Abstract
Gray platelet syndrome (GPS) is a rare hereditary hemorrhagic disorder characterized by macrothrombocytopenia and the absence of alpha-granules in platelets. Clinically, mild-to-moderate bleeding is the main manifestation, often accompanied by thrombocytopenia, splenomegaly, and myelofibrosis. Here, we present a case of a 15-year-old male patient with a history of hepatosplenomegaly, and thrombocytopenia for 8 years, who presented with sudden generalized abdominal pain. Despite initial suspicion of gastroenteritis, diagnostic imaging revealed an extensive hemoperitoneum. Subsequent genetic testing confirmed the diagnosis of GPS, which had not been previously identified. This case highlights the importance of considering inherited platelet disorders should be considered in adolescents with long-standing thrombocytopenia, and emphasizes the need for thorough evaluation in patients with suggestive symptoms.
Introduction
Spontaneous rupture of the normal spleen poses a diagnostic challenge, particularly when trauma is absent. Diagnosis of splenic rupture cannot always rely solely on the recognition of classical signs and symptoms such as left upper quadrant (LUQ) pain, guarding, and hemodynamic instability.
However, there are rare conditions that can predispose individuals to this complication. 1
Gray platelet syndrome (GPS) (OMIM #139090), also known as alpha(α)-reservoir disease, is a rare autosomal recessive disorder first described in the 1970s. It is characterized by the reduction or absence of platelet α granules and the proteins they contain. 2
Although splenomegaly is a known manifestation of GPS, there have been no previously reported cases of spontaneous splenic rupture as the initial presentation of GPS.
Herein, we present a case of spontaneous splenic rupture in a patient with GPS and discuss the clinical features, diagnostic challenges, and management strategies. By highlighting this case, we hope to contribute to the understanding of splenic complications in patients with rare platelet disorders like GPS.
Case Presentation
A 15-year-old male patient with a history of hepatosplenomegaly, isolated thrombocytopenia, and recurrent subjective undocumented fever for 8 years with no established diagnosis or positive family history for similar complaints, presented to the emergency department with sudden onset generalized abdominal pain, vomiting, diarrhea, and fever. On physical examination, he exhibited tachycardia, hypotension, and generalized abdominal tenderness with voluntary guarding, rectal examination showed no melena or fresh blood.
Initial laboratory tests revealed severe anemia, thrombocytopenia, leukocytosis, and metabolic acidosis. The patient was admitted to the Intensive care unit (ICU) with a provisional diagnosis of gastroenteritis with severe dehydration and metabolic acidosis and for subsequent anemia workup. Despite aggressive hydration and resuscitation measures, the patient’s abdominal pain worsened, accompanied by worsening tenderness and guarding. Ultrasonography showed moderate free fluid. A computed tomography (CT) scan was performed, revealing a large amount of high-density fluid, splenomegaly with heterogeneous hypodense lesions, and an area of liquefaction suggestive of infiltrative disease. No active bleeding source was identified (Figure 1).
Abdomen CT scan without contrast, coronal reconstruction. Showing a large amount of intraabdominal free fluid, splenomegaly with heterogeneous hypodense lesions.
Subsequent drop in hemoglobin prompted urgent exploratory laparotomy, which revealed a ruptured spleen and a significant hemoperitoneum of approximately 2 L. In addition, colon wall hematoma involving the cecum and sigmoid was noted, but no colonic perforation or injuries were identified.
Splenectomy was performed, and drains were inserted. The patient received packed red blood cells, platelets, and fresh frozen plasma during the procedure.
Postoperatively, the patient developed tachycardia, continuous oozing from multiple sites, and drain output containing blood. A second exploratory laparotomy was performed to achieve hemostasis. Coagulopathy was suspected, and the patient received additional blood products. After pediatrics consultation regarding the patient’s previous history of thrombocytopenia, he underwent bone marrow aspirate which showed that bone marrow cellularity was age-appropriate at 95% with normal trilineage hematopoiesis including megakaryocytes. No myelofibrosis or other infiltrative marrow pathology was found.
Whole exome sequencing was done to interestingly confirm the presence of autosomal recessive NBEAL2 gene homozygous mutation diagnosing GPS, in which according to the pediatrics geneticist report, this variant mutation has not been reported in the general population. Splenic histopathology revealed neutrophils below the capsular tear with intraparenchymal hemorrhage and lymphoid hyperplasia.
During the 2-month follow-up period, the patient developed partial portal vein thrombosis and was initiated on anticoagulation therapy. The patient was discharged with a lifelong penicillin prophylaxis regimen and advised to receive a pneumococcal vaccine after 2 weeks.
CBCs Results on Presentation and 1 Year Prior.
Abbreviations: CBC, complete blood count; RBC, red blood cells; MCV, mean corpuscular volume; RDW, red cell distribution width; WBC, white blood cells; MPV, mean platelet volume.
Discussion
Inherited thrombocytopenias are well recognized and have been subdivided into those with deficiency of storage organelles or defects in secretory mechanisms. 3 GPS is distinguished by moderate thrombocytopenia and platelet dysfunction, associated with their gray staining on the blood film, should not be missed if adequate attention is paid to examination of suitably prepared smears.
Gray platelet syndrome is characterized by the reduction or absence of platelet granules and associated proteins. 4 Typically, patients with GPS present in early adolescence or infancy, exhibiting bleeding tendencies, severe bleeding episodes, moderate thrombocytopenia, and the presence of excessively large agranular platelets on peripheral blood film examination. Notably, the almost complete absence of α-granules serves as a defining feature of GPS. 4
Platelet granules and their contents play a crucial role in hemostasis. 5 Normal platelets contain 6 types of granules, including dense granules, lysosomes, and peroxisomes, each serving distinct functions. Recent literature suggests the existence of subpopulations of particles with varying proteins and release mechanisms. The synthesis of platelet granule proteins occurs via endogenous synthesis through 2 pathways, with most granule proteins following 1 pathway while others, such as albumin and IgG, utilize a separate pathway. 5
Under electron microscopy, abnormal platelet granules in GPS patients reveal the deposition of dense material and debris in the Golgi area of platelets and megakaryocytes. Furthermore, the absence of microparticles and the presence of vacuoles containing dense material can be observed. Additional protein analysis of GPS patients’ platelets shows significant decreases in PDGF, TSP, and fibrinogen. 4
Neurobeachin-like 2 (NBEAL2) homozygosity for loss of function mutations is the causative pathogenesis of GPS. Most GPS-associated NBEAL2 mutations generate nonsense codons; frameshifts causing premature translation termination and/or changes in mRNA splicing was also reported, however, due to the rarity of this condition, data regarding NBEAL2 protein expression in GPS patients is very scarce. 6
Gray platelet syndrome must be considered in conjunction with immune thrombocytopenia, pseudo von Willebrand disease, thrombocytopenia with abnormal platelet function, myelodysplastic syndromes, and myeloproliferative neoplasms. Although gray platelets may be observed in normal individuals following Wright staining of peripheral blood smears anticoagulated with EDTA, a thorough evaluation of family history and other clinical features easily differentiates GPS from this benign condition. Treatment for GPS is primarily symptomatic hemostasis, with options including desmopressin, antifibrinolytics, glucocorticoids, and splenectomy. 5
Due to the rarity of GPS, related research has been limited. Early literature primarily focused on clinical analysis, ultrastructural changes, and biochemical alterations. However, recent advances in gene detection technology have facilitated breakthroughs in understanding the pathogenesis of GPS. An accurate diagnosis is crucial, as it can help avoid unnecessary splenectomy and ensure appropriate treatment options, including the infusion of allogeneic platelets when necessary. Unfortunately, the diagnosis of GPS continues to be overlooked, highlighting the importance of raising awareness within the medical community. 3
Bone marrow fibrosis commonly complicated GPS. A recent study indicated that 58% of patients had myelofibrosis at a median age of 28.5 years (range, 10-52 years). 2 No evidence of myelofibrosis was found on bone marrow examination in our patient. This case report sheds light on a rare occurrence of spontaneous splenic rupture in a patient with GPS and provides a comprehensive review of the literature as there are no other previous reports of splenic rupture in gray platelet syndrome. Recognizing the distinct characteristics of GPS, such as gray-staining platelets, moderate thrombocytopenia, and platelet dysfunction, is vital for prompt diagnosis and appropriate management. Interestingly, the diagnosis of GPS continues to be overlooked, highlighting the importance of increased awareness among health care professionals.
Conclusion
This case report highlights the occurrence of spontaneous splenic rupture in a patient with GPS. It emphasizes the need for early recognition and accurate diagnosis of GPS in patients with unexplained hepatosplenomegaly and hematological abnormalities. Effective communication between health care providers and genetic laboratories is essential for prompt identification of rare genetic disorders. Timely intervention, including splenectomy and blood product transfusions, is crucial in the management of splenic rupture. Long-term management should include prophylactic measures against infections and vigilant monitoring for thrombotic complications. Further research and case reports are warranted to enhance our understanding of the pathophysiology and optimal management strategies for GPS-associated complications.
Footnotes
Author Contributions
DB and LA contributed to writing the first draft. AH, YN, and FH contributed in data collection, and writing the final manuscript. KA supervised the project. All authors contributed to the article and approved the submitted version.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.
Ethical Approval
The study is exempt from ethical approval in our institution in Al-Makassed Hospital.
Informed Consent
Written informed consent was obtained from the patient’s father for the publication of this case report and accompanying images. The father is the legally competent person to do so in accordance with the applicable law. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.
Guarantor
YN is the guarantor of this case report, taking full responsibility for the integrity of the manuscript and ensuring that all questions related to its accuracy or completeness are addressed.
