DISEASES I3 Block, Test 1

ANEMIAS/RBC/Hb DISORDERS Also see attached for Lab Test criteria for anemia disorders.
Condition Name Associated Issue/Pathogenesis Patient Symptoms/Treatment
Megaloblastic anemia Regulation of Hematopoiesis by Folate
Aragon-Ching
Deficiency in folate causes erythroblasts to synthesize Hb but cannot replicate DNA
efficiently division incomplete and macrocytic cells are released into blood.
Homocysteine levels elevated.
Smear has macrocytic cells (filled with Hb) and neutrophils with 4+ lobes.
Fatigue, paleness (pallor), lightheadedness, and pancytopenia.
Treat via high dose of folic acid or N5-methyl THF (if post- chemo).
Pernicious megaloblastic anemia Regulation of Hematopoiesis by B12
Aragon-Ching
Deficiency in vitamin B12 (usually due to absorption), resulting in inactive

methionine synthase to convert folate into its active form. Homocysteine levels
elevated. In addition, methionine is not recycled and no SAM can be produced
lack of methylation on myelin sheaths myelin degeneration.
Methylmalonyl-CoA mutase also inactive. Methylmalonic acid levels elevated.
Anemia symptoms coupled with neurological problems and methylmalonic aciduria.
Treat via IM injection of hydroxycobalamin/B12.
Hereditary hemochromatosis Regulation of Hematopoeisis by Iron
C282Y mutation in HFE gene Decreased hepcidin expression in liver despite high
Fe levels Excess iron in circulation Can poison organs due to Fenton reaction
(OH production).
Joint pain, fatigue, diabetes, loss of libido, impotence, cardiomyopathy, heart failure, liver
cirrhosis
T
reat via phlebotomy. Iron deficiency anemia Regulation of Hematopoeisis by Iron
Aragon-Ching
Impaired growth and development, fatigue, weakness, tachycardia, shortness of breath,

Condition Name Associated Issue/Pathogenesis Patient Symptoms/Treatment

Deficiency caused by many factors (see Clinical Findings Chart) including issues
with diet, absorption, and chronic bleeding. unable to make heme unable to
make Hb lack of hemoglobinziation
in RBCs.
Smear has increased central pallor, microcytosis, anisocytosis, pencil cells, and target cells.
dizziness, irritability, decreased work productivity, PICA (ice and clay especially), angular
stomatitis (inflammation of lip corners), koilonychiae (thin/spoon nails)
Treat the underlying cause. Pt may or may not be responsive to iron supplement (with orange
juice). May need IV injection if absorption problem. - Oral supplement side effects:
d
iarrhea, constipation, cramps X-linked sideroblastic anemia Regulation of Hematopoiesis by Iron
Deficiency in ALAS-2 no heme synthesis iron accumulates in
mitochondria/surrounds nuclei. Can be caused by B
6

Pt may or may not be responsive to B

6

treatment.
deficiency or ALAS-2 mutation/deficiency. Aplastic anemia Hematopoeisis
Total failure of bone marrow to produce erythroblasts for RBC
formation Hereditary spherocytosis Hematopoeisis
RBC exhibit spherocytosis (loss of biconclave) prone to rupture causing hemoltyic
anemia and lack of O2 delivery Myelophthisic anemia Hematopoeisis
Space-occupying bone marrow lesions preventing RBC formation (fibrosis, tumors, granulomas)
Tear drop cells in blood smear.

Condition Name Associated Issue/Pathogenesis Patient Symptoms/Treatment

Severe renal failure Hematopoeisis
Burr cells in blood smear.
Sickle cell anemia Development: School-Aged Child with Sickle Cell
Hemaglobinopathies
Most commonly identified disease in newborn screen (1/500 African Americans).
SS: Beta globin gene missense mutation: glutamic acid valine Cells are
heterogenous and forms sickles during episodes. During deoxygenated states, Hb
stacks upon each other and aggregate into the sickle form. Can cause vasoocculation.
Other types: SC, S
thal,

Painful crisis, acute chest syndrome, risk for silent cerebral infarct, spleen enlargement,
avascular necrosis, hand/foot syndrome, complications from infection, renal issues,
osteonecrosis of hip and shoulders, proliferative retinopathy (Hb SC), leg ulcers, cholecystisis,

priapism
Life span: 40-50 yrs for SS; 60-70 for SC
Treatment
Early intervention from birth 6 yrs: penicillin prophylaxis, conjugate pneumococcal vaccine,
aggressive evaluations of any fever
Transfusions
Pain medicine and fluids
Hydroxyurea

Bone marrow transplant Anemia of chronic disease/chronic inflammation

SD
Aragon-Ching
Hypoproliferative anemia due to chronic non-hematologic condition (inflammatory response)
Conditions can be infectious, malignant, immunologic, traumatic
Infectious: TB, lung abscess, endocarditis, pulmonary, fungal AIDS
Treat underlying process while correcting any co-existent Fe deficiency. Some Pts also benefit
from EPO therapy.

Condition Name Associated Issue/Pathogenesis Patient Symptoms/Treatment

Inflammatory: rheumatoid arthritis, rheumatic fever, systemic lupus, regional enteritis,
ulcerative colitis, vasculitis
Malignancies: carcinomas, metastatic CA, 4odgkins, NHL, multiple myeloma
Misc: liver disease, thrombophlebitis, sterile abscesses, isch. Heart disease
Overwhelming presence of inflammatory cytokines which suppress erythropoiesis
and EPO production/response, also altered iron metabolism decreased utilization
of Fe (higher storage) Hemolytic anemia (general) Aragon-Ching
Causes: inherited intrinsic RBC defect or acquired defect Premature/accelerated
peripheral RBC destruction increased bilirubin, LDH, and decreased haptoglobin
Smear: spherocytes, schistocytes, polychromasia, immature nucleated RBCs Marrow: erythroid
hyperplasia, thinning in bones Hemolytic anemia due to G6PD deficiency
Aragon-Ching
G6PD protects RBCs from oxidative damage and maintains NADPH level. Def =
higher oxidative damage. Hemolysis.

X-linked inheritance. Forms:

A- 10-15% African Americans; retics are stress-resistant; milder
Mediterranean most common in whites; low retic levels; acute and fatal
Smear Heinz bodies, bite cells Hereditary spherocytosis
Aragon-Ching
AD inheritance. Mutant in band 4.1 protein resulting in decreased spectrin expression in RBC
(skeletal component of membrane).
Chronic anemia, splenomegaly, gallstones, aplastic crisis
Treat via splenectomy.

Condition Name Associated Issue/Pathogenesis Patient Symptoms/Treatment

Smear spherocytes, increased osomotic fragility Warmreacting immune hemolysis
Aragon-Ching
IgG antibodies bind to RBCs in warm temperatures (37C) phagocytosis. Positive
Coombs test.
Smear polychromasia, microspherocytes
Induced by idiopathic reasons, virus, neoplasia, connective tissue disorders, prior blood
transfusion/bone marrow transplant, drugs. Drugs: - Quinidine: innocent bystander; drug
complexes with Ab and
attaches nonspecific to RBC complement pathway activated - Penicilin: attaches
to RBC membrane and serves as a hapten against
Ab which directs them to the RBC - Methyldopa: alters RBC membrane to become an
antigen and
immunogenic (true autoimmune) - Others examples include sulfonamides, cephalosporins

Varies from mild to severe symptoms; hepatosplenomalgy in 1/3, thrombophlebitis, jaundice,

pallor, cardiopulmonary collapse
Treat via discontinuing all drugs, search for potential lymphoma or leukemia, control lysis with
corticosteroids... splenectomy if all else fails.
Cold-reacting immune hemolysis Aragon-Ching
IgM only bind to RBCs at low temperatures(<31C) phagocytosis by liver
macrophages Positive Donath-Landsteiner test.
Induced by idiopathic reasons, lymphoproliferative diseases, certain infections.
Vascular occlusion (pain/ulceration in toes and figures)
Treat via underlying disorder, plasma exchange, and and avoiding exposure to cold.
Transfusions must be done through a blood warmer. Carbon monoxide (CO) poisoning
Hemoglobin
High affinity binding to Hb unable to deliver O
2

Treat via 100% oxygen therapy.

. Evolutionary protection of distal histidine 7
prevents CO from binding linearly like it prefers (lowers affinity). Poisoning occurs when
concentration/pressure of CO is higher than O
2

. Methemoglobin Hemoglobin Chocolate cyanosis, chocolate

Condition Name Associated Issue/Pathogenesis Patient Symptoms/Treatment

Hb with Fe3+ rather than Fe2+ in heme. O
2

covered blood, cyanotic cannot bind.

symptomology Reduction
of iron due to oxidizing molecules (nitrates, ROS), drugs, and decreased NADH-cytochrome B
5

reductase (NADH-methemoglobin
Treat via methylene blue.
reductase).
Infusions are helpful for cyanide poisoning. Thalassemia
Hemoglobin
- Mutation in locus of control region no expression of globin genes - Point
mutation causing alternative splice site extension in second intron causing
additional 7 amino acids added to Hb

Target cells in blood smear. thalassemia Hemoglobinopathies

Mutation or deficiency in beta chain decreased RBC Hb increased free chains
precipitate out ineffective erythropoiesis, hemolysis, marrow expansion,
extramedullary hematopoiesis
Hereditary persistence of Hb F as a way to compensate deficiency.
Types
0-thal genes for beta Hb deleted no expression
+-thal genes mutated disease severity varies depending on amount of Hb A
produced and the problem
no or chain no Hb A
2

Hemoglobin Lepore hybrid chain replaces typical chain in Hb

Severe anemia, high output congestive failure, chipmunk faces, bones/skull hypertrophy
More symptoms with major diabetes, hypoparathyroidism, hypogonadism, infections from
transfusion, alloimmunization from transfusion
Treat via transfusions, comprehensive thalassemia center, hydroxyurea (for increased Hb F
production), iron chelation therapy (reduces potential for hemochromatosis organ damage),
stem cell transplant thalassemia Hemoglobinopathies
Point mutation or deletion in alpha chains decreased RBC Hb increased free
chains formation of abnormal Hb that have high
Hb H: microcytic anemia, splenomegaly, iron-loading, ineffective erythropoiesis, brisk hemolysis

Condition Name Associated Issue/Pathogenesis Patient Symptoms/Treatment

affinity for O
2

(Hb barts
4

; Hb H
4

)
Four genes code for alpha chains. Mutation leads to specific type.
Thal trait two genes nonfunctional; no-mild symptoms, 2-10% Hb Barts in newborns
o Homozygous + thal (-/-) 7% of Africans o Heterozygous 0 thal (/--)
common in SE Asia
Hb H disease/ thal major three genes nonfunctional (-/--) unstable Hb
o 20-40% Hb Barts in newborn; 5-40% Hb H in adults

 Hb Barts/0 homozygous --/--, no functional alpha genes

o Leads to eclampsia in mother and stillbirth
Hb Barts: Leads to eclampsia in mother and stillbirth
Sickle cell disease Hemoglobinopathies
See above.

LAB DIAGNOSIS FOR ANEMIAS

Condition Fe TIBC Tf Tf
Sat
Ftn LDH RBC Hb Hct MCV RDW PLT Retic Other
Iron deficiency anemia
N
Megaloblastic anemia N or

WBC: Hapt: Bili: Anemia of chronic disorders

N or
N or
N or
N or
N or

Hapt: N Bili: N WBC: N Hemolytic anemia Hapt:

B
ili: Hemochromatosis N Sideroblastic anemia
Thalessemia
Fe = serum iron TIBC = total iron-binding capacity Tf = serum transferrin Tf Sat = transferrin saturation
Ftn = serum ferritin LDH = serum lactate dehydrogenase RBC = red blood cell count Hb = serum
hemoglobin Hct = hematocrit (packed RBC volume) MCV = mean corpuscular volume RDW = red blood
cell distribution width (variation in RBC sizes) Retic = reticulocyte count PLT = platelet count WBC = white
blood cell count Hapt = serum hatpoglobin Bili = serum bilirubin

N or
N N or
N N or

LYMPHATIC TISSUE DISORDERS

Condition Name Associated Issue/Pathogenesis Patient Symptoms/Treatment
Tonsilitis Vascular and Lymphatic Organs
Infection of the tonsils
CLOTTING DISORDERS/BLOOD TRANSFUSIONS
Condition Name Associated Issue/Pathogenesis Patient Symptoms/Treatment
Bernard Soulier Syndrome Platelets
Glanzmanns thrombasthenia
Defects in cell membrane Chediak Hegashi disease Platelets
Storage pool disease decrease/absence of dense granules causing diminished
platelet aggregation Thrombocytopenia Platelets
Decreased platelet number... Can be due to genetic disorders - Tar baby syndrome, WiscottAldrich syndrome, May-Hegglin anomaly, Alport syndrome, and acquired amegakaryoctic
thrombocytopenic purpuria (AATP). Or due to acquired factors radiation exposure, drugs,
chemicals (especially benzenes), infections, bone marrow dysfunction

OR increased destruction: drug induced, ITP, TTP, DIC,

hypersplenism Immune thrombocytopenic purpura (ITP)
Platelets
Ig which binds to GPIIb/IIia, GP1b/IX no platelet adhesion or aggregation, rapid
destruction in RE system (spleen). Also Ig to megakaryocytes suppression of
thrombopoeisis.
Acute ITP: esp in children 4-6 boys and girls after infection; spontaneous duration Chronic ITP:
adults in women esp prior to menopause; not due to infection
Evidence of mucousal bleeding, easy bruising, menorrhagia, gingival bleeding, intracranial
bleeding
Treat via corticosteroids and splenectomy. Newer trials include IVIG, Rituximab, and
synthesized TPO.

Condition Name Associated Issue/Pathogenesis Patient Symptoms/Treatment

Thrombotic thrombocytopenia pupura (TTP)
Platelets
Ig against ADAMTS-13 metalloproteinase which cleaves VWF into its active form.
No clipping of VWF Increased platelet adhesion but no coagulation. MIs/death
easily occur.
Thrombocytopenia, microangiopathic hemolytic anemia, renal failure, fever, CNS symptoms
(confusion, loss of consciousness)
Treat via high doses of corticosteroids to suppress Ab production and put patients on plasma
exchange. Heparin induced thrombocytopenia (HIT)
Platelets
Ig form against unfractionated heparin (HMW) and FIV form immune complexes
which deposit on platelets surface. Platelets bind together and cause small
clots/get destroyed by RE system.
Use other anti-coagulants rather than heparin.

Preeclampsia Platelets
High BP and proteinuria
5-15% of pregnancies.
D
eliver ASAP. HELLP syndrome Platelets
Pregnancy-related. Includes hemolysis, elevated bili and SGOT, liver enzymes present in blood,
low platelets.
Nausea, malaise, abdominal pain
Deliver ASAP.
Neonatal alloimmune thrombocytopenia (NAIT)
Platelets
Fetal inheritance of platelet antigens not present in mother cross into placenta
and mother develops Ig
Treat via infusion of washed maternal platelets, early C- section.
Hemophilia A Coagulation
X-linked recessive inheritance, more common. Factor 8 deficiency prolonged PTT
Hemarthrosis, muscle bleeds, mucutaneous bleeds, intracranial bleeds, post dental/surgical
bleeds. Normal bleed after minor cut.
Treat via plasma/recombinant FVIII or DDAVP (to stimulate FVIII release).