Kasabach-Merritt Phenomenon (KMP) is a clinical syndrome characterized by thrombocytopenia, consumptive coagulopathy, and purpura associated with kaposiform hemangioendothelioma (KHE) or tufted angioma (TA). It was first reported in 1940 by Kasabach and Merritt as the initial clinical association of platelet sequestration with capillary hemangioma 2)4).
KHE and TA lie on the same tumor spectrum and are histologically similar. KHE is a locally aggressive tumor, whereas TA is benign. KMP occurs in approximately 70% of KHE patients and about 10% of TA patients. KMP is not associated with the more common infantile hemangioma. Infantile hemangiomas are GLUT-1 positive, whereas KHE and TA are GLUT-1 negative, allowing immunohistochemical differentiation.
Approximately 80% of KMP cases develop within the first year of life, with a median age of onset of 5 weeks 5). There are about 200 reported cases 5). There is no gender or ethnic predilection. The most common sites of involvement are the face, head, neck, thorax, abdomen/retroperitoneum, and extremities. The mortality rate of KMP is 20–40%, primarily due to refractory bleeding from consumptive coagulopathy 5).
KMP is a phenomenon associated with KHE or TA, not with infantile hemangioma (so-called strawberry hemangioma). Infantile hemangioma is a benign tumor that stops growing between 6 months and 2 years of age and spontaneously regresses in about 90% of cases by 7–9 years of age; its pathophysiology differs from that of KMP.
The subjective symptoms of KMP vary depending on the location and size of the underlying vascular tumor.
The clinical presentation of KMP varies depending on the location of the lesion.
Skin lesions
Purpura-like mass: A hard, purple, ill-defined plaque-like lesion. It rapidly enlarges and becomes markedly swollen.
Leathery texture: Palpation may reveal nodularity and warmth.
Hypertrichosis and hyperhidrosis: May be observed in the affected area.
Petechiae: Petechiae appear on the skin when platelet count is below 10,000.
Visceral Lesions
Retroperitoneal mass: The most common site of visceral lesions. Clinical identification is difficult due to the large space for expansion.
Abdominal distension: Appears as the tumor enlarges.
Signs of organ failure: May present with high-output heart failure and multi-organ failure.
Palpable mass: May be detected on abdominal palpation.
Ophthalmic Lesions
Eyelid swelling: TA presents as a painless, slow-growing swelling of the upper and lower eyelids. It may be mistaken for an infection.
Proptosis: Orbital KHE can cause proptosis.
Ptosis and astigmatism: Enlarging eyelid lesions can cause amblyopia.
Orbital compartment syndrome: The most serious complication, leading to optic nerve compression and vision loss.
The following findings are observed in laboratory tests.
Blepharal and orbital TA/KHE can cause blurred vision, diplopia, ptosis, and amblyopia. The most serious complication is orbital compartment syndrome, which can lead to vision loss due to optic nerve compression. Early diagnosis in infancy is important to prevent future amblyopia, strabismus, and astigmatism.
KMP develops as a complication of KHE or TA. KHE and TA are tumors characterized by abnormal proliferation of vascular endothelial cells, and are distinct from vascular malformations, which are congenital vascular anomalies.
Factors associated with the risk of developing KMP are as follows:
According to a review by Schmid et al., the proportion of KHE patients presenting with KMP varies by age: 79% in infancy, 47% at 1–5 years, 43% at 6–12 years, and 10% at 13–21 years1).
Diagnosis of KMP requires identification of the vascular tumor and confirmation of coagulation abnormalities.
MRI is useful for differentiating KHE from TA and assessing the extent of the lesion.
| Finding | KHE | TA |
|---|---|---|
| Enhancement pattern | Diffuse, ill-defined | Homogeneous, ill-defined |
| Infiltration into layers | Involving multiple layers | Confined to a single layer |
| Hemosiderin deposition | Present | Absent |
Angiography is useful for evaluating the feeding vessels and collateral circulation of vascular lesions associated with KMP, and is used in preoperative planning for embolization. Magnetic resonance angiography (MRA), which combines MRI and angiography, can provide the most informative imaging.
Histological diagnosis is not essential for the treatment of KMP, but biopsy may be considered to identify the subtype of vascular tumor.
The following diseases should be differentiated.
The goal of KMP treatment is to stabilize coagulopathy and reduce the size of the underlying tumor.
Corticosteroids are used as initial therapy due to their rapid response and ease of management, but their efficacy as monotherapy is limited. They are combined with sirolimus, which has anti-angiogenic and pro-apoptotic effects.
In a randomized controlled trial by Ji et al. (2020), 94.6% of the sirolimus plus prednisolone combination group achieved sustained platelet response after 4 weeks, compared to 66.7% in the sirolimus monotherapy group 1).
In a meta-analysis by Peng et al. (2019), the response rate for tumor shrinkage was 0.91 for sirolimus and 0.72 for vincristine, and for platelet normalization in KMP, sirolimus was 0.94 and vincristine was 0.82 1).
The main side effects of sirolimus are immunosuppression, elevated liver enzymes, hyperlipidemia, and stomatitis. Monitoring is required to ensure blood levels do not exceed 10–13 ng/mL 5).
After coagulopathy stabilizes, steroids are tapered considering side effects, and sirolimus is continued for several months.
Previously used as first-line in combination with steroids, it is now considered an adjunctive therapy due to the need for central venous catheter and risk of peripheral neuropathy1).
This is considered when the tumor is large, resistant to medical treatment, or has abundant feeding vessels. Bleomycin, ethanol, polyvinyl alcohol particles, etc. are used.
During KMP, surgical risk is high due to coagulopathy. It is considered after medical treatment normalizes platelet count and reduces tumor size. Solitary skin lesions can be cured by surgical resection.
Transfused platelets are trapped and consumed within the vascular tumor, worsening KMP. Additionally, angiogenic growth factors in transfused platelets may promote tumor growth 1). Platelet transfusion is not recommended except for active bleeding or before surgery.
The pathophysiology of KMP is not fully understood, but the complex vascular structure of KHE/TA is thought to play a central role.
The pathogenesis of KMP is explained by the following cycle.
This cycle continues until the tumor disappears or treatment is administered.
Severe KMP can lead to the following complications:
Platelets trapped within the tumor activate the coagulation cascade, leading to intratumoral hemorrhage. This hemorrhage causes rapid tumor enlargement, which in turn traps more platelets, creating a vicious cycle.
In a randomized controlled trial by Ji et al. (2022), the corticosteroid plus sirolimus combination group showed significantly faster improvement in coagulopathy of KMP compared to the sirolimus monotherapy group2).
Pérez et al. (2022) reported an adult KMS case where gastrointestinal bleeding completely disappeared 48 hours after administration of sirolimus 0.8 mg/m²5). Platelets recovered from 59,000 to 205,000/μL, and fibrinogen improved from less than 50 to 98 mg/dL. The mechanism of action of sirolimus is shown to be inhibition of the mTOR signaling pathway → suppression of VEGFR activation → inhibition of endothelial cell proliferation → lesion shrinkage.
KMP is a disease common in infants, but reports of adult-onset cases are also accumulating.
Ye et al. (2025) conducted a systematic review of KMP (Kasabach-Merritt syndrome) associated with hepatic angiosarcoma and analyzed 8 cases3). The median age was 66 years, platelets were 21–95×10⁹/L, and fibrinogen was typically less than 1.5 g/L. KMP associated with adult angiosarcoma has a poor prognosis, and surgical resection, if possible, was concluded to be the best treatment option.
Zhao et al. (2022) conducted a literature review of 26 cases of giant hepatic hemangioma and reported that 13 cases (50%) were complicated by KMP (KMS) 4). For unresectable lesions, steroids and alpha-interferon were first-line treatments, with vincristine and chemotherapy as subsequent therapies.
