Pediatric Antiphospholipid Antibody Syndrome Medication

Updated: Dec 11, 2018
  • Author: Barry L Myones, MD; Chief Editor: Lawrence K Jung, MD  more...
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Medication

Medication Summary

Very few studies have addressed the efficacy of any treatment protocol in antiphospholipid antibody syndrome (APS). Most are small retrospective analyses or anecdotal reports. Many prospective studies have included too few patients and have been hampered by a lack of homogeneity of test groups. The Sapporo criteria were established, in part, to ensure a uniform homogeneous test population in order to promote accurate prospective studies of treatment protocols for patients with antiphospholipid antibody syndrome.

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Antiplatelet agents

Class Summary

Aspirin inhibits prostaglandin synthesis, preventing formation of platelet-aggregating thromboxane A2. It is used in low doses to inhibit platelet aggregation and improve complications of venous stases and thrombosis. However, doses as low as 5 mg/kg appear to additionally inhibit prostacyclin, thus promoting a procoagulant state. No prevalence data on aspirin resistance in children has been reported. The effect of aspirin on platelet function can be assessed by optical platelet aggregometry or Platelet Function Analyzer (PFA-100). Ticlopidine does not inhibit cyclooxygenase and, in this way, differs from aspirin. It inhibits the primary and secondary phase of aggregation induced by adenosine 5'-diphosphate (ADP) and reduces platelet-derived growth factor. Ticlopidine may also impair platelet adhesion, resulting in prolonged bleeding time. Dipyridamole potentiates the inhibitory effects of aspirin on platelet aggregation.

Aspirin (Anacin, Ascriptin, Bayer Aspirin, Bayer Buffered Aspirin)

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.

Ticlopidine (Ticlid)

Used for livedoid vasculitis and thromboembolic disorders. Second-line antiplatelet therapy for patients who cannot tolerate or in whom aspirin therapy has failed.

Dipyridamole (Persantine)

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 PO anticoagulant therapy (with or without aspirin) in children with mechanical prosthetic heart valves.

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Anticoagulants

Class Summary

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 administered with heparin for several days until the international normalized ratio (INR) reaches the target range.

Heparin

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.

Enoxaparin (Lovenox)

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)

Warfarin (Coumadin)

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.

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Immunomodulators

Class Summary

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.

Immune globulin intravenous (Sandoglobulin, Gammagard, Gamimune, Gammar-P, Gamunex)

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%).

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Vasodilators

Class Summary

These agents are used to lower elevated blood pressure, decrease vasospasm, or prevent ischemia. Niacin is also used to decrease hyperlipidemia.

Nitroglycerin ointment (Nitrol, Nitro-Bid)

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.

Niacin (Niacor, Niaspan, Nicotinex, Slo-Niacin)

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.

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Drugs with effects on vascular endothelium, platelets, red blood cells

Class Summary

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.

Pentoxifylline (Trental)

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.

Hydroxychloroquine (Plaquenil)

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.

Cilostazol (Pletal)

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.

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Platelet count enhancers

Class Summary

These agents are used to augment platelet recovery.

Vincristine (Oncovin, Vincasar PFS)

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.

Danazol (Danocrine)

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.

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Other therapy with multiple actions

Class Summary

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. [86, 87, 88]

Bosentan (Tracleer)

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).

Epoprostenol (Flolan)

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.

Sildenafil (Viagra, Revatio)

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.

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Antilipemic Agent

Class Summary

Therapy for dyslipoproteinemia or hyperlipidemia may reduce vascular risk factors for thrombosis. In vitro and animal model evidence suggests decreased endothelial cell and granulocyte activation. [95, 91]

Atorvastatin (Lipitor)

The most efficacious of the statins at high doses. Inhibits 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA reductase), which in turn inhibits cholesterol synthesis and increases cholesterol metabolism. Reports have shown as much as a 60% reduction in LDL-C. The Atorvastatin versus Revascularization Treatment study (AVERT) compared 80 mg atorvastatin daily to standard therapy and angioplasty in patients with CHD. While events at 18 mo were the same between both groups, the length of time until the first CHD event occurred was longer with aggressive LDL-C lowering. The half-life of atorvastatin and its active metabolites is longer than that of all the other statins (ie, approximately 48 h compared to 3-4 h).

May modestly elevate HDL-C levels. Clinically, reduced levels of circulating total cholesterol, LDL-C, and serum TGs are observed.

Before initiating therapy, patients should be placed on a cholesterol-lowering diet for 3-6 mo; the diet should be continued indefinitely.

Pravastatin (Pravachol)

Effective in reducing circulating lipid levels and improving the clinical and anatomic course of atherosclerosis.

Simvastatin (Zocor)

Inhibits cholesterol synthesis and increases cholesterol metabolism.

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Biological response modulator

Class Summary

Targeted anti-B cell therapy has been used in the treatment of refractory idiopathic thrombocytopenic purpura (ITP) postsplenectomy. The use of this modality has been extrapolated to treatment protocols for antiphospholipid syndrome. [96, 97, 98]

Rituximab (Rituxan)

Indicated to reduce signs and symptoms for moderately-to-severely active rheumatoid arthritis in combination with methotrexate. For use in adults who have experienced an inadequate response to one or more TNF antagonist therapies. Antibody genetically engineered. Chimeric murine/human monoclonal antibody directed against the CD20 antigen found on surface of B-lymphocytes.

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