Platelet storage pool disorder: multidisciplinary planning in pregnancy.

A 32-year old primigravida woman presented for antenatal care giving a history that her mother had platelet storage pool disorder (PSPD). The patient was subsequently diagnosed with PSPD during her pregnancy and had a caesarean delivery for breech presentation at 39 weeks. In this paper, we discuss the basic science, inheritance pattern, symptoms and management of this condition, alongside the antenatal and intrapartum and postnatal management specific to it, highlighting the need for a multidisciplinary approach to care. PSPD refers to a group of rare conditions involving defects in platelet granule storage or secretion, which leads to abnormal aggregation and activation of platelets. There are both genetic and acquired forms of the condition. It is a functional platelet disorder, meaning platelet counts will usually remain in the normal range. The diagnosis may be suspected due to characteristic signs and symptoms, but patients may also be asymptomatic. There have been only a few documented cases of pregnant women with PSPD; therefore, management is not clear. Vaginal delivery is not contraindicated, however, postpartum haemorrhage should be anticipated and planned for the use of deamino D-arginine vasopressin (DDAVP), tranexamic acid, prophylactic oxytocics and prompt access to blood products, including platelets, if required. This case highlights the need for effective multidisciplinary teamwork between obstetricians, anaesthetists and haematologists to ensure high-quality care and enable careful intrapartum management planning.

Weak correlation of bleeding scores to platelet electron microscopy: A retrospective chart review of pediatric patients with delta-storage pool disorder.

BACKGROUND: Delta granule storage pool deficiency (δ-SPD) is a rare platelet disorder in which a deficiency of platelet granules leads to poor aggregation, resulting in varying clinical bleeding phenotypes. Children with δ-SPD have variable laboratory results, making the proper diagnosis and evaluation controversial. OBJECTIVES: To describe the demographic and laboratory trends of this population and to assess the value of electron microscopy in diagnostic evaluation and its correlation to bleeding symptoms. METHODS: We performed a retrospective review of 109 pediatric patients diagnosed with δ-SPD. We collected demographic information and bleeding scores using a validated bleeding assessment tool. A descriptive and exploratory analysis was performed. RESULTS: The majority of patients were female, with an average age at diagnosis of 11.61 years. Females were diagnosed at a significantly older age presenting most often with menorrhagia, while males presented most commonly with epistaxis. The majority showed normal lumiaggregometry, the mean platelet electron microscopy (PEM) value was 2.37, and the mean bleeding score was 6. Bleeding assessment tool and PEM had a significantly weak correlation. CONCLUSIONS: Patients with more dense granules per platelet had higher bleeding scores than those with fewer dense granules per platelet. The current body of evidence does not favor the use of PEM in routine clinical practice, and results are difficult to interpret. In patients with severe mucocutaneous bleeding symptoms and normal platelet aggregation studies, consideration should be given to an alternative diagnosis and further evaluation is warranted.

Variation in Platelet Delta Granules Over Time in Young Women Undergoing Evaluation for Heavy Menstrual Bleeding.

Delta-granule platelet storage pool deficiency (δ-PSPD) is a qualitative platelet function defect associated with variable bleeding phenotypes. Platelet electron microscopy (EM) is commonly utilized to evaluate for δ-PSPD, but intrapatient variability in platelet δ-granule numbers by EM is currently unknown. Fifteen young women aged 11 to 17 years presenting to a young women's hematology clinic for the evaluation of heavy menstrual bleeding underwent platelet EM testing at their initial hematology clinic visit and at 1 and 3 months later. Platelet aggregation of platelet-rich plasma by light transmission was also performed on all patients at their initial visit. Eight patients had average δ-granules per platelet consistently ≥2. Three patients were found to have average δ-granules per platelet <2 on initial testing, 2 of which reverted to ≥2 on subsequent testing. When initial average δ-granules per platelet was ≥2, initial repeat testing remained so in 83% (95% confidence interval [CI], 52%-98%) of cases and subsequent repeat testing remained so in 75% (95% CI, 43%-95%) of the cases. Platelet aggregation testing was abnormal in 53% of patients, and there was no apparent correlation between platelet EM findings and platelet aggregation testing. In this small group of young women presenting for the evaluation of bleeding symptoms, we found that almost half of the patients had substantial variability in platelet EM results. Given other identified limitations in platelet EM testing, and the intrapatient variability identified in this study, providers should use caution in utilizing EM in isolation to diagnose δ-PSPD.

Platelet granules - secretory and secretive.

The article reviews three recent publications addressing physiological and pathological aspects of platelet granules and release as well as limitations of recent screening tests for diagnosis of non-syndromic inherited δ-storage pool disease (1-3).

Usefulness of Flow Cytometric Mepacrine Uptake/Release Combined with CD63 Assay in Diagnosis of Patients with Suspected Platelet Dense Granule Disorder.

Dense granule disorder is one of the most common platelet abnormalities, resulting from dense granule deficiency or secretion defect. This study was aimed to evaluate the clinical usefulness of the flow cytometric combination of mepacrine uptake/release assay and CD63 expression detection in the management of patients with suspected dense granule disorder. Over a period of 5 years, patients with abnormal platelet aggregation and/or reduced adenosine triphosphate (ATP) secretion suggestive of dense granule disorder were consecutively enrolled. The flow cytometric assays were systematically performed to further investigate dense granule functionality. Among the 26 included patients, 18 cases showed impaired mepacrine uptake/release and reduced CD63 expression on activated platelets, consistent with δ-storage pool deficiency (SPD). Another seven patients showed decrease in mepacrine release and CD63 expression but mepacrine uptake was normal, indicating secretion defect rather than δ-SPD. Unfortunately, ATP secretion could not be measured in 7 out of the 26 patients due to insufficient sample and/or severe thrombocytopenia. This test combination provides a rapid and effective method to detect the heterogeneous abnormalities of platelet dense granule by distinguishing between storage and release defects. This combination is particularly advantageous for severely thrombocytopenic patients and pediatric patients in which only minimal sample is required.

Use of a microchip flow-chamber system as a screening test for platelet storage pool disease.

Platelet storage pool disease (SPD) is a platelet function disorder characterized by a reduction in the number or content of α-granules, dense granules, or both, and is diagnosed by specialized tests. Patients with SPD often present with prolonged bleeding time (BT), but the sensitivity and reproducibility of this test have limitations, often resulting in false negatives. It has recently been reported that an automated microchip flow-chamber system (T-TAS(®)) is useful in the assessment of anti-platelet therapy, and could have potential as a screening test for SPD. We examined the utility of T-TAS in three individuals from one family diagnosed with δ-SPD. The propositus had a mildly prolonged BT, and the standard tests for platelet function were close to the normal range. Whole blood samples were anti-coagulated with hirudin and applied to T-TAS microchips coated with collagen (PL-chips) at shear rates of 1000 and 2000 s(-1). Platelet thrombus formation (PTF) was monitored with a pressure sensor. Markedly depressed PTF was observed in all cases at both shear rates. These findings indicate that T-TAS is highly sensitive to the defect in these patients with SPD, and may represent a good candidate screening test for a wide range of platelet function disorders.

Hermansky-Pudlak syndrome: health care throughout life.

Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disease that displays genetic heterogeneity; there are 9 known subtypes. HPS is characterized by oculocutaneous albinism, a platelet storage pool deficiency and resultant bleeding diathesis, and lysosomal accumulation of ceroid lipofuscin. Patients with HPS, specifically those with the genotypes HPS-1, HPS-2, or HPS-4, are predisposed to interstitial lung disease. In addition, some patients with HPS develop granulomatous colitis. Optimal health care requires a thorough knowledge of the unique health risks and functional limitations associated with this syndrome.

Delta-storage pool disease as a mimic of abusive head trauma in a 7-month-old baby: a case report.

A seven-month-old baby was admitted to a hospital emergency department after collapsing suddenly while staying with his nanny. The baby displayed classic symptoms of shaken baby syndrome, including subdural haemorrhage, cytotoxic cerebral oedema, and bilateral retinal hemorrhages. Child protection services were informed, but both the parents and the nanny denied any involvement. In the subsequent weeks, the baby developed three other episodes of new subdural bleeding and a medico-legal investigation was started into the origin of the repeated subdural bleeding. Eventually, platelet aggregation tests and electron microscopy diagnosed a delta-storage pool disease; that is, a haemostatic disorder involving dense granules of the platelets. Initial minor blunt trauma may have resulted in subdural bleeding, while subsequent retinal haemorrhage could have been facilitated by the underlying haemostatic disorder. Delta-storage pool disease should be considered as a possible mimic of abusive head trauma similar to other rare conditions such as Menkes disease and type 1 glutaric aciduria.

Hermansky-Pudlak syndrome (HPS5) in a nonagenarian.

Hermansky-Pudlak syndrome (HPS) is an autosomal-recessive disorder clinically characterized by oculocutaneous albinism, bleeding diatheses, and lysosomal accumulation of ceroid lipofuscin, which in some cases may cause granulomatous colitis and pulmonary fibrosis. Any of these complications could result in a shortened life span for patients with HPS. We report a 92-year-old man with HPS 5 who, to our knowledge, is the oldest patient with HPS documented in the literature. This report highlights the importance of typing HPS to counsel patients regarding disease prognosis.

The Medich giant platelet syndrome: two new cases.

Hypogranular platelet disorders in human subjects are relatively rare. They include the gray platelet syndrome, αδ storage pool deficiency, the Hermansky-Pudlak syndrome, and the white platelet syndrome. Perhaps the rarest of them all is the Medich giant platelet disorder. No additional cases of this condition have been reported since description of the first case in 2004. This study describes two children with thrombocytopenia and giant, hypogranular platelets found shortly after birth. Electron microscopic study of their platelets revealed sheets of membrane wrapped into tubes resembling scrolls. The scroll-like structures were open at both ends and often filled with glycogen particles. The abnormal structures are identical to those found in the initial case. As a result, the disorder can now be referred to as the Medich giant platelet syndrome.

Platelet-mediated thrombolysis in patients with δ-storage pool deficiency: a thrombelastographic analysis.

We present the first thrombelastographic descriptions of three patients with δ-storage pool deficiency, a platelet disorder that involves a deficiency of dense granules and moderate bleeding. The patients demonstrated a 49-54% loss of platelet-mediated clot strength over a 1-2-h period after normal thrombus formation. This pattern persisted, with some attenuation of loss of strength following administration of epsilon aminocaproic acid, desmopressin and platelets for tonsillectomy. Assessment of platelet function in patients with platelet granule disorders can be accomplished with thrombelastographic methods in ambulatory and perioperative settings; however, the effects of therapy for this disorder cannot be monitored with thrombelastography without obtaining a blood sample prior to prophylactic hemostatic intervention.

[Congenital thrombocytopathies]. / Angeborene Thrombozytenfunktionsstörungen.

Inherited thrombocytopathies are much less frequent in comparison to acquired platelet function disorders. However, congenital disorders can lead to severe bleeding tendency and are often not diagnosed. They are induced by different platelet defects based on disorders of platelet adhesion, receptors, secretion and signal transduction. In some cases they are associated with thrombocytopenia, giant platelets and various comorbidities. This article gives an overview regarding diverse defects, their diagnosis and treatment options.

[Review: delta-storage pool disease]. / Mise au point : la maladie du pool vide plaquettaire.

Platelet storage pool disease is a qualitative platelet disorder associated with variable degrees of reduction in the numbers and contents of dense granules (delta-granules). Electron microscopy is the major tool for biological diagnosis. Patients presenting with this platelet disorder generally show a mild bleeding syndrome.

Diagnosing platelet delta-storage pool disease in children by flow cytometry.

Bleeding problems are symptomatic of platelet delta-storage pool diseases (SPDs) such as Hermansky-Pudlak syndrome. Although at present no cure is available for delta-SPD, early diagnosis is of great importance for prophylactic and supportive treatment. This study tested the usefulness of a flow cytometric assay for platelet serotonin in children. The assay was used to diagnose delta-SPD in a 10-year-old girl. Platelet serotonin levels were significantly lower in the patient than in all healthy control subjects (10 children and 10 adults). The serotonin results were supported by traditional tests, which are transmission electron microscopy of whole mounts and adenosine triphosphate release by lumi-aggregometry. The flow cytometric serotonin assay is a major improvement to current pediatric diagnostics. The advantages of this test are small sample volume of fresh or fixed/frozen platelets, availability of objective results within 2 hours of obtaining the blood sample, and automated analysis by flow cytometry.

Defective platelet responsiveness to thrombin and protease-activated receptors agonists in a novel case of gray platelet syndrome: correlation between the platelet defect and the alpha-granule content in the patient and four relatives.

BACKGROUND: We report a novel case of gray platelet syndrome (GPS). A 14-year-old boy had bleeding diathesis, mild thrombocytopenia, giant platelets with severe defect of alpha-granule secretory proteins, myelofibrosis and splenomegaly. METHODS AND RESULTS: Platelet function studies showed a marked reduction of aggregation and Ca(2+) mobilization by thrombin, protease-activated receptor 1 (PAR1)-activating peptide (AP) and PAR4-AP, PAR1 expression at 55% of normal levels, and a more than two hundred fold reduction of in vitro whole-blood thromboxane B(2) (TXB(2)) production. Sequencing of coding regions of the PAR1 gene failed to show abnormalities. This patient was initially classified as a sporadic case of GPS, as electron microscopy failed to identify giant platelets and/or alpha-granule deficiency in his relatives. However, further studies on the father and three other relatives showed a relative lack of platelet alpha-granule proteins by immunofluorescence microscopy, a defective platelet response to PAR4-AP, and severely reduced in vitro whole-blood TXB(2) production. On this basis, we suggest that in this family, GPS was transmitted in a dominant fashion with highly variable penetrance. CONCLUSIONS: Our study suggests that current diagnostic criteria fail to identify some patients with a mild GPS phenotype and that such patients might be identified by the methods cited above. It also better characterizes the pathogenesis of defective platelet responses to thrombin, and raises interesting questions on the correlation between abnormal PAR function and the lack of alpha-granule content in GPS.