Exam 13 - Heme15 - Hemolytic Anemia

Front 1

Definition:

... is the premature destruction of red blood cells

Hemolysis leads to anemia when ... is incapable of compensating for the blood cell destruction

Presenting symptoms depend upon the rate of hemolysis and severity of anemia

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Hemolysis
the bone marrow

Front 2

Pathophysiology:

Normal RBC survival is ... days; if survival of RBC’s is decreased and we can directly demonstrate increased ..., or increased production as compensation for destruction, we can support a diagnosis of hemolysis

Increased destruction is evidenced by ... and increased production is evidenced by ...

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120
destruction
hyperbilirubinemia
reticulocytosis

Front 3

Pathophysiology:

Using the presence of anemia to detect hemolysis will overlook most hemolytic destruction; anemia as evidence of hemolysis requires an RBC lifespan of ... days or less

Anemia as a result of hemolysis is only revealed when destruction increases to 6 to 8 fold normal because the ... can increase production by the same capacity

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20
bone marrow

Front 4

Pathophysiology:

If reticulocytosis and indirect hyperbilirubinemia are used to detect hemolysis, hemolytic process may be evident at an RBC lifespan of 40 to 50 days

All patients with reticulocytosis and indirect hyperbilirubinemia have a ... disorder; patients may have hemolysis but not be recognizable by anemia if the bone marrow is able to respond with a high rate of ...

Back 4

hemolytic
reticulocytosis

Front 5

Pathophysiology:

Hemolysis results from both hereditary and acquired defects of the red blood cell

All hereditary hemolytic disorders are a result of ...-corpuscular defects and acquired defects are ...-corpuscular in nature

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intra
extra

Front 6

Pathophysiology:

Hemolytic anemia is the end result mediated by a large number of ... and acquired disorders

The cause of premature RBC destruction is varied and can be the result of intrinsic membrane defects, abnormal hemoglobins, RBC enzymatic defects, immune-mediated destruction, mechanical RBC injury and the effect of hypersplenism

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hereditary

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Patholphysiology:

Hemolysis causes release of hemoglobin, lactate dehydrogenase (LDH), an increase in indirect bilirubinemia and increased ... in the urine from hemoglobin breakdown

Mild anemia may occur if hemolysis is mild and the bone marrow can compensate; severe anemia occurs if hemolysis is more vigorous or the bone marrow is profoundly ... such as in Parvovirus B19 infection

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urobilinogen
suppressed

Front 8

Genetic Causes of Hemolytic Anemia:

Genetic conditions of hemoglobin
-... cell anemia and mixed sickle syndromes
-Thalassemia

Genetic conditions of RBC metabolism
-... deficiency
-Pyruvate kinase deficiency

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Sickle
G-6-PD

Front 9

Genetic Causes of Hemolytic Anemia :

Genetic conditions of RBC membrane
-Hereditary ...
-Hereditary elliptocytosis

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spherocytosis

Front 10

Acquired Hemolytic Anemia:

Immune-mediated; Coomb’s positive
-... antibody autoimmune hemolytic anemia
*Idiopathic
*Systemic lupus erythematosis (SLE)
*Evan’s syndrome
*Drugs
*Chronic lymphocytic leukemia
-... antibody autoimmune hemolytic anemia
*Idiopathic cold hemaggluttinin syndrome
*Infectious mononucleosis and mycoplasma
*Paroxysmal cold hemoglobinuria
*Lymphoma

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Warm
Cold

Front 11

Acquired Hemolytic Anemia
Immune-mediated; Coomb’s positive

Drug-related hemolytic anemia
-...; hapten-mediate antibody against RBC
-Alpha-methyl dopa

Allo-immune hemolytic anemia
-Hemolytic disease of the ...
*Rh, ABO, etc
-Hemolytic reactions to ... blood, poor typing

Back 11

Penicillin
newborn
transfused

Front 12

Acquired Hemolytic Anemia:

Non-immune-mediated hemolysis
-Drugs; direct RBC membrane toxicity
-Toxins
-Trauma
-MAHA; TTP, HUS, DIC, and HELLP
-Infections; malaria, babesiosis, sepsis
-... disorders; PNH (Paroxysmal Nocturnal Hemoglobinuria)
-Liver disease

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Membrane

Front 13

Race Distribution of Sickle Cell Anemia:

Most hemolytic anemias ... race specific

Sickle cell disorders in the United States occur primarily in Africans, African Americans, some Arabic groups, and infrequently in Asian Indians

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are not

Front 14

Race Distribution of G-6-PD Deficiency:

There are multiple glucose-6-phosphatase deficiency types

There is a variant found primarily in West Africans and African Americans with about 10 per cent of African Americans carrying at least a ... variant gene

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single

Front 15

Race Distribution of G-6-PD Deficiency:

The ... variant occurs in some people of mediterranean and asian origin

G-6-PD is an X-linked recessive trait in which ... are carriers and ... are effected

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mediterranean
females
males

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Age Distribution of Hemolysis:

Although hemolytic anemia can occur at any age, ... aged and ... patients are more often affected, generally acquired hemolysis

Hereditary hemolysis generally occurs at ... ages

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middled
older
younger

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Differential Diagnosis:

Ineffective erythropoiesis; shares features of hemolysis with RBC breakdown prior to cell release from the bone marrow
-Thalassemia
-Myelodysplastic syndrome

Megaloblastic anemia
-... deficiency
-... deficiency

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B12
Folate

Front 18

Pathophysiology, Signs and Symptoms:

A patient requiring transfusion without evidence of blood loss or bone marrow suppression may have ...

Severe anemia may cause obvious symptoms but in compensated disease hemolysis may only be evident by ... testing

Intra-vasular hemolysis may cause loss of ... via the urine and superimposed ... deficiency

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hemolysis
laboratory
iron
iron

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Pathophysiology, Signs and Symptoms:

Hyperbilirubinemia associated with hemolysis may cause bilirubin ...

... produces dark, tea-colored urine and commonly occurs in patients with intravascular hemolysis

Patients with TTP may have syndrome of fever, neurologic changes, renal failure, thrombocytopenia, and MAHA

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gallstones
Hemoglobinuria

Front 20

Pathophysiology, Signs and Symptoms:

Penicillin, quinine, quinidine, and L-dopa among other agents may cause ..., usually as a result of immune-mediated destruction

Oxidant drugs, infectious and other stresses may cause hemolysis in ... deficiency by overwhelming oxidant stress tolerance

Angina, dyspnea, tachycardia, pain with walking, and weakness; may represent ... of cardiac, peripheral vascular and pulmonary disease from progressive anemia

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hemolysis
G-6-PD
decompensation

Front 21

Physical Findings:

Pallorous mucus membranes

Fluctuating jaundice

...
-Occurs in hereditary spherocytosis and elliptocytosis, some immune-mediated anemias bit not sickle cell or G-6-PD deficiency
-Suggests some acquired illnesses like CLL, other lymphomas and systemic lupus (SLE)

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Splenomegaly

Front 22

Physical Findings:

Bleeding and petechiae suggest TTP, HUS, DIC and HELLP syndrome

Butterfly malar rash and arthritis suggest ...

Lymphadenopathy and splenomegaly suggest diagnosis of CLL or other ...

Mild jaundice with bilirubin up to 4 mg/dl may indicate ... although gallbladder and liver disease must be excluded

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SLE
lymphoma
hemolysis

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Laboratory Studies and Features:

Complete blood count: Hb/Hct, WBC’s, and platelets

... varies according to severity of hemolysis and effectiveness of bone marrow response

TCP can occur in SLE, CLL, MAHA, TTP, HUS, DIC, HELLP and Evan’s Syndrome

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Hb

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Laboratory Studies and Features:

Morphological exam of peripheral smear
-Polychromasia may reflect reticulocytosis
-Spherocytes may indicate hereditary spherocytosis or AIHA
-Schistocytes suggest MAHA which can be seen in TTP, HUS, DIC, or mechanical damage
-May reveal underlying ... like CLL or peripheralizing lymphoma

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malignancy

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Laboratory Studies and Features:

RBC indices
-... MCV may be seen in hemolytic anemia which can occur in chronic intravascular hemolysis including PNH as a result of iron deficiency
-... MCV is usually due to megaloblastic anemia though can occur in liver disease and other disorders or with reticulocytosis
-High MCH and MCHC suggest ...

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Low
High
spherocytosis

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Laboratory Studies and Features:

Bone marrow will demonstrate erythroid ... without other particularities

Reticulocytosis
-Seen in but not specific for hemolysis
-Can be seen acutely in ... loss or after replacement of iron, folate, or B12 deficiency
-May not see reticulocytosis in bone marrow that is ... despite hemolysis

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hyperplasia
blood
suppressed

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Laboratory Studies and Features:

Lactate Dehydrogenase
-... LDH is a necessary but not specific laboratory abnormality in hemolysis
-LDH isoenzyme 1 and 2 are elevated in hemolysis but also in myocardial infarction and a variety of malignancies

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Elevated

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Laboratory Studies and Features:

Serum haptoglobin
-Low serum haptoglobin is invariably seen in moderate to severe hemolysis
-Decreased haptoglobin more likely in ... than ... hemolysis
-Serum haptoglobin is an acute phase reactant, and infection, chronic hemolysis, and other chronic reactive processes may ... haptoglobin levels to mask on-going hemolysis

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intravascular
extravascular
raise

Front 29

Laboratory Studies and Features:

Indirect bilirubinemia
-Unconjugated bilirubin is seen in hemolysis but also in Gilbert’s; an inherited bilirubin disorder
-Indirect bilirubinemia in hemolysis is generally less than 4mg/dl
-Levels of hyperbilirubinemia greater than 4mg/dl in hemolysis indicate inherent ... dysfunction or gallstone-induced ... disease

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liver
liver

Front 30

Laboratory Studies and Features:

... and serum ... are the most sensitive tests for hemolysis

Direct antiglobulin test (Coomb’s) is positive in 90+% of immune hemolysis

Urine free hemoglobin and hemosiderin suggest ... hemolysis; plasma haptoglobin is rapidly saturated with the excess free Hb filtered by the glomerulus

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LDH
haptoglobin
intravascular

Front 31

Laboratory Studies:

Cold agglutinins are cold-reacting antibodies; anti-I in mycoplasma infection, anti-i in mononucleosis, and anti-P in paroxysmal cold hemoglobinuria; usually bind complement causing ...-vascular hemolysis

A specific ... enzyme screen or Heinz body preparation can detect deficiency

Hemoglobin ... can demonstrate sickle cell disease

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intra
G-6-PD
electrophoresis

Front 32

Treatment:

Transfusion therapy
-Avoid transfusions in ... hemolysis but transfuse to alleviate cardio-pulmonary stress in any hemolytic process or vaso-occlusive injury in hemoglobinopathies

Discontinue offending medications
-... medications that can cause hemolysis or oxidants in immune-mediated hemolysis or G-6-PD deficiency

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immune
Discontinue

Front 33

Treatment:

Give ... which may be consumed in hemolysis and cause superimposed megaloblastosis

... are the best-established therapy in immune-mediated hemolysis

Intravenous immune globulin can limit immune-mediated hemolysis acutely (short term)

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folic acid
Glucocorticoids

Front 34

Treatment:

... can control hemolysis in hereditary spherocytosis and refractory extravascular immune-mediated hemolysis

Vincristine or Rituxan (...) may be helpful in refractory immune-mediated hemolysis

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Splenectomy
rituximab

Front 35

Treatment Process for Hereditary Spherocytosis or Elliptocytosis:

RBC membrane defects lead to formation of spherocytes that are rapidly cleared by the spleen; ... reduces the risk of bilirubin gallstones and ... is usually curative of the hemolysis

Only severe forms of elliptocytosis require ...

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cholecystectomy
splenectomy
splenectomy

Front 36

Treatment Process/Sickle Cell Anemia:

Vaso-occlusive crisis
-IV hydration while maintaining body warmth
-Supplemental oxygen
-IV or oral antibiotics for possible infection
-Narcotic analgesia for severe pain (patient-controlled analgesia) and NSAID’s for minor pain
-Careful exclusion of infection required, and treatment of reasonably suspected infection
-... to decrease Hb S density and abort the ischemic episode

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Blood transfusion

Front 37

Treatment Process/Sickle Cell Anemia:

Vaso-occlusive crisis
-Autosplenectomy from prior ischemic crises increases ... risk by the teen-age years; use therapeutic antibiotics in the acute setting and prophylactic antibiotics chronically
-Ischemic chest syndrome including chest pain, fever, dyspnea, and pulmonary infiltrates presents exactly like ... and must be distinguished

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infectious
pneumonia

Front 38

Treatment Process/Sickle Cell Anemia:

Aplastic crisis
-Progressive manifestations of anemia
-Triggered by Parvovirus B-19 which prevents ... and RBC production
-... may be effective against parvovirus and the patient almost always needs blood transfusion to restore sufficient oxygen delivery to relieve fatigue, weakness, malaise and sometimes ischemia

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reticulocytosis
IVIG

Front 39

Treatment Process/Sickle Cell Anemia:

Splenic sequestration crisis; acute painful splenic and abdominal distension
-Analgesia, IV fluids and ...

Hemolytic crisis; accelerated RBC destruction
-IV fluids and oxygen
-... of blood

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splenectomy
Transfusion

Front 40

Treatment Process/AIHA:

Symptomatic anemia/evident hemolysis
-Discontinue possible offending medications
-Give ... as primary immunosuppression
-IVIG, vincristine, Rituxan, and splenectomy as initial short-term or salvage therapies
-Transfusion therapy; ... in cold antibody mediated disease; difficult cross-matching, slow rate of administration; most compatible unit

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steroids
warmed

Front 41

Treatment Process/G-6-PD, Pyruvate Kinase, and Thalassemia:

Symptomatic anemia
-Establish a specific diagnosis
-Stop offending agents and provide support
-Transfuse for symptoms
-Remove excess ... in the chronically transfused

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iron