The Incidence of Thrombosis in Patients with Isolated Heparin Induced Thrombocytopenia.

Abstract Introduction: Heparin-induced thrombocytopenia type-II (HIT) is a serious prothrombotic disorder caused by heparin exposure. The incidence of thrombosis in patients with isolated HIT, defined as HIT without clinically evident thrombosis at the time of diagnosis, is not well established. Aim: The purpose of this prospective study was to determine the total incidence of thrombotic events after diagnosis of isolated HIT from radiographic evidence of asymptomatic deep venous thrombosis (DVT) plus radiographic confirmation of symptomatic thrombosis. Patients and Methods: We evaluated all patients with a positive enzyme-linked immunoassay (ELISA) for heparin-platelet factor 4 (PF4) antibody (Ab) daily at Massachusetts General Hospital from 10/10/05 to 5/13/06. Inpatients with (1) a positive PF4 Ab test, (2) thrombocytopenia, as defined by a ≥50% drop from baseline platelet count and/or a fall in platelet count to <150×109/L, in association with heparin exposure, (3) no signs or symptoms of thrombosis at time of the positive Ab test, and (4) no other definitive etiology of thrombocytopenia were considered to have isolated HIT and included for study. Patients with a prior diagnosis of HIT, DVT, pulmonary embolism, or peripheral arterial thrombosis were excluded. Within 72 hours of diagnosis and of initiation of a non-heparin anticoagulant, all included patients underwent radiographic examination for asymptomatic DVT in the lower extremities (LE). Objective evidence of thrombotic events other than LE DVT after the diagnosis was also recorded. Daily platelet count, type and timing of all anticoagulants, use of blood products, and PF4 Ab titer were collected to determine if there was an association between these factors and development of thrombosis. Mortality rate during hospitalization was also recorded. Results: Of the 158 patients with a positive heparin-PF4 Ab, 64 patients met criteria for study, 14 of which were lost to follow-up. Among the 50 remaining eligible patients, the total incidence of thrombosis was 20% (12% were found to have an asymptomatic thrombotic event and 8% developed a symptomatic thrombotic event). Development of thrombosis was independently associated with platelet transfusion (p=0.005) and with the degree of platelet count nadir as expressed by platelet count (p=0.038) or by percent decrease from baseline (p=0.031). There was no association between the PF4 Ab titer or the type and timing of non-heparin anticoagulant and development of thrombosis. The overall mortality rate in patients diagnosed with isolated HIT during hospitalization was 22%. Conclusion: The total incidence of thrombotic events in isolated HIT was 20%, with greater than half of the events being asymptomatic thromboses found only by radiographic examination. This high incidence of asymptomatic LE DVT suggests that routine investigation for LE DVT should be performed in this patient population and that patients with isolated HIT should be treated with a non-heparin anticoagulant. Our findings also confirm the current recommendation to avoid platelet transfusions in patients with isolated HIT as we found an increased rate of thrombosis associated with this practice.

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

Blood ◽

10.1182/blood.v122.21.2328.2328 ◽

2013 ◽

Vol 122 (21) ◽

pp. 2328-2328 ◽

Cited By ~ 1

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.

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Heparin-induced thrombocytopenia: when a low platelet count is a mandate for anticoagulation

Hematology ◽

10.1182/asheducation-2009.1.225 ◽

2009 ◽

Vol 2009 (1) ◽

pp. 225-232 ◽

Cited By ~ 14

Author(s):

Thomas L. Ortel

Keyword(s):

Platelet Count ◽

Heparin Therapy ◽

Severe Thrombocytopenia ◽

Drug Induced ◽

Platelet Factor ◽

Heparin Induced Thrombocytopenia ◽

Immune Mediated ◽

Number Of Patients ◽

Increased Risk ◽

Antibody Levels

Abstract Heparin-induced thrombocytopenia (HIT) is an immune-mediated disorder caused by the development of antibodies to platelet factor 4 (PF4) and heparin. The thrombocytopenia is typically moderate, with a median platelet count nadir of ~50 to 60 × 109 platelets/L. Severe thrombocytopenia has been described in patients with HIT, and in these patients antibody levels are high and severe clinical outcomes have been reported (eg, disseminated intravascular coagulation with microvascular thrombosis). The timing of the thrombocytopenia in relation to the initiation of heparin therapy is critically important, with the platelet count beginning to drop within 5 to 10 days of starting heparin. A more rapid drop in the platelet count can occur in patients who have been recently exposed to heparin (within the preceding 3 months), due to preformed anti-heparin/PF4 antibodies. A delayed form of HIT has also been described that develops within days or weeks after the heparin has been discontinued. In contrast to other drug-induced thrombocytopenias, HIT is characterized by an increased risk for thromboembolic complications, primarily venous thromboembolism. Heparin and all heparin-containing products should be discontinued and an alternative, non-heparin anticoagulant initiated. Alternative agents that have been used effectively in patients with HIT include lepirudin, argatroban, bivalirudin, and danaparoid, although the last agent is not available in North America. Fondaparinux has been used in a small number of patients with HIT and generally appears to be safe. Warfarin therapy should not be initiated until the platelet count has recovered and the patient is systemically anticoagulated, and vitamin K should be administered to patients receiving warfarin at the time of diagnosis of HIT.

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Heparin-induced thrombocytopenia occurring after surgical treatment of atrial myxoma: A case report

Srpski arhiv za celokupno lekarstvo ◽

10.2298/sarh0910540d ◽

2009 ◽

Vol 137 (9-10) ◽

pp. 540-544 ◽

Cited By ~ 1

Author(s):

Irena Djunic ◽

Dragica Tomin ◽

Nebojsa Antonijevic ◽

Sinisa Gradinac ◽

Mirjana Kovac ◽

...

Keyword(s):

Differential Diagnosis ◽

Platelet Count ◽

Correct Diagnosis ◽

Corticosteroid Treatment ◽

Clinical Score ◽

Atrial Myxoma ◽

Platelet Factor ◽

Heparin Induced Thrombocytopenia ◽

Unfractioned Heparin ◽

Left Atrial Myxoma

Introduction Heparin-induced thrombocytopenia (HIT) is an acquired, prothrombotic disorder, caused by antibodies to a complex of heparin and platelet factor 4 (PF4) that activates platelets, resulting in the release of procoagulant microparticles, thrombocytopenia occurrence, generation of thrombin, and frequent thromboses. Case Outline We present a case of severe HIT in a 68-year-old female, which occurred after cardiosurgery of the left atrial myxoma with the aim to point out the importance of differential diagnosis of thrombocytopenia in patients recently exposed to heparin. Platelet count dropped on the eleventh postoperative day, six days after unfractioned heparin and enoxaparine treatment, to 4?109/l. The correct diagnosis failed to be made at first. Since thrombocytopenia remained refractory to a corticosteroid treatment and platelet transfusion, the patient was hospitalized on the 13th postoperative day at the Institute of Hematology. The diagnosis of HIT was confirmed with the high-probability clinical score (4T's) and strongly positive antiheparin-PF4 (PaGIA) test as well as positive platelet aggregation test. The treatment started with a smaller therapeutic doses of danaparoid than recommended of 750 U intravenous bolus and was followed by continuous infusions of 100 U per 1 h and intravenous gammaglobulins in full dosage for four days. The platelet count started to rise on the third day and it was completely normalized on the 5th day of the therapy. Conclusion Treatment of severe HIT with small doses of danaparoid supplemented by intravenous gamma globulin was successful. Additional awareness of heparin-induced thrombocytopenia is needed, especially of HIT in differential diagnosis of thrombocytopenia in patients recently exposed to heparin.

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A practical approach to evaluating postoperative thrombocytopenia

Blood Advances ◽

10.1182/bloodadvances.2019001414 ◽

2020 ◽

Vol 4 (4) ◽

pp. 776-783 ◽

Cited By ~ 3

Author(s):

Leslie Skeith ◽

Lisa Baumann Kreuziger ◽

Mark A. Crowther ◽

Theodore E. Warkentin

Keyword(s):

Platelet Count ◽

Late Onset ◽

Practical Approach ◽

Drug Induced ◽

Heparin Induced Thrombocytopenia ◽

Replacement Surgery ◽

Device Implantation ◽

Increased Risk ◽

Posttransfusion Purpura ◽

Heparin Exposure

Abstract Identifying the cause(s) of postoperative thrombocytopenia is challenging. The postoperative period includes numerous interventions, including fluid administration and transfusion of blood products, medication use (including heparin), and increased risk of organ dysfunction and infection. Understanding normal thrombopoietin physiology and the associated expected postoperative platelet count changes is the crucial first step in evaluation. Timing of thrombocytopenia is the most important feature when differentiating causes of postoperative thrombocytopenia. Thrombocytopenia within 4 days of surgery is commonly caused by hemodilution and increased perioperative platelet consumption prior to thrombopoietin-induced platelet count recovery and transient platelet count overshoot. A much broader list of possible conditions that can cause late-onset thrombocytopenia (postoperative day 5 [POD5] or later) is generally divided into consumptive and destructive causes. The former includes common (eg, infection-associated disseminated intravascular coagulation) and rare (eg, postoperative thrombotic thrombocytopenic purpura) conditions, whereas the latter includes such entities as drug-induced immune thrombocytopenia or posttransfusion purpura. Heparin-induced thrombocytopenia is a unique entity associated with thrombosis that is typically related to intraoperative/perioperative heparin exposure, although it can develop following knee replacement surgery even in the absence of heparin exposure. Very late onset (POD10 or later) of thrombocytopenia can indicate bacterial or fungal infection. Lastly, thrombocytopenia after mechanical device implantation requires unique considerations. Understanding the timing and severity of postoperative thrombocytopenia provides a practical approach to a common and challenging consultation.

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Prediction of Heparin Induced Thrombocytopenia: Validation of an Experience-Based Computer Model.

Blood ◽

10.1182/blood.v110.11.3226.3226 ◽

2007 ◽

Vol 110 (11) ◽

pp. 3226-3226

Author(s):

Nicole L. Whitlatch ◽

David F. Kong ◽

Thomas L. Ortel

Keyword(s):

Predictive Accuracy ◽

Medical Center ◽

Confirmatory Test ◽

Multivariate Logistic Regression Model ◽

Clinical Value ◽

Laboratory Findings ◽

Platelet Factor ◽

Heparin Induced Thrombocytopenia ◽

Duke University ◽

Heparin Exposure

Abstract Background: Diagnosis of heparin-induced thrombocytopenia (HIT) requires certain clinical features along with the detection of platelet activating antibodies induced by heparin interaction with platelet factor 4 (PF4). Although the PF4 enzyme-linked immunoassay (ELISA) is a highly sensitive laboratory test, it is not specific. Adding excess heparin to the sample can confirm a positive PF4 ELISA result when it decreases antibody binding by 50% or more, potentially improving the specificity of the assay. We sought to determine the clinical value of the PF4 ELISA and confirmatory test by developing a predictive algorithm for HIT. Methods: We retrospectively identified 116 patients with positive anti-PF4/heparin antibodies at Duke University Medical Center in 2005. We collected data on all patients to allow for clinical classification as HIT positive or HIT negative. HIT positive patients had at least a 30% decline in platelet count after 4–14 days of heparin exposure, or within 48 hours if recent (within last 100 days) heparin exposure. Anti-PF4/heparin antibody titers were determined by ELISA using a confirmatory step with excess heparin. A multivariate logistic regression model was fitted to the 2005 data, to estimate the relationship between patient characteristics (including age, gender, race, and clinical service), laboratory findings (including peak PF4 titer, confirmatory positive status), and clinical HIT status (HIT positive versus HIT negative). The model was then validated on an independent sample of 97 patients with positive anti-PF4/heparin antibodies retrospectively identified at Duke University Medical Center from January to July of 2006. Results: We found no significant relationship between age, race, or gender and clinical HIT status. In multivariate analysis, the peak PF4 titer and confirmatory positive status were independent predictors of HIT. Figure 1 depicts median, 25th, and 75th percentiles of the predicted probabilities for the HIT-positive and HIT-negative patients in the 2005 training and 2006 test populations. The predictive accuracy on the 2005 training set (c-index 0.783, Somer’s Dyx 0.566) was maintained when the algorithm was applied to the independent 2006 test population (c-index 0.799, Somer’s Dyx 0.597). Figure 2 depicts the ROC curves for both patient populations. Conclusions: This is the first study to our knowledge that has demonstrated the clinical utility of the Heparin/PF4 ELISA confirmatory test for the diagnosis of HIT. Based upon the PF4 ELISA and confirmatory assays, a predictive computer algorithm can distinguish patients likely to have HIT from those who are not. Accurate predicted probabilities of HIT will enable clinicians to more rapidly initiate appropriate therapy. Figure Figure Figure Figure

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A Road Paved with Good Intentions: A Platelet Count-Based Alert to Facilitate Diagnosis of Heparin-Induced Thrombocytopenia

Blood ◽

10.1182/blood-2021-145891 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 756-756

Author(s):

Jori E. May ◽

Kimberly D. Martin ◽

Laura J. Taylor ◽

Eric L. Wallace ◽

Marisa B. Marques

Keyword(s):

Platelet Count ◽

Real Time ◽

Predictive Value ◽

Laboratory Testing ◽

Thrombotic Event ◽

Enzyme Linked Immunosorbent Assay ◽

Functional Assay ◽

Heparin Induced Thrombocytopenia ◽

Probability Score ◽

Elisa Testing

Abstract Background: Heparin-induced thrombocytopenia (HIT) is a rare disorder with potential to cause significant morbidity and mortality. Early identification and initiation of non-heparin anticoagulation can prevent devastating thrombotic events. However, over-testing is common and can lead to result misinterpretation, unnecessary heparin avoidance, and increased cost. When there is concern for HIT, guidelines from the American Society of Hematology recommend calculation of the 4Ts score to determine the need for laboratory testing. The Choosing Wisely® initiative recommends against laboratory testing in patients with a low probability score of ≤3. In patients with an intermediate or high probability score (≥4), screening with enzyme-linked immunosorbent assay (ELISA) is performed first. If positive, the diagnosis of HIT is confirmed with a functional assay, commonly the serotonin release assay (SRA). Methods: In an effort to increase recognition of HIT, providers at a large academic medical center received a non-interruptive alert in the electronic medical record (EMR) on all patients in whom the platelet count declined by ≥50% starting in Aug 2017. We performed a retrospective evaluation of 1) the number of alerts and 2) all ELISA results obtained with or without an alert, over a 90-day period (Dec 2019 to March 2020). A 4Ts score was calculated by chart review by the first author in real-time as the alert was sent (blinded to ELISA and SRA results). Among those patients with multiple alerts or test orders, the first instance was used for analysis. Demographic and clinical characteristics were reported using frequencies and percentages, means (standard deviation, SD), and medians (interquartile range, IQR). Patients with alerts and ELISA testing ordered were compared with 2 groups: 1) patients with alerts but no ELISA ordered; 2) patients with no alerts but ELISA ordered. Comparisons were performed using chi squared tests, Fisher's exact tests, t-tests and Wilcoxon rank-sum tests as appropriate. Results: In the 90-day observation period, 302 alerts were fired in 270 patients (Figure 1). Thirty alerts (28 patients, 10%) were generated for patients admitted for organ donation or post-stem cell transplantation, for whom platelet count decline was expected. Excluding these patients, there were 272 alerts in 242 patients (approximately 3 alerts per day in a 1,157-bed hospital). Of patients with alerts, 22 (8%) had a platelet count inaccuracy (i.e. platelets clump or another reason) and 18 (7%) did not receive heparin prior to platelet decline, for a cumulative total of 40 (15%) inappropriate alerts. In patients with an alert, the ELISA was ordered more frequently for those with a lower platelet nadir (77x10 9/L vs. 115x10 9/L, p<0.0001) or in those with a thrombotic event (11 patients (17%) vs. 6 patients (4%), p=0.0021) (Table 1). Those without an ELISA ordered were more likely to have a low 4Ts score (23 patients (36%) vs. 81 patients (58%), p<0.0001). In addition to 71 patients with an alert, an ELISA was also ordered for 67 patients without an alert (n=138) (Figure 1). Close to half of ELISA-tested patients had a low 4Ts score (n=51, 46%) (Figure 2). In patients with an alert and ELISA not ordered, 18 (27%) had an intermediate or high 4Ts score. Seven patients were diagnosed with HIT based on a positive SRA, 6 with an alert and 1 without. The alert demonstrated a sensitivity of 86% (95% CI, 59.8-100%) and specificity of 50% (95% CI, 41.8-58.9%) with a positive predictive value of 0.0845 (95% CI, 0.0198-0.1492) and negative predictive value of 0.9851 (95% CI, 0.9560-1.0000). Conclusion: An EMR alert based on platelet count decline had multiple shortcomings including frequent inappropriate firings and a lack of guidance on appropriate indications for testing. This evaluation of institutional testing practices indicates frequent use and misinterpretation of ELISA discordant with evidence-based guidelines. Although prompt diagnosis of HIT is important, alternative strategies for identification of at-risk patients and communication of recommended actions to providers should be considered. Because the 4Ts score includes variables difficult to automate in the EMR, our institution is exploring electronic consultation and real-time expert provider access to overcome these limitations. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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Spontaneous Heparin-Induced Thrombocytopenia and COVID-19 Infection

Blood ◽

10.1182/blood-2021-151590 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 4216-4216

Author(s):

Suneetha Amara

Keyword(s):

Platelet Count ◽

Conflicts Of Interest ◽

Hospitalized Patients ◽

Target Range ◽

Low Grade ◽

Primary Therapy ◽

Platelet Factor ◽

Heparin Induced Thrombocytopenia ◽

The Right ◽

D Dimer

Abstract Background and Objective: Heparin-induced thrombocytopenia (HIT) can develop if immune responses to infections become pathologic in the presence of heparins. Low molecular weight heparin or unfractionated heparin are recommended for prophylaxis and treatment of venous thromboembolic disease in hospitalized patients with Covid-19 infection but may trigger HIT. Our aim is to alert clinicians that HIT occurs in association with Covid-19 infections even in the absence of prior exposure and may not be easily recognized without a high index of suspicion. Case Summary: A 33-year-old previously healthy male was initially evaluated for low grade fever, dyspnea without hypoxia and cough. A Covid-19 PCR swab was negative despite a recent exposure. He was treated with azithromycin. However, his symptoms did not improve, he then developed right leg swelling and hypoxia, so he was re-evaluated. CTA of the chest showed bilateral pulmonary emboli and ground-glass opacities at the lung bases. Venous Duplex Ultrasound showed non-occlusive thrombus in the deep veins of right lower extremity. He was hospitalized and placed on oxygen and heparin. Covid-19 swab was negative again. Laboratory tests before heparin showed a decreased platelet count of 64,000 k/ul, elevated prothrombin time of 16.4 seconds, normal aPTT at 30.8 seconds, decreased serum fibrinogen at 120 mg/dl and markedly elevated D-dimer at 59,966 ng/ml. Lupus anticoagulant and anti-phospholipid antibody tests were negative. On heparin at the desired therapeutic aPTT target range, the right leg became significantly swollen and painful by day five. Platelet count had decreased further to 39,000 k/ul. Repeat doppler examination of the right leg now showed more severe and extensive deep venous thrombosis. D-dimer had increased to 125,133 ng/ml. The HIT 4T score was 4, suggesting intermediate probability. Rapid HIT immunoassays on 2 separate samples were positive. Heparin was discontinued and he was placed on argatroban. Serotonin release assays on 2 separate samples came back positive. Suspicion for Covid-19 infection remained high and so a Covid-19 serology sample was obtained which was positive for IgG. A repeat nasopharyngeal swab at this time turned positive. He did not receive any COVID specific treatments. As viability of his leg appeared threatened, he underwent right iliofemoral vein thrombectomy with arteriovenous fistula creation. He improved on argatroban and was transitioned to apixaban with gradual normalization of hemostasis laboratory parameters, improvement in hypoxemia and fading clinical symptoms, he was discharged home on day 15. Conclusion: Current consensus guidelines for thromboprophylaxis and treatment of thromboembolism in hospitalized patients with Covid-19 infection recommend heparins as primary therapy to reduce morbidity and mortality. However, our report in addition to the two previous reports of HIT in Covid-19 patients illustrate that HIT can be a complication in the setting of Covid-19 infection. Further, our report also highlights that HIT with thrombosis can occur in a spontaneous manner in the absence of prior heparin exposure, which has been so far studied only in bacterial infection with the hypothesis that Platelet factor 4 (PF4) can bind to negatively charged polysaccharides on the surface of bacteria, triggering an immune response. Disclosures No relevant conflicts of interest to declare.

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EFFECT OF A SYNTHETIC ANTICOAGULANT (MD 805) ON PLATELETS IN HUMAN VOLUNTEERS AND HEMODIALYSIS PATIENTS.

10.1055/s-0038-1643457 ◽

1987 ◽

Author(s):

T Matsuo ◽

T Yamada ◽

K Nakao

Keyword(s):

Platelet Count ◽

Thrombus Formation ◽

Normal Subjects ◽

Hemodialysis Patients ◽

Normal Range ◽

Synthetic Compound ◽

Platelet Factor ◽

Heparin Induced Thrombocytopenia ◽

Human Volunteers ◽

Platelet Release

Twelve normal subjects were injected with 5000 U of commercial mucous heparin with or without preloading of 1.0 g aspirin, and 0.2 mg/kg MD 805, an arginine derivative, which is a new synthetic compound with an extremely strong affinity for thrombin, at an interval of 4 weeks after each injection. Heparin injection with or without aspirin significantly increased platelet factor 4 release. In contrast, the preloading of aspirin significantly inhibited the decrease of platelet count and the elevation of /8 thromboglobulin induced by heparin. However, MD 805 had no effect on platelet release proteins, and adequate anticoagulation by APTT was still present 60 min after the injection. MD 805 shows no stimulative effects on platelets such as with heparin.In the case of the patient's study, three patients complicated with heparin induced thrombocytopenia plus thrombus formation in the extracorporeal circulation during hemodialysis, and were treated with MD 805 instead of heparin. The platelet counts in those patients quickly returned to within the normal range, and adequate anticoagulation was obtained in the following hemodialysis sessions and no further bleeding or clot formation was noted.In conclusion, MD 805 may represent a useful alternative anticoagulant in patients with heparin induced thrombocytopenia.

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Does the Platelet Factor 4 (PF4) ELISA Correlate with the Clinical Diagnosis of Type II Heparin-Induced Thrombocytopenia?.

Blood ◽

10.1182/blood.v106.11.2179.2179 ◽

2005 ◽

Vol 106 (11) ◽

pp. 2179-2179

Author(s):

Michael B. Streiff ◽

Thomas S. Kickler ◽

Edward G. Weir

Keyword(s):

Clinical Judgment ◽

Thrombotic Event ◽

Anticoagulation Therapy ◽

Serotonin Release ◽

Admission Diagnosis ◽

Type Ii ◽

Patient Age ◽

Platelet Factor ◽

Heparin Induced Thrombocytopenia ◽

Patient Âgé

Type II heparin-induced thrombocytopenia (HIT) is an antibody-mediated complication of heparin therapy that is associated with a consumptive thrombocytopenia and a high risk of thromboembolism. It is now known that antibodies associated with type II HIT recognize sites on PF4 when complexed with heparin. Due to technical challenges associated with the serotonin release assay, most clinicians rely on the PF4 ELISA to establish a laboratory diagnosis of HIT. However, it is unclear whether the ELISA has predictive value in identifying those patients who have clinically apparent disease and whether ELISA optical density (OD) measurements correlate with the development of thrombosis. We retrospectively reviewed the medical records of 103 sequential patients who tested positive for HIT by a commercial PF4 ELISA from 2000–2002. While blinded to ELISA OD values, we recorded patient age and gender, admission diagnosis, hospital course, type of heparin administered, route of administration, baseline and nadir platelet counts, timing of thrombocytopenia, HIT therapy, clinical thrombotic events within 30 days, and other potential causes of thrombocytopenia to determine the clinical likelihood of HIT. The association between OD values and both the clinical likelihood of HIT and objectively confirmed thrombotic events was analyzed using the Pearson Chi-square test. Median patient age was 62 yrs and 52% of patients were female. Those with cardiac disease, cancer, and venous thromboembolism constituted 44%, 19% and 9% of the study population, respectively. Median platelet count nadir was 40K/mL (range, 2K–90K), and average onset of thrombocytopenia was 6.5 days. Median ELISA OD value was 0.77 (0.40–3.81). The clinical likelihood of HIT was noted in 24/103(23%) patients, and 22(21%) suffered a thrombotic event. An ELISA OD >1.0 was significantly associated with the clinical likelihood of HIT (p=0.03), though OD values ranged from 0.41 to 3.81 among these patients. Neither an OD threshold of 1.0 or 1.5 was associated with thromboembolism (p=0.2 and p=0.1, respectively). In contrast, the clinical likelihood of HIT was significantly associated with subsequent thrombosis (p=0.002). ELISA results were not significantly associated with the extent or onset of thrombocytopenia, type of heparin or route administered, patient age or gender, admission diagnosis, or hospital course. In conclusion, PF4 ELISA OD values are significantly associated with the clinical likelihood of HIT but are not predictive of HIT on an individual patient basis. Clinical judgment but not ELISA OD values is associated with subsequent thromboembolism. In summary, the clinical likelihood of HIT, and not ELISA results, remains the best parameter by which to modify anticoagulation therapy in patients being assessed for HIT. Figure Figure

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Pattern of Platelet Recovery in Predicting Outcome in Heparin-Induced Thrombocytopenia and Thrombosis.

Blood ◽

10.1182/blood.v108.11.4085.4085 ◽

2006 ◽

Vol 108 (11) ◽

pp. 4085-4085

Author(s):

Indu Sabnani ◽

Ajaz Khan ◽

Patricia Tsang

Keyword(s):

Platelet Count ◽

Early Diagnosis ◽

Liver Dysfunction ◽

Patient Management ◽

Response To Therapy ◽

Cardiac Diseases ◽

Platelet Factor ◽

Platelet Recovery ◽

Heparin Induced Thrombocytopenia ◽

Recovery Group

Abstract Heparin-induced thrombocytopenia and thrombosis (HITT), a severe immune-mediated drug reaction, is often underdiagnosed. Early management of HITT with alternative anticoagulants can result in a favorable outcome. However, the morbidity and mortality associated with HITT remain high, posing challenges for patient management. We describe the clinical profile and pattern of platelet count recovery in a cohort of 34 patients diagnosed with HITT. This retrospective study consists of 164 patients screened for HITT over 18 months at our institution based on positive platelet factor 4 (PF4) IgG antibodies in the proper clinical setting. Patients who tested positive were divided on the basis of recovery of platelet count (increase to >100 × 109/L or by 1.5-fold by day 5 of diagnosis) into two groups: delayed and normal recovery. Of the 164 patients screened, 107 were admitted with cardiac diseases while 57 non-cardiac conditions. A total of 34 patients (21%) were tested positive for PF4 antibodies. Patients with underlying cardiac conditions were more likely to be diagnosed with HITT than non-cardiac patients (28% versus 7%, p=0.0012). The male to female ratio was 1:1.1, and the median age was 65 years. Nineteen of 34 patients (56%) had delayed platelet recovery, while the remaining 15 patients (44%) had normal platelet recovery by day 5. The mortality rate was 68% (13 of 19) in the delayed recovery group, compared to only 7% (1 of 15) in the normal recovery group (p=0.0004). Twelve of the 34 patients with liver dysfunction had delayed platelet recovery and died (figure 1). There were 6 venous and 5 arterial thrombotic episodes. A total of 13 patients (38%) were treated with Argatroban, a direct thrombin inhibitor (DTI) indicated for the treatment of HITT, but it did not seem to improve platelet recovery (Table 1). Eight of the 13 treated patients (62%) and 11 of the 21 untreated patients (52%) showed no platelet recovery by day 5. In conclusion, early diagnosis of HITT is critically important for patient management, and yet, diagnosis is often elusive due to a general lack of awareness of this condition. Underlying cardiac diseases appear to predispose patients to HITT, probably due to previous exposure and sensitization to heparin. Despite the availability of new anticoagulants, HITT remains an undertreated and highly fatal condition with overall mortality of 38% in our series. Underlying liver dysfunction appears to be associated with delayed platelet recovery and poor survival. Affect of DTI on platelet recovery needs to be further investigated. Optimal response to therapy requires early diagnosis and intervention. Further studies are necessary to enhance our understanding of this devastating condition to facilitate early diagnosis and proper treatment. Treatment and Survival of HITT Patients Outcome Treated with DTI Not treated Total Dead 6 7 13 Alive 7 14 21 Total 13 21 34 Pattern of Platelet Recovery in Patients with HITT with Delyaed Recovery > 5 days Pattern of Platelet Recovery in Patients with HITT with Delyaed Recovery > 5 days Pattern of Platelet Recovery in Patients with HITT with Delyaed Recovery < 5 days Pattern of Platelet Recovery in Patients with HITT with Delyaed Recovery < 5 days

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