Adherence to Guidelines for Monitoring for Heparin-Induced Thrombocytopenia in Patients Treated with Low Molecular Weight Heparin

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1282-1282
Author(s):  
Maarten ten Berg ◽  
Patricia Van den Bemt ◽  
Albert huisman ◽  
Fred Schobben ◽  
Toine Egberts ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Platelet Count ◽  
Clinical Guidelines ◽  
Low Molecular Weight Heparin ◽  
Low Molecular Weight ◽  
Platelet Factor ◽  
Heparin Induced Thrombocytopenia ◽  
Alternative Anticoagulation ◽  
Life Threatening ◽  
Platelet Count Monitoring

Abstract Laboratory monitoring for early detection of adverse drug reactions is recommended for many drugs. For patients treated with low molecular weight heparin (LMWH), the Summary of Product Characteristics (SPC) and clinical guidelines recommend to monitor the platelet count for heparin-induced thrombocytopenia (HIT), a potentially life-threatening adverse event, characterised by a typical drop in platelet count. When the platelet count drops without obvious explanation in these patients, testing for heparin-platelet factor 4 antibodies (HPF4-Ab) and initiating alternative anticoagulation are advised. In the current study adherence to recommended platelet count monitoring in clinical patients without thrombocytopenia-associated diseases treated with LMWH for at least five days at our institution, and adherence to recommended testing for HPF4-Ab and initiation of alternative anticoagulation in patients with potential HIT (defined as a drop of at least 50% in platelet count between days 5 and 14 following the start of LMWH treatment, or stopdate, whichever occurred first, compared to the highest platelet count within days 1–4) were investigated. Data from the Utrecht Patient Oriented Database (UPOD) were used for this retrospective cohort study. Inpatients exposed to the LMWHs dalteparin or nadroparin for at least five days during the period 2004–2005 were included. Patients with thrombocytopenia-related diseases were excluded. Firstly, adherence to recommended platelet count monitoring, based on recommendations from SPCs and clinical guidelines, was investigated. Secondly, the association between patient- and treatment characteristics and obtaining at least 2 platelets counts during treatment was investigated. Thirdly, adherence to recommended testing for HPF4-Ab and initiating treatment with danaparoid was investigated in patients with potential HIT. 6,804 patients with 7,770 episodes of LMWH treatment of at least five days were included. Adherence to the recommendations for platelet count monitoring from the SPC of nadroparin and dalteparin was 36.5% and 26.3% respectively. Adherence to the different platelet count monitoring recommendations from the 2002 clinical guideline on HIT was 23.0% and 41.5%. Obtaining at least 2 platelet counts during treatment was found to be strongly associated with ICU admission, previous UFH exposure, and a treatment duration of at least 10 days. There were 98 patients with potential HIT. Adherence to testing for HPF4-Ab in patients with potential HIT was 6.1%. Adherence to starting alternative anticoagulation in patients with potential HIT treatment was 0%. The results of this study suggest that adherence to recommendations for monitoring for HIT with LMWH is low at our institution. The results of this study justify to say that there is a need to think of appropriate actions for improving the awareness of HIT as an adverse reaction to LMWH, and to secure the safe use of LMWH.

Compliance with Platelet Count Monitoring Recommendations and Management of Possible Heparin-Induced Thrombocytopenia in Hospitalized Patients Receiving Low-Molecular-Weight Heparin

2009 ◽  
Vol 43 (9) ◽  
pp. 1405-1412 ◽  
Author(s):  
Maarten J ten Berg ◽  
Patricia MLA van den Bemt ◽  
Albert Huisman ◽  
Alfred FAM Schobben ◽  
Toine CG Egberts ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Platelet Count ◽  
Low Molecular Weight Heparin ◽  
Clinical Guideline ◽  
Hospitalized Patients ◽  
Surgical Patients ◽  
Low Molecular Weight ◽  
Heparin Induced Thrombocytopenia ◽  
Alternative Anticoagulation ◽  
Platelet Count Monitoring

Background: Summaries of product characteristics (SPCs) and clinical guideline recommendations are available for monitoring the platelet count for heparin-induced thrombocytopenia (HIT) in patients receiving low-molecular-weight heparin (LMWH). Testing for the presence of heparin-platelet factor 4 antibodies (HPF4-Ab) and starting alternative anticoagulation is recommended when HIT is suspected. Objective: To investigate the frequency of compliance with recommendations for platelet count monitoring and management of possible HIT in hospitalized patients receiving prophylaxis and treatment dosing of LMWH for at least 5 consecutive days. Methods: A retrospective cohort study within the Utrecht Patient Oriented Database (UPOD) was conducted. For all inpatients, all episodes of exposure to dalteparin or nadroparin for at least 5 consecutive days in 2004–2005 were selected. In 4 different nonexclusive groups of patients (all pts. receiving dalteparin, all pts. receiving nadroparin, surgical pts. with a prophylactic dose of either dalteparin or nadroparin, and pts. exposed to unfractionated heparin [UFH] within 100 days before receiving either dalteparin or nadroparin), compliance with recommendations for platelet count monitoring from SPCs and a clinical guideline was studied. The frequency of compliance with these recommendations was determined. In addition, it was determined whether patient and treatment characteristics were associated with regular platelet count monitoring. Finally, the frequency of testing for HPF4-Ab and the initiation of danaparoid treatment in patients with a drop of at least 50% in platelet count were investigated. Results: A total of 6804 patients, with 7770 episodes of LMWH treatment, were included in the analysis. The frequency of compliance with platelet count monitoring recommendations was 26.3% for all patients receiving dalteparin, 35.6% for all patients receiving nadroparin, 23.0% for surgical patients receiving prophylactic dosing of either dalteparin or nadroparin, and 41.5% for patients exposed to UFH within 100 days before the start of either dalteparin or nadroparin treatment. Regular platelet count monitoring was strongly positively associated with medical patients (relative risk [RR] 2.33), surgical patients (RR 2.03), critically ill patients (RR 2.60), and those with recent exposure to UFH (RR 2.19). The frequency of testing for HPF4-Ab was 5.4% and the initiation of alternative anticoagulation with danaparoid in patients with a 50% drop in platelet count was 0%. Conclusions: The results suggest that compliance with recommendations for platelet count monitoring and management of possible HIT is low at our institution. Policies and tools to improve compliance with recommended laboratory monitoring should be developed to secure the safe use of LMWH and other medications.

Thrombocytopenia Is More Common and Nadir Occurs Earlier with Unfractionated Heparin Than with Low Molecular Weight Heparin - Results from the Prospective Catch Registry.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2197-2197
Author(s):  
Stephan Moll ◽  
Charles S. Abrams ◽  
Lawrence Rice ◽  
Richard C. Becker ◽  
Peter B. Berger ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Platelet Count ◽  
Unfractionated Heparin ◽  
Low Molecular Weight Heparin ◽  
Heparin Therapy ◽  
P Value ◽  
Low Molecular Weight ◽  
Life Threatening ◽  
The Difference ◽  
Time To Onset

Abstract Background : Thrombocytopenia in the patient on heparin can have various etiologies, including benign reversible causes and serious, potentially life-threatening ones, such as heparin induced thrombocytopenia (HIT). Knowledge about the prevalence of and timecourse of thrombocytopenia in heparin-treated patients may be helpful to develop systems of alerting clinicians to possible HIT and determining how frequently to check blood counts to detect thrombocytopenia that may be heralding HIT. Methods : The CATCH registry is a prospective registry of inpatients enrolled between March 2003 and April 2004 at over 50 US hospitals in 3 strata: [1] receiving > 96 hours of unfractionated heparin (UFH) or low molecular weight heparin (LMWH), [2] developing thrombocytopenia (platelets >50% reduction from baseline or <150,000/mm3) in the cardiac care unit and [3] patients on whom HIT tests were ordered. Here we present the data of the prolonged heparin stratum. Results : 1,121 and 861 patients received UFH and LMWH, respectively, for > 96 hours. A platelet count decrease of > 50 % from baseline was seen more frequently in patients on UFH than in patients on LMWH (10.7% and 7.9 %, respectively; p = 0.03). The parameters that predicted development of thrombocytopenia in the UHF group were length of heparin therapy, body mass index, and admission to a cardiac service; the only parameter predicting thrombocytopenia in the LMWH group was length of LMWH treatment. Of the patients with decreased platelet count by > 50 % from baseline (for UFH n = 120; for LMWH n = 68), this drop occurred in the UFH group at a median of 3.0 days after initiation of heparin and at a median of 4.0 days in the LMWH group. The difference in timing between the 2 groups was not statistically significant (p = 0.205). The platelet nadir was reached after a median /mean of 4.0 / 7.4 days in the UFH group, and 8.0 / 11.4 days in the LMWH group. This was statistically significantly different between the 2 groups (p-value = 0.0025). Conclusions : A platelet count decrease of > 50 % from baseline occurs frequently in inpatients treated with prolonged heparin. It occurs slightly more frequently on UFH than on LMWH. The median time to onset of thrombocytopenia (> 50 % decrease from baseline) occurs early, at 3–4 days. Daily platelet count checks in the first few days of heparin therapy may be helpful to rapidly discover thrombocytopenia that may then prompt HIT testing.

Heparin-Induced Thrombocytopenia: Prevalence in a Large Cohort of Patients and Confirmed Role of PF4/Heparin Complex as the Main Antigen for Antibodies

1997 ◽  
Vol 3 (3) ◽  
pp. 203-209 ◽  
Author(s):  
Fabrizio Fabris ◽  
Immacolata Cordiano ◽  
Federica Salvan ◽  
Leopoldo Saggin ◽  
Giuseppe Cella ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Platelet Count ◽  
Platelet Factor 4 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Low Molecular Weight ◽  
Dependent Manner ◽  
Platelet Factor ◽  
Heparin Induced Thrombocytopenia ◽  
Heparin Treatment ◽  
Daily Dose

We performed a retrospective study on the prevalence of heparin-induced thrombocytopenia (HIT) in 233 patients receiving hog mucosa heparin therapy. Of these, 82 patients received s.c. calcium heparin, 130 patient received unfractionated (UF) i.v. heparin, and 21 patients received low molecular weight heparins (LMWH). An additional four patients, referred to our consultation and diagnosed by us as having clinically active type II HIT (HIT-II) were also studied. The mean platelet count of the 233 patients receiving heparin showed a significant decrease after 2 days of heparin treatment and a following significant increase 6 days later (basal: 257 ± 147 x 109 platelets/L; day 2: 239 ± 122, p < 0.0002; day 6: 286 ± 119, p < 0.004). Of the 212 patients receiving UF heparin, 13 (6%) fulfilled the criteria for HIT-II: seven of these had received i.v. heparin (mean daily dose 26,600 ± 4,082 IU ± SD) and six had received s.c. heparin (mean daily dose 21,428:t 6,900 IU). Their mean basal platelet count was 226 ± 100 SD × 109 platelets/L and the nadir during heparin treatment was 78 ± 39 x 10 9 platelets/L. Thrombotic complications occurred in four (30.7%) of the 13 patients with HIT-II. Since the immunological mechanism has been demonstrated for HIT-II and since platelet factor 4 (PF4) was identified as the co-factor for the binding of heparin-related antibodies, we set up our own enzyme-linked immunosorbent assay (ELISA) for testing antibodies against PF4/heparin complex bound through electrostatic bridges to the solid phase. The highest binding capacity of HIT-related IgG to the multimolecular complex was obtained at 20 μg/ml for PF4 and 3 μg/ml for heparin, corresponding to 250 ng of PF4 and 42 ng of heparin in each microtiter well. Such binding was inhibited in a dose-dependent manner by increasing amounts of heparin, protamine hydrochloride, and a monoclonal antibody anti-human PF4 clone 1OB2. We observed that HIT-related antibodies bound also to PF4/LMWH complexes but the optimal PF4/glycosaminoglycan ratio appeared more critical for LMWH (enoxaparin, fraxiparin, and pamaparin) than for UF heparin. Sera from eight patients with HIT-II were tested by PF4/heparin ELISA; six of these had IgG against the complex PF4/heparin and three also had IgM. The persistence of HIT-related antibodies was investigated in three patients: in one such antibodies were still detectable 3 years after the acute episode, while in the other two, they disappeared after 6 months and 1 year, respectively. Key Words: Heparin-related anti body—Platelet factor 4 (PF4)—Heparin—Low molecular weight heparin—Thrombocytopenia—Thrombosis.

scholarly journals Clinical Appearance and Diagnosis of Heparin Induced Thrombocytopenia

2021 ◽  
pp. 466-471
Author(s):  
Gunduz T ◽  
Cakir M ◽  
Bakirci EM ◽  
DEGIRMENCI H
Keyword(s):  
Molecular Weight ◽  
Unfractionated Heparin ◽  
Low Molecular Weight Heparin ◽  
Low Molecular Weight ◽  
Heparin Induced Thrombocytopenia ◽  
Clinical Appearance ◽  
Treatment Management ◽  
Life Threatening ◽  
Life Threatening Complication

Heparin-İnduced Thrombocytopenia (HIT) is a life-threatening complication that occurs in a small percentage of exposed patients (e.g. unfractionated heparin, Low Molecular Weight Heparin [LMWH]) regardless of dose and treatment management.

Heparin-induced Thrombocytopenia: Yet Another Treatment Paradox?

2001 ◽  
Vol 85 (06) ◽  
pp. 947-949 ◽  
Author(s):  
Theodore Warkentin
Keyword(s):  
Molecular Weight ◽  
Unfractionated Heparin ◽  
Platelet Activation ◽  
Low Molecular Weight Heparin ◽  
Clinical Situation ◽  
Low Molecular Weight ◽  
Platelet Factor ◽  
Heparin Induced Thrombocytopenia ◽  
Prevention And Treatment ◽  
Underlying Theme

SummaryFew topics in medicine rival heparin-induced thrombocytopenia (HIT) for the unexpected twists and turns enough to rival the plot of many a mystery novel. The underlying theme- anticoagulant-induced thrombosis- seems improbable, but is well-established: despite thrombocytopenia, patients rarely bleed spontaneously or even exhibit petechiae (1); rather, thrombosis develops in 30-75% of patients with HIT, depending upon the clinical situation, and in proportions far greater than expected based on the original reason for receiving heparin (2-4).But even beyond this fundamental contradiction, there exists for the unwary and uninformed practitioner several counterintuitive treatment paradoxes. One is the dichotomous nature of low-molecular-weight heparin (LMWH) respecting prevention and treatment of HIT. LMWH is far less likely to cause HIT than standard, unfractionated heparin (4, 5). Yet, for the patient with acute HIT caused by unfractionated heparin, LMWH is contraindicated (6, 7). The reason: LMWH preparations contain some heparin molecules with 12 or greater saccharide units, which are sufficiently long to bind platelet factor 4 (PF4), creating the multimolecular complexes bearing the HIT antigens. Consequently, ongoing platelet activation, thrombocytopenia, and thrombosis occur in many patients so treated (8).

A Benchmark for Platelet Count Monitoring with Low-Molecular-Weight Heparin: Expanding Implementation of National Patient Safety Goals

2009 ◽  
Vol 43 (9) ◽  
pp. 1519-1521
Author(s):  
Sarah A Spinler
Keyword(s):  
Molecular Weight ◽  
Patient Safety ◽  
Platelet Count ◽  
Low Molecular Weight Heparin ◽  
Thrombin Inhibitor ◽  
Low Molecular Weight ◽  
Initial Management ◽  
National Patient ◽  
Monitoring Protocols ◽  
Platelet Count Monitoring

Practitioners in US hospitals are implementing anticoagulation dosing and monitoring protocols to improve the safety of anticoagulation, consistent with National Patient Safety Goal 03.05.01. An audit of the Utrecht Patient Oriented Database of patients treated with low-molecular-weight heparin (LMWH) at the University Medical Center Utrecht revealed low compliance with platelet count monitoring as well as initial management of suspected heparin-induced thrombocytopenia (HIT). Limitations to this work included the inability to exclude other drug-induced causes of thrombocytopenia and their definition of the frequency of platelet count monitoring for compliance in patients given venous thromboembolism prophylaxis. Despite these limitations, the authors’ work represents the first published report on extending the quality of heparin anticoagulation management to platelet count monitoring and evaluation for HIT in a large patient population. Clinicians should include evaluations of compliance with platelet count monitoring with unfractionated heparin and LMWH, as well as appropriateness of the initial management strategies for HIT, and direct thrombin inhibitor protocols in their patient safety practice assessments.

scholarly journals Severe Autoimmune LMWH-Induced Thrombocytopenia Presenting with Aortic Thromboses, Adrenal Hemorrhage and Pulmonary Embolism: Response to High-Dose Intravenous Immunoglobulin

2018 ◽  
Vol 13 (3) ◽  
pp. 29-34
Author(s):  
Joshua Nero ◽  
Patricia Araneta ◽  
Theodore E Warkentin ◽  
Otto Moodley
Keyword(s):  
Emergency Department ◽  
Molecular Weight ◽  
Pulmonary Embolism ◽  
Platelet Count ◽  
Low Molecular Weight Heparin ◽  
Adrenal Hemorrhage ◽  
Low Molecular Weight ◽  
High Dose ◽  
Heparin Induced Thrombocytopenia ◽  
Delayed Onset

The occurrence of heparin-induced thrombocytopenia (HIT) in the setting of low-molecular-weight heparin (LMWH) exposure is uncommon, with incidence reported at around 0.2%. Delayed-onset (autoimmune) HIT in the setting of LMWH use is rarer, with only two other case reports in the literature. An 83-year old man was admitted to hospital for an acute exacerbation of chronic obstructive pulmonary disease, receiving low-molecular-weight heparin (LMWH, tinzaparin) while in hospital for prophylaxis against deep venous thrombosis (DVT). One day after discharge, he presented to the emergency department with acute chest pain and dyspnea. Computed tomography revealed bilateral pulmonary embolism, multiple abdominal aortic thromboses, and unilateral adrenal hemorrhage, and he was given a bolus of intravenous unfractionated heparin (UFH) in the emergency department. His platelet count (prior to UFH bolus) was found to be markedly reduced (39 × 109/L) from normal values two days prior. We suspected heparin-induced thrombocytopenia (HIT) to have caused the thrombocytopenia and thromboses (arterial and venous), and thus anticoagulation therapy was changed from heparin to argatroban. His HIT assay was strongly positive, including features of autoimmune reactivity (serum-induced platelet activation in the absence of heparin). HIT developing after exposure to tinzaparin is relatively rare, and use of a scoring system helped to facilitate an early diagnosis. Additionally, this case demonstrates heparin-independent platelet activation, a marker for autoimmune HIT (aHIT).  The patient's serum tested strongly positive for IgG-specific anti-PF4/heparin EIA and serotonin release assay. The presence of these antibodies would also explain the further decline in his platelet count to 10 x 109/L after he received a bolus dose of heparin at the beginning of his second hospitalization. This case highlights the third reported case of delayed-onset HIT in the setting of LMWH, and the rapid response to high-dose intravenous immunoglobulin.

Efficacy of Fondaparinux in the Treatment of Heparin-Induced Thrombocytopenia with Venous Thromboembolism: Reduction of Thromboembolic Burden, Normalization of Platelet Count and Disappearance of Anti-Platelet Factor 4/Heparin Antibodies.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 575-575 ◽  
Author(s):  
Franco Piovella ◽  
Marisa Barone ◽  
Chiara Beltrametti ◽  
Chiara Piovella ◽  
Andrea M. D’Armini ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Platelet Count ◽  
Venous Thromboembolism ◽  
Platelet Factor 4 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Surgical Patient ◽  
Low Molecular Weight ◽  
Low Molecular Weight Heparins ◽  
Platelet Factor ◽  
Heparin Induced Thrombocytopenia

Abstract Heparin-induced thrombocytopenia (HIT) and heparin-induced thrombocytopenia with thrombosis (HITT) may develop during anticoagulant treatment in patients submitted to various regimens of unfractionated or low-molecular weight heparins. Several molecules have been studied as alternative anticoagulants in patients with HIT or HITT, including danaparoid, argatroban, lepirudin. Lepirudin requires dosage adjustments in patients with renal insufficiency and has potential for antibody formation. Argatroban requires dosage adjustments in patients with hepatic insufficiency. Argatroban increases the International Normalized Ratio (INR) when co-administered with warfarin, leading to dosage difficulties when transitioning to warfarin therapy. Anticoagulation of patients with HIT or HITT may be limited by antibodies cross-reactivity with danaparoid and by new generation of antibodies with lepirudin. Fondaparinux is the first of a new class of synthetic antithrombotics: the selective inhibitors of coagulation factor Xa. It is the most advanced competitor of low molecular weight heparins, which are the reference drugs in prophylaxis and treatment of venous thromboembolism. Fondaparinux does not bind to platelet factor 4 (PF4) and does not react with anti-PF4/heparin antibodies in in vitro testing. We treated 20 patients who develop HIT (3 patients) or HITT (17 patients, of whom 4 had both DVT and PE). Nine patients were previously submitted to extracorporeal circulation with unfractionated heparin (UFH) followed by low-molecular weight heparin (LMWH) for major cardiac surgery. The remaining patients had been previously treated with either UHF or LMWH at therapeutic or prophylactic dosage in internal medicine or surgery wards. In the 17 patients who developed HITT, we applied therapeutic dosages of fondaparinux, i.e. 7.5 mg QD or lower, accordingly with their bleeding risk. To the remaining patients with HIT we gave prophylactic dosages of fondaparinux, i.e. 2.5 mg QD. Patients with HITT were treated for 4 to 25 days before starting warfarin. Fondaparinux was stopped when INR of 2.0 or more was reached. All patients showed a significant reduction of their thromboembolic burden. One episode of major bleeding was recorded in a post-surgical patient. All patients but one showed sustained normalization of the platelet number. In the remaining patient platelet count remained unchanged. Treatment was switched from fondaparinux to lepirudin and after few days her platelets reverted to close-to-normal levels. In seven patients, submitted to therapeutic dosages of fondaparinux, anti-PF4/heparin antibody titers were determined using a PF4/heparin enzyme-linked immunosorbent assay (ELISA): in all cases antibody levels progressively decreased close to disappearance by 30–45 days. This series of cases provides further evidence for the safety and efficacy of fondaparinux in the treatment of both HIT or HITT.

scholarly journals An Ovarian Cancer Patient Presenting Heparin - Induced Thrombocytopenia after use of Low - Molecular - Weight Heparin: A Case Report of Rare Condition

2018 ◽  
pp. 1
Author(s):  
Yasin Durmuş ◽  
Yalin Ay Karyal ◽  
Cigdem Kilic ◽  
Caner Cakir ◽  
Dilek Yuksel ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Low Molecular Weight Heparin ◽  
Ovarian Cancer Patient ◽  
Rare Condition ◽  
Low Molecular Weight ◽  
Heparin Induced Thrombocytopenia ◽  
Normal Limits ◽  
Heparin Treatment ◽  
Threatening Condition ◽  
Life Threatening

<p>Heparin-induced thrombocytopenia is a rare and life-threatening condition of exposure to heparin. A case of heparin-induced thrombocytopenia due to the low molecular weight heparin was presented. Pulmonary emboli and progressively decreased number of thrombocytes developed during the low molecular weight heparin treatment. For that reason, the heparin-induced thrombocytopenia was diagnosed. The heparin was ceased and fondaparinux treatment initiated. Platelet levels returned to normal limits within six days. The delaying in diagnosis of heparin-induced thrombocytopenia causes serious outcomes. The physician must be careful and keep in mind be developed of this clinical condition in patient under heparin treatment.</p>

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