Heparin-Induced Thrombocytopenia in Healthy Individuals with Continuous Heparin Infusion

AbstractThe risk for developing heparin-induced thrombocytopenia in healthy individuals is thought to be low, but monitoring recommendations remain controversial. Therefore, a retrospective cohort study was conducted to identify the incidence of thrombocytopenic events in a healthy research population exposed and re-exposed to continuous intravenous (IV) unfractionated heparin. The Division of Sleep Medicine and the Centre for Clinical Investigations at Brigham and Women's Hospital, Boston, Massachusetts, United States, instituted a standardized platelet monitoring procedure for all research protocols that involved heparin to detect platelet count decreases. Protocol-related frequent blood sampling required use of continuous IV unfractionated heparin infusion (5,000 unit/L in 0.45% saline at 40 mL/h) to maintain line patency over extended periods of IV access. From the years 2009 to 2012, a total of 273 healthy volunteers enrolled in Sleep Medicine research protocols met study criteria as having been exposed and/or re-exposed to continuously infused intravenous heparin for at least 4 hours. The mean continuous heparin exposure time was 88 ± 82 SD hours with a total of 397 heparin exposure and re-exposure events. Platelet count measurements were obtained on 629 occasions, representing a range from 2 to 9 draws per participant. No platelet count decrease of more than 50% was detected. There were no detected adverse bleeding or thrombotic events. In this retrospective study of healthy volunteers involved in a rigorously applied inpatient platelet monitoring protocol, heparin exposure and re-exposure did not lower platelet concentration and, therefore, does not appear to be associated with increased risk of HIT in this population.

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

Blood ◽

10.1182/blood.v108.11.1049.1049 ◽

2006 ◽

Vol 108 (11) ◽

pp. 1049-1049 ◽

Cited By ~ 1

Author(s):

Rachel P. Rosovsky ◽

Omar I. Abdel-Wahad ◽

Elizabeth M. Van Cott ◽

David J. Kuter

Keyword(s):

Platelet Count ◽

Mortality Rate ◽

Massachusetts General Hospital ◽

Thrombotic Event ◽

Radiographic Examination ◽

Platelet Factor ◽

Heparin Induced Thrombocytopenia ◽

Total Incidence ◽

Objective Evidence ◽

Heparin Exposure

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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The incidence of heparin-induced thrombocytopenia in hospitalized medical patients treated with subcutaneous unfractionated heparin: a prospective cohort study

Blood ◽

10.1182/blood-2002-07-2201 ◽

2003 ◽

Vol 101 (8) ◽

pp. 2955-2959 ◽

Cited By ~ 194

Author(s):

Bruno Girolami ◽

Paolo Prandoni ◽

Piero M. Stefani ◽

Cinzia Tanduo ◽

Paola Sabbion ◽

...

Keyword(s):

Platelet Count ◽

Unfractionated Heparin ◽

Odds Ratio ◽

Thromboembolic Complication ◽

High Rate ◽

Clinical Settings ◽

Medical Patients ◽

Thromboembolic Complications ◽

Heparin Induced Thrombocytopenia ◽

Medical Wards

Abstract Although heparin-induced thrombocytopenia (HIT) is a known complication of intravenous unfractionated heparin (UFH), its incidence in medical patients treated with subcutaneous UFH is less well defined. To determine the incidence of HIT in this category of patients, the platelet count was performed at baseline and then every 3 ± 1 days in 598 consecutive patients admitted to 2 medical wards and treated with subcutaneous UFH for prophylactic (n = 360) or therapeutic (n = 238) indications. The diagnosis of HIT was accepted in the case of a platelet drop of 50% or more and either the demonstration of heparin-dependent antibodies or (when this search could not be performed) the combination of the following features: (1) the absence of any other obvious clinical explanation for thrombocytopenia, (2) the occurrence of thrombocytopenia at least 5 days after heparin start, and (3) either the normalization of the platelet count within 10 days after heparin discontinuation or the earlier patient's death due to an unexpected thromboembolic complication. HIT developed in 5 patients (0.8%; 95% CI, 0.1%-1.6%); all of them belonged to the subgroup of patients who received heparin for prophylactic indications. The prevalence of thromboembolic complications in patients with HIT (60%) was remarkably higher than that observed in the remaining 593 patients (3.5%), leading to an odds ratio of 40.8 (95% CI, 5.2-162.8). Although the frequency of HIT in hospitalized medical patients treated with subcutaneous heparin is lower than that observed in other clinical settings, this complication is associated with a similarly high rate of thromboembolic events.

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Differential Diagnosis of Hereditary and Acquired Thrombocytopenia By the Immature Platelet Fraction and Thrombopoietin Levels

Blood ◽

10.1182/blood.v126.23.1049.1049 ◽

2015 ◽

Vol 126 (23) ◽

pp. 1049-1049 ◽

Cited By ~ 1

Author(s):

Fabio Luiz Bandeira Ferreira ◽

Marina Pereira Colella ◽

Samuel de Souza Medina ◽

Maiara Marx Luz Fiusa ◽

Loredana Nilkenes Gomes da Costa ◽

...

Keyword(s):

Bone Marrow ◽

Differential Diagnosis ◽

Platelet Count ◽

Healthy Volunteers ◽

Complete Blood Count ◽

Conflicts Of Interest ◽

Bone Marrow Failure ◽

Healthy Individuals ◽

Technical Limitation ◽

Immature Platelet Fraction

Abstract Introduction: The differential diagnosis of hereditary and acquired thrombocytopenias can be challenging, especially when between immune thrombocytopenia (ITP) and less well characterized hereditary thrombocytopenias (HT) such as MYH9-related disorders. Fundamental differences in the management of these two conditions add clinical relevance to the search for novel parameters that differentiate these conditions. The immature platelet count (IPF) represents the fraction of platelets with higher RNA content, and in analogy to the reticulocyte count for erythropoiesis is a biomarker of thrombopoietic activity. In a recent report (Miyazaki et al, 2015), IPF values that were more than 5-fold higher than those observed in ITP patients were reported in a population of 15 patients with HT. However, whether this increased values represented a real increase in thrombopoietic activity, or reflected a technical limitation of IPF determination in large platelets could not be clarified. Here, we aimed to evaluate the role of IPF determination in the differential diagnosis between HT and several forms of acquired thrombocytopenia in a larger and more diverse population of patients. We also evaluated thrombopoietin (TPO) levels in HT compared to ITP, to further investigate the mechanisms by which extremely large IPF values are observed in HT. Methods: IPF and mean platelet volume (MPV) were prospectively determined using a Sysmex XE5000 hematologic analyzer (as part of the complete blood count) in a cohort of patients with post-chemotherapy thrombocytopenia (n=56), bone marrow failure (myelodysplastic syndromes and aplastic anemia; n=22), ITP (ITP; n=105) and inherited thrombocytopenias (n=27). The latter population consists of a well-defined cohort of individuals with HT thrombocytopenia characterized by clinical, familial, laboratory and molecular data. TPO levels were determined by ELISA (R&D Systems) in 21 HT patients and 22 ITP patients matched for platelet count and age. A group of 178 healthy volunteers were used to determine normal IPF and MPV values. Results: Median platelet counts were similar in post-chemotherapy patients (CTx) (32.0*109/L), bone marrow failure (BMF) (33.5*109/L), ITP (52.0*109/L) and HT (52.0*109/L) (P=0.15). Similar IPF levels were observed in CTx and BMF patients (5.6%; IQR 3.4-8.8% and 6.5%; IQR 3.5-13.7%. Compared to these two groups, higher IPF values were observed in both ITP (12.3%; 7.0-21.0%) and HT patients (29.8%; 17.5-56.4%) (both P values < 0.05). In addition, IPF were significantly higher in HT compared to ITP (Kruskall-Wallis test and Dunn's post test,P=0.001). MPV values were different between HT and CTx/BMF groups, but could not differentiate ITP from HT. TPO levels. The accuracy of IPF to discriminate HT from all other causes of thrombocytopenia estimated by ROC analysis was 0.88 (CI95%0.8-0.96, p<0.0001). Similar TPO levels were observed in platelet count-matched ITP, HT patients and healthy volunteers without thrombocytopenia. Interestingly, TPO presented marked correlations with both platelet count (Rs = - 0.61, P=0.002) and IPF (Rs= 0.59, P=0.003), even with TPO levels in the same range of healthy individuals. In contrast, no significant correlation could be observed between TPO and IPF or platelet count in HT patients. Conclusions: IPF represents an informative biomarker for the differential diagnosis of hereditary and acquired thrombocytopenias, and accurately differentiates ITP from the most common HT. As expected, TPO levels in patients with ITP were not higher than in individuals with normal platelets counts. The inverse correlation between TPO and platelet count in these patients confirm a blunted TPO response to thrombocytopenia in these patients. Similarly, patients with HT did not present increased TPO levels compared to healthy individuals. Accordingly, increased IPF levels in these patients cannot be attributed to higher TPO levels. Disclosures No relevant conflicts of interest to declare.

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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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Lack of In Vitro Cross-Reactivity Predicts Safety of Low-Molecular Weight Heparins in Heparin-Induced Thrombocytopenia

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/107602969700300109 ◽

1997 ◽

Vol 3 (1) ◽

pp. 58-62 ◽

Cited By ~ 3

Author(s):

Sherif S. Farag ◽

Heten Savoia ◽

Cindy J. O'Malley ◽

Katherine M. McGrath

Keyword(s):

Molecular Weight ◽

Platelet Count ◽

Platelet Aggregation ◽

Unfractionated Heparin ◽

Cross Reactivity ◽

Low Molecular Weight ◽

Low Molecular Weight Heparins ◽

Aggregation Assay ◽

Heparin Induced Thrombocytopenia

Alternative anticoagulation in patients with heparin-induced thrombocytopenia (HIT) is often problematic. The relatively high cross-reactivity rate reported for the low-molecular-weight heparins (LMWH) has discouraged their use in this setting. This study has investigated the safety of using the LMWH Fragmin, based on a negative heparin-dependent platelet aggregation test using the latter, in patients with proven HIT. Fifty-three evaluable patients with clinical and laboratory evidence of HIT were evaluated for cross-reactivity with Fragmin using a Fragmin-dependent platelet aggregation test. In 20 of 38 patients who showed no in vitro cross-reactivity. Fragmin was substituted for unfractionated heparin. The outcome of these 20 patients was evaluated and compared to that of the remaining 33 patients, in whom anticoagulates were ceased or warfarin or Orgaran was used. Eighteen of 20 patients treated with Fragmin increased their platelet count by ≥50 x 109/l from a mean nadir of 57.9 ± 4.7 x 109/l within 2.8 ± 0.29 days following substitution of Fragmin for unfractionated heparin. Twenty-eight of the 33 remaining patients who did not receive Fragmin increased their platelet count by ≥50 x 109/l from a mean nadir of 53.0 ± 4.8 x 109/l within 3.0 ± 0.29 days. In seven patients (two treated with Fragmin), response could not be evaluated due to death within 36 h of cessation of heparin or discharge from hospital. The results indicate that in vitro cross-reactivity testing employing a heparin-dependent platelet aggregation assay can be safely used to select patients with HIT for further anticoagulation with LMWH. Key Words: Fragmin—Crossreactivity—Heparin-induced thrombocytopenia.

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Management of the multiple phases of heparin-induced thrombocytopenia

Thrombosis and Haemostasis ◽

10.1160/th16-02-0084 ◽

2016 ◽

Vol 116 (11) ◽

pp. 835-842 ◽

Cited By ~ 13

Author(s):

Adam Cuker

Keyword(s):

Platelet Count ◽

Key Management ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Vena Cava ◽

Hepatic Function ◽

Heparin Induced Thrombocytopenia ◽

Increased Risk ◽

Count Recovery

SummaryThe clinical course of heparin-induced thrombocytopenia (HIT) may be separated into five sequential phases: 1. suspected HIT, 2. acute HIT, 3. subacute HIT A, 4. subacute HIT B, and 5. remote HIT. Each phase confronts the clinician with a unique set of management questions. In this review, the phases of HIT are defined and key management questions associated with each phase are discussed. Among patients with Suspected HIT, I use the 4Ts score to determine which patients have a sufficiently high probability of HIT to justify discontinuation of heparin and initiation of a non-heparin parenteral anticoagulant. An algorithm for selecting an appropriate non-heparin anticoagulant based on the patient’s clinical stability, renal and hepatic function, drug availability, and physician comfort is provided. In patients with Acute HIT, I generally avoid prophylactic platelet transfusion and inferior vena cava filter insertion because of a potential increased risk of thrombosis. I perform 4-limb screening compression ultrasonography. In patients with symptomatic thromboembolism or asymptomatic proximal deep-vein thrombosis, I treat with anticoagulation for three months. In patients without thrombosis, I discontinue anticoagulation upon platelet count recovery. I do not transition patients to an oral anticoagulant until platelet count recovery (i. e. Subacute HIT A). I increasingly choose direct oral anticoagulants over vitamin K antagonists in this setting because of their greater convenience and safety. In Subacute HIT B and Remote HIT, I use heparin for cardiovascular surgery, whereas I use bivalirudin in patients with Acute HIT and Subacute HIT A in whom surgery cannot be delayed.

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ASH evidence-based guidelines: is the IgG-specific anti-PF4/heparin ELISA superior to the polyspecific ELISA in the laboratory diagnosis of HIT?

Hematology ◽

10.1182/asheducation-2009.1.250 ◽

2009 ◽

Vol 2009 (1) ◽

pp. 250-252 ◽

Cited By ~ 22

Author(s):

Adam Cuker ◽

Thomas L. Ortel

Keyword(s):

Differential Diagnosis ◽

Platelet Count ◽

Small Bowel ◽

Unfractionated Heparin ◽

Small Bowel Obstruction ◽

Laboratory Testing ◽

Laboratory Diagnosis ◽

Evidence Based ◽

Heparin Induced Thrombocytopenia ◽

Evidence Based Guidelines

Abstract You are asked to consult on a 76-year-old man admitted to the hospital with pneumonia and thrombocytopenia. Ten days before the current admission, he had undergone surgery to repair a small bowel obstruction. A preoperative platelet count had been normal. Following surgery, he received subcutaneous unfractionated heparin thromboprophylaxis until his discharge on post-operative day 5. In your differential diagnosis for the patient’s thrombocytopenia, you consider heparin-induced thrombocytopenia (HIT) and wish to order laboratory testing. In addition to a polyspecific anti-PF4/heparin ELISA for the diagnosis of HIT, your laboratory has recently begun to offer an IgG-specific ELISA. You wonder which of these assays performs better in the diagnosis of HIT.

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Dosing Patterns and Outcomes in African American, Asian, and Hispanic Patients with Heparin-Induced Thrombocytopenia Treated with Argatroban.

Blood ◽

10.1182/blood.v112.11.3403.3403 ◽

2008 ◽

Vol 112 (11) ◽

pp. 3403-3403

Author(s):

Marcie J Hursting ◽

Ik-Kyung Jang

Keyword(s):

African American ◽

Platelet Count ◽

African Americans ◽

Clinical Outcomes ◽

Major Bleeding ◽

Heparin Induced Thrombocytopenia ◽

Increased Risk ◽

Hispanic Patients ◽

Ischemic Complications ◽

Dosing Patterns

Abstract Nonwhites, as compared with whites, have increased risk for thromboembolic complications in heparin-induced thrombocytopenia (HIT) (Lewis et al, Chest 2006). To better characterize the risk in nonwhite patients, we retrospectively evaluated dosing patterns and clinical outcomes in African American, Asian, and Hispanic patients administered argatroban therapy for clinically diagnosed HIT. Patients were from previously reported, multicenter, prospective studies of argatroban therapy (2 mcg/kg/min, adjusted to achieve aPTTs 1.5–3 times baseline) in HIT (defined as an otherwise unexplained platelet count <100 x109/L, or 50% reduction in platelet count, following heparin therapy). For African American (n=52), Asian (n=13), and Hispanic (n=14) patient groups, baseline characteristics, therapeutic argatroban dose and duration, aPTTs during therapy, and clinical outcomes (death, including death due to thrombosis; amputation, including amputation secondary to ischemic complications of HIT; new thrombosis; and major bleeding within a 37-day period) were summarized and compared. Among groups, no differences were detected in demographic or baseline features, excepting weight (median values: 62, 77 and 85 kg, respectively, for Asians, African Americans, and Hispanics). Median baseline platelet counts were 45–71 x109/L, and approximately 50% of patients in each group had HIT-related thrombosis before argatroban was initiated. Each group received a similar duration of argatroban therapy (4.0–5.5 days), yet Asians needed a lesser dose (1.0 mcg/kg/ min, versus 1.9 mcg/kg/min in other groups) to achieve comparable aPTTs (61–69 s). New thrombosis occurred most often in African Americans (21%, versus 7–8% in other groups) and when baseline HIT-related thrombosis was present (9/13 events, 69%). Amputation occurred most often in Hispanics (21%, versus 0–12% in other groups) and when diabetes was present (6/9 events, 67%). Mortality was 21–31%, and mortality due to thrombosis was 0–7%. Asians had the lowest frequency of any thrombotic-related outcome (composite of death due to thrombosis, amputation secondary to ischemic complications of HIT, or new thrombosis: 8%, versus 27–29% in other groups). Two patients, each African American, experienced major bleeding (gastrointestinal), for an overall major bleeding rate of 2.5% and by-group rates of 0–4%. Although limited by small group sizes, our study is among the first to characterize outcomes in minority patients administered nonheparin therapy for HIT. Our findings suggest that, despite achieving comparable levels of anticoagulation with argatroban, African Americans and Hispanics are higher risk patients than Asians for poor outcomes in HIT and also that in minority patients with adverse outcomes, baseline HIT-related thrombosis or diabetes is often present.

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