AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Background

Hemangiomas, the most common tumors of infancy, typically undergo rapid postnatal growth for several months, followed by a prolonged phase of involution. The combination of hemangioma, thrombocytopenia, and coagulopathy is termed Kasabach-Merritt syndrome (KMS). The hemangioma may be an obvious superficial lesion or a lesion within a visceral organ or even within the brain. Thrombocytopenia is often severe (ie, <50,000 platelets/mm³). Thrombocytopenia and consumptive coagulopathy are not complications of all hemangiomas, and size alone does not determine which hemangiomas are associated with thrombocytopenia and coagulopathies. KMS is an infrequent but potentially fatal complication of rapidly growing hemangiomas in infants.

Pathophysiology

The thrombocytopenia associated with hemangiomas is caused by a localized consumptive coagulopathy. The vascular lesion causes platelet trapping and activation, with consumption of coagulation factors. The activation of platelets also promotes further growth of vascular tissue.

The cause of the lesions associated with KMS is unknown, and whether the underlying lesion in KMS is a single anatomic entity or a heterogenous group of entities is unclear. Several types of vascular tumors have been associated with KMS (eg, capillary and cavernous hemangiomas, infantile hemangioendothelioma, Kaposiform hemangioendothelioma [KHE], lymphangioma, tufted angioma [TA]). KMS is associated more often with KHE and TA vascular tumors than with common hemangiomas.

Frequency

United States

Hemangiomas are common vascular tumors that occur in as many as 2.5% of neonates. Most are benign, and 70-80% regress by age 7 years. Some hemangiomas are life threatening; 1 hemangioma in 300 is associated with coagulopathy.

Mortality/Morbidity

Mortality and morbidity rates are influenced by the anatomic location, depth, and extent of the hemangioma. Other causes of morbidity and mortality include infections and organ toxicity, usually as a result of therapy.

• Bleeding, which is secondary to the consumptive coagulopathy, is the primary cause of death. Untreated KMS has a 10-37% mortality rate.
• Hemolytic anemia resulting from physical damage to the red blood cells (RBCs) may be mild, moderate, or severe. Direct antibody test (DAT) or Coombs test results are negative in patients with anemia, and anemia is secondary to microangiopathic destruction of the RBCs.
• Heart failure often occurs in affected infants as a result of the large volume of blood flowing through the giant hemangioma.

Race

KMS has no racial predilection.

Sex

Incidence is slightly increased in females.

Age

• Although infants younger than 1 year are most commonly affected, older children and adults have developed KMS.
• Include KMS in the differential diagnosis of chronic thrombocytopenia at any age.

CLINICAL

Section 3 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

History

• Visible cutaneous giant hemangioma or multiple smaller hemangiomas are often the presenting features in patients with KMS. Most hemangiomas are located on the extremities. Some infants and older children with visceral hemangiomas present with an enlarged abdomen. Those with hepatic hemangiomas also may present with hepatomegaly or jaundice. These hemangiomas may continue to enlarge during the first 18 months of life.
• The thrombocytopenia and consumptive coagulopathy associated with KMS may not be prominent initially. However, as the hemangioma enlarges and the infant ages, symptoms may worsen. Affected infants may present soon after birth or may not come to medical attention for several months. Affected individuals rarely present as late as the second or third decade of life.
• Petechiae, bruising, and frank bleeding may be the initial symptoms prompting medical treatment.
• The large volume of blood circulating through the hemangioma may cause high-output congestive heart failure in infants. Cardiovascular compromise or collapse, petechiae, and bleeding may resemble acute overwhelming sepsis. When no cutaneous hemangioma is present, the physician must search for hemangiomas located in a visceral organ (eg, spleen, liver, brain).
• Lesions may be painful.

Physical

• A cutaneous hemangioma is usually obvious, often appearing as a large irregular bruise. These hemangiomas may occur anywhere on the body and may grow throughout the first 12-18 months of life. Hemangiomas are often circumscribed by widespread, overlying, shiny and dusky, purple skin.
• Physical signs of high-output cardiac failure include tachycardia, feeding difficulty, and shock.
• Affected infants may exhibit petechiae, bruising, and bleeding.
• Pallor may be evident in patients with significant anemia.

Causes

The underlying cause of large cutaneous or visceral hemangiomas is unknown.

DIFFERENTIALS

Section 4 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Other Problems to be Considered

Arteriovenous malformation
Hereditary hemorrhagic telangiectasia
Extensive hemangiomas
Diffuse neonatal hemangiomatosis (DNH)
Angiosarcoma
Hemangioblastoma
Hepatic hemangiomas
Port-wine stain
Congenital hemangiopericytoma
Classic capillary hemangioma of infancy
Kaposiform hemangioendothelioma of infancy and childhood
Cystic teratoma
Tufted angioma or angioblastoma
Infantile fibrosarcoma
Infantile myofibromatosis
Lumbar lipomyelomeningocele
Encephalocele
Epithelioid hemangioendothelioma
Thrombocytopenia

WORKUP

Section 5 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Lab Studies

• Complete blood count (CBC) with differential, reticulocyte count, platelet count, and peripheral smear are needed to evaluate for microangiopathic hemolytic anemia and thrombocytopenia.
• • Platelets may be larger than normal when they are released early from the bone marrow.
  • Burr cells and schistocytes may be present in patients with microangiopathic hemolytic anemia.
• Prothrombin time (PT) and activated partial thromboplastin time (aPTT) are prolonged in patients with significant disseminated intravascular coagulation (DIC).
• Fibrinogen levels are low in patients with significant DIC.
• Fibrin degradation products (FDPs) and D-dimer levels are elevated in patients with DIC.
• • A D-dimer test is usually more sensitive than the test for FDPs.
  • Low-grade chronic DIC may be present.

Imaging Studies

• Perform appropriate radiographs, CT scans, and MRIs of areas involved with known hemangiomas. These studies are advisable even when all hemangiomas are cutaneous. Scans are important to determine the extent of the visible hemangiomas and to evaluate the child for possible visceral hemangiomas.
• If KMS is suspected in patients who have no visible hemangiomas, obtain CT scans or MRIs of the head, chest, abdomen, and pelvis to search for visceral hemangiomas.
• Doppler flow studies may help differentiate a solid mass from a hemangioma.

Other Tests

• Perform other tests as needed for clinical evaluation. For example, blood cultures may be appropriate to exclude the possibility of sepsis, and chromosome tests may be needed to exclude certain genetic syndromes.

Procedures

• Radionuclide imaging
• • Scans that use chromium isotope 51, indium In 111 oxine–labeled platelets, or iodine I 131–labeled fibrinogen probably are more sensitive than CT scans or MRIs for delineating the size and number of hemangiomas.
  • Radionuclide scans are infrequently used, since the diagnosis is usually made clinically. In certain centers, these scans may not be readily available.
  • Strongly consider scintigraphic studies when the etiology of the thrombocytopenia remains uncertain.
• No procedures are needed initially. If a complete excision cannot be performed, avoid performing a biopsy because it may lead to uncontrolled bleeding at the site.

Histologic Findings

Thrombi containing platelets and fibrin are found within a proliferation of vascular tissue. Varying degrees of fibrosis and necrosis may occur within the lesion.

It has been suggested that the term hemangioma be reserved for the proliferative vascular lesions in infants that have a natural history of several months' rapid growth followed by spontaneous regression. This is the typical natural history of the lesions in true KMS. Platelet thrombi have been found in microscopic sections of the lesions. Stasis and fibrin thrombi are believed to be central to the pathogenesis of the coagulopathy, with resultant consumption of platelets and coagulation factors, elevated levels of fibrinogen-fibrin degradation products, and microangiopathic fragmentation of red blood cells.

Staging

While formal staging is not usually performed, documenting the extent of the invasion of the hemangioma into normal tissue is important for possible subsequent treatment with surgery or radiation. Hemangiomas do not metastasize.

TREATMENT

Section 6 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Medical Care

• Selected patients with no or mild thrombocytopenia and coagulopathy may be evaluated on an outpatient basis. However, as hemangiomas grow, these infants often require inpatient evaluation and treatment because most develop significant thrombocytopenia and DIC.
• KMS management involves hastening hemangioma regression, interfering with platelet trapping within the lesion, and supporting the patient with transfusions.
• Treatment with intermittent pneumatic compression, either alone or in combination with other therapies, has helped some patients. Compression is most useful when the hemangioma is located on an extremity. Encircle the hemangioma with a blood pressure cuff and gradually increase pressure to midway between the systolic and diastolic blood pressures. The cuff is inflated intermittently (ie, 90 seconds' compression, 30 seconds' rest). A cuff can be used for an extended period. Compression with surgical hose stockings may help. Compression treatment may be a helpful modality before attempting other potentially more toxic treatments.
• Radiation therapy is indicated in patients with severe disease. Although low radiation doses usually have been used with some success, carefully weigh the long-term adverse effects of radiotherapy in very young children (eg, risk of malignancy, decreased bone growth in the radiated field) against the problems caused by the hemangioma.

Surgical Care

• Complete resection of the hemangioma is very effective when possible. Thrombocytopenia and DIC resolve after the lesion is removed. Surgical resection, when possible, is the most effective treatment of vascular lesions complicated by KMS.
• Depending on the location of the tumor, general surgery, thoracic surgery, or neurosurgery may be needed for excision or ligation of the vessels feeding the hemangioma. Wide local excision is recommended but may be difficult. The large size and infiltrative growth pattern of the vascular lesion may cause complications (eg, hemorrhage, obstruction, respiratory compromise).
• Amputation may be necessary for intractable lesions involving a limb.
• Some lesions are surgically inaccessible and require nonsurgical treatment modalities.
• Interventional radiologic procedures use polyvinyl alcohol or absolute ethanol to embolize/sclerose the vessels of the hemangioma. Another technique involves injecting polyvinyl beads to stop feeder blood supply.
• Treatment with the tunable dye laser (TDL) may help patients with diffuse cutaneous hemangiomas.

Consultations

• Pediatric hematologists are needed to manage the complex hemostatic problems of patients with KMS and to administer and manage many of the medications needed for the most fulminant cases.
• Consultations with neonatal or pediatric intensive care specialists may be needed, based on the age of the patient.

Diet

• No special diet is required.
• Depending on the medical conditions, infants may require IV nutrition.

Activity

The location of the hemangioma and patient tolerance determine activity restrictions.

MEDICATION

Section 7 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

No single therapy has been proven most effective. 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 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 categories may have been used to treat KMS.

Drug Category: Corticosteroids

These agents stabilize blood vessels and reduce fibrinolysis.

Drug Category: Antiangiogenic agents

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.

Drug Category: Blood viscosity&#8211;improving agents

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

Drug Category: Anticoagulants

These agents decrease microthrombus formation in hemangiomas.

Drug Category: Antiplatelet drugs

These agents decrease microthrombus formation.

Drug Category: Antifibrinolytic agents

These agents inhibit thrombus breakdown, thus interfering with DIC. They are often administered with cryoprecipitate in patients with KMS.

Drug Category: Antineoplastic agents

These agents have an antiproliferative effect on tumor cells.

FOLLOW-UP

Section 8 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Further Inpatient Care

• Patients with the fulminant form of KMS require supportive care, including replacement therapy with platelets, fibrinogen concentrate, fresh frozen plasma (FFP), cryoprecipitate and antifibrinolytic drugs, and antiplatelet agents.

Further Outpatient Care

• Continue supportive treatments on an outpatient basis.

In/Out Patient Meds

• Continue supportive inpatient treatments.

Transfer

• Transfer neonates with giant hemangiomas and DIC to a facility with a neonatal ICU (NICU) capable of providing supportive care. Infants who present very early are likely to have a more severe form of KMS, and they require extensive intervention.
• The need to transfer an older child depends on the level of care necessary to support the patient. The general recommendation is to transfer to a tertiary care center all children who require medications other than steroids or who require support using blood products.

Complications

• Various complications of KMS relate to the site of the hemangioma. For example, hemangiomas of the chest that invade the thorax can compromise lung expansion and cause respiratory insufficiency.
• Bleeding secondary to DIC and unresponsive to platelet transfusions can cause death.
• Toxicity can result from the agents used to treat KMS (eg, secondary malignancy from radiation therapy).
• Some patients may experience high-output cardiac failure, which may lead to death.
• Ulceration and bleeding into the hemangioma can occur in patients with KMS.

Prognosis

• Patients in whom KMS is recognized and properly treated usually have an excellent prognosis because the DIC resolves as the hemangioma recedes and because KMS does not recur. Therefore, most children do well if they reach age 2 years.
• Patients in whom KMS is untreated have a 10-37% mortality rate, primarily due to bleeding.

Patient Education

• Once the diagnosis of KMS is confirmed, inform parents regarding the signs of congestive heart failure and thrombocytopenia (ie, DIC) in infants. These signs include difficulty feeding, petechiae, bruising, hematuria, and bloody stools.

MISCELLANEOUS

Section 9 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Medical/Legal Pitfalls

• Evaluate any infant with unexplained thrombocytopenia, with or without evidence of DIC, for visceral or hidden hemangiomas (especially of the spleen). Without prompt and appropriate attention, these forms of KMS are associated with high mortality rates.
• Evaluate patients for malignancy because malignant lesions may resemble the lesions seen in patients with KMS.

Special Concerns

• An association of KMS with trisomy 21 mosaicism is uncommon; however, 43% of children with Down syndrome have cutaneous vascular lesions. One child has been reported with Down syndrome and KMS.

ACKNOWLEDGMENTS

Section 10 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

The authors and editors of eMedicine gratefully acknowledge the contributions of previous author Carlos Suarez, MD to the development and writing of this article.

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

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Article Last Updated: Jun 22, 2006