Heparin-induced Thrombocytopenia With Thrombosis Research Articles

Successful Treatment With the Oral Factor Xa Inhibitor Edoxaban in Heparin-Induced Thrombocytopenia With Thrombosis.

Heparin-induced thrombocytopenia with thrombosis (HITT) is a rare immune reaction to the drug heparin that causes increased blood clotting, putting patients at risk for arterial and venous thromboembolism which can have severe consequences. We present a case of HITT successfully treated with the direct oral anticoagulant (DOAC), edoxaban. A 56-year-old man had surgery to remove a colorectal mass. After discharge, he developed chest discomfort, shortness of breath, and low oxygen levels and was diagnosed with a right-sided lobar pulmonary embolism. His platelet count dropped, his tests confirmed a diagnosis of HITT, and he was initially treated with fondaparinux. After showing clinical and laboratory improvement, he was switched to edoxaban. Despite being diagnosed with colonic adenocarcinoma during follow-up, the patient's platelet count returned to normal, and he did not experience any more blood clots or serious bleeding events. The use of DOACs like edoxaban as potential therapies for HITT is promising; further research is being conducted to evaluate their effectiveness, safety, and potential benefits for treating this acquired high-risk thrombophilia.

Incidence and clinical outcomes of heparin-induced thrombocytopenia: 11year experience in a tertiary care university hospital.

Heparin-induced thrombocytopenia (HIT) is a rare immuno-mediated adverse reaction with high thrombotic and mortality risk. To evaluate incidence and outcomes of HIT cases diagnosed at a tertiary care hospital from 2007 to 2018. A retrospective study was conducted. Patients with suspected HIT underwent 4Ts score assessment and anti-heparin PF4 IgG antibodies ELISA screening test. If the latter was positive, platelet aggregation test (PAT) was performed. If the latter was positive, any form of heparin was stopped, alternative anticoagulants were started and then overlapped with warfarin. HIT incidence was calculated by dividing HIT cases by the mean yearly number of admitted patients over 11years. Follow-up was 90days. Among 2125 screening tests, 96 (4.5%) were positive with confirmatory PAT in 82/90 (3.8% for missing data in 6). Median age was 75; 39 patients were surgical and 51 medical. The median 4Ts score was 5. Unfractionated heparin was employed in 34 (37%). HIT incidence was 0.16/1000/patient/years (95% CI: 0.12-0.23) in surgical and 0.15/1000/patient/years (95%: 0.12-0.20) in medical patients. HIT with thrombosis (HIT-T) was observed in 31 patients (0.05/1000/patient/years 95% CI: 0.04-0.1), with venous thromboses in 25 (80%). HIT without thrombosis was observed in 59 patients (0.1/1000 patient/years; 95% CI: 0.08-0.13, twofold vs HIT-T). All cause mortality was 25.5% (95% CI: 17.6-35.4), major bleeding 7.7% (95% CI:3.2-15.3), and thromboembolic complications 3.3% (95% CI:1.1-9.3). HIT is a rare event with high mortality, despite the use of non heparin anticoagulants.

ACUTE HEPARIN-INDUCED THROMBOCYTOPENIA WITH DELAYED IN-STENT SUBACUTE THROMBOSIS OF DRUG ELUTING STENTS, INTRACARDIAC THROMBOSIS, BIVENTRICULAR HEART FAILURE, AND HYPOXIA

TOPIC: Cardiovascular Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: Heparin-induced thrombocytopenia (HIT) is a fatal complication in patients with an average exposure of one to two weeks or can be rapid (< 24hrs) on re-exposure. In susceptible patients, antibodies directed against platelet factor 4 and heparin complexes cause HIT with thrombosis (HITTS). An average incidence of HIT is 0.1%-5% in patients on heparin therapy [1] CASE PRESENTATION: A 73-year-old female with a history of coronary disease, hypertension, and hyperlipidemia came to an outside hospital with a persistent cough, dyspnea, and acute hypoxia. She was treated for acute heart failure exacerbation and non-ST segment elevation myocardial infarction (NSTEMI) based on workup. An echocardiogram (ECHO) revealed an ejection fraction (EF) of 50%. She underwent staged percutaneous coronary intervention (PCI) and placement of an everolimus-based stent in the left anterior descending artery (LAD) followed by another stent in the left circumflex artery (LCX) after three days. Following stent placements, she went into pulmonary edema and was placed on noninvasive ventilation and was transferred to our institute to further manage acute hypoxic respiratory failure. Her hypoxia worsened, requiring endotracheal intubation, vasopressor support. She was treated for heart failure exacerbation and pneumonia. A repeat ECHO revealed two right ventricular thrombi with a severe decline in biventricular EF (Figure A). Anticoagulation with heparin was started, followed by a decline in platelet count > 50% due to HIT on day two, and was switched to argatroban (Figure B). Blood work showed NSTEMI, and a coronary angiogram revealed in-stent thrombosis of both stents (Figure C). Repeat successful PCI to LAD, and LCX with thrombus aspiration was completed. The patient had a complicated clinical course and never recovered DISCUSSION: As age increases, the risk of HIT gets higher [1]. HIT increases early mortality by 50% and embolic events by 20%-50%[2,3]. An increased HIT risk in females with cardiopulmonary bypass, hemodialysis, and vascular surgery was observed [4]. Venous thrombosis may be associated with surgery and arterial thrombosis with cardiovascular disease [5]. HIT antibody rate in patients with ACS is high and can induce symptoms in the absence of thrombocytopenia [6]. The odds of early stent thrombosis are < 1%[7]. The occurrence of thrombosis during therapeutic heparin anticoagulation is a concern for HITTS regardless of platelet counts and duration of therapy. Acute NSTEMI due to in-stent and intracardiac thrombosis due to HITTS is rare CONCLUSIONS: HITTS should be suspected in coronary thrombosis of unknown origin. Immediate heparin discontinuation and alternate anticoagulation are a must in HITTS, which can present with normal platelet counts REFERENCE #1: Hogan M, Berger JS. Heparin-induced thrombocytopenia (HIT): Review of incidence, diagnosis, and management. Vasc Med. 2020;25(2):160-73 REFERENCE #2: Solanki J, Shenoy S, Downs E, Palkimas S, Goldman S, Sharma AM. Heparin-Induced Thrombocytopenia and Cardiac Surgery. Semin Thorac Cardiovasc Surg. 2019;31(3):335-44 REFERENCE #3: Warkentin TE. Think of HIT. Hematology Am Soc Hematol Educ Program. 2006;408-414. doi:10.1182/asheducation-2006.1.408 DISCLOSURES: No relevant relationships by Tarang Patel, source=Web Response No relevant relationships by SACHIN PATIL, source=Web Response No relevant relationships by Shyam Shankar, source=Web Response No relevant relationships by Tushar Tarun, source=Web Response No relevant relationships by Ritika Verma, source=Web Response

COVID-19 Disease, Women's Predominant Non-Heparin Vaccine-Induced Thrombotic Thrombocytopenia and Kounis Syndrome: A Passepartout Cytokine Storm Interplay.

Coronavirus disease 2019 (COVID-19) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) constitute one of the deadliest pandemics in modern history demonstrating cardiovascular, gastrointestinal, hematologic, mucocutaneous, respiratory, neurological, renal and testicular manifestations and further complications. COVID-19-induced excessive immune response accompanied with uncontrolled release of cytokines culminating in cytokine storm seem to be the common pathogenetic mechanism of these complications. The aim of this narrative review is to elucidate the relation between anaphylaxis associated with profound hypotension or hypoxemia with pro-inflammatory cytokine release. COVID-19 relation with Kounis syndrome and post-COVID-19 vaccination correlation with heparin-induced thrombocytopenia with thrombosis (HITT), especially serious cerebral venous sinus thrombosis, were also reviewed. Methods: A current literature search in PubMed, Embase and Google databases was performed to reveal the pathophysiology, prevalence, clinical manifestation, correlation and treatment of COVID-19, anaphylaxis with profuse hypotension, Kounis acute coronary syndrome and thrombotic events post vaccination. Results: The same key immunological pathophysiology mechanisms and cells seem to underlie COVID-19 cardiovascular complications and the anaphylaxis-associated Kounis syndrome. The myocardial injury in patients with COVID-19 has been attributed to coronary spasm, plaque rupture and microthrombi formation, hypoxic injury or cytokine storm disposing the same pathophysiology with the three clinical variants of Kounis syndrome. COVID-19-interrelated vaccine excipients as polysorbate, polyethelene glycol (PEG) and trometamol constitute potential allergenic substances. Conclusion: Better acknowledgement of the pathophysiological mechanisms, clinical similarities, multiorgan complications of COVID-19 or other viral infections as dengue and human immunodeficiency viruses along with the action of inflammatory cells inducing the Kounis syndrome could identify better immunological approaches for prevention, treatment of the COVID-19 pandemic as well as post-COVID-19 vaccine adverse reactions.

Laboratory testing for suspected COVID-19 vaccine-induced (immune) thrombotic thrombocytopenia.

COVID‐19 (coronavirus disease 2019) represents a pandemic, and several vaccines have been produced to prevent infection and/or severe sequelae associated with SARS‐CoV‐2 (severe acute respiratory syndrome coronavirus 2) infection. There have been several reports of infrequent post vaccine associated thrombotic events, in particular for adenovirus‐based vaccines. These have variously been termed VIPIT (vaccine‐induced prothrombotic immune thrombocytopenia), VITT (vaccine‐induced [immune] thrombotic thrombocytopenia), VATT (vaccine‐associated [immune] thrombotic thrombocytopenia), and TTS (thrombosis with thrombocytopenia syndrome). In this report, the laboratory test processes, as utilised to assess suspected VITT, are reviewed. In published reports to date, there are notable similarities and divergences in testing approaches, potentially leading to identification of slightly disparate patient cohorts. The key to appropriate identification/exclusion of VITT, and potential differentiation from heparin‐induced thrombocytopenia with thrombosis (HITT), is identification of potentially differential test patterns. In summary, testing typically comprises platelet counts, D‐dimer, fibrinogen, and various immunological and functional assays for platelet factor 4 (PF4) antibodies. In suspected VITT, there is a generally highly elevated level of D‐dimer, thrombocytopenia, and PF4 antibodies can be identified by ELISA‐based assays, but not by other immunological assays typically positive in HITT. In addition, in some functional platelet activation assays, standard doses of heparin have been identified to inhibit activation in suspected VITT, but they tend to augment activation in HITT. Conversely, it is also important to not over‐diagnose VITT, given that not all cases of thrombosis post vaccination will have an immune basis and not all PF4‐ELISA positive patients will be VITT.

Heparin-Induced Thrombocytopenia Presenting as Splenic Hemorrhage Following Cardiac Surgery: A Case Report

Heparin induced thrombocytopenia with thrombosis (HIT) is a paradoxical prothrombotic complication of anticoagulant therapy. We report a case of atraumatic splenic hemorrhage due to splenic vein thrombosis as main indicator to diagnosis of HIT. The presentation is reminiscent of the rare bilateral adrenal hemorrhage due to adrenal necrosis that occurs in HIT. Alternative anticoagulation is mainstay of therapy for HIT despite hemorrhage, given the underlying acquired hypercoagulability.

The Incidence of Heparin Induced Thrombocytopenia before and after the Implementation of the Venous Thromboembolism Thromboprophylaxis Protocols within Eastern Health

Background: A recognized complication of exposure to heparin is the development of heparin-induced thrombocytopenia (HIT) and heparin-induced thrombocytopenia with thrombosis (HITT). The frequency of HIT in patients exposed to unfractionated heparin (UFH) is higher than those exposed to low-molecular-weight heparin (LMWH). Where the use of unfractionated heparin is not necessary, HIT may be largely preventable by using LMWH rather than UFH on an institution-wide scale. At our institution, UFH was largely substituted by the LMWH for thromboprophylaxis gradually throughout 2014 with the implementation of the venous thromboembolism (VTE) thromboprophylaxis protocols. The VTE thromboprophylaxis protocols had their final implementation at the beginning of 2015. Objectives: - To determine the incidence of HIT and HITT before and after the implementation of the VTE thromboprophylaxis protocols within Eastern Health. - ACP Learning Objective: Educate learners about the risk of using UFH as well as alternative treatment for DVT prophylaxis (LMWH). Methods: Charts of all patients who had HIT screening assays requested between January 1, 2012 and December 31, 2017 were examined to determine which patients went on to have positive screening assays as well as positive confirmatory testing. The type of heparin which the patient was exposed was recorded, the sequelae of HITT within 30 days of medication exposure, as well as the correlation of these findings with the implementation of the VTE thromboprophylaxis protocols. Preliminary Results: In surgical patients the average number of confirmed cases of HIT per year decreased by 51%, and the average number of confirmed cases of HITT per year decreased by 83% after implementation of thromboprophylaxis protocols. In medical patients the average number of confirmed cases of HIT per year decreased by 15%, and the average number of confirmed cases of HITT per year decreased by 47% after implementation of thromboprophylaxis protocols. Between 2012 and 2017 a total of 24 patients experienced HITT, resulting in 33 poor outcomes, including: pulmonary embolism, cerebrovascular accident, DVT, ischemic bowel, arterial thrombosis, venous thrombosis, cardiac thrombus, splenic infarct, and death. The majority of patients experiencing HITT had a history of UFH usage, be it alone or in combination with LMWH, equaling 19 out of 24 patients. Preliminary Conclusion: The incidence of HIT and HITT was reduced after the implementation of the VTE prophylaxis protocols. Further Direction: The next step in the project involves assessing the statistical significance of the above results and assessing the data from 2018 in the same manner as above. Disclosures Young: Sanofi-Aventis: Honoraria, Research Funding. Chitsike:Sanofi-Aventis: Honoraria, Research Funding; Bayer: Research Funding; Bristol Myers Squib: Honoraria; Pfizer: Honoraria; Servier: Honoraria.

Emerging Role of Direct Oral Anticoagulants in the Management of Heparin-Induced Thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) and heparin-induced thrombocytopenia with thrombosis (HITT) are rare but potentially limb- and life-threatening complications of heparin therapy. Continuation of heparin or low-molecular-weight heparin is contraindicated due to platelet activation in the presence of (heparin-dependent) HIT antibodies. Primary treatment options currently include argatroban, fondaparinux, or bivalirudin. However, the parenteral administration routes and interference of argatroban with traditional coagulation markers complicate management. The goal of this review is to assess the viability of direct oral anticoagulants as an alternative treatment option in patients with HIT/HITT. Their use in HIT/HITT is reasonable, given absent cross-reactivity preformed with HIT antibodies. Furthermore, their rapid onset of action and induction of effective anticoagulation provide a favorable basis for their use in this condition. Herein, we summarize 3 studies and 8 case reports comprising 56 patients in whom direct oral anticoagulants were used in the treatment of HIT/HITT.

Medical and Economic Burden of Heparin-Induced Thrombocytopenia: A Retrospective Nationwide Inpatient Sample (NIS) Study.

In recent years, US hospitals have switched from use of unfractionated heparin to use of low-molecular-weight heparin, which is associated with lower risk of heparin-induced thrombocytopenia (HIT). In the study reported here, we retrospectively searched the Nationwide Inpatient Sample (NIS) for patients who were at least 18 years old and received a diagnosis of HIT between 2009 and 2011. Our goal was to get an updated perspective on the incidence and economic impact of HIT. We calculated the incidence of HIT overall and in subgroups of patients who underwent cardiac, vascular, or orthopedic surgery. We compared characteristics of patients with and without HIT and compared characteristics of patients with HIT with thrombosis (HITT) and HIT patients without thrombosis. Of 98,636,364 hospitalizations, 72,515 (0.07%) involved HIT. Arterial and venous thromboses were identified in 24,880 (34.3%) of HIT cases. Men were slightly more likely to have a HIT diagnosis (50.1%), but women had higher rates of HIT after cardiac surgery (odds ratio [OR], 1.41; 95% confidence interval [CI], 1.26-1.58) and vascular surgery (OR, 1.42; 95% CI, 1.29-1.57). Rates of HIT were 0.53% (95% CI, 0.51%-0.54%) after cardiac surgery, 0.28% (95% CI, 0.28%-0.29%) after vascular surgery, and 0.05% (95% CI, 0.05%-0.06%) after orthopedic surgery. HIT and HITT cases were significantly (P ⟨ 0.001) more likely than non-HIT cases to be fatal (9.63% and 12.28% vs 2.19%), and they had significantly higher costs and longer inpatient stays. HIT and especially HITT are associated with increased mortality, costs, and length of stay. Journal of Hospital Medicine 2017;12:94-97.

Activated Platelet-Derived and Leukocyte-Derived Circulating Microparticles and the Risk of Thrombosis in Heparin-Induced Thrombocytopenia: A Role for PF4-Bearing Microparticles?

Though the presence of platelets-derived microparticles (MPs) have previously been described in heparin-induced thrombocytopenia (HIT), the mechanism of thrombosis in HIT remains poorly understood. We aimed to assess the presence and origin of MPs in patients with HIT and their possible contribution to HIT with thrombosis (HITT). Forty-five patients with HIT and 45 matched hospitalized patients with not confirmed HIT (HIT-negative) were enrolled. Twelve HIT patients (27%) developed HITT. MPs expressing phosphatidylserine (Annexin V-MP), activated platelet-derived (P-Selectin+), activated leukocyte-derived (L-Selectin+), PF4-bearing and tissue factor-bearing (TF+) MPs were measured by flow-cytometry. HIT patients showed significantly higher median levels of P-Selectin+, L-Selectin+, PF4-bearing, L-Selectin+/TF + MPs than HIT-negative; PF4-bearing MP showed the highest statistical difference. As compared to HIT patients, HITT patients showed a trend of higher median levels of all MP subtypes considered but the differences were not statistically significant. Only levels of activated-leukocyte/TF + MPs (L-Selectin + CD142+) were significantly higher (P = 0.015). Sensitive analyses showed that HIT patients with activated-leukocyte/TF + MPs above the cut-off (52 MP/µL) had an odds ratio (OR) for thrombosis of 3.78 (95%CI, 0.98-14.5, P = 0.045). The combination of activated-leukocyte/TF + MPs and PF4-bearing-MPs above the cut-off (1416 MP/uL) resulted in a higher risk of HITT (OR 4.49 (95% CI, 1.17-8.05, P = 0.014). We showed for the first time the presence of circulating PF4-bearing MPs derived from activated platelets in patients with HIT; activated leukocyte/TF + MPs are associated with an increased thrombotic risk. Our findings confirm that HIT antibodies complexes may determine a TF-driven prothrombotic state through the activation of platelets and leukocytes. © 2017 International Clinical Cytometry Society.

Bivalirudin Anticoagulation for a Pediatric Patient with Heparin-Induced Thrombocytopenia and Thrombosis Requiring Cardiopulmonary Bypass for Ventricular Assist Device Placement

The direct thrombin inhibitor bivalirudin is an option for anticoagulation in patients with heparin induced thrombocytopenia (HIT) requiring cardiopulmonary bypass (CPB). There are a limited number of reports of pediatric patients in which bivalirudin has been used for anticoagulation for CPB. We present the case of an 11 year old male with acute onset heart failure secondary to idiopathic dilated cardiomyopathy that developed heparin induced thrombocytopenia with thrombosis (HITT). The patient was anticoagulated in the operating room with bivalirudin and placed on CPB for insertion of a HeartWare® Ventricular Assist Device (Heartware®). Modified techniques were utilized. This included use of the Terumo CDI 500 (Terumo Cardiovascular Systems, Inc.) in-line blood gas monitor which contains a heparin coated arterial shunt sensor. We flushed this sensor with buffered saline preoperatively and noted no significant decrease in platelet count postoperatively. The patient was successfully placed on the ventricular assist device and was subsequently listed for heart transplantation.

Pulse-spray catheter-directed thrombolysis with urokinase and argatroban for thrombo-occlusion of an inferior vena cava filter due to heparin-induced thrombocytopenia with thrombosis

A 50-year-old man developed acute sub-massive pulmonary thromboembolism and proximal deep venous thrombosis. A continuous intravenous infusion of unfractionated heparin (UFH) was started, and an inferior vena cava (IVC) filter was implanted. He developed symptomatic complete obstruction of the filter 6 days after the initiation of UFH, and he was transferred to our hospital. We started pulse-spray catheter-directed thrombolysis (CDT) with urokinase. However, thrombocytopenia occurred 11 days after the initiation of heparin. We suspected heparin-induced thrombocytopenia (HIT) with thrombosis (HITT), and switched from UFH to argatroban. In addition, we continued pulse-spray CDT. As a result, thrombocytopenia improved and thrombolysis was successful without complications of recurrent thromboembolism or bleeding, leading to retrieval of the IVC filter. The antigen assay for HIT was strongly positive, supporting our diagnosis. In patients with suspected HIT it is important to switch from heparin to an alternative anticoagulant as soon as possible, and pulse-spray CDT with urokinase and argatroban as anticoagulant therapy may be effective treatment for thrombo-occlusions of IVC filters in patients with HITT.<Learning objective: Thrombo-occlusion is a serious complication of inferior vena cava filters. Anticoagulant therapy alone is not effective for dissolving thrombo-occlusions of inferior vena cava filters. In patients with heparin-induced thrombocytopenia with thrombosis, pulse-spray catheter-directed thrombolysis with urokinase and argatroban as anticoagulant therapy may be effective treatment for venous thrombo-occlusion.>

Medical and Economic Burden of Heparin-Induced Thrombocytopenia: Data from the National Inpatient Sample 2009-2011

▪BackgroundAlthough generally safe, heparin use can trigger an immune response in which platelet factor 4-heparin complexes set off an antibody-mediated cascade that can result in heparin-induced thrombocytopenia (HIT). Although older studies report incidences as high as 5% in high-risk subgroups of surgical patients, recent studies report a much lower incidence (0.02% of hospital admissions and <0.1-0.4% among patients exposed to heparin). As hospitals transition to the less immunogenic low molecular weight heparins, reassessment of the overall national burden of HIT would help inform needs for monitoring strategies for this potentially fatal complication of anticoagulation.MethodsWe used the 2009-2011 National Inpatient Sample database to identify patients aged ≥18 years with primary and secondary diagnoses of HIT (International Classification of Diseases, 9th Revision, Clinical-Modification [ICD-9-CM] code 289.84). We derived the prevalence rate of HIT overall as well as among subgroup of patients undergoing 3 types of surgeries (cardiac, vascular and orthopedic surgeries). We compared characteristics of patients diagnosed with versus without HIT, and HIT with thrombosis (HITT) versus those without thrombosis. Statistical analysis was performed using Stata 13.1, which accounted for the complex survey design and clustering. We used a 2-sided p- value of <0.05 to determine statistical significance.ResultsWe identified 72,515 cases of HIT among a total of 98,636,364 hospitalizations (0.07%). Arterial and venous thromboses were identified in 24,880 (34.3%) of cases with HIT. Males were slightly more likely to be diagnosed with HIT (50.12% vs. 49.88%, odds ratio, OR 1.48, 95% CI: 1.46-1.51), but females had higher rates of post-cardiac and vascular surgery-associated HIT (OR: 1.41, 95% confidence interval, CI: 1.26-1.58, p<0.001 and OR 1.42, 95% CI: 1.29-1.57, p<0.001 respectively). Prevalence rates of HIT among cardiac, vascular and orthopedic surgeries were 0.53% (95% CI: 0.51-0.54%), 0.28% (95% CI: 0.28-0.29%) and 0.05% (95% CI: 0.05-0.06%) respectively. Patients with HIT and HITT were significantly more likely to be fatal than cases without diagnosed HIT (9.63% and 12.28% versus 2.19% respectively, p<0.001), and have significantly higher costs ($137401 and $179735 versus $35905) and length of stay (14.07 and 16.51 days versus 4.76 days).ConclusionAlthough rates of HIT appear lower in the modern era of widespread low molecular weight heparin use, patients undergoing cardiac and vascular surgeries remain at significant risk. Even in recent years, one-third of patients with HIT develop thrombosis, which significantly increases mortality, cost and length of stay. Strategies to monitor and mitigate that risk in high-risk patients appear to be warranted.Table 1In-hospital mortality, mean LOS and Mean hospital charges for patients with heparin induced thrombocytopenia (HIT) and HIT with thrombosis (HITT)No HITHITPHIT without thrombosisHITTPIn-hospital mortality2.19%9.63% (OR 4.75, 95% CI 4.45-5.08)<0.0018.24%12.28% (OR 1.56, 95% CI 1.40-1.74)<0.001Mean LOS (days)4.76 (95% CI 4.71-4.82)14.07 (95% CI 13.67-14.48)<0.00112.80 (95% CI 12.38-13.23)16.51 (95% CI 15.96-17.06)<0.001Mean total hospital charge (USD)35905 (95% CI 34626- 37185)137401 (95% CI 129369-145433)<0.001115456 (95% CI 108251-122661)179735 (95% CI 168582-190889)<0.001HIT= Heparin induced thrombocytopenia; HITT= Heparin induced thrombocytopenia with thrombosis; LOS=Length of stay; USD=US Dollars. DisclosuresNo relevant conflicts of interest to declare.

Systemic treatments for the prevention of venous thrombo-embolic events in paediatric cancer patients with tunnelled central venous catheters

Children with cancer are at higher risk of thrombosis than children without cancer. This is a result of the disease itself but also of the cancer treatment and the presence of a central venous catheter. In this review, we investigated whether systemic treatments can prevent thrombosis. We identified six studies; two studies investigated low molecular weight heparins, one antithrombin supplementation and one cryoprecipitate and/or fresh frozen plasma supplementation; one study compared antithrombin supplementation with low molecular weight heparin and antithrombin supplementation, and another investigated warfarin. The addition of low molecular weight heparins to antithrombin supplementation did result in a lower number of symptomatic thromboses. This was statistically significant. We could not detect an effect of systemic preventive treatments in comparison with no treatment, and no difference was noted in the number of participants who suffered from major or minor bleeding. However, the overall number of participants was very small; a similar study with a larger population of participants might yield different results.

Refractory heparin induced thrombocytopenia with thrombosis (HITT) treated with therapeutic plasma exchange and rituximab as adjuvant therapy

We report a case of refractory heparin-induced thrombocytopenia with thrombosis (HITT) with prolonged thrombocytopenia and multiple thrombotic complications that failed to improvedespite aggressive treatment. A 60year old female with a prior history of venous thromboemoblism was admitted with an acute pulmonary embolism, and developed HITT after several days on heparin therapy. She suffered multiple complications including bilateral venous limb gangrene, acute renal failure, and refractory thrombocytopenia, leading us to use multimodality therapy including therapeutic plasma exchange (TPE) and rituximab immunosuppression. The patient had transient improvements in her thrombocytopenia with TPE, and rituximab was added in an attempt to reduce antibody production. She eventually required bilateral limb amputation, and only after removal of the gangrenous limbs did her platelet count show sustained improvement. We discuss the possible contribution of infection to her prolonged course.

Monitoring the Direct Thrombin Inhibitors

1. George A. Fritsma, MS MT (ASCP)[⇑][1] 1. The Fritsma Factor, Your Interactive Hemostasis ResourceSM, Fritsma & Fritsma LLC, Birmingham, AL 1. Address for Correspondence: George A. Fritsma MS MT (ASCP), The Fritsma Factor, Your Interactive Hemostasis ResourceSM, Fritsma & Fritsma LLC, 153 Redwood Drive, Birmingham, AL 357173, 205-655-0687, George{at}fritsmafactor.com. 1. Diagram the physiology of the direct thrombin inhibitors 2. Distinguishe between argatroban and bivalirudin. 3. Provide the means for monitoring direct thrombin inhibitors. The direct thrombin inhibitors (DTIs), intravenous argatroban and bivalirudin and oral dabigatran, reversibly bind and inactivate free and clot-bound thrombin without activating antithrombin (AT, antithrombin III, ATIII), thereby suppressing coagulation at the final stage of the cascade.1 Argatroban or bivalirudin are substituted for unfractionated heparin (UFH) or low molecular weight heparin (LMWH) when heparin-induced thrombocytopenia with thrombosis (HIT) is suspected or confirmed, as they do not interact with the HIT antibody.2 When HIT is suspected, the risk of either venous or arterial thrombosis is 50% for 30 days after heparin withdrawal unless argatroban or bivalirudin is employed. Coumadin is contraindicated in HIT as it is prothrombotic for the first 5 days of administration. Dabigatran has been cleared for prevention of venous thromboembolic (VTE) disease in Europe and Canada and for prevention of stroke in atrial fibrillation in the US. As the first new oral anticoagulant cleared by the FDA since 1954, dabigatran is beginning to take its place in the formulary. Laboratory scientists are challenged to find clinically effective means to monitor its plasma concentration. Argatroban Argatroban (Novostan®; GlaxoSmithKline, Research Triangle Park, NC) is a non-protein l-arginine derivative with a molecular weight of 527 Daltons.3 Argatroban was FDA-cleared in 1997 for anticoagulation in HIT.4 Argatroban may be used for prophylaxis, treatment, and also for anticoagulation during percutaneous cardiac intervention (PCI, cardiac catheterization) for patients with HIT.5 The physician initiates the argatroban intravenous infusion at 2 μg/kg/min or in patients with liver disease at 0.5 μg/kg/min. During PCI, a bolus of… ABBREVIATIONS: APTT or PTT - activated partial thromboplastin time; AT - antithrombin; CAD – coronary artery disease; DTI - direct thrombin inhibitor; DVT - deep venous thrombosis; ECT-ecarin clotting time; FDA - US Food and Drug Administration; HIT - heparin-induced thrombocytopenia with thrombosis; INR - international normalized ratio; LMWH - low molecular weight heparin; PE - pulmonary embolism; PCI - percutaneous intervention (cardiac catheterization); PiCT - prothrombinase-induced clotting time; PT - prothrombin time; RI - reference interval; RUO - research use only; TCT - thrombin clotting time; TPA - tissue plasminogen activator; UFH - unfractionated heparin; VTE - venous thromboembolism. 1. Diagram the physiology of the direct thrombin inhibitors 2. Distinguishe between argatroban and bivalirudin. 3. Provide the means for monitoring direct thrombin inhibitors. [1]: #corresp-1

Treatment and Prevention of Heparin-Induced Thrombocytopenia: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines

Heparin-induced thrombocytopenia (HIT) is an antibody-mediated adverse drug reaction that can lead to devastating thromboembolic complications, including pulmonary embolism, ischemic limb necrosis necessitating limb amputation, acute myocardial infarction, and stroke. The methods of this guideline follow the Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement. Among the key recommendations for this article are the following: For patients receiving heparin in whom clinicians consider the risk of HIT to be > 1%, we suggest that platelet count monitoring be performed every 2 or 3 days from day 4 to day 14 (or until heparin is stopped, whichever occurs first) (Grade 2C). For patients receiving heparin in whom clinicians consider the risk of HIT to be < 1%, we suggest that platelet counts not be monitored (Grade 2C). In patients with HIT with thrombosis (HITT) or isolated HIT who have normal renal function, we suggest the use of argatroban or lepirudin or danaparoid over other nonheparin anticoagulants (Grade 2C). In patients with HITT and renal insufficiency, we suggest the use of argatroban over other nonheparin anticoagulants (Grade 2C). In patients with acute HIT or subacute HIT who require urgent cardiac surgery, we suggest the use of bivalirudin over other nonheparin anticoagulants or heparin plus antiplatelet agents (Grade 2C). Further studies evaluating the role of fondaparinux and the new oral anticoagulants in the treatment of HIT are needed.

The Direct Medical Costs Associated with Suspected Heparin-Induced Thrombocytopenia

Heparin-induced thrombocytopenia (HIT) is an adverse drug reaction associated with heparin exposure. Sunnybrook Health Sciences Centre, a tertiary-care adult academic hospital, has cared for an average of 100 cases of suspected HIT per year. Although the management of suspected HIT is resource intensive, few studies have assessed the cost burden associated with HIT, and none have assessed the costs of suspected HIT. The objective of this study was to identify and quantify the direct medical costs associated with suspected (confirmed and negative) HIT at a hospital in Canada. A cost-of-illness analysis was conducted in patients with suspected HIT during 2005. Resource utilization variables included (i) laboratory tests to investigate HIT; (ii) HIT-safe anticoagulant use; (iii) diagnostic imaging related to HIT or its treatment; and (iv) additional hospital days attributed to HIT. The average costs per case of confirmed HIT, confirmed HIT with thrombosis (HITT) and negative HIT were calculated in $Can, year 2007 values. Confirmed HITT cases incurred substantially greater costs ($Can34 155, range 358-202 069; n = 12) than confirmed HIT cases without thrombosis ($Can4575, range 39-16 373; n = 8). The average cost of care for a negative HIT case was $Can119 (range 39-4181; n = 88). This is the first study to quantify the costs associated with suspected HIT cases. These cases increase the costs of hospital care and provide further justification for HIT prevention strategies.

Heparin Platelet Factor 4 Antibody Positivity in Pseudothrombocytopenia

Pseudothrombocytopenia (PTCP) is a laboratory event of platelet clustering related to drugs used for anticoagulation. This condition is engendered by autoantibodies against platelets in usually EDTA-anticoagulated blood. Pseudothrombocytopenia has no clinical significance but when evaluated as true thrombocytopenia, this misconception may lead to unnecessary diagnostic procedures. Heparin-induced thrombocytopenia with thrombosis (HITT) is a complication of heparin treatment caused by heparin platelet factor 4 (HPF-4) antibodies, leading to platelet activation and hypercoagulability. In our study, 48 patients with PTCP and 36 healthy volunteers were included. Heparin platelet factor 4 antibody positivity was detected in 12 patients from PTCP group; nobody from control group had. Citrated serum samples and peripheral blood smears showed normal platelet count. Of the 4 patients using heparin derivative, 1 (2.1%) had antibody positivity but without any bleeding symptoms. In conclusion, HPF-4 antibody positivity might be a risk factor for PTCP. Clinicians should be aware of this kind of condition.

Heparin-Induced Thrombocytopenia and Extracorporeal Membrane Oxygenation: A Case Report and Review of the Literature

Heparin-induced thrombocytopenia (HIT) is an immune-mediated coagulation side effect of heparin therapy characterized by thrombocytopenia and by a paradoxical prothrombotic state following heparin exposure when thrombotic or thromboembolic events accurse, the condition is classified as Heparin-induced thrombocytopenia with thrombosis (HITT). We report a case of HITT with evidence of small-vessel arterial thrombosis in a 5-day-old newborn receiving extracorporeal membrane oxygenation (ECMO) for congenital diaphragmatic hernia, and our attempt of bivalirudin alternative treatment. We also review previous reports regarding HIT and ECMO with the alternative management in this unique population.