Kasabach–Merritt Syndrome

Kasabach–Merritt syndrome (or phenomenon) is

the association of a vascular tumor and throm-

bocytopenic coagulopathy (Enjolras et al. 2000). It is a

life-threatening, localized consumptive coagulopathy,

characterized by profound thrombocytopenia and

microangiopathic anemia.

In 1940, Kasabach and Merritt described the

first case of Kasabach–Merritt syndrome with

a case report of consumptive coagulopathy associa-

ted with a hemangioma. However, it is now recog-

nized that Kasabach–Merritt syndrome is usually

associated with Kaposiform hemangioendothelioma

and tufted angioma, rather than the classic

involuting hemangioma of infancy (Enjolras et al.

1997).

Synonyms and Related Disorders

Hemangioma-thrombocytopenia syndrome

Genetics/Basic Defects

1. Genetics

a. Sporadic in majority of cases

b. Autosomal dominant inheritance in rare reports

c. Can be a part of recognized syndromes

2. Pathophysiology (Hall 2001)

a. Platelet trapping by abnormally proliferating

endothelium within the hemangioma, resulting

in the activation of platelets with a secondary

consumption of clotting factors

b. Continued consumption of both platelets and

clotting factors along with the initiation of

fibrinolysis eventually resulting in intralesional

bleeding which manifests as rapid enlargement

of the hemangioma

Clinical Features

1. Diverse clinical presentation (Enjolras et al. 2000;

Hall 2001)

a. Type of hemangiomas

i. Kaposiform hemangioendothelioma: often

found in noncutaneous sites such as the

retroperitoneum, mediastinum, and pelvis,

as well as the skin

ii. Tufted angioma

iii. Mixture of Kaposiform hemangioen-

dothelioma and tufted angioma

iv. Not “true” common hemangioma of infancy

b. Reddish brown skin lesion progressing to

a violaceous bulging mass

i. Often painful

ii. Aggressive infiltration with ulceration

iii. Bruising in other areas

iv. Possible infection

c. Bleeding from thrombocytopenia and intravas-

cular coagulopathy

d. Increase in size and becoming tense, woody,

and purplish of preexisting hemangiomas during

pregnancy

2. Cutaneous involvement of Kaposiform

hemangioendothelioma

a. Smooth, shiny, dark purple, indurated, tender,

and poorly delineated

b. Nearly always single

H. Chen, Atlas of Genetic Diagnosis and Counseling, DOI 10.1007/978-1-4614-1037-9_139,# Springer Science+Business Media, LLC 2012

1219

3. Visceral involvement of hemangiomata

a. Single

b. Multiple

c. Isolated within one organ as single or diffuse

lesions

d. Retroperitoneal hemangiomata

i. Often giant in size

ii. Easily missed clinically: diagnosis suspected

in patients presenting with an unexplained

thrombocytopenia and coagulopathy

iii. Generally associated with high mortality

4. Diffuse and multiple nature

a. Diffuse infantile (neonatal) hemangiomatosis

i. Presence of multiple cutaneous and visceral

hemangiomata

ii. High morbidity and mortality

b. Intraosseous and soft tissue hemangiomata

5. Lifelong hemangioma in adults

a. Hormone alterations and increase in blood

volume in pregnancy may affect preexisting

lesions, triggering episodes of acute dissemi-

nated intravascular coagulation

b. Development of acute consumptive coagulopathy

after surgery of other unrelated tumor

6. Thrombocytopenic coagulopathy in patients with

hemangiomata as a part of a recognized syndrome

a. Klippel–Trenaunay syndrome

i. A rare congenital generalized mesodermal

abnormality

ii. Macular vascular nevus, skeletal/soft tissue

hypertrophy

iii. Venous and lymphatic anomalies including

viscera and facial hemangiomata

b. Blue rubber bleb nevus syndrome

i. Multiple cutaneous cavernous hemangiomata

ii. Cutaneous and occasional visceral

hemangiomata

c. Gorham–Stout disease (“vanishing bone

disease”)

i. Massive osteolysis (Gorham sign)

ii. Followed by replacement of the bony matrix

by proliferating thin-walled vascular and

lymphatic channels

iii. Extension of these angiomatous masses into

soft tissues

7. Prognosis

a. Incomplete regression of the lesion after months

or years

b. Visceral involvement

i. Mediastinum

ii. Neck

iii. Retroperitoneum

iv. Pelvis

c. Hemorrhage by aggressive invasion

d. Petechiae, ecchymoses, or purpura

e. Profound thrombocytopenia

f. Anemia

g. Congestive heart failure

h. Severe infections

i. Residual lesions after “cure” of Kasabach–Merritt

phenomenon (Enjolras et al. 2000)

i. Common after the resolution of thrombocy-

topenia and coagulopathy

ii. Clinical patterns

a) Cutaneous red stain with or without asso-

ciated red papules

b) Telangiectatic streaks and swelling

c) A minor, firm, irregular subcutaneous

mass assessed by palpation or deep

infiltration evidenced by CT scan or MRI

d) Sequelae in muscles and/or joints

j. Overall mortality (estimated to be 20–30%)

(El-Dessouky et al. 1988) due to complications

such as (Enjoiras et al. 1990):

i. Disseminated intravascular coagulation

ii. Respiratory failure due to a pressured

airway

iii. High-output heart failure due to presence of

a huge tumor

Diagnostic Investigations

1. Laboratory studies (Hall 2001)

a. Generally severe thrombocytopenia: occurs in

1–2 per 300–700 cases of hemangioma

b. Consumptive coagulopathy

i. Prominent fibrinogenopenia

ii. Usually elevated fibrin split (degradation)

products

iii. Usually elevated D-dimers (a measure of

fibrin split products)

iv. Depressed clotting factors V and VII

2. Ultrasound, MRI, or CT

a. To assess extent of the lesions

b. To identify the occult lesions

1220 Kasabach–Merritt Syndrome

3. Histology to determine subtypes of hemangioma

a. Kaposiform hemangioendothelioma of infancy

and childhood

i. The most frequently reported histological

type

ii. A locally aggressive, low-grade malignant

tumor

iii. Lobules or sheets of tightly packed spindle

cells or more rounded endothelial cells and

pericytes

iv. Infiltrative pattern of the cellular areas in the

dermis and subcutaneous fat and muscles,

generally containing few obvious vascular

lumina

v. Aggregates of rounded dilated capillaries,

lined by attenuated endothelial cells with

small dark nuclei and filledwith red blood cells

vi. Containing lymphatic-like vessels

b. Tufted angioma

i. A benign lesion

ii. Small tufts or lobules of rounded capillaries

with small lumina

iii. Tufts: discrete and evenly distributed in a

cannon ball pattern, characterized by periph-

eral crescentic slit-like vessels and fibrosis

iv. Aggregates of rounded dilated capillaries,

lined by attenuated endothelial cells with

small dark nuclei and filledwith red blood cells

Genetic Counseling

1. Recurrence risk

a. Patient’s sib: not increased unless a parent is

affected

b. Patient’s offspring: 50% in case of autosomal

dominant inheritance

2. Prenatal diagnosis: Prenatal diagnosis of fetal facial

hemangioma in a case of Kasabach–Merritt

syndrome

3. Management (Ryan et al. 2010)

a. General premise regarding treatment: Resolution

of the lesion will lead to a correction of the

consumptive coagulopathy, which is heralded

by a recovery in the platelet count.

b. Principle of management of thrombocytopenia

in Kasabach–Merritt syndrome should be to

“treat the patient and not the numbers.”

c. Prompt and vigorous management

i. Help to optimize the outcome

ii. No one treatment modality established as

consistently efficacious

d. Blood product support in the presence of sudden

decompensation or enlargement of the lesion

i. Fresh frozen plasma

ii. Cryoprecipitate if fibrinogen still less than

1.0 g/L

iii. Platelets transfusion should be reserved for

thrombocytopenic patient who is actively

bleeding or in preparation for a surgical

procedure.

iv. Tranexamic acid for profound fibrinolysis

e. Simple or single lesion

i. Vascular ligation

ii. Embolization

iii. Surgical excision

a) Surgical removal of a giant heman-

gioma: usually hazardous in the

presence of an uncontrolled consumptive

coagulopathy

b) Supporting and stabilizing hemostasis

while trying to remove or ablate the

lesion

c) Partial resection of tumor, reduction of

tumor blood, and vincristine chemother-

apy (Shen et al. 2010): Since the huge

tumor is the major cause of rapid platelet

destruction, the partial removal of the

tumor and U-shaped suture to reduce

tumor blood supply would reduce the

platelet destruction and, therefore, improve

the clinical condition, followed by skin

graft or flaps of the wound, and vincristine

chemotherapy necessary to prevent the

enlargement of the remaining tumor.

f. Diffuse or extensive lesions

i. Prednisone

ii. Alpha interferon

g. Adjuvant therapies

i. Vincristine

ii. Localized radiotherapy

iii. Combination chemotherapy (vincristine,

cyclophosphamide)

iv. Antifibrinolytic or antiplatelet agents

(tranexamic acid, ɛ-amino caproic acid,

pentoxifylline, ticlopidine)

Kasabach–Merritt Syndrome 1221

h. Potential future therapies

i. Laser therapy

ii. Antiangiogenic agents

iii. Pegylated recombinant human megakaryo-

cyte growth and development factor

(peg-rHuMGDF)

References

Alvarez-Mendoza, A., Lourdes, T. S., Ridaura-Sanz, C., et al.

(2000). Histopathology of vascular lesions found in

Kasabach–Merritt syndrome: Review based on 13 cases.

Pediatric and Developmental Pathology, 3, 556–560.Biban, P. (2003). Kasabach–Merritt syndrome and interferon

alpha: Still a controversial issue. Archives of Disease inChildhood, 88, 645–646.

Billio, A., Pescosta, N., Rosanelli, C., et al. (2001). Treatment

of Kasabach–Merritt syndrome by embolisation of a giant

liver hemangioma. American Journal of Hematology, 66,140–141.

Blei, F. (1998). Successful multimodal therapy for kaposiform

hemangioendothelioma complicated by Kasabach–Merritt

phenomenon: Case report and review of the literature.

Pediatric Hematology and Oncology, 15, 293–305.Brizel, H. E., & Raccuglia, G. (1965). Giant hemangioma with

thrombocytopaenia-radioisotope demonstration of platelet

sequestration. Blood, 26, 751–756.Cheerva, A. C., Bartolone, C., & Raj, A. B. (2010). Pediatric

Kasabach–Merritt syndrome. Medscape reference. Updated

Feb 23, 2010. Available at: http://emedicine.medscape.com/

article/956136-overview

de Terlizzi, M., Bonifazi, E., Toma, M. G., et al. (1988).

Kasabach–Merritt syndrome: Successful management of

coagulopathy with heparin and cryoprecipitate. PediatricHematology and Oncology, 5, 325–328.

Dresse, M. F., David, M., Hume, H., et al. (1991). Successful

treatment of Kasabach–Merritt syndrome with prednisone

and epsilon-aminocaproic acid. Pediatric Hematology andOncology, 8, 329–334.

El-Dessouky, M., Azmy, A. F., Raine, P. A. M., et al. (1988).

Kasabach–Merritt syndrome. Journal of Pediatric Surgery,23, 109–111.

Enjoiras, O., Riche, M. C., Merland, J. J., et al. (1990). Manage-

ment of alarming hemangiomas in infancy. Pediatrics, 85,491–498.

Enjolras, O., Mulliken, J. B., & Wassef, M. (2000). Residual

lesions after Kasabach–Merritt phenomenon in 41 patients.

Journal of the American Academy of Dermatology, 42,225–235.

Enjolras, O., Wassef, M., & Mazoyer, E. (1997). Infants with

Kasabach–Merritt syndrome do not have “true” hemangi-

omas. Journal of Pediatrics, 130, 631–640.Esterly, N. B. (1983). Kasabach–Merritt syndrome in infants.

Journal of the American Academy of Dermatology, 8,504–513.

Esterly, N. B. (1995). Cutaneous hemangiomas, vascular stains

and malformations, and associated syndromes. CurrentProblems in Dermatology, 7(3), 65–108.

Frevel, T., Rabe, H., Uckert, F., et al. (2002). Giant cavernous

haemangioma with Kasabach–Merritt syndrome: A case

report and review. European Journal of Pediatrics, 161,243–246.

Gianotti, R., Gelmetti, C., & Alessi, E. (1999). Congenital

cutaneous multifocal kaposiform hemangioendothelioma.

American Journal of Dermatopathology, 21, 557–561.Haisley-Royster, C., Enjolras, O., Frieden, I. J., et al. (2002).

Kasabach–Merritt phenomenon: A retrospective study

of treatment with vincristine. Journal of PediatricHematology/Oncology, 24, 459–462.

Hall, G. W. (2001). Kasabach–Merritt syndrome: Pathogenesis

and management. British Journal of Haematology, 112,851–862.

Hatley, R. M., Sabio, H., Howell, C. G., et al. (1993). Successful

management of an infant with a giant hemangioma of the

retroperitoneum and Kasabach–Merritt syndrome with

alpha-interferon. Journal of Pediatric Surgery, 28,1356–1357; discussion 1358–1359.

Hesselmann, S., Micke, O., Marquardt, T., et al. (2002). Case

report: Kasabach–Merritt syndrome: a review of the thera-

peutic options and a case report of successful treatment

with radiotherapy and interferon alpha. British Journal ofRadiology, 75, 180–184.

Kasabach, H. H., & Merritt, K. K. (1940). Capillary hemangi-

oma with extensive purpura. Report of a case. AmericanJournal of Diseases of Children, 59, 1063–1070.

Krafchik, B. R., Hendricks, L. K., & Faquet, G. B. (2010).

Kasabach–Merritt syndrome. Medscape reference. Updated

Feb 22, 2010. Available from: http://emedicine.medscape.

com/article/202455-overview

Larsen, E. C., Zinkham, W. H., Eggleston, J. C., et al. (1987).

Kasabach–Merritt syndrome: Therapeutic considerations.

Pediatrics, 79, 971–980.Lee, J. H., Jr. (1967). Kirk RF: Pregnancy associated with giant

hemangiomata, thrombocytopenia, and fibrinogenopenia

(Kasabach–Merritt syndrome). Report of a case. Obstetricsand Gynecology, 29, 24–29.

Ogino, I., Torikai, K., Kobayasi, S., et al. (2001). Radiation

therapy for life- or function-threatening infant hemangioma.

Radiology, 218, 834–839.Ozsoylu, S. (2002). Treatment of Kasabach–Merritt syndrome

by megadose methylprednisolone. Pediatric Hematologyand Oncology, 19, 373–374.

Phillippe, M., Acker, D., & Frigoletto, F. D., Jr. (1980). Preg-

nancy complicated by the Kasabach–Merritt syndrome.

Obstetrics and Gynecology, 56, 256–258.Powell, J. (1999). Update on hemangiomas and vascular

malformations. Current Opinion in Pediatrics, 11, 457–463.Respondek-Liberska, M., Janiak, K., Jakubek, A., et al. (2002).

Prenatal diagnosis of fetal face hemangioma in a case

of Kasabach–Merritt syndrome. Ultrasound in Obstetrics &Gynecology, 19, 627–629.

Ryan, C., Price, V., John, P., et al. (2010). Kasabach–Merritt

phenomenon: A single centre experience. European Journalof Haematology, 84, 97–104.

1222 Kasabach–Merritt Syndrome

Shen, W., Cui, J., Chen, J., et al. (2010). Kasabach–Merritt with

partial resection of tumor, reduction of tumor blood,

and vincristine chemotherapy. The Journal of CraniofacialSurgery, 21, 215–216.

Singh, G., & Rajendran, C. (1998). Kasabach–Merritt syndrome

in two successive pregnancies. International Journal ofDermatology, 37, 690–693.

Kasabach–Merritt Syndrome 1223

a b

Fig. 1 (a–b) An infant with Kasabach–Merritt syndrome showing a giant cavernous hemangioma over most of the chest

a b c

Fig. 2 (a–c) A patient with blue rubber bleb nevus syndrome

1224 Kasabach–Merritt Syndrome