Overview

Kasabach-Merritt Phenomenon (KMP) is a life-threatening, consumptive coagulopathy associated with an underlying vascular tumor. KMP is characterized by severe thrombocytopenia, microangiopathic anemia, hypofibrinogenaemia, and elevated fibrin split products in the presence of a rapidly enlarging tumor. The coagulopathy is likely related to the sequestration of platelets and clotting factors within the vascular lesion resulting in systemic disseminated intravascular coagulation and a high propensity for patients to clot and bleed. Kasabach and Merritt first described this consumptive coagulopathy in a 2-month-old boy with a giant capillary hemangioma and purpura. However, recent studies support an association of KMP with the vascular tumors kaposiform hemangioendothelioma (KHE) and tufted angioma (TA), not infantile hemangioma. The clinical presentation and laboratory findings of KMP, as well as the histopathology and treatment of KMP and the underlying vascular tumors are discussed.

Clinical presentation

KMP typically has its onset early in infancy with a median age of onset of 5 weeks. In approximately 50% of cases, KMP was associated with a vascular tumor diagnosed at birth with 90% of published cases diagnosed before 1 year of age. Boys and girls were equally affected. KMP was most often associated with a rapidly growing, large (>5 cm) solitary tumor commonly involving extremities, trunk, or face and neck. Most of these tumors involved subcutaneous and deep structures and were locally invasive. Skin over the tumors was most often described as deep red to purple in color with an advancing ecchymotic rim. The tumors were often warm and leathery to palpation with a nodular feel. Widespread cutaneous petechiae were often seen in subjects with platelet counts less than 10,000. Signs and symptoms of bleeding were seen in more than 50% of children with KMP at presentation in one report. Subjects with retroperitoneal or visceral lesions presented with abdominal distention, signs of organ dysfunction, or high-output heart failure often without cutaneous signs.

Laboratory and radiographic findings

All subjects with KMP had profound thrombocytopenia and hypofibrinogenemia with elevated fibrin split products (D-dimers), suggestive of an active consumptive coagulopathy. Platelet counts at the time of diagnosis ranged from 6000 to 98,000 with fibrinogen levels less than 100 mg/dL; whereas, D-dimers were always greater than 1. Pretreatment prothrombin times (PT) and activated partial thromboplastin time (PTT) were not routinely measured, but ranged from normal to significantly prolonged. In one series, 80% of subjects presented with anemia at diagnosis. Evidence of intravascular hemolysis, including red blood cell fragmentation, elevated LDH, and hyperbilirubinemia, was a common finding.

MRI was the most frequently used modality to assess vascular tumors associated with KMP. These tumors were described as diffusely enhancing masses isointense to muscle on T1-weighted and hyperintense on T2-weighted sequences. The tumors involved multiple tissue planes and had poorly defined margins. Cutaneous thickening and fat stranding were common features. Superficial draining vessels were often dilated, but vessels in the tumor were small and infrequent. Signal voids consistent with hemosiderin deposits were often noted on MRI.

Vascular pathology associated with KMP

Seminal studies in the 1990s challenged the long-held belief that KMP was a complication of infantile hemangiomas and definitely showed the association of KMP with KHE and TA ( Fig. 1 ). Of the 40 biopsy samples from 52 subjects in these studies, 35 were diagnosed with KHE; whereas, 5 were called TA. None had histology or clinical features consistent with infantile hemangioma. Since then, biopsies of most lesions associated with KMP have shared the same histopathologic features. Indeed, the original case described by Kasabach and Merritt of a 2-month-old child with a capillary hemangioma with purpura was likely a KHE.

A 15-day-old girl with large, invasive kaposiform hemangioendothelioma with Kasabach-Merritt syndrome.

KHE is a locally aggressive vascular tumor characterized by sheets and lobules of round and spindle shaped endothelial cells that form crescentic vascular spaces and, less commonly, round capillary-like spaces. Superficial tumors infiltrate the dermis and subcutaneous tissues; whereas, deep and visceral lesions extensively involve and entrapp normal adjacent structures. Fibrin and platelet-rich microthrombi are frequently identified within the tumor tissue suggesting areas of platelet trapping and blood destruction. Endothelial cells in the tumor nodules are positive for CD31, CD34, and FLI1, but negative for the hemangioma-specific markers GLUT1 and LeY. TA associated with KMP present as cutaneous lesions with small, discrete nodules of capillary vessels situated in the deep dermis, hypodermis, or both, with an evenly distributed cannonball pattern with peripheral crescentic slitlike vessels and dense fibrosis. Capillary lumens are typically small, lined by attenuated endothelial cells, and often filled with erythrocytes. Both TA and KHE are known to occur in association with lymphatic abnormalities thought to be an intrinsic part of the lesion, not just a result of lymphatic obstruction by the tumor. The striking similarities in the histologic features of KHE and TA and the observation that both entities have been described within the same tumor have led some to speculate that KHE and TA are the same disease on a continuum.

Why KMP develops exclusively in the setting of KHE or TA is currently unknown. Lyons and colleagues have speculated that it is the unique architectural or endothelial composition found in KHE and TA that promote platelet trapping and a consumptive coagulopathy. In contrast to the ordered treelike vasculature of infantile hemangioma, convoluted capillaries arise directly off large vessels in KHE and TA resulting in turbulent flow-promoting platelet activation and aggregation. Furthermore, unique characteristics of the endothelial tumor cells within KHE and TA may promote platelet adhesion and activation. However, only a percentage of patients diagnosed with TA or KHE have an associated consumptive coagulopathy, arguing that other features, such as tumor size, may be an important determinant. The observation that most patients diagnosed with KMP are a few weeks or months of age could possibly be explained by proportionately larger tumors in this age group, or suggest other important developmental differences in platelet or endothelial function that may result in an increased susceptibility for development of KMP in young patients with KHE or TA.