and survival were compared between the oseltamivir-treated and untreated group. The factors associated with survival were analyzed by multivariable Cox analysis.Results: A total of 82 patients were included. All patients developed thrombocytopenia after initiating VA-ECMO. Twenty-three patients received oseltamivir (O+ group), and 59 did not use oseltamivir (O− group). During the first 8 days after VA-ECMO initiation, the platelet count in the O+ group was higher than that in the O− group (all P < 0.05). The patients in the O+ group had a higher median nadir platelet count (77,000/μl, 6,000–169,000/μl) compared with the O− group (49,000/μl, 2,000–168,000/μl; P = 0.04). A nadir platelet count of <50,000/μl was seen in 26% of the patients in the O+ group, compared with 53% in the O− group (P = 0.031). No significant difference in survival from cardiac failure was seen between the O+ and O− group (48 vs. 56%, P = 0.508). The Sequential Organ Failure Assessment (SOFA) score on initiation of VA-ECMO were independently associated with survival (OR = 1.12, 95% confidence interval (95% CI): 1.02–1.22, P = 0.015).Conclusions: Oseltamivir could ameliorate VA-ECMO-related thrombocytopenia. These findings suggested the prophylactic potential of oseltamivir on severe thrombocytopenia associated with the initiation of VA-ECMO.

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)

Cyclical Thrombocytopenia— a Rare but Fatal Imitator of Idiopathic Thrombocytopenia

AbstractLearning Objective 1: Recognize the patterns needed for diagnosing cyclical thrombocytopeniaLearning Objective 2: Distinguish the potentially life threatening features of cyclical thrombocytopenia as compared to idiopathic thrombocytopeniaCase Report: A 42 year old female of Eastern European origin, with a past medical history of systemic lupus erythematosis (SLE), was referred to outpatient hematology for management of her presumed diagnosis of idiopathic thrombocytopenia (ITP). Previous treatments including Aspirin, Eltrombopag, Azathioprine, Prednisone, Rituximab, Intravenous Immunoglobulin (IVIG) and splenectomy had been unsuccessful in raising her platelet count. The patient experienced symptoms of thrombocytopenia which included diffuse petechiae, mucosal petechiae, self-limiting epistaxis and significant menorrhagia which required hysterectomy. Symptoms were intermittent and occurred approximately once a month.Upon investigating the patient's previous lab work, a cyclic pattern of thrombocytopenia alternating with rebound thrombocytosis was revealed. A nadir of platelet count as low as 1000/mm3 with a peak count of as high as 2,000,000/mm3 was observed occurring approximately every 28 days. Interestingly, a similar pattern was noticed in the white blood cell levels. A correlation was also seen with her reproductive hormone levels, with luteinizing hormone running synchronously and estradiol cycling inversely to the platelet trends. This laboratory pattern, coupled with her lack of response to the aforementioned therapies, allowed us to make a diagnosis of cyclical thrombocytopenia (CT). Although the patient did not always experience symptoms during periods of rebound thrombocytosis, over the years, thrombotic events included lower extremity deep venous thrombosis and a myocardial infarction thought to be a result of peaked platelet levels.Treatment since the diagnosis of CT was made included Eltrombopag, Romiplostim, and Prednisone with dose adjustment at two-week intervals depending on her most recent platelet levels. Hormone therapy was trialed using Premarin, a conjugated estrogen therapy. Concurrent management of SLE with Belimumab was also held for a period of time. A combination of these interventions decreased the life threatening peaks but failed to inhibit platelet nadirs.Discussion: Cyclical thrombocytopenia is a rare but potentially life threatening condition. A recent literature review identified only 51 reported cases. Correlation with cyclical leukocytosis is found in a small subset of CT patients making it a more uncommon variant. Diagnosis is challenging and most patients are misdiagnosed with ITP. Differentiating CT from ITP is crucial to prevent life threatening thrombotic events. Differentiating factors include rebound cyclical thrombocytosis alternating with cyclical thrombocytopenia. These cycles typically occur every 28 days. CT patients may have a history of thrombotic events in addition to typical ITP symptoms and may fail to respond to conventional ITP therapies. CT predominantly affects pre-menopausal females, however, post-menopausal females and men may also be affected. The pathophysiology of CT is poorly understood. Multiple theories exist including intermittent autoimmune destruction of platelets, cyclical fluctuations of megakaryocytes, and abnormal biochemical signaling between cytokines and hematopoietic cells. An association with female reproductive hormones and a positive response to hormone therapy has also been documented in the literature. More research is needed to fully understand the pathogenesis of CT. Such an understanding may increase identification of the disease, provide better treatment modalities, and prevent poor outcomes in these patients. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Heparin-Induced Thrombocytopenia with Very High Antibody Titer Is Associated with Slower Platelet Recovery

Introduction: HIT is a relatively common and potentially catastrophic prothrombotic disorder caused by platelet activating antibodies targeting complexes of platelet factor 4 (PF4) and heparin. Diagnosis rests on clinical features coupled with serologic assays, most commonly an ELISA for heparin-PF4 antibodies. The ELISA optical density (OD) is a surrogate for antibody titer, an OD < 1 conveying a likelihood for pathogenic platelet-activating antibodies of < 1%, while OD > 2.0 confirms clinically suspected platelet activating antibodies in about 90%. The treatment for HIT is alternative anticoagulation, effecting platelet recovery >100,000 usually within 3 days and in the great majority within 7 days. We and others have observed very delayed platelet recovery (sometimes for weeks; “persisting HIT”) and this appeared more common with high titer antibodies. We did a retrospective analysis of 116 patients with HIT from single institution to investigate whether high titres of antibodies in HIT is associated with prolong time to platelet recovery and its potential impact on overall survival.Method: We retrospectively reviewed 116 patients diagnosed with HIT in our institution from 2009 to 2017 using our hospital database. Charts were reviewed for clinical comorbidities, association of surgery, thromboembolic events, type of alternative anticoagulation used on HIT diagnosis, platelet nadir count and time to recovery, and the relationship to ELISA OD. For statistical analysis, patients with HIT were categorized into 3 cohorts based on OD 1 to OD equal or less than 2.5, OD 2.5 to OD equal or less than 3 and OD more than 3 (Table 1). Patients with OD less than or equal to 2.5 was chosen as the reference group. A competing risk analysis based on the Fine & Gray method investigated differences in cumulative incidence of platelet recovery among the cohorts. Death before recovery was treated as a competing risk. Pooled t- test analysis was used to study correlation between OD and survival.Results: Median age of 116 patients was 65 years (63-68 ; 95% CI). 60.3% of the patients were male. Median value of initial platelet count during admission was 212k. Median value of nadir platelet count after diagnosis of HIT was 47k. 90% had surgery prior to diagnosis of HITT. 57% of patients with HIT had thromboembolic disease. 53%; 15% and 9% of patients were transitioned to Coumadin, NOACs and Arixtra respectively after initially getting treated with alternative anticoagulation Bivalirudin for HIT. Out of 116 patients, 101 patients (87%) of patients had platelet recovery in median of 6 days. The heparin OD value is significantly different between the two cohorts (p=0.0485) based on a pooled t-test. We further categorized all the patients into 3 cohorts based on their PF4 OD to study its impact on time to platelet recovery as shown in Table 1.There was no significant difference in recovery time between patients with OD between 2.5 and 3.0 and those less than 2.5 (p = 0.7207). The estimated hazard ratio of 0.921 [95% CI: (0.588, 1.444)], implying that patients with a higher OD value were likely to take slightly longer to recover their platelet count. However there was a statistically significant difference in platelet recovery time for patients OD greater than 3.0 (p = 0.0260) with hazard ratio 0.598 [95% CI: (0.380, 0.940)] compared to the reference group (see Figure 1). In-hospital mortality was 24.14% (28 patients) but was not significantly different by ELISA OD (p=0.7432). There is ongoing analysis of relationship of ELISA OD to thrombotic complications.Conclusion: Time to platelet recovery was significantly increased in HIT patients with heparin-PF4 OD value > 3. The lack of impact on overall survival probably relates to the fact that most deaths with HIT are related to underlying disorders (multiorgan failure, severe cardiac disease, cancer) rather than complications of HIT per se. A larger prospective study might further clarify the impact of PF4 OD on HIT treatment and outcomes. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Incidence and Outcome of Severe Thrombocytopenia Associated with Zika Virus Infection - Puerto Rico, 2016

Introduction: There are many etiologies for thrombocytopenia, such as viral suppression, disseminated intravascular hemolysis, and immune thrombocytopenic purpura (ITP). Zika virus (ZIKV) recently emerged in the Americas and was first detected in Puerto Rico in late 2015. ZIKV disease is generally mild; however, it has been infrequently associated with life-threatening outcomes including severe thrombocytopenia. We sought to define incidence and outcomes of ZIKV disease patients with thrombocytopenia.Methods: We reviewed the medical records of patients with reported thrombocytopenia (platelet count ≤ 100,000 cells/µL) among patients with ZIKV disease (defined by detection of ZIKV nucleic acid by RT-PCR or anti-ZIKV IgM antibody by ELISA and the presence of symptoms) that had been reported via passive surveillance. Among patients with confirmed thrombocytopenia, we collected data on medical history, interventions, and patient outcomes. Cases of severe thrombocytopenia were defined by: a) platelet count <20,000 cells/µL; or b) platelet count <50,000 cells/µL with a clinical diagnosis of and treatment for ITP. Cases in which another likely cause of thrombocytopenia was identified (e.g., sepsis, immunosuppression) were excluded from analysis. Data were collected in REDCap®.Results: Of 37,878 patients with ZIKV disease reported during 2016, a total of 436 had reported thrombocytopenia. Among patients with medical records available for review, 48 (0.1%) had confirmed thrombocytopenia in the absence of an identified etiology. Twelve of these 48 patients (25%) had severe thrombocytopenia (Table 1), and 36 (75%) had non-severe thrombocytopenia.Median age of patients with severe and non-severe thrombocytopenia was 39.5 years (range: 2-88) and 49 years (range: 1-88 years), respectively; 7 (58%) and 19 (53%) were male. Two (17%) patients with severe and 3 (8%) with non-severe thrombocytopenia had a history of ITP. All patients reported recent illness, which most frequently included rash (73%) and/or fever (77%). Median nadir platelet count of patients with severe and non-severe thrombocytopenia was 12,500 cells/µL (range: 1,000-30,250) and 70,000 cells/µL (range: 24,000-100,000), respectively, which occurred a median of 5.7 days (range: 1.4-15.6) and 4.5 days (range: 0.4-34.1) after symptom onset. Blood smears were performed in 9 (75%) patients with severe and 18 (50%) with non-severe thrombocytopenia. No patients with severe thrombocytopenia and 1 (2.8%) patient with non-severe thrombocytopenia had fragmented red blood cells; visualization of platelets on smear was consistent with low platelet counts. Whereas 11 (30.6%) patients with non-severe thrombocytopenia had petechiae, hematuria, or gingival bleeding, all (100%) patients with severe thrombocytopenia had hemorrhagic manifestations including petechiae (66.7%), hematuria (33.3%), ecchymoses (50%), gastrointestinal bleeding (25%), or intracranial hemorrhage (8.3%). Only patients with severe thrombocytopenia were diagnosed with ITP. Only patients with severe thrombocytopenia received platelet transfusion (n = 4; 33.3%) and/or intravenous immunoglobulin (IVIG) (n = 5; 41.7%). The patients with severe thrombocytopenia that received IVIG all had an up-trending platelet count after IVIG administration. Eight (66.6%) patients with severe thrombocytopenia and 9 (25.0%) with non-severe thrombocytopenia received steroids. Among those who received platelet transfusions, the median platelet count increase following transfusion was 6,000 cells/µL; 25% had a decreased platelet count following transfusion. Outcomes among patients with severe or non-severe thrombocytopenia included hospitalization (100% vs. 53%), admission to the intensive care unit (33% vs. 0%), and death (8.3% vs. 0%).Conclusions: Thrombocytopenia appears to be an uncommon occurrence in patients with ZIKV infection. Though rare, severe thrombocytopenia associated with ZIKV disease can be fatal; treatment is necessary. Platelet transfusions alone may not be effective, whereas administration of corticosteroids and IVIG may be of benefit in some cases. Further study is needed to characterize the pathogenesis of ZIKV-associated severe thrombocytopenia and interventions associated with survival. Appropriate diagnosis of the underlying etiology of thrombocytopenia is time-sensitive and crucial to improving patient outcome. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.