UAMS Hematology exam 3 notes

Anemias + Thalassemias

IDA lab results

Decreased: Hct, Hgb (makes them hypo/micro, the cells continue dividing in wait for more iron that never comes)

First the stores go down

Second the RBCs are made with less iron

Third the Hgb and Hct deplete

Fourth the symptoms appear

Hemosiderosis lab results (iron overload)

serum iron range

50-160 ug/dL

TIBC range

250-499 ug/dL

% Transferrin sat range

20-55%

Ferritin range

Fe: 12-160 ng/mL

Ma: 40-400 n/mL

What lab results are the basis for Microcytic anemias

Decreased: MCH, MCHC, MCV

Increased: RDW

Hypo/micro cells

Hemochromatosis lab results

Increased: Iron, Transferrin sat, ferritin, Hgb, Hct

Also increased liver enzymes: AST, ALT

Lead poisoning lab results

Decreased: MCV, Hgb

Coarse Basophilic stippling.

Seen on slides for Sideroblastic Anemia

Heme not made properly, iron has nowhere to go.

Leads to build up and forming of ringed sideroblasts.

In mature cells it makes pappenheimer bodies.

Will see Dimorphic RBCs and Ringed Sideroblasts.

Anemia of Chronic disease/inflammation lab results

Decreased: Serum iron, TIBC

Increased Ferritin.

Soluble Transferrin receptors: Normal

Megaloblastic anemia lab results

Decreased: RBC, WBC, Plt, Retics

Increased: MCV, Bili, LD

Aplastic anemia lab results

Pancytopenia

Decreased: WBC, RBC, Plt, retics

Increased: Infections

Anemia bleeding or bruising

Nc/Nc 

Hypoplastic BM (90:10, normal is 50:50 ), more fat present

Falconi anemia characteristics 

Autosomal recessive chromosomal instability

Short stature

Hypogonadism

Hypocellular BM

Dyskeratosis Congenia characteristics

BM failure disease

Abnormal skin (white spots)/nails 

Oral leukoplakia

Shwachman-Bodian-Diamond Syndrome characteristics

pancreatic insufficiency

Skeletal abnormalities

Neutropenia leads to immune dysfunction

Sweat chloride test is Normal

Acquired Idiopathic Aplastic anemia characteristics

50-75% of aplastic anemias

Acquired secondary aplastic anemia characteristics

25% of cases

Old antibiotics (chloramphenicol)

Industrial chemicals (Benzene)

Insecticides (DDT)

Radiation

Infections (viral (TB, Hep, HIV, IM))

Myelodysplastic Syndromes lab results

Nc/Nc anemia

MCV slightly increased, but also possibly decreased in classic sideroblastic anemia

Neutropenia/thrombocytopenia

Megaloblastiod features

Agranular neuts

Asynchrony

Ringed sideroblasts

Basophilic stippling

Pappemheimer bodies

Other N/N anemia lab results

Though N/N, can be slightly low.

Decreased: serum iron, TIBC

Increased: Ferritin

Acute blood loss lab results

In recovery: many retics

In a few hours increased: WBCs and Plts

Hereditary Spherosytosis lab results

Defective RBC membrane: ankyrin, spectrin

Increased: MCH/MCHC (>36%), LD, Bilirubin, Osmotic fragility, autohemolysis, Retics

Spherocytes, Aniso, polychromasia

Mild jaundice, Anemia, Enlarged spleen

European decent

May need splenectomy in severe cases, or treat with folic acid till old enough (over 6yrs)

Hereditary Elliptocytosis lab results

Normal: MCV, MCHC, MCH

Everything else normal, not really a terrible thing

Autosomal dominant

Pyropoikilocytosis

Heat makes the RBCs break

G6PD deficiency lab results

Heinz bodies ( Reduced glutathione), polychromasia, N/N, early destruction of RBcs hence the hemolytic name.

African american males, sex linked

Watch for certain anti malarials and fava beans

Fluorescent Spot test

Pyruvate kinase deficiency lab results

Embden meyerhoff pathway, 90% energy

Not enough ATP made to make stuff

Decreased: Hgb, Hct

Jaundice, Retics, echinocytes

Possible splenectomy if sever enough

What are the Extracellular defect hemolytic anemias

• Infections
• Chemicals and toxins
• Physical agents
• Microangiopathic hemolytic anemia
• Hypersplenism
• General systemic disorders

Immune hemolytic anemia

What are the Intra cellular hemolytic anemias

Hereditary Defects
• Red cell membrane defects
• Enzyme defects
• Hemoglobinopathies
• Thalassemia

Acquired
• Paroxysmal nocturnal hemoglobinuria

What are the membrane defect hemolytic anemias

The hereditary ones (spherocytes, elliptopcytes, stomatocytes etc.)

Stomatocyte hereditary membrane defect

imbalance of cations (Na, K)

Commonly acquired through alcoholism, meds, malignancy

rare causes dehydrated S H, K gets nside but Na cannot, leading to no water in cells.

Acanthocyte membrane defect

Think liver and lipids

ABETALIPOPROTEINEMIA

Paroxymal Nocturanl Hemoglobinuria lab results

Acquired with intracellular defects, Abnormality of HSC membranes, due to somatic mutation.

RBCs more sensitive to complement lysis

Decreased: CD 55 (decay accelerating factor/DAF), CD59 (Membrane inhibiting of reactive lysis/MIRL)

Worst hemolysis in sleep, due to increased CO2/slight drop in blood pH.Pt sees red urine and wonders why, first morning or after surgery/exercise

Pancytopenia, Retics, episodic hemoglobinuria, HA of unknown origin

Screen with sugar water test, confirm with Hams test

Warm Autoimmune hemolytic anemia lab results

Mainly idiopathic, but also secondary to CLL.lymphoma

70%, 

Transfuse as last resort,glucocorticoids to supress antibodies,

Spherocytes, polychromaisa, Positive DAT (differs the HS and this)

Cold AIHA lab results

Often secondary to infection (MP, IM)

Antibodies react to I/i antigen on RBCs

Acrocyanosis, Anemia symptoms, Polychromasia, Agglutinated cells,  specimen agglutinates at low temps, Positive DAT

Hgb and Hct not always low (variable)

Keep Pt warm

March hemoglobinuria lab results

AKA sports anemia, trauma from physical disruptions

Dark urine from hgb/hemosiderin

Minimal disease

Microangiopathic Anemia lab results

Cells fragmented by fibrin in vessels or defective heart valve

Schistocytes

Seen in Coag disorders (DIC, HELLP, HUS, TTP)

Treat primary coag disorder.

Chemical, Microorganism, Physical agents lab results

Retics and polychromasia

Overall abnormal tests for HA

Increased: Unconjugated Bili, LD, Urine/stool urobili, urine hgb/hemosiderin.

Decreased: haptoglobin, hct (unless compensated)

MCV N or slight increase

Retics, BM RBC hyperplasia, fragments, spherocytes, polychromasia, agglutination

Specific tests for specific diseases

• Autoimmune Hemolytic Anemia – DAT

• Hemoglobinopathies – Hemoglobin Electrophoresis

• G6PD Deficiency – Heinz bodies; G6PD assay

• Hereditary Spherocytosis and Elliptocytosis – Osmotic
Fragility

• PNH – Sucrose Hemolysis and Ham Test

What is a Hemoglobinopathy

Abnormal amount of globin chains or globin chain being abnormal itself

Sickle cell lab results

Valine substitutes glutamic aicd on 6th position of beta chain, those molecules migrate to form the sickle cell structure, deformed cells removed by spleen.

Autosomal recessive, belt (africa, middle east, USA)

Associated with malaria

Trait wil be normal until oxygen <40%

Disease will go in spurts/crisis, infarts to bone, eyes, brain ,abdomen. possible aplastic crisis, anemia, sensitive to infections.

Kinda treat symptoms, stay hydrated.

N/N with sickle forms, autosplenectomy signs, target cells when not in crisis.

Increased: bili, retics, WBCs

Solubility test/hemoglobin electrophoresis for diagnosis

Hgb C disease lab results

Lysine substituted for glutamic acid on 6th position of beta chain, mild chronic anemia with splenomegaly.

African americans.

N/N, lots of target cells, Hgb c crystals

Solubility and hgb electrophoresis to diagnose

treatment not normally needed

Hgb Sc disease lab results

Positive sickle cell solubility test

Hgb electrophoresis to diagnose

Still has some effects of sickle cell, but less damaging.

Hgb E disease lab results

beta chain variant

Mild chronic HA, increased target cells, H/M anemia.

SE asian decent

Negative Solubility test

Beta thalassemia lab results

genetic disorder causing abnormal amount of mRNA that makes reduced or absent beta chains (major, minor/intermediate).

Mediterranian, SE asia, saudi arabia, africa

Silent carrier: heterozygous, no abnormalities

Minor: hetero state, mild HA, m/h cells, no symptoms.

Intermediate: mild-moderate HA, m/h cells, moderate symptoms, transfusion independence.

Major: homozygous state, severe HA, m/h cells, severe symptoms, transfusion dependent

B thalassemia Major lab results

No hgb A, increased A2/F (mostly F)

Decreased: Hgb, Hct, indicies

Increased: RBC, RDW

Marked expansion of marrow spaces (tries to make cells but doesnt work, cells are inclusion ridden), extreme skeletal damage.

Marked aniso/poik, M/H rbcs, target cells, NRBCs, Basophilic stippling

Transfusions throughout lifetime, HSC transplants, possible gene therapy for treatment

B thalassemia trait lab results

Mild anemia, M/H RBCs, target cells, Basophilic stippling (resembles IDA).

Decreased: Indices.

Few symptoms, may become more evident in pregnancy 

A Thalassemia lab results

Genetic deletion, 4 genes available on chromosome 16 to delete (B only has 2 on chromosome 11)

1 gene deletion: 30% African americans, no symptoms, normal hematology values

2 gene deletion trans (one from each side): no symptoms, slight hypo/micro cells, african american.

2 gene deletion trans(two from one side): no symptoms, slight hypo/micro RBCs, Asians

3 gene deletion: sever HA, aka Hgb H (H has 3 lines), mostly Hgb H (tetramer of Beta chains, Asians

4 gene deletion: Hydrops fatalis, aka Hgb Bart (tetramer of G chains) (bart has 4 letters), always fatal, no Hgb A/A2/F, Asians

Hereditary persistence of Fetal Hgb lab results

Hgb F doesnt switch to A (beta chain not produced)

carriers: 15-35% hgb F

Homozygous: 100% hgb F

Random mixed Abnormal Hgb disorders

Hgb S—B thalassemia: very severe, use electrophoresis

Hb Hammersmith (unsure of what it is other than an unstable hgb variant).

Hb Gun Hill (see comment above)

Increased O2 Affinity (left shift)

Hgb doesn’t release O2 to tissues.

Cause erythropoietin to activate, increasing RBCs.

makes decreased Oxygen tension in blood.

Decreased O2 Affinity (Right shift)

More Oxygen is released to tissues, decreased erythropoietin.

Slight anemia seen 

Most common is Hgb Kansas (a2b2) (cyanosis and normal oxy tension)

Corrected retic count

(% retics x Pt hct) / normal hct (depends on sex)

Pt hct = 35, Retic % should be 2-3%

Pt hct <25%, retic % should be 3-5%

retic production index formula

corrected retic % / maturation time in days

40-45% = 1

35-39% = 1.5

25-34% = 2

15-24% = 2.5

<15% = 3

Anemias requiring a BM 

megaloblastic anemia: asynchrony, hypersegment neuts, giant metamyelocytes, no iron in Bm (unless sideroblastic anemia)

Test for Microcytic anemia

Hgb electrophoresis

Kliehauer Betke for Hgb f 

ferritin, Iron, TIBC for IDA

test for N/N anemias

Sickle cell solubility 

DAT

osmotic fragility

Enzyme deficiencies

Sucrose, Ham, Flow cytometry for PNH

Haptoglobin, urine urobili/hemosiderin (intra vs extra hemolysis)

Reticulocytes (tells if hemolytic or hypo proliferative disorder)

Bili/LD

tests for Macrocytic anemia

B12/Folate

Erythropoietin (intramedullary increase)

Schilling test

liver enzymes

Bm for myelodysplasia

review inclusions

Heinz bodies: hgb, not seen on wrights

DNA: howell jolly bodies, NRBC.

RNA: Retics, Basophilic stippling

Iron: ringed sideroblasts, pappenheimer bodies.

Hct formula

(RBC x MCV) / 10

Agglutination will increase

Lipemia will increase hgb, not mcv.

What is the most common anemia in the world?

Malaria, causes rbc removal.