Medication Summary
No single therapy has been proved most effective in patients with Kasabach-Merritt syndrome (KMS). Multiple treatments have been used in many infants. Treatments that are effective in some patients have no benefit for others. Many of these medications have serious adverse effects, especially in patients with thrombocytopenia and disseminated intravascular coagulation (DIC), and should be administered only by physicians with expertise in this area.
The medications listed below are among the most frequently used, though other medications in these and other categories may also have been used to treat KMS. Most of these medications are not approved by the US Food and Drug Administration (FDA) for treatment of KMS.
Corticosteroids
Class Summary
Systemic corticosteroids are synthetic chemicals that stabilize blood vessels and reduce fibrinolysis. They have been successfully used to treat proliferative vascular lesions; treatment of KMS is usually not as successful. High-dose oral prednisone (2-4 mg/kg/day) can rapidly increase the platelet count.
Prednisone (Rayos)
Prednisone may decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear leukocyte (PMN) activity. It may increase the sensitivity of arterioles and precapillaries to vasoconstriction and may competitively inhibit other hormonal agents.
Prednisolone (Pediapred, Prelone, Orapred, Millipred)
Prednisolone may decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear leukocyte (PMN) activity. It may increase the sensitivity of arterioles and precapillaries to vasoconstriction and may competitively inhibit other hormonal agents.
Triamcinolone (Amcort)
Triamcinolone is used for inflammation responsive to steroids. It decreases inflammation by suppressing migration of PMNs and reversing capillary permeability.
Methylprednisolone (Solu-Medrol, Depo-Medrol, A-Methapred)
Methylprednisolone is used for inflammation responsive to steroids. It decreases inflammation by suppressing migration of polymorphonuclear leukocyte (PMN) activity and reversing capillary permeability.
Immunomodulators
Class Summary
Antiangiogenic agents are naturally produced proteins that have antiviral, antitumoral, and immunomodulatory actions. Interferon alfa, beta, and gamma may be administered topically, systemically, or intralesionally. Antiangiogenic agents have a direct antiproliferative effect against vascular tumors. Agents in development include thalidomide, vascular endothelial growth factor (VEGF), receptor inhibitors (SU 5416), and anti-VEGF antibodies.
Interferon alfa-2b (Intron A)
Interferon alfa-2b is a protein product manufactured by means of recombinant DNA technology. The mechanism of its antitumor activity is not clearly understood; however, direct antiproliferative effects against malignant cells and modulation of host immune response may play important roles.
Interferon alfa is a protein product manufactured by means of recombinant DNA technology. It appears to produce its antiangiogenic effect by down-regulating the expression of basic fibroblast growth factor (bFGF) in the rapidly proliferating vascular lesion. The proliferative phase of growth is characterized by high bFGF expression, which then falls during involution of the lesion.
Vascular proliferative lesions vary in response to treatment with interferon. Most patients have been treated with interferon alfa-2a; however, some lesions have been treated with good results with interferon alfa-2b. Their similar clinical and in vitro effects on angiogenesis suggest that the 2 agents may have similar efficacy in these vascular lesions. Not all lesions respond to interferon alfa therapy.
Pegylated interferon alfa-2a (Pegasys)
PEG-IFN alfa-2a consists of IFN alfa-2a attached to a 40-kd branched PEG molecule. PEG-IFN has sustained absorption, a slower rate of clearance, and a longer half-life than unmodified IFN, which permits more convenient once-weekly dosing and significantly improves quality of life for patients.
Hemorheologic Agents
Class Summary
Blood viscosity−improving agents improve blood flow through hemangiomas and decrease microthrombus formation.
Pentoxifylline
Pentoxifylline may alter the rheology of red blood cells (RBCs), thereby reducing blood viscosity.
Anticoagulants, Hematologic
Class Summary
Anticoagulants decrease microthrombus formation in hemangiomas.
Heparin
Heparin augments the activity of antithrombin III (ATIII) and prevents conversion of fibrinogen to fibrin. It does not actively lyse but inhibits further thrombogenesis. It prevents reaccumulation of clot after spontaneous fibrinolysis.
Enoxaparin (Lovenox)
Enoxaparin is a low-molecular-weight heparin (LMWH) produced by partial chemical or enzymatic depolymerization of unfractionated heparin (UFH). It binds to ATIII, enhancing its therapeutic effect. The heparin-ATIII complex binds to and inactivates activated factor X (Xa) and factor II (thrombin). LMWH differs from UFH in that it has a higher ratio of antifactor Xa to antifactor IIa.
Enoxaparin does not actively lyse but is able to inhibit further thrombogenesis. It prevents reaccumulation of clot after spontaneous fibrinolysis. Advantages include intermittent dosing and a decreased requirement for monitoring. Heparin antifactor Xa levels may be obtained if necessary to establish adequate dosing.
Enoxaparin prevents deep vein thrombosis (DVT), which may lead to pulmonary embolism (PE) in surgical patients at risk for thromboembolic complications. It is used for prevention in hip replacement surgery, knee replacement surgery, or abdominal surgery in those at risk for thromboembolic complications, as well as in nonsurgical patients at risk for thromboembolic complications secondary to severely restricted mobility. It is used with warfarin to treat acute DVT with or without PE (inpatient) or acute DVT without PE (outpatient).
There is no use in checking the activated partial thromboplastin time (aPTT); the drug has a wide therapeutic window, and the aPTT does not correlate with the anticoagulant effect. The average duration of treatment is 7-14 days.
Antiplatelet Drugs
Class Summary
Antiplatelet agents decrease microthrombus formation.
Ticlopidine
Ticlopidine
Ticlopidine is a second-line antiplatelet therapy for patients who cannot tolerate aspirin therapy or in whom aspirin therapy fails.
Dipyridamole (Persantine)
Dipyridamole is used to complement the usual warfarin therapy. It is a platelet adhesion inhibitor that possibly inhibits RBC uptake of adenosine (itself an inhibitor of platelet reactivity). In addition, dipyridamole may inhibit phosphodiesterase activity, leading to increased cyclic-3', 5'-adenosine monophosphate within platelets and formation of the potent platelet activator thromboxane A2. It may enhance the effects of aspirin.
Antifibrinolytic Agents
Class Summary
Antifibrinolytic agents inhibit thrombus breakdown, thus interfering with DIC. They are often administered with cryoprecipitate in patients with KMS.
Aminocaproic acid (Amicar)
Aminocaproic acid is a lysine analogue that inhibits fibrinolysis through inhibition of plasminogen activator substances and, to a lesser degree, through antiplasmin activity. It is widely distributed, with a half-life of 1-2 hours. Peak effect occurs within 2 hours, and hepatic metabolism is minimal. Aminocaproic acid may be administered either orally or intravenously (IV).
Tranexamic acid (Cyklokapron, Lysteda)
Tranexamic acid is an alternative to aminocaproic acid; it inhibits fibrinolysis by displacing plasminogen from fibrin.
Antineoplastic Agents
Class Summary
Antineoplastic agents inhibit tumor cell growth and proliferation. The standard dosage is 1-1.5 mg/m2 or 0.05-0.065 mg/kg once weekly.
Vincristine (Vincasar PFS)
The mechanism by which vincristine acts is uncertain; it may involve a decrease in reticuloendothelial cell function or an increase in platelet production. However, neither of these mechanisms fully explains this agent's effect in patients with thrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome (HUS).
Cyclophosphamide
Cyclophosphamide is a cyclic polypeptide that suppresses some humoral activity. In high doses, affects B cells by inhibiting clonal expansion and suppression of production of immunoglobulins. With long-term low-dose therapy, affects T cell functions.
Chemically related to nitrogen mustards, cyclophosphamide is biotransformed by cytochrome P-450 in the liver to its active metabolite, 4-hydroxycyclophosphamide, which alkylates the target sites in susceptible cells in an all-or-none type reaction. As alkylating agents, active metabolites may act through cross-linking of DNA, which may interfere with growth of normal and neoplastic cells. In autoimmune diseases, the mechanism of action is thought to involve immunosuppression due to destruction of immune cells via DNA cross-linking.
Dactinomycin (Cosmegen)
Dactinomycin intercalates between guanine and cytosine base pairs, inhibiting protein synthesis and DNA and RNA synthesis. It is administered in a free-flowing vein or central catheter.
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Leg with a Kaposiform hemangioendothelioma, lesion associated with Kasabach-Merritt Syndrome.
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Back of an arm showing the typical bruising associated with Kasabach-Merritt Syndrome.
