The Risk of Major Bleeding in Patients with Suspected Heparin-Induced Thrombocytopenia (HIT)

Abstract Introduction: Without prompt treatment, heparin-induced thrombocytopenia (HIT) is associated with a daily rate of life- and limb-threatening thrombosis of 6.1%. Current recommendations are to empirically treat a patient with an intermediate or high pre-test likelihood of HIT with a non-heparin (alternative) anticoagulant while awaiting HIT laboratory test results. The real-world bleeding rates of empiric treatment with an alternative anticoagulant in patients with suspected HIT have not been well-described. We assessed the rates of major bleeding in a prospective cohort of patients with suspected HIT. Because HIT is generally considered a prothrombotic and not a prohemorrhagic disorder, we hypothesized that major bleeding would be less common in alternative anticoagulant-treated patients with HIT than in treated patients who were ultimately determined not to have HIT. Methods: From June 2012 to January 2015, we enrolled 310 patients with suspected HIT at the Hospital of the University of Pennsylvania and an affiliated community hospital. All patients underwent HIT laboratory testing with a poly-specific PF4/heparin ELISA and in-house serotonin release assay. Patients were adjudicated to be HIT-positive or HIT-negative by an independent adjudication panel of HIT experts based on clinical course and results of HIT laboratory testing. We retrospectively reviewed the electronic health record to assess for the presence of a major bleeding event from the time of suspicion of HIT until hospital discharge or death. Major bleeding events were defined by International Society on Thrombosis and Haemostasis (ISTH) criteria (fall in hemoglobin ≥2 g/dL, transfusion of ≥2 units of packed red blood cells, fatal bleed, bleed occurring in a critical organ and/or requiring a repeat surgical intervention). Secondary outcomes of progressive or new thrombosis following suspicion of HIT testing, in-hospital and 30-day mortality were also assessed. Patients were considered to be treated for suspicion for HIT if they received an alternative anticoagulant following a HIT laboratory test order. The demographics and clinical features of patients defined by adjudicated HIT status were compared using the Wilcoxon test and chi-square tests for continuous and for categorical variables, respectively. The proportion of bleeding and thrombotic events were compared between groups using a chi-square test. All analyses were performed using Stata v14.2. Results:The demographics of our cohort by adjudicated HIT status are displayed in Table 1. 44 patients in the cohort were adjudicated to be HIT-positive and 266 were adjudicated HIT-negative. 42/44 (95.5%) HIT-positive patients and 116 of 266 (43.6%) HIT-negative patients received an alternative anticoagulant. Of those who were empirically treated with an alternative anticoagulant, the median duration of treatment was 3 days (IQR 2-5.5) in HIT-negative patients, compared with 11.5 days (IQR 6-16) in the HIT-positive group (p=0.001). The majority of treated patients received argatroban (88.0% of HIT-positive patients and 76.7% of HIT-negative patients). In those patients who received an alternative anticoagulant, a major bleeding event occurred in 40.9% of HIT positive patients and 44.8% HIT negative patients (p=0.45).The majority of major bleeding events met ISTH criteria based on hemoglobin fall or blood transfusion (Table 2). New or progressive thrombosis following suspicion for HIT was more common in HIT-positive patients (35.7%) than in patients who were HIT-negative and treated (15.5%) or not treated (11.3%) (p=0.001) (Table3). Conclusions: Contrary to our hypothesis, HIT was not protective against bleeding. A similar proportion of HIT-positive patients had ISTH major bleeding compared with HIT-negative patients treated with an alternative anticoagulant. The current paradigm for empiric treatment of patients with suspected HIT may need to be reconsidered in light of our findings of greater than expected bleeding associated with treatment. Limitations of our study include relatively small size, recruitment from a single health system, and predominant use of a single alternative anticoagulant (argatroban). Further studies are needed to determine whether our results apply to other centers and other alternative anticoagulants. Disclosures Pishko: Novo Nordisk: Research Funding. Cuker:Synergy: Consultancy; Genzyme: Consultancy; Kedrion: Membership on an entity's Board of Directors or advisory committees; Spark Therapeutics: Research Funding.

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P3758Clinical characteristics and outcomes of atrial fibrillation patients with thrombocytopenia: the Fushimi AF Registry

European Heart Journal ◽

10.1093/eurheartj/ehz745.0610 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

K Ishigami ◽

Y Aono ◽

S Ikeda ◽

K Doi ◽

Y An ◽

...

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Platelet Count ◽

Major Bleeding ◽

Bleeding Event ◽

Bleeding Events ◽

Major Bleeding Event ◽

Entire Cohort ◽

Severe Group ◽

The Mean

Abstract Background Thrombocytopenia is sometimes found in routine blood tests and is reported as a risk factor of major bleeding events and incidence of all-cause death after percutaneous coronary intervention. However, the influence of thrombocytopenia on clinical outcomes in patients with atrial fibrillation (AF) remains unknown. Purpose We aimed to investigate relationship between baseline platelet count and clinical outcomes such as all-cause death, hospitalization for heart failure, and the major bleeding event in AF patients. Methods The Fushimi AF Registry was designed to enroll all of the AF patients in Fushimi-ku, Kyoto. Fushimi-ku is densely populated with a total population of 283,000 and is assumed to represent a typical urban community in Japan. Follow-up data with baseline platelet counts were available in 4,179 patients from March 2011 to November 2018. We divided the entire cohort into 3 groups according to baseline platelet level: No thrombocytopenia (≥150,000/μL, n=3,323), Mild thrombocytopenia (100,000–149,999/μL, n=707), and Moderate/severe thrombocytopenia (≤99,999/μL, n=149). Results In the entire cohort, the mean age was 73 years, 40% were women, and the mean body weight and body mass index was 59 kg and 23.1 kg/m2, and the median platelet count were 192,000/μL (interquartile range 156,000 to 232,000/μL), respectively. Compared to No thrombocytopenia, patients with thrombocytopenia were older (No vs. Mild vs. Moderate/severe; 73.3 years vs. 76.5 years vs. 75.8 years, p<0.0001), more likely to have heart failure (27.0% vs. 32.8% vs. 41.6%, p<0.0001), more likely to have chronic renal disease (35.7% vs. 42.6% vs. 57.7%, p<0.0001), and had higher CHADS2 score (2.05 vs. 2.17 vs. 2.34, p=0.0039) and CHA2DS2-VASc score (3.40 vs. 3.52 vs. 3.71, p=0.0416). Patients with thrombocytopenia had lower hemoglobin (13.0 vs. 12.8 vs. 11.6, p<0.0001) than No thrombocytopenia. However, prevalence of previous major bleeding events was comparable between three groups (4.66% vs. 4.67% vs. 5.37%, p=0.92) On Kaplan-Meier analysis, the incidence of all-cause death was higher in Mild group (hazard ratio [HR] 1.51; 95% confidence interval [CI] 1.28–1.77) and Moderate/severe group (HR 2.97; 95% CI 2.28–3.80) than No group (Figure 1). The incidence of hospitalization for heart failure was higher in Mild group (HR 1.62; 95% CI 1.31–1.99) and Moderate/severe group (HR 2.64; 95% CI 1.76–3.81) than No group (Figure 2). The incidence of major bleeding event was higher in Mild group (HR 1.46; 95% CI 1.11–1.91) and Moderate/severe group (HR 2.45; 95% CI 1.41–3.91) than No group (Figure 3). Conclusion Thrombocytopenia in AF patients was associated with higher incidence of all-cause death, hospitalization for heart failure, and major bleeding event in the Fushimi AF Registry. Acknowledgement/Funding Pfizer, Bristol-Myers Squibb, Boehringer Ingelheim, Bayer Healthcare,and Daiichi-Sankyo

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Major Bleeding with Ibrutinib: More Than Expected

Blood ◽

10.1182/blood.v128.22.3229.3229 ◽

2016 ◽

Vol 128 (22) ◽

pp. 3229-3229 ◽

Cited By ~ 11

Author(s):

Paul R Kunk ◽

Joesph Mock ◽

Michael E. Devitt ◽

Surabhi Palkimas ◽

Jeremy Sen ◽

...

Keyword(s):

Adverse Events ◽

Major Bleeding ◽

Research Funding ◽

Bleeding Event ◽

Lymphocytic Leukemia ◽

Significant Activity ◽

University Of Virginia ◽

Bleeding Events ◽

Major Bleeding Events

Abstract Introduction: Ibrutinib is a Bruton's tyrosine kinase inhibitor that has significant activity in treating lymphoma. While approved for patients with Chronic Lymphocytic Leukemia (CLL) and Mantle Cell Lymphoma (MCL), its activity in other lymphomas and solid tumors is under investigation and its use is increasing dramatically. Overall it is well tolerated compared to chemotherapy, but bleeding has emerged as a common adverse event with rates as high as 50% and major bleeding around 3% (Jones, abstract #1990, 2014 ASH Annual Meeting). As the use of ibrutinib increases outside of a clinical trial setting, the rate of major bleeding is likely to rise. Methods: To better understand the risk of bleeding in ibrutinib treated patients, we reviewed all patients at the University of Virginia and satellite clinics who were treated with ibrutinib between January 2012 and May 2016. Patients were required to be treated for at least 1 month with documented follow up for assessment of adverse events. Medical charts were reviewed for age, gender, ibrutinib indication and dose, length of treatment, concurrent medications, blood tests and bleeding events. All forms of anti-platelets and anticoagulants drugs, as well as medications interacting with cytochrome P450 3A4 (3A4), which metabolizes ibrutinib, were recorded. All bleeding events were recorded and graded according the Common Toxicity Criteria for Adverse Events, v4.0. Major bleeding events were reviewed by all investigators. Results: Eighty-nine patients were identified. Eighteen patients were excluded for insufficient follow up leaving 71 patients for analysis. Median age was 73 years old (44-92) with 74% male. The most common indications for treatment were CLL (65%) and MCL (27%). Most patients were treated with either 420mg (64%) or 560mg (21%). Median length of time on ibrutinib was 412 days, most with ongoing use at time of data collection. Seventy percent of patients were also treated with an anti-platelet medication, mostly aspirin for CAD with several patients on multiple anti-platelet medications. Seventeen percent were treated with an anti-coagulant, mostly apixaban for atrial fibrillation. Thirteen percent of patients (9/71) were treated with combined anti-platelet and anti-coagulant medications. Ten percent of patients were treated with a medication that has a moderate or strong interaction with 3A4. Bleeding of any grade occurred in 56% of patients, mostly bruising and epistaxis. Major bleeding, defined as grade 3 or higher, occurred in 18% of patients. Three patients developed major bleeding after an invasive procedure without ibrutinib being held. One patient died as a result of peri-procedural bleeding. Of the 9 patients treated with combined anti-platelet and anti-coagulant therapy, 78% suffered a major bleeding event. Of the ten patients on ibrutinib alone, without concurrent use of an anti-platelet, anti-coagulant or 3A4 drug interaction, no major bleeding events occurred. Conclusion: In this study examining real world use of ibrutinib, the rates of major bleeding are higher than previously reported. Most patients who suffered major bleeding were also treated with an anti-coagulant and/or anti-platelet medication. As the use of ibrutinib increases outside of clinical trials, a careful review of medications should be performed in addition to adherence to perioperative drug withholding guidelines. Patients requiring anti-coagulant and/or anti-platelet medications while on ibrutinib need careful consideration of the risks and benefits given the higher incidence of bleeding in this population. Table 1 Table 1. Disclosures Portell: AbbVie: Research Funding; Roche/Genentech: Research Funding; Infinity: Research Funding; Acerta: Research Funding. Williams:Janssen and Pharmacyclics: Research Funding; University of Virginia: Employment.

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Major Bleeding Complications Among Patients Treated with Ibrutinib and Concomitant Antiplatelet, Anticoagulant, or Supplemental Therapy

Blood ◽

10.1182/blood.v128.22.4387.4387 ◽

2016 ◽

Vol 128 (22) ◽

pp. 4387-4387 ◽

Cited By ~ 4

Author(s):

Aaron Pavlik ◽

Hallie Barr ◽

Emily Dotson ◽

John C. Byrd ◽

Kristie A. Blum ◽

...

Keyword(s):

Clinical Trial ◽

Board Of Directors ◽

Major Bleeding ◽

Research Funding ◽

Bleeding Event ◽

Antiplatelet Agents ◽

Bleeding Complications ◽

Bleeding Events ◽

Advisory Committees ◽

Major Bleeding Events

Abstract Background: Ibrutinib, an orally bioavailable small molecular inhibitor of Bruton's tyrosine kinase (BTK), is an approved therapy for chronic lymphocytic leukemia (CLL), relapsed mantle cell lymphoma (MCL) and Waldenstrӧm's macroglobulinemia (WM). Beyond B lymphocytes, BTK signaling is important for collagen-mediated platelet activation, and BTK inhibition has been associated with primary hemostatic bleeding events (Levade et al Blood 2014). Although serious bleeding events have been uncommon (1-5%) in clinical trial populations, there is limited data describing the potential for increased serious bleeding incidence when ibrutinib is co-administered with other agents affecting the clotting cascade or platelet function. Methods: We conducted a retrospective cohort study to evaluate the incidence of major bleeding in patients receiving ibrutinib concomitantly with antiplatelet agents (non-steroidal anti-inflammatory agents, ADP inhibitors), anticoagulants (heparins, warfarin, novel oral anticoagulants), or supplements with potential anticoagulant activity (vitamin E and fish oil). Major bleeding events were identified using criteria developed by the International Society on Thrombosis and Haemostasis (Schulman et al J Thromb Haemost 2005). Patients 18-89 years of age and treated with ibrutinib for CLL, MCL, or WM between March 1, 2010 and March 1, 2015 were included. The primary endpoint of this study was the incidence of major bleeding events, but we also sought to identify risk factors associated with the development of major bleeding, focusing on potential drug interactions. Based on the historic prevalence of major bleeding in ibrutinib clinical studies, we calculated that at least 20 major bleeding events would need to be identified in order to perform blinded multinomial regression on the collected data of an estimated 400 patients. Results: 437 eligible patients were included in the analysis. Patients were overwhelmingly male (71.4%) and white (94.8%), with a mean age of 67.1 years (range: 29-89). 53.1% received ibrutinib as participants of a clinical trial, and the remainder received standard-of-care ibrutinib treatment. The table (upper panel) summarizes use of concomitant antihemostatic agents by presence or absence of major bleeding events. Characteristics of the major bleeding events are further detailed in the lower panel. The most commonly observed concomitant antihemostatic medication was aspirin, with 147 patients (33.6%) being exposed to aspirin within the study period. Fourteen instances of major bleeding were observed, corresponding to an overall incidence of 3.2%. These major bleeding events all occurred in CLL patients receiving ibrutinib at the standard dose of 420 mg daily. Two patients had platelet counts less than 50 k/µL at time of the bleeding event. One-half of the major bleeding events were observed in the absence of an antihemostatic medication, and 2 of the observed major bleeding events resulted in death (1 received concomitant warfarin). Fourteen patients (3.3%) in the group without major bleeding were on anticoagulation, 4 being warfarin. The most common sites of major bleeding were gastrointestinal (50%), intracranial (14.3%) and thoracic (14.3%). While most patients developing major bleeding permanently discontinued ibrutinib (57.1%), approximately one third of the patients who developed major bleeding subsequently resumed ibrutinib following resolution of the bleeding event. Subsequently, these patients did not experience a recurrent major bleeding event. The rate of major bleeding did not meet power to detect statistical differences in bleeding events when comparing concomitant therapy, Conclusions: Our observed incidence of major bleeding is consistent with previous controlled clinical trials, suggesting similar safety profile when ibrutinib is used outside of a controlled setting. Major bleeding events were uncommon despite the frequent co-administration of antiplatelet agents. However, because we modified practice early to avoid therapeutic anticoagulation during ibrutinib therapy whenever possible, the number of patients receiving such drugs in combination was small and precludes inferences regarding safety. Table Table. Disclosures Blum: Pharmacyclics: Research Funding. Awan:Innate Pharma: Research Funding; Pharmacyclics: Consultancy; Novartis Oncology: Consultancy. Woyach:Acerta: Research Funding; Karyopharm: Research Funding; Morphosys: Research Funding. Christian:Pharmacyclics: Research Funding; Janssen: Research Funding. Jones:Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics, LLC, an AbbVie Company: Membership on an entity's Board of Directors or advisory committees, Research Funding.

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LO94: Evaluation of stroke and bleeding outcomes among patients managed in the emergency department for newly diagnosed atrial fibrillation

CJEM ◽

10.1017/cem.2020.148 ◽

2020 ◽

Vol 22 (S1) ◽

pp. S41-S42

Author(s):

S. Niaz ◽

C. Kirwan ◽

N. Clayton ◽

M. Mercuri ◽

K. de Wit

Keyword(s):

Atrial Fibrillation ◽

Emergency Department ◽

Major Bleeding ◽

Bleeding Event ◽

National Guidelines ◽

Bleeding Events ◽

Chads2 Score ◽

Major Bleeding Event ◽

Ischemic Attack ◽

New Diagnosis

Introduction: Atrial Fibrillation (AF) is the most common arrhythmia seen in patients presenting to the emergency department (ED). AF increases the risk of ischemic stroke which can be mitigated by anticoagulant prescription. National guidelines advise that emergency physicians initiate anticoagulation when AF is first diagnosed. We aimed to evaluate the 90-day incidence of stroke and major bleeding among emergency patients discharged home with a new diagnosis of AF. Methods: This was a health records review of patients diagnosed with AF in two EDs. We included patients ≥ age 18, with a new diagnosis of AF who were discharged from the ED, between 1st May 2014 and 1st May 2017. Using a structure review we collected data on CHADS65 and CHADS2 scores, contraindications to direct oral anticoagulant (DOAC) prescription and initiation of anticoagulation in the ED. Patient charts were reviewed for the diagnosis of stroke, transient ischemic attack (TIA), ischemic gut, ischemic limb or other systemic embolism within 90 days of the index ED presentation. We extracted data on major bleeding events within 90 days, defined by the International Society of Thrombosis and Haemostasis criteria. All data were extracted in duplicate for validation. Results: We identified 399 patients fulfilling the inclusion criteria, median age 68 (IQR 57-79), 213 (53%) male. 11 patients were already prescribed an anticoagulant for another indication and 19 had a contraindication to prescription of a DOAC. 48/299 (16%) CHADS65 positive patients were initiated on an anticoagulant, 3 of whom had a contra-indication to initiation of anticoagulation in the ED (1 dual antiplatelet therapy, 2 liver cirrhosis). 1/100 CHADS65 negative patients was initiated on anticoagulation. The median CHADS2 score was 1 (IQR 0-2). Among the 49 patients initiated on anticoagulation, 3 patients had a stroke/TIA within 90 days, 6.1% (95% CI; 2.1-16.5%). There were no bleeding events 0.0% (95% CI; 0.0-7.3%). Among the 350 patients who were not initiated on anticoagulation in the ED, 4 patients had a stroke/TIA 1.1% (95% CI; 1.1-2.9%) within 90 days and 2 patients had a major bleeding event. Conclusion: Prescription of anticoagulation for new diagnoses of AF was under-utilized in these EDs. The 90-day stroke/TIA rate was high, even among those given an anticoagulant prescription in the ED. No patient had an anticoagulant-associated bleeding event.

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Soluble glycoprotein VI is a predictor of major bleeding in patients with suspected heparin-induced thrombocytopenia

Blood Advances ◽

10.1182/bloodadvances.2020002861 ◽

2020 ◽

Vol 4 (18) ◽

pp. 4327-4332 ◽

Cited By ~ 1

Author(s):

Allyson M. Pishko ◽

Robert K. Andrews ◽

Elizabeth E. Gardiner ◽

Daniel S. Lefler ◽

Adam Cuker

Keyword(s):

Major Bleeding ◽

Platelet Transfusion ◽

Bleeding Event ◽

Bleeding Risk ◽

Enzyme Linked Immunosorbent Assay ◽

Sample Collection ◽

Bleeding Events ◽

Heparin Induced Thrombocytopenia ◽

Glycoprotein Vi ◽

Major Bleeding Events

Abstract We have shown that patients with suspected heparin-induced thrombocytopenia (HIT) have a high incidence of major bleeding. Recent studies have implicated elevated soluble glycoprotein VI (sGPVI) levels as a potential risk factor for bleeding. We sought to determine if elevated sGPVI plasma levels are associated with major bleeding events in patients with suspected HIT. We used a cohort of 310 hospitalized adult patients with suspected HIT who had a blood sample collected at the time HIT was suspected. Plasma sGPVI levels were measured by using enzyme-linked immunosorbent assay. Patients were excluded who had received a platelet transfusion within 1 day of sample collection because of the high levels of sGPVI in platelet concentrates. We assessed the association of sGPVI (high vs low) with International Society on Thrombosis and Haemostasis major bleeding events by multivariable logistic regression, adjusting for other known risk factors for bleeding. Fifty-four patients were excluded due to recent platelet transfusion, leaving 256 patients for analysis. Eighty-nine (34.8%) patients had a major bleeding event. Median sGPVI levels were significantly elevated in patients with major bleeding events compared with those without major bleeding events (49.09 vs 31.93 ng/mL; P < .001). An sGPVI level >43 ng/mL was independently associated with major bleeding after adjustment for critical illness, sepsis, cardiopulmonary bypass surgery, and degree of thrombocytopenia (adjusted odds ratio, 2.81; 95% confidence interval, 1.51-5.23). Our findings suggest that sGPVI is associated with major bleeding in hospitalized patients with suspected HIT. sGPVI may be a novel biomarker to predict bleeding risk in patients with suspected HIT.

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The Effect of BMI and Gender on Bleeding Events when Rivaroxaban Is Administered for Thromboprophylaxis Following Total Hip and Total Knee Arthroplasty

Seminars in Thrombosis and Hemostasis ◽

10.1055/s-0038-1676319 ◽

2018 ◽

Vol 45 (02) ◽

pp. 180-186 ◽

Cited By ~ 3

Author(s):

Eugene Krauss ◽

Nancy Dengler ◽

Barry Simonson ◽

Kathleen Altner ◽

Madison Daly ◽

...

Keyword(s):

Venous Thromboembolism ◽

Major Bleeding ◽

Total Joint Arthroplasty ◽

Bleeding Event ◽

Joint Arthroplasty ◽

Morbidly Obese ◽

Bleeding Events ◽

Major Bleeding Event ◽

Major Bleeding Events ◽

And Gender

AbstractRivaroxaban is approved in Europe and the United States for thromboprophylaxis following total joint arthroplasty. As the rate of obesity increases, confirming safety and efficacy in this patient population is paramount. This retrospective chart review assessed the efficacy and safety of rivaroxaban between two body mass index (BMI) groups: normal or overweight (< 30 kg/m2) and obese or morbidly obese (≥30 kg/m2). Safety outcome was a major bleeding event, defined as a decrease in hemoglobin of at least 2 g/dL from postoperative day 1(POD 1) to discharge or a blood transfusion of at least two units. Efficacy outcome was venous thromboembolism within 35 days postoperatively. There were 68 (68/1,241; 5.48%) major bleeding events. There was no significant association between major bleeding events and BMI in the univariable analysis (p < 0.36). However, after adjusting for other factors in the multivariable model, there was a significant interaction between BMI and gender (p < 0.001). Among males, the incidence of major bleeding events was three times greater in obese/morbidly obese subjects as compared with normal/overweight male subjects (odds ratio [OR]: 3.09, 95% confidence interval [CI]: 1.25, 7.62). Among females, incidence of having a major bleeding event was almost two times greater in normal/overweight subjects as compared with obese/morbidly obese female subjects (OR: 2.17, 95% CI: 1.10, 4.35). Incidence of venous thromboembolism was 0.4% in each group. The authors' study results highlight a previously unexplored association between BMI and gender-dependent differences in bleeding outcomes when rivaroxaban is used for thromboprophylaxis following total joint arthroplasty.

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Major Bleeding Outcomes for Admitted Immune Thrombocytopenia Patients with Platelets Less Than 10K: A Single Center Experience

Blood ◽

10.1182/blood-2020-140162 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 21-22

Author(s):

Rawan Hammoudeh ◽

Yaser Alkhatib ◽

Qutaiba Sabha

Keyword(s):

Major Bleeding ◽

Platelet Transfusion ◽

Bleeding Event ◽

Severe Bleeding ◽

Minor Bleeding ◽

Bleeding Events ◽

Major Bleeding Event ◽

History Of ◽

The Cost ◽

Hemoglobin Drop

Introduction Immune thrombocytopenia (ITP) is one of the most common causes of thrombocytopenia in adults. Majority of patients are asymptomatic or might have symptoms primarily related to mucocutaneous or minor bleeding events, while severe bleeding is uncommon. ITP patients who develop severe bleeding require urgent hospitalization, but asymptomatic/minor bleeding patients might be successfully treated as outpatient. In several occasions, the latter group of patients are admitted to the hospital to initiate treatment when their platelets are very low (i.e. less than 10K). In this study we aimed to evaluate the incidence of major bleeding and medical necessity for admitting this group to the hospital. Methods We conducted a retrospective chart review of 559 charts with an ICD code of ITP between March 2017 to March 2020. We excluded all patients who presented with a platelet above 10K, other co-existing hematological disorders or malignancies, first presentation with platelets less than 10K with no prior known history of ITP, and charts of patients who left against medical advice prior to initiation of treatment. The definition of major bleeding included intracranial hemorrhage, or any bleeding with more than 1 gm hemoglobin drop. Minor bleeding included epistaxis, gum bleeding, hematuria, vaginal or minor GI bleeding that didn't result in hemoglobin drop. We found a total of 66 ITP patients who were admitted to the hospital because of platelet count of less than 10K, of which 54 had minor or no bleeding episode, while 12 patients presented with major bleeding episode. Results Between the period of March 2017 to March 2020, a total of 66 patients with a known history of ITP were admitted to the hospital with platelet count of less than 10K, of which 54 patients (82%) had either only minor bleeding (n=10), or no evidence of bleeding (n=44) and 12 patients (18%) presented with major bleeding. The major bleeding events were distributed as follows: Hematuria due to kidney stone (n=1), traumatic ICH ((n=4), spontaneous ICH (n=1), and GI bleed (colon mass (n=1), erosive gastropathy(n=1), angiodysplasia (n=1), esophageal varices (n=2), and gastric ulcer (n=1)). None of the asymptomatic/minor bleeding patients developed any major bleeding event before, during or after hospitalization. The average LOS for asymptomatic/minor bleeding patients was 4.65 days (range 1-45 days), compared to 9.14 days (range 2-20 days) for patients with major bleeding. All the 12 patients (100%) with major bleeding received platelet transfusions during hospitalization, while 23 asymptomatic/minor bleeding patients (42%) received platelet transfusion. Discussion Major bleeding in patients with acute ITP is usually a clear indication for hospitalization, however there is lack of data to support admitting asymptomatic/minor bleeding ITP patients when platelets are less than 10K. Our data showed that no major bleeding event has developed in asymptomatic/minor bleeding patients at time of presentation, during hospitalization or after discharge. All 12 patients with major bleeding presented with a bleeding event that warranted their admission, of which 1 patient had spontaneous bleeding, while the rest had a clear medical reason for the major bleeding, which was likely exacerbated by thrombocytopenia. Since assessing the risk of bleeding is an important step in considering prophylactic platelet transfusion for those with platelets less than 10K, 42% of asymptomatic/minor bleeding patients received platelet transfusion during admission indicating that more than half didn't have high risk features. Inpatient hospitalization carries a high financial burden on both the patient and the healthcare system, increases the risk of hospital acquired infections and in-hospital complications. Asymptomatic/Minor bleeding patients in our study had average LOS of 4.65 days, and all were treated with regimens that can be given as an outpatient including steroids, IVIG, and in some occasions Rituximab and/or thrombopoietin stimulating agents increasing the cost of their hospital stay. Based on our observation, we are able to conclude that this particular group of patients would possibly benefit from close monitoring of signs and symptoms, labs, and treatment all in the outpatient setting. Further studies are needed to evaluate the cost effectiveness and long-term outcome in these patients. Disclosures No relevant conflicts of interest to declare.

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Haemorrhagic stroke and major bleeding after intervention with biological aortic valve prosthesis: risk factors and antithrombotic treatment

European Heart Journal Supplements ◽

10.1093/eurheartj/suaa007 ◽

2020 ◽

Vol 22 (Supplement_C) ◽

pp. C26-C33

Author(s):

Christina Christersson ◽

Elisabeth Ståhle ◽

Lars Lindhagen ◽

Stefan James

Keyword(s):

Aortic Valve ◽

Major Bleeding ◽

Bleeding Event ◽

Haemorrhagic Stroke ◽

Coagulation Cascade ◽

Valve Prosthesis ◽

Antithrombotic Treatment ◽

Bleeding Events ◽

Major Bleeding Event ◽

Biological Prosthesis

Introduction The majority of patients with severe aortic stenosis are recommended intervention with a surgical biological prosthesis (bioSAVR) or a transcatheter aortic valve intervention (TAVI). The antithrombotic strategies after aortic valve intervention vary and include drugs targeting both platelets and the coagulation cascade. Long-term exposure and changes of antithrombotic treatment influence the risk of both bleeding and thromboembolic events.The aim was to describe an unselected sample of patients who have experienced haemorrhagic stroke and other major bleeding events after biological aortic prosthesis, their antithrombotic treatment and changes of treatments in relation to the bleeding event.All patients performing an bioSAVR or a TAVI 2008–2014 were identified in the SWEDEHEART registry and included in the study (n = 10 711). The outcome events were haemorrhagic stroke and other major bleeding event. Information of drug exposure was collected from the dispensed drug registry.The incidence rate of any bleeding event was 2.85/100 patient-years the first year after aortic valve intervention. Heart failure and atrial fibrillation were present more often in patients with a first haemorrhagic stroke or other major bleeding event compared to without. The proportion of exposure to warfarin was 28.7% vs. 21.3% in patients with and without a haemorrhagic stroke. Comparable figures were 31.2% vs. 19.0% in patients with and without other major bleeding event. During 1 month prior a haemorrhagic stroke or other major bleeding event 39.4% and 38.0%, respectively, of the patients not previously exposed to antithrombotic treatment started warfarin or single antiplatelet therapy.Major bleeding events are not uncommon after aortic valve intervention with a biological prosthesis. Evaluation of comorbidities and previous bleeding might improve risk stratification for bleeding in these elderly patients. The pattern of change of antithrombotic treatment was similar in the groups with and without a bleeding event and in most patients the antithrombotic regime was unchanged the month before an event.

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Patient Harm from Repetitive Blood Draws and Blood Waste in the ICU: A Retrospective Cohort Study

Blood ◽

10.1182/blood-2019-127394 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 57-57

Author(s):

Thomas Bodley ◽

Maverick Chan ◽

Lauren Clarfield ◽

Olga Levi ◽

Avery Longmore ◽

...

Keyword(s):

Blood Cell ◽

Major Bleeding ◽

Red Blood Cell ◽

Sofa Score ◽

Bleeding Event ◽

Severity Of Illness ◽

Red Blood Cell Transfusion ◽

Bleeding Events ◽

Major Bleeding Event ◽

Major Bleeding Events

Introduction: Frequent blood testing in the intensive care unit (ICU) is instrumental to patient diagnosis, monitoring, and titration of invasive therapies. However, there is a growing appreciation that a significant proportion of ICU blood tests are reflexive and unnecessary.1,2 Serial phlebotomy is associated with extended hospital length of stay and acquired anemia in the general hospital population.3 Since patients in the ICU are prone to developing anemia,4,5 they are likely at increased risk of harm from serial phlebotomy. In response, multiple recent campaigns advocate for physician restraint in laboratory test ordering.6,7 However, relatively little is known about the effect of excessive phlebotomy on outcomes in critically ill patients. Better understanding of ICU phlebotomy practices, and harms associated with serial testing, is important in planning, implementing, and evaluating phlebotomy reduction interventions. Objectives: 1) Quantify average daily phlebotomy volume for ICU patients including blood discarded as waste when accessing vascular devices. 2) Identify if average daily phlebotomy volume is an independent risk factor for ICU acquired anemia (hemoglobin < 80 g/L) or the need for red blood cell transfusion. 3) Explore the relationship between daily phlebotomy volume and hospital mortality. Methods: This was a retrospective cohort study at an academic tertiary care center in Toronto, Ontario, utilizing hospital administrative data, laboratory data, and select chart review. Index Medical Surgical ICU admissions between September 2014 and August 2015 with an ICU stay of three days or greater were included. Major bleeding events were defined as a hemoglobin drop of 30 g/L within a 24 hour period. Average daily phlebotomy volumes were calculated using the number of samples received by the lab multiplied by standard blood volumes required for each sample type. A bedside prospective audit was conducted in March 2018 to quantify average blood volume discarded as waste during phlebotomy. Blood discard/waste data were summarized with descriptive statistics, but not included in further analysis. Multivariable logistic regression was used to study the association between average daily phlebotomy volume and each of: nadir hemoglobin (< 80 g/L), the need for red blood cell transfusion, and hospital mortality. Patients with a major bleeding event were excluded from the regression. Control variables included sex, age, ICU length of stay, admission hemoglobin, and admission Sequential Organ Failure Assessment (SOFA) score. Results: There were a total of 525 index patient admissions, mean age 62.1 yr, 41% female (Table 1). Fifty-two (52) patients had a major bleeding event in the ICU. Mean phlebotomy volume per patient day was 28.3 mL (95% CI 27.4 - 29.1 mL, stdev 10.1 mL). Mean bedside waste during the phlebotomy audit (total of 144 blood draws) varied by vascular access: 3.9 mL for arterial, 5.5 mL for central venous, and 6.25 mL for peripherally inserted catheters. The mean estimated daily bedside waste for phlebotomy was 14.8 mL per patient day. Outcomes of logistical regression, excluding patients with major bleeding events, are summarized in Table 2. Average daily phlebotomy volume (mL) was predictive of nadir hemoglobin < 80 g/L (parameter estimate 0.091, p <0.001), the need for red blood cell transfusion (0.092, p<0.001), and inpatient mortality (0.053, <0.001). For every 5 mL increase in average daily phlebotomy, the odds ratio (OR) for nadir hemoglobin < 80 g/L was 1.58 (95% CI 1.31 - 1.90) and the OR for a red cell transfusion was 1.58 (95% CI 1.33 - 1.87). Conclusion: Daily ICU phlebotomy volume is associated with ICU acquired anemia and the need for red blood cell transfusion, including in a multivariable model with patient demographics, major bleeding events, and severity of illness as estimated by day 1 SOFA score. However, the ICU admission SOFA score was only weakly predictive of mortality, and the unexpected association between average daily phlebotomy and mortality needs to be further explored. It is possible that in this data set day 1 SOFA score did not completely control for severity of illness. Our findings support the need for ongoing phlebotomy stewardship interventions in the ICU. We suggest ICU acquired anemia and the need for red blood cell transfusion are appropriate patient outcome measures to evaluate stewardship interventions. Disclosures No relevant conflicts of interest to declare.

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Bleeding and Thrombotic Adverse Events in Hospitalized Patients Under Empiric Treatment for Suspected Heparin-Induced Thrombocytopenia While Awaiting Confirmatory Testing

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/1076029621996473 ◽

2021 ◽

Vol 27 ◽

pp. 107602962199647

Author(s):

Kaitlyn C. Dykes ◽

Cassandra A. Johnson ◽

Jerald Z. Gong ◽

Steven E. McKenzie ◽

Holleh D. Husseinzadeh

Keyword(s):

Adverse Events ◽

Watchful Waiting ◽

Prediction Models ◽

Bleeding Event ◽

Retrospective Chart Review ◽

Bleeding Risk ◽

Heparin Induced Thrombocytopenia ◽

Empiric Treatment ◽

Heparin Anticoagulation ◽

Management Groups

Empiric management in suspected heparin-induced thrombocytopenia (HIT) is challenging due to imperfect prediction models, latency while awaiting test results and risks of empiric therapies. When there is high clinical suspicion for HIT, cessation of heparin and empiric non-heparin anticoagulation with FDA-approved argatroban is recommended. Alternatively off-label fondaparinux or watchful waiting have been utilized in clinical practice. Outcomes of patients empirically managed for HIT have not been compared directly in clinical trials and patients that ultimately do not have HIT are often overlooked. Clinicians need studies investigating empiric management to guide decision making in suspected HIT. In this study, adverse events (AE) were categorized and compared in patients being evaluated for HIT while undergoing empiric management by non-heparin anticoagulation with argatroban or fondaparinux, both at therapeutic or reduced doses, or watchful waiting with or without heparin. AE were defined as new thrombosis confirmed on imaging or new bleeding event after HIT was first suspected. A retrospective chart review of 312 patients tested for HIT at an academic hospital was conducted. 170 patients met inclusion criteria. Patients were excluded if the 4Ts score was < 4. The 4Ts score is a pretest probability for HIT based on thrombocytopenia degree, timing, alternative causes and presence of thrombosis. Included patients were divided according to management groups and compared with logistic regression analysis. Bleeding risk significantly differed between management groups (p = 0.002). Despite adjustment for bleeding risk, fondaparinux was associated with increased AE, (p = 0.03, OR = 5.81), while argatroban was not. There was no difference in AE based on time to initiation of empiric treatment and no advantage to reduced dosing with either anticoagulant. These findings challenge assumptions surrounding empiric HIT management.

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