scholarly journals HIT: Secondary Drop Phenomenon in Platelets

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4198-4198 ◽  
Author(s):  
Nikhil Mukhi ◽  
Sabina Saakova ◽  
Vaibhav Verma ◽  
Gurinder Sidhu
Keyword(s):  
Platelet Count ◽  
Positive Predictive Value ◽  
Sample Size ◽  
Predictive Value ◽  
Serotonin Release ◽  
Small Sample ◽  
Prior Exposure ◽  
Release Assay ◽  
Secondary Drop ◽  
4T Score

Abstract Background: Heparin-induced thrombocytopenia (HIT) is a pro-thrombotic and potentially lethal disorder caused by platelet-, endothelial-, and monocyte-activating antibodies that target multimolecular complexes of platelet factor 4 (PF4) and heparin. HIT is reported to occur in 0.2% to 5% of heparin-treated adults. Due to the diagnostic dilemma posed by the disease, various pre-test probability systems have been proposed. The most widely used 4Ts score has demonstrated high sensitivity but is limited by observer bias and its limited utility for intermediate scores. The anti-PF4/heparin antibody testing has sensitivity close to 100%, but its poor positive predictive value, low specificity and long turnaround time may lead to misdiagnosis and unnecessary treatment. Hence functional assays like 14C-serotonin release assay (SRA) are used for confirmation of diagnosis. These tests are highly specific for diagnosis but their use is restricted to a small number of reference laboratories. In this study, we describe a phenomenon which is seen in HIT patients and will help to improve the positive predictive value of 4T score. Hypothesis: Initial heparin exposure leads to a transient decrease in platelet count(less than 50% from presentation) which recovers close to baseline in a few days. Recovery from the transient drop is followed by a steeper drop in platelet count. This second substantial decline in platelet count is characteristic of HIT. Methods and objectives: We screened all hospitalized patients from 2008-2013 with ICD9 code for HIT (289.84) at discharge from Kings County Hospital and SUNY Downstate. One hundred fifty four patients were screened. Only patients with positive anti-PF4/heparin antibody test (HAT) and 14C-serotonin release assay (SRA) were included in the study. Results: Of the 154 patients, 54 patients had a positive HAT; 11 had positive HAT and SRA. Of the 11 patients included in the study, 4 (36.4%) were on VTE prophylaxis with unfractionated heparin (UFH), 6 (54.5%) were on UFH drip and 1 (9%) was on therapeutic dose of Enoxaparin. Out of 11 patients (81.2%), 9 were male with a median age of 68. Ten out of 11 patients (91%) demonstrated the transient platelet-reduction phenomenon. The median platelet count for these patients on admission was 239k/µl. The initial decline was seen on day 4.5 (median) to nadir platelet count of 148K/µl (median) which signifies a 38% drop. Platelet count normalized to baseline by Day 7 to 245K/µl (median) which is a 39% recovery. The secondary drop occurred on median Day 14 to 68K/µl (median) which is a 68% reduction since the recovery. This secondary drop was uniformly associated with HIT. The data is demonstrated by means of a graph as shown below. Figure 1 One patient in the study did not demonstrate this phenomenon. He developed HIT on day 4 of UFH exposure which is suggestive of pre-formed antibodies. Data regarding patient's prior exposure couldn't be obtained. Figure 1. One patient in the study did not demonstrate this phenomenon. He developed HIT on day 4 of UFH exposure which is suggestive of pre-formed antibodies. Data regarding patient's prior exposure couldn't be obtained. Conclusion: The exact mechanism of this transient platelet-reduction phenomenon stays unclear. In this small retrospective analysis, however, we observed this phenomenon in 91% of patients. All patients in this study had intermediate 4Ts scores; hence there may be a utility of this phenomenon in guiding treatment. Given the small sample size of patients, it is difficult to extrapolate this data to the general population. A multicentric study with larger sample size may help us in determining the utility of this phenomenon as a supplement to 4T score for HIT. Disclosures No relevant conflicts of interest to declare.

scholarly journals Performance of the New Automated Latex Immunoturbidometric Assay in the Diagnosis of Heparin Induced Thrombocytopenia: A Single Institution Experience

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4689-4689
Author(s):  
Sriman Swarup ◽  
Somedeb Ball ◽  
Nimesh Adhikari ◽  
Anita Sultan ◽  
Khatrina Swarup ◽  
...  
Keyword(s):  
Positive Predictive Value ◽  
Negative Predictive Value ◽  
Sensitivity And Specificity ◽  
Predictive Value ◽  
Serotonin Release ◽  
Small Sample ◽  
Second Phase ◽  
Heparin Induced Thrombocytopenia ◽  
Study Population ◽  
Release Assay

Introduction: Heparin induced thrombocytopenia (HIT) is a severe prothrombotic condition, usually triggered by exposure to heparin products. It is characterized by platelet activation induced by the formation of antibodies to the platelet factor 4 (PF4)/ heparin polyanion complexes. Diagnostic algorithm includes clinical scoring (4T score) alongside serological test for detection of these antibodies (HIT-Ab), while serotonin release assay (SRA) remains the gold- standard for confirmation. The automated latex immunoturbidometric assay (LIA) has recently been FDA approved as a screening tool for HIT and is a potential alternative to the conventional particle immunofiltration assay (PIFA) for time-sensitive detection of HIT-Ab to guide treatment considerations. We recently introduced LIA in our institution. In this study, we present our experience with LIA in comparison to PIFA in the diagnosis of HIT. Methods: We retrospectively reviewed the charts of all the patients on whom a PIFA was ordered between March 2017 and March 2018 in our hospital. We collected information on the results of the PIFA and SRA (if available). We replaced PIFA with LIA for HIT screening. Then, we introduced a structured protocol for diagnosis of HIT in our institution by incorporating 4T scoring alongside LIA order in the electronic medical record (EMR), in December 2018. We reviewed the EMR of all the patients on whom HIT-Ab test (LIA) was ordered between January and June of 2019, and collected similar information as before. All the data were compiled in a single master excel sheet for calculation of performance characteristics (sensitivity, specificity, positive and negative predictive values) for both PIFA and LIA. A patient was considered to have the diagnosis of HIT if the result of SRA was available and positive. Results: In the first phase, a total of 31 orders for SRA was noted against 170 PIFA orders. Five patients had a positive SRA, of whom two were PIFA negative. Half the patients with a negative SRA result were positive for PIFA. Hence, the sensitivity and specificity of PIFA test for our study population were noted to be 60% and 50%, respectively. PIFA had a positive predictive value (PPV) of mere 18.75% for the diagnosis of HIT, whereas the negative predictive value (NPV) was found to be 86.66%. Introduction of structured protocol for HIT diagnosis substantially reduced the number of inappropriate SRA orders in the second phase. On review of data for six months with the new HIT-Ab test LIA, SRA was ordered in only eight patients, to go with 69 orders for the LIA. The result of LIA was positive in all three patients with a positive SRA, whereas it was false positive in four instances. Only one patient was negative for both LIA and SRA during this period. LIA was found to be 100% sensitive and 20% specific for the diagnosis of HIT in our sample. PPV and NPV for LIA were 42.85% and 100%, respectively. Conclusion: The sensitivity and specificity of LIA were found to be 100% and 20%, respectively, in our study population, which is different from the earlier report (Warkentin et al. 2017). The small sample size is a limitation of our study. Higher PPV and NPV for LIA, with its quick turnaround time, make it a useful alternative for the time-sensitive determination of post-test probability for HIT in patients. [HIT- Ab- Heparin Induced Thrombocytopenia Antibody, PIFA- Particle Immunofiltration Assay, LIA- Latex Immunoturbidometric Assay, SRA- Serotonin Release Assay, +ve- Positive, -ve - Negative, PPV- Positive Predictive Value, NPV- Negative Predictive Value] Disclosures No relevant conflicts of interest to declare.

Incidence of Thrombosis in Serotonin Release Assay Negative Patients and Correlation with Pretest Heparin-Induced Thrombocytopenia Scoring System.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1816-1816 ◽  
Author(s):  
Christopher Hueser ◽  
Anjali J Patel ◽  
John N Allan
Keyword(s):  
Platelet Count ◽  
Scoring System ◽  
Thrombotic Event ◽  
Study Groups ◽  
Serotonin Release ◽  
Single Institution ◽  
Heparin Induced Thrombocytopenia ◽  
Significant Difference ◽  
Release Assay ◽  
4T Score

Abstract Introduction: Heparin-induced thrombocytopenia (HIT) is an immune mediated, adverse effect related to both unfractionated heparin (UFH) and low-molecular weight heparin (LMWH). HIT may result in significant morbidity and mortality. The serotonin release assay (SRA) is utilized in conjunction with clinical information to diagnosis HIT. Employment of the pretest clinical scoring system, known as the “4Ts”, classifies patients as having a low, intermediate or high probability for developing HIT. Previous investigators have reported clinically diagnosed HIT in patients with a negative SRA. However, there is no systematic study evaluating such a group of patients. We determined the frequency of thromboses in SRA negative patients and determined the correlation between the 4T score in patients with and without thromboses. Methods: We report a descriptive, single institution, retrospective study of 181 consecutive samples over the course of one year sent to the Coagulation Laboratory of St. Louis University for the work up of suspected HIT. A total of 142 patients were eligible. Patients with SRA negative samples were evaluated for evidence of thrombosis. Diagnosis of a thrombotic event was made by computed tomography (CT), venous Doppler ultrasonography (US), and ventilation-perfusion scanning (V/Q). Defined patient study groups were: all evalulable patients (PALL), patients with thromboses (TPOS) and patients without thromboses (TNEG). Analyses, between each patient group, the 4T score, mean platelet count prior to heparin therapy, and mean platelet nadirs were performed. Results: The overall incidence of proven thromboses in evaluable SRA negative patients was 14.8% (n=21). Of the 21 thromboses, 17(81.0%) were deep venous thromboses (DVT), 3(14.3%) were DVT and pulmonary embolus (PE), and 1(0.7%) was an isolated PE. A significant difference in 4T score was observed between TPOS vs PALL (p<0.0001) and TPOS vs TNEG (p<0.0001) groups. There was no difference between the patient groups PALL vs TNEG (p=0.985). No statistically significant difference between the study groups was seen for either initial platelet averages (TPOS vs PALL [p=0.8923], TPOS vs TNEG [p=0.2091], PALL vs TNEG [p=0.2550]) or nadirs (TPOS vs PALL [p=0.4664], TPOS vs TNEG [p=0.3763], PALL vs TNEG [p=0.7860]). Total Evaluable Patients (PALL) Patients without Thrombosis (TNEG) Patients with Thrombosis (TPOS) * Missing data was included in calculations for patients without thrombosis n 142 (100%) 110 (77.46)/121(85.2%)* 21(14.8%) Avg. 4T Score 3.23 (±1.81) 2.79 (±1.61)* 5.50 (±0.83) Avg. Initial Platelet Count (1X10 9 /L) 198.98 (±97.19) 194.16 (±99.39)* 223.90 (±79.31) Avg. Platelet Nadir (1X10 9 /L) 75.02 (±48.57) 73.41 (±46.47)* 82.86 (±59.42) Avg. Platelet Drop (1X10 9 /L) 123.96 (62.30%) 94.77 (48.81%)* 141.04 (62.99%) NO Data* 11 11(7.75%)* NA Conclusions: A higher incidence of thrombotic events in SRA negative patients was seen compared to historical data. A strong positive and negative correlation exists between high and low 4T scores, respectively, and the probability of thromboses from HIT. Prospective data are needed to address the incidence of thrombosis for patients in whom the pretest probability of HIT is high and in whom the SRA is negative. Studies evaluating the utility of serial SRA testing in such patients may lead to earlier identification of those at high risk for thromboses. Limitations of this study were the retrospective design, single institution, and the lack of serial SRA testing.

scholarly journals Clinical Significance of the Serotonin Release Assay and Platelet Count Monitoring After Cardiac Surgery

2017 ◽  
Vol 24 (6) ◽  
pp. 944-949 ◽  
Author(s):  
Shinya Motohashi ◽  
Takefumi Matsuo ◽  
Hidenori Inoue ◽  
Makoto Kaneko ◽  
Shunya Shindo
Keyword(s):  
Cardiac Surgery ◽  
Platelet Count ◽  
Clinical Course ◽  
Serotonin Release ◽  
Enzyme Linked Immunosorbent Assay ◽  
Heparin Induced Thrombocytopenia ◽  
Release Assay ◽  
Immunological Assays ◽  
Platelet Count Monitoring ◽  
The Relationship

Heparin-induced thrombocytopenia (HIT) is one of the serious complications in patients who undergo cardiac surgery. However, there remains a major problem in diagnosing HIT because the current immunological assays for detection of HIT antibody have limitations. Furthermore, the clinical course of thrombocytopenia in this surgery makes it increasingly difficult to diagnose HIT. We investigated the relationship between platelet count and HIT antibody in 59 patients who underwent cardiac surgery using cardiopulmonary bypass (CPB). The number of postoperative HIT antibody-positive patients evaluated using enzyme-linked immunosorbent assay kit (polyanion IgG/IgA/IgM complex antibodies/antiplatelet factor 4 enhanced) was 37 (62.7%). In contrast, platelet activation by HIT antibody was evaluated using the serotonin release assay (SRA). More than 20% and 50% release of serotonin was obtained from 12 patients (20.3%) and 8 patients (13.6%), respectively. The levels of d-dimer were significantly different on postoperative day 14 between SRA-positive and SRA-negative groups; however, postoperative thrombus complication was not detected using sonography in the patients with positive serotonin release at all. After being decreased by the operation, their platelet count recovered within 2 weeks in both groups equally. In our study, although the patients were positive in the platelet activating HIT antibody assay, they remained free from thrombosis and their platelet count recovered after early postoperative platelet decrease. Therefore, in addition to the SRA, monitoring of platelet count might be still considered an indispensable factor to facilitate the prediction of HIT thrombosis prior to manifestation in the patients undergoing cardiac surgery using CPB.

Incidence of Heparin-Induced Thrombocytopenia in Patients With Newly Implanted Mechanical Circulatory Support Devices

2021 ◽  
pp. 106002802110387
Author(s):  
Long To ◽  
Dana Attar ◽  
Brittany Lines ◽  
Melissa McCarty ◽  
Hassan Nemeh ◽  
...  
Keyword(s):  
Negative Predictive Value ◽  
Predictive Value ◽  
Mechanical Circulatory Support ◽  
Serotonin Release ◽  
Circulatory Support ◽  
Anticoagulation Management ◽  
Heparin Induced Thrombocytopenia ◽  
Mechanical Circulatory Support Devices ◽  
High Negative Predictive Value ◽  
Release Assay

Background: Heparin exposure and device-related thrombocytopenia complicate the diagnosis of heparin-induced thrombocytopenia (HIT) in patients receiving mechanical circulatory support (MCS). To improve anticoagulation management for patients with newly implanted MCS devices, incidence of confirmed HIT needs to be further characterized. Objectives: The purpose of this study is to describe the incidence of HIT and clinical utility of the 4Ts score in patients with newly implanted MCS devices. Methods: This is a retrospective analysis of MCS patients receiving unfractionated heparin from 2014 to 2017. The primary end point was incidence of laboratory-confirmed HIT. Strong positive, likely positive, low probability, and negative HIT categories were established based on heparin-induced platelet antibody (HIPA) and serotonin release assay (SRA). Secondary end points include characterization of platelet trends, argatroban use, incidence of HIT among each of the MCS devices, and utility of 4Ts score. Results: A total of 342 patient encounters met inclusion criteria, of which 68 HIPA tests and 25 SRAs were ordered. The incidence of HIT was 0.88% (3/342) and 4.4% (3/68) in patients with suspected HIT. Of the 68 HIPA tests, 3 (4.4%) were considered strong positive and 3 of the 25 SRAs were positive. Median 4Ts score was 4 [2.5-4] and optical density 0.19 [0.11-0.54]. The positive predictive value for the 4Ts score was 0.15 (CI = 0.03-0.46) and negative predictive value, 0.93 (CI = 0.82-0.98). Conclusion and Relevance: HIT occurs infrequently with newly implanted MCS devices. The 4Ts score appears to have a high negative predictive value for ruling out HIT.

Frequency and Clinical Impact of Platelet Factor 4-Specific Antibodies in Patients Undergoing Extracorporeal Membrane Oxygenation

2019 ◽  
Vol 119 (07) ◽  
pp. 1138-1146 ◽  
Author(s):  
Caroline Vayne ◽  
Marc-Antoine May ◽  
Thierry Bourguignon ◽  
Eric Lemoine ◽  
Eve-Anne Guery ◽  
...  
Keyword(s):  
Platelet Count ◽  
Extracorporeal Membrane Oxygenation ◽  
Serotonin Release ◽  
Clinical Impact ◽  
Platelet Factor 4 ◽  
Ecmo Circuit ◽  
Platelet Factor ◽  
Specific Antibodies ◽  
Release Assay ◽  
Specific Igg

Introduction/Objectives Extracorporeal membrane oxygenation (ECMO) provides circulatory support in patients with severe heart failure, but the frequent use of unfractionated heparin exposes patients to high risk of heparin-induced thrombocytopenia (HIT). We prospectively evaluated the development and clinical impact of platelet factor 4 (PF4)-specific antibodies (Abs) during ECMO and whether specific biological characteristics could predict HIT. Materials and Methods From 2014 to 2018, we studied 57 adults who underwent an ECMO for at least 5 days. The plasma samples collected daily were tested for PF4-specific Abs using immunoassays to detect immunoglobulin (Ig) G, A, and M isotypes or only IgG. Serotonin release assay was performed without and with PF4 to detect pathogenic Abs. Results Twenty-nine patients (50%) were positive for PF4-specific Abs (IgG, A, M), with IgG in 17/57 (30%) and 16 of them (94%) were immunized within 10 days. PF4-specific IgG Abs did not affect the clinical or biological course of most patients. HIT was suspected in only two patients with ECMO circuit dysfunction and unexpected platelet count decrease after day 5. High levels of PF4-specific IgG were detected in both patients, and HIT was confirmed by a serotonin release assay, which was also more sensitive when exogenous PF4 was present. Conclusion PF4-specific Abs are common during ECMO but are mostly non-pathogenic and not associated with a less favorable prognosis. However, an abnormal platelet count evolution, in particular if associated with ECMO circuit dysfunction, should prompt the search for pathogenic PF4-specific IgG.

Correlation Of Heparin Confirmatory Test (HCT) With Optical Density (OD) and Serotonin Release Assay (SRA) In The Diagnosis Of Heparin Induced Thrombocytopenia (HIT)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4754-4754 ◽  
Author(s):  
Ravneet Thind ◽  
Danielle Heidemann ◽  
Sundara Raman ◽  
Philip Kuriakose
Keyword(s):  
Optical Density ◽  
Predictive Value ◽  
Serotonin Release ◽  
Thrombin Inhibitors ◽  
Confirmatory Test ◽  
Functional Assay ◽  
Heparin Induced Thrombocytopenia ◽  
Laboratory Confirmation ◽  
Confirmation Test ◽  
Release Assay

Introduction Heparin-induced thrombocytopenia (HIT) is a potentially fatal, thrombotic complication of heparin therapy mediated by antibodies to complexes between platelet factor 4 (PF4) and heparin. Accurate and rapid diagnosis with prompt commencement of therapy are imperative as delays in treatment are associated with an increasing risk of thrombosis, amputation, or death. On the flip side, initiation of therapy with direct thrombin inhibitors without laboratory confirmation carries a significant risk of bleeding. Two types of laboratory tests are available for detection of these antibodies: a widely available immunoassay (ELISA), which is very sensitive to the presence of anti-heparin/PF4 antibodies, but is less specific to the clinical syndrome of HIT because of detection of non-pathological antibodies. The Serotonin Release Assay (SRA) is a functional assay that is now considered the gold standard for confirmatory diagnosis of HIT due to its high specificity. However, the downside of SRA is the cost involved, limited availability and a turnaround time of 5-7 days. As such, a heparin confirmatory test (HCT) with excess heparin has been in use since mid 2011 on positive ELISA samples in our laboratory to improve test specificity. This test is more cost and time efficient, with a turnover time of no more than 48 hours. As noted in prior studies, inhibition of a positive ELISA result by 50% or more in the presence of excess heparin is considered confirmatory of heparin-dependent antibodies. Likewise a negative confirmatory test is defined as a decrease of 50% or less in antibody binding in the presence of heparin. Aim a) Correlation of Heparin Confirmatory test (HCT) with strength of HIT ELISA, vis-à-vis optical density (OD) of 0.4 - 0.99 and OD of >/= 1.0. b) Correlation of HCT results with SRA, to see if the latter can be replaced by the heparin confirmatory test. Patients and Methods A retrospective chart review of adult patients hospitalized at our institution with suspected HIT from July 2011 until January 2013 was done. There were 101 such patients. All patients who had a positive HIT ELISA, then had HCT as per our standard lab practice, with an SRA test done for diagnosis/confirmation of HIT, as per standard clinical practice. Historically, the major strength of SRA assay is its specificity. The optical density on HIT ELISA and SRA results were then compared with the Heparin Confirmatory test to establish clinical significance. Results Of the 101 patients tested for HIT ELISA, 49 were positive. HCT and SRA were performed on all 49 samples, 1 out of which was reported as indeterminate. Hence 48 samples were used for primary analysis, comparing HCT to the OD as well as the SRA results. Out of 48 patients, 6 had positive SRA with Heparin inhibition of >50% (sensitivity 6/6 = 100%). Remaining 42 patients had negative SRA, 7 out of which had Heparin inhibition of <50% (specificity 7/42 = 16.6%). All 7 patients with a negative HCT had a negative SRA, making the negative predictive value of the HCT 100%; however positive predictive value was only 14.6% (6/41). There was no correlation between the OD and Heparin Confirmation test. Conclusions Although there is data suggesting that there might be some value to the Heparin Confirmation test, we were unable to show a significant correlation between HCT and OD or between HCT and SRA. The prospect of having a cost effective and rapid assay for laboratory confirmation of HIT will always be a relevant need. We feel that a larger, prospective study should be conducted to definitively assess the relationship between HCT and SRA. Disclosures: No relevant conflicts of interest to declare.

scholarly journals P.038 Bilateral carotid thrombi and cerebral infarction as a manifestation of heparin-induced thrombocytopenia with normal platelet count: a case report

2019 ◽  
Vol 46 (s1) ◽  
pp. S24 ◽  
Author(s):  
P Malla
Keyword(s):  
Platelet Count ◽  
Sudden Onset ◽  
Serotonin Release ◽  
Heparin Induced Thrombocytopenia ◽  
Platelet Counts ◽  
Normal Platelet ◽  
Bilateral Carotid ◽  
Upper And Lower Extremities ◽  
Release Assay ◽  
Discharge From Hospital

Background: This is the first report of Heparin induced thrombocytopenia (HIT) presenting as bilateral carotid thrombi and multiple cerebral infarcts. Methods: 54 year old woman presented with sudden onset of right arm numbness and weakness two days after discharge from hospital. During her hospitalization 9 days prior, she underwent colovesicular fistula repair, received heparin subcutaneously for DVT prophylaxis and had normal platelet counts. Results: On this admission, MRI Brain showed scattered multiple acute infarcts within the cortex of bilateral cerebral hemispheres. CT angiography head /neck showed non-occlusive thrombi at the carotid bifurcations bilaterally. Platelet count on admission was 267 K/uL q which decreased to 125 K/uL the next day, after which heparin was started for the carotid thrombi. The platelet count rapidly decreased further to 79 K/uL leading to suspicion for HIT and switching to Argatroban. HIT and serotonin release assay were positive confirming the diagnosis of HIT. CT chest and tranthoracic echocardiogram was normal. Venous Duplex of bilateral upper and lower extremities were negative for DVTs.Hypercoaguable evaluation was negative. Conclusions: This case highlights the importance of identifying HIT as a cause of arterial thrombosis and stroke even with normal platelet counts in the clinical setting of recent heparin use.

scholarly journals Is N-Hacking Ever OK? A simulation-based study

2019 ◽  
Author(s):  
Pamela Reinagel
Keyword(s):  
Positive Predictive Value ◽  
Sample Size ◽  
Predictive Value ◽  
False Positive ◽  
Hypothesis Test ◽  
False Positive Rate ◽  
False Positives ◽  
Wide Range ◽  
Positive Rate ◽  
Incremental Sampling

AbstractAfter an experiment has been completed and analyzed, a trend may be observed that is “not quite significant”. Sometimes in this situation, researchers incrementally grow their sample size N in an effort to achieve statistical significance. This is especially tempting in situations when samples are very costly or time-consuming to collect, such that collecting an entirely new sample larger than N (the statistically sanctioned alternative) would be prohibitive. Such post-hoc sampling or “N-hacking” is condemned, however, because it leads to an excess of false positive results. Here Monte-Carlo simulations are used to show why and how incremental sampling causes false positives, but also to challenge the claim that it necessarily produces alarmingly high false positive rates. In a parameter regime that would be representative of practice in many research fields, simulations show that the inflation of the false positive rate is modest and easily bounded. But the effect on false positive rate is only half the story. What many researchers really want to know is the effect N-hacking would have on the likelihood that a positive result is a real effect that will be replicable: the positive predictive value (PPV). This question has not been considered in the reproducibility literature. The answer depends on the effect size and the prior probability of an effect. Although in practice these values are not known, simulations show that for a wide range of values, the PPV of results obtained by N-hacking is in fact higher than that of non-incremented experiments of the same sample size and statistical power. This is because the increase in false positives is more than offset by the increase in true positives. Therefore in many situations, adding a few samples to shore up a nearly-significant result is in fact statistically beneficial. In conclusion, if samples are added after an initial hypothesis test this should be disclosed, and if a p value is reported it should be corrected. But, contrary to widespread belief, collecting additional samples to resolve a borderline p value is not invalid, and can confer previously unappreciated advantages for efficiency and positive predictive value.

scholarly journals Power, positive predictive value, and sample size calculations for random field theory-based fMRI inference

2019 ◽  
Author(s):  
Dirk Ostwald ◽  
Sebastian Schneider ◽  
Rasmus Bruckner ◽  
Lilla Horvath
Keyword(s):  
Field Theory ◽  
Positive Predictive Value ◽  
Random Field ◽  
Sample Size ◽  
Predictive Value ◽  
Multiple Testing ◽  
Statistical Power ◽  
Random Field Theory ◽  
Sample Size Calculations ◽  
Cluster Level

AbstractRecent discussions on the reproducibility of task-related functional magnetic resonance imaging (fMRI) studies have emphasized the importance of power and sample size calculations in fMRI study planning. In general, statistical power and sample size calculations are dependent on the statistical inference framework that is used to test hypotheses. Bibliometric analyses suggest that random field theory (RFT)-based voxel- and cluster-level fMRI inference are the most commonly used approaches for the statistical evaluation of task-related fMRI data. However, general power and sample size calculations for these inference approaches remain elusive. Based on the mathematical theory of RFT-based inference, we here develop power and positive predictive value (PPV) functions for voxel- and cluster-level inference in both uncorrected single test and corrected multiple testing scenarios. Moreover, we apply the theoretical results to evaluate the sample size necessary to achieve desired power and PPV levels based on an fMRI pilot study.

scholarly journals Platelet count splenic diameter ratio as predictor for esophageal varices in patients with cirrhosis: a diagnostic evaluation study

2019 ◽  
Vol 7 (12) ◽  
pp. 4535
Author(s):  
Sunil Mathew ◽  
Sachin Chacko ◽  
Tomy Philip ◽  
R. N. Sharma ◽  
Kanniyan Binub
Keyword(s):  
Platelet Count ◽  
Positive Predictive Value ◽  
Esophageal Varices ◽  
Predictive Value ◽  
Evaluation Study ◽  
Diameter Ratio ◽  
Diagnostic Evaluation ◽  
Esophageal Variceal ◽  
Esophageal Variceal Bleeding ◽  
Non Invasive

Background: Esophageal variceal bleeding is one among the common complication of cirrhosis which is fatal. Latest studies are focusing more on using non-invasive techniques to classify cirrhotic patients according to their risk of having varices. The platelet count-splenic diameter ratio is considered as one such parameter and is used in predicting esophageal varices in patients with cirrhosis. Objectives of the study was to assess the utility of platelet count-splenic diameter ratio as a useful non- invasive parameter in predicting the presence/ absence /size of esophageal varices in patients with cirrhosis.Methods: Diagnostic evaluation study was done in a tertiary hospital of Kerala state India. 93 adults above the age of 18 yrs with diagnosis of cirrhosis was selected and detailed history, physical, systemic examination and imaging was done. The degree of correlation between platelet count-splenic size ratio and the presence/absence/size of esophageal varices was studied along with its utility as an independent non- invasive marker. Frequency was expressed in percentages.Results: Best cut-off for prediction of esophageal varices Grade 1 was platelet count/spleen diameter ratio of 954, which had Specificity of 85.7% and Positive predictive value of 94.1% Cut-off for prediction of Grade 2 esophageal varices was platelet count/spleen diameter ratio of 916 which had a Sensitivity of 78.9%, Specificity of 88.9%. Whereas cut-off for prediction of Grade 3 esophageal varices was a ratio of 899 which had a high Sensitivity of 88% and Negative predictive value of 93.6 % but Specificity was only 64.7% and Positive predictive value of 47.8% only.Conclusions: The platelet count splenic diameter ratio is accurate to be used as screening tool to predict the presence of Grade 2 Esophageal varices in Patients with Cirrhosis. More studies need to be done around the globe for more evidence.

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