Late third trimester diagnosis of congenital giant hemangioma complicated by the Kasabach-Merritt phenomen: a case report and literature review

Abstract Objective. To describe the case of a large cervical mass diagnosed in the late third trimester with development of Kasabach-Merritt phenomenon (KMP) in the immediate postnatal period, along with a literature review. Methods. Description of case-report and literature search through Medline/Pubmed, performed from inception to December 2022 for articles relating to the pre and postnatal diagnosis of KMP. Results. A 36-year-old multiparous woman was admitted to hospital for contractions at 40 weeks of gestation, in an otherwise uneventful pregnancy. Admission’s ultrasound showed the presence of a voluminous mass of 14x15 cm of the posterior side of the neck, highly vascularized, and no signs of hemodynamic imbalance. Postnatally, blood tests showed the presence of severe anemia and thrombocytopenia requiring several transfusions of blood, plasma, platelets and clotting factors. Due to the association of congenital hemangioma and thrombocytopenia a diagnosis of KMP was made. After attempts of conservative treatment, surgical removal was needed to stop the hematological cascade with regression of symptoms. The review of the literature identified 14 articles including 9 cases of prenatally suspected KMP and 6 diagnosed in the immediate postnatal period and without signs of fetal hydrops. Adverse perinatal outcome, in terms of postnatal death/termination of pregnancy, was observed in 67% of cases (6/9) in the prenatally suspected group and 33% of cases in those with a postnatal diagnosis of KMP. Fetal hydrops was present in 83% of cases with adverse perinatal outcome. Conclusions. The Kasabach-Merrit syndrome is a rare condition, which can have a dangerous evolution when it develops in utero or in the immediate postnatal period carrying a risk of perinatal mortality of approximately 50%. Even if the fetus shows no signs of anemia or heart failure, the risk of developing it in the immediate postnatal period is high and should be mentioned to the couple.


Introduction
The presence of vascular anomalies in the prenatal period places the fetus at risk of non-immune hydrops fetalis secondary to two mechanisms: the first is the establishment of a hyperdynamic circulation, which mainly occurs in vascular malformations; the second is the entrapment of platelets within the lesion with consequent thrombocytopenia and hypofibrinogenemia, a cascade typically present in vascular tumors [1].In the latter case, the Kasabach-Merritt phenomenon (KMP) occurs.The onset of KMP, present in about 1% of vascular anomalies, is predominantly a neonatal diagnosis which is rarely discussed in prenatal counseling.We describe a case-report of KMP arising in the immediate postnatal period in a fetus with a large congenital hemangioma of the posterior side of the neck along with a literature review of KMP cases diagnosed in the prenatal or immediate postnatal period.
development of KPM and literature search performed from inception until December 2022 in PubMed (Medline).For the purpose of the search, a combination of key terms was used which included "giant congenital hemangioma," "Kasabach-Merritt phenomenon," "fetal hydrops."Full-text article and abstract with available information on the time of onset of KMP and histotype of the lesion were included in the study [2].

Case-report
A 36-year-old woman, with two previous spontaneous delivery, referred herself for contractions at 40 weeks of gestation.The pregnancy was uneventful, and her routine ultrasound scans showed no fetal abnormalities.The growth scan, performed at 30 week's gestation as per local protocol, showed a normal fetal growth and normal anatomy.Given the low risk of the pregnancy, no further ultrasound scans were scheduled.At admission's ultrasound, a voluminous soft tissue lesion measuring 14 � 15 cm was seen on the posterior side of the neck.The mass had a predominantly cystic appearance and was highly vascularized.Amniotic fluid was normal and umbilical artery and middle cerebral artery pulsatility index were normal.Fetal growth was consistent with the gestational age and there was no signs of ascites or edema.Cardiotocography was normal and uterine activity was detected.At vaginal examination the cervix was three centimeters dilated, fully effaced and softened and, due to the presence of regular uterine activity, a diagnosis of active labor was made.A cesarean section was offered to the woman due to the risk of labor dystocia related to the large neck mass and a healthy male weighting 4515 g was delivered.After birth, the presence of a very voluminous exophytic mass of 11 � 10 cm covering the cervical and dorsal regions was confirmed (Figure 1).The mass was purplish red in color with pale peripheral halo and important central depression, covered by smooth, shiny skin with multiple telangiectasia.The consistency was taut elastic, with well-defined margins.The newborn was initially kept under surveillance in our Neonatal Intensive Care Unit (NICU) and then transferred to a secondary pediatric hospital with availability of pediatric surgery.In the first day of life, blood tests demonstrated the presence of severe thrombocytopenia (platelet 13.000x10 3 /mL), anemia (Hb 11 g/dl) and increase in D-dimer values (>20 g/mL) secondary to the abnormal vascularization of the mass.After multidisciplinary counseling including the hematologist, dermatologist, cardiologist and pediatric surgeons, a diagnosis of a Rapidly Involuting Congenital Hemangioma (RICH) with a superimposed KMP was made and treatment with prednisone 5 mg per day and acetylsalicylic acid 10 mg per day was started.After one month, despite the pharmacological treatment and partial reduction in size of the mass the neonate had persistent thrombocytopenia and signs of coagulopathy, requiring multiple blood and platelets transfusions.A transfemoral sclero-embolization of the lesion was performed but it was complicated by the development of a large inguinal hematoma at the level of the catheter insertion.Notwithstanding the surgical evacuation of the hematoma, a clinical hemorrhagic diathesis could not be managed by medical treatment with blood, platelets and plasma transfusions and the neonates had persistent signs of right cardiac overload.Subsequently, the cervical lesion was removed by surgery and histology showed a GLUT-1 negative tumor confirming RICH diagnosis.After surgery, child's conditions improved rapidly, and subsequent followup showed a normal neurological and motor development.

Literature review
The literature review found 14 cases summarized in Table 1.Nine articles reported on prenatal diagnosis of a vascular lesion with the clinical suspicion of KMP, mainly because of the presence of fetal hydrops and/or signs of anemia [3][4][5][6][7][8][9][10]. Five articles reported on prenatal diagnosis of a vascular lesion without signs indicative for KMP, which was diagnosed in the immediate postnatal period [11][12][13][14].The histotype of the lesion varied from congenital hemangioma and vascular anomalies, including those secondary to the Klippel-Trenaunay-Weber syndrome (KTWS), to the more aggressive form of kaposiform hemangioendothelioma.No genetic abnormalities were reported either prenatally or postnatally.The mean gestational age at diagnosis was 32 weeks for the prenatal group and 33.5 weeks in the postnatal group.Overall, postnatal death or termination of pregnancy was reported in 57% of cases (8/14), but it increased to 66.7% (6/9) in cases with a prenatal suspicion of KMP due to the presence of fetal hydrops or signs of anemia.Fetal hydrops was present in 83% of cases with adverse perinatal outcome.

Discussion
The Kasabach-Merritt phenomenon was first described by Kasabach, a radiologist, and Merritt, a pediatrician, that reported the association between thrombocytopenia and a giant hemangioma of the left leg of a 2month-old infant [15].Clinically is characterized by the triad of thrombocytopenia, microangiopathic and hemolytic anemia and consumptive coagulopathy [16,17].This clinical picture is secondary to the presence of rare vascular malformations and tumors, where platelets are trapped within the abnormal structure of the vessels, with a consequent reduction in the number of platelets circulating in the blood [18].At the same time, the turbulence of the blood flow, determined by the abnormal vascularization of the mass, causes the formation of micro-clots with secondary consumption of coagulation factors and mechanical destruction of red blood cells.KSP is a lifethreatening condition with a reported mortality rate of 10-40% [19].
Some authors report that KMP is related only to the presence of clinical entities such as tufted angioma and kaposiform hemangioendothelioma [1, 18,20,21].However, both our case and the review of the literature show that congenital hemangioma and vascular anomalies secondary to KTWS can also cause KMP.
The differential diagnosis in the prenatal period between these different entities is, although not easy, important because it can affect prognosis.Congenital hemangioma is a rare, benign, vascular tumor secondary to rapid endothelial cells proliferation, that is fully formed at birth.The vascular neoformation is evident as a dark red swelling mass, usually large, most frequently located under the skin, on the limbs, trunk, face and neck.Sometimes The differential diagnosis between congenital hemangioma and other types of cervical mass can be difficult in the prenatal period, especially when located in the cervical area.The majority of neck masses are lymphatic malformations (46%) and teratomas (37%), while cervical thymic cysts and hemangioma/hemangioendothelioma are rarer (6% and 11%, respectively) [22].Anterior cervical masses are more common than posterior.Among anterior masses cervical teratoma is the most frequent, while cystic hygroma usually locates posteriorly and congenital hemangiomas can be located at different sites [7].However, case series focusing on posterior locations of vascularized cervical masses have shown that these lesions are most frequently congenital hemangiomas [12].
A careful study of the ultrasound appearance of the cervical mass may be helpful in the prenatal differential diagnosis and in defining the prognosis: congenital hemangioma can be solid or mixed (cystic component and solid component), vascularized on color Doppler, and may presents calcifications; kaposiform hemangioendothelioma may present as a mass of variable dimensions, vascularized, with signs of erosion of adjacent structures; teratomas appear as lesions with mixed content (cystic and solid), vascularized on color Doppler and with calcifications; lymphangioma are mainly cystic, poorly vascularized and without calcifications [12].Intrauterine MRI can be a complementary investigation for differential diagnosis [23].
It is not clear why in some cases the presence of a vascular lesion causes the development of KMP in the prenatal period with the presence of hydrops fetalis and poor prognosis for the fetus, while in others the fetus is hemodynamically stable in utero but presents signs of consumptive coagulopathy immediately after birth.
The size of the lesion does not appear to be the cause for the development of hydrops fetalis, as our case was the one with the largest dimension of the mass, but the fetus was hemodynamically stable.Not even the type of lesion seems to be important, given that among the cases reported in the literature, an adverse pregnancy outcome has been reported in cases of congenital hematoma as well as in kaposiform hemangioendothelioma. What could instead be important is the gestational age at diagnosis, given that in cases with prenatal suspicion of KMP the gestational age at diagnosis was lower than in cases without signs of hydrops.In support of the role of gestational age at diagnosis, the two cases of postnatal death in the group of postnatal onset of KMP were those with the earlier gestational age at diagnosis of the mass, even if fetal hydrops was not present.Therefore, we could hypothesize that the earlier the gestational age at the onset of the mass, the more likely the risk of platelet trapping and consumptive coagulopathy typical of KMP, that may or may not result in fetal hydrops with a worsen prognosis.
Prenatal diagnosis of a vascularized mass surely implies a careful surveillance of fetal well-being to exclude signs of heart failure and fetal hydrops, which is certainly a negative prognostic sign.However, in the absence of hydrops, the couple should be informed prenatally about the possibility that the newborn may present signs of consumptive coagulopathy in the context of KMP and that the earlier the gestational age the higher the risk.This eventuality entails a postnatal mortality risk of approximately 30% and the newborn may need to be transferred to a specialized center.We believe that this aspect is the main clinical implication of the article and should be stressed to the couple.
Regarding our case, the neonatal outcome was good as the newborn was hemodynamically stable and there was time for the transfer to a tertiary care center.Furthermore, the mass was posterior and there was no displacement of the mediastinal structures that may require delivery with the EXIT (ex-utero intrapartum treatment) procedure.However, if the diagnosis had been made before giving birth, a dedicated ultrasound could be performed to evaluate the characteristics of the mass and any displacement of the trachea also with the help of an intrauterine MRI (Magnetic Resonance Imaging).Lastly, the birth would have been planned at a tertiary level facility in order to avoid the transfer of a potentially hemodynamically unstable newborn.
The limitations of the study lie in its nature of casereport and nonsystematic review of the literature.However, this case highlights the importance of performing an ultrasound evaluation upon admission of the patient to exclude the presence of ultrasound anomalies that developed in the late third trimester of pregnancy and even if the last scan was performed at 30 weeks.The issue of third trimester ultrasound is particularly important as in many countries it is not performed at all due to a cost-effective policy or it is set at 30-32 weeks.However, notwithstanding the limitation of the study, we believe that this case-report strengthen the need of an ultrasound at 35-36 weeks in order to diagnose late third trimester anomalies.

Figure 1 .
Figure 1.Postnatal appearance of the newborn with a giant congenital hemangioma located in the posterior side of the neck.

Table 1 .
Articles reporting on the occurrence of the Kasabach-Merritt phenomen, divided by the time of onset.JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE vascular lesions are located at the level of the internal organs, such as the liver.