Bernard-Soulier Syndrome from the Perspective of the Obstetrician: A Case Report with a Review of the Literature.

OBJECTIVE: Bernard-Soulier syndrome (BSS) is one of the rare inherited platelet disorders that is characterized by macrothrombocytopenia and adhesion abnormality due to the absence or malfunctioning of the membrane GPIb-IX-V complex. There is no high-quality evidence on obstetric management of BSS owing to its rarity. Here we report an uncomplicated delivery of an adolescent with BSS and review the literature on the topic of BSS and pregnancy. METHODS: PUBMED, EMBASE, COCHRANE, and Google Scholar databases were searched up to April 2022 without language and year restriction using the terms "Bernard Soulier" and "Pregnancy". The primary objectives were to evaluate maternal and fetal outcomes. The secondary objectives were to analyze pregnancy complications, gestational age at delivery, mode of delivery, administered prophylaxis, treatment approaches, duration of postpartum hospitalization, and the postpartum requirement of blood and blood product. RESULTS: The patient was a 19-year-old and 39-week pregnant woman who was diagnosed with BSS at the age of 10 by flow cytometry and genetic analysis. Single donor platelet transfusions and oral tranexamic acid were administered as prophylaxis at the peripartum period. She was delivered by cesarean section due to failure of labor. The postpartum period was uneventful for both mother and neonate. In the literature review, postpartum hemorrhage (PPH) was found in 52.9% (27/51) of deliveries. Late PPH occurred more frequently than early PPH (35.3 and 31.4%, respectively). 49% (25/51) of pregnancies had severe thrombocytopenia, and antepartum hemorrhage was observed in 11.8% (6/51) of those. The platelet count was in close relation to antenatal complications. 64.7% (33/51) of the patients were delivered via cesarean section. PPH and late PPH were found to be more common in those who delivered vaginally compared to those who delivered by caesarean section. It was observed that PPH was less common in women who were given prophylaxis in the peripartum period. CONCLUSION: BSS is an inherited macro-thrombocytopathy that may cause adverse maternal and neonatal outcomes. The optimal mode and timing of delivery remain unclear. A multidisciplinary approach with prophylaxis at the peripartum period should be applied.

Bernard-Soulier syndrome in pregnancy with retinal detachment: a rare phenomenon.

Bernard-Soulier syndrome (BSS) is a rare congenital bleeding disorder of the platelet, and it is mainly inherited as an autosomal recessive trait. It is caused by both qualitative and quantitative deficiency of the platelet membrane glycoprotein (GP) Ib-IX-V receptor complex, thereby causing abnormal platelets adhesion.We report a case of a primigravida in her 20s with history of BSS diagnosed in childhood due to family history. Her preconception period was challenging as she suffered from severe menorrhagia often requiring hospital admission, blood and platelet transfusions.At 35 weeks gestation, she developed temporal crowded retinal detachment of the left eye and had a successful left scleral buckling surgery under general anaesthesia (GA).She had a multidisciplinary team care with a successful elective GA caesarean section at 39+3 weeks gestation with peridelivery platelet transfusion and intravenous recombinant factor VIIa. Regional anaesthesia, intramuscular injections and anticoagulation were avoided.

Perforated hemorrhagic cholecystitis in a patient with Bernard-Soulier syndrome.

Bernard-Soulier syndrome is an inherited coagulopathy, with an incidence of one per million. Hemorrhagic cholecystitis is a rare and life-threatening complication of acute cholecystitis. Less than 50 patients have been reported in the previous literature. Bleeding diathesis and anticoagulant treatment are well-known predisposing factors for hemorrhagic cholecystitis. We present a 57-year-old male patient who was referred to our department with a complaint of right upper quadrant abdominal pain. Contrast-enhanced computed tomography revealed a high-density mass associated with the gallbladder lumen, and blood clot in the gallbladder lumen and hemoperitoneum which were compatible for hemorrhagic cholecystitis and gallbladder perforation. The patient underwent urgent cholecystectomy. Hemorrhagic cholecystitis often manifests as typical acute cholecystitis presentation; but several clinical findings such as fever, lower gastrointestinal bleeding or severe intraabdominal bleeding-related hypovolemic shock may also occur. Most of the described cases in prior literature have been reported to use anticoagulant medications. This report describes the second hemorrhagic cholecystitis patient with inherited bleeding diathesis and the first case with Bernard-Soulier syndrome.

Invasive procedures in the oral cavity of individuals with Bernard-Soulier syndrome: An integrative review.

AIM: Bernard-Soulier syndrome (BSS) is an inherited bleeding disorder characterized by macroplatelets and thrombocytopenia, prolonged bleeding time, and a prevalence of less than 1 in 1,000,000. In view of the recognition of the risk of bleeding and the management of daily surgical practice in these patients, adequate strategies are necessary to provide the safest care. This article aims to perform an integrative review of the literature on the management of invasive procedures in the oral cavity of individuals with BSS. METHOD: The PubMed/Medline and LILACS databases were searched using Boolean operators related to BSS, bleeding disorders, and oral care. RESULTS: As a result, only five articles with the main theme were included: one letter to the editor and four case reports, described chronologically as to date of publication, classification of the article, and medical/odontological measures taken. CONCLUSION: We conclude with this review the need for adequate knowledge of surgeons regarding coagulation disorders and the need to discuss and plan procedures with the hematology team, as well as the importance of the notion of management of possible complications resulting from invasive treatments in the oral cavity of patients with BSS.

Acquired Bernard-Soulier syndrome and hypodysfibrinogenaemia because of multiple myeloma.

We describe a case of a patient with multiple myeloma with initial presentation simulating a bleeding disorder. Detailed coagulation work-up showed hypodysfibrinogenaemia along with a platelet function defect consistent with acquired Bernard-Soulier syndrome (BSS). Multiple plasma exchanges led to significant improvement in his bleeding symptoms. To the best of our knowledge, this is the first described case of simultaneous presentation of hypodysfibrinogenaemia and BSS secondary to multiple myeloma.

A Case of Bernard-Soulier Syndrome due to a Novel Homozygous Missense Mutation in an Exon of the GP1BA Gene.

Bernard-Soulier syndrome (BSS) is an extremely rare autosomal recessive bleeding disorder clinically characterized by macrothrombocytopenia and a mucocutaneous bleeding tendency. A 1-year-old Chinese patient who was born to consanguineous parents was diagnosed with early onset of BSS. Gene sequencing and bioinformatics analysis were conducted. We identified a novel homozygous missense mutation (c.790T>C) in the GP1BAgene that causes an amino acid residue substitution of a cysteine with an arginine that might have a deleterious effect on the protein function as predicted by bioinformatics analysis. If a patient has clinical manifestations that include recurrent mucocutaneous bleeding, a mean platelet volume and platelet-large cell ratio above normal levels, and giant platelets on a peripheral smear and has consanguineous parents, a diagnosis of BSS can be suspected. In these situations, gene sequencing for mutations in the GPIb-IX-V complex is necessary.

Nontraumatic Orbital Subperiosteal Hematoma in a Case of Bernard-Soulier Syndrome With Bilateral Pansinusitis.

Orbital subperiosteal hemorrhages are usually due to trauma. However, nontraumatic subperiosteal hemorrhages have also been rarely reported. Here, the authors present a 13-year-old boy with Bernard-Soulier syndrome who presented with right orbital subperiosteal hemorrhage causing optic neuropathy which was surgically drained with full visual recovery.The authors describe a case of rare coagulopathy (Bernard-Soulier syndrome) and pansinusitis presenting with nontraumatic subperiosteal hemorrhage.

Management of haemostasis during dental extraction in a Bernard-Soulier syndrome child.

The Bernard-Soulier syndrome also known as hemorrhagioparous thrombocytic dystrophy, is a rare autosomal recessive bleeding disorder. Macrothrombocytopenia and increased bleeding time are the two main features of this syndrome. There is a reduced adherence of giant platelets to the subendothelium due to a deficiency of glycoprotein GPIb-V-IX complex. Routine dental extraction in a patient with a bleeding disorder can lead to life-threatening complications and there are very few specific protocols for the same. Here, we present a case report describing haemostasis management during dental extraction in a 7-year-old female child, suffering from this syndrome. It was observed that the preoperative and postoperative human leucocyte antigen-matched platelet transfusion, systemic intraoperative tranexamic acid and minimally traumatic procedure improved bleeding control and management.

Patients with Bernard-Soulier syndrome and different severity of the bleeding phenotype.

Bernard-Soulier syndrome is a rare (1:1million), hereditary bleeding disorder caused by defects of the platelet GPIb-IX-V complex. Patients suffer from mucocutaneous bleedings. Typical are thrombocytopenia, giant platelets and impaired agglutination after stimulation with ristocetin. In populations in which consanguineous marriages are common the frequency of the disorder is increased because Bernard-Soulier syndrome is mostly inherited autosomal recessively. Genetic analyses of the disease-related genes may help to gain more insights regarding the phenotype/genotype correlation. Here, we investigated several patients with Bernard-Soulier syndrome from different families. We analyzed two patients with severe bleeding symptoms from one family of middle east origin and confirmed the diagnosis by identifying a pathogenic variant in GP1BB. We compared phenotype/genotype correlation of this GP1BB mutation with the GP9 (p.Asn61Ser) European founder mutation present in 9 patients out of 4 families for whom we also performed molecular genetic analysis.

[Bernard-Soulier syndrome and pregnancy: a case report]. / Syndrome de Bernard-Soulier et grossesse : à propos d'un cas.

Bernard-Soulier syndrome is an inherited bleeding disorder. Due to the rarity of the combination of this syndrome and pregnancy, data on the clinical course and outcome of pregnancy in women with Bernard-Soulier syndrome is scattered in individual case reports and there is no consensus in the management of SBS. In some patients, the pregnancy course was uneventful while in others post partum hemorrhage was the most common complication. We report our experience about the perioperative management of a pregnant woman with Bernard-Soulier syndrome.

Bernard Soulier Syndrome associated with acute myeloid leukemia.

Bernard Soulier Syndrome is a very rare congenital bleeding disorder characterized by deficiency in glycoprotein Ib (Gp Ib) which is vital for clot formation. We present a case of 21-year-old girl with onset of menorrhagia since 4 months. She was investigated and diagnosed to be a case of AML-M4 with associated Gp Ib deficiency.

Trombocitopenia familiar de plaquetas gigantes: caso clínico / Familiar Thrombocytopenia of Giant Platelets: Clinical Case

La trombocitopenia es causa frecuente de consulta en hematología pediátrica. La mayoría de veces la baja de plaquetas es por desorden de destrucción autoinmune, raramente el padecimiento tiene un comportamiento familiar-hereditario. Se presenta el caso de una paciente de 11 años de edad, conocida desde los 3 años por trombocitopenia en el rango de 50,000/mm , fue evaluada por posibilidad de desórdenes autoinmunescon estudios inmunológicos básicos: complementos, ANA, Anti ADN, factor reumatoide y los resultados fueron normales. Tratada en varias ocasiones con prednisona oral, antiRh y con inmunoglobulina intravenosa (IGIV). Se le ha brindado seguimiento prolongado por trombocitopenia que resultó ser familiar; encontrando doce afectados, que incluyen abuela materna, madre, tíos, primos y hermana. Las características clínicas y la morfología plaquetaria fueron finalmente suficientes para conducir a diagnóstico inusual: el síndrome de Bernard-Soulier (SBS). El diagnóstico fue sugerido por el frotis de sangre periférica (FSP)...

Recurrent jejunal bleeding due to angiodysplasia in a Bernard-Soulier patient.

Angiodysplasia of the gastrointestinal tract consists of ectasia of the submucosal vessels of the bowels and may lead to acute or chronic bleeding. The presence of a coagulopathy will increase the frequency and the severity of gastrointestinal bleeding, whether spontaneously or medically. In literature, few cases of Bernard-Soulier syndrome associated with gastrointestinal angiodysplasia have been reported. We hereby present a female patient known to have Bernard-Soulier syndrome presenting with persistent bleeding due to jejunal angiodysplasia, which, to our knowledge, is the eighth reported case in the medical literature. The patient responded to tranexamic acid (antifibrinolytic agent) with gradual reduction in required transfusions until cessation of bleeding.

Occurrence of thrombosis in congenital thrombocytopenic disorders: a critical annotation of the literature.

Patients with a low platelet count are prone to bleeding. The occurrence of a thrombotic event in congenital thrombocytopenic patients is rare and puzzling. At least nine patients with Glanzmann thrombasthenia have been reported to have had a thrombotic event, eight venous and one arterial (intracardiac, in the left ventricle). On the contrary, three patients with Bernard-Soulier syndrome have been shown to have had arterial thrombosis (myocardial infarction) but no venous thrombosis. Finally, seven patients with the familiar macrothrombocytopenia due to alterations of the MYH9 gene have been reported to have had thrombosis (five myocardial infractions, one ischemic stroke, one deep vein thrombosis and one portal vein thrombosis). The significance of these findings is discussed with particular emphasis on the discrepancy between venous and arterial thrombosis seen in patients with Glanzmann thrombasthenia and Bernard-Soulier syndrome.

Myocardial infarction in two cousins heterozygous for ASN41HIS autosomal dominant variant of Bernard-Soulier syndrome.

Bernard-Soulier Syndrome is characterized by thrombocytopenia with large platelets and defective aggregation to ristocetin. The bleeding tendency is variable but may be severe. The syndrome is due to genetic defects of the GPIb-V-IX complex and it has been maintained to be protective from thrombotic events. Here we present the first two cases of documented M.I. in two cousins, heterozygous for the Arg41His mutation which is responsible for a dominant form of Bernard-Soulier Syndrome. In one of the two patients an aneurysm of the aorta was also present. The patients had a mild bleeding tendency which was severely aggravated by treatment with antiplatelet drugs. These clinical observations are in contrast with experimental studies which demonstrate that Bernard-Soulier-like strains of mice show a decreased thrombus generation in several experimental settings.

Successful perioperative management for a breast cancer patient with Bernard-Soulier syndrome.

We herein report the first case of a Bernard-Soulier syndrome (BSS) patient undergoing a surgical procedure for breast cancer. BSS is a rare hereditary thrombocytopathy associated with defects of the platelet glycoprotein complex glycoprotein Ib/V/IX and characterized by large platelets, thrombocytopenia, and severe bleeding symptoms. Because of the rarity of BSS, there are as yet no defined protocols for the perioperative management, which can be very complex and challenging in patients with coagulopathies, in particular BSS. In this case we successfully performed both an interventional examination as well as mastectomy with axillary lymph node dissection, under the preventive and intermittent transfusion of platelets. No intra- or postoperative bleeding complications occurred. Unfortunately, the patient was diagnosed as having metastatic disease involving liver, lungs, and bones 10 months after the surgery. She had received 1st, 2nd, and 3rd line chemotherapy without severe adverse events. However, gastrointestinal bleeding appeared after she was treated with 4th line chemotherapy. Finally, she succumbed 22 months after the breast surgery.

Use of Glubran 2 and Glubran tissue skin adhesive in patients with hereditary bleeding disorders undergoing circumcision and dental extraction.

Patients with bleeding disorders are at a high risk of bleeding complications during surgical procedures. Cyanoacrylates have been used successfully in many procedures and surgeries. This study was undertaken to evaluate the effectiveness of Glubran 2 and Glubran tissue skin adhesive (Glubran Tiss) in patients with hereditary bleeding disorders who underwent circumcision or dental extraction. Seven patients with congenital bleeding disorders who underwent circumcision or dental extraction were evaluated during 2009. A historical control group was considered for comparison. Glubran 2 acrylic glue was applied in cases of dental extraction and Glubran Tiss in circumcision. The patients were followed up for 6 months to detect complications. Five patients had hemophilia A, one patient had hemophilia B, and one patient had Bernard-Soulier syndrome; six were boys or men and one was a girl. Mean age was 15±8 years (range 5 to 25 years). The results in all patients under circumcision were good with significantly less factor consumption (P=0.043). But in patients who underwent dental extraction, Glubran was effective only in a 5-year-old girl with mandibular premolar tooth extraction, but not successful in a 21-year-old man with extraction of maxillary wisdom tooth. After 6 months of follow-up, no complications were observed in any patients. Our experiences in this small series of patients suggest that adjunct use of Glubran Tiss, in addition to systemic replacement therapy, can be effective in the control of bleeding in patients with hemophilia who undergo circumcision, and helps to lessen factor consumption. But, further studies with larger sample size are needed. However, our experience in using Glubran in dental extraction was not successful.