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Kasabach-Merritt Syndrome
Introduction
Kasabach-Merritt phenomenon (KMP), first described in 1940, is a rare but life-threatening coagulopathy of infancy which presents with thrombocytopenia, microangiopathic hemolytic anemia, and consumptive coagulopathy in the setting of a rapidly enlarging vascular tumor. It is exclusively associated with the vascular tumors kaposiform hemangioendothelioma (KHE) and tufted angioma (TA), which exist along the same neoplastic spectrum. Treatment includes supportive therapy and management of the underlying tumor.[1][2][3][4]
Etiology
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Etiology
KMP occurs exclusively as a complication of KHE and TA, which are rare, benign vascular tumors that typically present in infancy.[5] KHE and TA are classified as having intermediate malignant potential as they are locally aggressive but are not known to metastasize.[6][7][8]
Epidemiology
While the precise incidence of KHE and TA are not known, they are noted to be rare and estimated to be 0.07/100,000 in one article based on observed cases at a large center.[9] However, KMP may affect up to 70% of all patients with KHE and up to 10% of patients with TA.[10][5][9][11] Both genders and all ethnicities appear to be affected equally. Tumors typically present in early infancy, with a mean age of diagnosis in one case series of 2 months.[9] Rarely KHE may present in adulthood, and in adulthood is typically not associated with KMP.
Pathophysiology
Both KHE and TA have a convoluted vascular architecture that likely contributes to the pathophysiologic mechanisms of KMP. It is theorized platelets become trapped in the lesion, leading to platelet activation and fibrinogen consumption.[5][12] This theory is supported by positive immunohistochemistry staining for the platelet marker CD61 within the vascular lumen of lesions, as well as localized consumption of radiolabeled fibrinogen.[5] It is noted that the risk of KMP increases with increasing depth of the lesion and with intrathoracic or retroperitoneal involvement.[9]
The morbidity and mortality of KMP are high with reported mortality up to 30%.[10][13][5] Death usually occurs from life-threatening hemorrhage, cardiac failure, or invasion of the underlying vascular lesion into local structures. Retroperitoneal lesions are associated with increased mortality, potentially due to delay in diagnosis.
Histopathology
KHE and TA have similar histopathologic features but differ in their clinical behavior. KHE is locally aggressive and may involve multiple tissue planes; whereas, TA is benign and typically confined to a single tissue plane.[10] They both arise from capillary and lymphatic endothelium and are notable for their convoluted vascular architecture. Both have identical histopathologic staining, including staining positive for D2-40, LYVE1, Prox-1, and negative for GLUT-1. Because of this KHE and TA are thought to exist on the same neoplastic spectrum.[10][5]
History and Physical
KHE typically presents as an enlarging, firm, purpuric cutaneous or soft tissue lesion. It may be indurated, with a pebbly texture and poorly defined margins. KHE may involve the trunk, extremities, or retroperitoneum. Up to 10% of all KHE cases are not cutaneous.[5] TA is typically described as a series of violaceous macules and papules and usually involves the trunk. Both lesions may be associated with overlying hypertrichosis or hyperhidrosis.
Infants affected by KMP who have cutaneous involvement of KHE or TA will present with a rapidly enlarging pre-existing lesion that becomes tense, purpuric, or ecchymotic, is markedly painful. The swelling may be dramatic. Of note, if the lesion involves the retroperitoneum, the enlarging lesion may not be readily apparent on physical exam.
Evaluation
Diagnosis of KMP requires laboratory evaluation and identification of an underlying vascular tumor. Laboratory evaluation should include a complete blood count, coagulation panel, and PTT and PTT. Thrombocytopenia may be severe. Coagulation studies will reveal a prolonged PT and PTT, hypofibrinogenemia, and increased D-dimer. [11][5]
When identifying the underlying, cutaneous lesion, physical examination may be sufficient. If a visceral tumor is suspected, further imaging such as MRI may be useful in establishing both the presence of the tumor and its local extent. MRI may show significant gadolinium enhancement with dermal and subcutaneous thickening. [10][11]Biopsy of the suspected underlying lesion should be considered to establish the identity of the underlying lesion but is typically not possible if KMP is already present due to the risk of bleeding.
Treatment / Management
Treatment of KMP is largely supportive and aimed at preventing life-threatening complications while addressing the underlying tumor. While the thrombocytopenia of KMP may be profound, life-threatening hemorrhage is, in fact, rare, and platelet transfusion is not recommended except in the cases of active bleeding. Transfused platelets may become trapped in the tumor and lead to further abnormal coagulation, worsening KMP. [5] Symptomatic anemia should be treated with red blood cell transfusion. In cases of bleeding or as preparation for surgery, cryoprecipitate may be administered.[14][15][16](B3)
Treatment of the underlying tumor is critical in KMP. Surgery is the definitive management for both KHE and TA. However, it is often not possible given ill-defined tumoral borders and the invasion of multiple tissue planes and local structures. Furthermore, once KMP develops, surgery is inadvisable given the hemodynamic risks. Embolization may be possible if a single feeding vessel is present. However, tumors usually have multiple feeding vessels. Embolization also carries the risk of necrosis of local structures. Radiation therapy can induce regression, however, carries the risk of developmental delay, growth delay, and secondary malignancy. [5][17][18](B3)
Multiple medical therapies have demonstrated promise in the treatment of KHE and TA. Historically steroids are typically first-line treatment. For patients who respond, clinical response is usually seen within 2 weeks, after which steroids should be tapered slowly.[13][17] If regression cannot be achieved, seen in approximately one-third of patients, vincristine and mTOR inhibitors such as sirolimus may be used. In 2013 the Journal of Pediatrics published expert consensus guidelines which recommended combination steroid and vincristine as first-line therapy, with steroid monotherapy recommended if vincristine is not readily available.[16](B2)
Differential Diagnosis
- Angiosarcoma
- Arteriovascular malformations
- Consumption coagulopathy
- Hemangioblastoma
- Hepatic hemangiomas
- Immune thrombocytopenic purpura
- Infantile hemangioma
- Teratoma
- Neuroblastoma
- Subcutaneous fat necrosis
Pearls and Other Issues
Congenital hemangiomas (CH) may also present with thrombocytopenia and a disturbed coagulation profile; however, this phenomenon is transient and distinct from KMP which is progressive and not expected to resolve spontaneously.
Enhancing Healthcare Team Outcomes
The diagnosis and management of KMP is with an interprofessional team that includes a hematologist, radiologist, intensivist, pediatrician, nurse practitioner, and the primary care provider. Once the diagnosis is made, the treatment is largely supportive and includes prevention of life threatening complications like hemorrhage. The underlying tumor must be treated. Both surgery and embolization have been used but both carry high risk of injury to adjacent structures. In some children, radiation may induce regression of the mass, but the therapy can also lead to growth retardation and induction of secondary malignancies.
Many potent chemotherapeutic agents have been used but the response is variable and not always predictable. The outlook for most children with KMP is guarded.[10][19] (Level V)
References
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