You are in: eMedicine Specialties > Pediatrics: General Medicine > Rheumatology Antiphospholipid Antibody SyndromeArticle Last Updated: Aug 23, 2007AUTHOR AND EDITOR INFORMATIONSection 1 of 11
  Author: Barry L Myones, MD, Associate Professor, Departments of Pediatrics and Immunology, Pediatric Rheumatology Section, Baylor College of Medicine; Director of Research, Pediatric Rheumatology Center, Texas Children's Hospital Barry L Myones is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American College of Rheumatology, American Heart Association, American Society for Microbiology, Clinical Immunology Society, and Texas Medical Association Coauthor(s): Deborah McCurdy, MD, Consulting Staff, Department of Pediatrics, Division of Allergy/Immunology/Rheumatology, Mattel Children's Hospital, University of California at Los Angeles 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 D Sherry, MD, Professor of Pediatrics, Division of Rheumatology, University of Pennsylvania; Director of Clinical Rheumatology, Children's Hospital of Philadelphia; Daniel Rauch, MD, FAAP, Director, Pediatric Hospitalist Program, Associate Professor, Department of Pediatrics, New York University School of Medicine; Steven R Neish, MD, SM, Director of Pediatric Cardiology Fellowship Program, Department of Pediatrics, Baylor College of Medicine Author and Editor Disclosure Synonyms and related keywords: anti-phospholipid antibody syndrome, Hughes syndrome, Hughes' syndrome, antiphospholipid syndrome, anti-phospholipid syndrome, APS, APLS, Sneddon syndrome, Sneddon's syndrome, thrombosis, primary antiphospholipid syndrome, PAPS, secondary antiphospholipid syndrome, antiphospholipid, aPl, deep venous thrombosis, arterial occlusive events, migraine headache, Raynaud phenomenon, transient ischemic attack, TIA, systemic lupus erythematosus, SLE, lupus anticoagulant, LAC, migraine headache, peripheral vasospasm, thrombocytopenia, anticardiolipin antibody, aCL antibody, cerebrovascular accident, myocardial infarction, endocarditis, pulmonary emboli INTRODUCTIONSection 2 of 11
  BackgroundAntiphospholipid (aPL) antibodies have been found in association with clinical symptoms such as deep venous thrombosis, arterial occlusive events (eg, stroke, myocardial infarction), and recurrent fetal loss. They are also associated with vasospastic phenomena such as migraine headache, Raynaud phenomenon, and transient ischemic attack (TIA). The terminology associated with aPL antibodies has been fraught with misnomers. Conley and Hartmann observed a prolongation in the prothrombin time (PT) in a series of patients with systemic lupus erythematosus (SLE), which was later termed the "lupus anticoagulant" (LAC). This term is misleading for the following reasons:
aPL antibodies associated with vaso-occlusive events without any underlying disease process is termed the primary antiphospholipid syndrome (PAPS). The presence of aPL antibodies and a vaso-occlusive event superimposed on an underlying disease, such as SLE or malignancy, is a secondary antiphospholipid syndrome. Preliminary classification criteria for "definite" APS were proposed in a report from the Eighth International Symposium on Antiphospholipid Antibodies and were published in Arthritis and Rheumatism.1 The purpose of the report was to define the essential features of APS in order to facilitate studies of treatment and causation. This definition was intended to encompass the clinical and laboratory features most closely associated with aPL in prospective studies based on the strongest experimental evidence. The hope was to use the "cleanest" patient populations for basic research and clinical treatment studies. These criteria were not meant to supplant the physician's clinical judgment in making the diagnosis in any particular patient. Although features such as migraine headache, peripheral vasospasm, and thrombocytopenia were excluded from the published criteria, they were argued to be valid and useful clinical parameters in arriving at the diagnosis of APS in the clinical setting at the Ninth International Symposium on Antiphospholipid Antibodies. In a consensus conference held at the 11th International Symposium on Antiphospholipid Antibodies, existing evidence on clinical and laboratory features of APS was appraised and amendments to the Sapporo criteria were proposed. The criteria were reiterated to be used for clinical research to define homogenous populations for studies. Therefore, in order to address the needs of clinicians and to expand the data for future research, the discussion included definitions on features of APS that were not included in the updated criteria for use clinically and in research. These were published as the "International Consensus Statement on an Update of the Classification Criteria for Definite Antiphospholipid Syndrome (APS)" in J Thrombosis Haemost.2 Updated Clinical Criteria
In research studies of patient populations that contain more than one type of pregnancy morbidity, investigators are strongly encouraged to stratify subjects according to the 3 groups above. Updated Laboratory Criteria
Investigators are strongly advised to classify patients with APS into one of the following categories:
A patient must meet at least one clinical and one laboratory criterion for a diagnosis of APS. Classification of APS should be avoided if less than 12 weeks or more than 5 years separate a positive aPL test and the clinical manifestation. Patients with APS participating in research studies should be further grouped according to the presence or absence of additional risk factors for thrombosis. Patients should not be excluded from APS trials because of coexistent inherited or acquired factors for thrombosis. Patients with APS participating in research studies who fulfill the revised classification criteria should be classified separately from patients with “features associated with APS” or with “noncriteria features of APS.” These features, which were discussed by the consensus panel but not included in the revised criteria, include the following:
PathophysiologyThe mechanism or mechanisms by which the antiphospholipid antibodies interact with the coagulation cascade to produce clinical events are largely speculative and have not been clearly elucidated. The presence of preexisting or coincident vascular (endothelial) damage along with the identification of an aPL antibody as requisites for the emergence of a thrombotic complication has been coined the "2-hit" hypothesis.
FrequencyUnited StatesaPL antibodies are reportedly present in 1-15% of the general population (higher in elderly persons). These antibodies are believed to be present in as many as 70% of patients with SLE; however, the frequency rate of APS (ie, aPL antibodies plus a clinical event) is far lower. In patients with SLE, a history of thrombosis was reported in 61% of those with positive test results for LAC, in 52% of those who had positive anticardiolipin antibodies, and 24% of those who had no aPL antibodies. InternationalNo major differences have been noted between frequency rates in the Mortality/MorbidityMortality and morbidity are related to clinical manifestations. An increased incidence of the following is seen in young individuals:
RaceOverall, no specific race predilection has been observed.
Sex
Age
CLINICALSection 3 of 11
HistoryVasospastic or vaso-occlusive events can occur in any organ system; thus, a thorough history should be taken, and an organ-specific review of systems should be performed. A broad spectrum of involvement ranging from rapidly progressive to clinically silent and indolent may be present.
PhysicalPhysical findings are specific to the affected organ and can involve any organ system. Catastrophic antiphospholipid syndrome (APS) is a multisystem failure secondary to thrombosis, infarction, or both and has a picture of microangiopathy on histology.
CausesThe causes of APS are unknown (see Pathophysiology). The association of thrombotic events with preexisting or coincident vascular perturbation is emphasized by the high incidence of APS in patients with the following conditions:
DIFFERENTIALSSection 4 of 11
Adrenal Insufficiency Antithrombin III Deficiency Consumption Coagulopathy Endocarditis, Bacterial Hepatitis A Hepatitis B Hepatitis C Mixed Connective Tissue Disease Mononucleosis and Epstein-Barr Virus Infection Myocardial Infarction in Childhood Parvovirus B19 Infection Pulmonary Infarction Rheumatic Fever Rheumatic Heart Disease Syphilis Systemic Lupus Erythematosus Thrombasthenia Thromboembolism Tuberculosis Vasculitis and Thrombophlebitis
|
| Drug Name | Aspirin (Anacin, Ascriptin, Bayer Aspirin, Bayer Buffered Aspirin) |
|---|---|
| Description | Used for antiplatelet effect. Inhibits prostaglandin synthesis, preventing formation of platelet-aggregating thromboxane A2. May be used in low dose to inhibit platelet aggregation and improve complications of venous stases and thrombosis. |
| Adult Dose | 1-2 mg/kg/d PO for antiplatelet effect |
| Pediatric Dose | Limited comparative data regarding effective antiplatelet dose in pediatrics has been reported; 1-2 mg/kg/d PO is a typical dose |
| Contraindications | Documented hypersensitivity; liver damage, hypoprothrombinemia, vitamin K deficiency, bleeding disorders, asthma; because of association of aspirin with Reye syndrome, do not use in children (<16 y) with influenzalike illnesses |
| Interactions | 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 | D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus |
| Precautions | May cause transient decrease in renal function and aggravate chronic kidney disease; avoid use in patients with severe anemia, with history of blood coagulation defects, or taking anticoagulants |
| Drug Name | Ticlopidine (Ticlid) |
|---|---|
| Description | Used for livedoid vasculitis and thromboembolic disorders. Second-line antiplatelet therapy for patients who cannot tolerate or in whom aspirin therapy has failed. |
| Adult Dose | 250 mg PO bid |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity; neutropenia or thrombocytopenia, liver damage, and active bleeding disorders |
| Interactions | Effects may decrease with coadministration of corticosteroids and antacids; toxicity increases when taken concurrently with theophylline, cimetidine, aspirin, or NSAIDs |
| Pregnancy | B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals |
| Precautions | Discontinue if absolute neutrophil count decreases to <1200/mcL or if platelet count falls to <80,000/mcL |
| Drug Name | Dipyridamole (Persantine) |
|---|---|
| Description | Used for thromboembolic disorders to complement usual aspirin or warfarin therapy. Platelet adhesion inhibitor that possibly inhibits RBC uptake of adenosine, which is an inhibitor of platelet reactivity. In addition, may inhibit phosphodiesterase activity, leading to increased cyclic-3',5'-adenosine monophosphate within platelets and formation of the potent platelet-activator thromboxane A2. Used alone or in combination with low-dose aspirin therapy as indicated above. Also used in combination with low-dose oral anticoagulant therapy (with or without aspirin) in children with mechanical prosthetic heart valves. |
| Adult Dose | 75-400 mg/d PO divided tid/qid |
| Pediatric Dose | <12 years: 3-6 mg/kg/d PO divided tid >12 years: Administer as in adults |
| Contraindications | Documented hypersensitivity |
| Interactions | Theophylline may decrease the hypotensive effects; antiplatelet activity of dipyridamole may increase heparin toxicity |
| Pregnancy | B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals |
| Precautions | Caution in hypotension; medication has peripheral vasodilating effects |
Unfractionated intravenous heparin and fractionated LMW subcutaneous heparin are the choices for initial anticoagulation therapy. If warfarin is chosen as maintenance therapy, it is initiated and concurrently administrated with heparin for several days until the international normalized ratio (INR) reaches the target range.
| Drug Name | Heparin |
|---|---|
| Description | Used for thromboembolic disorders. Augments activity of antithrombin III and prevents conversion of fibrinogen to fibrin. Does not actively lyse but is able to inhibit further thrombogenesis. Prevents reaccumulation of clot after spontaneous fibrinolysis. Used as a continuous infusion while initiating PO warfarin therapy. |
| Adult Dose | Initial dose: 40-170 U/kg IV Maintenance infusion: 18 U/kg/h IV Alternatively, 50 U/kg/h IV initially, followed by continuous infusion of 15-25 U/kg/h; increase dose by 5 U/kg/h q4h prn using PTT results (PTT at 2 X baseline) |
| Pediatric Dose | Initial dose: 50 U/kg IV Maintenance infusion: 15-25 U/kg/h IV Increase dose by 2-4 U/kg/h q6-8h prn using PTT results (PTT at 2 X baseline) |
| Contraindications | Documented hypersensitivity; subacute bacterial endocarditis, active bleeding, history of heparin-induced thrombocytopenia |
| Interactions | Digoxin, nicotine, tetracycline, and antihistamines may decrease effects; NSAIDs, aspirin, dextran, dipyridamole, and hydroxychloroquine may increase heparin toxicity |
| 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 | In neonates, preservative-free heparin recommended to avoid possible toxicity (gasping syndrome) by benzyl alcohol, which is used as preservative; caution in severe hypotension and shock; monitor for bleeding in peptic ulcer disease, menstruation, increased capillary permeability, and when giving IM injections |
| Drug Name | Enoxaparin (Lovenox) |
|---|---|
| Description | Used for thromboembolic disorders. Prevents DVT, which may lead to PE in patients undergoing surgery who are at risk for thromboembolic complications. Enhances inhibition of factor Xa (preferentially) and thrombin (factor IIa) by increasing antithrombin III activity. The ratio of antifactor Xa to antifactor IIa activity is approximately 4:1 (1:1 for unfractionated heparin) |
| Adult Dose | Prophylaxis (average dose): 30 mg SC q12h Treatment (suggested dose): 1 mg/kg/dose SC q12h |
| Pediatric Dose | Not established; suggested dose for prophylaxis: <2 months: 0.75 mg/kg/dose SC q12h >2 months: 0.5 mg/kg/dose SC q12h Suggested dose for treatment: <2 months: 1.5 mg/kg/dose SC q12h >2 months: 1 mg/kg/dose SC q12h Adjust dose by monitoring anti–factor Xa and aPTT |
| Contraindications | Documented hypersensitivity; major bleeding, thrombocytopenia |
| Interactions | Platelet inhibitors or PO anticoagulants such as dipyridamole, salicylates, aspirin, NSAIDs, sulfinpyrazone, and ticlopidine may increase risk of bleeding |
| Pregnancy | B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals |
| Precautions | If thromboembolic event occurs despite LMW-heparin prophylaxis, discontinue drug and initiate alternate therapy; elevation of hepatic transaminases may occur but is reversible; heparin-associated thrombocytopenia may occur with fractionated LMW heparins; 1 mg of protamine sulfate reverses effect of approximately 1 mg of enoxaparin if significant bleeding complications develop |
| Drug Name | Warfarin (Coumadin) |
|---|---|
| Description | Used for thromboembolic disorders. 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 an INR in the range of 2.5-3.5. |
| Adult Dose | 5-15 mg/d PO qd for 2-5 d; adjust dose according to desired INR (range 2.5-3.5) |
| Pediatric Dose | Administer weight-based dose of 0.05-0.34 mg/kg/d PO; adjust dose according to desired INR (range 2.5-3.5) |
| Contraindications | Documented hypersensitivity; severe liver or kidney disease; open wounds or GI ulcers |
| 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 of warfarin 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, gemfibrozil, acetaminophen, and sulindac |
| Pregnancy | X - Contraindicated; benefit does not outweigh risk |
| Precautions | Do not switch brands after achieving therapeutic response; caution in active tuberculosis or diabetes mellitus; patients with protein C or protein S deficiency are at risk of developing skin necrosis; abrupt withdrawal of warfarin may result in a thrombotic event |
Immune globulin is a purified preparation of gamma globulin derived from large pools of human plasma. It is composed of 4 subclasses of IgG antibodies, approximating the distribution of human serum. IgA-depleted products are also low in the IgG4 component.
| Drug Name | Immune globulin intravenous (Sandoglobulin, Gammagard, Gamimune, Gammar-P) |
|---|---|
| Description | Used for autoimmune diseases. Neutralizes circulating myelin antibodies through antiidiotypic antibodies; down-regulates proinflammatory cytokines, including INF-gamma; blocks Fc receptors on macrophages; suppresses inducer T and B cells and augments suppressor T cells; blocks complement cascade; promotes remyelination; may increase CSF IgG (10%). |
| Adult Dose | 2 g/kg IV over 2-5 d |
| Pediatric Dose | Not established Suggested dose: 1-2 g/kg IV over 2-5 d |
| Contraindications | Documented hypersensitivity; IgA deficiency; IgE/IgG anti-IgA antibodies |
| Interactions | Globulin preparation may interfere with immune response to live virus vaccine (MMR) and reduce efficacy (do not administer within 3 mo of vaccine) |
| 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 | Check serum IgA before IVIG administration (use IgA-depleted product [eg, Gammagard S/D]); infusions may increase serum viscosity and thromboembolic events; infusions may increase risk of migraine attacks, aseptic meningitis (10%), urticaria, pruritus, or petechiae (2-5 d postinfusion to 30 d) Increases risk of renal tubular necrosis in elderly patients and in diabetes mellitus, volume depletion, and preexisting kidney disease; laboratory result changes associated with infusions include elevated antiviral or antibacterial antibody titers for 1 mo, 6-fold increase in ESR for 2-3 wk, and apparent hyponatremia |
These agents are used to lower elevated blood pressure, decrease vasospasm, or prevent ischemia. Niacin is also used to decrease hyperlipidemia.
| Drug Name | Nitroglycerin ointment (Nitrol, Nitro-Bid) |
|---|---|
| Description | Causes relaxation of vascular smooth muscle by stimulating intracellular cyclic guanosine monophosphate production. The result is a decrease in blood pressure. Onset of action for ointment is 20-60 min. Duration of effect is 2-12 h. |
| Adult Dose | 2% ointment (20 mg/g): Apply 1-2 in topically to chest wall or extremity with occlusive dressing (eg, Tegaderm) q8h Adjust dose for clinical effect |
| Pediatric Dose | 2% ointment (20 mg/g): Apply 0.5-1 in topically to chest wall or extremity with occlusive dressing (eg, Tegaderm) q8h Adjust dose for clinical effect |
| Contraindications | Documented hypersensitivity; severe anemia, shock, postural hypotension, head trauma, closed-angle glaucoma, or cerebral hemorrhage |
| Interactions | Aspirin may increase serum nitrate concentrations; marked symptomatic orthostatic hypotension may occur with coadministration of calcium channel blockers (dose adjustment of either agent may be necessary) |
| 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 | Caution in coronary artery disease and low systolic blood pressure; care must be taken to avoid placing fingers in mouth or near eyes |
| Drug Name | Niacin (Niacor, Niaspan, Nicotinex, Slo-Niacin) |
|---|---|
| Description | Also called nicotinic acid or vitamin B-3. Component of 2 coenzymes necessary for tissue respiration, lipid metabolism, and glycogenolysis; inhibits synthesis of VLDL. Used as a dietary supplement and as adjunctive treatment of hyperlipidemias, peripheral vascular disease, circulatory disorders, and treatment of pellagra. Onset of action within 20 min (extended release within 1 h). Duration of effect 20-60 min (extended release 8-10 h). Half-life 45 min. |
| Adult Dose | 50-100 mg PO tid with an upward titration until desired effect is obtained or until adverse effects are not tolerable (used in hyperlipidemia at a dosage range of 1.5-6 g/d PO divided tid) Once dosage established, sustained-release capsule or tablet can be used |
| Pediatric Dose | Not established Suggested dose: Administer as in adults with gradual upward titration |
| Contraindications | Documented hypersensitivity; severe hypotension; arterial hemorrhage; active liver disease or unexplained significant increases in AST and ALT levels; large doses of niacin, especially when administered in a sustained-release form (associated with severe hepatotoxicity); a definite and recent history of peptic ulcer disease (can reactivate ulcers); GERD |
| Interactions | Cutaneous vasodilation may be a problem if high dose used with peripheral dilators, such as nitroglycerin, or with adrenergic blocking agents Taking aspirin 30-60 min before first dose of the day may help alleviate prostaglandin-mediated adverse effects of niacin (ie, flushing, itching, headache); clonidine may inhibit niacin-induced flushing May decrease effect of PO hypoglycemic agents, may inhibit uricosuric effects of sulfinpyrazone and probenecid, and may increase risk of myopathy with lovastatin |
| 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 | Caution in patients with gallbladder disease or diabetes mellitus and in those predisposed to gout; monitor blood glucose; may elevate uric acid levels; pregnancy category C when used at doses higher than RDA; some products may contain tartrazine |
These drugs appear to have multiple mechanisms in the prevention of thrombosis and vascular spasm. The exact mechanisms are largely unexplained, but the properties of these drugs include changes in RBC rheology, inhibition of platelet adhesiveness/activation, inhibition of TNF-alpha production, and decreases in neutrophil and endothelial cell activation.
| Drug Name | Pentoxifylline (Trental) |
|---|---|
| Description | Used in vascular disease. May alter rheology of RBCs, which, in turn, reduces blood viscosity. Improves peripheral perfusion and vascular spasm in Raynaud phenomenon and vasculopathy/vasculitis. Other effects include inhibition of platelet adhesiveness/activation, inhibition of TNF-alpha production, and decrease in neutrophil and endothelial cell activation. |
| Adult Dose | 400 mg PO tid pc; may reduce frequency to bid if GI or CNS adverse effects occur |
| Pediatric Dose | Not established Suggested doses: <25 kg: Not established; doses of 20 mg/kg/d PO divided tid (and higher) have been used in Kawasaki disease; doses of 30 mg/kg/d have been infused IV over 6-h periods in preterm infants; doses of 40-60 mg/kg/d have been used in peripheral vascular disease 25-40 kg: 400 mg PO bid >40 kg: 400 mg PO tid Decrease dose frequency if GI or CNS adverse effects occur |
| Contraindications | Documented hypersensitivity; cerebral and/or retinal hemorrhage |
| Interactions | Coadministration with cimetidine or theophylline, increases effect/toxic potential; pentoxifylline increases effect of antihypertensives |
| 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 | Caution in renal impairment |
| Drug Name | Hydroxychloroquine (Plaquenil) |
|---|---|
| Description | Inhibits platelets, chemotaxis of eosinophils, and locomotion of neutrophils and impairs complement-dependent antigen-antibody reactions. Hydroxychloroquine sulfate 200 mg is equivalent to 155 mg hydroxychloroquine base and 250 mg chloroquine phosphate. |
| Adult Dose | 310 mg (base) PO qd or bid for several wk depending on response; 155-310 mg/d for prolonged maintenance therapy |
| Pediatric Dose | 3-5 mg base/kg/d PO qd or divided bid; not to exceed 7 mg/kg/d |
| Contraindications | Documented hypersensitivity; psoriasis; retinal and visual field changes attributable to 4-aminoquinolones |
| Interactions | Serum levels increase with cimetidine; magnesium trisilicate may decrease absorption |
| 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 | Caution in hepatic disease, G-6-PD deficiency, psoriasis, and porphyria; not recommended for long-term use in children (but has been used for long courses in the treatment of JRA); perform periodic (6 mo) ophthalmologic examinations especially for color and peripheral vision; test periodically for muscle weakness |
| Drug Name | Cilostazol (Pletal) |
|---|---|
| Description | Affects vascular beds and cardiovascular function. May improve blood flow by altering rheology of RBCs. Produces nonhomogenous dilation of vascular beds, with more dilation in femoral beds than in vertebral, carotid, or superior mesenteric arteries. Cilostazol and its metabolites are inhibitors of phosphodiesterase III and, as a result, cyclic AMP is increased, which leads to inhibition of platelet aggregation and vasodilation. |
| Adult Dose | 100 mg PO bid at least 30 min ac or 2 h pc Decrease to 50 mg bid if coadministering drugs that inhibit clearance (see interactions) |
| Pediatric Dose | <12 years: Not established >12 years: Administer as in adults |
| Contraindications | Documented hypersensitivity; CHF; coadministration with grapefruit juice |
| Interactions | Inhibitors of CYP3A4 (eg, diltiazem, erythromycin, grapefruit juice, itraconazole, ketoconazole, macrolide antibiotics) or CYP2C19 (eg, ketoconazole, omeprazole) may increase levels |
| 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 | Caution in renal impairment; do not prescribe or administer without thoroughly reading complete prescribing information |
These agents are used to augment platelet recovery.
| Drug Name | Vincristine (Oncovin, Vincasar PFS) |
|---|---|
| Description | Mechanism of action for treatment of thrombocytopenia is uncertain. May involve a decrease in reticuloendothelial cell function or an increase in platelet production. However, neither of these mechanisms fully explains the effect in TTP and HUS. |
| Adult Dose | 0.4-1.4 mg/m2 IV; not to exceed 2 mg/dose IV push; repeat weekly prn for effect |
| Pediatric Dose | 1-2 mg/m2 IV; not to exceed 2 mg/dose IV push; repeat weekly prn for effect |
| Contraindications | Documented hypersensitivity; IT administration (may be fatal) |
| 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), and 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 | Caution in severe cardiopulmonary disease, hepatic impairment (adjust dose), or preexisting neuromuscular dysfunction |
| Drug Name | Danazol (Danocrine) |
|---|---|
| Description | Synthetic steroid analog with strong antigonadotropic activity (inhibits LH and FSH) and weak androgenic action. Increases levels of C4 component of complement and reduces attacks associated with angioedema. In hereditary angioedema, danazol increases level of deficient C1 esterase inhibitor. |
| Adult Dose | 200-600 mg/d PO divided bid/tid Angioedema: 200 mg PO bid/tid; after favorable response, decrease the dosage by 50% or less at intervals of 1-3 mo or longer if the frequency of attacks dictates; if an attack occurs, increase the dosage by up to 200 mg/d |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity; seizure disorders; hepatic, renal, or hepatic insufficiency; lactation; conditions influenced by edema; undiagnosed genital bleeding; porphyria |
| Interactions | Decreases insulin requirements and increases effects of anticoagulants; may increase carbamazepine levels |
| Pregnancy | X - Contraindicated; benefit does not outweigh risk |
| Precautions | Caution in seizure disorders and renal, hepatic, or cardiac insufficiency |
Medications with vasodilatory and antiplatelet activity with specific usage in the treatment of pulmonary hypertension and/or healing of refractory skin ulcerations have been administered in patients with APS.
| Drug Name | Bosentan (Tracleer) |
|---|---|
| Description | Endothelin-receptor antagonist indicated for the treatment of pulmonary arterial hypertension in patients with WHO class III or class IV symptoms to improve exercise ability and decrease rate of clinical worsening. Inhibits vessel constriction and elevation of blood pressure by competitively binding to the endothelin-1 (ET-1) receptors ETA and ETB in endothelium and vascular smooth muscle. This leads to a significant increase in the cardiac index (CI) associated with significant reduction in pulmonary artery pressure (PAP), pulmonary vascular resistance (PVR), and mean right atrial pressure (RAP). Due to teratogenic potential, can only be prescribed through the Tracleer Access Program (1-866-228-3546). |
| Adult Dose | <40 kg: 62.5 mg PO bid; not to exceed 125 mg/d >40 kg: 62.5 mg PO bid for 4 wk initially, then increase to 125 mg PO bid |
| Pediatric Dose | Not established; recommended <12 years: 10-20 kg: 31.25 mg PO qd for 4 wk initially, then increase to 31.25 mg PO bid >20-40 kg: 31.25 mg PO bid for 4 wks initially, then increase to 62.5 mg PO bid >40 kg: 62.5 mg PO bid for 4 wks initially, then increase to 125 mg PO bid >12 years: Administer as in adults |
| Contraindications | Documented hypersensitivity; coadministration with cyclosporin A or glyburide |
| Interactions | Toxicity may increase when concomitantly administered with inhibitors of isoenzymes CYP450 2C9 and CYP450 3A4 (eg, ketoconazole, erythromycin, fluoxetine, sertraline, amiodarone, and cyclosporine A); induces isoenzymes CYP450 2C9 and CYP450 3A4, which cause a decrease in plasma concentrations of drugs metabolized by these enzymes, including glyburide and other hypoglycemics, cyclosporin A, warfarin, hormonal contraceptives, simvastatin, and, possibly, other statins; hepatotoxicity increases with concomitant administration of glyburide; coadministration with sildenafil increases bosentan levels by 50% and reduces sildenafil levels by 63% |
| Pregnancy | X - Contraindicated; benefit does not outweigh risk |
| Precautions | Causes at least 3-fold elevation of liver aminotransferase levels (ie, ALT, AST) in about 11% of patients; may elevate bilirubin levels (serum aminotransferase levels must be measured prior to initiation of treatment and then monthly); caution in patients with mildly impaired liver function (avoid in patients with moderate or severe liver impairment); not recommended while breastfeeding; monitor hemoglobin levels after 1 and 3 mo of treatment and every 3 mo thereafter; exclude pregnancy before initiating treatment and prevent thereafter by use of reliable contraception (hormonal contraception may not be effective, see interactions); headache and nasopharyngitis may occur |
| Drug Name | Epoprostenol (Flolan) |
|---|---|
| Description | Prostacyclin, PGI2 analogue that has potent vasodilatory properties. Elicits immediate onset of action. Half-life is approximately 5 min. In addition to vasodilator properties (all vascular beds), also contributes to inhibition of platelet aggregation (activates intracellular adenylate cyclase and results in increased CAMP in platelets) and plays role in inhibition of smooth muscle proliferation. |
| Adult Dose | 2 ng/kg/min by continuous IV infusion; increase by increments of 2 ng/kg/min q15min as tolerated (monitor adverse effects) To decrease dose, reduce dose by 2 ng/kg/min decrements at intervals of at least 15 min |
| Pediatric Dose | Not established; recommend: 1-2 ng/kg/min continuous IV infusion, then increase in increments of 1-2 ng/kg/min q15min as tolerated |
| Contraindications | Documented hypersensitivity; CHF with severe LV dysfunction; chronic use in patients that develop pulmonary edema during initiation |
| Interactions | Coadministration with anticoagulants may increase bleeding risk due to shared effects on platelet aggregation (although typically coadministered with anticoagulants to reduce thromboembolic risk); additional blood pressure reduction may occur with other drugs that lower blood pressure (eg, diuretics, antihypertensive agents, other vasodilators); coadministration with MAOIs may cause additive hypotensive effect; sympathomimetics antagonize hypotensive effect |
| Pregnancy | B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals |
| Precautions | Abrupt withdrawal, interruptions in delivery, or large dose reductions may precipitate rebound pulmonary hypertension; dose-limiting adverse effects include nausea, vomiting, headache, and hypotension; unless contraindicated, coadminister with anticoagulants to reduce risk of thromboembolism |
| Drug Name | Sildenafil (Viagra, Revatio) |
|---|---|
| Description | FDA-approved for pulmonary hypertension. Promotes selective smooth muscle relaxation in lung vasculature possibly by inhibiting phosphodiesterase type 5 (PDE5). This results in subsequent reduction of blood pressure in pulmonary arteries and increase in cardiac output. Elicits vasodilation and inhibits platelet aggregation. Also aids in healing refractory skin ulcerations. |
| Adult Dose | 20 mg PO tid |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity; concurrent or intermittent using of organic nitrates in any form |
| Interactions | CYP3A4 substrate; potentiates vasodilatory effect of NO, resulting in potentially fatal drop in blood pressure; coadministration with ketoconazole, erythromycin, or cimetidine increases plasma sildenafil concentrations; coadministration with rifampin decreases plasma levels; coadministration with bosentan increases bosentan levels by 50% and reduces sildenafil levels by 63% |
| Pregnancy | B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals |
| Precautions | Caution in patients with retinitis pigmentosa; a small number of patients have genetic disorders of retinal phosphodiesterases; adverse effects include headaches (16%), flushing (10%), upset stomach (7%), nasal congestion (4%), and a blue haze at the periphery of vision (3%); adverse effects occur more often in men taking the 100-mg dose; serious adverse effects occur in patients with severe heart disease and those who are taking nitrates, observed rates of MI were 1.7 vs 1.4 per 100 man-years for sildenafil vs placebo groups respectively; sudden vision loss caused by nonarteritic anterior ischemic optic neuropathy (NAION) has been associated with PDE-5 inhibitors following use for ED, analysis is ongoing to determine causality |