Kaposiform haemangioendothelioma: clinical features, complications and risk factors for Kasabach–Merritt phenomenon

Summary

Background

Few studies have reported the clinical features, complications and predictors of Kasabach–Merritt phenomenon (KMP) associated with Kaposiform haemangioendothelioma (KHE).

Objectives

To determine the clinical characteristics present at diagnosis and to identify features that may aid clinicians in managing KHE.

Methods

We conducted a cohort study of 146 patients diagnosed with KHE.

Results

KHE precursors or lesions were present at birth in 52·1% of patients. In 91·8% of patients, lesions developed within the first year of life. The median age at diagnosis of KHE was 2·3 months (interquartile range 1·0–6·0). The extremities were the dominant location, representing 50·7% of all KHEs. Among KHEs in the cohort, 63·0% were mixed lesions (cutaneous lesions with deep infiltration). Approximately 70% of patients showed KMP. A KHE diagnosis was delayed by ≥ 1 month in 65·7% of patients with KMP. Patients with KMP were more likely to have major complications than patients without KMP (P = 0·023). Young age (< 6 months), trunk location, large lesion size (> 5·0 cm) and mixed lesion type were associated with KMP in a univariate analysis. In the multivariate analysis, only age [odds ratio (OR) 11·9, 95% confidence interval (CI) 4·07–34·8; P < 0·001], large lesion size (OR 5·08, 95% CI 2·24–11·5; P < 0·001) and mixed lesion type (OR 2·96, 95% CI 1·23–7·13; P = 0·016) were associated with KMP.

Conclusions

Most KHEs appeared before 12 months of age. KHEs are associated with various major complications, which can occur in combination and develop early in the disease process. Young age, large lesion size and mixed lesion type are important predictors of KMP.

Kaposiform haemangioendothelioma (KHE) is a rare vascular neoplasm that typically arises during infancy or early childhood. The estimated prevalence of KHE is 0·91 in 100 000 children. Rare cases have also been reported in adults.¹ KHE shows a locally aggressive behaviour without distant metastasis. Patients with KHE may develop a life-threatening thrombocytopenia and consumptive coagulopathy, known as Kasabach–Merritt phenomenon (KMP). Additionally, KHE can be complicated by severe anaemia from intralesional haemorrhage and haematoma formation. These factors lead to rapid tumour growth and infiltration, haemodynamic instability and the compression of vital structures.^2,3

KHE has notably high morbidity and mortality rates (up to 30%) due to severe associated complications and a lack of effective interventions. Although resection is the definitive treatment, total excision is either impossible or too destructive in KHE because these lesions may not be well circumscribed. In many patients, multiple agents with variable adjuvant therapies are given in sequence or in combination.⁴ The combination of systemic corticosteroids and vincristine is the mainstay of KMP treatment in many centres, and the treatment is listed as the first-line therapy in current guidelines.^5,6 The impact and risk of KHE are a tangible concern given the young age, high complication rate and aggressive treatment.

However, to date, most studies of KHE have been restricted to case reports and small case series of limited generalizability, and few large studies have been conducted,^1,7–11 constraining our ability to form a better understanding of the clinical features of KHE. To address this issue, we conducted a retrospective cohort study to assess the clinical presentation and complications of KHE and analysed the risk factors for developing KMP in patients with KHE. Based on previous research, we hypothesized that age, tumour size and anatomical location would be significant predictors of KMP associated with KHE.

Patients and methods

Using a computer medical records database, we compiled a list of patients who were diagnosed with KHE and seen in four tertiary medical centres over a 10-year period between January 2006 and December 2015. Institutional review board approval for this retrospective multicentre case series was obtained at West China Hospital of Sichuan University and each participating site.

All available charts were retrieved and reviewed. The diagnosis of KHE was based on histological data and/or clinical features, according to the findings published previously.^2,3 Written descriptions and photographs of the individual lesions were used to map each lesion. Imaging files were reviewed by two radiologists with extensive experience in the imaging characteristics of vascular anomalies. Based on the depth of tissue or organ involvement, lesions were classified into three groups: superficial, mixed and deep. Superficial KHEs were lesions involving the dermis, subcutaneous tissue and deep fascia. Mixed KHEs were defined as cutaneous lesions with deep infiltration into muscle, bone, intrathoracic sites or retroperitoneal sites. Deep KHEs were defined as noncutaneous lesions located in the mediastinum, retroperitoneum, internal organs, bones and joints.^1,12

Major complications, which were observed before or at the time of diagnosis, were defined as events that were life threatening or could result in long-term morbidity. KMP was defined as a platelet count of < 100 × 10⁹ cells L⁻¹.¹ Other major complications included severe acquired hypofibrinogenaemia (a fibrinogen level < 1·0 g L⁻¹), severe anaemia (a haemoglobin concentration < 80 g L⁻¹), active organ bleeding (e.g. pulmonary haemorrhage, intracranial bleeding or gastroenterological bleeding), compression of vital structures, bone–joint invasion, a decreased range of motion and severe pain, among others.

Data are presented as the mean with range or the median with the interquartile range (IQR) for continuous variables and as frequencies with percentages for qualitative variables. The Mann–Whitney test was used for variables with non-normal distributions. Baseline demographics and clinical characteristics were assessed for potential associations with developing KMP. Univariate analyses of potential risk factors were performed using Fisher’s exact test or a χ²-test, with the odds ratios (ORs) and 95% confidence intervals (CIs) of KMP reported for each factor. To evaluate further the relative risk of developing KMP, we conducted multivariate logistic regression analyses with variables identified in the univariate analyses as potential independent factors for the development of KMP. Statistical analyses were conducted using SPSS 22·0 for Windows (IBM, Armonk, NY, U.S.A.). P-values < 0·05 were considered statistically significant.

Results

Patient characteristics

In total, 146 patients were diagnosed with KHE during the study period. Twenty-two other patients whose lesions could not be clearly diagnosed or for whom insufficient information was available were excluded. The baseline characteristics of the patients are summarized in Table 1. There was a slight male predominance, with a ratio of 1·2 : 1. Prenatal diagnosis of a tumour was made by ultrasound and/or magnetic resonance imaging in seven cases. In 52·1% of patients, nascent or florid lesions were visible or detectable at birth, whereas 91·8% of patients developed lesions within the first year of life. The median age at discovery of the tumour lesion was 0·0 months (IQR 0–3). The median age at diagnosis of KHE was 2·3 months (IQR 1·0–6·0).

Table 1.

Baseline characteristics of children with Kaposiform haemangioendotheliomas (KHEs) (n = 146)

Sex, n (%)
Male	80 (54·8)
Female	66 (45·2)
Gestational age, n (%)
Term (37–42 weeks)	135 (92·5)
Premature (< 37 weeks)	11 (7·5)
Age at discovery of tumour lesion (months)
Mean (range)	3·5 (0–540·0)
Median (IQR)	0·0 (0–3·0)
Age at diagnosis of KHE (months)
Mean (range)	16·6 (0·0–552·0)
Median (IQR)	2·25 (1·0–6·0)
KHE location, n (%)
Head, face and neck	38 (26·0)
Extremity	74 (50·7)
Trunk	55 (37·7)
Multiple locations	21 (14·4)
KHE morphology, n (%)
Superficial	36 (24·7)
Mixed	92 (63·0)
Deep	18 (12·3)
Maximum tumour dimension (cm)
Mean (range)	9·1 (3·5–24·0)
Median (IQR)	7·0 (6·0–12·0)

IQR, interquartile range.

Tumour characteristics

The most common anatomical location of the lesions was the extremities, followed by the trunk and head–neck area (Table 1). Twenty-one patients (14·4%) had KHE lesions that extended into more than one anatomical region. The thigh was the single most frequently involved site and was affected in 26 of 146 cases (17·8%). Two patients had multifocal lesions. One patient with mediastinal and thoracic vertebrate invasion had pathologically confirmed neck lymph node metastasis. Most KHEs were classified as mixed subtype (92, 63·0%), while 36 (24·7%) were classified as superficial and 18 (12·3%) were classified as deep (Fig. 1).

Fig 1.

Kaposiform haemangioendotheliomas (KHEs) can be classified based on the depth of the lesions. Superficial lesion: (a) subsequent pathologically confirmed KHE on the left shoulder of a 4-month-old boy; (b) coronal T2-weighted magnetic resonance imaging (MRI) shows the lesion involving the dermis, subcutaneous tissue and deep fascia. Mixed lesion: (c) congenital KHE associated with Kasabach–Merritt phenomenon on the left thigh of a 4-week-old girl; (d) coronal T2-weighted MRI reveals a hyperintense mass with reticular stranding in multiple tissue planes and ill-defined margins. Deep lesion: (e) pathologically confirmed KHE in the left hip. An anteroposterior pelvis radiograph demonstrates striking changes in bone destruction involving the ilium and femur. (f) Coronal T2-weighted MRI reveals a hyperintense lesion confined to the bone and joint area.

The retroperitoneum was the most frequent extracutaneous location (nine of 18), followed by the bone–joint–muscle area (six of 18), peritoneal cavity (three of 18; one lesion simultaneously involved the retroperitoneum) and the thoracic cavity (one of 18). The mean size of an individual KHE was 8·8 4·7 cm, with a median of 7·5 cm. The KHE sizes ranged from pinpoint lesions (2·0 cm) to 25·0 cm. Overall, 71·9% of patients showed rapid growth or expansion of their tumours, where the KHE volume changed within days or weeks. A minority (2·7%) showed no changes in lesion size.

Major complications

KMP occurred in 102 patients (69·9%). The median platelet count was 21 × 10⁹ cells L⁻¹ (IQR 9–37) at the initial presentation of KMP. The age at onset of KMP ranged from the first day of life to 60·0 months, with a median age at disease onset of 1·0 months. The median duration from the presentation of KMP to the diagnosis of KHE was 0·63 months (IQR 0–1·25). Overall, KMP was evident at birth in 40 newborns (39·2%), including seven patients whose lesions had been identified prenatally. Ninety-three patients (91·2%) had their index episode of KMP within the first 6 months of age. Only four cases of KMP occurred after 1 year of age.

In total, 49 of 102 patients (48·0%) had no evidence of KMP at the initial assessment of the lesions, but KMP developed later (Fig. 2). The median duration from the assessment of the lesion to the episode of KMP was 1·25 months (IQR 0·5–3·0). The diagnosis of KHE was delayed ≥ 1 month after the presentation of KMP in 65·7% of patients. In four patients, all of whom had deep lesions, KMP was noted before the identification of a tumour mass. Lesions involving the mediastinum and lesions in the peritoneal cavity were all associated with KMP. A high incidence of KMP (seven of nine cases) was also noted in lesions with retroperitoneal involvement. Conversely, lesions in the head–neck area and lesions in the extremities were less frequently associated with KMP. All six deep lesions confined within the bone–joint–muscle area were not associated with KMP.

Fig 2.

A rapidly enlarging Kaposiform haemangioendothelioma involving the anterior chest wall. (a) A previously healthy 3·5-month-old boy presented with sudden development of a ‘pink’ mass on his anterior chest wall for 1 week (day 0; 1 day before referral). His platelet count was normal at 139 × 10⁹ cells L⁻¹. The mass had become progressively more indurate and purpuric (b: day 1, c: day 2). (d) Ecchymosis was evident with telangiectasia (day 5). His platelet count dropped to 26 × 10⁹ cells L⁻¹.

Major complications other than thrombocytopenia were also recorded (Table 2). Two common haematological events included severe acquired hypofibrinogenaemia and severe anaemia, which occurred in 53 and 20 patients, respectively. These two complications were KMP specific and were not found in patients without KMP. Twenty-six patients had tumour-induced compression of vital structures. Other common events were bone–joint invasion or destruction, decreased range of motion and chronic pain. These musculoskeletal complications were observed in both patients with KMP and patients without KMP, although musculoskeletal complications (e.g. decreased range of motion) are typically more prevalent in patients without KMP (P < 0·01). Relatively uncommon events included acute heart failure, active organ bleeding, pericardial effusion and pleural effusion, all of which occurred only in the patients with KMP. The difference in the overall rate of major complications per patient between patients with KMP and patients without KMP was statistically significant (2·2 vs. 0·9 events per patient, respectively; P = 0·023).

Table 2.

Major complications in patients with Kaposiform haemangioendotheliomas with or without Kasabach—Merritt phenomenon (KMP) (n = 146)

Events	With KMP (n = 102)	Without KMP (n = 44)	P-value
Thrombocytopenia	102	0	NA
Severe acquired hypofibrinogenaemia	53	0	NA
Compression of vital structures	22	4	0·098a
Respiratory distress and/or tract obstruction	10	1
Visual compromise	8	0
Biliary tract obstruction	1	2
Intestinal obstruction	2	0
Urinary tract obstruction	1	0
Facial nerve palsy	0	1
Severe anaemia	20	0	NA
Bone—joint invasion	7	12	0·001b
Decreased range of motion	4	13	< 0·001a
Severe pain	1	9	< 0·001a
Pericardial effusion	6	0	NA
Active organ bleeding	4	0	NA
Acute heart failure	3	0	NA
Pleural effusion	2	0	NA
Total	224	38	0·023c

NA, not applicable. P-values were calculated with

^aFisher’s exact test

^bχ²-test and

^cMann—Whitney test.

Treatment

The mean length of follow-up for the entire cohort was 2·1 years (range 0·2–9·0). Four patients who received a recommendation for observation had unchanged or slightly enlarged lesions during follow-up. The remaining 142 patients received at least one therapy. The management and treatment protocols were variable. Of these 142 patients, 131 underwent medical treatment after the presence of KMP and/or the diagnosis of KHE.

Three patients who initially had no sign of KMP were treated before the presence of KMP. Two of these three patients had congenital lesions: one had been treated with prednisolone, and the other had been treated with propranolol. The third patient was a boy who was referred because he presented with swelling of the right leg and foot. His initial working diagnosis was osteomyelitis. Multiple courses of antibiotic therapy had been administered for approximately 4 weeks before referral, but no response was observed. Treatment with prednisolone was started after the pathological confirmation of KHE, without any improvement. Subsequently, the patient presented with severe thrombocytopenia (Fig. S1; see Supporting Information).

Eight patients without KMP were treated before pathological examination. Of these eight patients, five with congenital lesions had undergone treatment, including complete surgical excision (two), prednisolone (one), propranolol (one) and sirolimus (one) (Fig. S2; see Supporting Information). Three patients with postnatal lesions were referred because of cutaneous vascular tumours. These patients exhibited insensitivity to prednisolone and/or propranolol treatment, requiring a switch to surgical excision (one of three) or sirolimus (two of three) (Fig. S3; see Supporting Information).

Risk factors for Kasabach–Merritt phenomenon

As shown in Table 3, a univariate analysis was performed to analyse the risk factors for KMP. Compared with the patients whose lesions were discovered at ≥ 12 months, those whose lesions were discovered at < 6 months had higher odds of developing KMP (OR 59·0, 95% CI 7·38–472; P < 0·001). Lesions involving the trunk were more likely to have KMP than nontrunk lesions. We also found that mixed lesions were four times more likely to show KMP than superficial lesions. Additionally, compared with patients whose lesions were sized < 5 cm, those with lesions ≥ 5 cm were more likely to experience KMP. The ORs of KMP were 6·80 and 14·2 for lesions 5–8 cm and ≥ 8 cm, respectively (Table 3).

Table 3.

Risk factors for Kasabach—Merritt phenomenon (KMP) based on univariate analysis

Variable	With KMP (n = 102)a	Without KMP (n = 44)a	P-value	OR (95% CI)
Age at discovery of tumour lesion (months)
≥ 12	1 (7)	14 (93)
6–12	4 (36)	7 (64)	0·13	8·00 (0·75–85·7)
< 6	97 (80·8)	23 (19·2)	< 0·001	59·0 (7·38–472)
Sex
Female	46 (70)	20 (30)
Male	56 (70)	24 (30)	0·97	1·01 (0·62–1·66)
Gestational age
Term	94 (69·6)	41 (30·4)
Premature	8 (73)	3 (27)	1·00	1·11 (0·50–2·06)
Location
Not trunk	54 (59)	37 (41)
Trunk	48 (87)	7 (13)	< 0·001	4·70 (1·92–11·5)
Morphology
Superficial	18 (50)	18 (50)
Deep	10 (56)	8 (44)	0·70	1·25 (0·40–3·89)
Mixed	74 (80)	18 (20)	0·001	4·11 (1·79–9·45)
Tumour size (cm)
< 5	6 (26)	17 (74)
5–8	36 (71)	15 (29)	< 0·001	6·80 (2·24–20·6)
≥ 8	60 (83)	12 (17)	< 0·001	14·2 (4·63–43·3)

OR, odds ratio; CI, confidence interval.

^aValues are n (%).

Based on the statistically significant differences evident in the univariate analysis, the results of the multivariate regression analysis indicated that age at discovery of the tumour lesion, morphology and tumour size were independent risk factors for KMP. Conversely, the tumour location failed to reach independent significance in the multivariate analysis (Table 4).

Table 4.

Risk factors for Kasabach–Merritt phenomenon based on multivariate regression analysis

Variable	P-value	Odds ratio (95% CI)
Age at discovery of tumour lesion	< 0·001	11·9 (4·07–34·8)
Location	0·075	3·16 (0·89–11·2)
Morphology	0·016	2·96 (1·23–7·13)
Tumour size	< 0·001	5·08 (2·24–11·5)

P-values < 0·05 are statistically significant. CI, confidence interval.

Discussion

Over 50% of KHE lesions were present at birth. The other lesions developed after the neonatal period, most often during the first year of life. However, later onsets during childhood, adolescence and even adulthood have been observed. In contrast to previous studies suggesting an equal sex ratio,^9,13 our study demonstrated that KHE lesions were slightly more common among male than female patients. The clinical presentation of KHE was variable and ranged from a cutaneous lesion with a wide variety of appearances to a deep mass, depending on the lesion size, lesion location, lesion extension into the deep tissue and vital organs and associated complications. Although most patients experienced symptom progression and/or rapid lesion enlargement, a small subgroup of patients was asymptomatic, and their lesions remained unchanged or grew slowly.

Complications of KHE are common and severe. Severe thrombocytopenia, being the most definitive and distinguishing factor impacting the symptoms of KMP, represents one criterion that patients with KHE must meet to be considered as having the coagulopathy of KMP. Additional features are commonly identified in the constellation of symptoms that make up KMP, and our goal was to document their frequency. According to our definition of KMP, namely a platelet count < 100 × 10⁹ cells L⁻¹, approximately 70% of the patients had KMP. Our results corroborated and extended the findings of Fernández et al.¹⁴ that patients with KMP had a higher risk of major complications than patients without KMP. In addition to providing information on the severe thrombocytopenic characteristic of KMP, our study provided novel data indicating that over half of the patients with KMP manifested severe acquired hypofibrinogenaemia and that one-fifth of these patients experienced severe anaemia.

Continued progression of profound thrombocytopenia together with consumptive coagulopathy and hypofibrinogenaemia with fibrin degradation products eventually results in intralesional bleeding, which leads to rapid tumour growth and infiltration. Although it was not statistically significant, we demonstrated that compression of vital structures was more commonly observed in patients with KMP than in patients without KMP. Furthermore, active organ bleeding that is due mainly to coagulopathy can occur in patients with KMP. In patients with mediastinum involvement, KMP could be associated with pericardial effusion and pleural effusion.^15,16

Although life-threatening complications were rare in patients without KMP, we found that these patients were more likely to experience musculoskeletal complications before or at the time of diagnosis. Lesions in the bone–joint–muscle area impaired mobility and caused painful joint contractures at the involved site over time. Importantly, residual musculoskeletal complications have also been reported in patients with KMP, long-term pharmacological treatment notwithstanding.⁷ Muscular atrophy and bone changes can result from tumour infiltration of the muscles, bone and joint structures and haematoma formation during the active phase of KMP.⁷ These pathological changes subsequently lead to prominent fibrosis and disabling contractures. The main challenge for clinicians involves preventing any of these musculoskeletal complications from ever occurring, thus improving the exercise capacity and quality of life of patients with KHE.

Prompt diagnosis and initiation of therapy are critical in KMP, which is associated with high mortality and morbidity if untreated. Although 39·2% of patients experienced KMP at birth, our data demonstrated that KMP occurred relatively later after the initial discovery of the lesion (median duration of 1·25 months) in nearly half of the patients. Additionally, our study revealed a mismatch between the age at presentation of KMP and the age at diagnosis of KHE (when most patients were seen by specialists). The findings presented here suggest that early referral of these high-risk patients to experienced physicians is advised to prevent deadly complications. Furthermore, previous studies have demonstrated that early treatment, especially when started shortly after birth and coincident with the onset of KMP, is associated with better long-term outcomes and fewer sequelae. Recent studies have demonstrated a satisfactory efficacy of sirolimus in the treatment of KHE and KMP.^12,17 Unlike traditional regimens based around vincristine, sirolimus has the advantage of oral administration without the need for central venous access; thus, treatment can be immediately available. Increased awareness of KHE is required for early diagnosis and prompt treatment to prevent severe complications.

Platelet activation, trapping and consumption are the basic pathophysiologies of KMP. Consumptive coagulopathy is believed to be triggered by the accumulation of platelets and coagulation factors within lesions. However, it is noteworthy that KMP is not a systemic process that is observed in disseminated intravascular coagulation. Instead, KMP is a localized process developing within the tumour.¹⁸ It remains unclear which patients have the greatest risk for developing KMP. KMP is reported mostly in patients with large lesions and lesions observed at birth.¹ Notably, the patients in our study whose lesions were discovered before 6 months of age had a more than 59-fold increased risk of developing KMP.

Another potent risk factor for KMP was the presence of a large lesion; this result has also been reported in other studies. Mulliken and Young suggested that KHE lesions > 5 cm were more likely to be associated with KMP than smaller lesions (< 5 cm).¹⁹ Gruman et al.²⁰ noted that KHE lesions < 8 cm in diameter were less likely to trap platelets in sufficient quantities to cause KMP. These findings, together with our results, support the notion that younger patients with a relatively large lesion are at high risk for developing KMP. Additionally, the size of the cohort and details of the recordings allowed us to quantify the association between the tumour size and the KMP incidence. Our study provided compelling evidence that a patient with a tumour lesion sized 5–8 cm was 6·8 times more likely to develop KMP, and an even higher risk was observed in patients with lesions ≥ 8 cm.

Previously, KHEs were classified using various approaches.^1,11,14 Frequently, KHE was categorized according to whether it was associated with KMP. An important descriptive classification is related to the depth of tumour infiltration; the risk of KHE increases with increased depth and infiltration of the lesion. We found that a deep lesion was not a significant factor for KMP in our group. Theoretically, deep lesions in the bone–joint–muscle area may be physically constrained from expansion. These lesions tended to be more focal and were more likely to be smaller than mixed lesions. Unlike superficial lesions, infiltrative mixed lesions, including lesions in the muscle and bone, are more likely to develop KMP.

Remarkably, lesions in the trunk were positively associated with KMP in the univariate analysis, although lesions in the trunk were not significant in the multivariate analysis. However, several differences in the anatomical subsite locations of the trunk lesions were notable between the patients with and without KMP. We found that all lesions that involved the mediastinum or peritoneal cavity were associated with KMP. A report by Gruman et al.²⁰ of 10 patients with KHE without KMP showed that none of them had retroperitoneal lesions. In the present study, although the frequency of KMP in the retroperitoneal lesions was high, we identified two patients with retroperitoneal lesions that were not associated with KMP. Similar findings have been reported by other investigators.^1,21 Theoretically, small retroperitoneal lesions without KMP might not be detectable unless they become clinically evident.²⁰

The limitations of this study include its retrospective approach. Multiple neonates and young infants with congenital lesions did not experience KMP when referred to our departments, and several of these congenital lesions were treated. Perhaps these lesions would have grown faster and developed KMP if they had not been treated. Furthermore, the high rate of complications in our cases might reflect a referral bias because many patients who were enrolled in our study were likely to be at higher risk. They are thus not completely generalizable to primary-care practice. However, this is the largest study of KHE to date, and, despite its limitations, we believe that our study will provide useful information that may aid clinical practice.

In summary, our study describes the largest assessment of KHE to date and provides detailed information regarding correlations between KHE characteristics and specific KHE subtypes. We have demonstrated that the clinical characteristics of KHE are variable and can be nonspecific. Although KHE is rare, most KHEs can cause clinically significant problems. Additionally, we have shown that KMP is common in KHE, occurring early in the course of the disease and accounting for most life-threatening complications. The identified risk factors, such as a younger age, large lesion size and mixed lesion type, enable a better risk stratification and individualized treatment of KHE. Furthermore, our findings reiterate the importance of viewing KHE beyond a single-disease framework and managing KHE in the context of the multiple associated morbidities.

Supplementary Material

Fig S2. Pathologically confirmed congenital Kaposiform haemangioendothelioma in the left leg

Fig S2. Pathologically confirmed congenital Kaposiform haemangioendothelioma in the left leg.

Fig S1. Pathologically confirmed Kaposiform haemangioendothelioma involving the right leg and foot

Fig S1. Pathologically confirmed Kaposiform haemangioendothelioma involving the right leg and foot.

Fig S3. Pathologically confirmed Kaposiform haemangioendothelioma involving the right knee

Fig S3. Pathologically confirmed Kaposiform haemangioendothelioma involving the right knee.

Video S1 Author Video.

Video S1 Author video.

Powerpoint S1 Journal Club Slide Set

Powerpoint S1 Journal Club Slide Set.

What’s already known about this topic?

• Kaposiform haemangioendothelioma (KHE) has notably high mortality and morbidity rates due to severe associated complications.

What does this study add?

• We demonstrate that Kasabach–Merritt phenomenon (KMP) is common in patients with KHE and contributes to various life-threatening complications, which can develop early in the disease course.

• Significant predictors of KMP include young age, large lesion size and mixed-type lesion.

• Recognition of the clinical characteristics of KHE and the factors that predict KMP will enable clinical decision making.