Silent hemorrhage: Unraveling the insidious rectal bleeding in hermansky-pudlak syndrome Free

First described in 1959, Hermansky-Pudlak Syndrome (HPS) is an autosomal recessive disorder that affects vesicle biogenesis, resulting in dysfunction of lysosome-related organelles, including melanosomes and platelet-dense bodies. HPS is a rare disorder, with an estimated prevalence of 1 in 1,000,000 people worldwide. Affected platelets lack delta-dense granules, which contain crucial substances like serotonin, calcium, and adenine nucleotides necessary for platelet aggregation during blood clotting. Oculocutaneous albinism, excessive bleeding, and systemic complications due to the buildup of ceroid lipofuscin present variably depending on the subtype. Eleven HPS types are recognized, with types 1, 2, 4, and 10 linked to severe disease.

A 69-year-old Puerto Rican male with a known medical history of albinism, hypercholesterolemia, hypothyroidism, irritable bowel syndrome, diverticulosis, and presumed Von Willebrand Disease (VWD) presented to the hematology service for evaluation of prolonged bleeding. This patient reported experiencing notable epistaxis and excessive bruising in childhood. He added that his skin was lighter compared to his eleven siblings. Past surgical history is significant for bleeding complications following routine procedures, such as elective cholecystectomy, nail avulsion, and third molar exodontia. Family history revealed that the mother and father were second-degree cousins. In 2021, this patient began experiencing intermittent and profuse rectal bleeding lasting several days. In 2024, he presented to the emergency department for rectal bleeding lasting three days. Contrast computed tomography of the abdomen and pelvis did not identify the source of extravasation. Complete blood count showed a downtrend in hemoglobin and hematocrit. Platelet counts were within normal limits. Due to persistent hematochezia, evaluation by colonoscopy was pursued. Colonoscopy revealed extensive diverticula involving most of the colon and large first-degree internal hemorrhoids. Outpatient work-up for VWD did not demonstrate any abnormalities in Factor VIII level, Von Willebrand antigen, or activity. Electron microscopy revealed the absence of dense bodies in the platelets. Genetic sequencing by the Mayo Clinic confirmed the diagnosis of HPS. Homozygous deletion of the HPS3 gene identified in this analysis is common in individuals of central Puerto Rican ancestry.

Yair et al. first described a mutation in a new gene responsible for a uniquely milder form of the disease found in a genetic isolate from central Puerto Rico (HPS-3). Clinically, Type 3 presents with milder oculocutaneous albinism, bleeding propensity, and no pulmonary complications. Colitis has been reported, although not currently supported by any available literature. Hence, there is a favorable prognosis in this subset. HPS-3is not confined to individuals of Puerto Rican descent. Research conducted by Huzing et al. identified eight patients of Ashkenazi Jewish heritage who also presented with this condition. This finding underscores the significance of the founder effect and highlights the importance of increasing awareness of HPS among other populations. Of those, no colitis was associated. Hussain et al. also conducted a retrospective study to demonstrate the occurrence of colitis and its relation to genotype in 2006; 3 of 3 patients having undergone endoscopic evaluation with HPS-3 had no histological evidence of colitis.

Attention is given to those in pregnancy, menstruation, and patients' forgoing surgical procedures. Anti-fibrinolytics, such as aminocaproic acid and tranexamic acid, can decrease bleeding. Perioperatively, HPS patients should receive desmopressin acetate (DDAVP), but responsiveness testing should be conducted prior, as not all affected respond. Recombinant factor VIIa has also been used preemptively with success. A patient undergoing total thyroidectomy received four 120 μg/kg doses every two hours and six 100 μg/kg doses every three hours without any postoperative bleeding. Another patient with therapy-refractory menorrhagia was treated with a single injection of 100 μg/kg body weight recombinant factor. This case highlights the need for more recognition of a highly variable phenotypically expressed congenital platelet disorder. Screening patients with hypopigmentation and bleeding disorders may be beneficial and appropriate. Identification would assist in prognosis as well as prophylaxis against severe bleeding.