7. RBC Pathology Flashcards by Andrew Niemann

What is a reduction of the total circulating red cell mass below normal limits, decreased O2 carrying capacity = tissue hypoxia, patients are pale, weak, and easily fatigued with malaise, mild dyspnea, dx via hematocrit (ratio of packed RBC to total blood volume) or hemoglobin?

Anemia

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Microcytic normochromic = disorder of hemoglobin synthesis mostly due to iron deficieny
Normocytic normochromic = diverse things
and what is generally due to impaired maturation of RBC precursors in the bone marrow?

Macrocytic Anemia

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Mean cell volume MCV= average volume of a red cell expressed in femtoliters (80-100)
Mean cell hemoglobin = avg content of hemoglobin per red cell expressed in picograms
Mean cell hemoglobin concentration MCHC= avg concentration of hemoglobin in a given volume of red cells (both two above change color of RBC)
What is the coefficient of variation of red cell volume, elevated implying the marrow is pumping out reticulocytes and is a reactive phenomenon observed in states of anemia with functioning marrow?

Red Cell Distribution Width

hematocrit / 3 = hemoglobin

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Anemia is associated with paleness, weakness, malaise, easy fatigability, lowered oxygen content of the circulating blood leads to dyspnea on mild exertion DOE and or shortness of breath, chronic hypoxia may result in fatty change of the liver myocardium and?

kidney

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Acute blood loss due to intravascular volume loss, if massive leads to CV collapse, shock and death, is NC/NC anemia, see decreased hematocrit and low oxygenation- EPO is released from kidneys, HCT is NOT useful during acute blood loss because is relative concentration of red cells, not the total red cell mass. reticulocytes are produced in 5 days, MCC of acute blood loss is?

Trauma

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What type of blood loss shows anemia only if the rate of loss exceeds the marrow regenerative capacity or when iron reserves are depleted, male and posmenopausal women with thisv should assume to be COLON cancer until proven otherwise?

Chronic blood loss

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What anemia shows red cell life span of less than 120 days, elevated EPO levels, accumulation of hemoglobin degradation products (unconjugated bilirubin), there are inc erythroid precursors in marrow d/t inc epo production, prominent reticulocytosis in PB, hemosiderosis, extramed hematopoiesis if severe and chronically may lead to elevated bilirubin in bile and pigment gallstones?

Hemolytic Anemia

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Extravascular hemolysis occurs in the mo of the spleen, predisposed by RBC membrane injury, reduced deformability or opsonization, clinically see anemia, splenomegaly, jaundice, decreased haptoglobin (protein that binds to Hgb in plasma to kill RBC), usually treated by doing what?

Spleenectomy! becuase rbc damage occurs here

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Intravascular hemolysis is RBC rupture due to mechanical injury, complement fixation, intracellular parasites or extracellular toxins, see anemia, hemoglobinemia, hemoglobinuria, hemosiderinuria, jaundice, NO splenomegaly, renal hemosiderosis due to iron accum, excess unconj bilirubin, free hemoglin oxidized to methemoglobin when what is deplete, which is MARKEDLY decrased in this?

Haptoglobin (low haptoglobin = hemolysis)

**MC hemolysis

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What is an inherited disorder due to intrinsic defects of the red cell membrane skeleton, RBCs become spheroid, less deformable and more vulnerable to splenic sequestration and destruction, mainly extravasc hemolysis, northern europe, AD, mutation in ankyrin, band 3, band 4.2 causing reduced stability of lipid bylayer and loss of membrane fragments occurs as RBCs age- become spheroid and trapped in spleen and destroyed by mo after 10 days?

Hereditary Spherocytosis

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Hereditary Spherocytosis is asso with small dark staining (hyperchromic) red cells lacking the central zone of pallor, splenomegaly and cholelithiasis in 50% of patients due to pigment stones, see inc RDW and MHCH, pt present with anemia, splenomegaly and jaundice, inc risk of asplastic crisis due to parvo19 since it stops hematopoiesis for a few weeks, low RBC levels, tx is what, which will resolve the anemia but howell jolly bodies residual RNA remain?

Splenectomy - spherocytes persist- no anemia

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What is an enzyme in hexose monophosphate shunt, normally reduces NADP to NADPH, which reduces RBC glutathione and protects against oxidative stress due to fava beans, antimalaria drugs (quinidine, primaquine, chloroquine) sulfonamides, nitrofurantoins, infection inflammation?

Glucose 6 Phosphate Dehydrogenase G6PD

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Glucose 6 Phosphate Dehydrogenase G6PD is prominent in AA and less severe, see episodic hemolysis due to oxidative stress, causes hemoglobin sulfhydryl crosslinking and protein denaturation, cross linking of reactive sulfhydryl groups on globin chains become denatured and form membrane bound precipitates called heinz bodies (dark inclusions visible with crystal violet)- when mo remove these inclusions they create BITE cells or become spherocytic, what is the inheritance?

X Linked Recessive

hemolysis is greater in mediterranean variant
anemia, hemoglobinemia, hemoglobinuria

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NOTE
HbA = a2b2
HbA2= a2b2 (high is B thalassemia minor/trait)
HbC
HbF= a2gamma2 (high HbF is B-thalassemia major)
HbH= B4
HbS= a2bs2 (sickle cell trait)
Hemoglobin Barts= gamma4

Usually
HbA is NL
no HbS/C/F/A2 in normal adults

at birth gamma/alpha chains are high
after birth gamma drops, beta rises, a stays high

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What is hereditary hemoglobinopathy due to a point mutation which provides PROTECTION agains v. faciparum malaria, intracellular parasites consume O2, and decrease pH, promoting sickling and distorted cells and cleared more rapidly by phagocytes keeping parasite loads down?

Sickle Cell Trait (HbS/A, a2bs2)

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What is hereditary hemoglobinopathy due to a point mutation in the 6th position conferring a glutamate to valine substitution in B-globin that promotes polymerization of deoxygenated hemoglobin, leading to red cell distortion, hemolytic anemia, microvascular obstruction, ischemic tissue damage, note heterozygotes are only affected in settings of profound hypoxia?

Sickle Cell Anemia/Disease (HbS/S, Bs2/Bs2)

*HbF is protective- give hydroxyurea

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Sickle Cell Anemia/Disease (HbS/S, Bs2/Bs2) forms sickle shape, rate and degree depends on interactions iwht other types of hemoglobbin in the cell, HbA interferes with the polymerization of the HbS, dec MCHC levels causes a milder disease due to intracellular hydration, decreased pH increases sickling, slow transit through cap beds increases sicking- which are found most commonly in the bone marrow, inflamed tissues and?

spleen

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What disease is 1 of each mutant gene, heterozygotes with RBCs that lose salt and water = dehydration, [Hb] is then increased and there is a tendency for polymerization, glutamic acid to lysine, Crystals are seen on blood smear, is a more mild than sickle cell disease?

HbSC Disease

crystalline form HbSC- symptomic compared to HbCC

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Sickle Cell on peripheral blood shows sickled cells, reticulocytosis, and target cells due to RBC dehydration, along with anisocytosis and poikilocytosis, complications include autosplenectomy due to trapping of RBCs in cords and sinuses causing infarction and fibrosis, see expansion of marrow causing prominent cheekbones and changes in skull that resemble crewcut, facial bones known as?

chipmunk facies

*pigmented galllstones

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Sickle Cell Anemia/Disease causes severe hemolytic anemia associted with hyperbilirubinemia, sickled cells, vasoocclusive crises are most imp complication due to episodes of hypoxic injury and infarction causing pain, no predisposing cause IDd, occurs in bones, lungs liver brain spleen penis, WHAT is MC in children and often difficult to distinguish from osteomyelitis?>

Painful Bone Crises

vasoocclusion in bones leads to swollen hands feet - **African american infants 6months = dactylitis = hand foot syndrome

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Sickle Cell Anemia/Disease is assoc with what which is vaso crisis of lungs, assoc with fever cough chest pain and pulm infiltrates, MCC of death in adult pts with sickle cell anemia***, causes vasodilation, slowing blood flow which increases dehydration, acidemia, and deoxygenation creasting a cycle, may require transfusion or fatal?

Acute Chest Syndrome

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Sickle Cell Anemia/Disease is assoc with priapism, sequestration crisis (death), hyposthenuria which is hypertonicity of renal medulla leading to inability to concentrate urine, stroke, retinopathy due to vascular occlusion, increased infection with encapsulated organisms, and aplastic crises with what is common where there is infection of RBC progenitor which causes a transient cessation of erythropoiesis and worsening of anemia?

Parvovirus 19*

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Sickle Cell Anemia/Disease is dx based on clincal sx and labs testing of hemoglobin, metabisulfite screen +++ in both disease and trait, prenatal amniocentesis or chorionic bx, 90% live to 20, 50% to 50+, tx with hydroxyurea and HSC transplant, WHAT is the MCC of death in children with sickle cell anemia causing septicemia and meningitis, vaccinating can dec risk?

Haemophilus Influenza (has capsule!)

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What is a group of disorders due to inherited mutations that decrease synthesis of either the a-globin or b-globin chains that compose adult HbA (a2b2), there are 2aglobin genes (4alleles) on chr 16, and 1b globin gene (2 alleles) on chr 11, causes anemia, tissue hypoxia, RBC hemolysis due imbalance of globin chain synthesis - anemia due to dec. RBC production and dec RBC lifespan**?

Thalassemia

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What type of Thalassemia is due to dysregulation of B globin chains, see microcytic hypochromic RBCS with subnormal O2 transport capacity, RBC diminished due to imbalance of a/b globin synthesis, causes RBC microcytosis, ineffective erythropoiesis*, excessive iron absorption, anemia because HgA1 (a2b2) produced insufficiently = ineffective erythro?

B-Thalassemia ***anemia is not via hemolysis***

B0 Thalassemia is absent synthesis of B globin chain, MC mutation is chain terminator creating premature stop cocdons, B+Thalassemia is reduced synthesis of Bglobin chain d/t splicing mutation, without these leads to unpaire achains that precipitate in RBC precursors causing insoluble inclusions, when lack erythropoeisis see suppressed hepcidin which regulates iron, so commonly with see secondary?

hemochromatosis (inc abs iron from gut with dec hepcidin) note: hereditary/primary you see increased ferritin which is storage form of iron*

in B-Thalassemia you see anisocytosis (variable RBC size), poikilocytosis (variable shape), hypochromic, target cells, fragmented RBCs, massive erythroid hyperplasia, iron overload with hemosiderosis and secondary hemocromatosis, affecting heart liver and pancrease, what is see which is an indicator of toxic injury to RBCs?

Basophilic Stippling

What type of B-thalassemia is asso with *homozygous BThalassemia (B0B0/B+B+/B0B+), have a severe transfusion dependent anemia beginning at 6-9months, commonly in mediterranean countries,africa and SE Asia, see ***HIGH HbF***, see hepatosplenomegaly due to extravasc hemolysis, massive erythroid hyperplasia of skull and face, tx requires chronic transfusions - survive to 30s?

B-Thalassemia Major with HIGH HbF

What B-Thalassemia is in heterozygous alleles suchs as B+/Bwildtype or Bwildtype/B0, much more common, mild asymptomatic, microcytic hypochromic, basophilic stippling and target cells, mild erythroid hyperplasia, can be mistaken for iron deficiency anemia in pregnancy, see increased ***HbA2***, normal HbF?

B-Thalassemia Minor/Trait *Note: BThalassemia due to point mutations that lead to defects in transcritpion, splicing, or translation of B globin mRNA

a-Thalassemia are inherited gene deletions leading to absent or reduced synthesis of a-globin chains, infants: unpaired y-globin chains form tetramers called hemoglobin barts, Adults: unpaired B-globin for tetramers called HbH, B and Y chains are more soluble than a-globulin chains and for more stable homotetramers leadins to hemolysis and ineffective erythropoiesis which are ?

less severe than in B thalassemia ***Gene deletion is MCC of a-Thalassemia

There are 4 alleles on chr 16 for a-globin, 1 allele deleted is asymptomatic, 2 deleted is mild anemia with inc RBC count- Cis deletion = asian-symptomatic, trans deletion = african american-asx,]-> this is known as a-thalassemia trait which is clinically similar to bthalassemia minor, 3 deletions causes severe anemia = HbH tetramers, and 4 alleles deleted causes hemoglobin barts and what occurs in utero?

LETHAL in utero = hydrops fetalis

HbH disease is 3 deletions of aglobin genes, MC in asians, form tetramers of Bglobin chains called HbH, has extreme increased affinity for O2 --- tissue hypoxia disproportionate to the level of Hb (not useful for O2 delivery to tissue), Hbh is prone to oxidation leading to precipitation and intracellular inclusions promoting RBC sequestration and phagocytosis in the spleen, does not require transfusion and resemble what disease?

B-Thalassemia intermedia

What occurs due to 4 mutations of aglobulin leading to tetramers of GAMMAglobin called hemoglobin barts in the fetus- greatly increased affinity for O2 causing tissue hypoxia, fetal distress during 3rd trimester, see severe pallor, generalized edema, massive hepatosplenomegaly?

Hydrops Fetalis

What is an acquired mutation of phosphatidylinositol glycan complementation group A gene PIGA, enzyme essential for synthesis of certain membrane associated complement regulatory proteins, with it absent causes cells susceptible to destruction by complement, X-linked mutation subject to lionization, it is the ONLY hemolytic anemia caused by an acquire genetic defect?

Paroxysmal Nocturnal Hemoglobinuria PNH

Paroxysmal Nocturnal Hemoglobinuria PNH is deficient in CD55 DAF, CD59 membrane inhibitor or reactive lysis, clinically RBC prone to lysis by complement caused by C5-9 MAC, 25% show paroxysmal and nocturnal- shallow nighttime breathing leads to resp acidosis and activates complement, TYPICAL is chornic hemolysis, heme iron is lost in urine, 10% develop AML or myelodysplastic syndrome, dx via flow cytometry detection of RBCs deficient in GPI linked proteins (CD59), MCC of death is WHAT?

Venous Thrombosis of hepatic, portal or cerebral veins *tx with eculizumab (prevents C5 conversion to c5a)

What anemias are due to antibodies bound to RBCs causing their premature destruction (hemolytic/ autoimmune**), diagnosed via prsence of abs and complement on RBCs, direct coombs test: RBCs are mixed with donor *serum*-screen, agglutinations means pt has RBCs coated with antibodies, indirect coombs test- pt serum mixed with donor *RBCs*- agglutination means patient has antibodies to pts RBCs?

Immunohemolytic Anemias IHAs

What type of Immunohemolytic Anemias IHAs is the MC, 50% idiopathic, also caused by drugs, AI such as SLE, path usually due to IgG abs, extravasc hemolysis, IgG coated RBCs bind Fc receptors on phagocytes, RBC partially removed, becomes spherocyte- sequestered in spleen= splenomegaly, antigenic drugs via IV bind RBCs, 1-2 weeks later hemolysis occurs- commonly due to PCN or cephalosporins?

Warm Antibody Type Immunohemolytic Anemia IgG Abs active at 37C

What type of Immunohemolytic Anemias IHAs is IgM abs bind RBCs avidly at low temps, acute is self limited rarely induced clinically important hemolysis (mycoplasma/ mononucleosis), chornic is symptomatic idiopathic or due to B cell neoplasms (CLL)- IgM antibodies hard to tx, clinical:extremity vascular beds where temps are <37C, lead to obstruction with pallor cyanosis and raynauds?

Cold Agglutinin Type IgM abs activate below 37C

What type of Immunohemolytic Anemias IHAs is IgG auto abs bind to P group antigen on RBC surface in cool peripheral regions, causes paroxysmal cold hemoglobinuria which is rare and fatal, when RBCs circulate to warm central regions, complement mediated lysis occurs more efficiently, common in children POST VIRAL INFECTIONS?

Cold Hemolysin Type IgG antibodies active below 37C

What may cause hemolytic anemia- often due to prosthetic cardiac valves and microangiopathic disorders- luminal narrowing due to depo of fibrin and platelets causing shear stress that injures passing RBCs, red cell fragments (schistocytes) aka burr cells, helmet cell, triangle cells on blood smear?

HA due to RBC trauma

NOTE: microangiopathic hemolytic anemia is MC seen in DIC but also occurs in TTP and HUS, malignant HTN, SLE and disseminated cancer...

yas

What anemia is due to impairment of DNA synthesis that leads to ineffective hematopoiesis and distinctive morphologic changes- abnormally large erythroid precursors and RBCs, MC due to vitamin B12 or folic acid deficiency(coenzymes for thymidine and methionine synthesis), see macro-ovalocytes=large oval RBCs***, appear hyperchromatic, MHCH not elevated, anisocytosis/poikilocytosis, dec reticulocyte count (means marrow not functioning well) and HYPER segemented neutrophils >5lobes?

Megaloblastic Anemias

In Megaloblastic Anemias, the marrow is hypercellular due to inc hemato precursors that may replace fat, pro-megaloblasts are large w basophilic cytoplasm, delayed nuclear maturation, giant metamyelocytes+ band forms, pancytopenia as marrow hyperplasia occurs due to increased EPO but abnormal DNA syn, there are large?

megakaryocytes with multilobate nuclei

What type of anemia is autoimmune gastritis that impairs the production of intrinsic factor IF which is required for vitamin B12 uptake in the gut, median age is 60, affects all populations - scandinavians, likely genetic, see chronic atrophic gastritis with loss of parietal cells, due to **autoreactive T cell response causing gastric mucosal injury** (cause damage) and auto ab which DONT cause dz but are there for diagnosis, anemia develops, associated with thyroiditis adernalitis and other AI diseases?

Pernicious Anemia (type of megaloblastic) dx: megaloblastic anemia, leukopenia with hypersegmented granulocytes, low serum B12, elevated homocysteine and methymalonic acid which is always seen in B12 def

What deficiency causes atrophic glositis beey red tongue, demyelination of dorsal and lateral spinal tracts causing spastic paraparesis, sensory ataxia, and paresthesias of lower limbs, see megaloblastic anemia, increased homocysteine and methylmalonic acid, hematocrit shjould rise 5 days after readmin along with increased reticulocytes, inc. homocysteine can cause athersclerosis and thrombosis, accum of methylmalonic acid in the SC can cause neuro disease?

B12 Deficiency

What deficiency results in a megaloblastic anemia having the same path features as B12 def, but it has not neurological sequalae, def leads to suppressed synthesis of DNA which is the common denominator of this and VITb12 def and it mediates the cause of megaloblastosis, *methylmalonic acid is NORMAL. *exclude b12 def before administering this drug?

Folic Acid deficiency = Anemia of Folate def

What is a set of diseases that can be acute or chronic, due to problems in the synthesis of heme, most inherited, some acquired, problems with BM leads to anemia and splenomegaly, probelms in liver leads to liver damage and inc risk in hepatocellular carcinoma, Chronic: skin= very sensitive to sunlight leading to blisters and abnl hair growth, teeth are stained, acute: referred pain from thorax and abdomen, seizures, hallucinations and general psychosis?

Porphyria

NOTE: • Causes of Vitamin B12 Deficiency • Impaired absorption • Achlorhydria (impairs B12 release from food) • Gastrectomy causes loss of intrinsic factor • Loss of exocrine pancreas function (impairs B12 release from haptocorrin) • Loss of pepsin secretion • Resection of the terminal ileum • Malabsorption syndromes (including *fish* tapeworms Diphyllobothrium latum) • Increased requirements (pregnancy, hyperthyroidism, disseminated cancer, chronic infection) • Pernicious anemia (antibodies to intrinsic factor)

NOTE:• Anemia of Folate vs anemia due to Vitamin B12 deficiency • Normal [methylmalonate] • No neurological signs and symptoms • Increased homocysteine (same as B12 anemia) but methylmalonate concentrations are normal • Neurological changes do not occur in folate deficiency anemia • Diagnosed via demonstration of decreased folate levels in the serum or RBCs • Rule out B12 deficiency before treating with folate • folate may exacerbate neurological defects of B12 deficiency

What is the MC nutritional disorder of the world due to dietary lack, impaired absorption, increased requirement, and in the western world MC due to chronic blood loss, signs/sx related to inadqeuate hemoglobin synthesis?

Iron Deficiency

Ferritin is the storage form of iron, ubiquitous protein iron complex found at highest lesvels in the liver spleen BM and skeletal m,located in the cytosol and lysosomes, partially degraded protein shells of ferritin = hemosiderin granules, plasma ferittin derived largely from storage pool of iron, directly related to body iron levels, what are partially degraded protein shells of ferritin, see on prusian blue stain, disappearance of stainable iron from mo in the BM = diagnostically significant finding of iron def?

Hemosiderin Granules

What is synthesized and release from the liver in reponse to increases in intrahepatic iron levels, and regulates iron absorption in the PROXIMAL DUODENUM, inhibs iron transfer from enterocyte to plasma by binding ferroportin, causes endocytosis and degredation of ferroportin, these levels directly relate to total body iron stores?

Hepcidin

What anemia is due to dietary lacks, impaired absorption, increased requirement in growing kids and pregnancy, chronic blood loss*** due to GI bleed= GI cancer, seen as absence of stainable iron from macrophage in BM, *microcytic hypochromic anemia in blood smears but is normocytic and normochromic in the beginning, inc central pallor in RBCs, minimal hemoglobin, *poikilocytosis (pencil cells) is characteristic?

Iron Deficient Anemia

Iron Deficient Anemia clinical see spoon nails or koilonychia, alopecia, atropic tongue and gastric mucosa, intestinal malabsorption, pica- desire to eat non food like dirt and clay, what syndrome may be seen and is microcytic hypochromic anemia, atrophic glossitis and esophageal webs?

Plummer Vinson Syndrome

Iron Deficient Anemia is diagnosed via decreased hemoglobin and hematocrit, MC/HC anemia, decreased* serum iron and ferritin (store form), increased iron binding capacity, decreased transferrin, inhibition of hepcidin synthesis, TIBC is always inverse of ferritin, with low serum?

hepcidin which normally inhibits iron absortion, in deficiency-trying to absrob more so why it is low hepcidin inhibs ferroportin which is the channel to allow absorption of iron through basolateral enterocyte

What anemia is MCC of anemia in hospitalized pts, due to reduced proliferation of erythroid progenitors and impaired iron utilization due to chronic microbial infections, immune disorders, or neoplasms, see microcytic hypochromic anemia (or NC/NC), occurs in setting of persistent systemic inflam- IL6 stimulates inc in hepatic prod of hepcidin, assoc w low serum iron, reduced TIBC, abdundant STORED iron in macrophages?

Anemia of Chronic Disease *systemic inflammation via IL6

What anemia is a syndrome of primary hematopoietic failure and attendant pancytopenia, AI is the MCC but HSC problems can also be inherited or acquired= idiopathicc in 65%, two major mechanisms: extrinsince, immune mediated, and stem cell abnormalities, BM biopsy needed for diagnosis?

Aplastic Anemia

Aplastic Anemia can be due to whole body irradiation, chemo drugs or benzene, chloramphenicol, gold salts, hepatitis D and E*, telomerase mutation, short telomeres, fanconi anemia- AR defective protein complex for DNA repair- early in life with hypoplasia of kidney or spleen and bone anaomalies of thumbs or radii, Th1 cell are activated against antigens leading to IFNY and TNF to suppress and kill hemato progenitors, on histo you get a dry tap with?

hypocellular marrow mainly replaced FAT ``` granulocytopenia = bacterial infection thrombocytopenia= abnormal bleeding ```

Aplastic Anemia clinically see anemia with weakness pallor and dyspnea, petechiae and ecchymoses, neutropenia with persistent infections or sudden onset of fever and chills, reiculocytopenia, RBC are Macrocytic/Normochromic, NO splenomegaly, tx with BM transplant and immunosuppression with prognosis 5yr 75%, what virus did he talk about 75 times that causes Aplastic Anemia?

Parvovirus 19

What aplasia is primary marrow DO in which only erythroid progenitors are suppressed, associated with thymoma and large granular lymphocytic leukemias, drugs, autoimmune, parvovirus 19, met carcinoma and spent phase MPS, parvo is transient in normal individuals, may lead to aplastic crisis in pts with mod to severe hemolytic anemia due to brief cessation of erythropoiesis?

Pure Red Cell Aplasia

What anemia is marrow failure where space occupying lesions replace normal marrow elements leading to destruction of architecture, leukoeryhtroblastosis- abnl release of nucleated erythroid precursors, and even more immature than bands, teardrop RBCs, MCC is metastatic caner from the breast lung or prostate, also ft of spent phase MPD?

Myelophthisic Anemia Note: Myelophthisic disease is met tumor involving marrow or marrow fibrosis causing what was listed along with pancytopenia and depressed hematopoiesis

chronic renal failure is associated with anemia that is proportional to the severity of the uremia, causing kidneys to produce less EPO, decreasing RBCs, hepatocellular liver failure causes decrease marrow function causing macrocytic anemia, and endocrine disorders such as what may be assocaited with mild NC NC anemia?

Hypothyroidism

What polycythemia is abnormally high red cell count usually with an associated increase in the hemoglobin level, where hemoconcentration due to dec plasma volume - commonly due to dehydration, from water depriovation, prolonged vom/diarrhea, excessive diuretic use, or Gaisbock syndrome= stress polycythemia seen in HTN obese and anxious pt?

Relative Polycythemia

What polycythemia is increase in total red cell mass, primarily due to polycythemia vera= intrinsic abnl of hematopoietic precursors (myeloproliferative DO), or secondarily due to red cell precursors responding to increased levels of EPO such as phys response at high altitudes or EPO producing tumors or HIF1a stabilization (RCC)?

Absolute Polycythemia primary is low EPO secondary is HIGH EPO - seen in hypoxia COPD or lung disease too

What is the MCC of primary absolute polycythemia, a myeloproliferative DO assocaited with mutations leading to EPO indepedent growth of red cell progenitors, familial EPO receptor mutations can also induce EPO independent receptor activation, HIF1a = hypoxia induced factor that stimulates the transcription of EPO gene?

Polycythemia Vera THICK BLOOD

Excessive bleeding may be due to increased fragility of vessels, platelet deficiency or dysfunction or derangement of coagulation, which can occur along or in combination, what time asses the extrinsic pathway (primary pathway in vivo) and common coag paths, clotting of plasma after adding tissue thromboplastin and Ca, prolonged due to def or dysfxn of Factor V *VII* x, prothrombin or fibrinogen- measured in pts taking coumadin?

Prothrombin Time PT "Play Tennis OUTside"

What time asses the intrinsic and common coagulation pathways, clotting of plasma after adding koalin cephalin or Ca, prolonged due to def or dysfxn of V, *VIII,IX, X, XI, XII, prothrombin or fibrinogen, mesured in patients taking heparin?

Partial Thromboplastin Time PTT "Play Table Tennis INside"

What are obtained on anticoagulated blood using an electronic particle counter, abnl platelet counts are best confirmed by inspection of a peripheral blood smear, as clumping of platelets can cause spurious thrombocytopenia during automated counting and high counts may indicative of a Myeloproliferative disorder MPD such as essential thrombocythemia?

Platelet counts

Vessel wall abnormalities causing bleeding disorders, are relatively common, lead to petichiae and purpura without serious bleeding can sometimes bleed into more serious places, labs show platelets normal, PT PTT and bleeding time normal, commonly due to infection with neisseria, or what which causes cutaneous petechiae and purpura without thrombocytopenia?

Drug reaction due to immune complex deposition with resulting hypersensitivity vasculitis

What is systemic hypersensitivity due to immune complex deposition (mainly IgA) in the glomerular mesangial region, purpuric rash, colicky abdominal pain, polyarthralgia and acute glomerulonephritis is commonly seen?

Henoch Schonlein Purpura

What syndrome is an AD disorder of TGFB, patients have dilated tortuous thin walled vessels, bleeding can occur anywhere but MC under the mucous membranes of the nose*** epistaxis, tongue mouth eyes and GI tract, serious bleeding, see thinning of walls with telangiestatic formations, chr 9-AD, endoglin CD105 gene, *most frequent symptom is NOSE BLEEDS?

Hereditary Hemorrhagic Telangiectasia (weber-osler rendu syndrome)

What by definition is reduced platelet count of less than 100,000, less than 10,000 need transfusion, less than 20,000 see spont bleeding, 20-50,000 exacerbates posttraumatic bleeding, most bleeds involve small vessels of the skin and mucous membranes, most feared complication is intracranial bleeding, PT and PTT will be normal?

Thrombocytopenia

Causes of Thrombocytopenia include decreased production in aplastic anemia or leukemia, drugs or alcohol excess (megakaryo supp.), occur in pt with HIV* or myelodysplastic syndromes, sequestration and dilution also cause it, along with what which is due to inc consumption of platelets, mechanical injury, DIC/TTP/HUS, immune mediated destruction of platelets ITP, AI such as allo-antibodies = transfusion of IgG crossing the placenta?

DECREASED platelet survival

What is primary or secondary autoantibodies IgG destruction of platelets, secondary assoc with SLE HIV and Bcell -CLL, MC in women less than 40, 3x MC in females, primarily due to auto AB against platelets, removal of opsonized platelets by spleen but NO splenomegaly, tx with splenectomy, spleen BM and blood affected but not specific, see bleeding into skin and mucosal surfaces w insidious onset, NL PTT/PT low platelet count, NL megakaryocytes*, dx of exclusion?

Chronic Immune Thrombocytopenic Purpura ITP

Chronic Immune Thrombocytopenic Purpura ITP is assoc with melena, hematuria or excessive menstrual flow, subarachnoid hemorrhage and intracerebral hemorrhage are serious and fatal complications but are rare in treated pts, NO* splenomegaly or lymphadenopathy if present think ITP secondary to CLL, there will be large what in peripheral blood?

LARGE PLATELETS + inc megakaryocytes and low platelets

What is a disease of childhood which appeasrs 1-2 weeks after self limited viral infection, effects both sexes, auto antibodies to platelets develop but resolve in 6 months, severe cases of thrombocytopenia can be treated with glucocorticoids, about 20% develop childhood form of chronic ITP :( ?

Acute Immune Thrombocytopenic Purpura ITP

What is assoc with drugs such as quinine quinidine (malaria drugs) and vancomycin that bind platelet glycoproteins and create antigenic determinants that are recognized by antibodies, abs to the drug or the modified platlet molecules leads to macrophage ingestion and platelet removal, true auto abs may be induce by agents, platelet inhibitory agents that binds glycoprotein IIb/IIIa can also lead to creation of an immunogenic epitope?

Drug induced Thrombocytopenia

What is a lifethreatening venous and arterial thrombosis, antibodies form the HEPPF4 complexes (platelet factor 4) activates platelets and promotoes thrombosis even in the setting of thrombocytopenia, occurs 5-14 days after therapy DVT causes PE with thrombocytopenia (which is usually associated with bleeding**), tx is discontinue threapy and another anti clotting must be used?

Heparin Induced Thrombocytopenia HIT

What thrombocytopenia is one of the MC hematologic manifestations of this infection, virus infects megakaryocytes that express cd4 and cxcr4, infected cells are prone to apoptosis and impaired ability to produce platelets, see b cell hyperplasia and dysregulation leading to auto ab that may be directed against platelets?

HIV associated Thrombocytopenia

what is intravascular thrombi causing a microangiopathic hemolytic anemia and widespread organ dysfunction and the attendant consumption of platelets leading to thrombocytopenia, includes TTP, HUS, where PTT and PT are NORMAL (in DIC these will be abnormal)?

thrombotic micoangiopathy

What thrombotic micoangiopathy is hylaine thrombi occluding the capillaries of all organs in the body, assoc with ADAMTS13* decreased either inherited or acquired, MC in females clinically associated with a PENTAD of fever, thrombocyotpenia, microangiopathic hemolytic anemia, *transient neuro deficits* (mental changes), and renal failure, PT/PTT normal, tx with plasmapheresis?

Thrombotic Thrombocytopenic Purpura TTP *only way to tell between TTP and HUS is ADAMTS3 mutation

What thrombotic micoangiopathy is assoc with fever thrombocytopenia, microangiopathic hemolytic anemia and renal failure*, there are two types including typical which is due to endothelial damage with Ecoli 157H7 dysentery in undercooked beef- see bloody diarrhea, and atypical type seen in acquired or inherited defect of complement factor H CD46 or factor I?

Hemolytic Uremic Syndrome HUS

What syndrome is defective adhesion of platelets to subendothelial matrix (BS adhesion), inherited def of platelet membrane glycoprotein complex Ib-IX, is a receptor for vWF and essential for normal platelet adhesion so subendo matrix, pt have severe bleeding tendency, with *abnormally large platelets *GIANT platelets, absent aggregation to ristocetin, will aggregate to ADP, collagen, epinephrine and thrombin?

Bernard Soulier Syndrome

What is due to defective platelet aggregation, AR def of glyocprotein IIb/IIIa which bridge formation between platelets by binding fibrinogen, failure of platelets to aggregate in the rpesenc of ADP collagen epinephrine or thrombin, bleeding tendency severe, aggregates to ristocetin, NORMAL sized platelets?

Glanzmann Thrombasthenia

Bleeding due to coagulation factor def often occur into the GI and urinary tracts and into weight bearing joints (hemiarthrosis), oozes blood for days after a tooth extraction, develops a hemarthrosis after minor stress on a knee joint is suggestive of what, not vWF?

Hemophilia A/B

What is produced by endothelial cells, megarkaryocytes, and stabilizes factor VIII, when it is deficient, factor VIII is missing and this prolongs PTT, promotes adhesion of platelets to the subendothelial matrix, occurs via glycoprotein 1b, measured using ristocetin agglutination test?

Von Willebrand Factor vWF

What is the MC inherited bleeding disorder of humans, AD dz presenting with spontaneous bleeding from mucous membranes, excess bleeding from wounds or menorrhagia, usually mild hemostatic stress, labs show normal platelet, plasma protein level reduced, factor VIII decreased, prolonged PTT* as seen in Hemophilia A (VIII) and Hemophilia B (IX)?

von Willebrand Disease *give desmopressin before dental work and surgery

von Willebrand Disease has 3 types, type 1 is AD with mild mod deficiency, quantitative defect, MC subtype, usually point mutation, ptt enlonged, what type is AR with very low levels and severe clinical manifestations, quantitative defect, factor VIII stability is affected, may resemble hemophilia usually frameshift or deletion mutation at both alleles, PTT prolonged, **hemarthrosis seen (uncommon tho)?

Type 3!

What disease is due to factor VIII deficiency, which is an essential cofactor for factor IX in the coagulation cascade, and is the MC hereditary disease assoc w lifethreatening bleeding, most severe is X chromosome inversion= no synthesis, X linked recessive, point mutation, and risk of bleeding corresponds to degree of def (inversion is worst), see easy bleeding, hematomas, no petechiae***, prolongedPTT but NORMAL pt, tx with recomb factor VIII infusions?

Hemophilia A *******MC associated with HEMORRHAGIC HEMARTHROSES see loss range of motion, muscle loss, destruction of joint

What is a factor IX deficiency that is xlinked recessive and clnically identical to hemophilia A, with prolonged PTT and normal PT (intrinsic pathway affected), dx via assaying factor levels, treat with recomb factor IX?

Hemophilia B = Christmas Disease

What is acute subacute or chronic thrombo-hemorrhagic dz with excessive activation of coagulation and formation of thrombi in the microvasculature of the body= consumption of platelets (thrombocytopenia) fibrin, and coagulation factors, fibrinolysis activation, with sx including tissue hypoxia, infarction, hemorrhage, two main triggers inlcuding release of tissue factor into circulation or widespread injury to endothelial cells?

Disseminated Intravascular Coagulation DIC

Consequences of Disseminated Intravascular Coagulation DIC are widespread deposition of fibriin in microcirculation causing thrombosis- consumption of platelets leading to bleeding, along with ischemia, MC due to obstetric complicatoins (acute DIC-bleeding diathesis), or carcinomatosis (chronic DIC= thrombotic complications), clinically see bleed from everywhere, resp signs and symptoms (dyspnea cyanosis), neuro signs such as convulsions and coma, oliguria and acute renal failure and circulatory failure and?

SHOCK