Storage Pool Disease Research Articles

Platelet storage pool disease in hybrid rats. F1 fawn-hooded rats derived from crosses with their putative ancestors (Rattus norvegicus).

Fawn-hooded rats have a hemorrhagic disorder known as platelet storage pool deficiency. Parent stocks of Fawn-hooded, Long-Evans, and Wistar (DAB) rats and the progeny of their reciprocal crosses were studied for coat color and percentage 14C-serotonin uptake and secretion by blood platelets. Progeny of Fawn-hooded and Wistar reciprocal crosses were dark- or light-hooded, whereas all reciprocal crosses with the Long-Evans stock were dark-hooded. The light or fawn hood was significantly associated with the reduced serotonin uptake and secretion characteristic of storage pool efficiency.

Thrombocytopathic purpura associated with eosinophilia

An acquired bleeding syndrome associated with eosinophilia occurs in South-east Asia, mainly in children. Bleeding is known to result from impaired platelet function. This paper reports seven previously healthy young adults from Singapore who exhibited this syndrome. Bleeding was confined mainly to the skin and mucosal surfaces; no unusual clinical findings were noted. The bleeding tendency was transient. Intestinal helminths were found in four cases; five were mildly thrombocytopenic at onset. Platelet aggregation abnormalities were transient and the pattern suggested storage pool disease; this is discussed in relation to recent studies of the syndrome. The possible pathogenic role of eosinophilia and parasitism is also discussed.

Platelet density analysis: a tool for the detection of acquired storage pool disease in man.

This study was designed to evaluate the usefulness of platelet density analysis in the detection of acquired storage pool defects in human patients. Two groups of patients were investigated: 19 subjects affected with a myeloproliferative disorder (group I) where abnormal platelets are released from the megakaryocytes and 11 patients hospitalized in an intensive care unit (Group II) where normal platelets are injured in the circulation. Platelet density distribution after isopycnic centrifugation on a discontinuous stractan density gradient, dense granule markers (serotonin, ATP and ADP) and alpha granule markers (intraplatelet beta-thromboglobulin and platelet factor 4) were simultaneously determined. An increased proportion of the percentage of light platelets was observed in 16 patients of group I and nine of group II; an increased ATP/ADP ratio was observed in 12 patients of group I and 10 of group II. Both the tests were abnormal in 11 patients of group I and nine of group II. In group I, the level of serotonin was low and was related to the percentage of light platelets. The alpha granule specific proteins were normal in the two groups. These results indicate that platelet density analysis may serve as a screening test to detect exhausted platelets in human diseases.

Platelet density analysis: a tool for the detection of acquired storage pool disease in man

Summary. This study was designed to evaluate the usefulness of platelet density analysis in the detection of acquired storage pool defects in human patients. Two groups of patients were investigated: 19 subjects affected with a myeloproliferative disorder (group I) where abnormal platelets are released from the megakaryocytes and 11 patients hospitalized in an intensive care unit (Group II) where normal platelets are injured in the circulation. Platelet density distribution after isopycnic centrifugation on a discontinuous stractan density gradient, dense granule markers (serotonin, ATP and ADP) and alpha granule markers (intraplatelet beta‐thromboglobulin and platelet factor 4) were simultaneously determined. An increased proportion of the percentage of light platelets was observed in 16 patients of group I and nine of group II; an increased ATP/ADP ratio was observed in 12 patients of group I and 10 of group II. Both the tests were abnormal in 11 patients of group I and nine of group II. In group I, the level of serotonin was low and was related to the percentage of light platelets. The alpha granule specific proteins were normal in the two groups. These results indicate that platelet density analysis may serve as a screening test to detect exhausted platelets in human diseases.

Oculocutaneous albinism, platelet storage pool disease, and progressive lupus nephritis

Oculocutaneous albinism, platelet storage pool disease, and progressive lupus nephritis

Oculocutaneous Albinism, Platelet Storage Pool Disease, and Progressive Lupus Nephritis

Systemic lupus erythematosus (SLE) was seen in a patient with oculocutaneous albinism and platelet storage pool disease (Hermansky Pudlak syndrome). Although the patient had severely compromised platelet function, lupus nephritis developed nonetheless, which progressed to end-stage renal disease. The role of platelets in the pathogenesis of the nephritic process is discussed, and it is concluded that release of platelet granular constituents, particularly serotonin, is not required for the microvascular damage of SLE.

Platelet storage pool disease in women

Menstrual abnormalities in adolescents are usually diagnosed as dysfunctional uterine bleeding. It is generally regarded as characteristic of the young hypophyseal-pituitary system, which with time will stop naturally. The possibility of platelet storage pool diseases as a cause of irregular bleeding is often overlooked. We have treated five patients with proven or suspected platelet storage pool disease who had a history of adolescent hypermenorrhea and other bleeding. Patients with this type of history should have a comprehensive hematologic evaluation because platelet storage pool disease is not demonstrated by conventional coagulation studies. Our patients were treated with medroxyprogesterone acetate, oral contraceptives, and an avoidance of aspirin.

Bleeding Time in Rats: A Comparison of Different Experimental Conditions

The tail bleeding time (BT) in rats definitely varies according to the method applied. Of the various variables that may influence BT, we have evaluated the position (horizontal or vertical) of the tail, the environment (air or saline), the temperature (4 degrees, 23 degrees or 37 degrees C) and the type of anaesthesia. Transection of the tail tip cannot be used to screen drugs active on platelet function since it is sensitive to coagulation defects. Template BT in contrast is not modified by heparin and is sensitive to defects of platelet number and function ("storage pool disease", dipyridamole-like drugs, exogenous prostacyclin). In contrast the test fails to detect aspirin-induced platelet dysfunction. The evidence reported indicates that thromboxane A2-prostacyclin balance is not a factor regulating BT. Aspirin treatment however may be a precipitating factor when associated with other abnormalities of platelet function. Template BT is a valid screening test for platelet disorders and for antiplatelet drugs.

Prostaglandin Synthesis in Aorta and Platelets of Fawn-Hooded Rats with Platelet Storage Pool Disease and Its Response to Cholesterol Feeding

Fawn-hooded (FH) rats possess a hereditary bleeding diathesis and platelet function defect, which is presumably the result of a storage pool deficiency. In this study, we have investigated the prostaglandin synthesis capacity of platelets and aorta from FH rats as compared to Sprague Dawley (SD) rats, after 2 months on a normal or 1% cholesterol diet. No difference was found in thromboxane B2 (TXB2) production by platelets of FH as compared to SD rats. Cholesterol-feeding resulted in an increased TXB2 production by SD platelets, but not FH platelets. FH rat aorta was found to convert significantly less arachidonic acid (AA) to 6-keto-prostaglandin-F1 alpha (PGF1 alpha) and cholesterol-feeding stimulated this reduced capacity. In contrast, cholesterol-feeding in the SD rat reduced aortic 6-keto-PGF1a production. Aggregation of platelet-rich plasma by AA was enhanced in the cholesterol-fed FH rat. This result suggests the possibility of an influence of platelet aggregability on aortic prostacyclin production.

Haemorrhagic thrombocytopathy associated with dilatation of the platelet--membrane complex.

We evaluated eight patients from four families because of a history of excessive bleeding. Most patients had prolonged bleeding times, absent secondary wave of platelet aggregation in response to epinephrine, collagen and adenosine diphosphate (ADP), and defective 14C-serotonin release and platelet factor 3 availability. These findings are characteristic of a platelet release defect. Electron-microscopy examination of the platelets of seven patients revealed a common abnormality. From 30% to 70% of the platelets in any given sample exhibited a prominent membrane complex and dilated, tortuous surface-connected canalicular system ('swiss-cheese' platelet). In two patients there was coincident storage-pool disease, but the remainder had adequate dense bodies and a normal ratio of ATP to ADP. SDS-polyacrylamide gel electrophoresis of platelet proteins and glycoproteins showed no abnormalities. The patency of the canalicular system was demonstrated in one patient by the observation that dense bodies appeared in the cannaliculi and outside the platelets following collagen-induced aggregation of polylysine-treated platelets. Since platelet-aggregation responses to the calcium ionophore A23187 were normal, we conclude that the defective platelet function in these patients may be due to impaired calcium mobilization from the morphologically abnormal membrane complex.

Platelet adenine nucleotides and arachidonic acid metabolism in the myeloproliferative disorders

Platelet aggregation to collagen, adenosine diphosphate and arachidonic acid has been investigated in 17 patients with various myeloproliferative states. Ten patients who had abnormalities of aggregation to collagen and/or ADP were also all found to have diminished intracellular and releasable adenine nucleotides but aggregation to arachidonic acid was normal. Seven other patients who had normal aggregation responses had normal platelet adenine nucleotides. In the ten patients with abnormal platelet function platelet cyclo-oxygenase activity was normal but in two patients platelet lipoxygenase activity was reduced. Thromboxane B 2 production during collagen stimulation was found to be normal suggesting normal release of endogenous arachidonic acid. These findings suggest that the platelet defect in myeloproliferative states is due to an acquired storage pool disease.

Platelet abnormalities in thermal injury. Study of platelet-dense bodies stained with mepacrine.

A study on platelets was done in 13 patients with severe burns during the period immediately following the thermal injury. For each patient it is possible to define a period, usually beginning around the 8th day postburn, characterised by decrease of ADP and 5-HT in the platelets and by an increase in the ATP/ADP ratio. These abnormalities strongly suggest an acquired storage pool disease. Study of the dense bodies by mepacrine labelling during this period suggests that the platelets release their contents but retain the structures labelled by mepacrine.

The Mouse Pale Ear Pigment Mutant as a Possible Animal Model for Human Platelet Storage Pool Deficiency

The mouse pigment mutant pale ear, ep/ep, which has a defect in kidney lysosomal enzyme secretion, had prolonged bleeding on experimental injury. Platelet counts and platelet protein did not differ from normal. There was, however, a deficiency in the platelet dense granule contents, serotonin, ATP, and ADP. Furthermore, a marked reduction of platelet dense granules was observed by electron microscopy. The results suggest that pale ear is a useful animal model in the study of platelet storage pool disease. Studies on this mutant and other pigment mutants have established that one gene can regulate at least three subcellular organelles, including the melanosome, the lysosome, and the platelet dense granule.

The mouse pale ear pigment mutant as a possible animal model for human platelet storage pool deficiency

The mouse pigment mutant pale ear, ep/ep, which has a defect in kidney lysosomal enzyme secretion, had prolonged bleeding on experimental injury. Platelet counts and platelet protein did not differ from normal. There was, however, a deficiency in the platelet dense granule contents, serotonin, ATP, and ADP. Furthermore, a marked reduction of platelet dense granules was observed by electron microscopy. The results suggest that pale ear is a useful animal model in the study of platelet storage pool disease. Studies on this mutant and other pigment mutants have established that one gene can regulate at least three subcellular organelles, including the melanosome, the lysosome, and the platelet dense granule.

One more variety of 'storage pool disease'

One more variety of 'storage pool disease'

'Storage Pool Disease' of Platelets

A women with congenital cavernous hemangiomas and a bleeding diathesis since childhood was found to have a qualitative platelet defect characterized by the absence of a second-phase aggregation induced by epinephrine, adenosine diphosphate (ADP), and collagen, accompanied by decreased levels of adenosine triphosphate (ATP) and ADP, with a high ATP-ADP ratio consistent with the diagnosis of "storage pool disease" of the platelets. There was no evidence of disseminated intravascular coagulation or circulating antiplatelet antibodies. The bleeding tendency responded to platelet transfusion.

'Storage pool disease' of platelets. Association with multiple congenital cavernous hemangiomas

'Storage pool disease' of platelets. Association with multiple congenital cavernous hemangiomas

Storage pool disease: comparative fluorescence microscopical, cytochemical and biochemical studies on amine-storing organelles of human blood platelets.

The platelet content of ATP, ADP, serotonin (5-HT), dopamine, noradrenaline and adrenaline as well as the net uptake of radiolabelled 5-HT and mepacrine were subnormal in six patients with Storage Pool Disease (SPD). Fewer amine-storing organelles were found by fluorescence microscopy with the fluorescent probe mepacrine and by electron microscopy with a cytochemical (uranaffin) reaction specific for 5'-phosphonucleotides. Both methods showed that SPD platelets have atypical organelles with a reduced capacity to store amines, 5'-phosphonucleotides and mepacrine. The changes were most marked in platelets of the two patients who also had oculocutaneous albinism.

Release of VIII R:Ag and VIII R:WF during thrombin and collagen induced aggregation

Platelet VIII R:Ag and VIII R:WF release was measured during platelet aggregation using collagen and thrombin. In a washed platelet system it was shown that normal platelets released one fourth to one third of the VIII R:Ag and VIII R:WF measured in the platelet extract after freezing and thawing. Platelets from patients with storage pool disease or patients treated with aspirin did not release VIII R:Ag or VIII R:WF using collagen and only a small amount with thrombin. VIII R:Ag and VIII R:WF were not released from platelets of patients with von Willebrand disease even from platelets of those patients who showed normal amount of platelet VIII R:Ag.

Detection of an Acquired Platelet Storage Pool Disease in Three Patients with a Myeloproliferative Disorder

Detection of an Acquired Platelet Storage Pool Disease in Three Patients with a Myeloproliferative Disorder