scholarly journals Testing for Heparin Induced Thrombocytopenia: Comparison of Practice at an Academic Center with Choosing Wisely Guidelines

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3469-3469
Author(s):  
DiMaria C Erica ◽  
Alex Trussler ◽  
Dyba Janique ◽  
David Lee ◽  
Michael J. Rauh ◽  
...  
Keyword(s):  
Research Funding ◽  
Clinical Characteristics ◽  
Low Risk ◽  
Choosing Wisely ◽  
Observer Variability ◽  
Heparin Induced Thrombocytopenia ◽  
Inter Observer Variability ◽  
Test Probability ◽  
4T Score ◽  
Heparin Exposure

Abstract Background: The American Society of Hematology Choosing Wisely Guidelines 2014 recommend against testing for treatment of Heparin Induced Thrombocytopenia (HIT) in individuals at low risk, defined by a 4T score ≤ 3. Diagnosis of HIT relies on a combination of clinical characteristics and laboratory testing. The 4T score is a pretest probability score that defines clinical characteristics of HIT with reported negative predictive value of 99.8%. A new scoring model, the HIT Expert Probability (HEP) score, was introduced in 2010 and postulated to reduce inter-observer variability. The primary objective of this study was to examine compliance with guidelines at our institution; a 456 bed university hospital. Secondary objectives were to compare the performance of the 4T and HEP score in regards to inter-observer variability and the predictive value of low risk scores. Methods: Local practice is initial testing with anti-PF4 antibody enzyme immunoassay (EIA), and subsequent reflex serotonin release assay (SRA) if the EIA is positive or indeterminate. Consecutive patients with requests for HIT testing were identified from laboratory records. With Research Ethics Board approval, retrospective chart review was conducted by 3 reviewers who independently applied 4T and HEP scores; discrepancies were resolved by consensus. Adverse events including thrombosis, skin necrosis, heparin infusion reactions, bleeding (classified as major by ISTH criteria) and mortality were recorded. Inter-observer variability was assessed using the intraclass correlation (ICC). Results: Between 2013 January 1 and 2015 Feb 21, 76 patients were referred for EIA testing. Excluded from this analysis were 7 patients with prior history of HIT or with testing requested from an outside institution. Of the remaining 69, median age was 67 years (range 24-90), 36 (56%) were male, 49 (71%) admitted with a medical diagnosis and 20 (29%) under a surgical service. Hematology service was consulted at some point during admission in 25 (36%). Pretest probability was documented in 16 (23%). A greater percentage of patients with documented pre-test probability had a hematology consult 11 (69%) than patients without 5 (31%). Also, 36 (86%) patients without a documented pre-test probability were considered low risk by the 4T score. Table 1.Scoring systemPre-test probabilityTotalN=69 (%)EIA positiveSRA positive*4TLow (≤3)42 (61)9 (13)1* (1)Intermediate (4-5)25 (36)10 (14)4 (6)High (6-8)2 (3)2 (3)1 (1)HEPLow (≤2)35 (51)7 (10)1* (1)Intermediate (2-5)20 (29)17 (25)1 (1)High (≥6)14 (20)7 (10)4 (6)*If SRA inconclusive, result confirmed with anti-PF4 IgG**Admitted with ischemic leg requiring catheter directed thrombolysis. Rapid onset thrombocytopenia within 24 hours of heparin exposure. Prior heparin exposure 150 days prior. Heparin stopped. No alternative anti-coagulation. No sequelae of HIT. The ICC for the pre-test probabilityscores was0.796(95% CI 0.714- 0.860) for 4T and 0.742 (95% CI- 0.645-0.821) for HEP score. By risk category, ICC for 4T score was 0.667 (95% CI 0.553 - 0.765) and HEP score was 0.702 (95% CI 0.553 - 0.765). HIT testing was performed in patients classified as low risk; 42 (61%) according to 4T and 35 (45%) according to HEP score. Among the 42 classified as low risk by 4T score, heparin was held in 26 (55) % pending results of testing and alternative anticoagulation commenced in 14 (33%) (fondaparinux 13, argatroban 1), at prophylactic dose in 12 and at therapeutic dose in 1 without a separate indication for anticoagulation. One low risk patient suffered major bleeding and 2 had thrombotic events. Overall, bleeding occurred in 10 (14%), major in 6 (9%), and thrombotic events occurred in 9 (13%). One patient presenting with septic shock, who developed thrombocytopenia with 4T score of 4, received argatroban and died on the same day from intracranial hemorrhage. All cause mortality during admission was 23 (33%). Conclusion: Compliance with Choosing Wisely Guidelines at our institution is low, and potentially associated with unnecessary financial expenditure and patient harm due to over-testing and over-treatment. We did not observe benefit of the more complex HEP score over the 4T score. Efforts are underway to increase awareness and align practice with recommendations. Disclosures James: Biogen Idec: Honoraria; Bayer: Honoraria, Research Funding; Octapharma: Honoraria, Research Funding; Baxter: Honoraria; CSL Behring: Honoraria, Research Funding.

scholarly journals Enforcing the 4T: Including a Hard Stop 4T Calculator into the Electronic Medical Record for Heparin Induced Thrombocytopenia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2442-2442
Author(s):  
Thomas A Ollila ◽  
Adam Zayac ◽  
Adam J Olszewski ◽  
Ross W Hilliard ◽  
David Riley ◽  
...  
Keyword(s):  
Quality Of Care ◽  
Positive Predictive Value ◽  
Predictive Value ◽  
Clinical Management ◽  
Research Funding ◽  
Heparin Induced Thrombocytopenia ◽  
Alternative Anticoagulation ◽  
4T Score ◽  
Heparin Exposure

Abstract Background: Among many causes of thrombocytopenia acquired during hospitalization, heparin-induced thrombocytopenia (HIT), an immune complex-mediated thrombogenic state with high morbidity and mortality, is one of the most feared etiologies. The clinical '4T' score is an established method to assess risk for HIT and guide immediate management(Lo, Juhl et al. 2006). However, the 4T score is not consistently used by clinicians, leading to potential over-testing and suboptimal management of suspected HIT. Our objective in this Quality Improvement (QI) project was to implement a mandatory 4T calculator (4TC) into the electronic medical record (EMR) to improve the positive predictive value of HIT antibody (HITA) testing, decrease the incidence of testing of low-risk patients, and to improve clinical management of suspected HIT. Methods: We developed a 4TC that assisted clinicians by integrating EMR-derived data on heparin exposure and the five most recent platelet counts with a link to an online calculator as well as clinical suggestions (Figure). As a part of this QI project, clinicians were required to enter the calculated 4T score before ordering a polyspecific HITA assay, which serves as the screening test for HIT in our institution. We reviewed laboratory records for all HITA tests performed over a six-month period, including 3 months before and after the implementation of a "hard stop" for HITA order in the EMR. We extracted data on the ordering hospital service team, 4T score documented in notes (if any), as well as quality of care indicators including rates of clinically recommended heparin cessation and initiation of alternative anticoagulation in the subgroup of patients with intermediate or high 4T score at the time of HITA order. In this QI project, we refrained from any statistical testing and summarized pre-specified outcome measures: incidence of HITA testing, positive predictive value of the HITA assay, and quality of care indicators. Results: We identified 99 (53 prior to the 4TC and 46 post) cases of HITA orders in the study period, among which there were 4 cases of confirmed HIT (either with positive IgG or positive serotonin-release assay [SRA]). Three HIT cases occurred after the 4TC was implemented. After the implementation of the 4TC, the positive predictive value for the HITA assay increased from 9% to 21%. The rate of clinically appropriate heparin order discontinuation increased from 72% to 88%, as did the initiation of alternative anticoagulation from 14% to 27%. HITA assay was most commonly ordered by the internal medicine service (35% of tests), non-cardiac intensive care service (30%), coronary care and cardiothoracic surgery services (21%), neurology (5%), and general surgery/other services (9%). Implementation of the 4TC did not significantly change this distribution, but the overall incidence of HITA orders decreased from 4.0 to 3.4 per 1000 admissions. We observed a high frequency of confirmatory SRA testing requested (18%), which is the reflex confirmatory test performed at our institution, even in cases of negative polyspecific HITA or HIT IgG. Conclusions: Addition of a 4T score calculator into the EMR which provides immediate feedback on patient's prior heparin exposure and recent platelet counts allows clinicians to consistently use the 4T score when considering HIT. Importantly, it also helps to educate non-hematologists on the proper management of HIT. Improved predictive value of the HITA assay suggests that our 4TC led to ordering HITA in a more appropriate patient population. We also demonstrated improved quality of care for suspected HIT, with increased rates of heparin cessation and initiation of alternative anticoagulation in patients with intermediate or high pre-test probability. Identifying clinical teams that order a disproportionate number of HITA assays will help us to direct education to improve clinical management. This QI project has led to other areas of improvement, particularly with regard to rational ordering of the SRA. At only three months of review since implementation of the 4TC, we have noted an improvement in the management of suspected HIT and a slight reduction in the incidence of testing. With continued review, we hope to demonstrate further improvement, as practitioners continue to use the 4TC and rely on clinical rationale rather than reflexive laboratory testing when evaluating thrombocytopenia in the hospital. Disclosures Olszewski: TG Therapeutics: Research Funding; Spectrum Pharmaceuticals: Consultancy, Research Funding; Genentech: Research Funding. Reagan:Alexion: Honoraria; Takeda Oncology: Research Funding; Pfizer: Research Funding.

scholarly journals A Single Institution's Adherence to Heparin-Induced Thrombocytopenia and Thrombosis Testing Guidelines

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4720-4720
Author(s):  
Kristine Gade ◽  
Jack Melson ◽  
Alex Jepsen ◽  
Surabhi Palkimas ◽  
Bethany Horton ◽  
...  
Keyword(s):  
Laboratory Testing ◽  
Choosing Wisely ◽  
Antibody Assay ◽  
Heparin Induced Thrombocytopenia ◽  
Probability Score ◽  
Low Probability ◽  
To Receive ◽  
Test Probability ◽  
4T Score ◽  
Platelet Antibody

Abstract Introduction: What was once an under-recognized clinical entity, heparin induced thrombocytopenia and thrombosis (HITT) has become a well-recognized and frequently tested disease. HITT is a serious and potentially fatal antibody mediated drug reaction to platelet factor 4 and early identification and treatment is essential. The 4T score is well-validated to guide appropriate testing of HITT where a low-probability score of 0-3 equates to a 99.8% negative predictive value for HITT2,3. In an effort to promote cost-conscious care and efficient use of healthcare resources, the American Society of Hematology (ASH) recommends against testing for HITT if the 4T score is 3 or less4. HITT laboratory testing at our institution is not restricted based on 4T score. We hypothesize that many providers are not following cost-conscious guidelines regarding HITT testing at our institution. Methods: We performed a single-institution retrospective analysis of patients who had a heparin-induced platelet antibody assay with reflexive serotonin release assay ordered between July 1, 2016 to July 1, 2017 at the University of Virginia Medical Center (UVA). We primarily assessed how our institution's ordering of heparin-induced platelet antibody for HITT compared to ASH's Choosing Wisely recommendation of forgoing laboratory testing on patients with a 4T score of 0-3 by retrospectively calculating 4T scores on all patients who had laboratory testing4. Patients were also assessed for episodes of bleeding and clotting and were scored on severity via the CTCAE and ISTH grading systems. Data on anticoagulant used after HITT testing was collected. We also checked to see if the blood specimen for assay was collected 2 hours after last heparin product as recommended by lab. Patients were excluded if they were not inpatient when their heparin-induced platelet antibody assay was drawn or if they were transferred or discharged immediately after assay was collected. Ultimately, of the initial 196 patients who had heparin-induced platelet antibody assay collected during this time frame, 184 patients were included for analysis. Results: Of the 184 patients who had a heparin-induced platelet antibody assay sent and were included in analysis, 55.4% of the patients (n=102) had a low pre-test probability of HITT with a 4T score of less than or equal to 3. Of the patients who had HITT testing sent, only 44% (n=81) received treatment with a non-heparin anticoagulant. Of the 102 patients who had a low pre-test probability of HITT with a 4T score of ≤3, 37.3% (n=38) were placed on an alternative anticoagulant. Of this low pre-test probability of HITT cohort, 7.8% (n=8) experienced bleeding as a complication. Interestingly, 15.5% (n=29) of all patients who had HITT testing continued to receive heparin products while awaiting results. Additionally, 19.3% (n=36) of samples were drawn within 2 hours of receiving heparin products. Conclusion: The guidelines for HITT testing and treatment have been well-validated and widely disseminated. Despite providers' familiarity with this clinical entity, the results depict that ordering practices at our institution do not follow guidelines in cost-conscious ordering nor in standard of treatment. Applying ASH's Choosing Wisely recommendation of not ordering laboratory testing on patients with a 4T low-probability score of 0-3, we see that 55.6% of the HITT assays ordered in this time period were inappropriate and at a cost of $455 to the institution per assay resulted in $46,865 of unnecessary health care costs to our institution in one year's time. This does not include the cost of alternative anticoagulation. Heparin costs just $0.04 per mL while argatroban costs $3.81 per mL and bivalirudin $12 per mL resulting in a 100 to 300 fold cost increase respectively. Standard work regarding HITT assay collection and treatment does not exist at our institution. Of concern, 15.5% of patients continued to receive heparin products after HITT testing was sent. The results of this study prompted implementation of a quality improvement project to decrease inappropriate HITT testing and standardize treatment of suspected HITT via an electronic medical record order set that uses the 4T score to suggest appropriate ordering of assays. We plan to collect data on changes in our ordering practices after this intervention. Disclosures No relevant conflicts of interest to declare.

scholarly journals Heparin-Induced Thrombocytopenia Antibody Testing and Its Cost Effectiveness: Taking a Financial HIT

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2343-2343 ◽  
Author(s):  
Anusiyanthan Isaac Mariampillai ◽  
Josephine Pineda Dela Cruz ◽  
Harry Staszewski ◽  
Nina D'Abreo
Keyword(s):  
High Risk ◽  
Cost Analysis ◽  
Healthcare System ◽  
Acquisition Cost ◽  
Average Cost ◽  
Hospitalized Patients ◽  
Low Risk ◽  
Heparin Induced Thrombocytopenia ◽  
4T Score ◽  
Heparin Exposure

Introduction Heparin induced Thrombocytopenia (HIT) is a life threatening condition that can lead to significant morbidity and mortality in hospitalized patients. Thrombocytopenia in the setting of unfractionated heparin (UFH) exposure is a common occurrence in hospitalized patients and its diagnosis and management is associated with increased costs to the healthcare system. There is a 5-10X decreased risk of HIT with low molecular weight heparin (LMWH)(Martel N, et al. Blood. 2005;106 (8):2710-2715) while the incidence with fondaparinux is much more rare (Warkentin TE et al; Blood 2005, 106: 3791-3796). We conducted a single center, retrospective study to assess the correlation of HIT antibody (Ab) testing to '4T' score and the associated financial burden in our institution. Method Data collection Using retrospective chart review, we identified 78 hospitalized patients between 11/11/15 and 6/7/16 from various departments that underwent HIT Ab testing. The '4T' score was calculated as per Table 1. Data including admission service, type and duration of anticoagulation (AC) prior to and after HIT testing, HIT Ab and Serotonin release assay (SRA) positivity, type and duration of non-heparin AC and days of hospitalization were collected. HIT Ab was measured using platelet factor 4 complexed polyvinyl sulfonate (PVS) coated to the wells of a microtiter plate (Labcorp Burlington Test 150075). Patients with positive HIT (Optic Density>0.4) were reflexed to confirmatory SRA (LabCorp Burlington Test 150018). Cost Analysis Pharmacy acquisition cost of non-heparin AC (argatroban /fondaparinux) used as empiric treatment during the HIT testing period was recorded. Pharmacy acquisition cost was also used to predict cost of prophylactic LMWH and fondaparinux for the same duration. Daily dose of continuous UFH was standardized to a 70Kg patient/day. The cost of testing for HIT incurred by the facility was obtained. Statistical analysis was done using ANOVA on VassarStats.net online computation. Results Seventy eight patients had HIT Ab evaluated (Table 2). 26.9% (n=21) had a positive HIT Ab test, and 2.5% had a positive SRA test (n=2). Of the 78 cases analyzed, 48 were categorized as low risk, 24 as intermediate, and 8 as high using the 4T score. HIT Ab testing was positive in 23.9% of low risk, 29% of intermediate risk and 37.5% of high risk patients. SRA was positive in only 2.5% of cases; 1 in the low risk and 1 in the high risk group (n=2) (Table 2). Breakdown of AC during hospital stay showed that 52% (n=41) had UFH on admission, 70% (n=29) of which was for DVT prophylaxis; however 56% (n=23) of these did not have heparin exposure within 100 days of admission. 18% (n=14) were placed on SCDs, 6 of which had no known heparin exposure within 100 days of admission. 23% (n=18) were exposed to prophylactic LMWH, 2.5% (n=2) to therapeutic LMWH, 1.2% (n=1) to dabigatran, apixaban and fondaparinux each (Table 3). Cost Analysis The total average cost per patient with suspected HIT requiring laboratory evaluation was $431.15 (n=78). If a patient required full dose non-heparin anticoagulation, the average cost increased to $1274.98 per patient (n=20) and average duration of anticoagulation was 4 days. Average length of hospitalization for patients suspected of HIT was 18.7 days. Using enoxaparin as an anticoagulation during this period would have cost on average $68.46 per patient, while the use of fondaparinux would cost $179.01. Conclusion Evaluation for HIT and empiric management poses a significant burden of expense on our strained healthcare system. The 4T score has been useful in predicting HIT positivity in other studies (Lo GK, J Thromb Haemost. 2006 Apr;4(4):759-65). In this study conducted in a real-world clinical setting however, we found the 4T score was not universally applied to calculate pretest probability. A suspicion of HIT cost on average $431 per patient per hospitalization. A positive HIT Ab lead to an expense of $955. Confirmed HIT by SRA, resulted in an expense of $1557 per patient per hospitalization. Of note, length of stay and patient discomfort was not included in the analysis. Improved education regarding pretest probability using 4T score is warranted, however using LMWH or non-heparin alternative as DVT prophylaxis may be the most cost-effective approach in today's cost-conscious, high-value healthcare system. Disclosures No relevant conflicts of interest to declare.

The Use of the Pre-Test Clinical Score (4T’s) Alone Does Not Detect All Diagnoses of Heparin-Induced Thrombocytopenia in the Critically Ill.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1244-1244
Author(s):  
Kirsty M Cuthill ◽  
Andrew Retter ◽  
David A Gurney ◽  
Gary W Moore
Keyword(s):  
Renal Failure ◽  
Critically Ill ◽  
Scoring System ◽  
Surgical Patients ◽  
British Society ◽  
Heparin Induced Thrombocytopenia ◽  
High Prevalence ◽  
Test Probability ◽  
Heparin Exposure ◽  
Elisa Result

Abstract Background: Heparin induced thrombocytopenia (HIT) is a prothrombotic adverse drug reaction to heparin. The 4T scoring system is a well validated system for assessing the pre-test probability of HIT and has a high negative predictive value for excluding HIT in most clinical situations, however, only a minority of patients have been evaluated in the ICU setting. The critically ill pose different challenges when compared with other medical and surgical patients. They have increased rates of thrombotic and haemorrhagic complications. Thrombocytopenia is reported in approximately 30–50%. We examined our ICU experience to evaluate the pairing of the 4T scoring system and EIA-GTI PF4 ELISA assay to evaluate their diagnostic accuracy in confirming a diagnosis of HIT in the acute setting. The gold standard measure is the serotonin release assay (SRA), but this is not routinely available in the UK. Methods: This single centre, retrospective, observational study involved reviewing the records of 75 consecutive patients investigated for HIT on our ICU from February 2006 to April 2008. We follow the British Society of Haematology guidelines for the management of HIT. Initial testing is with the EIA-GTI PF4 assay (positive if >0.4 OD) coupled with a heparin induced platelet activation assay (HIPA). Results: During the 26 months studied, 3.5% of ICU admissions were screened for HIT. A diagnosis of HIT, defined in this study as an intermediate or high 4T pre-test probability score and an ELISA result >0.7 OD was present in 0.46%. 45% of patients were medical, 40% had cardiothoracic surgery, the remaining 15% were general surgical patients. 66% had three or more organ failure, 70% received haemofiltration. Severe sepsis and haemofiltration were alternative causes of thrombocytopenia in 97% of patients. The 4T’s were used to risk stratify patients, 68% of patients had a low score, 29% were at intermediate risk and 3% had a high probability of HIT. 76% of patients with a low pre test probability had a negative ELISA and none developed a thrombosis. 4 (8%) patients with a low pre-test probability had a positive ELISA with an optical density >0.7 OD. 4 patients had a low pre-test probability but a positive ELISA, none of whom developed a thrombus. 2 patients had a positive ELISA and a positive HIPA, both had an intermediate pre-test probability. 1 patient had a negative ELISA (<0.4 OD) in the context of a high pre-test probability, he became thrombocytopenic on repeated heparin exposure. There was no correlation between a high pre-test probability and the magnitude of the ELISA result. 10 patients were treated with lepirudin, 2 developed haemorrhage requiring interruption of anticoagulation and transfusion. Discussion: The incidence of HIT recorded over the 26 month study period at GSTT is similar to the incidence of 0.3 -0.5% reported by Selleng. No diagnoses of HIT were missed after increasing our ELISA threshold from 0.4 - 0.7 OD. Neither the 4T pre-test probability nor the EIA GTI PF4 ELISA alone are sufficient to exclude a diagnosis of HIT. The 4T scoring system although well validated system may not work as well in the critically ill. The high prevalence of thrombocytopenia and alternative causes of thrombocytopenia mean the presence of thrombosis and the timing of the thrombocytopenia post heparin exposure are the major discerning features. Lo has previously reported the potential to over diagnose HIT by 100% when using the EIAGTI ELISA (Lo GK. Am J Hematol.2007; 82: 1037–43). The positive ELISA results in those patients with a low pre-test probability may be false positives secondary to cross-reacting autoantibodies. The high prevalence of acute renal failure highlights the importance of making an accurate diagnosis of HIT. Use of lepirudin in renal failure is associated with an increased risk of haemorrhage. We use 10% of the standard dose in patients with renal failure, haemorrhage occurred despite intensive monitoring in 20% of the patients. Our study is limited by its retrospective design and the lack of SRA testing. We recommend that both tests are performed in patients at risk of HIT. Increasing the positive ELISA threshold to 0.7 OD improves the specificity of the ELISA for detecting clinically significant heparin/PF4 antibodies in critically ill patients.

Spontaneous Heparin-Induced Thrombocytopenia Syndrome: Two New Cases and a Proposal For Defining This Disorder

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2328-2328 ◽  
Author(s):  
Theodore E. Warkentin ◽  
Paul Andrew Basciano ◽  
Richard A. Bernstein
Keyword(s):  
Platelet Count ◽  
Platelet Activation ◽  
Research Funding ◽  
Left Vertebral Artery ◽  
Platelet Factor ◽  
Shoulder Hemiarthroplasty ◽  
Heparin Induced Thrombocytopenia ◽  
Activation Assay ◽  
Count Recovery ◽  
Heparin Exposure

Abstract Introduction Heparin-induced thrombocytopenia (HIT) is a transient, autoimmune-like, prothrombotic disorder caused by heparin-dependent, platelet-activating IgG reactive against platelet factor 4/heparin (PF4/H). There is an emerging literature (Am J Med 2008;121:632-6. J Thromb Haemost 2008;6:1598-1600; Thromb Haemost 2013;109:669-75) pointing to rare instances of “spontaneous” HIT in patients without preceding heparin. We report 2 new cases and propose a definition for this controversial disorder. CASE #1. A 62-y.o. man presented with left middle cerebral artery stroke and thrombocytopenia (platelet count, 65×109/L). There was no previous history of thrombocytopenia, surgery, hospitalization, or heparin exposure. Clot extraction performed with heparin was complicated by further platelet count decline to 27 (nadir) and progressive thrombosis of the carotid artery. Aspirin was started, and the platelets recovered to >150 by day 13. CASE #2. A 54-y.o. female developed right leg swelling, left-upper extremity weakness/paresthesias, and thrombocytopenia (61×109/L) 15 days post-shoulder hemiarthroplasty; no intra-/postoperative heparin had been given. Brain MRI demonstrated acute infarct in the left posterior inferior cerebellar artery territory; angiography showed non-visualization of the left vertebral artery. Ultrasound revealed right lower-limb deep-vein thrombosis. Heparin treatment resulted in further platelet count fall to 37 (nadir). Treatment with argatroban, followed by fondaparinux, was associated with platelet count recovery to >150 by day 39. Methods Testing for HIT antibodies was performed by commercial EIA-IgG/A/M (Immucor GTI Diagnostics), in-house EIA-IgG (McMaster), and serotonin-release assay (SRA). Results Both patients’ sera (obtained before any heparin administration) tested strongly positive for HIT antibodies (Table), including strong platelet activation at 0.1 and 0.3 IU/mL heparin, as well as at 0 U/mL heparin, with no platelet activation at 100 IU/mL heparin: these serological features are characteristic of “delayed-onset HIT” (Ann Intern Med 2001;135:502-6). Antibody reactivity declined markedly by 2 to 4 weeks (including loss of platelet-activating properties at 0 IU/mL heparin), in keeping with the usual transience of HIT antibodies (N Engl J Med 2001;344:1286-92), and paralleling both patients’ platelet count recovery. Discussion These cases further support spontaneous HIT as an unusual explanation for acute arterial stroke and thrombocytopenia. One patient had preceding orthopedic surgery, an event previously reported with spontaneous HIT (Thromb Haemost 2013;109:669-75). The strong serum-dependent platelet activation at 0 IU/mL heparin helps to explain how thrombocytopenia and thrombosis can occur in a patient not receiving heparin. RECOMMENDATION. Based on the serological findings of these and previous cases, we propose that a definitive diagnosis of spontaneous HIT syndrome should be based upon all of the following criteria: thrombocytopenia, thrombosis, lack of proximate heparin exposure, strong-positive PF4-dependent immunoassay(s), and a strong-positive platelet activation assay featuring both heparin-dependent (e.g., high heparin neutralization) and heparin-independent platelet activation (at 0 IU/mL heparin). Disclosures: Warkentin: Pfizer Canada: Honoraria; Paringenix: Consultancy; Immucor GTI Diagnostics: Research Funding; WL Gore: Consultancy; GSK: Research Funding.

scholarly journals Testing for Heparin Induced Thrombocytopenia in Hospitalized Patients: In Line with Evidence?

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1957-1957
Author(s):  
Udhayvir Singh Grewal ◽  
Shiva Jashwanth Gaddam ◽  
Sahith Reddy Thotamgari ◽  
Tyiesha Brown ◽  
Kavitha Beedupalli ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
Heparin Therapy ◽  
Hospitalized Patients ◽  
Antibody Testing ◽  
Drug Induced ◽  
Platelet Factor ◽  
Heparin Induced Thrombocytopenia ◽  
Clinical Probability ◽  
Test Probability ◽  
4T Score

Abstract Background: Heparin-induced thrombocytopenia (HIT) is an immune complication of heparin therapy caused by antibodies to complexes of platelet factor 4 (PF4) and heparin. Both clinical probability and laboratory testing are needed for establishing a diagnosis of HIT. The 4Ts clinical scoring system, due to a very high negative predictive value when low, offers a robust means to exclude a diagnosis of HIT. However, these strategies are under-employed in clinical practice and limited evidence indicates a high prevalence of over-testing for HIT. Methods: This retrospective analysis was conducted to identify patients who underwent heparin/PF4 antibody testing over a period of 12 months. The testing was performed using an ELISA-based IgG anti-heparin/PF4 antibody assay and an optical density (OD) of 0.4 was used as a cut-off for a positive value. Electronic medical records were reviewed for 4T score documentation, anti-PF4 results, SRA testing and 4T scores were retrospectively calculated for all the patients. SAS v9.4 (Cary, NC) was used for statistical analysis. Results: A total of 105 patients who underwent anti-PF4 antibody testing were included for analysis. Majority of the patients in our cohort were admitted in an intensive care unit setting (75/105,71.4%). On chart review, only 17 patients (16.2%) were noted to have documentation of 4T score. Based on the retrospectively calculated 4T scores, 60 patients (57.1%) had low pre-test probability, 41 (39%) had intermediate pre-test probability and 4 (3.8%) patients were noted to have high pre-test probability. Anti-PF4/heparin antibodies were positive in 9 patients, of which 5 (55.5%) patients did not undergo concomitant SRA testing. Out of 9, 4 (44.4%) had weakly positive (0.4-1.0 OD units), 2 (21.1%) had strongly positive (1.0-2.0 OD units) and 2 (21.1%) patients had very strongly positive (>2 OD units) anti-PF4 antibody titers. Out of 105 patients, SRA was tested in 11 patients (10.5%) and was noted to be positive in 1 (0.95%). Overall, 2 patients were diagnosed and treated for HIT, out of which the diagnosis was not confirmed with SRA in 1 patient (due to high pre-test probability and very strong anti-PF4 titers). In the remaining patients, sepsis (48, 46.6%) and drug-induced thrombocytopenia (29, 28.2%) emerged as the most common possible causes of thrombocytopenia. Conclusion: Among hospitalized patients, over-testing for HIT is common. Practices to promote 4T score documentation and evidence-based anti-PF4 testing may help prevent unnecessary costs associated with serological testing and costly alternate anticoagulants. To improve overall outcomes, clinicians should also attempt to identify and treat other more likely causes of thrombocytopenia, especially in patients with low pre-test probability for HIT. Disclosures No relevant conflicts of interest to declare.

scholarly journals Low-Risk Polycythemia Vera Treated with Phlebotomies: Clinical Characteristics, Hematologic Control and Complications in 358 Patients from the Spanish Registry of Polycythemia Vera

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3621-3621
Author(s):  
Ana Triguero ◽  
Alexandra Pedraza ◽  
Manuel Pérez ◽  
María Isabel Mata ◽  
Beatriz Bellosillo ◽  
...  
Keyword(s):  
Polycythemia Vera ◽  
Research Funding ◽  
Clinical Characteristics ◽  
Treatment Strategies ◽  
Myeloproliferative Disorders ◽  
Primary Prophylaxis ◽  
Low Risk ◽  
Major Hemorrhage ◽  
Risk Patients

Abstract Introduction: Current recommendations for patients with low-risk polycythemia vera (PV) include hematocrit (Htc) control with phlebotomies and primary prophylaxis of thrombosis with low-dose aspirin. There is scarce information regarding the hematological control, the incidence of complications and the need for cytoreduction in PV patients treated with phlebotomies only. Methods: A total of 358 patients with low-risk PV (<60 years old and without history of thrombosis) from the Spanish Registry of Polycythemia Vera were included in the present study. PV-related symptoms and blood counts were collected at 6, 12, 18, 24, 36, 48 and 60 months from diagnosis while the patients were treated with phlebotomies only. The duration of the treatment with phlebotomies, the indication of starting cytoreduction and the incidence of thromboembolic and hemorrhagic events during the cytoreduction-free period was also analyzed. Results: Baseline characteristics at the time of diagnosis are described in Table 1. Table 2 summarizes the main hematological and clinical characteristics under treatment with phlebotomies. Inadequate control of the Htc (> 45%) was reported in 61-70% of the patients, leukocytosis >15x10 9/l in 10% and thrombocytosis >1000x10 9/l in 5%. In addition, about 20% of the patients had pruritus and 10% had microvascular symptoms. Of the 358 patients included, 275 (77%) required cytoreduction, 261 (73%) with hydroxyurea and 14 (4%) with IFN. The main indication of cytoreduction was thrombocytosis (20%), followed by age >60 years old (15%) and microvascular symptoms (13%). Median duration of cytoreduction abstention was 4.7 (0.1-30.4) years being significantly longer in patients younger than 50 years (6 and 2 years for patients younger and older than 50 years, respectively, p<0.0001). With a follow-up of 1659 person-years under phlebotomy only treatment, 14 thrombosis were observed (arterial n=9, venous n= 5), 12 hemorrhages (major n=4, minor n=8) and 4 solid tumors (1 melanoma and 3 non-cutaneous carcinomas). The incidence of complications during the cytoreduction-free period by person-years was: 0.8% for thrombosis, 0.2% for major hemorrhage and 0.2% for second neoplasia. The median follow-up until last visit including the time after starting cytoreductive therapy was 8.4 (0.2-39) years. Of 14 deaths observed, none occurred during the phlebotomy period. Half of the patients died from PV related reasons but the other 50% were not related. The median survival estimation by K-M was 36.5 years. Disease progression was documented in 27 (7.5%) patients, 26 of them to myelofibrosis, 1 to myelodysplastic syndrome and none to acute leukemia. Progression to myelofibrosis occurred during the cytoreduction-free period in 5 patients (1.4%) after a median of 5.8 years (Range: 4.9-8.9). Conclusions The incidence of thrombotic and hemorrhagic complications was very low in this series of low-risk patients treated with phlebotomies, even though only 30-40% of patients maintained the Htc <45%. The data from the present study show that low-risk patients have different therapeutic needs than other PV patients and support the development of new treatment strategies. Representing the Spanish Group of Myeloproliferative Disorders. GEMFIN Figure 1 Figure 1. Disclosures Bellosillo: Qiagen: Consultancy, Speakers Bureau; Roche: Consultancy, Research Funding; Thermofisher Scientific: Consultancy, Speakers Bureau. Ferrer Marin: Cty: Research Funding; Incyte: Consultancy, Research Funding; Novartis: Speakers Bureau. Garcia Gutierrez: Novartis: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Incyte: Consultancy, Honoraria, Research Funding.

Utility of Optical Density Values from Heparin-Platelet Factor 4 Antibody Testing and Probability Scoring Models To Diagnose Patients with Heparin Induced Thrombocytopenia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1475-1475
Author(s):  
Kim A. Janatpour ◽  
Robert C. Gosselin ◽  
William E. Dager ◽  
Andrew Lee ◽  
John T. Owings ◽  
...  
Keyword(s):  
High Risk ◽  
Optical Density ◽  
Predictive Value ◽  
Platelet Factor 4 ◽  
Platelet Factor ◽  
Predictive Values ◽  
Heparin Induced Thrombocytopenia ◽  
Sensitivity Specificity ◽  
Test Probability ◽  
4T Score

Abstract Background: Heparin induced thrombocytopenia (HIT) is a potentially life threatening complication of heparin administration caused by antibodies directed to the heparin-platelet factor 4 (PF4) complex and characterized by thrombocytopenia with a seemingly paradoxical high risk of thrombosis. Diagnosis is challenging, and is based on both clinical suspicion and laboratory detection of heparin-PF4 antibodies. The Warkentin 4 T’s “pre-test” probability and Chong’s “post-test” probability models have been developed to aid the diagnosis of HIT. Enzyme-linked immunoabosorbant assay (ELISA) laboratory measurement of heparin-PF4 antibodies is commonly used but has a low positive predictive value for thrombosis. Recent reports suggest that using an ELISA optical density (OD) value of ≥ 1 may improve the predictive value for thrombosis. Methods: We performed a retrospective analysis of 105 patients with suspected HIT who were treated with a direct thrombin inhibitor and evaluated the anti-heparin-PF4 ELISA OD values and Warkentin 4 T’s scores for sensitivity, specificity, and positive and negative predictive values (PPV and NPV, respectively) using the Chong’s score to define HITBoth the manufacturer’s OD threshold of 0.4 and ≥ 1 were evaluated. Table 1. Comparison of sensitivity, specificity, and predictive values for 4 T’s and OD levels, alone and in combination Sensitivity (%) Specificity (%) NPV (%) PPV (%) For calculations, Chong’s categories of definite/probable and unlikely were used to define presence or absence of HIT. 4T’s score (high and low) 81 100 80 100 OD level 0.4 69 75 65 78 OD level ≥1 38 85 52 77 4T’s + OD 0.4 94 100 94 100 4T’s +OD ≥1 69 85 81 75 Results: The sensitivity, specificity and predictive value of ELISA alone were inferior to the 4 T’s clinical scorings system. The sensitivity and negative predictive values of the 4T’s score were improved by considering positive or negative ELISA test results. Conclusions: Consistent with previous reports, the PPV of a high probability 4T score alone was 100%. Thus, ELISA results might not change clinical decisions in this situation. Alternative anticoagulation might be inappropriately withheld in 20% of patients if a low probability 4T score alone were to be used for decision-making. The addition of ELISA data using an OD level of 0.4 increased the NPV to a threshold that might be considered clinically acceptable (94%) to withhold therapy. Addition of an OD level of ≥ 1 did not improve the PV of the 4 T’s. However, in contrast to other studies that found better predictive value to using this higher OD threshold, our study group was limited to people considered high risk for HIT. Validation of this strategy in a prospective trial with clinical endpoints should be considered.

External Validation Of The HIT Expert Probability (HEP) Score, a Novel Pre-Test Probability Model For Heparin-Induced Thrombocytopenia Based On Broad Expert Opinion

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1699-1699
Author(s):  
Lee Joseph ◽  
Marcelo P.V. Gomes ◽  
Firas Al Solaiman ◽  
Julie St John ◽  
Asuka Ozaki ◽  
...  
Keyword(s):  
Expert Opinion ◽  
Laboratory Testing ◽  
Expert Panel ◽  
Vascular Medicine ◽  
Heparin Induced Thrombocytopenia ◽  
Scoring Model ◽  
Clinical Scoring ◽  
Consultative Service ◽  
Test Probability ◽  
4T Score

Abstract Introduction The diagnosis of heparin-induced thrombocytopenia (HIT) is challenging due to the overlap of its clinical features with other entities, variable specificity of ELISA-based tests, poor availability of functional tests such as the serotonin release assay (SRA) and suboptimal positive predictive values of pre-test probability clinical scoring models, such as the 4T and Lillo-Le Louėt models. Improved diagnostic tools are desirable to guide early therapeutic decisions in patients with suspected HIT and to reduce inappropriate use of alternative anticoagulants. The HIT Expert Probability (HEP) Score, a pre-test probability clinical scoring model for HIT based on broad expert opinion, has recently been proposed to improve the diagnosis of HIT compared to the 4T score. We sought to externally and prospectively validate the HEP score. Methods Pre-test probability of HIT was prospectively assessed for 51 consecutive patients referred to the Cleveland Clinic Vascular Medicine Consultative Service for evaluation of possible HIT between August 1, 2012 and February 1, 2013. Electronic medical records were reviewed to obtain clinical, biochemical (including IgG specific HIT ELISA and SRA tests) and imaging data, and two Vascular Medicine fellows independently applied the 4T and HEP scores for each patient. Two independent HIT expert adjudicators rendered a diagnosis of HIT likely or unlikely. Both scorers and adjudicators were blinded to the Results of HIT laboratory testing, consultative service inputs and scores generated by other raters. Results The median 4T and HEP scores were 4.5 [range 3.0, 6.0] and 5 [range 3.0, 8.5], respectively. Interobserver agreement was lower for the HEP Score compared to 4T score, intraclass correlation coefficient: 0.50 (95% CI 0.16–0.85) vs. 0.69 (0.54–0.86). There were no significant differences between area under receiver-operating characteristics curves of 4T and HEP score against HIT ELISA testing (0.62 vs. 0.58, P = 0.62), SRA (0.74 vs. 0.73, P = 0.97), expert panel diagnosis (0.71 vs. 0.79, P = 0.20), concordant HIT ELISA and SRA (0.76 vs. 0.72, P = 0.65), and positive SRA or positive HIT ELSA with HIT likely expert panel diagnosis (0.73 vs. 0.75, P = 0.80). The HEP score model was 100% sensitive and 17% specific for determining the presence of HIT as defined by positive SRA or positive HIT ELISA with HIT likely expert panel diagnosis compared to 4T score (sensitivity, 94%; specificity 38%) (Figure 1, Table 1). Conclusion The HEP and 4T scores are excellent screening pre-test probability models for HIT, however, in this prospective validation study, test characteristics for the diagnosis of HIT based on confirmatory laboratory testing and expert opinion are similar. Given the complexity of the HEP scoring model compared to that of the 4T model, further validation of the HEP score is warranted prior to widespread acceptance. Disclosures: Kim: Philips US: Consultancy; GE: Research Funding.

scholarly journals Disease and Clinical Characteristics of Patients with Myelofibrosis Enrolled in the MOST Study

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4190-4190
Author(s):  
Aaron T. Gerds ◽  
Roger M. Lyons ◽  
Philomena Colucci ◽  
Patricia Kalafut ◽  
Dilan Paranagama ◽  
...  
Keyword(s):  
Research Funding ◽  
Clinical Characteristics ◽  
The United States ◽  
Treatment Patterns ◽  
Low Risk ◽  
Normal Range ◽  
Employment Equity ◽  
Oncology Research ◽  
Risk Patients ◽  
Equity Ownership

Introduction: Myelofibrosis (MF) is a chronic Philadelphia chromosome-negative myeloproliferative neoplasm characterized by progressive bone marrow (BM) fibrosis, extramedullary hematopoiesis, splenomegaly, constitutional symptoms, and shortened survival. Data pertaining to the clinical characteristics and treatment patterns of patients with low-risk MF are limited; most studies have focused on patients with intermediate- and high-risk MF. The ongoing Myelofibrosis and Essential Thrombocythemia Observational STudy (MOST) was designed to characterize the demographics, disease burden, patient-reported outcomes, and management of patients with MF or essential thrombocythemia (ET) in clinical practices throughout the United States (NCT02953704). This analysis describes demographic and clinical characteristics of patients with low-risk MF enrolled in MOST. Methods: MOST is an ongoing multicenter, non-interventional, longitudinal, prospective, observational study in patients with MF or ET. Eligible patients with MF were at least 18 years old and had low- or intermediate-1 (INT-1) risk by age alone according to the Dynamic International Prognostic Scoring System (DIPSS). Patients participating in blinded investigational drug trials, having life expectancy ≤6 months, or having other concurrent myeloid malignancies were excluded. Data from patient records were entered into an electronic case report form during usual-care visits over a planned 36-month observation period. Data were analyzed with descriptive statistics. Results: A total of 232 patients with MF were enrolled between November 29, 2016 and March 29, 2019 at 124 sites. Two-hundred patients with low-risk (n=77) or INT-1 risk by age alone (n=123) MF were included in this analysis (data cut-off date, June 17, 2019); 32 patients were excluded due to incorrect risk categorization (n=27) or unanswered prognostic factors at enrollment (n=5). At enrollment, the median age was 68 (range, 35-88) years, 58% were aged >65 years, 49% were women, and 89% were white. Thirteen patients (7%) had a documented family history of MF, ET, or polycythemia vera. Of 157 patients with manual spleen assessment at enrollment, 55 (35%) had palpable splenomegaly; median spleen length was 7 (range, 1‒22) cm in 35 patients with available measurements. The median time from MF diagnosis to enrollment was 1.7 (range, 0.0-37.7) years; most patients (75%) were diagnosed within 5 years of enrollment. Of patients with available data, 93% (185/200) were reported to have undergone BM biopsy/aspiration and 82% (162/198) had mutation testing (MT) at the time of diagnosis; most patients had received both BM biopsy and MT (151/196 [77%]). Data from MT conducted prior to or within 30 days of diagnosis were available for 142 patients (71%); 134/142 patients (94%) were tested for a JAK2 mutation, of whom 95/134 (71%) were positive (Table 1). At enrollment, approximately half of patients with available data (97/190 [51%]) had hemoglobin below normal range, and approximately one-third had platelets (68/188 [36%]) or leukocytes (58/186 [31%]) above normal range (Table 2). The most common signs reported at the time of enrollment included lactate dehydrogenase greater than the upper limit of normal (41%), palpable spleen (31%), and leukocytosis (>11 × 109/L; 24%). Across both risk groups, 111 patients (56%) were receiving MF-directed monotherapy at enrollment (low-risk, 43/77 [56%]; INT-1 by age alone, 68/123 [55%]). Low-risk patients received hydroxyurea (HU; 23/43 [54%]), ruxolitinib (15/43 [35%]), interferon (4/43 [9%]), or anagrelide (1/43 [2%]); INT-1 patients received ruxolitinib (30/68 [44%]), HU (28/68 [41%]), interferon (8/68 [12%]), or anagrelide (2/68 [3%]). Five patients (3%) were receiving >1 MF-directed therapy. Less than half of low- (34/77 [44%]) and INT-1- (50/123 [41%]) risk patients were receiving no MF-directed therapy at enrollment. Conclusion: These real-world data provide insight into the clinical characteristics, diagnosis, and treatment patterns of patients with low- or INT-1 risk (by age alone) MF in the United States. Data from this trial will help characterize the rate at which patients transition from low- or INT-1-risk disease to higher risk categories of disease and how management is affected by disease progression. Disclosures Gerds: Sierra Oncology: Research Funding; Imago Biosciences: Research Funding; Incyte: Consultancy, Research Funding; Celgene Corporation: Consultancy, Research Funding; CTI Biopharma: Consultancy, Research Funding; Pfizer: Consultancy; Roche: Research Funding. Lyons:Texas Oncology: Equity Ownership; Amgen: Consultancy; McKesson: Other: Leadership. Colucci:Incyte: Employment, Equity Ownership. Kalafut:Incyte: Employment, Equity Ownership. Paranagama:Incyte: Employment, Equity Ownership. Verstovsek:Promedior: Research Funding; Blueprint Medicines Corp: Research Funding; CTI BioPharma Corp: Research Funding; Genetech: Research Funding; Pragmatist: Consultancy; Pharma Essentia: Research Funding; Astrazeneca: Research Funding; Ital Pharma: Research Funding; Protaganist Therapeutics: Research Funding; Constellation: Consultancy; Incyte: Research Funding; Roche: Research Funding; NS Pharma: Research Funding; Celgene: Consultancy, Research Funding; Gilead: Research Funding; Novartis: Consultancy, Research Funding; Sierra Oncology: Research Funding.

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