Heparin-Induced Thrombocytopenia in Cancer

2011 â—½  
Vol 9 (7) â—½  
pp. 781-787 â—½  
Author(s):  
Benjamin J. Miriovsky â—½  
Thomas L. Ortel
Keyword(s):  
Cancer Patients â—½  
Common Finding â—½  
Clinical Settings â—½  
Drug Induced â—½  
Heparin Induced Thrombocytopenia â—½  
Increased Risk â—½  
Risk For Thrombosis â—½  
Important Drug

Heparin-induced thrombocytopenia is a common and clinically important drug-induced complication that can cause life- and limbthreatening thrombosis. Epidemiologically, the disease has been studied in many different clinical settings, but little is known about it in cancer patients, a population at increased risk for thrombosis and thus exposure to heparin products. Additionally, thrombocytopenia is a common finding in cancer patients. The convergence of these variables highlights the importance of an increased understanding of the disease in cancer patients.

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

Hematology â—½  
2009 â—½  
Vol 2009 (1) â—½  
pp. 225-232 â—½  
Author(s):  
Thomas L. Ortel
Keyword(s):  
Platelet Count â—½  
Heparin Therapy â—½  
Severe Thrombocytopenia â—½  
Drug Induced â—½  
Platelet Factor â—½  
Heparin Induced Thrombocytopenia â—½  
Immune Mediated â—½  
Number Of Patients â—½  
Increased Risk â—½  
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.

scholarly journals Drug-induced QT interval prolongation in cancer patients

Oncology Reviews â—½  
2011 â—½  
Vol 4 (4) â—½  
pp. 223
Author(s):  
Torben K. Becker â—½  
Sai-Ching J. Yeung
Keyword(s):  
Cancer Patients â—½  
Qt Interval â—½  
Alkylating Agents â—½  
Torsade De Pointes â—½  
Interval Prolongation â—½  
Drug Induced â—½  
Vascular Disruption â—½  
Qt Interval Prolongation â—½  
Increased Risk â—½  
Multiple Drugs

Cancer patients are at an increased risk for QT interval prolongation and subsequent potentially fatal Torsade de pointes tachycardia due to the multiple drugs used for treatment of malignancies and the associated symptoms and complications. Based on a systematic review of the literature, this article analyzes the risk for prolongation of the QT interval with antineoplastic agents and commonly used concomitant drugs. This includes anthracyclines, fluorouracil, alkylating agents, and new molecularly targeted therapeutics, such as vascular disruption agents. Medications used in the supportive care can also prolong QT intervals, such as methadone, 5-HT3-antagonists and antihistamines, some antibiotics, antifungals, and antivirals. We describe the presumed mechanism of QT interval prolongation, drug-specific considerations, as well as important clinical interactions. Multiple risk factors and drug–drug interactions increase this risk for dangerous arrhythmias. We propose a systematic approach to evaluate cancer patients for the risk of QT interval prolongation and how to prevent adverse effects.

scholarly journals A practical approach to evaluating postoperative thrombocytopenia

Blood Advances â—½  
2020 â—½  
Vol 4 (4) â—½  
pp. 776-783 â—½  
Author(s):  
Leslie Skeith â—½  
Lisa Baumann Kreuziger â—½  
Mark A. Crowther â—½  
Theodore E. Warkentin
Keyword(s):  
Platelet Count â—½  
Late Onset â—½  
Practical Approach â—½  
Drug Induced â—½  
Heparin Induced Thrombocytopenia â—½  
Replacement Surgery â—½  
Device Implantation â—½  
Increased Risk â—½  
Posttransfusion Purpura â—½  
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.

Dietary Hypercholesterolemia Enhances Heparin-Induced Thrombocytopenia/Thrombosis: A Prothrombotic Risk Factor in a Transgenic Mouse Model.

Blood â—½  
2005 â—½  
Vol 106 (11) â—½  
pp. 56-56 â—½  
Author(s):  
Michael P. Reilly â—½  
Scott K. Dessain â—½  
Scott M. Taylor â—½  
M. Anna Kowalska â—½  
Mortimer Poncz â—½  
...  
Keyword(s):  
Mouse Model â—½  
Atherogenic Diet â—½  
Standard Diet â—½  
Generation Model â—½  
Drug Induced â—½  
Platelet Factor â—½  
Thrombotic Risk â—½  
Heparin Induced Thrombocytopenia â—½  
Increased Risk

Abstract Heparin-induced thrombocytopenia/thrombosis (HIT/T), the most frequent drug-induced immune thrombocytopenia, is a common cause of life- and limb-threatening thrombosis. Although heparin/platelet factor 4 (PF4) antibodies are detected in many patients treated with heparin, there is little understanding of why only a subset of patients develops thrombosis. We recently produced and characterized the first mouse model that recapitulates the salient features of the disease. A second generation model, designated IIA/hPF4-mPF4KO, expresses human FcγRIIA and PF4 but lacks endogenous mouse PF4. These models allow systematic investigations of factors that contribute to pathogenic consequences of HIT/T antibodies. In the current study, we hypothesize that hypercholesterolemia, a known stimulus for atherosclerosis, endothelial dysfunction, and platelet hyperreactivity, would augment thrombosis in our mouse model of HIT/T. Age and sex-matched IIA/hPF4-mPF4KO mice were fed an atherogenic diet (Paigen diet) (AD; 15% cocoa butter, 1% cholesterol, 0.5% cholate) (n=10) or maintained on standard diet (SD; 4.5% fat, no cholate) (n=10). Mice fed the AD for only 4 weeks had significantly increased cholesterol levels (173 ± 29 mg/dl vs. 50 ± 18 mg/dl for SD-fed; p < 0.0001). Mice were then injected with 30 U heparin and KKO, a mouse monoclonal heparin/PF4 antibody. The mean nadir platelet count in AD-fed mice was 34.6% ± 9.1 lower than that in the SD-fed mice (p< 0.0001). Thrombin-anti-thrombin III (TAT) levels, which reflect thrombin generation in vivo, in the AD-fed mice increased from 32 ± 5 μg/at baseline to 79 ± 16 μg/l (p < 0.0001) coincident with the platelet nadir. In contrast, SD-fed mice, with a less profound fall in platelets, showed no increase in TAT. Histological examination showed multiple platelet-fibrin thrombi in lungs and livers of AD-fed mice, whereas the SD-fed mice showed no histological evidence of thrombosis. Thus, in our mouse model, short-term diet-induced hyperlipidemia significantly increases the severity of heparin/PF4 antibody-mediated thrombocytopenia and thrombosis. Our studies provide evidence that a specific host factor can enhance the pathologic effects of heparin/PF4 antibodies in vivo and contribute to thrombotic risk in patients with HIT/T. An increased understanding of the contribution of prothrombotic factors not only will facilitate identification of patients with heparin/PF4 antibodies who are at increased risk of thrombosis, but also provide novel approaches to treatment of HIT/T.

scholarly journals Refractory Heparin-Induced Thrombocytopenia With Cerebral Venous Sinus Thrombosis Treated With IVIg, Steroids, and a Combination of Anticoagulants: A Case Report

2019 â—½  
Vol 7 â—½  
pp. 232470961983232 â—½  
Author(s):  
Mia Gonzales â—½  
Amrish Pipalia â—½  
Andrew Weil
Keyword(s):  
Sinus Thrombosis â—½  
Cerebral Venous Sinus Thrombosis â—½  
Venous Sinus â—½  
Small Subset â—½  
Severe Thrombocytopenia â—½  
Platelet Factor â—½  
Heparin Induced Thrombocytopenia â—½  
Venous Sinus Thrombosis â—½  
Increased Risk â—½  
Risk For Thrombosis

Heparin-induced thrombocytopenia (HIT) type II is caused by antibody production that bind complexes between heparin and platelet factor 4 leading to platelet consumption and thrombosis. In a small subset of cases referred to as autoimmune HIT, the antibodies activate platelets even in the absence of heparin. Refractory HIT is a type of autoimmune HIT in which thrombocytopenia persists for weeks after heparin discontinuation and carries increased risk for thrombosis and more severe thrombocytopenia. We present a case of refractory HIT with cerebral venous sinus thrombosis (CVST) that was successfully treated with a change in anticoagulant alongside steroids and a second trial of intravenous immunoglobulin (IVIg).

598: Increased Risk of Newly Diagnosed Comorbidities in Prostate Cancer Patients Treated with Androgen Deprivation Therapy

2007 â—½  
Vol 177 (4S) â—½  
pp. 200-200 â—½  
Author(s):  
Andrea Gallina â—½  
Pierre I. Karakiewicz â—½  
Jochen Walz â—½  
Claudio Jeldres â—½  
Quoc-Dien Trinh â—½  
...  
Keyword(s):  
Prostate Cancer â—½  
Cancer Patients â—½  
Androgen Deprivation Therapy â—½  
Androgen Deprivation â—½  
Newly Diagnosed â—½  
Increased Risk

VTE risk assessment in cancer

Onkologische Welt â—½  
2016 â—½  
Vol 07 (01) â—½  
pp. 20-25
Author(s):  
I. Pabinger â—½  
C. Ay
Keyword(s):  
Risk Assessment â—½  
Cancer Patients â—½  
Medical Oncology â—½  
Clinical Importance â—½  
Cancer Surgery â—½  
Ambulatory Setting â—½  
Oncology Patients â—½  
Related Factors â—½  
Risk Assessment Models â—½  
Increased Risk

SummaryVenous thromboembolism (VTE) in patients with cancer is associated with an increased morbidity and mortality, and its prevention is of major clinical importance. However, the VTE rates in the cancer population vary between 0.5% - 20%, depending on cancer-, treatment- and patient-related factors. The most important contributors to VTE risk are the tumor entity, stage and certain anticancer treatments. Cancer surgery represents a strong risk factor for VTE, and medical oncology patients are at increased risk of developing VTE, especially when receiving chemotherapy or immunomodulatory drugs. Also biomarkers have been investigated for their usefulness to predict risk of VTE (e.g. elevated leukocyte and platelet counts, soluble P-selectin, D-dimer, etc.). In order to identify cancer patients at high risk of VTE and to improve risk stratification, risk assessment models have been developed, which contain both clinical parameters and biomarkers. While primary thromboprophylaxis with lowmolecular- weight-heparin (LMWH) is recommended postoperatively for a period of up to 4 weeks after major cancer surgery, the evidence is less clear for medical oncology patients. Thromboprophylaxis in hospitalized medical oncology patients is advocated, and is based on results of randomized controlled trials which evaluated the efficacy and safety of LMWH for prevention of VTE in hospitalized medically ill patients. In recent trials the benefit of primary thromboprophylaxis in cancer patients receiving chemotherapy in the ambulatory setting has been investigated. However, at the present stage primary thromboprophylaxis for prevention of VTE in these patients is still a matter of debate and cannot be recommended for all cancer outpatients.

A Hexagonal (II) Phase Phospholipid Neutralization Assay for Lupus Anticoagulant Identification

1993 â—½  
Vol 70 (05) â—½  
pp. 787-793 â—½  
Author(s):  
Douglas A Triplett â—½  
Linda K Barna â—½  
Gail A Unger
Keyword(s):  
Hemophilia A â—½  
Clinical Laboratory â—½  
Neutralization Assay â—½  
Confirmatory Test â—½  
Specific Factor â—½  
Clinical Settings â—½  
Drug Induced â—½  
Variable Screening â—½  
Routine Clinical Laboratory

SummaryLupus anticoagulants (LAs) are immunoglobulins (IgG, IgM, or both) which interfere with in vitro phospholipid (PL) dependent tests of coagulation (e.g. APTT, dilute PT, dilute Russell Viper Venom Time). These antibodies may be identified in a wide variety of clinical settings. With the exception of heparinized patient samples, the presence of LAs is often the most common cause of an unexplained APTT in a routine clinical laboratory. The diagnosis of LAs is difficult due to variable screening reagent sensitivity and intrinsic heterogeneity of LAs. Recently, Rauch and colleagues have shown human monoclonal hybridoma LAs were inhibited by hexagonal (II) phase PLs. In contrast, lamellar phase PLs had no effect. We have evaluated a new assay system, Staclot LA®, which utilizes a hexagonal (II) phase PL (egg phosphatidylethanolamine [EPE]) as a confirmatory test for LAs. Plasma samples from the following patient populations were studied: LA positive, heparinized, oral anticoagulated, hemophilia A and B, and specific factor inhibitors (factors V, VIII, IX). Unlike previous studies, the LA positive patients were a mixed population including: autoimmune diseases, drug-induced, and post-infection. Our findings confirm the specificity of hexagonal (II) phase PL neutralization of LAs.

EFFECTS OF SMOKING ON THE DISEASE PROGNOSIS IN CANCER PATIENTS

2019 â—½  
Vol 65 (3) â—½  
pp. 321-329
Author(s):  
David Zaridze â—½  
Anush Mukeriya
Keyword(s):  
Smoking Cessation â—½  
Cancer Patients â—½  
Malignant Tumors â—½  
Scientific Data â—½  
Second Primary â—½  
Primary Tumors â—½  
Smoking Intensity â—½  
Risk Of Death â—½  
Disease Prognosis â—½  
Increased Risk

Smoking not only increases the risk of the development of malignant tumors (MT), but affects the disease prognosis, mortality and survivability of cancer patients. The link between the smoking of cancer patients and increased risk of death by all diseases and oncological causes has been established. Mortality increases with the growth of the smoking intensity, i.e. the number of cigarettes, smoked per day. Smoking is associated with the worst general and oncological survivability. The statistically trend-line between the smoking intensity and survivability was observed: each additional unit of cigarette consumption (pack/year) leads to the Overall Survival Reduction by 1% (p = 0.002). The link between smoking and the risk of developing second primary tumors has been confirmed. Smoking increases the likelihood of side effects of the antitumor therapy both drug therapy and radiation therapy and reduces the treatment efficacy. The smoking cessation leads to a significant improvement in the prognosis of a cancer patient. Scientific data on the negative effect of smoking on the prognosis of cancer patients have a major clinical importance. The treatment program for cancer patients should include science-based methods for the smoking cessation. The latter is fundamentally important, taking into account that the smoking frequency among cancer patients is much higher than in the population.

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