Hemolytic Anemias

RBC defects in RBC membrane, metabolism, Hgb content (hemoglobinopathies):

intrinsic

RBC defects caused by malaria, drugs, immune hemolysis, trauma, microangiopathic (MAHA: TTP, HUS, DIC):

extrinsic

site of hemolysis that is related to RBC fragmentation (DIC, heart prosthetic pathways):

intravascular

site of hemolysis that is macrophage-mediated, in spleen, BM, or liver:

extravascular

main abnormality formed in intravascular hemolytic anemias:

schistocytes

main abnormality formed in extravascular hemolytic anemias:

spherocytes

total bilirubin is ____ in intravascular hemolytic anemias.

increased

total bilirubin is ____ in extravascular hemolytic anemias.

increased

indirect (unconjugated) bilirubin is ____ in intravascular hemolytic anemias.

increased

indirect (unconjugated) bilirubin is ____ in extravascular hemolytic anemias.

increased

direct (conjugated) bilirubin is ____ in intravascular hemolytic anemias.

normal

direct (conjugated) bilirubin is ____ in extravascular hemolytic anemias.

normal

LDH (LD1) is ____ in intravascular hemolytic anemias.

increased

LDH (LD1) is ____ in extravascular hemolytic anemias.

increased

haptoglobin is ____ in intravascular hemolytic anemias.

decreased

haptoglobin is ____ in extravascular hemolytic anemias.

decreased

free hemoglobin is ____ in intravascular hemolytic anemias.

increased

free hemoglobin is ____ in extravascular hemolytic anemias.

increased

hemopexin is ____ in intravascular hemolytic anemias.

decreased

hemopexin is ____ in extravascular hemolytic anemias.

decreased

urine urobilinogen is ____ in intravascular hemolytic anemias.

increased

urine urobilinogen is ____ in extravascular hemolytic anemias.

increased

urine free hemoglobin is ____ in intravascular hemolytic anemias.

positive

urine free hemoglobin is ____ in extravascular hemolytic anemias.

negative

urine methemoglobin is ____ in intravascular hemolytic anemias.

positive

urine methemoglobin is ____ in extravascular hemolytic anemias.

negative

urine prussian blue staining of urine sediment is ____ in intravascular hemolytic anemias.

positive

urine prussian blue staining of urine sediment is ____ in extravascular hemolytic anemias.

negative

hemoglobin, HCT, and RBC count is ____ in intravascular hemolytic anemias.

decreased

hemoglobin, HCT, and RBC count is ____ in extravascular hemolytic anemias.

decreased

most intrinsic RBC defects are inherited; however, ____ is an exception as it is intrinsic but acquired.

PNH

a 5 year old girl was seen by her physician several days before the current visit and was diagnosed with pneumonia. she was prescribed a standard course of antibiotics. her mother has brought her to the physician again because the girl’s urine began to darken after the first visit and now is alarmingly dark. the girl has no history of anemia, and there is no family history of any hematologic disorder. the CBC shows a mild anemia, polychromasia, and a few schistocytes. this anemia could be categorized as:

a. acquired, fragmentation

b. acquired, macrophage mediated

c. hereditary, fragmentation

d. hereditary, macrophage mediated

acquired, fragmentation

a patient has a personal and family history of a mild hemolytic anemia. the patient has consistently elevated levels of total and indirect serum bilirubin and urinary urobilinogen. the serum haptoglobin level is consistently decreased, whereas the reticulocyte count is elevated. the latter can be seen as polychromasia on the patient’s peripheral blood film. spherocytes are also noted. which one of the findings reported for this patient is inconsistent with a classical diagnosis of fragmentation hemolysis?

a. elevated total and indirect serum bilirubin

b. elevated urinary urobilinogen

c. decreased haptoglobin

d. spherocytes on the peripheral blood film

spherocytes on the peripheral blood film

an intrinsic defect of mutations in proteins which maintain vertical attachments:

hereditary spherocytosis

mostly mutations in ankyrin and spectrin:

hereditary spherocytosis

RBCs lose surface area (low s/v ratio), lose deformability, destroyed by the spleen leading to ____ hemolysis, or some RBCs may endure further membrane modifications forming microspherocytes.

extravascular

refers to the triad in hereditary spherocytosis:

anemia, splenomegaly, jaundice

hallmark of ____ is spherocytosis (not specific), with increased polychromasia indicative of reticulocytosis (up to 10%):

hereditary spherocytosis

RBC indices of hereditary spherocytosis have high ____ (> 36 mg/dL).

MCHC

RBC indices of hereditary spherocytosis have high ____ (> 4%).

CHCM

indirect bilirubin is ____ in hereditary spherocytosis.

increased

LDH is ____ in hereditary spherocytosis.

increased

haptoglobin is ____ in hereditary spherocytosis.

decreased

childhood hemolytic anemia, family history of similar abnormalities, uniform spherocytes on PBS is highly suggestive of:

hereditary spherocytosis

family history, splenomegaly, high MCHC, reticulocytosis, and spherocytes on the PBS is indicative of:

hereditary spherocytosis

in hereditary spherocytosis, osmotic fragility test would be ____

increased

in hereditary spherocytosis, eosin-5’-maleimide (EMA) binding test is ____.

decreased

defects in horizontal interactions:

hereditary elliptocytosis

95% of cases of hereditary elliptocytosis is a mutation in ____ genes (alpha and beta).

spectrin

RBCs become elliptical over time in hereditary elliptocytosis. true or false?

true

severe form of hereditary elliptocytosis in which RBCs are fragmented on heating due to low stability (41-45°C):

HPP

extreme poikilocytosis, MCV is very low (50-65 fL), fragmentation, microspherocytosis, and elliptocytosis (similar to burns):

HPP

RBC membrane is highly permeable and deficiency in stomatin protein or mutation in RhAG protein:

overhydrated hereditary stomatocytosis

dehydrated hereditary stomatocytosis may also be known as:

hereditary xerocytosis

defect in membrane cation permeability causing RBCs to become dehydrated:

dehydrated hereditary stomatocytosis

a patient has anemia that has been worsening over the last several months. the hemoglobin level has been declining slowly, with a drop of 1.5 g/dL of hemoglobin over about 6 weeks. polychromasia and anisocytosis are seen on the peripheral blood film, consistent with the elevated reticulocyte count and RDW. serum levels of total bilirubin and indirect fractions are normal. the urinary urobilinogen level also is normal. when these findings are evaluated, the conclusion drawn that the anemia does not have a hemolytic component. based on the data given here, why was hemolysis ruled out as the cause of anemia?

a. the decline of hemoglobin is too gradual to be associated with hemolysis

b. the elevation of the reticulocyte suggests a malignant cause

c. evidence of increased protoporphyrin catabolism is lacking

d. elevated RDW points to an anemia of decreased production

evidence of increased protoporphyrin catabolism is lacking

which of the following sets of test results is typically expected with chronic fragmentation hemolysis? (*refer to image)

c

rare chronic, intravascular hemolytic anemia, acquired membrane defect:

PNH

RBCs lack CD55 and CD59 in:

PNH

in PNH, the absence of CD55 and CD59 renders RBCs susceptible to lysis by ____.

complement

RBCs display mosaicism where some RBCs are normal and some are abnormal:

PNH

what level of PNH shows normal level of CD55 and CD59 with little or no lysis?

type I

what level of PNH shows partial CD55 and CD59 deficiency with relative resistance to lysis?

type II

what level of PNH shows complete deficiency in CD55 and CD59 and is highly sensitive to lysis?

type III

most common RBC types in PNH:

combination of I and III

detection of CD55 and CD59 by flow cytometry is the confirmatory test of ____.

PNH

critical to RBCs as it is the only means to produce NADPH to maintain a healthy supply of reduced glutathione:

G6PD

G6PD enzyme is encoded on the ____ chromosome.

X

most common RBC enzyme defect:

G6PD deficiency

african males with ____ (A- variant) are protected against plasmodium falciparum malaria.

G6PD deficiency

oxidizing drugs, infections, and fava beans are triggers of acute hemolytic anemia in:

G6PD deficiency

G6PD deficiency anemia is moderate to severe with usually ____ RBCs.

normocytic/normochromic

denatured Hgb that is only seen in supravital stains:

heinz bodies

in G6PD deficiency, serum haptoglobin is very ____.

decreased

in G6PD deficiency, indirect bilirubin is ____.

increased

in G6PD deficiency, LDH is ____.

increased

in G6PD deficiency, plasma hemoglobin (intravascular hemolysis) is ____.

increased

a patient experiences an episode of acute intravascular hemolysis after taking primaquine for the first time. the physician suspects that the patient may have G6PD deficiency and orders an RBC G6PD assay 3 days after the hemolytic episode began. how will this affect the test result?

a. absence of enzyme activity

b. false decrease in enzyme activity due to hemoglobinemia

c. false increase in enzyme activity due to reticulocytosis

d. no effect on enzyme activity

false increase in enzyme activity due to reticulocytosis

key enzyme of the glycolytic pathway:

pyruvate kinase

catalyzes the conversion of phosphenolpyruvate to pyruvate forming ATP:

pyruvate kinase

PK deficiency causes premature destruction of ____.

RBCs

clinical presentation includes anemia, jaundice, splenomegaly and gallstones (chronic hemolysis):

PK deficiency

in PK deficiency, ____ experience severe anemia.

neonates

in PK deficiency, ____ experience severe to compensated anemia.

adults

echinocytes (burr cells) are highly indicative of:

PK deficiency

conditions where RBC survival is shortened because of antibody-mediated mechanisms:

immune hemolytic anemia

some antibodies of immune hemolytic anemia are able to activate ____.

complement

in immune hemolytic anemia, RBCs with antibodies or complement are removed by ____ (extravascular).

macrophages

in immune hemolytic anemia, RBCs with antibodies or complement are removed by ____ (intravascular).

complemented mediated hemolysis

in immune hemolytic anemia, RBCs with antibodies or complement cannot be removed by a combination of extravascular and intravascular processes. true or false?

false

____ mediated hemolysis can result in both extravascular and intravascular hemolysis.

IgM

____ mediated hemolysis is predominantly extravascular RBCs removed by macrophages in the spleen/liver.

IgG

immune hemolytic anemia is DAT ____.

positive

premature RBC destruction and anemia caused by autoantibodies that bind to the RBC surface with or without complement activation:

autoimmune hemolytic anemia

what are the 4 types of autoimmune hemolytic anemias?

WAIHA, CAD, PCH, mixed AIHA

what is the most common type of autoimmune hemolytic anemia?

WAIHA

what immunoglobulin is associated with WAIHA?

IgG

what is the optimum reactivity temperature of autoantibody for WAIHA?

37°C

what is the complement activation for WAIHA?

variable

what is type of hemolysis is primarily associated with WAIHA?

extravascular