Higher Risk Of Thrombocytopenia Research Articles

Toxicity profiles of antibody-drug conjugates for anticancer treatment: a systematic review and meta-analysis.

Antibody-drug conjugates are attractive targeted agents in anticancer treatment because of their unique mechanism of action and reduced toxicity. Little is known about the spectrum of adverse events associated with antibody-drug conjugates, despite tens of clinical trials. A systematic review of randomized controlled trials evaluating antibody-drug conjugate efficacy in anticancer treatment was conducted. PubMed, EMBASE, and ClinicalTrial.gov were searched for relevant studies. Meta-analyses assessed the odds ratios (ORs) of 12 treatment-related symptoms and toxicities in patients treated with antibody-drug conjugates compared with those receiving other anticancer agents without antibody-drug conjugates. All-grade and high-grade (grade ≥3) toxicities were examined. Twenty studies involving 10 075 patients were included. Compared with control groups, antibody-drug conjugates were associated with a higher risk of all-grade fatigue (OR = 1.25, 95% confidence interval [CI] = 1.08 to 1.45), anorexia (OR = 1.36, 95% CI = 1.09 to 1.69), nausea (OR = 1.46, 95% CI = 1.09 to 1.97), and sensory neuropathy (OR = 2.18, 95% CI = 1.27 to 3.76) as treatment-related symptoms. Patients treated with antibody-drug conjugates had a statistically significantly lower risk of all-grade febrile neutropenia (OR = 0.46, 95% CI = 0.22 to 0.96). Conversely, they had a higher risk of thrombocytopenia (OR = 2.07, 95% CI = 1.00 to 4.31), increased alanine aminotransferase (OR = 2.51, 95% CI = 1.84 to 3.40), and increased aspartate aminotransferase (OR = 2.83, 95% CI = 2.04 to 3.93). Subgroup analysis showed a similar toxicity profile when comparing the solid tumors with hematologic malignancy groups and the antibody-drug conjugate vs antibody-drug conjugate plus chemotherapy groups, except for some neurologic and hematologic adverse events. This comprehensive profile of adverse events associated with antibody-drug conjugate-based treatment shows an increase in various types of all-grade treatment-related symptoms and adverse events, although no increase in high-grade adverse events was seen.

Platelet is the early predictor of bronchopulmonary dysplasia in very premature infants: an observational cohort study

BackgroundA previous study showed that the lungs are involved in the biogenesis of platelets (PLTs). Thus, the present study aimed to investigate the association between bronchopulmonary dysplasia (BPD), a chronic lung disease, and PLT parameters in very premature infants.MethodsThe study subjects were premature infants with a gestational age of ≤ 30 weeks and birth weight of ≤ 1500 g in a preterm birth cohort study recruited between January 1, 2015, and August 31, 2019. BPD was defined as the need for oxygen supplementation more than 28 days after birth. The PLT count, mean platelet volume (MPV), platelet distribution width (PDW), and plateletcrit (PCT) level were compared between BPD and non-BPD infants. A generalized estimating equation model was used to adjust for confounding factors. A forward stepwise logistic regression model was used to calculate the adjusted odds ratio (OR) for thrombocytopenia in the BPD group. Receiver operating characteristic curve analysis was performed to assess the predictive value of PLT count combined with gestational age (GA) and birth weight (BW) for BPD.ResultsThe final study subjects were 134 very premature infants, namely, 64 infants with BPD and 70 infants without BPD. The BPD infants had lower PLT counts (F = 4.44, P = 0.03) and PCT levels (F = 12.54, P = 0.00) than the non-BPD infants. However, the MPV (F = 14.25, P = 0.00) and PDW (F = 15.04, P = 0.00) were higher in the BPD group. After adjusting for potential confounding factors, the BPD infants had a higher risk of thrombocytopenia than the non-BPD infants (adjusted aOR 2.88, 95% CI 1.01–8.15), and the risk of BPD was increased in very premature infants with a PLT count ≤ 177*109/L (OR 4.74, 95% CI 1.93–11.62) at the end of the second week. In the multivariate predictive model, it was showed that the AUC area (0.85), sensitivity (0.88), specificity (0.70) and Youden index (0.58) are improved using PLT counts ≤ 177*109/L combined with GA and BW.ConclusionsAbnormal PLT parameters were observed in BPD infants, and a PLT count ≤ 177*109/L was a potential risk factor for the development of BPD in very premature infants.

Assessment of ethnic difference in the incidence of thrombocytopenia induced by trastuzumab emtansine (T-DM1): A meta-analysis.

e15096 Background: Trastuzumab emtansine (T-DM1) has been proved its value and efficacy in advanced metastatic cancer disease as well as in the adjuvant setting. However, there is an increasing concern in T-DM1-induced thrombocytopenia (TCP), which also showed difference of incidence in races. This meta-analysis, combining available data from all single-agent T-DM1 studies to date, aimed to evaluate the incidence of treatment-related thrombocytopenia of T-DM1 and the differences between Asian and non-Asian patients. Methods: We conducted a systematic search of the relevant published clinical studies of T-DM1 that reported safety profile including thrombocytopenia, from 1980 to March of 2020 using PubMed, Embase, and the Cochrane database. Screening and data extraction were conducted by two independent reviewers. Pooled-effect estimates calculated with fixed-effects or random-effects model were expressed as incidence with 95% CIs. Results: A total of 29 studies involving 6188 patients were included. The incidence of all-grade thrombocytopenia in Asian patients was 0.39 (95%CI 0.11-0.67) and 0.29 (95%CI 0.23-0.35) in non-Asian patients. And the incidence of the grade 3 or higher thrombocytopenia in Asians was 0.20 (95%CI 0.10-0.29), in non-Asians was 0.02 (95%CI 0.01-0.03). Gastrointestinal cancer type and the dose of 2.4 mg/kg Q3W T-DM1 treatment were both associated with the higher incidence of grade 3 or higher thrombocytopenia. Conclusions: Asian patients have the higher risk of thrombocytopenia induced by T-DM1. Clinicians should have an awareness of careful observation in platelet counts when patients receive T-DM1 therapy.

Correlation of clinical outcome with laboratory parameters in children with dengue infection: An appraisal from a tertiary children’s hospital in India

Introduction: Dengue infection is caused by the dengue virus (arbovirus), the incidence of which is increasing in India. In dengue endemic settings, early diagnosis and monitoring for complications are important, especially in children. Concurrent testing of NSI antigen, dengue specific IgG and IgM will help to diagnose patients with suspected dengue fever. Objective: To correlate the clinical profile and outcome of dengue fever with detection of NSI antigen, dengue specific IgG and IgM antibody, hematological and biochemical parameters and blood component utilization. Methods: All children presenting to Rainbow hospital and diagnosed with dengue infection using NS1 and dengue specific IgG and IgM antibody during a one year period (1st November 2016 to 31st October 2017) were included in the study. The haemogram and biochemistry parameters were done using automated analyzers. Inpatients were classified as severe or non-severe based on clinical and/or laboratory evidence. The degree of association between clinical parameters and disease severity in relation to NS1 positivity was expressed as an odds ratio. Results: Among 213 children diagnosed, 126 were treated as inpatients and the rest as outpatients. The age range of the study sample was 6 months to 15 years. NS1 positivity was observed in 72.3 % patients. NS1 positivity, when compared to severity of disease was significant (Odds ratio: 2.3; p Conclusions: Using all three tests (NS1, dengue specific IgM and IgG) was useful, as in 59 (27.7%) patients, despite a negative NS1, based on a positive dengue antibody response (IgG and/or IgM), the patients were admitted and monitored. NS1 positivity was associated with a higher risk of thrombocytopenia in this study.

Prognosis of Unfractioned Heparin versus Low Molecular Weight Heparin in Pumlonary Embolism : Review Article

Anticoagulation is the mainstay treatment of pulmonary embolism. Using low molecular weight heparin versus unfractionated heparin remains a matter of debate. Objectives: the aim of this review is to study the prognosis of using low molecular weight versus unfractionated heparin in treatment of pulmonary embolism. Methods: PubMed and Cochrane library were searched for articles comparing the efficacy of low molecular weight heparin and unfractionated heparin in management of pulmonary embolism. Ten related results were selected for review. Results: Literatures studies indicated that low molecular weight heparin was effective in therapeutic treatment of acute sub-massive and massive pulmonary embolism. It was as effective as intravenous unfractionated heparin. It was not associated with higher risk of major, minor bleeding, or thrombocytopenia. Low molecular weight heparin was as effective as unfractionated heparin in prophylaxis of deep venous sinus thrombosis as well as pulmonary embolism. Discussion: Low-molecular-weight heparin seemed to be as effective safe as intravenous unfractionated heparin for the treatment as well as prophylaxis of pulmonary embolism. It was also safe with no major bleeding risk or higher risk of thrombocytopenia. Conclusion: Both low molecular weight and unfractionated heparin had similar efficacy and safety in management of PE.

Anticoagulation for people with cancer and central venous catheters.

Central venous catheter (CVC) placement increases the risk of thrombosis in people with cancer. Thrombosis often necessitates the removal of the CVC, resulting in treatment delays and thrombosis-related morbidity and mortality. To evaluate the relative efficacy and safety of anticoagulation for thromboprophylaxis in people with cancer with a CVC. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 12, 2012), MEDLINE Ovid (January 1966 to February 2013), and EMBASE Ovid (1980 to February 2013). We handsearched conference proceedings, checked references of included studies, used the 'related citations' feature within PubMed, and searched clinicaltrials.gov for ongoing studies. Randomized controlled trials (RCTs) comparing the effects of any dose of unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), vitamin K antagonists (VKA), or fondaparinux with no intervention or placebo or comparing the effects of two different anticoagulants in people with cancer and a CVC. Teams of two review authors independently used a standardized form to extract data in duplicate. They resolved any disagreements by discussion. They extracted data on risk of bias, participants, interventions, and outcomes. Outcomes of interest included mortality, symptomatic deep venous thrombosis (DVT), asymptomatic DVT, major bleeding, minor bleeding, infection, and thrombocytopenia. Where possible, we conducted meta-analyses using the random-effects model. Of 9559 identified citations, we included 12 RCTs (17 publications) reporting follow-up data on 2823 participants. Two of the RCTs included children. Of the 10 RCTs including 2564 adults, one compared prophylactic dose heparin with low-dose VKA. Three RCTs compared VKA with no VKA and four RCTs compared heparin with no heparin. Two additional trials had three separate arms comparing heparin, VKA, and no intervention. Prophylactic-dose heparin, compared with no heparin, was associated with a statistically significant reduction in symptomatic DVT (risk ratio (RR) 0.48; 95% confidence interval (CI) 0.27 to 0.86; moderate-quality evidence). However, results did not confirm or exclude a beneficial or detrimental effect of heparin on mortality (RR 0.82; 95% CI 0.53 to 1.26; moderate-quality evidence), major bleeding (RR 0.49; 95% CI 0.03 to 7.84; low-quality evidence), infection (RR 1.00; 95% CI 0.54 to 1.85; moderate-quality evidence); thrombocytopenia (RR 1.03; 95% CI 0.80 to 1.33; moderate-quality evidence), or minor bleeding (RR 1.35; 95% CI: 0.62 to 2.92). Low-dose VKAs, compared with no VKAs, were associated with a statistically significant reduction in asymptomatic DVT (RR 0.43; 95% CI 0.30 to 0.62). Results did not confirm or exclude a beneficial or detrimental effect of VKAs on mortality (RR 1.04; 95% CI 0.89 to 1.22; low-quality evidence), symptomatic DVT (RR 0.51; 95% CI 0.21 to 1.22; low-quality evidence), major bleeding (RR 7.60; 95% CI 0.94 to 61.49; very-low-quality evidence), or minor bleeding (RR 3.14; 95% CI 0.14 to 71.51). The use of heparin, compared with VKA was associated with a statistically significant increase in thrombocytopenia (RR 3.73; 95% CI 2.26 to 6.16; low-quality evidence) and asymptomatic DVT (RR 1.74; 95% CI 1.20 to 2.52). However, results did not show or exclude a beneficial or detrimental effect on any of the other outcomes of interest (very-low-quality evidence). Compared with no anticoagulation, we found a statistically significant reduction of symptomatic DVT with heparin and asymptomatic DVT with VKA. Heparin was associated with a higher risk of thrombocytopenia and asymptomatic DVT when compared with VKA. However, the findings did not rule out other clinically important benefits and harms. People with cancer with CVCs considering anticoagulation should balance the possible benefit of reduced thromboembolic complications with the possible harms and burden of anticoagulants.

Platelet profile is associated with clinical complications in patients with vivax and falciparum malaria in Colombia.

Thrombocytopenia is a common complication in malaria patients. The relationship between abnormal platelet profile and clinical status in malaria patients is unclear. In low and unstable endemic regions where vivax malaria predominates, the hematologic profiles of malaria patients and their clinical utility are poorly understood. The aim of this study was to characterize the thrombograms of malaria patients from Colombia, where Plasmodium vivax infection is common, and to explore the relationship between thrombograms and clinical status. Eight hundred sixty-two malaria patients were enrolled, including 533 (61.8%) patients infected with Plasmodium falciparum, 311 (36.1%) patients infected with Plasmodium vivax and 18 (2.1%) patients with mixed infections. The most frequently observed changes were low platelet count (PC) and high platelet distribution width (PDW), which were observed in 65% of patients; thrombocytopenia with <50,000 platelets/µL was identified in 11% of patients. Patients with complications had lower PC and plateletcrit (PT) and higher PDW values. A higher risk of thrombocytopenia was identified in patients with severe anemia, neurologic complications, pulmonary complications, liver dysfunction, renal impairment and severe hypoglycemia. The presence of thrombocytopenia (<150,000 platelets/µL) was associated with a higher probability of liver dysfunction. Young age, longer duration of illness and higher parasitemia are associated with severe thrombocytopenia. Our study showed that thrombocytopenia is related to malaria complications, especially liver dysfunction. High PDW in patients with severe malaria may explain the mechanisms of thrombocytopenia that is common in this group of patients.

Incidence, Temporal Trends, and Predictors of Thrombocytopenia Among HIV-Infected Persons Treated with Combined Antiretroviral Therapy (cART)

AbstractAbstract 69 Background:Thrombocytopenia (TP) is a relatively common disorder in HIV-infected Persons, and may be a challenging illness to treat, mainly because of its multifactorial aetiology. The underlying pathophysiology includes accelerated immune-mediated peripheral PLT destruction and impaired PLT production by the infected megakaryocytes of the bone marrow. Moreover, TP can also occur as a secondary phenomenon in HIV-positive patients, due to hypersplenism, bone marrow infiltration from infections of lymphoma, or myelosuppressive effects of medications. However, the epidemiology and predictors of TP in the era of potent HIV antiretroviral therapy has not been well defined. In a recent retrospective-matched case–control study of HIV-infected adult outpatients with (n=73) and without (n=73) TP, authors found that TP was significantly associated with HCV infection, cirrhosis, and uncontrolled HIV replication (Marks KM et al. J AIDS 2009). Antiretroviral therapy interruption among patients with well-controlled HIV infection has been associated with an increased incidence of thrombocytopenia, especially among those with a low baseline platelet count or a history of HIV-related thrombocytopenia (Bouldouyre MA et al. J AIDS 2009). Methods:The study was carried out in the Icona Foundation Study Cohort. All previously naïve starting cART with normal value of platelet count (PC) were included. TP has been defined as PC <100 × 109/L persisting in at least 2 consecutive determinations for at least 3 consecutive months. For each patient person-years of follow-up (PYFU) while receiving cART were calculated, and used to estimate the incidence rate of TP. A multivariable Poisson model was performed to elucidate the contribution of HIV viremia, immune reconstitution, HCV infection, ARV drug-class, and other potential risk factors for TP. Current HIV-RNA and CD4 count entered into the model as time-dependent covariates. Results:A total of 2,771 patients were included: 69.4% male, median age 36 yrs (IQR: 32–41), 38.5% HCV+. At initiation of cART, CD4 count and HIV-RNA were 295 cells/mmc and 4.75 log10 cp/mL, respectively. Mean value of baseline PC was 189 × 109/L (IQR 149–231). Overall patients contributed to 13,787 PYFU. During follow-up, 105 patients developed a TP accounting for an incidence rate of 7.6/1000 PYFU (95%CI 6.3–9.2). PC <20,000 was found in 5.7%, 20,000-50,000 in 12.4%, 50,000-100,000 in 81.4%. A trend for a reduction in the TP incidence rates over the last years was found (1997-1999: 9.8/1000 pyrs; 2000–2004: 4.6/1000 pyrs; 2005–2009: 4.5/1000 pyrs; P at Chi-square for temporal trend<0.001). At multivariable model, a higher risk of TP was associated with male gender (HR 1.99; 95%CI 1.19–3.32; P=0.008), and HCV co-infection (HR 3.45; 95%CI 2.23–5.33; P<0.001). Moreover, both lower level of current CD4 (HR 1.67 for 0–200 vs >350 cell/mmc; 95%CI 1.02–2.64; P=0.039) and detectable HIV viremia (HR 1.47 for each log10 cp/ml increase; 95%CI 1.25–1.73; P<0.001) were significantly associated with TP onset. No association with ARV drug-class was found. Conclusions:Thrombocytopenia remains a relatively common disorder in the late HAART era, with an overall 7.6 * 1000 PYFU, even if a trend for a reduced incidence over the last years was observed. In a large unselected cohort of antiretroviral naïve starting treatment, HCV co-infection, cirrhosis at baseline, uncontrolled HIV replication and lower current CD4 count were all independent predictors of TP. Furthermore in our study, the association with HCV-infection was independent from cirrhosis suggesting that mechanisms other than advanced liver disease may play a role in HIV/HCV-coinfected patients. In this cohort of treated patients, we found a strong association of TP with uncontrolled HIV replication and lower current CD4, these findings confirm the benefit of antiretroviral therapy on HIV-related thrombocytopenia.ON BEHALF OF THE ICONA FOUNDATION STUDY GROUP Disclosures:No relevant conflicts of interest to declare.

Can meta-analysis suggest carboplatin/paclitaxel as a reference arm in randomized trials of first-line chemotherapy for advanced non-small cell lung cancer?

e19039 Background: The validity of adapting carboplatin/paclitaxel (CbP) as a reference arm in randomized trials of first-line chemotherapy for advanced non-small-cell lung cancer has not been fully evaluated. Methods: We performed a meta- analysis on trials identified through a literature search. The analysis included randomized trials comparing CbP with cisplatin-based third- generation (3G) regimens. Results: Of 160 articles screened, seven randomized trials were eligible for the analysis. The pooled hazard ratio (HR) for overall survival showed that CbP was not an inferior regimen to cisplatin-based 3G regimens (HR=1.04; 95% confidence interval, 0.96–1.13; p=0.296). On focusing on 3G agents other than vinorelbine, we observed a marginally significant improvement in survival with cisplatin-based regimens (HR=1.08; 95% confidence interval, 0.99–1.18; p=0.080). CbP generally involved a higher risk of thrombocytopenia and peripheral neuropathy but a lower risk of anemia, nausea, and toxic deaths. Conclusions: There is no evidence that CbP was significantly inferior to cisplatin-based 3G regimens in terms of efficacy. However, since CbP was less inclined to result in better survival, the preferred use of CbP as a reference arm in randomized trials instead of cisplatin-based 3G regimens may depend on the purpose of the trial. No significant financial relationships to disclose.

Orbofiban: higher risk of thrombocytopenia

Orbofiban: higher risk of thrombocytopenia

Orbofiban: higher risk of thrombocytopenia

Orbofiban: higher risk of thrombocytopenia