You are in: eMedicine Specialties > Pediatrics: General Medicine > Allergy and Immunology Hypereosinophilic SyndromeArticle Last Updated: Dec 19, 2007AUTHOR AND EDITOR INFORMATIONSection 1 of 10
  Author: Bruce M Rothschild, MD, Professor of Medicine, The Northeastern Ohio Universities College of Medicine; Director, Arthritis Center of Northeast Ohio; Adjunct Professor, Department of Biomedical Engineering, University of Akron Bruce M Rothschild is a member of the following medical societies: American Association for the Advancement of Science, American College of Rheumatology, American Federation for Clinical Research, American Heart Association, American Society for Clinical Pharmacology and Therapeutics, International Skeletal Society, New York Academy of Sciences, and Sigma Xi Editors: James M Oleske, MD, MPH, François-Xavier Bagnoud Professor of Pediatrics, Director, Division of Pulmonary, Allergy, Immunology and Infectious Diseases, Department of Pediatrics, New Jersey Medical School; Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc; David J Valacer, MD, Consulting Staff, Hoffman La Roche Pharmaceuticals; David Pallares, MD, Clinical Assistant Professor, Department of Pediatrics, Division of Allergy and Immunology, University of Louisville; Harumi Jyonouchi, MD, Associate Professor, Department of Pediatrics, Division of Pulmonary Allergy/Immunology and Infectious Diseases, UMDNJ-New Jersey Medical School Author and Editor Disclosure Synonyms and related keywords: disseminated eosinophilic collagen disease, endomyocardial disease, eosinophilia, eosinophilic leukocytosis, myeloproliferative, lymphocytic, idiopathic, hypereosinophilic syndrome, endomyocardial fibrosis, platelet-derived growth factor receptor alpha, PDGFRA, secondary endocarditis, anemia, thrombocytopenia, ascites, hepatic thrombosis, Budd-Chiari syndrome, Raynaud phenomenon, thrombotic phenomenon, mastitis, dementia, endomyocardial fibrosis, myocarditis, arrhythmia, congestive heart failure, valvular incompetence, mitral regurgitation tricuspid regurgitation, aortic valve disease, vesiculobullous rash, papulonodular rash, livido reticularis, angioedema, cellulitis, erythroderma, erythema annulare, subungual petechiae, digital necrosis, multifocal bursitis, pauciarticular arthritis, small-bowel necrosis, sclerosing cholangitis, chronic active hepatitis, enterocolitis, pancreatitis, hepatosplenomegaly, pleuritis, pulmonary hypertension, encephalopathy, pupillotonia, keratoconjunctivitis sicca, episcleritis, retinal vein thrombosis INTRODUCTIONSection 2 of 10
  BackgroundHypereosinophilic syndrome varies from an asymptomatic phenomenon to a life-threatening multisystem disease. It is characterized by an eosinophil count of more than 1500/μL (usually many more) for more than 6 months and multiorgan involvement in the absence of other causes of eosinophilia and in the absence of eosinophil blast cells in the marrow or blood. Three subtypes are recognized: myeloproliferative, lymphocytic, and idiopathic.1 Hypereosinophilic syndrome is very rare in children. PathophysiologyExtrinsic hypereosinophilia appears to be caused by eosinophilopoietin cytokines, including interleukin 5 (IL-5), interleukin 3 (IL-3), and granulocyte/monocyte cell–stimulating factor (GM-CSF); large numbers of circulating eosinophils result. Toxicity is related to fibrosis, especially endomyocardial fibrosis, which is caused by eosinophil granules, including cationic granule proteins (eg, eosinophil-derived neurotoxin, eosinophil peroxidase, major basic protein, eosinophil cationic protein, transforming growth factor alpha and beta), tumor necrosis factor alpha, interleukin 1 alpha (IL-1a), macrophage inflammatory protein, interleukin 6 (IL-6), interleukin 8 (IL-8), IL-5, IL-3, and GM-CSF. Urokinase-induced plasminogen activation and factor XII-dependent reactions predispose the patient to thrombotic reactions. FrequencyWorldwide, hypereosinophilia is rare, especially in children. Mortality/MorbidityDeath generally results from primary heart damage or secondary endocarditis. Survival is prolonged if the sequelae of organ damage, especially cardiac organ damage, can be controlled. Mean survival is 9 months; the 3-year survival rate is reported to be 12%. Poor prognostic indicators include the following:
RaceThe prevalence is low, with a racial distribution of cases as follows: 78% whites, 18% blacks, and 4% Asian Americans. SexHypereosinophilic syndrome has a 55.3% male predominance in the pediatric population.2 The male-to-female ratio is 9:1 in adults. AgePersons aged 5-80 years can have hypereosinophilic syndrome. Persons aged 41-50 years are most commonly affected. The disease is rare in children. One report documents a case of eosinophilia (WBC count, 80,000/μL with 63% eosinophils) in an infant born to a mother with hypereosinophilic syndrome.3 The child's eosinophil count returned to normal in 8 months. CLINICALSection 3 of 10
HistoryHypereosinophilia syndrome is a multisystem disease with symptoms related to eosinophil proteins and thrombotic phenomenon. Constitutional symptoms include fever, night sweats, anorexia, weight loss, fatigue, and nausea. Alcohol intolerance is occasionally noted.
PhysicalPhysical findings are those of a multisystem disease associated with thrombotic phenomenon and include the following:
CausesThe cause is unknown, except in PDGFRA-associated hypereosinophilic syndrome, in which the formation of the fusion FLIP1L1/PDGFRA gene (secondary to a 4q12 microdeletion) is identified. DIFFERENTIALSSection 4 of 10
Agammaglobulinemia Asthma Behcet Syndrome Colitis Hodgkin Disease Hookworm Infection Human Immunodeficiency Virus Infection Loffler Syndrome Lymphadenopathy Myelodysplasia Myelofibrosis Myocardial Infarction in Childhood Myocarditis, Nonviral Myocarditis, Viral Neurocysticercosis Non-Hodgkin Lymphoma Omenn Syndrome Pancreatitis and Pancreatic Pseudocyst Pericardial Effusion, Malignant Pericarditis, Bacterial Pericarditis, Viral Polyarteritis Nodosa Pulmonary Hypertension, Idiopathic Sjogren Syndrome Strongyloidiasis Superior Mesenteric Artery Syndrome Trichinosis Trypanosomiasis Ulcerative Colitis Vasculitis and Thrombophlebitis Veno-occlusive Hepatic Disease Visceral Larva Migrans Wegener Granulomatosis
|
| Drug Name | Prednisone (Deltasone, Meticorten, Orasone, Sterapred) |
|---|---|
| Description | Immunosuppressant for treatment of autoimmune disorders; may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. Stabilizes lysosomal membranes and suppresses lymphocytes and antibody production. |
| Adult Dose | 60 mg/d PO; eventually taper or change to alternate-day regimen |
| Pediatric Dose | 1 mg/kg PO qd; eventually taper or change to alternate-day regimen |
| Contraindications | Documented hypersensitivity; active infection; ocular herpes simplex; chickenpox, measles, or live virus exposure |
| Interactions | Coadministration with estrogens may decrease clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase glucocorticoid metabolism (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics |
| Pregnancy | B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals |
| Precautions | May mask infections; abrupt discontinuation of glucocorticoids when used >2 wk may cause adrenal crisis; may cause hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections |
These drugs are used to inhibit DNA synthesis, but only case reports of their effectiveness are available.
| Drug Name | Hydroxyurea (Hydrea) |
|---|---|
| Description | Interferes with DNA synthesis. Used to reduce total leukocyte count to <10,000/µL. Requires 7-14 d for effectiveness. |
| Adult Dose | 1-3 g/d PO, continued as long as no significant reduction in platelet count occurs |
| Pediatric Dose | 20-30 mg/kg/d PO |
| Contraindications | Documented hypersensitivity; bone marrow depression, leukopenia <2500/µL, or thrombocytopenia <100,000/µL; pancreatitis |
| Interactions | Potentiates pancreatitis with antiretroviral medications; coadministration with fluorouracil can increase neurotoxicity |
| Pregnancy | D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus |
| Precautions | Closely monitor blood counts at least weekly; severe anemia requires resolution before initiating therapy; renal failure requires dose adjustment; erythema occurs if individual has received radiation therapy in past; produces anemia, which often requires blood transfusion, and thrombocytopenia, which occasionally requires platelet transfusion |
| Drug Name | Vincristine (Oncovin) |
|---|---|
| Description | Used to reduce total leukocyte count to <10,000/µL. Effective in 1-3 d and spares bone marrow toxicity but may cause paresthesias. |
| Adult Dose | 1.5-2 mg IV as a single dose at 2-wk intervals |
| Pediatric Dose | <10 kg: 0.05 mg/kg IV >10 kg: 1.5-2 mg/m2 IV Not to exceed 2 mg/dose |
| Contraindications | Documented hypersensitivity; IT administration (may be fatal); bone marrow depression; cytopenia; demyelinating form of Charcot-Marie-Tooth syndrome |
| Interactions | Acute pulmonary reaction may occur when taken concurrently with mitomycin-C; asparaginase, CYP3A4 inhibitors (eg, itraconazole, quinupristin/dalfopristin, sertraline, ritonavir), GM-CSF (eg, sargramostim, filgrastim), or nifedipine increase toxicity; CYP3A4 inducers (eg, carbamazepine, phenytoin, phenobarbital, rifampin) may decrease effects |
| Pregnancy | D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus |
| Precautions | Ensure vascular access intact because extravasation produces severe tissue damage; if severe tissue damage occurs, injection of hyaluronidase and application of heat helps disperse drug and reduce damage; do not inject directly but only through IV access line established as nonleaking; obtain CBC count before each dose; does not cross blood-brain barrier, but do not administer intrathecally; avoid eye contamination; hydrate patient to avoid uric acid nephropathy; if uric acid elevations are severe, consider allopurinol prophylaxis; if bilirubin >3 mg/dL, reduce dose by 50%; may cause paresthesias |
| Drug Name | Cyclophosphamide (Cytoxan) |
|---|---|
| Description | Used to reduce total leukocyte count to <10,000/µL. |
| Adult Dose | 50-125 mg/d PO |
| Pediatric Dose | 10-15 mg/kg IV q7-10d; alternatively, 3-5 mg/kg IV twice weekly or 1-5 mg/kg/d PO |
| Contraindications | Bone marrow depression, cytopenia |
| Interactions | Allopurinol may increase risk of bleeding or infection and enhance myelosuppressive effects; may potentiate doxorubicin-induced cardiotoxicity; may reduce digoxin serum levels and antimicrobial effects of quinolones Chloramphenicol may increase half-life while decreasing metabolite concentrations; may increase effect of anticoagulants; coadministration with high doses of phenobarbital may increase rate of metabolism and leukopenic activity; thiazide diuretics may prolong cyclophosphamide-induced leukopenia and neuromuscular blockade by inhibiting cholinesterase activity |
| Pregnancy | D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus |
| Precautions | Monitor blood counts and perform urinalyses weekly; complicates general anesthesia; toxicity increased in adrenalectomized (possibly also steroid-treated) patients; may compromise wound healing; treatment >90 d increases likelihood of sterility induction |
| Drug Name | Busulfan (Myleran) |
|---|---|
| Description | Used to reduce total leukocyte count to <10,000/µL. |
| Adult Dose | 4-8 mg/d PO |
| Pediatric Dose | 60 mcg/kg/d PO or 1.8 mg/m2/d PO |
| Contraindications | Bone marrow depression, cytopenia |
| Interactions | Thioguanine increases toxicity; acetaminophen, phenytoin, or itraconazole may decrease clearance; high doses of cyclophosphamide and busulfan may cause cardiac tamponade |
| Pregnancy | D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus |
| Precautions | Requires extreme vigilance in monitoring; requires weekly blood counts because WBC count may actually increase in first 10-15 d of treatment, do not alter dose for apparent inadequate response; patient must promptly report fever, sore throat, local infection, bleeding, any anemia-indicative symptom, breathing difficulties, or weakness |
| Drug Name | Methotrexate (Rheumatrex) |
|---|---|
| Description | Used to reduce total leukocyte count to <10,000/µL. |
| Adult Dose | 30 mg PO 2-3 times/wk |
| Pediatric Dose | Not established; perhaps, 30 mg/m2 PO qwk |
| Contraindications | Documented hypersensitivity; alcoholism; hepatic insufficiency; documented immunodeficiency syndromes; preexisting blood dyscrasias (eg, bone marrow hypoplasia, leukopenia, thrombocytopenia, significant anemia); renal insufficiency |
| Interactions | Intestinal absorption reduced by tetracycline, chlorambucil, nonabsorbable broad-spectrum antibiotics; hepatotoxicity increased by etretinate or other retinoids; may decrease theophylline clearance; charcoal lowers levels; coadministration with etretinate may increase hepatotoxicity; response may be decreased by folic acid or its derivatives contained in some vitamins Probenecid, NSAIDs, salicylates, procarbazine, and sulfonamides, including TMP-SMZ, can increase plasma levels; may decrease phenytoin plasma levels; may increase plasma levels of thiopurines; fatal reactions reported when administered concurrently with NSAIDs |
| Pregnancy | D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus |
| Precautions | Monitor blood counts closely; elimination reduced in impaired renal function, ascites, or pleural effusion; liver disease may preclude use; decisions about folic acid replacement must be individualized |
| Drug Name | Chlorambucil (Leukeran) |
|---|---|
| Description | Used to reduce total leukocyte count to <10,000/µL. |
| Adult Dose | 4-10 mg/m2/d PO for 4 consecutive days every other mo |
| Pediatric Dose | 0.1-0.2 mg/kg/d PO; use for minimal time because of risk of secondary malignancies |
| Contraindications | Blood dyscrasias, thrombocytopenia, leukopenia, severe anemia |
| Interactions | None reported |
| Pregnancy | D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus |
| Precautions | Requires weekly blood counts; may cause chromosome damage and sterility; do not administer within 4 wk of radiation therapy; induces secondary malignancies; caution in history of seizure disorders or current bone marrow suppression; total doses >6.5 mg/kg increases risk of irreversible bone marrow damage |
| Drug Name | Etoposide (VP16-213, VePesid) |
|---|---|
| Description | Podophyllotoxin derivative that acts as topoisomerase II inhibitor to cause DNA damage. |
| Adult Dose | 50-100 mg/m2/d PO on days 1, 3, and 5 |
| Pediatric Dose | Administer as in adults |
| Contraindications | Documented hypersensitivity; IT administration may cause death; blood dyscrasias, thrombocytopenia, leukopenia, severe anemia |
| Interactions | May prolong the effects of warfarin and increase methotrexate clearance; cyclosporine and etoposide have additive effects in the cytotoxicity of tumor cells |
| Pregnancy | D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus |
| Precautions | Closely monitor blood counts before each cycle; withhold therapy platelet count <50,000/µL or absolute neutrophil count <500/µL; administer as slow infusions over 30-60 min; anaphylactic reactions can occur; reduce dose in presence of renal insufficiency; do not use acrylic or acrylonitrile/butadiene/styrene (ABS) plastics in the infusions |
| Drug Name | Interferon alfa 2a or 2b (Roferon-A, Intron-A) |
|---|---|
| Description | Empirically applied to many diseases as immunomodulator. Acts at biologically active sites in eosinophil action. |
| Adult Dose | 8 million U/d IM/SC initially, then 2 million U/d or 5-7 million U 3 times per wk |
| Pediatric Dose | Not established; consider 2.5-5 million U/m2/d IM/SC; deaths reported with doses of 30 million U/m2/d |
| Contraindications | Documented hypersensitivity |
| Interactions | Reduces theophylline clearance |
| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus |
| Precautions | Assess CBC counts before therapy; check preservative and biologic source to ensure patient is not allergic; brands not interchangeable; avoid tasks requiring mental alertness after high dose therapy; warn patient that depression and suicidal ideation are adverse effects; can cause flulike symptoms; caution in severe hepatic or renal insufficiencies, seizure disorders, multiple sclerosis, or compromised CNS |
| Drug Name | Cyclosporine (Sandimmune, Neoral) |
|---|---|
| Description | Inhibits T-cell clonal release of eosinophilopoietin cytokines. |
| Adult Dose | 2.5 mg/kg/d PO; not to exceed 10 mg/kg/d; toxicity problematic at high dose |
| Pediatric Dose | Not established; possibly 2.5 mg/kg/d PO; not to exceed 10 mg/kg/d; toxicity problematic at high dose |
| Contraindications | Documented hypersensitivity; uncontrolled hypertension or malignancies; do not administer concomitantly with PUVA or UVB radiation in psoriasis because may increase risk of cancer |
| Interactions | NSAIDs or grapefruit juice increase levels; octreotide may decrease levels by interfering with bioavailability; increases digoxin, methotrexate, and diclofenac levels; coadministration with other nephrotoxic drugs (eg, amphotericin B, ketoconazole, tacrolimus, cimetidine, ranitidine, gentamicin, tobramycin, vancomycin, trimethoprim, sulfamethoxazole, NSAIDs) may potentiate renal dysfunction; CYP3A4 inhibitors (eg, diltiazem, nicardipine, verapamil, fluconazole, itraconazole, ketoconazole, clarithromycin, erythromycin, methylprednisolone, allopurinol, bromocriptine, danazol, metoclopramide, indinavir, nelfinavir, ritonavir, saquinavir) may increase levels; CYP3A4 inducers (eg, rifampin, carbamazepine, phenobarbital, phenytoin, ticlopidine) may decrease levels Live attenuated virus vaccines may not result in protective immunization when administered with cyclosporine or within 3-12 mo following discontinuation of cyclosporine |
| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus |
| Precautions | Monitor BUN, creatinine, and serum bilirubin levels, BP, and LFT results q2wk for first 3 mo and monthly thereafter; reduce dose by 25% if hypertension occurs; may increase risk of infection and lymphoma; reserve IV use for only patients who cannot take drug PO |
| Drug Name | Sorafenib (Nexavar) |
|---|---|
| Description | Multikinase inhibitor that targets serine/threonine and tyrosine receptor kinases in both the tumor cell and the tumor vasculature. Targets kinases involved in tumor cell proliferation and angiogenesis, thereby decreasing tumor cell proliferation. These kinases include RAF kinase, VEGFR-2, VEGFR-3, PDGFR-beta, KIT, and FLT-3. |
| Adult Dose | 400 mg PO bid 1 h ac or 2 h pc |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity |
| Interactions | CYP450 2B6 and 2C8 inhibitor; predominantly eliminated by UGT1A1 pathway (caution when coadministered with other drugs eliminated by UGT1A1 [eg, irinotecan]); coadministration with warfarin may increase INR or bleeding |
| Pregnancy | D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus |
| Precautions | Common adverse reactions include hand or foot skin reaction and rash (modify dose); may increase risk of hemorrhage, cardiac ischemia and/or infarction, alopecia, pruritus, or diarrhea; caution with severe hepatic impairment (ie, Child-Pugh C) |
| Drug Name | Imatinib mesylate (Gleevec) |
|---|---|
| Description | Specifically designed to inhibit tyrosine kinase activity of the bcr-abl kinase in Ph+ leukemic chronic myeloid leukemia (CML) cell lines. Well absorbed after PO administration, with maximum concentrations achieved within 2-4 hours. Elimination is primarily in feces in form of metabolites. FDA-approved for chronic hypereosinophilic syndrome in adults. Also indicated to treat pediatric patients with Ph+ chronic phase CML whose disease has recurred after stem cell transplant, or have demonstrated interferon alpha resistance. |
| Adult Dose | 100-400 mg PO qd with food |
| Pediatric Dose | Up to 260 mg/m2/d PO with food |
| Contraindications | Documented hypersensitivity |
| Interactions | CYP3A4 inhibitors (eg, ketoconazole, itraconazole, erythromycin, clarithromycin) increase imatinib distribution; CYP3A4 substrates (eg, simvastatin) increases imatinib maximum concentration by a factor of 2-3.5-fold; CYP3A4 inducers (eg, phenytoin, dexamethasone, carbamazepine, rifampin, phenobarbital, St. John's Wort) decrease imatinib AUC by approximately one-fifth of typical AUC; likely to increase blood levels of drugs that are substrates of CYP2C9, CYP2D6, and CYP3A4/5 (eg, benzodiazepines, dihydropyridine calcium channel blockers, HMG-CoA reductase inhibitors, warfarin) |
| Pregnancy | D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus |
| Precautions | Dose must be reduced or interrupted if edema or anemia occur, transaminases or bilirubin become elevated, or grade 3-4 neutropenia or thrombocytopenia develop; Stevens Johnson syndrome has been reported; pediatric patient commonly experience musculoskeletal pain; may cause/exacerbate CHF or left ventricular dysfunction, monitor patients with preexisting cardiac disease); complete blood counts and liver function testing are advised weekly for 1 month, biweekly for a month and then every 2-3 months; do not breast feed |
Dapsone is a sulfone antimicrobial. Its anti-inflammatory action, which enables its use for dermatologic conditions, is not fully understood but does not appear to be associated with its antibacterial action.
| Drug Name | Dapsone (Avlosulfon) |
|---|---|
| Description | Sulfone specifically useful for skin involvement. |
| Adult Dose | 50-300 mg/d PO |
| Pediatric Dose | Not established; consider 0.8-4 mg/kg/d PO; not to exceed 100 mg/d |
| Contraindications | Documented hypersensitivity; G-6-PD or methemoglobin reductase deficiencies; hemoglobin M or hemolysis-inducing conditions |
| Interactions | May inhibit anti-inflammatory effects of clofazimine; hematologic reactions may increase with folic acid antagonists (eg, pyrimethamine); monitor for agranulocytosis during the second and third months of therapy; probenecid increases toxicity; coadministration with trimethoprim may increase toxicity of both drugs; because of increased in renal clearance, levels may significantly decrease when administered concurrently with rifampin |
| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus |
| Precautions | Perform weekly CBC counts for first month; then perform WBC counts monthly for 6 mo; then semiannually; discontinue if significant reduction in platelets, leukocytes, or hematopoiesis observed Caution in methemoglobin reductase deficiency, G-6-PD deficiency (patients receiving >200 mg/d), or hemoglobin M because of high risk for hemolysis and Heinz body formation; caution in patients exposed to other agents or conditions (eg, infection, diabetic ketosis) capable of producing hemolysis; peripheral neuropathy can occur (rare); phototoxicity may occur when exposed to UV light |
These agents are used in an effort to reduce frequency of thrombotic events. Warfarin and aspirin have well-established roles in preventing thrombosis. Warfarin acts as an anticoagulant by antagonizing vitamin K in its role as a cofactor in the carboxylation process of coagulation factors II, VII, IX, and X. Aspirin possess antiplatelet ability by permanently inactivating cyclooxygenase (COX) activity of prostaglandin synthase-1 and prostaglandin synthase-2 (ie, COX-1 and COX-2).
Thromboxane A2 (TXA2) induces platelet aggregation and vasoconstriction. Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit TXA2 by reversible inhibition of COX-1. The level of reversible inhibition provided by NSAIDS may be inadequate to effectively block platelet aggregation in vivo. However, the NSAID indobufen, which is not available in the United States, is a potent inhibitor and has biochemical activity comparable to aspirin. Further investigation of effective antiplatelet drugs is essential to overcome obstacles associated with aspirin (eg, toxicity, resistance).
| Drug Name | Warfarin (Coumadin) |
|---|---|
| Description | Used to achieve sufficient anticoagulation to prevent thrombotic events. Interferes with hepatic synthesis of vitamin K–dependent coagulation factors. Used for prophylaxis and treatment of venous thrombosis, pulmonary embolism, and thromboembolic disorders. Adjust dose to maintain INR of 2-3 in absence of associated anticardiolipin syndrome. |
| Adult Dose | 5-15 mg/d PO qd for 2-5 d initially adjusted according to desired INR (ie, 2-3); maintenance dose must be monitored periodically by INR; if recurrent emboli occur, maintain INR of 3-3.5 |
| Pediatric Dose | 0.1-0.2 mg/kg/d PO, adjust doses over initial 5 d according to target INR; then monitor maintenance dose with periodic INR and adjust accordingly |
| Contraindications | Documented hypersensitivity; severe liver or kidney disease; open wounds or GI ulcers; recent or contemplated CNS, eye, or major trauma surgery; GI, genitourinary or respiratory bleeding; dissecting aorta; infectious endocarditis or pericarditis |
| Interactions | Drugs that may decrease anticoagulant effects include griseofulvin, carbamazepine, glutethimide, estrogens, nafcillin, phenytoin, rifampin, barbiturates, cholestyramine, colestipol, vitamin K, spironolactone, PO contraceptives, and sucralfate Medications that may increase anticoagulant effects include PO antibiotics, phenylbutazone, salicylates, sulfonamides, chloral hydrate, clofibrate, diazoxide, anabolic steroids, ketoconazole, ethacrynic acid, miconazole, nalidixic acid, sulfonylureas, allopurinol, chloramphenicol, cimetidine, disulfiram, metronidazole, phenylbutazone, phenytoin, propoxyphene, sulfonamides, gemfibrozil, acetaminophen, and sulindac |
| Pregnancy | X - Contraindicated; benefit does not outweigh risk |
| Precautions | PT must be monitored weekly until stable at desired INR and then monthly or with changes in concomitant medication or diet; do not switch brands after achieving therapeutic response; caution in active tuberculosis or diabetes mellitus; patients with protein C or S deficiency are at risk of developing skin necrosis |
| Drug Name | Aspirin (Anacin, Ascriptin, Bayer) |
|---|---|
| Description | Inhibits prostaglandin synthesis, preventing formation of platelet-aggregating TXA2. May be used in low dose to inhibit platelet aggregation and improve complications of venous stases and thrombosis. |
| Adult Dose | 81 mg/d PO or 1 mg/kg/d PO; some patients need as much as 12 times typical dose |
| Pediatric Dose | Administer as in adults |
| Contraindications | Documented hypersensitivity; liver damage, hypoprothrombinemia, vitamin K deficiency, bleeding disorders, asthma, porphyria; do not use in children (<16 y) with flu because of association with Reye syndrome |
| Interactions | Increases toxicity of lithium, methotrexate, and possibly cyclosporine (especially renal with methotrexate, cyclosporine); may impair diuretic effectiveness Effects may decrease with antacids and urinary alkalinizers; corticosteroids decrease salicylate serum levels; additive hypoprothrombinemic effects and increased bleeding time may occur with coadministration of anticoagulants; may antagonize uricosuric effects of probenecid and increase toxicity of phenytoin and valproic acid; doses >2 g/d may potentiate glucose lowering effect of sulfonylurea drugs |
| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus |
| Precautions | Pregnancy category D near term; assess ADP- and collagen-induced platelet aggregation to titer the aspirin; may cause transient decrease in renal function and aggravate chronic kidney disease; avoid in severe anemia, history of blood coagulation defects, or current anticoagulant use |
Hypereosinophilic Syndrome excerpt
Article Last Updated: Dec 19, 2007
