Pregnancy-related Kasabach-Merritt phenomenon with pleural effusion: A case report and literature review.

Sir,

A group of diseases caused by giant hemangioma, complicated with thrombocytopenia, have been defined as the Kasabach–Merritt syndrome (KMS) since the first case reported by Dr. Kasabach and Dr. Merritt in 1940.[1] In 2018, International Society for the Study of Vascular Anomalies, defined the Kasabach–Merritt phenomenon (KMP) as a phenomenon specifically caused by Kaposiform hemangioendothelioma (KHE) or tufted angioma.

The etiology and the pathogenesis of KMP are unclear. The intravascular coagulopathy characteristic of KMP is likely secondary to platelet trapping, given the distinct endothelial architecture of the associated vascular tumors. Once the process initiates, subsequent consumption of fibrinogen and coagulation factors will occur, and the process will eventually lead to the development of fibrinolysis. Adult KMP is rare. We speculate that pregnancy may be a risk factor for adult KMP. We present a case of pregnant woman with pleural effusion with typical clinical and histological findings along with specific immunohistochemistry markers of KMS.

A 23-year-old primigravida was first admitted to the hospital due to dyspnea at 37 weeks of gestation in 2015. Thoracic ultrasonography showed massive pleural effusion [Figure 1b]. A diagnosis of cutaneous hemangioma had been made when she was 10 years old. During the physical examination upon admission, subcutaneous hemangiomas distributing over the left anterior neck and chest, extending to the posterior shoulder region, were found. The lesion became deep purple and was scattered with blisters on the surface during the course of pregnancy [Figure 1a]. A complete blood count and coagulation studies revealed a platelet count of 76 × 109/L and a fibrinogen level of 2.11 g/L (2.38–4.98 g/L). We performed a thoracentesis to relieve the patient's breathing difficulties [Figure 1c]. Clinical biochemistry tests indicated that the fluid was thoracic exudate. Laboratory tests for infections, tuberculosis, and malignancy were all negative. Then, the obstetrician did a cesarean delivery. The platelet and coagulation tests returned to normal within 4 days after her delivery. She was initially diagnosed with pregnancy-associated thrombocytopenia. The patient requested to be discharged at that time. We observed that pleural effusion drainage volume gradually decreased and disappeared on the fourth postoperative week without any treatment during the follow-ups. At the same time, the skin lesions became lighter than before, and the blisters gradually resolved after the cesarean section. There were no further episodes of pleural effusion or thrombocytopenia in 5 years.

Figure 1

(a) Images of the lesion on admission, which was violaceous, purpuric, and with blisters on the surface. The boundary is not clear. (b) Thoracic ultrasonography showed massive pleural effusion. (c) Bloody pleural effusion

The same conditions occurred in the third trimester of her second pregnancy with no clinical manifestations such as fever and expectoration in 2020. After the cesarean section, the patient was transferred to the respiratory unit. The white blood cell counts were normal this time. Procalcitonin and C-reactive protein were all negative. Chest computer tomography showed no evidence of pneumonia, which ruled out infectious pleural effusion. Considering the pregnancy and the emaciation of the patient, tuberculous pleural effusion was not excluded. Thus, tuberculin test and erythrocyte sedimentation rate test were done, and the results came back negative. Normal echocardiogram and normal brain natriuretic peptide level did not support a diagnosis of heart failure, which might lead to pleural effusion. Computed tomographic pulmonary angiography (CTPA) was done, and pulmonary embolism was not found. We performed the thoracoscopic examination [Figure 2a] and a skin biopsy after the cesarean section. The pleural [Figure 2b-d] and skin [Figure 3a-f] biopsy revealed KHE. The tumor had a characteristic feature of round glomeruloid configuration [Figure 3a and b] and expressed vascular markers CD31 and CD34 [Figure 3c and d]. According to the test results, both unilateral pleural effusion and the KMP were attributed to the KHE.

Figure 2

(a) Abundant subpleural capillaries in the visceral layer under the thoracoscopy. (b) Multinodular tumor composed of sheets of spindled cells, well-formed capillary-like vessels, and occasional crescent-shaped vascular spaces, “Glomeruloid” clusters of rounded to epithelioid endothelial cells (HE ×40). (c and d) Immunohistochemical results: CD31 (+), CD34 (+), CKpan(-)、D2-40(partial +), Ki-67 (+ 1%), SMA (partial +), and Vimentin(+)

Figure 3

(a) The tumor consists of infiltrating nodules with fibrous connective tissue septa (hematoxylin and eosin staining, HE ×40). (b) The proliferative nodule consists of a crisscross of short spindle cell strands and slitlike or crescent blood vessels like in glomerulus; cytoplasm is abundant, eosinophilic. (HE × 100). (c–f) Immunohistochemical results: CD31 (+), CD34 (+), D2-40 (+), Desmin(-), FVVIII-R-Ag (+), Ki67 (8%), and SMA (+)

To our knowledge, the cases of KHE with pleural effusion and KMP in adults have not been reported. It is the first instance reported in which pregnancy induced KMP and pleural effusion associated with KHE and preeclampsia. We aim to provide new information about this entity and contributions to better treatment.

It has been previously reported that pregnancy may induce adult KMP.[2] There are only four references available about KMP associated with pregnancy.[2345] All of four patients suffered KMP in the third trimester of pregnancy, among whom two patients had got KMP before cesarean section. The other two patients had KMP after cesarean section.[24] One patient had hemangiomas in the right lower abdomen which are close to the incision of cesarean section.[4] Thus, it is possible to cause KMP by the surgical skin injury. The other one[2] developed severe KMP after cesarean section. Considering preeclampsia in the patient before cesarean section, it is speculated that hormonal changes during pregnancy and preeclampsia may be the high risk factors in causing KMP. However, there are few references on pregnancy-related KMP at present. Thus, there is a need to summarize more cases. In our patient, thrombocytopenia occurred for both later period pregnancies. It is widely known that the most frequent cause of low platelets in pregnancy is gestational thrombocytopenia (GT), a benign condition that typically induces a mild thrombocytopenia in late pregnancy and does not require any specific intervention. Obstetric causes account for approximately 20% of cases. However, the diagnosis of GT is an exclusive diagnosis. In a differential diagnosis, one should consider at least two other entities that may closely mimic pregnant pleural effusion and thrombocytopenia. One is preeclampsia, which is characterized by new onset hypertension above 140/90 after 20 weeks gestation, accompanied by at least one additional feature including proteinuria, renal insufficiency, impaired liver function, thrombocytopenia, pulmonary edema, and/or new-onset headache unresponsive to simple analgesia. Our patient had no clinical manifestations and positive test results of preeclampsia, and the pleural effusion was bloody exudate, rather than clear and leakage. So, the diagnosis of preeclampsia/HELLP was excluded. The other is pulmonary thromboembolism. Our patient was excluded by examination of CTPA.

KHE involving the thorax is extremely rare, as only a few cases were reported.[6] Intrathoracic lesions were identified in 3 and 10% of patients with KHE by two of the largest retrospective studies, which involved more than 100 patients with KHE.[17] It may be related to hormone changes during pregnancy, and the specific mechanisms remain to be further explored.

The treatment experience of pregnant women with KMP is scarce. Based on previous reports of pregnant women with KMP, a short course of glucocorticoid therapy is likely an effective treatment in stabilizing the patient, and glucocorticoid could be used in subsequent treatments. Terminating the pregnancy may also be an effective treatment for KMP and pleural effusion. After terminating pregnancy, our patient's platelets count returned to normal, and the pleural effusion gradually resolved. There are no standard guidelines in treating KHE. A variety of treatment options, ranging from monotherapy to combinations of medicines, have been suggested. Commonly used drugs are corticosteroids, aspirin, ticlopidine, vincristine, interferon alfa-2a, paclitaxel, epsilon aminocaproic acid, and nonselective beta blockers. Recently, many researchers provided evidence that supports the use of vincristine or sirolimus as first-line therapies for KHE.[8]

In conclusion, pregnancy may be a risk factor for adult pleural effusion and KMP. The potential for a refractory coagulopathy presenting as KMP should be considered in any patient who presents with extensive hemangiomas.

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