Pediatric Kasabach-Merritt Syndrome Medication

No single therapy has been proven 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 listed medications are among the most frequently used, although other medications in these and other categories may have been used to treat Kasabach-Merritt syndrome. Most of these medications are not approved by the US Food and Drug Administration (FDA) for treatment of Kasabach-Merritt syndrome.

Class Summary

These agents stabilize blood vessels and reduce fibrinolysis.

Prednisone (Deltasone, Meticorten, Orasone, Sterapred)

May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity.

Class Summary

These agents have a direct antiproliferative effect against vascular tumors. Antiangiogenesis agents in development include thalidomide, vascular endothelial growth factor (VEGF), receptor inhibitors (SU 5416), and anti-VEGF antibodies.

Interferon alfa-2a and alfa-2b (Roferon-A, Intron A)

Protein product manufactured by recombinant DNA technology; alpha interferons appear to produce their 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 they may have similar efficacy in these vascular lesions. Not all lesions respond to alfa interferon therapy.

Class Summary

These agents improve blood flow through hemangiomas and decrease microthrombus formation.

Pentoxifylline (Trental)

May alter rheology of RBCs, which reduces blood viscosity.

Class Summary

These agents decrease microthrombus formation in hemangiomas.

Heparin

Augments activity of antithrombin III and prevents conversion of fibrinogen to fibrin; does not actively lyse but inhibits further thrombogenesis; prevents reaccumulation of clot after spontaneous fibrinolysis.

Enoxaparin (Lovenox)

Produced by partial chemical or enzymatic depolymerization of unfractionated heparin (UFH). Binds to antithrombin III, enhancing its therapeutic effect. The heparin-antithrombin III complex binds to and inactivates activated factor X (Xa) and factor II (thrombin).

Does not actively lyse but is able to inhibit further thrombogenesis. Prevents reaccumulation of clot after spontaneous fibrinolysis.

Advantages include intermittent dosing and decreased requirement for monitoring. Heparin antifactor Xa levels may be obtained if needed to establish adequate dosing.

LMWH differs from UFH by having a higher ratio of antifactor Xa to antifactor IIa compared to UFH.

Prevents DVT, which may lead to pulmonary embolism in patients undergoing surgery who are at risk for thromboembolic complications. Used for prevention in hip replacement surgery (during and following hospitalization), knee replacement surgery, or abdominal surgery in those at risk of thromboembolic complications, or in nonsurgical patients at risk of thromboembolic complications secondary to severely restricted mobility during acute illness.

Used to treat DVT or PE in conjunction with warfarin for inpatient treatment of acute DVT with or without PE or for outpatient treatment of acute DVT without PE.

No use in checking aPTT (drug has wide therapeutic window and aPTT does not correlate with anticoagulant effect).

Average duration of treatment is 7-14 d.

Class Summary

These agents decrease microthrombus formation.

Ticlopidine (Ticlid)

Second-line antiplatelet therapy for patients who cannot tolerate aspirin therapy or in whom aspirin therapy fails.

Dipyridamole (Persantine)

Used to complement usual warfarin therapy. Platelet adhesion inhibitor that possibly inhibits RBC uptake of adenosine, itself 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. May enhance effects of aspirin.

Class Summary

These agents inhibit thrombus breakdown, thus interfering with DIC. They are often administered with cryoprecipitate in patients with Kasabach-Merritt syndrome.

Aminocaproic acid (Amicar)

Lysine analog that inhibits fibrinolysis via inhibition of plasminogen activator substances; to a lesser degree, through antiplasmin activity.

Widely distributed. Half-life is 1-2 h. Peak effect occurs within 2 h. Hepatic metabolism is minimal. Can be used PO/IV.

Tranexamic acid (Cyklokapron)

Alternative to aminocaproic acid; inhibits fibrinolysis by displacing plasminogen from fibrin.

Class Summary

These agents have an antiproliferative effect on tumor cells.

Vincristine (Oncovin, Vincasar PFS)

Mechanism of action is uncertain; may involve a decrease in reticuloendothelial cell function or an increase in platelet production; however, neither of these mechanisms fully explains effect in patients with TTP and HUS.

Cyclophosphamide (Cytoxan, Neosar)

Cyclic polypeptide that suppresses some humoral activity. Chemically related to nitrogen mustards. Activated 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 an alkylating agent, the mechanism of action of the active metabolites may involve cross-linking of DNA, which may interfere with growth of normal and neoplastic cells.

Biotransformed by cytochrome P-450 system to hydroxylated intermediates that break down to active phosphoramide mustard and acrolein. Interaction of phosphoramide mustard with DNA considered cytotoxic.

When used in autoimmune diseases, mechanism of action is thought to involve immunosuppression due to destruction of immune cells via DNA cross-linking.

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.

Dactinomycin (Actinomycin-D, Cosmegen)

Intercalates between guanine and cytosine base pairs, inhibiting protein synthesis and DNA and RNA synthesis. Administered in a free-flowing vein or central catheter.