Ch. 15 - RBC Disorders Flashcards

Question

Anemia of Acute Blood Loss:

Answer 1

* effects are mainly due to loss of intravascular volume which if massive can lead to CV collapse, shock and death * results in hemodilution due to blood volume restoration from intravascular shift, lowering hematocrit * reduction in O2 results in increased erythropoietin → stimulating CFU-E * takes 5 days for retics to appear in peripheral blood * if bleeding is significant results in massive decrease in BP → increased adrenergic hormones → mobilization of granulocytes and leuocytosis * initially RBCs appear normocytic normochromic however after production increases see macrocytes due to reticulocytosis along with thrombocytosis

Answer 2

• shortened RBC life span below the normal 120 days • elevated EPO levels – and compensatory increase in erythropoiesis • accumulation of hemoglobin degradation products - destruction of senescent RBCs takes place in macrophages abundant in spleen, liver and bone marrow • in both types see increase in unconjugated bilirubin Morphology: increased number of erythroid precursors (normoblasts) in marrow, retics in blood, hemosiderin, EMH if severe in liver, spleen and LN’s, elevated biliary excretion resulting in pigment gallstones

Answer 3

destruction of RBCs w/in phagocytes • caused by alterations that render RBCs less deformable → red cell sequestration and phagocytosis by macrophages located w/in splenic cords • see anemia, splenomegaly*** and jaundice, decrease in plasma haptoglobin (an alpha1 globulin that binds free Hgb and prevents its excretion in the urine)

Answer 4

less common • caused by mechanical injury, complement fixation, intracellular parasites, exogenous toxic factors • mechanical injury due to prosthetic valves, thrombotic narrowing or repeated physical trauma such as marathon running • see anemia, hemoglinemia, hemoglobinuria, hemosiderinuria, and jaundice, depleted serum haptoglobin • as serum haptoglobin is depleted free Hgb oxidizes to methemoglobin (brown color seen in urine) • renal hemosiderosis- accumulation of iron released from Hgb accumulating in renal tubular cells • NOTE: splenomegaly is NOT seen here!

Answer 5

• HS is an inherited disorder caused by intrinsic defects in RBC membrane skeleton → renders cells spheroid, less deformable and vulnerable to splenic sequestration and destruction. • autosomal dominant – more common in northern Europe • caused by diverse mutations that lead to insuffic. of membrane skeletal components – and decreased RBC life to 10-20 days: mutations in ankyrin, band 3, spectrin, band 4.2 Morphology: • spherocytosis: small, hyperchromic RBCs lacking central zone of pallor • retics, marrow hyperplasia, hemosiderosis, mild jaundice • cholelithiasis – pigment stones • moderate splenomegaly

Answer 6

* RBCs have increased MCH concentration due to dehydration and loss of K+ * chronic hemolytic anemia → splenomegaly, jaundice (30% present asymptomatic) * Aplastic crises: usually triggered by an acute parvovirus infection, which infects and kills red cell progenitors, causing red cell production to cease until an immune response commences, generally in 1 to 2 weeks. Because of the reduced life span of HS red cells, cessation of erythropoiesis for even short time periods leads to sudden worsening of the anemia. Transfusions may be necessary to support the patient until the immune response clears the infection. * Hemolytic Crises: intercurrent events leading to increased splenic destruction of red cells (e.g., infectious mononucleosis); these are clinically less significant than aplastic crises. tx: Splenectomy – due to spleen causing premature death of RBC’s – after splenectomy the spherocytes persist but the anemia is corrected (but more prone to sepsis)

Answer 7

* Abnormalities in the hexose monophosphate shunt or glutathione metabolism resulting from deficient or impaired enzyme function reduce the ability of red cells to protect themselves against oxidative injuries and lead to hemolysis. * most common triggers are infections , in which oxygen-derived free radicals are produced by activated leukocytes - viral hepatitis, pneumonia, and typhoid fever are most likely * can also be caused by drugs (primaquine, chloquine, sulfonamides) and food (fava beans) * X-linked recessive: more common in Mediterranea and middle east Morphology: • Heinz bodies: reactive sulfahydryl groups on globin chains – shows up as little spots • “Bite cells” – splenic cord macrophages pluck out Heinz bodies, resulting in deformed RBCs • spherocytes Clinical Presentation: • oxidants cause intravascular and extravascular hemolysis • hemolysis is greater in people with highly unstable G6PD Mediterranean variant • only older cells are at risk for lysis – thus it is self-limiting and hemolysis stops when only younger G6PD-replete red cells remain • see reticulocytes in recovery phase • occurs intermittently: thus splenomegaly and cholelithiasis are absent

Answer 8

* caused by a point mutation in β-globin that promotes the polymerization of deoxygenated hemoglobin, leading to red cell distortion, hemolytic anemia, microvascular obstruction, and ischemic tissue damage. * Sickle cell disease is caused by a point mutation in the sixth codon of β-globin that leads to the replacement of a glutamate residue with a valine residue. Sickle Cell Trait: 8-10% of African Americans are heterozygous for HbS o HbS has protection against falciparum malaria: due to stiffened cells being cleared more rapidly and impairing the formation of knobs created by the parasite o red cells don’t sickle except under conditions of profound hypoxia o milder sickling Sickle cell disease: almost all of the Hgb in red cell is HbS o less severe if HbF remains Pathogenesis: • Increased MCHC: intracellular dehydration increases the MCHC, facilitating sickling • Decrease in pH: reduces the O2 affinity of Hgb and increases fraction of deoxygenated HbS • Sickling occurs in microvascular beds when they remain for longer periods of time – blood flow is sluggish in spleen and BM and vascular beds that are inflamed • with repeated bouts of sickling, RBCs become more dehydrated, dense, rigid → irreversibly sickled • Microvascular occlusions: red cell membrane damage, due to sharp sticky sickle red cells → aggregate and obstruct → hypoxia → increased sickling

Answer 9

Morphology: • sickled cells, reticulocytosis, target cells • Howell-Jolly bodies due to asplenia • cheekbones are prominent and skull marrow expanded due to EMH • pigment gallstones, hyperbili due to increased Hgb breakdown • autosplenectomy: spleen is enlarged in early childhood, but with time result sin splenic infarction and progressive shrinking • infarctions in bones, brain, kidney, liver, retina,

Answer 10

Clinical features: • hemolytic anemia – w/ retics, hyperbilirubenemia and irreversibly sickled cells Vaso-occlusive crises, aka pain crises, are episodes of hypoxic injury and infarction that cause severe pain in the affected region o infection, dehydration and acidosis all favor sickling and can act as a trigger o involves bones, lungs, liver, brain, spleen and penis o Priapism: hypoxic damage and erectile dysfunction o loss of visual acuity o crippling Acute chest syndrome: vaso-occlusive crisis involving the lungs → fever, cough, c/p, pulmonary infiltrates – very dangerous Sequestration crises occur in children with intact spleens. Massive entrapment of sickled red cells leads to rapid splenic enlargement, hypovolemia, and sometimes shock. Aplastic crises stem from the infection of red cell progenitors by parvovirus B19, which causes a transient cessation of erythropoiesis and a sudden worsening of the anemia. * Chronic → impairment of growth and development and organ damage affecting the spleen, heart, kidneys, and lungs. * Increased susceptibility to infection with encapsulated organisms due to altered spleen fn: . Pneumococcus pneumoniae and Haemophilus influenzae septicemia and meningitis * ddx made clinically and by use of metabisulfite which induces sickling, along with Hgb electrophoresis * tx: hydroxyurea: increases HbF levels, and has anti-inflammatory effect

Answer 11

* group of disorders caused by inherited mutations that decrease the synthesis of either the α-globin or β-globin chains that compose adult hemoglobin, HbA (α β ), leading to anemia, tissue hypoxia, and red cell hemolysis related to the imbalance in globin chain synthesis → decreased red cell production and life span * chromosome 16 = alpha chain * chromosome 11 = beta chain * β-thalassemia is caused by deficient synthesis of β chains, whereas α-thalassemia is caused by deficient synthesis of α chains. * Mediterranean basin, Middle East, tropical Africa, the Indian subcontinent, and Asia – protection against malaria

Answer 12

• caused by mutations that diminish the synthesis of β globin genes • β0 mutations = absent β globin gene synthesis • β+ mutations = reduced, but detectable β synthesis Pathogenesis: • splicing mutations are the most common cause – mutations exist w/in introns/exons and destroy the normal RNA splice junctions • deficit in HbA synth. produces hypochromic, microcytic red cells with subnormal O2 transport capacity, and there is a dimished survival of red cells and their precursors due to imbalance in alph and beta-globin synthesis • Unpaired α chains precipitate within red cell precursors, forming insoluble inclusions→membrane damage → apoptosis of red cells, and makes them prone to splenic sequestration and extravascular hemolysis • insoluble inclusions → ineffective erythropoiesis → massive erythroid hyperplasia in marrow and extensive EMH (in liver, spleen, LN’s) → erodes bony cortex and produces skeletal abnormalities • erythroid progenitors of EMH steal O2 → further oxygen depletion in other tissues → severe cachexia in untreated pts. • ineffective erythropoiesis → excessive absorption of dietary iron (high EPO suppresses hepcidin) → secondary hemochromatosis

Answer 13

* Mediterranean countries, parts of Africa, and Southeast Asia * anemia manifests 6-8 mos after birth, with Hgb levels 3-6 gm/dL Morphology: • anisocytosis (variation in size), poikilocytosis (variation in shape), microcytosis and hypochromia • target cells (Hgb collects at the center of the cell), basophilic stippling (erythrocytes show small dots at periphery), fragmented cells • elevated retic count • normoblasts (red cell precurors) are seen in periphery • striking expansion of hematopoietically active marrow: bones of face and skull show erosion → “crew cut” appearance • enlargement of spleen due to EMH • Hemosiderosis (due to extravascular lysis) and secondary hemochromatosis (accumulation of iron in liver, heart and other organs due to suppression of hepcidin) → iron deposition in heart, liver and pancreas Clinical Features: • untreated children suffer from growth retardation and die at early age due to anemia • cheekbones and other bony prominences are enlarged and distorted • hepatosplenomegally due to EMH • patients req. heavy transfusion → cardiac disease resulting from iron overload and secondary hemochromatosis (must be treated with iron chelators) • with transfusions and iron chelation, survival is possible to third decade • Hematopoietic stem cell transplantation is the only therapy offering a cure and is being used increasingly.

Answer 14

* much more common than β-thalassemia major * patients are heterozygous carriers of a β+ or β0 allele * patients are usually asymptomatic. Anemia, if present, is mild * peripheral blood smear typically shows some red cell abnormalities, including hypochromia, microcytosis, basophilic stippling, and target cells. Mild erythroid hyperplasia is seen in the bone marrow. * . Hemoglobin electrophoresis usually reveals an increase in HbA2 (α2δ2 ) to 4% to 8% of the total hemoglobin (normal, 2.5% ± 0.3%), reflection of an elevated ratio of δ-chain to β-chain synthesis. * HbF levels are generally normal or occasionally slightly increased. (In major they are very increased!) * Iron deficiency can usually be excluded through measurement of serum iron, total iron-binding capacity, and serum ferritin. * The increase in HbA2 is diagnostically useful

Answer 15

• caused by inherited deletions that result in reduced or absent synthesis of α-globin chains • anemia stems both from a lack of adequate hemoglobin and the presence of excess unpaired globin chains (β, γ, and δ) • Hemoglobin Barts: excess unpaired γ-globin chains form γ4 tetramers in newborns • HbH: excess β-globin chains form β4 tetramers in older children and adults • Because free β and γ chains are more soluble than free α chains and form fairly stable homotetramers, hemolysis and ineffective erythropoiesis are less severe than in β-thalassemias. Clinical Features: • clinical syndromes are determined by number of alpha-globin genes that are deleted, and severity is proportional to number of alpha globin genes that are deleted

Answer 16

Silent Carrier State: • deletion of a single alpha-globin gene Alpha-Thalassemia trait: • deletion of two alpha globin genes from a single chromosome or deletion of one alpha globin gene from each of two chromosomes • more common in Asia/Africa • see small red cells (microcytosis), minimal/no anemia, no abnormal physical signs, HbA2 levels are normal or low (a gene that in humans codes for the alpha globin chain of hemoglobin) Hemoglobin H Disease: • HbH disease caused by deletion of three alpha-globin genes • more common in Asian populations • HbH = tetramers of Beta globin – has high affinity for O2 → tissue hypoxia disproportionate to level of Hgb • moderately severe anemia similar to B-thalassemia intermedia Hydrops Fetalis: • most severe form of alpha thalassemia, caused by deletion of all four alpha-globin genes • Hemoglobin Barts formed, that have high affinity for O2 and deliver very little O2 tissues • fetal distress is seen in third trimester of pregnancy • fetus shows severe pallor, generalized edema, massive hepatosplenomegally • lifelong dependence on blood transfusions for survival

Answer 17

* a disease that results from acquired mutations in the phospha¬tidylinositol glycan complementation group A gene (PIGA), an enzyme that is essential for the synthesis of certain membrane-associated complement regulatory proteins. * rare, the only hemolytic anemia caused by an acquired genetic defect. * as a result of PIGA mutations the GPI genes are deficient, causing mutations that occur in a hematopoietic stem cell progeny * Red cells deficient in these GPI-linked factors are abnormally susceptible to lysis or injury by complement. This manifests as intravascular hemolysis , which is caused by the C5b-C9 membrane attack complex. * tendency for red cells to lyse at night is explained by a slight decrease in blood pH during sleep, which increases the activity of complement. CF's: • anemia ranges from mild to severe • hemosiderinuria: loss of heme iron in the urine → iron deficiency anemia • **thrombosis = leading cause of death, 40% of patients suffer from venous thrombosis, often involving the hepatic, portal, or cerebral veins – 5-10% of patients develop AML or MDS • Flow Cytometry for DDx, detects red cells lack of CD59 proteins

Answer 18

- Antibodies bind to red cells → premature destruction | - “autoimmune hemolytic anemias”

Answer 19

patients red cells are mixed with sera containing abs that are specific for human IgG or complement, if either of the IgG or complement is present on the surface of the RBCs then it causes agglutination, which appears as clumping

Answer 20

patients serum is tested for its ability to agglutinate commercially available red cells bearing particular defined antigens (used to characterize Ag target and temp dependence of responsible Ag)

Answer 21

(IgG Antibodies Active at 37°C) • most common form (idiopathic, SLE, AI disorders, drugs, lymphoid neoplasms) • IgG causes extravascular hemolysis • loss of membrane → red cells to spherocytes → splenic sequestration Causes: o Antigenic Drugs: hemolysis follows large IV doses of penicillin or cephalosporins – which bind to RBC membranes and are recognized by antidrug Abs o Tolerance-breaking drugs: alpha-methyldopa

Answer 22

(IgM Antibodies Active Below 37°C) • sometimes appear after mycoplasma infection, infectious mononucleosis (EBV), CMV, influenza, HIV • disorder is self-limited and Abs rarely induce imp. hemolysis clinical sx occur where IgM binds in vascular beds where temp may fall – fingers, toes and ears → vascular obstruction causing pallor, cyanosis and Raynaud phenomenon

Answer 23

(IgG Antibodies Active Below 37°C) • “paroxysmal cold hemoglobinuria” – rare and sometimes fatal intravascular hemolysis and hemoglobinuria • IgGs bind to RBCs in periphery → lysis via complement when RBCs reach warm central areas • occurs mainly in children following viral infections

Answer 24

• most commonly caused by individuals with cardiac valve prostheses (artificial mechanical valves)- hemolysis stems from shear forces produced by turbulent blood flow and pressure gradients across damaged valves Microangiopathic hemolytic anemia: is most commonly seen with disseminated intravascular coagulation, but it also occurs in thrombotic thrombocytopenic purpura (TTP), hemolytic-uremic syndrome (HUS), malignant hypertension, systemic lupus erythematosus, and disseminated cancer. o ***The common pathogenic feature in these disorders is a microvascular lesion that results in luminal narrowing, often due to the deposition of fibrin and platelets. These vascular changes produce shear stresses that mechanically injure passing red cells. Regardless of the cause, traumatic damage leads to the appearance of red cell fragments ( schistocytes ), “burr cells,” “helmet cells,” and “triangle cells” in blood smears.

Answer 25

- most common and important anemias associated with red cell underproduction are those caused by nutritional deficiencies, followed by those that arise secondary to renal failure and chronic inflammation. - ex: Megaloblastic anemia, iron deficiency anemia, anemia of CD, aplastic anemia, pure red cell aplasia, polycythemia - less common disorders that lead to generalized bone marrow failure, such as aplastic anemia, primary hematopoietic neoplasms, and infiltrative disorders that lead to marrow replacement (e.g., metastatic cancer and disseminated granulomatous disease).

Answer 26

Pernicious anemia and folate deficiency • due to impairment of DNA synth that leads to ineffective hematopoiesis and dinstinctive large erythroid precursors and cells • VitB12 and Folate are both coenzymes reqd for synth of thymidine – thus results in impaired DNA synth. Morphology: • macro-ovalocytes: larger than normal, with lots of hgb • hyperchromic cells without MCHC increase • anisocytosis, poikilocytosis • retic count is low • neutrophils show nuclear hypersegmentation • megaloblastic changes in erythroid development • giant metamyelocytes and band forms • marrow hyperplasia as a response to increased EPO, howevere the messed up DNA synth causes ineffective hematopoiesis → pancytopenia

Answer 27

* VitB12 is called “cobalamin” * Vit B12 is freed from binding proteins in food through action of pepsin in the stomach and binds to salivary protein called haptocorrin * in duodenum B12 is released from haptocorrin by action of pancreateic proteases and associated with intrinsic factor (IF) * IF-B12 complex is transported to ileum where it is endocytosed by ileal enterocytes that express a receptor for IF called cubulin * Within ileal cells, VitB12 associated with carrier protein trancobalamin II and is secreted into the plasma * Transcolbalamin II delivers Vit B12 to liver and other cells of the body

Answer 28

1. Vit B12 and folate are reqd for essential cofactor in conversion of homcysteine to methionine for methionine synthase (ultimately yielding thymine for DNA synthesis) 2. Vit B12 is reqd for isomerization of methylmalonyl CoA to Succinyl CoA – thus deficiency results in increased plasma and urine levels of methylmalonic acid → leads to formation of abnormal fatty acids into neuronal lipids a. neurological complications assoc. w/ VitB12 defic. are not improved with folate administration Note: the neurologic complications of B12 deficiency. Tend to exhibit spastic paraparesis, sensory ataxia and severe parathesias of the lower limbs.

Answer 29

• Pernicious anemia = form of megaloblastic anemia caused by autoimmune gastritis that impairs production of IF, required for vitamin B12 uptake from the GI tract • more prevalent in Scan¬dinavian and other Caucasian populations - median age at diagnosis is 60 years, and it is rare in people younger than 30 • is believed to result from an autoimmune attack on the gastric mucosa resulting in chronic atrophic gastritis. o Type I Auto-Ab: blocks binding of VitB12 to IF o Type II Auto-Ab: prevents binding of IF-VitB12 complex to ileal receptor o Type III Auto-Ab: nonspecific • autoantibodies are of diagnostic utility, but they are not thought to be the primary cause of the gastric pathology; rather, it seems that an autoreactive T-cell response initiates gastric mucosal injury and triggers the formation of autoantibodies. o associated with other AI disorders: AI thyroiditis and adrenalitis Morphology: • megaloblastic anemia • stomach shows diffuse chronic gastritis and fundic gland atrophy, affecting both chief cells and parietal cells • glandular epithelium is replaced by mucus-secreting goblet cells → metaplasia called intestinalization • tongue becomes shiny and beefy, atrophic glossitis • parenteral admin of VitB12 correct megaloblastic changes in marrow, but gastric atrophy and achlorydria persist Clinical Features: • insidious onset – detect serum Abs to IF often • increased risk of gastric carcinoma

Answer 30

production of pepsin is low/loss of pepsin secretion occurring in older adults, results in VitB12 not being readily released from proteins in food

Answer 31

IF is not secreted in the stomach, and thus not available for uptake in the stomach

Answer 32

can remove or damage the site of intrinsic factor-vitamin B12 complex absorption.

Answer 33

(particularly those acquired by eating raw fish) compete with the host for B12 and can induce a deficiency state.

Answer 34

• Pregnancy, hyperthyroidism, disseminated cancer, and chronic infection: result in an increased demand for vitamin B12 and thus can produce a relative deficiency, even with normal absorption.

Answer 35

* megaloblastic anemia * CNS lesions – demyelination of dorsal and lateral spinal tracts, sometimes followed by loss of axons → spastic paraparesis, sensory ataxia, severe parasthesias in lower limb * elevated homocysteine levels → risk for atherosclerosis and thrombosis, may increase incidence of vascular disease

Answer 36

1. moderate to severe megaloblastic anemia 2. leukopenia with hypersegmented granulocytes 3. low serum B12, and 4. elevated serum levels of homocysteine and methymalonic acid. Note: In a true case of pernicious anemia, reticulocytosis and a rising HCT begins about 5 days after parenteral administration of B12. * tx: administration of B12 reverses/halts neuro defects, but gastric changes and risk of carcinoma are not affected

Answer 37

* results in a megaloblastic anemia having the same pathologic features as that caused by vitamin B deficiency. * Metabolic processes dependent upon Folate: (1) purine synthesis, (2) conversion of homocysteine to methionine, which also reqs. B12, (3) deoxythymidylate monophosphate synthesis (dTMP) * entirely dependent on dietary sources for their folic acid: vegetables such as lettuce, spinach, asparagus, and broccoli. Certain fruits (e.g., lemons, bananas, melons) Etiology: decreased intake, increased reqs, impaired utilization • chronic alcoholics: cirrhosis results in trapping of folate within the liver, excessive urinary loss and disordered metabolism of folate • Sprue: malabsorption syndrome • Drugs: anticonvulsant, oral contraceptives • Increased DNA synthesis: relative deficiency seen in pregnancy, infancy, hyperactive hematopoiesis, disseminated cancer • Methotrexate: folic acid antagonist → affects rapidly growing cells in bone marrow and GI tract ** Differences from VitB12 deficiency: serum homocysteine levels are increased, but methylmalonate concentrations are normal. Neurological changes do NOT occur

Answer 38

Microcytic, hypochromic anemia • The most common nutritional disorder in the world: most common in developing nations, but in the US seen in toddlers, adolescent girls(menstruation) and women of child-bearing age (before menopause). o chronic blood loss is the most common cause of iron deficiency in the western world! • dietary iron in the US obtained from animal products and the rest (albeit inorganic) from vegetables • In IDA, ferritin levels < 12 μg/L, in iron overload, levels approaching 5000 μg/L may be seen. o iron excretion is through the shedding of mucosa and skin epithelial cells, up to 1 to 2 mg lost each day Etiology: 1. dietary lack (impoverished, teens), 2. impaired absorption (Celiacs), 3. increased req (pregnant, CD), 4. occult blood loss (menstruation, GI bleed) o Sprue: “Celiac Disease” – impairs iron absorption and other fats are malabsorbed → chronic diarrhea Morphology: • microcytic, hypochromic anemia • anemia only appears when iron stores are completely depleted and this is accompanied by low serum iron, low ferritin levels, low transferrin saturation levels. • Prussian blue stain indicates disappearance of stainable iron from macrophages in the bone marrow • Poikilocytosis in form of small “pencil cells” is also seen Clinical Presentation: • depletion of iron cells → koilonychias, alopecia, atrophic changes in tongue and gastric mucosa and intestinal malabosorption • depletion of iron in CNS → appearance of Pica, affected individuals consume non-foodstuffs • Plummer- Vinson syndrome (esophageal webs, m/h anemia and atrophic glossitis)

Answer 39

regulates iron absoption, released from the liver in response to increases in intrahepatic iron levels – it is resp. for inhibiting iron transfer through binding to ferroportin and causing it to be endocytosed and degraded o as hepcidin levels rise, iron becomes trapped w/in duodenal cells and is lost as cells are sloughed o with low iron levels, hepcidin synth falls o anemia of chronic disease: see increased inflammatory mediators → increased hepcidin → decreased iron absorption o Ineffective erythropoiesis: i.e. β thal major and myelodysplastic syndromes, suppress hepcidin levels even when iron stores are high

Answer 40

1. HCT and Hgb are decreased 2. Serum iron and ferritin are low 3. TIBC is high (low transferrin saturation = high TIBC) 4. serum hepcidin is low 5. hypochromia, microcytosis, modest poikilocytosis

Answer 41

* Impaired red cell production associated with chronic diseases that produce systemic inflammation is likely the most common type of anemia in hospitalized patients in the US * Stems from reduction of erythroid progenitors and impaired iron utilization Three major categories: o chronic microbial infections: osteomyelitis, bacterial endocarditis, lung absesses o chronic immune disorders: RA and enteritis o neoplasms such as carcinomas of lung/breast and HL inflammation → high hepcidin → low serum iron, reduced TIBC and abundant stored iron in tissue macrophages o IL-6 stimulates hepcidin → reduced transfer of iron from storage pool o hepcidin suppresses EPO → EPO levels are very low high hepcidin levels → enhances the body’s ability to fend off infections that req. iron for pathogenicity (i.e. H. influenza) Clinical Features: • anemia is mild, dominant sx are those of underlying disease • normocytic/normochromic, or hypochromic/microcytic (as anemia of ID)

Answer 42

• syndrome of chronic primary hematopoietic failure and pancytopenia Causes: o majority of patients due to AI mechanisms, usually aqd; o chemical agents (chemo causing bone marrow suppression) o idiosyncratic fashion following exposure to drugs – chloramphenicol and gold salts o viral infections: viral hepatitis o whole body irradiation can destroy HSC’s o defects in telomerase Fanconi Anemia: rare autosomal recessive disorder that causes defects in complex reqd for DNA repair Other causes: 1. defects in telomerase found in 5-10% 2. abnormally short telomeres seen in 50% of patients **Two major mechanisms thought to be involved in the majority of cases: extrinsic immune-mediated suppression of marrow progenitors, and an intrinsic abnormality of stem cells : see Th1 cells that are activated causing IFNgamma and TNF that suppress and kill HSC’s

Answer 43

Morphology: • hypocellular bone marrow that is largely devoid of HSC, often only fat cells, fibrous stroma and scattered lymphocytes and plasma cells • “dry tap” – due to marrow aspirates not being filled with cells • granulocytopenia, thrombocytopenia, causing mucocutaneous bacterial infections and abnormal bleeding Clinical Features: • insidious onset • anemia is progressive with weakness, pallor, dyspnea • thrombocytopenia → petchiae and ecchymoses • neutropenia → persistent minor infections and s/o of chills, fever, prostration • splenomegaly is usually absent • red cells are slightly macrocytic and normochromic • reticulocytopenia • marrow is hypocellular (as opposed to ALL or MDS) • 5 year survival

Answer 44

• pure red cell plasia is a primary marrow disorder where only erythroid progenitors are suppressed – most cases stem from autoimmune phenomenon Etiology: • thymoma – have to remove thymoma for tx • large granular lymphocytic leukemia • drug exposure, AI disorders • Parvovirus B19 infection: preferentially infects and destroys RBC progenitors – if person already has severe hemolytic anemia then even a brief cessation of erythropoiesis results in rapid worsening of anemia, producing an aplastic crisis

Answer 45

form of marrow failure in which space-occupying lesions replace normal marrow elements o commonest cause is metastatic cancer – carcinomas of breast, lung, prostate o spent phase of myeloproliferative disorders o All cause marrow fibrosis and result in release of nucleated erythroid precursors and immature granulocytic forms (leukoerythroblastosis) into peripheral smears o teardrop-shaped red cells: deformed during release from bone marrow

Answer 46

* anemia is proportional to uremia | * due to diminished synth of EPO by damaged kidneys → inadequate RBC production

Answer 47

• folate and iron deficiencies are seen in this setting, and anemia is often slightly macrocytic due to lipid abnormalities associated with liver failure, which cause RBC membranes to acquire phospholipid and cholesterol as they circulate in the peripheral blood

Answer 48

: abnormally high RBC count, usually with corresponding increase in Hgb level Relative Polycythemia: when there is hemoconcentration due to decreased plasma volume – results from dehydration due to water deprivation or prolonged vomiting or diarrhea, diuretics Absolute Polycythemia: when there is an increase in total red cell mass o Primary form: results from an intrinsic abnormality of hematopoietic precurors (Polycythemia Vera) o Secondary: when red cell progenitors are responding to increased levels of EPO (ex. EPO elaborating tumors)

Answer 49

This test assesses the extrinsic and common coagulation pathways. The clotting of plasma after addition of an exogenous source of tissue thromboplastin (e.g., brain extract) and Ca2+ ions is measured in seconds. A prolonged PT can result from deficiency or dysfunction of factor V, factor VII, factor X, prothrombin, or fibrinogen

Answer 50

This test assesses the intrinsic and common clotting pathways. The clotting of plasma after addition of kaolin, cephalin, and Ca2+ ions is measured in seconds. Kaolin activates the contact-dependent factor XII, and cephalin substitutes for platelet phospholipids. Prolongation of the PTT can be due to deficiency or dysfunction of factors V, VIII, IX, X, XI, or XII, prothrombin, or fibrinogen, or to interfering antibodies to phospholipid.

Answer 51

ex. infections, drug rxns, scurvy, ehlers-danlos syndrome, HSP, hereditary hemorrhagic telangiectasia, perivascular amyloidosis - most often present with small hemorrhages (petechiae and purpura) in the skin or mucous membranes, particularly the gingivae. On occasion, however, more significant hemorrhages occur into joints, muscles, and subperiosteal locations, or take the form of menorrhagia, nosebleeds, gastrointestinal bleeding, or hematuria. • The platelet count and tests of coagulation (PT, PTT) are usually normal, pointing by exclusion to the underlying problem.

Answer 52

vessel wall abnormality problem induce petechial and purpuric hemorrhages, particularly meningococcemia, other forms of septicemia, infective endocarditis, and several of the rickettsioses (which have predilection for endothelium --> damage). • Due to microbial damage to the microvasculature (vasculitis) and disseminated intravascular coagulation.

Answer 53

problem of vessel wall sometimes induce cutaneous petechiae and purpura without causing thrombocytopenia. • vascular injury is mediated by the deposition of drug-induced immune complexes in vessel walls, which leads to hypersensitivity ( leukocytoclastic ) vasculitis = brisk vasculitis due to neutrophil response

Answer 54

causes vessel wall abnormality --> bleeding disorder microvascular bleeding that results from collagen defects that weaken vessel walls. • same mechanism may account for the spontaneous purpura that are commonly seen in older adults and the skin hemorrhages that are seen with Cushing syndrome, in which the protein-wasting effects of excessive corticosteroid production cause loss of perivascular supporting tissue.

Answer 55

Henoch-Schönlein purpura: systemic immune disorder (systemic IgA deficiecy) of unknown cause that is characterized by a purpuric rash, colicky abdominal pain, polyarthralgia, and acute glomerulonephritis. • results from the deposition of circulating immune complexes of IgA within vessels throughout the body and within the glomerular mesangial regions.

Answer 56

bleeding disorder caused by vessel wall abnormality (also known as Weber-Osler-Rendu syndrome ) : autosomal dominant disorder that can be caused by mutations in at least five different genes, most of which modulate TGF-β signaling. • dilated, tortuous blood vessels with thin walls that bleed readily • Bleeding can occur anywhere, but it is most common under the mucous membranes of the nose (epistaxis), tongue, mouth, and eyes, and throughout the gastrointestinal tract. Of all the conditions, serious bleeding is most often associated with hereditary hemorrhagic telangiectasia

Answer 57

bleeding disorder caused by vessel wall abnormality weakens blood vessel walls and causes bleeding. • This complication is most common with amyloid light-chain (AL) amyloidosis and often manifests as mucocutaneous petechiae.

Answer 58

= count less than 100,000 platelets/µL • 20,000 to 50,000 platelets/µL → posttraumatic bleeding, • 20,000 platelets/µL → spontaneous (nontraumatic) bleeding. • Normal PT and PTT. • associated bleeding usually involves small vessels and can more seriously cause intracranial bleeding

Answer 59

1. Decreased Platelet production: a. conditions that depress marrow output: i.e. drugs and alcohol b. HIV may infect megakaryocytes and inhibit platelet production c. MDS 2. Decreased Platelet survival a. immune thrombocytopenia: destruction of platelets by deposition of Abs or immune complexes b. Alloantibodies: arise when platelets are transfused or cross the placenta c. non-immunologic causes: DIC and thrombotic microangiopathies d. mechanical injury 3. Sequestration a. spleen normally sequesters 30% to 35% of the body's platelets, but this can rise to 80% to 90% when the spleen is enlarged, producing moderate degrees of thrombocytopenia. 4. Dilution a. massive transfusions

Answer 60

Chronic Immune Thrombocytopenic Purpura (ITP): • caused by autoantibody mediated destruction of platelets o can occur in the setting of a variety of predisposing conditions and exposures (secondary – i.e.: SLE, HIV, CLL) or in the absence of any known risk factors (primary or idiopathic) Pathogenesis: • Autoantibodies: directed against platelet membrane glycoproteins IIb-IIIa or Ib-IX, can be demonstrated in the plasma and bound to platelet surfaces in about 80% of patients o majority of cases, the antiplatelet antibodies are of the IgG class. o antiplatelet antibodies act as opsonins that are recognized by IgG Fc receptors expressed on phagocytes, leading to increased platelet destruction o autoantibodies may also bind to and damage megakaryocytes leading to decreases in platelet production that further exacerbate the thrombocytopenia • thrombocytopenia is usually markedly improved by splenectomy, indicating that the spleen is the major site of removal of opsonized platelets o splenic pulp is high in plasma cells → thus removal results in source of autoABs

Answer 61

Morphology: • principal changes of thrombocytopenic purpura are found in the spleen, bone marrow, and blood, but are not specific. • Secondary changes related to the bleeding diathesis may be found in any tissue or structure in the body. • spleen is of normal size – however see congestion of sinusoids and enlargement of splenic follicles • marrow reveals a modestly increased number of megakaryocytes • peripheral blood often reveals abnormally large platelets (megathrombocytes) due to accelerated thrombopoiesis Clinical Features: • adults women younger than 40 • insidious onset characterized by bleeding into the skin/mucosal surfaces • cutaneous bleeding seen in pinpoint hemorrhages • petechiae → echymoses • hx of easy bruising, nosebleeds, bleeding from the gums, and hemorrhages into soft tissues from relatively minor trauma. • disease may manifest first with melena, hematuria, or excessive menstrual flow. • Subarachnoid hemorrhage and intracerebral hemorrhage are serious and sometimes fatal complications • Splenomegaly and lymphadenopathy are uncommon in primary disease (if present, think ITP or B-cell neoplasm) • low platelet count, normal or increased megakaryocytes in the bone marrow, and large platelets in the peripheral blood • PT and PTT are normal tx: most patients respond to glucocorticoids and splenectomy

Answer 62

Acute Immune Thrombocytopenic Purpura: • Also caused by autoantibodies • Acute ITP is mainly a disease of childhood occurring with equal frequency in both sexes • Symptoms appear abruptly often 1 to 2 weeks after a self-limited viral illness, which appears to trigger the development of autoantibodies although the mechanism(s) are not clear. • Unlike chronic ITP, acute ITP is self-limited usually resolving spontaneously within 6 months • Glucocorticoids are given only if the thrombocytopenia is severe. • 20% of children, usually those without a viral prodrome, thrombocytopenia persists. These less fortunate children have a childhood form of chronic ITP that follows a course similar to the adult disease.

Answer 63

• can induce thrombocytopenia through direct effects on platelets and secondary to immunologically-mediated platelet destruction quinine, quinidine, and vancomycin- all bind platelet glycoproteins and in one way or another create antigenic determinants that are recognized by antibodies Heparin-induced thrombocytopenia (HIT) o Type I: occurs rapidly after initiation of therapy. Generally resolves and typically is of little importance o Type II: Less common. more clinically important. Begins 5-14 days after initiation of therapy. Results in severe, sometimes life threatening venous and arterial thromboses (even in the setting of thrombocytopenia)

Answer 64

* Thrombocytopenia is one of the most common hematologic manifestations of HIV infection. * Both impaired platelet production and increased destruction contribute. * CD4 and CXCR4, the receptor and coreceptor, respectively, for HIV are found on megakaryocytes, allowing these cells to be infected → megakaryocytes to be apoptosed * HIV infection also causes B-cell hyperplasia and dysregulation which predisposes to the development of autoantibodies → opsonize platelets, promoting their destruction by mononuclear phagocytes in the spleen

Answer 65

Thrombotic Thrombocytopenic Purpura (TTP) and Hemolytic-Uremic Syndrome (HUS) • They are caused by insults that lead to excessive activation of platelets, which deposit as thrombi in small blood vessels o intravascular thrombi cause a microangiopathic hemolytic anemia and widespread organ dysfunction, and the attendant consumption of platelets leads to thrombocytopenia. • While DIC and thrombotic microangiopathies share features such as microvascular occlusion and microangiopathic hemolytic anemia, they are pathogenically distinct. o In TTP and HUS (unlike in DIC), activation of the coagulation cascade is not of primary importance, and hence laboratory tests of coagulation, such as the PT and PTT, are usually normal.

Answer 66

Thrombotic Thrombocytopenic Purpura = the pentad of fever, thrombocytopenia, microangiopathic hemolytic anemia, transient neurologic deficits and renal failure o deficiency in plasma enzyme ADAMTS13 o ADAMTS13 nomally degrades vWF, in its absence, these multimers accumulate in plasma and promote platelet activation and aggregation + endothelial injury → TTP exacerbation o inherited or acquired

Answer 67

Hemolytic-Uremic Syndrome (HUS) • HUS = microangiopathic hemolytic anemia and thrombocytopenia (absence of neurologic symptoms) the prominence of acute renal failure, and its frequent occurrence in children. o associated with infectious gastroenteritis caused by Escherichia coli strain O157:H7 infection, which elaborates a Shiga-like toxin → alters endothelial cell fn causing platelet activation and aggregation o children are at higher risk – suspect with bloody diarrhea o treated supportively

Answer 68

= associated w/ defects in complement factor H, membrane cofactor protein (CD46) or factor I (all of which normally act to prevent excessive activation of the alternative C’ pathway)

Answer 69

- Inherited disorders of platelet function can be classified into three pathogenically distinct groups: (1) defects of adhesion, (2) defects of aggregation, and (3) disorders of platelet secretion (release reaction). ex. bernard-soulier syndrome, glanzmann thrombasthenia,

Answer 70

= defective adhesion of platelets to subendothelial matrix. • caused by an inherited deficiency of the platelet membrane glyco¬protein complex Ib-IX. • This glycoprotein is a receptor for vWF and is essential for normal platelet adhesion to the subendothelial extracellular matrix. • Affected patients have a variable, often severe, bleeding tendency. (defective adhesion)

Answer 71

Defective platelet aggregation: Glanzmann thrombasthenia • transmitted as an autosomal recessive trait. • platelets fail to aggregate in response to adenosine diphosphate (ADP), collagen, epinephrine, or thrombin because of deficiency or dysfunction of glycoprotein IIb-IIIa, an integrin that participates in “bridge formation” between platelets by binding fibrinogen • bleeding tendency is often severe.

Answer 72

Acquired Defects of platelet function: 1. aspirin: irreversible inhibitor of COX1, which is reqd for synth of thromboxaneA2 and prostaglandins – these mediators play imp. role in platelet aggregation → antiplatelet effects 2. Uremia

Answer 73

Disorders of platelet secretion are characterized by the defective release of certain mediators of platelet activation, such as thromboxane and granule-bound ADP.

Answer 74

* Bleeding due to isolated coagulation factor deficiencies most commonly manifests as large posttraumatic ecchymoses or hematomas, or prolonged bleeding after a laceration or any form of surgical procedure * Unlike bleeding seen with thrombocytopenia, bleeding due to coagulation factor deficiencies often occurs into the gastrointestinal and urinary tracts and into weight-bearing joints (hemarthrosis). * most common and important inherited deficiencies of coagulation factors affect factor VIII (hemophilia A), and factor IX (hemophilia B). Deficiencies of vWF (von Willebrand disease) influences both coagulation and platelet function. * Acquired deficiencies usually involve multiple coagulation factors and can be based on decreased protein synthesis or a shortened half-life. Vitamin K deficiency results in the impaired synthesis of factors II, VII, IX, X and protein C • Many of these factors are made in the liver and are therefore deficient in severe parenchymal liver disease.

Answer 75

* Factor VIII is an essential cofactor of factor IX, which converts factor X to factor Xa – mostly made in sinusoidal endothelial cells and Kupffer cells * Once factor VIII reaches the circulation it binds to vWF, which is produced by endothelial cells * vWF stabilizes factor VIII which has a half-life of about 2.4 hours when free and 12 hours when bound to vWF in the circulation * vWF promotes the adhesion of platelets to subendothelial matrix through bridging interactions b/w platelet glycoprotein Ib-IX, vWF and matrix components such as collagen * Upon vascular injury, the second pool of vWF binds collagen in the subendothelial matrix causing platelet adhesion * Factor VIII fn = measured by coagulation assays * vWF fn = measured by ristocetin agglutination test

Answer 76

* most common inherited bleeding disorder of humans * bleeding tendency is usually mild and often goes unnoticed until some hemostatic stress, such as surgery or a dental procedure, reveals its presence * symptoms = spontaneous bleeding from mucous membranes (e.g., epistaxis), excessive bleeding from wounds, or menorrhagia * transmission is usually autosomal dominant * wide variability in gene expression through families – due in part to modifying genes that influence circulating levels of vWF, which show a wide range in normal populations

Answer 77

quantitative defects in vWF. • Type I = autosomal dominant disorder characterized by a mild to moderate vWF deficiency, accounts for about 70% of all cases – associated with a spectrum of mutations that interfere with maturation of vWF protein and result in rapid clearance from the plasma • Type 3 (an autosomal recessive disorder) = very low levels of vWF and correspondingly severe clinical manifestations o Because a severe deficiency of vWF has a marked effect on the stability of factor VIII, some of the bleeding characteristics resemble those seen in hemophilia o disease is usually caused by deletions or frameshift mutations involving both alleles

Answer 78

= qualitative defects in vWF * autosomal dominant disorder * vWF is expressed in normal amounts, but missense mutations are present that lead to defective multimer assembly. * Large and intermediate multimers, representing the most active forms of vWF, are missing from plasma. * accounts for 25% of all cases and is associated with mild to moderate bleeding.

Answer 79

can be treated with desmopressin, which stimulates vWF release, or with infusions of plasma concentrates containing factor VIII and vWF.

Answer 80

(Factor VIII deficiency): • most common hereditary disease associated with life-threatening bleeding o tendency toward easy bruising and massive hemorrhage after trauma or operative procedures o “spontaneous” hemorrhages frequently occur in regions of the body that are susceptible to trauma, particularly the joints, where they are known as hemarthrose o Recurrent bleeding into the joints leads to progressive deformities that can be crippling o Petechiae are characteristically absent. X-linked recessive trait → affects mainly males * exhibits a wide range of clinical severity that correlates well with the level of factor VIII activity * > 1% of normal → severe disease; 2% to 5% of normal → moderately severe disease; 6% to 50% of normal levels →mild disease variety of mutations: most severe deficiencies result from an inversion involving the X chromosome that completely abolishes the synthesis of factor VIII o Mutations permitting some active factor VIII to be synthesized are associated with mild to moderate disease ** DDx: Prolonged PTT and a normal PT (due to abnormality in intrinsic pathway) treated with infusions of recombinant factor VIII

Answer 81

(“Christmas Disease”, Factor IX Deficiency): • disorder clinically indistinguishable from factor VIII deficiency • X-linked recessive trait and shows variable clinical severity • the PTT is prolonged and the PT is normal • Ddx: possible only by assay of the factor levels • treated with infusions of recombinant factor IX.

Answer 82

* thrombohemorrhagic disorder characterized by the excessive activation of coagulation and the formation of thrombi in the microvasculature of the body * occurs as a secondary complication of many different disorders * consumption of platelets, fibrin, and coagulation factors and, secondarily, activation of fibrinolysis • symptoms relating to the tissue hypoxia and infarction caused by the microthrombi; hemorrhage caused by the depletion of factors required for hemostasis and the activation of fibrinolytic mechanisms Etiology: • not a primary disease – occurs in the course of a variety of clinical conditions → pathologic activation of coagulation or the impairment of clot-inhibiting mechanisms • Two major mechanisms trigger DIC: (1) release of tissue factor or other, poorly characterized procoaagulants into the circulation, and (2) widespread injury to endothelial cells. • endothelial injury → TNF induces endothelial cells to express tissue factor on surface and decrease expression of thrombomodulin, shifting balances towards coagulation • DIC most often assoc. w/ obstetric complications, malignant neoplasms, sepsis and major trauma

Answer 83

1. widespread deposition of fibrin: → ischemia and microangiopathic hemolytic anemia – due to fragmentation of RBCs as they squeeze through narrowed microvasculature 2. consumption of platelets and clotting factors → hemorrhagic diathetsis (plasmin cleaves fibrin and also digests factors V and VIII, reducing their concentration)

Answer 84

Morphology: • thrombi in brain, heart, lungs, kidneys, adrenals, spleen, liver • bilateral renal cortical necrosis from small thrombi in glomeruli • hyaline membranes in lungs • microinfarcts in CNS • “Waterhouse-Friderichsen syndrome” = massive adrenal hemorrhages Clinical Features: • onset can be fulminant, as in endotoxic shock or amniotic fluid embolism, or insidious and chronic, as in cases of diffuse carcinomatosis or retention of a dead fetus o 50% of the affected are obstetric patients having complications of pregnancy – usually reversible • microangiopathic hemolytic anemia ; dyspnea, cyanosis, and respiratory failure; convulsions and coma; oliguria and acute renal failure; and sudden or progressive circulatory failure and shock • acute DIC- obstetric complications or major trauma = bleeding diathesis • chronic DIC - cancer patients = thrombotic complications

Answer 85

= fever and chills, sometimes with mild dyspnea, within 6 hours of a transfusion of red cells or platelets • most common reaction, sx are short lived

Answer 86

* Patients with IgA deficiency- the reaction is triggered by IgG antibodies that recognize IgA in the infused blood product – potentially fatal * Urticarial allergic reactions (wheels and hives that itch)- triggered by the presence an allergen in the donated blood product that is recognized by IgE antibodies in the recipient – usually tx with antihistamines

Answer 87

• caused by preformed IgM antibodies against donor red cells that fix complement. o high affinity “natural” IgM antibodies, usually against polysaccharide blood group antigens A or B, bind to red cells and rapidly induce complement-mediated lysis, intravascular hemolysis, and hemoglobinuria. o Fever, shaking chills, and flank pain appear rapidly • most commonly stem from an error in patient identification or tube labeling that allows a patient to receive an ABO incompatible unit of blood • direct Coombs test is typically positive

Answer 88

caused by antibodies that recognize red cell antigens that the recipient was sensitized to previously, for example through a prior blood transfusion. These are typically caused by IgG antibodies to foreign protein antigens and are associated with a positive direct Coombs test and laboratory features of hemolysis (e.g., low haptoglobin and elevated LDH)

Answer 89

• severe, frequently fatal complication in which factors in a transfused blood product trigger the activation of neutrophils in the lung microvasculature • more frequently in patients with preexisting lung disease. Clinical presentation: • dramatic sudden onset respiratory failure, during or soon after a transfusion. • Diffuse bilateral pulmonary infiltrates that do not respond to diuretics are seen on chest imaging. • fever, hypotension and hypoxemia. • treatment is largely supportive and the outcome is guarded; mortality is 5% in uncomplicated cases and up to 67% in those who were severely ill.

Answer 90

* Most bacterial infections are skin flora, indicating that the contamination occurred at the time that the product is taken from the donor * bacterial contamination is much more common in platelet preparations (b/c must be stored at room temp) * sx: fever, chills, hypotension * HIV rate of transmission = 1 in 2 million * Hep C = 1 in 1 million * Hep B = 1 in 500,000

Answer 91

schisocytes

Answer 92

if abnormal, think vWF

Answer 93

hereditary spherocytosis

Answer 94

TTP confirmed by demonstration of von Willebrand factor monomers in the serum. These abnormalities are produced by small platelet-fibrin thrombi in small vessels in multiple organs. The heart, brain, and kidney often are severely affected.

Answer 95

Failure to correct PTT by normal plasma indicates the presence of an inhibitor in the patient's serum. About 15% of patients with hemophilia eventually develop an inhibitor to factor VIII. The antiphospholipid syndrome has similar PT and PTT findings because an inhibitor is present, but these patients have thromboses and bleeding, typically in adulthood, and without a family history.

Answer 96

leads to an abnormal PT.

Answer 97

The hemolysis that accompanies sickle cell anemia results in an increased indirect hyperbilirubinemia, which favors the development of gallstones containing bilirubin pigment. Cirrhosis can occur because of hemochromatosis in β- thalassemia major. Chronic atrophic gastritis leads to loss of parietal cells, and the resulting vitamin B12 malabsorption causes pernicious anemia. Stillbirths suggest thalassemia major. Esophageal webs occur rarely in the setting of chronic iron deficiency anemia.

Answer 98

prostatic adenocarcinoma that has metastasized to the bone. High alkaline phosphatase, hypercalcemia, and a leukoerythroblastic pattern in the peripheral blood (immature WBCs and RBCs) are a consequence of the tumor acting as a space-occupying lesion. Myelophthisic anemias also may be caused by infections.

Answer 99

TTP The absence of ADAMTS-13 gives rise to large multimers of vWF that promote widespread platelet aggregation, and the resulting microvascular occlusions in brain, kidney, and elsewhere produce organ dysfunction, thrombocytopenia, microangiopathic hemolytic anemia (MAHA), and bleeding.

Answer 100

Glanzmann Thrombasthenia

Ch. 15 - RBC Disorders Flashcards

(125 cards)