PAROXYSMAL COLD HEMOGLOBINURIA 691 PAPPENHEIMER BODIES Basophilic red blood cell inclusions, often in small clusters near the periphery of the cell. They are composed of ferritin aggregates, or of mitochondria or phagosomes containing aggregated ferritin. They often occur in reticulocytes . The associated disorders include: Splenectomy (post) Sideroblastic anemia Lead toxicity PARAPROTEINEMIA See Monoclonal gammopathies . PARIETAL CELL ANTIBODIES See Gastric disorders . PAROXYSMAL COLD HEMOGLOBINURIA (PCH) A very rare form of cold autoimmune hemolytic anemia characterized by acute episodes of massive hemolysis following cold exposure. The disease was frequently diag- nosed during the latter half of the 19th century because of its supposed association with congenital or tertiary syphilis. Now PCH occurs as an acute febrile illness associated with viral syndromes, particularly the childhood exanthems. There is usually one self-limited attack of acute intravascular hemolysis with hemoglobinuria . The prognosis is good. A chronic form of the disorder is characterized by recurrent episodes of hemolysis precipi- tated by exposure to cold temperature. The cause of autoantibody production in PCH is unknown. There are no known racial or genetic predispositions. During severe chilling, blood flowing through skin capillaries is exposed to low temperatures. The antibody (see Donath-Landsteiner test ) is biphasic, and early-acting complement components bind to red blood cells at lowered temperatures. Upon return of the cells to 37°C in the central circulation, the cells are rapidly lysed by activation of the terminal complement sequence through C9. The Donath-Landsteiner antibody dissociates from the red blood cells at body temperature. Constitutional symptoms are prominent during the paroxysm. After cold exposure, the patient develops aching pains in the back or legs and abdominal cramps. Chills and fever follow. Urine passed after onset of symptoms typically shows hemoglobinuria, which, with the general symptoms, lasts a few hours. The hemoglobin level can drop rapidly in a severe attack. Chronic anemia, raised reticulocyte count , hemoglobinemia, and hyperbilirubinemia may be present, depending on the frequency and severity of attacks. Complement titers are depressed during an acute episode because of consumption in the hemolytic reaction. Spherocytes and erythro- phagocytosis by monocytes and neutrophils are typically found on the blood film during an attack. Leukopenia is seen early in the attack, followed by neutrophilia . The urine may be dark red or brown due to the presence of hemoglobin or methemoglobin. The direct antiglobulin (Coombs) test is positive during and following a paroxysm, but negative between attacks. The positive reaction is due to coating of surviving red cells with complement. The Donath-Landsteiner antibody is a nonagglutinating IgG that binds 3393_book.fm Page 691 Thursday, October 25, 2007 5:17 PM 692 PAROXYSMAL NOCTURNAL HEMOGLOBINURIA in the cold and readily dissociates at room temperature and above. The antibody is detected in vitro by the biphasic Donath-Landsteiner test. In this test, the patient’s fresh serum is incubated initially with red cells at 4°C and the mixture warmed to 37°C. Intense hemolysis occurs. Antibody titers rarely exceed 1:16. The Donath-Landsteiner antibody usually has specificity for the P blood group antigen. This is a unique IgG complement- activating antibody that hemolizes P1 and P2 red cells but not p or Pk cells. The anti-P autoantibody usually binds at temperatures below 20°C. If the cells are exposed to anti- P at low temperatures in the presence of complement, C1q attaches to the membrane, and if the suspension is warmed to 25°C or higher, the complement activity concludes with hemolysis. PCH must be distinguished from chronic cold-agglutinin disease , which manifests episodic hemolysis and hemoglobinuria, a distinction made primarily in the laboratory. Patients with PCH lack high titers of cold agglutinins . Other disorders with similar clinical presentation are distinguished by history and by appropriate serologic studies. Acute attacks can be prevented by avoidance of cold. Further treatment is rarely neces- sary. If for some reason red blood cell transfusion is required, P-antigen-positive cells would have to be used due to the rarity of P-antigen-negative donors. Blood should be transfused using an in-line blood warmer at 37 ° C and keeping the patient warm. Most patients with chronic idiopathic PCH survive for many years despite occasional paroxysms of hemolysis. Splenectomy is not likely to be of help, but plasmapheresis may temporarily reduce hemolysis. PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (PNH) An acquired intrinsic red blood cell defect due to hematopoietic stem cell deficiency of glycosylphosphidylinositol (GPI). It is postulated that an environmental toxin induces a mutation of PIG-A gene of hematopoietic stem cells. The abnormal clone expands within the bone marrow, probably due to decreased NK-cell activity compared with normal cells, thus replacing the hematopoietic stem cell pool and giving rise to aplastic anemia , dys- erythropoiesis ( myelodysplasia ), or to PNH, where red blood cells, and to a lesser extent granulocytes and platelets, have a deficiency of surface proteins, leading to complement - mediated lysis. 406,407 Pathophysiology The characteristic defect of increased sensitivity of red blood cells to complement-mediated lysis, either by the classical or by the alternative pathways. This can be precipitated by various factors: Lowering of pH ( acidified serum test ) Reduction in ionic strength ( sucrose lysis test ) Coating of red blood cells with antibody such as anti-A Increase in magnesium concentration Treatment with cobra venom Previously, it was thought that lowering of blood pH during sleep explained nocturnal hemoglobinuria, but this is disputed. Several red blood cell membrane proteins attached to GPI are deficient in PNH, e.g., leukocyte alkaline phosphatase, acetyl cholinesterase, urokinase plasminogen activator, 3393_book.fm Page 692 Thursday, October 25, 2007 5:17 PM PAROXYSMAL NOCTURNAL HEMOGLOBINURIA 693 and several other proteins that regulate complement function. The hereditary absence of CD59 antigen in these patients is critical in producing clinical PNH with a significant degree of hemolysis. The conversion of N-acetylglucosamine and glucosamine-phospho- inositol to monolipids is defective, so that GPI cannot be manufactured normally. Absence of “decay accelerating factor” (DAF/CD55) — which acts to accelerate the destruction of erythrocyte-bound C3 convertase, leading to its action on surface-bound C3d being amplified — was thought by some to be the basic pathologic lesion. Granulocytes and platelets, and possibly lymphocytes, also show increased complement-mediated lysis. Occasionally the abnormal clone disappears completely, but transition to an acute leu- kemia, though rare, has been well documented. Clinical Features Although the classical passage of dark brown urine first thing in the morning occurs in only a minority of patients, all show clinical or laboratory signs of a chronic intravascular hemolysis . This can be initiated by: Episodes of infection Strenuous exercise Surgery Injection of radiological contrast dyes Transfusion of whole blood Free plasma hemoglobin absorbs nitric oxide that is essential for smooth-muscle func- tion. Iron lost in the urine as hemosiderin or hemoglobin results in iron deficiency , which may be exaggerated by gastrointestinal tract bleeding associated with severe thrombocy- topenia from bone marrow aplasia or dyserythropoiesis. Treatment with oral iron has been known to exacerbate the hemolysis, mainly because the iron raises erythrocyte output, including PNH cells. This added hemolysis is not clinically significant. Symptoms during a paroxysm are caused by disturbances of smooth-muscle function. They include abdominal pain of a colicky nature, and there may be abdominal tenderness, dysphagia, erectile failure, and severe lethargy. Renal tract manifestations include hypo- posthenuria, abnormal tubular function, and impaired creatinine clearance, though sig- nificant renal impairment is very rare. Severe headaches and pain in the eyes are common. The most serious complication is venous thromboembolic disease due to platelet GPI deficiency and activation by complement. There is a predilection for intra-abdominal veins. Hepatic vein thrombosis (Budd-Chiari syndrome) carries a particularly poor prognosis. Microthrombi in the pulmonary vasculature results occasionally in pulmonary hyperten- sion. Thrombosis of major cerebral vessels is rare, but in some the headaches are due to thrombosis of small vessels in the cerebral cortex. Pregnancy with PNH carries a high risk of severe thrombotic complications. Anticoagulation throughout pregnancy may be required. The clinical course is variable. Median survival is 10 years, the common causes of morbidity and mortality being thrombosis and bone marrow failure. Laboratory Features Anemia of variable severity occurs in most, but not all, patients, and is usually associated with a mild-to-moderately raised reticulocyte count . This may be associated either with 3393_book.fm Page 693 Thursday, October 25, 2007 5:17 PM 694 PARVOVIRUS a macrocytic anemia or with myelodysplasia (MDS), but if there is severe iron deficiency , there will be a microcytic anemia . Neutropenia and thrombocytopenia are usually present, but seldom to a severe degree. The bone marrow usually shows a variable degree of erythroid hyperplasia, but it may be hypoplastic or show dyserythropoietic changes. In iron-deficient patients, stainable iron is not present. Hemoglobinuria occurs in a minority of patients, but hemosiderinuria is usually demonstrable. Screening tests are the acidified serum test and the sucrose lysis tests . Confirmation of diagnosis is demonstration of a deficiency of GPI-linked molecules on the surface of hematopoietic cells by flow cytometry demonstration of immunophenotypes CD14 + , CD16 + , CD24 + , CD55 + , and CD59 + . Management Supportive care with red blood cell transfusion is often needed. Theoretically, washed red blood cells should be used to avoid transfusing complement, but unwashed packed red blood cells are probably equally satisfactory. Iron deficiency should be corrected by attention to the source of red blood cell loss as well as giving oral iron supplements. Lifelong prophylactic oral anticoagulation with warfarin is needed for those patients experiencing recurrent venous thromboses. Treatment of the Budd-Chiari syndrome is by thrombolytic therapy followed by oral anticoagulants. Because of the high risk of throm- bosis, where possible, elective surgery should be avoided. Androgens and glucocorticoids have been used with mixed results and are probably only useful as short-term measures in patients with aplastic anemia, where they occasion- ally result in improvement of peripheral-blood counts. Erythropoietin may benefit a minority of patients. Trials of complement inhibitor eculzimab are in progress; preliminary results show excellent control of hemolysis. Allogeneic stem cell transplantation is poten- tially curative in younger patients, though overall results have been rather disappointing compared with those obtained for uncomplicated aplastic anemia. PARVOVIRUS Direct infection of erythroid precursors by a small, nonenveloped single-stranded DNA virus consisting of 5500 nucleotides. A particular strain, parvovirus B19, is pathogenic to humans and causes a variety of different diseases (see Table 125). Their lack of envelope and small DNA content render them extremely stable to heat and lipid solvents, and hence they are readily transmitted by blood transfusion and coagulation factor concentrates (see Transfusion transmitted infection). Immunoglobulin (Ig) G and IgM can be detected by enzyme-linked immunosorbent assay and immunofluorescence. TABLE 125 Disorders Induced by Parvovirus B19 Infection Fifth disease a Polyarthropathy Pure red cell aplasia Hydrops fetalis Transient erythroblastopenia of childhood a Also called erythema infectiosum or “slapped cheek” disease. 3393_book.fm Page 694 Thursday, October 25, 2007 5:17 PM P BLOOD GROUPS 695 About 50% of the population has serological evidence of past infection. Immunocom- petent patients develop acute self-limiting illnesses, or even asymptomatic seroconversion, and no specific therapy is required. Those who have a chronic hemolytic anemia, e.g., hereditary spherocytosis and sickle cell disease, may suffer from infections that cause erythroid aplastic crisis. Most patients have a spontaneous remission, but some have a persistent pure red cell aplasia. Characteristically, giant pronormoblasts are found in the bone marrow of acutely infected patients, with confirmation provided by detection of specific IgM or IgG in the serum and by a polymerase chain reaction (PCR) in patients unable to mount an immune response. PATHOGEN-RECOGNITION MOLECULES (PRM) Receptors on the surface of cells, particularly histiocytes (macrophages), that recognize pathogens. These can enter the cell and either become resident in the cytoplasm or are destroyed. Toll-like receptors (TLRs), upon activation, induce intercellular signaling pathways that activate microcidal responses. Other PRMs are nucleotide-binding oligomerization domain proteins (NODs). Genetic mutations affecting NODs are associated with Blau’s syndrome (arthritis, skin rashes, and uveitis), Crohn’s disease (see Intestinal tract disor- ders — chronic inflammatory disease), and sarcoidosis. P BLOOD GROUPS A specific antigen–antibody system arising from the P and globoside blood group systems and the globoside collection of blood group antigens; located on red blood cells (RBCs), lymphocytes, and monocytes (see Blood groups). Biochemistry Like the ABO(H), Lewis, and I blood group antigens, the P blood group antigens are carbohydrates. Production of the Pk, P, and P1 antigens is through different biosynthetic pathways: the P1 antigen has been assigned to the P blood group system, the P antigen to the globoside system, and Pk and Luke (LKE) antigens to a separate “collection.” Pk and P antigens are also detected on erythroblasts, fibroblasts, and vascular endothelium cells. Genetics and Phenotypes Biosynthetic pathways are complex and incompletely understood. The phenotypes are summarized in Table 126. As with ABH antigens, genes code for glycosyl transferases that catalyze the transfer of monosaccharides onto carbohydrate precursors. TABLE 126 Phenotypes of the P and Associated Blood Group Systems RBC Phenotype Frequency in Caucasians P1 + (P1) 75% P1 − (P2) 25% P1k very rare P2k very rare p very rare 3393_book.fm Page 695 Thursday, October 25, 2007 5:17 PM 696 PEARSON-MARROW-PANCREAS SYNDROME Antibodies and Their Clinical Significance Anti-P1 is sometimes found in the plasma of P1 (P2) persons. The antibody is almost always naturally occurring and is of the IgM class. Anti-P1 is sometimes errone- ously called anti-P (see below). The apparent incidence of anti-P1 is dependent upon the pretransfusion testing meth- ods in use, as most examples show activity only at temperatures below 37°C. At temperatures below 20°C, anti-P1 can be demonstrated in a high proportion of patients’ sera. Anti-P1 only very rarely causes hemolytic blood transfusion complications if incom- patible RBCs are transfused. It can be ignored for the purposes of transfusion if it is inactive at 37°C in direct agglutination or antiglobulin methods. Provision of blood for patients with anti-P1 should not be difficult. Anti-P1 does not cause hemolytic disease of the newborn (HDN) for the same reasons that ABO HDN is rare (see ABO (H) blood groups). Anti-PP1Pk (anti-Tja) is regularly found in the plasma of individuals with the very rare phenotype p, and anti-P is regularly found in P1k and P2k individuals. These antibodies can be either IgM or IgG. Anti-Tja and anti-P are usually complement binding and hemolytic in vitro. They can give rise to severe blood transfusion complications involving intravascular hemol- ysis if incompatible RBCs are transfused. It is therefore essential to select alloge- neic blood of the correct phenotype, but the rarity of these phenotypes is such that this will not always be possible. Autologous blood transfusion will be the method of choice whenever possible. There appears to be a significantly increased risk of spontaneous abortion in women who have the p phenotype, in particular if anti-Tja of the IgG3 subclass is present. Patients with paroxysmal nocturnal hemoglobinuria usually have auto anti-P that acts as a biphasic hemolysin. PEARSON-MARROW-PANCREAS SYNDROME See Sideroblastic anemia. PEL-EBSTEIN FEVER See Hodgkin disease. PELGER-HUËT ANOMALY A nuclear hypolobulation of granulocytes (best seen in neutrophils). The condition can be inherited or acquired. The inheritance is autosomally dominant (incidence 1:1000 to 1:10,000), and typically bilobed neutrophils are seen, with occasional mononuclear forms (Figure 95). In the rare homozygous patient, all neutrophils are mononuclear. Pelger-Huët cells appear to be functionally normal, and increased infections are not seen. The acquired form (often called pseudo-Pelger-Huët cells) classically occurs in myelo- dysplasia, but other conditions, e.g., myxedema, can also give rise to this appearance. The Pelger-Huët cells of myelodysplasia are often hypogranular and functionally defective. 3393_book.fm Page 696 Thursday, October 25, 2007 5:17 PM PERIPHERAL-BLOOD-FILM EXAMINATION 697 PELIOSIS The occurrence of cystic spaces in the spleen and liver filled with blood. They are usually an incidental finding in the parafollicular areas of lymphoid follicles, particularly in the marginal zones. They can cause hepatosplenomegaly and are associated with thromb- ocytopenia. PENTOSE PHOSPHATE PATHWAY See Red blood cell — metabolism. PERFORINS Monomeric proteins present in the granules of NK lymphocytes and cytotoxic T-lympho- cytes. They are probably produced in the spleen. They are activated by the cascade of serine proteases, one of which is immunologically homologous with the ninth component of complement, to form pores in the target cell membrane. Deficiency of perforins is an autosomally recessive disorder of dysregulated immune response: familial hemophagocytic lymphohistiocytosis. 262a The patients have a febrile illness with hepatosplenomegaly, pancytopenia, hyperglyceridemia, CSF pleocytosis (50%), and widespread neurological abnormalities. The bone marrow is hypoplastic or aplastic, with hemophagocytosis evident. 408 PERIPHERAL-BLOOD-FILM EXAMINATION Microscopic examination of a stained blood film. This provides information for: Diagnosis of blood disorders Checking the blood count parameters obtained from automated instruments Blood films are routinely prepared from EDTA specimens up to 3 h following venepunc- ture. Alternatively, they can be prepared using freshly collected capillary or nonanticoag- ulated venous blood. Use of nonanticoagulated blood results in platelet clumping. The traditional wedge smear remains the most popular. It should be 2.5 to 3.0 cm long and 2.0 to 2.5 cm wide and have a smooth surface free from holes and ridges with a short feather edge. The film is stained by a Romanowsky method, the principal components of which are Azure B and Eosin Y. FIGURE 95 Diagrammatic representation of nuclear shapes in Pelger-Huët anomaly. 3393_book.fm Page 697 Thursday, October 25, 2007 5:17 PM 698 PERIPHERAL-BLOOD-FILM EXAMINATION Low-power examination is undertaken first to ensure satisfactory distribution of cells. The feather edge should then be examined to exclude the presence of platelet clumping or leukocyte clumping, which would render platelet and differential leukocyte counting unreliable. A readable area of the film is where red cells are evenly distributed, just touching but without appreciable overlap. Systematic examination of red cells, leuko- cytes, and platelets is then undertaken, 409 with particular attention to the following characteristics: Red blood cells 1. Depth of staining (hemoglobin content) • Normochromia, hyperchromia • Anisochromia, polychromasia • Hypochromia 2. Size of cells • Normocyte (discocyte), macrocyte • Microcyte, dimorphism • Anisocytosis 3. Poikilocytosis Regular • Codacyte (target cell) • Dacrocyte (teardrop cell) • Drepanocyte (sickle cell) • Elliptocyte (ovalocyte) • Leptocyte (thin cell) • Microspherocyte • Spherocyte • Pincer cell • Stomatocyte Irregular • Crenated cells (artifacts) • Pyknocyte (irregular contracted cell, bite cell) • Spiculated (Burr) cells: acanthocyte, echinocyte • Fragmented cells: keratocyte (horn cell), schistocyte (helmet cell) 4. Inclusions • Nucleated red blood cell (orthochromatic normoblasts) • Howell-Jolly bodies • Basophilic stippling (punctate basophilia) • Heinz bodies • Pappenheimer bodies • Malaria Plasmodium spp. • Bartonella parasites • Babesia parasites 3393_book.fm Page 698 Thursday, October 25, 2007 5:17 PM PERIPHERAL T-CELL LYMPHOMA, UNSPECIFIED 699 Granulocytes (neutrophils, eosinophils, and basophils) 1. Nucleus • Segmentation — hypersegmented and band-form neutrophils • Pelger-Huët anomaly • Pseudo-Pelger cells • May-Hegglin anomaly • Pyknocytosis 2. Granules • Toxic granulation • Alder-Reilly anomaly 3. Vacuoles 4. Inclusions — bacteria, ehrlichosis morulae 5. Dohle bodies 6. Immature granuloctyes (myeloblasts, myelocytes, metamyelocytes) Mononuclear cells (monocytes and lymphocytes) 1. “Reactive” lymphocytes — plasma cells, Mott cells 2. Atypical mononuclear cells 3. Immunoblasts (Turk cells) 4. Lymphoblasts, monoblasts, lymphoma cells Platelets 1. Giant platelets — Bernard-Soulier syndrome 2. Granular depletion — Gray platelet syndrome 3. Platelet clumping 4. Platelet satellitism PERIPHERAL-BLOOD STEM-CELL TRANSPLANTATION (PBSC transplantation) See Autologous bone marrow transplantation. PERIPHERAL T-CELL LYMPHOMA, UNSPECIFIED (Rapaport: diffuse poorly differentiated lymphoma, diffuse mixed lymphocytic-histiocytic lymphoma; Lennert: lymphoepithelioid cell lymphoma; Lukes-Collins: T-immunoblastic lymphoma) See also Lymphoproliferative disorders; Non-Hodgkin lymphoma. A predominantly nodal heterogeneous group of aggressive T-cell lymphomas. They are characterized by having widespread disordered lymphoid follicles showing a diffuse or occasionally interfollicular cellular proliferation. This ranges from atypical small cells to medium-sized or large cells; most contain a mixed population of small and large atypical cells, and even those with a predominance of medium-sized or large cells often contain a broad spectrum of cell sizes. The neoplastic cells often have irregular nuclei and vary considerably in size and shape, with occasional large, hyperchromatic cells that may resemble Reed-Sternberg (RS) cells, but true RS cells are rare or absent. Admixed eosino- phils or epithelioid histiocytes may be numerous. There is a T-zone variant and a lym- phoepithelioid cell variant. The immunophenotype of the tumor cells shows variation in 3393_book.fm Page 699 Thursday, October 25, 2007 5:17 PM 700 PERNICIOUS ANEMIA T-cell-associated antigens (CD3 +/− , CD2 +/− , CD5 +/− , CD7 −/+ ) and B-cell-associated antigens. Most nodal cases are CD4 + , CD8 − , and CD30 + in the large-cell variants. Cytogenetic analysis usually shows rearrangement of TCR genes, with Ig genes being germline. The cellular origin is a peripheral T-cell in various stages of transformation. Clinical Features These comparatively uncommon tumors comprise less than 15% of lymphomas in Europe and the U.S., but are more common in other parts of the world. Patients are usually adults presenting with nodal involvement but also with hepatosplenomegaly, bone marrow infiltration, and other visceral disturbances. Occasionally, eosinophilia or hematophago- cytic syndromes are present. The clinical course is usually aggressive and the prognosis poor, with overall survival rates of 30% at 5 years, even with treatment, as relapses are more common than in B-cell lymphomas of similar histologic grades. Staging See Lymphoproliferative disorders. Treatment See also Non-Hodgkin lymphoma. The standard treatment strategy has been CHOP chemotherapy (see Cytotoxic agents) at initial presentation and peripheral stem cell transplantation (PSCT) for relapsed patients. PERNICIOUS ANEMIA See Addisonian pernicious anemia. PETECHIAE Red or bluish lesions of less than 3 mm in diameter visible in the skin, deep to the epidermis. They fail to disappear upon application of pressure, as they occur due to extravasation of blood. In contrast, lesions with an intact vasculature, vascular lesions, will blanch upon pressure. Petechiae tend to occur in crops and resolve over 3 to 5 days. They are a common manifestation of purpura (see Hemorrhagic disorders). PEUTZ-JEGHER’S SYNDROME See Oral mucosa disorders. PHAGOCYTOSIS The internalization of particulate matter by cells into cytoplasmic vesicles. It is a form of endocytosis in which large particles (e.g., cell debris) are taken up and engulfed into a cell. The particle is progressively surrounded by cell pseudopodia in which actin-binding proteins accumulate. Lysosomes fuse with the particle, so that the resulting endocytic vesicle is converted into a phagosome. Phagocytes are neutrophils, monocytes, and histiocytes (macrophages) derived from the same myeloid progenitor stem cell. Activation of phagocytes initiates “respiratory burst,” which kills phagocytosed organisms. 3393_book.fm Page 700 Thursday, October 25, 2007 5:17 PM [...]... for platelet-specific alloantibodies and platelet autoantibodies is performed using the indirect platelet immunofluorescence test, although this also detects HLA antibodies Therefore, a test for platelet-specific antibodies, such as the monoclonal antibody-specific immobilization of platelet antigen assay, should also be used Immune-mediated platelet refractoriness is managed by providing HLA-matched platelets... immune, which leads to partial release of platelet granule contents Continued circulation of such depleted platelets can lead to bleeding through a partial storage-pool-like defect Chronic hypoglycemia can produce a similar defect by failure of normal-platelet glucosebased metabolism Adverse drug reactions174,412 (see Table 1 28) comprise the commonest causes of an acquired platelet-function disorder Of... PHOSPHOGLYCEROMUTASE An enzyme of the Embden-Meyerhof pathway of red blood cell metabolism, which reversibly catalyzes the reaction 3-phosphoglycerate to 2-phosphoglycerate Deficiency of this enzyme has not been reported PHOSPHOHEXOSE ISOMERASE An enzyme of the Embden-Meyerhof pathway of red blood cell metabolism that catalyzes the conversion of glucose 6-phosphate to fructose 6-phosphate Deficiency causes a hemolytic... plasmacytomas, where an increase in plasmablasts may confer a worse prognosis PLASMA CELL See also Lymphocytes — B-cells; Immunoglobulins An end-stage B-lymphocyte with an eccentric round nucleus with “clock-face” chromatin pattern The cytoplasm is strongly basophilic apart from a perinuclear light-staining Golgi body They are rarely seen in normal peripheral blood but are prominent in chronic inflammatory... types of platelet-specific granules Platelet-specific granules are either dense osmophilic granules (dense bodies, δ-granules) or α-granules Dense bodies contain 60% of the platelet storage pool of adenine nucleotides (such as adenosine diphosphate) and serotonin Dense-body adenine nucleotides do not readily exchange with other adenine nucleotides in the platelet metabolic pool The α-granules contain... cell types, such as coagulation factors Major contents of αgranules include VWF, platelet factor 4, β-thromboglobulin, thrombospondin, factor V, fibrinogen, fibronectin, platelet-derived growth factor, high-molecular-weight kininogen, and tissue plasminogen activator inhibitor-1 Contents of the platelet-specific granules are secreted in response to aggregating stimuli Platelets have a number of specific... further stimulate these processes Among the content of platelet α-granules are several coagulation factors, such as factor V, fibrinogen, and high-molecular-weight kininogen Upon secretion from the α-granule, these factors reach high local concentrations Platelets function to provide a local phospholipid surface for these factors to work upon, particularly factor V This procoagulant activity of platelets... (thrombocytopenia) or platelet-function disorders Their treatment depends entirely upon the cause Platelet Antagonists Inhibition of platelet aggregation can be induced by the action of drugs These antiplatelet drugs are widely used for prevention of thrombosis (see Arterial thrombosis; Venous thromboembolic disease) Aspirin, ticlopidine, and clopidogrel are effective for long-term prophylaxis .82 ,86 3393_book.fm... in thrombocytopenia and platelet-function disorders Epithelial webs in the posterior wall with iron deficiency (Plummer-Vinson, Patterson-Kelly syndromes) Postcricoid carcinoma, complicating epithelial webbing Lymphoproliferative disorder of the tonsils Nasopharyngeal carcinoma associated with Epstein-Barr virus (EBV) infection; adoptive immunotherapy to EBV-specific T-cells has a potential therapeutic... genetic components and the environment Most commonly used in hematology to define cell-surface antigenic profile, such as the use of monoclonal antibodies in immunophenotyping for the diagnosis of leukemias and antisera for the characterization of red blood cell antigens (see Blood groups) PHI BODIES Polyribosomal spindle-shaped hydrogen peroxide-positive parent organelles in the cytoplasm of blast cells . treatment is rarely neces- sary. If for some reason red blood cell transfusion is required, P-antigen-positive cells would have to be used due to the rarity of P-antigen-negative donors. Blood. PERNICIOUS ANEMIA T-cell-associated antigens (CD3 +/− , CD2 +/− , CD5 +/− , CD7 −/+ ) and B-cell-associated antigens. Most nodal cases are CD4 + , CD8 − , and CD30 + in the large-cell variants KINASE An enzyme of the Embden-Meyerhof pathway of red blood cell metabolism responsible for the conversion of 1,3-diphosphoglycerate (1,3-DPG) to 3-phosphoglycerate, thus gen- erating adenosine triphosphate