scholarly journals Inference from longitudinal laboratory tests characterizes temporal evolution of COVID-19-associated coagulopathy (CAC)

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Colin Pawlowski ◽  
Tyler Wagner ◽  
Arjun Puranik ◽  
Karthik Murugadoss ◽  
Liam Loscalzo ◽  
...  

Temporal inference from laboratory testing results and triangulation with clinical outcomes extracted from unstructured electronic health record (EHR) provider notes is integral to advancing precision medicine. Here, we studied 246 SARS-CoV-2 PCR-positive (COVIDpos) patients and propensity-matched 2460 SARS-CoV-2 PCR-negative (COVIDneg) patients subjected to around 700,000 lab tests cumulatively across 194 assays. Compared to COVIDneg patients at the time of diagnostic testing, COVIDpos patients tended to have higher plasma fibrinogen levels and lower platelet counts. However, as the infection evolves, COVIDpos patients distinctively show declining fibrinogen, increasing platelet counts, and lower white blood cell counts. Augmented curation of EHRs suggests that only a minority of COVIDpos patients develop thromboembolism, and rarely, disseminated intravascular coagulopathy (DIC), with patients generally not displaying platelet reductions typical of consumptive coagulopathies. These temporal trends provide fine-grained resolution into COVID-19 associated coagulopathy (CAC) and set the stage for personalizing thromboprophylaxis.

Author(s):  
Colin Pawlowski ◽  
Tyler Wagner ◽  
Arjun Puranik ◽  
Karthik Murugadoss ◽  
Liam Loscalzo ◽  
...  

Temporal inference from laboratory testing results and their triangulation with clinical outcomes as described in the associated unstructured text from the provider notes in the Electronic Health Record (EHR) is integral to advancing precision medicine. Here, we studied 181 COVIDpos and 7,775 COVIDneg patients subjected to 1.3 million laboratory tests across 194 assays during a two-month observation period centered around their SARS-CoV-2 PCR testing dates. We found that compared to COVIDneg at the time of clinical presentation and diagnostic testing, COVIDpos patients tended to have higher plasma fibrinogen levels and similarly low platelet counts, with approximately 25% of patients in both cohorts showing outright thrombocytopenia. However, these measures show opposite longitudinal trends as the infection evolves, with declining fibrinogen and increasing platelet counts to levels that are lower and higher compared to the COVIDneg cohort, respectively. Our EHR augmented curation efforts suggest a minority of patients develop thromboembolic events after the PCR testing date, including rare cases with disseminated intravascular coagulopathy (DIC), with most patients lacking the platelet reductions typically observed in consumptive coagulopathies. These temporal trends present, for the first time, fine-grained resolution of COVID-19 associated coagulopathy (CAC), via a digital framework that synthesizes longitudinal lab measurements with structured medication data and neural network-powered extraction of outcomes from the unstructured EHR. This study demonstrates how a precision medicine platform can help contextualize each patients specific coagulation profile over time, towards the goal of informing better personalization of thromboprophylaxis regimen.


Animals ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1478
Author(s):  
Lorenzo G. T. M. Segabinazzi ◽  
Giorgia Podico ◽  
Michael F. Rosser ◽  
Som G. Nanjappa ◽  
Marco A. Alvarenga ◽  
...  

In light of PRP’s increasing popularity in veterinary practice, this study aimed to compare three manual methods to prepare and cool equine PRP. The blood of 18 clinically healthy mares was collected via venipuncture in a blood transfusion bag (method 1), blood tubes (method 2), and a syringe (method 3). In method 1, samples were double centrifuged; method 2 involved one centrifugation, and in method 3 the syringe was kept in an upright position to sediment for 4 h. After processing with three methods, PRP and platelet-poor plasma (PPP) were extracted and assessed for red (RBC) and white blood cell counts (WBC), platelet counts, and viability. In a subset of mares (n = 6), samples were processed with the three methods, and PRP was evaluated at 6 and 24 h postcooling at 5 °C. Method 1 resulted in the highest and method 3 in the lowest platelet concentration (p < 0.05), and the latter also had greater contamination with WBC than the others (p < 0.001). Platelet viability was similar across treatments (p > 0.05). Cooling for 24 h did not affect platelet counts in all methods (p > 0.05); however, platelet viability was reduced after cooling PRP produced by method 3 (p = 0.04), and agglutination increased over time in all methods (p < 0.001). The three methods increased (1.8–5.6-fold) platelet concentration in PRP compared to whole blood without compromising platelet viability. In conclusion, all three methods concentrated platelets and while cooling affected their viability. It remains unknown whether the different methods and cooling would affect PRP’s clinical efficacy.


Obesity ◽  
2007 ◽  
Vol 15 (11) ◽  
pp. 2846-2854 ◽  
Author(s):  
Luenda E. Charles ◽  
Desta Fekedulegn ◽  
Terika McCall ◽  
Cecil M. Burchfiel ◽  
Michael E. Andrew ◽  
...  

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1074-1074 ◽  
Author(s):  
James B. Bussel ◽  
Vivek Patel ◽  
Cynthia Dunbar ◽  
Stephen Lemery ◽  
Krista Tibbs ◽  
...  

Abstract Background: GMA161 is a humanized version of a monoclonal anti-Fcγ-RIII antibody, 3G8, that was in clinical trial in the second half of the 1980s. Infusion of 25 mg of 3G8 (0.25–0.5mg/kg) resulted in transient but dramatic responses in approximately 50% of refractory ITP patients who did not respond to IVIG. It was unclear why certain patients did not respond. Since 3G8 is a mouse monoclonal antibody, it could not be reinfused because of the development of HAMA. Furthermore, there was marked neutropenia and depletion of NK cells (the CD16-expressing leukocytes) and there were significant fever-chill-vomiting reactions that were triggered by the antibody-Fcγ-RIII interaction. Preventing the reactions required a cocktail of methylprednisolone, diphenhydramine, acetaminophen and metaclopramide. GMA161, in addition to being humanized, has the Fc portion denuded of carbohydrates to reduce the binding of its Fc portion to Fc receptors. Methods: The first cohort of 4 patients with chronic ITP (table) and platelet counts &lt; 30,000/ul each received a single infusion of 0.1 mg/kg of GMA161 over 30 minutes. Results: Two of the 4 patients responded with peak platelet counts of 108,000/ul (from 27,000/ul) and 45,000/ul (from 11,000/ul) [figure 1]. Both had had ITP for &gt; 20 years, failed splenectomy and also failed multiple previous therapies including rituximab, cyclophosphamide, steroids, danazol, and IVIg among others. The responses to GMA161 were short-lived, lasting between 7 and 10 days and, as shown in figure 1, the platelet counts peaked at slightly different times. Figure 2 illustrates the dramatic decrease in the WBC count occurring immediately after infusion but then rapidly returning to baseline; this decrease was apparent in all types of white cells, not just neutrophils. The first patient had marked chills, fever, and vomiting 2 hours after infusion; this was reminscent of reactions to 3G8. She received IV methylprednisolone with resolution. The second patient had mild-moderate nausea. The third and fourth patients received acetaminophen, diphenhydramine and ondansetron premedication and had no adverse events. Conclusions: The findings are exciting because this cohort received the starting (lowest) dose of GMA161, 0.1mg/kg, and yet had reasonable activity. The toxicity was minimal with appropriate premedication. In the next cohort, better responses may be anticipated since they will be receiving 0.3 mg/kg. The hope would be that repeated dosing might have a more lasting effect, in at least a subset of patients. GMA161: Cohort #1 Patient ID Age (yrs) Sex Splenectomy Duration of Disease (ITP) Months Major Bleeding Major Diagnoses Previous Treatments #1 29 Female Yes 90 No Anemia 7 #2 32 Female Yes No #3 70 Male Yes 300 No Diabetes 4 #4 59 Female Yes 120 Yes (ICH) Stroke/Asthma 6 Figure 1: Platelet counts of Responders to GMA 161 treatment Figure 1:. Platelet counts of Responders to GMA 161 treatment Figure 2: Mean White Blood Cell Counts of patients treated with GMA 161 Figure 2:. Mean White Blood Cell Counts of patients treated with GMA 161


2019 ◽  
Vol 110 (2) ◽  
pp. 461-472 ◽  
Author(s):  
Tammy Y N Tong ◽  
Timothy J Key ◽  
Kezia Gaitskell ◽  
Timothy J Green ◽  
Wenji Guo ◽  
...  

ABSTRACTBackgroundThere may be differences in hematological parameters between meat-eaters and vegetarians.ObjectiveThe aim of this study was to perform cross-sectional analyses of hematological parameters by diet group in a large cohort in the United Kingdom.MethodsA complete blood count was carried out in all UK Biobank participants at recruitment (2006–2010). We examined hemoglobin, red and white blood cell counts, and platelet counts and volume in regular meat eaters (>3 times/wk of red/processed meat consumption, n = 212,831), low meat eaters (n = 213,092), poultry eaters (n = 4815), fish eaters (n = 10,042), vegetarians (n = 6548), and vegans (n = 398) of white ethnicity and meat eaters (n = 3875) and vegetarians (n = 1362) of British Indian ethnicity.ResultsIn both white and British Indian populations, compared with regular meat eaters (or meat eaters in Indians), the other diet groups had up to 3.7% lower age-adjusted hemoglobin concentrations (difference not significant in white vegan women) and were generally more likely to have anemia (e.g., 8.7% of regular meat eaters compared with 12.8% of vegetarians in white premenopausal women; P < 0.05 after Bonferroni correction). In the white population, compared with regular meat eaters, all other diet groups had lower age- and sex-adjusted total white cells, neutrophils, lymphocytes, monocytes, and eosinophils (P-heterogeneity < 0.001 for all), but basophil counts were similar across diet groups; in British Indians, there was no significant difference in any of the white blood cell counts by diet group. Compared with white regular meat eaters, the low meat eaters, poultry eaters, fish eaters, and vegans had significantly lower platelet counts and higher platelet volume, whereas vegetarians had higher counts and lower volume. Compared with British Indian meat eaters, vegetarians had higher platelet count and lower volume.ConclusionsIn the UK Biobank, people with low or no red meat intake generally had lower hemoglobin concentrations and were slightly more likely to be anemic. The lower white blood cell counts observed in low and non-meat eaters, and differences in mean platelet counts and volume between diet groups, warrant further investigation. This observational study was registered at http://www.isrctn.com/ as ISRCTN10125697.


2017 ◽  
Vol 11 (02) ◽  
pp. 166-172 ◽  
Author(s):  
Carlos Rodrigo Camara-Lemarroy ◽  
Guillermo Delgado-Garcia ◽  
Juan Gilberto De la Cruz-Gonzalez ◽  
Hector Jorge Villareal-Velazquez ◽  
Fernando Gongora-Rivera

Introduction: Mean platelet volume (MPV) has been shown to reflect the inflammatory burden in different inflammatory and autoimmune diseases. Our objective was to analyze the MPV in patients with tuberculous (TBM) and bacterial meningitis (BM). Methodology: The demographic and clinical data of 73 consecutive patients that presented with either BM (n = 35) or TBM (n = 38) were retrospectively analyzed, as well as that of 28 age- and sex-matched controls. Results: MPV was 8.78 ± 1.58 fL in patients with BM and 6.42 ± 1.39 fL in the TBM group (p < 0.05). In the control group, MPV was 7.4 ± 0.66 fL, significantly higher and lower when compared with TBM and BM, respectively. MPV was significantly associated with diagnosis (adjusted OR: 5.15, 95% CI: 1.090–23.7; p = 0.03). With the optimal cut-off value of 7.62 fL, MPV had 82% sensibility and 78% specificity for the differential diagnosis of TBM versus BM. Lower platelet counts, higher serum creatinine, higher white blood cell counts, and higher blood-cerebrospinal fluid glucose ratio were also predictive of BM. Conclusions: Platelet counts were lower and MPV was higher in patients with BM compared to patients with TBM.  Platelet indices, available in routine bloodwork, could be useful in the early differential diagnosis of these entities.


2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Sho Nakakubo ◽  
Masaru Suzuki ◽  
Keisuke Kamada ◽  
Yu Yamashita ◽  
Junichi Nakamura ◽  
...  

Abstract Background No clinical scoring system has yet been established to estimate the likelihood of coronavirus disease (COVID-19) and determine the suitability of diagnostic testing in suspected COVID-19 patients. Methods This was a single-center, retrospective, observational study of patients with suspected COVID-19 and confirmed COVID-19. Patient background, clinical course, laboratory and computed tomography (CT) findings, and the presence of alternative diagnoses were evaluated. Clinical risk scores were developed based on clinical differences between patients with and without COVID-19. Results Among 110 patients suspected of having COVID-19, 60.9% underwent polymerase chain reaction (PCR) testing based on the judgment of physicians. Two patients were found to have COVID-19. The clinical characteristics of 108 non-COVID-19 patients were compared with those of 23 confirmed COVID-19 patients. Patients with COVID-19 were more likely to have a history of high-risk exposures and an abnormal sense of taste and smell. The COVID-19 group had significantly higher rates of subnormal white blood cell counts, lower eosinophil counts, and lower procalcitonin levels than the non-COVID-19 group. When blood test results, CT findings, and the presence of alternative diagnoses were scored on an 11-point scale (i.e., “COVID-19 Clinical Risk Score”), the COVID-19 group scored significantly higher than the non-COVID-19 group, more than four points in the COVID-19 group. All non-COVID patients who did not undergo PCR had a score of 4 or less. Conclusions The COVID-19 Clinical Risk Score may enable the risk classification of patients suspected of having COVID-19 and can help in decision-making in clinical practice, including appropriateness of diagnostic testing. Further studies and prospective validation with an increased sample size are required.


1960 ◽  
Vol 199 (5) ◽  
pp. 824-828 ◽  
Author(s):  
D. O. Anderson ◽  
D. M. Whitelaw

Lymphocytes from the thoracic duct of rats were injected intraperitoneally into homologous rats previously exposed to 900 rads of total body radiation. Repeated white blood cell counts, platelet counts and polychromatophilia and reticulocyte counts provided no evidence that the transplanted cells were able to repopulate the bone marrow.


2015 ◽  
Vol 8 ◽  
pp. CCRep.S18085 ◽  
Author(s):  
Daizo Yaguchi ◽  
Nobuyuki Marui ◽  
Masaki Matsuo

We encountered three adult patients with flu-like symptoms diagnosed with human parvovirus B19 (HPV-B19) infection. Blood serum analysis also revealed leukopenia, with white blood cell counts (WBCs) of 1,000–2,000/mL and low platelet counts of 89–150 × 109/L. Typical skin rash was absent in one patient. Bone marrow examination of another patient showed hypoplastic marrow with <5% blast cells. All patients recovered without administration of granulocyte colony-stimulating factor (G-CSF). Therefore, HPV-B19 infection with leukopenia should be considered in adult patients with leukopenia during erythema infectiosum epidemics, even if typical clinical findings (ie, skin rash) are absent. Further, the fact that three cases were observed over the stated time period at our hospital, which is located in Nagoya city, showed a transition to a slightly higher level of incidence than the annual average.


1996 ◽  
Vol 76 (02) ◽  
pp. 184-186 ◽  
Author(s):  
Kenji lijima ◽  
Fumiyo Murakami ◽  
Yasushi Horie ◽  
Katsumi Nakamura ◽  
Shiro Ikawa ◽  
...  

SummaryA 74-year-old female developed pneumonia following herpes simplex encephalitis. Her white blood cell counts reached 28,400/μl, about 90% of which consisted of granulocytes. The polymorphonuclear (PMN) elastase/α1-arantitrypsin complex levels increased and reached the maximum of 5,019 ng/ml, indicating the release of a large amount of elastase derived from the granulocytes. The mechanism of PMN elastase release was most likely to be granulocyte destruction associated with phagocytosis. The cleavage of fibrinogen and fibrin by PMN elastase, independent of plasmin, was indicated by the presence of the fragments in immunoprecipitated plasma from the patient corresponding to elastase-induced FDP D and DD fragments and the absence of fragments corresponding to plasmin-induced FDP D and DD fragments on SDS-PAGE. These findings suggested that the large amount of PMN elastase released from the excessive numbers of granulocytes in this patient with herpes simplex encephalitis and pneumonia, induced the cleavage of fibrinogen and fibrin without the participation of plasmin.


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