Hematology Flashcards
anemia - morphologic approach
microcytic (MCV<80)
- iron deficiency
- thalassemia, sickle cell
normocytic (MCV 80-100)
- anemia of chronic dz
- anemia of chronic renal failure
- multifactorial (micro and macro balance out)
- sickle cell
macrocytic (MCV>100)
- Folic acid and Vit. B12 deficiency
- alcoholics, liver dz
- myelodysplastic syndrome
anemia and reticulocyte counts
reticulocytes are erythrocytes newly released from marrow (1-2 days)
- still have small amount of RNA in them
- can use to determine if anemia is decreased production (low retic count) vs. increased destruction (high retic count) since marrow is trying to pump out RBC to compensate
causes of anemia from:
- decreased production
- increased destruction
dec. production:
- lack of nutrients (iron, it B12, folate)
- bone marrow suppression (aplastic anemia,chemo)
- low trophic factors (CKD - low expo, low thyroid, testosterone)
- anemia of chronic dz (low sensitivity to expo)
inc destruction:
- blood loss (chronic)
- hemolytic: either inherited (sickle cell, thalassemia) to acquired (autoimmune, drug induced)
iron tests
serum iron
transferrin: binds iron in circulation
- TIBC
- % saturation = serum iron/TIBC
- Ferritin: iron stores
iron deficiency anemia: causes, s/sx, labs, tx
Causes:
- increased requirements: bleeding (GI, menses), growth periods (pregnancy, lactation)
- inadequate supply: intestinal malabsorption, gastric bypass surgery, Ca+ inhibits absoprtion
S/sx:
- microcytic anemia
- koilonychia (spoon nails)
- glottitis/esophageal webs (Plummer-Vinson syndrome)
- restless legs
- Pica
- hair loss
Labs:
- low serum iron
- low ferritin
- TIBC is high (trying to bind iron) but % saturation low
- reticulocytes high
Tx:
- oral iron therapy (ferrous sulfate 325 BID)
- recheck ferritin 6-8wks
- vit C helps
hemoglobinopathies - 2 types
sickle cell disease
- heterozygous (trait)
- homozygous (SC anemia)
thalassemias
- alpha: 4 subtypes
- beta has 2 subtypes
normal adult hemoglobin - results of electrophoresis
HgB A: 95-98%
HgB A2: 1.5-3.5%
Hgb F (fetal): 0.5-1%
sickle cell hemoglobinopathy
Due to presence of abnormal HgB S, on deoxygenation, cells sickle and cause damage to vessels and trapping of dense sickle cells
- splenic infarction with hypoxia (altitude)
- hematuria common
Dx:
- presence of HgB S on electrophoresis
sickle cell trait (heterozygous)
usually asymptomatic
only develop crises at high altitudes (hypoxia triggers), or high stress situations (illness)
over time, can develop micro infarcts resulting in kidney damage and cardiac damage
sickle cell anemia (homozygous): definition, clinical findings
chronic hemolysis and pain crises
- anemia
- rectioculocytosis (high b/c trying to compensate for destruction)
- hyperbilirubinemia
Clinical:
- cardiac sxs from chronic overload (CHF) and micro infarcts/fibrosis
- infections (strep pneuma and H. Flu) that spleen socially takes care of
- gallstones
- renal failure
- painful crisis in hands and feet (from micro thrombi)
- osteomyelitis (salmonelli typhi)
sickle cell pain crisis: cause, tx
can last days to weeks
cause:
- dehydration
- infection
- stress
caution (these require transfusion):
- acute chest syndrome
- splenic necrosis
manage:
- hydration +/- bicarb
- oxygen
- pain meds
- folate to support hemolysis
- tx infection
Beta-thalassmia
labs:
- dec. or absent HbGA, increased HbGF and A2
- Mediterranean descent
b-thal minor (trait)
- homozygous
- chronic anemia (not symptomatic)
- dx: HgB electrophoresis: HbA w/ raised HbF and HbA2
- tx: usually no tx needed
b-thal major (Colley anemia)
- homozygous
- severe anemia
- sx: liver and spleen enlargement, stunted growth, bony deformities (chipmunk facies), hepatosplenomegaly, jaundice, cirrhosis, and thrombophilia.
- dx: HgB electrophoresis: no beta chains synthesized; only HbF and HbA2
- tx: bone marrow transplant; supportive care
alpha thalassemia syndromes
HgB chain affected: alpha globin chain pathology
Two alpha chain deletion:
- common in Asians (alpha-th-1) or blacks (alpha-th-2)
- typically mild.
Presence of one alpha chain: Hemoglobin H disease
- patients manifest a variant of chronic hemolytic anemia.
Absence of all four alpha chains = hydrops
- results in stillbirth
anemia of chronic disease (anemia of inflammation) - basics, causes, dx, tx
induced by inflammatory cytokines and hepcidin
- results in normocytic anemia
- reduction in RBC production in bone marrow
causes: MANY
Dx:
- low serum iron
- HIGH ferritin
- TIBC is low and % saturation low
- reticulocytes low
Tx:
- erythropoietin (EPO)
hemolytic anemia
caused by premature breakdown of RBCs
- hereditary spherocytosis (RBC membrane defects): see spherocytes that get chopped up by spleen; tx: remove spleen
- autoimmune processes (+ COOMBs)
- tx with prednisone - G6PD deficiency: usually drugs or FAVA BEANS stimulate hemoysis; see bite cells and Heinz bodies
- Drugs: antimalarials, analgesics (acetyl salicylic acid), chemo
Labs:
- high reticulocyte count
- inc. serum LDH
- high indirect jaundice
- positive COOMBS (if autoimmune)
- reduced serum heptoglobin
aplastic anemia
PANCYTOPENIA
- recurrent infections (low WBCs)
- mucosal hemorrhage (low platelets)
- fatigue, dyspnea (low RBCs)
marrow is profoundly hypocellular with dec. in all elements
- low reticulocyte count
cause: chemo, drugs, radiation, infection, unknown
Tx:
- hematopoietic cell (stem cell) transplantation
- immunosupressive regimes
- supportive management (IVIG)
vitamin B-12 deficiency (versus folate deficiency)
related to macrocytic anemia as well as neurologic symptoms
- serum B12 may be low or normal (which makes it tough for dx)
cause:
- pernicious anemia: autoimmune cause of B12 deficiency (antibodies to intrinsic factor)
sxs:
- depression, dementia, ataxia, slow reflexes, etc.
Dx:
- methylmalonic acid high in B12 deficiency
- homocysteine high in both B12 and folate deficiency
Tx:
- give B12 (cobalamin) SQ or PO
folic acid deficiency
cause:
- nutritional deficiency (gastric bypass, alcoholic)
sxs:
- depression, dementia, ataxia, slow reflexes, etc.
dx:
- serum folic acid level
- monitor progress with homocysteine
tx:
- Folic acid 1 mg daily
NOTE: higher demands in pregnancy
thrombocytopenia - most common cause
splenic sequestration (in enlarged spleen) - can be ETOH induced
idiopathic thrombocytopenia purpura (ITP)
idiopathic with autoimmune features
- kids: follows viral illness; self-limited
- adults: idiopathic, autoimmune
s/sx:
- petechial hemorrhage
- mucosal bleeding
- thrombocytopenia (<20,000)
Dx: diagnosis of exclusion
- confirm not lab error (clumping of platelets)
Tx:
1st line: steroids
2nd: splenectomy
thrombotic thrombocytopenia purpura (TTP)
rare disease; often triggered by systemic inflammatory process (HIV, malignancy, meds)
sxs: FAT-RN F: fever A: hemolytic anemia (schistocytes, helmet cells) T: thrombocytopenia R: renal impairment N: neurologic: sz, AMS
Tx:
- large-volume plasmapheresis (get rid of broken cells)
- immunosuppressive agents
platelet defect vs. clotting factor deficiency
platelet defect
- bleed in skin, mucous membranes, GI tracts
- bleeding after minor cuts; small ecchymosis
- petechiae
- mild bleeding after surgery
clotting factor deficiency
- bleed in soft tissues (joints, muscles)
- large, palpable ecchymosis
- no petechiae
- muscle hematoma common
- delayed, severe bleeding after surgery
coagulation tests
PT (prothrombin time)/INR: measures extrinsic pathway
- up in vit K deficiency, Coumadin, liver dz, DIC
PTT (partial thromboplastin time): measures intrinsic pathway
- up in vit K deficiency, Heparin, liver dz, DIC, hemophilia, vWD
D-dimer: specific to plasmin degradation of fibrin (picks up presence of clots)
- positive in DIC, PE, DVT
coagulation pathway
Intrinsic Pathway: factors released into blood from platelets (ten, 10, 2, 1); endothelial cells are damaged, negatively charged surface, activates TEN, 10, II, I
o Twelve – factor XII (activated by negative surface)
o Eleven – Factor Xi
o Nine – Factor IX
o 10 – Factor X – common pathway
o 2 – Factor II (prothrombin)
o 1 – Factor I (fibrinogen)
o Note: factor XIII: makes fibrin bonds even stronger – adds net or mesh of fibrin
Extrinsic pathway: factors released by damaged tissue (tissue factor – comes from outside blood)
o Tissue factor activates Factor VII
o Factor VII activates Factors X and V
• Common pathway
Note: intrinsic and extrinsic pathways meet at Factor X and form common pathway:
• Prothrombin → thrombin (enzyme = prothrombinase)
• Fibrinogen → fibrin (enzyme = thrombin)
• Fibrin strands bind to all platelets and strong clot is formed
von Willebrand disease (VWD) - definition, tx
most common bleeding disorder
- heavy menses, mucosal or prolonged bless, post surgery bleeds
- vWF is either defective or deficient
Labs (mostly normal)
- PTT and bleeding time slightly elevated
- vWF levels may be low
- platelet aggregation test abnormal
tx:
- DDAVP (desmopressin / synthetic vasopressin/ADH): inc. plasma WWF levels by stimulating secretion by endothelium
- platelet or factor VIII transfusion
hemophilias (bleed too much) - 2 types
clotting factor disorders - severe bleeds into joints / post-op (vs. low platelets)
sex-linked recessive
- genes on X chromosome
hemophilia A:
- deficient or defective factor VIII
hemophilia B (aka Christmas Tree dz) - deficient or defective factor IX
thrombophilia / hyper coagulation disorders
factor V Leiden mutation
- resistent to protein C = unopposed coagulation pathway
Anti-Thrombin III deficiency: unchecked coagulation
Protein C&S deficiency: more rapid thrombin formation
Prothrombin gene mutation: inc. prothrombin levels
Disseminated Intravascular Coagulation (DIC) - definition, population, causes, s/sx, tx
systemic d/o that causes both clot formation (thrombosis) and bleeding (hemorrhage)
- endothelial damage creates many clots, use up clotting factors and then bleed
population: hospital admits
causes:
- tissue damage on large scale: burns, trauma, sepsis, vasculitis
- procoagulant in blood: cancer, placental abruption
- severe allergic reaction
s/sx:
- bleeding, petechiae
- renal: oliguria, ARF
- dyspnea
- thromboembolism: DVT, PE, CVA
- seizures, coma
Labs: PT/INR, PTT, fibrinogen, TT all affected
tx:
- fix underlying cause and support (replace blood, clotting factors, etc.)
trousseau syndrome
slower DIC that occurs in malignancy
acute lymphocytic leukemia (ALL)
- T Cell or B Cell
General info:
- peak incidence: 3-5
- Philadelphia chromosome is adults (higher risk; uncommon)
- risks: radiation, prior chemo, solvents, Downs
- sx: BM failure, infections, bleeding, LAD, WBC abnormality (high or low)
acute myeloid leukemia (AML)
General info:
- peak incidence: age 60
- > 30% blasts in peripheral blood
- Auer Rods formed by aggregation of myeloid granules (in smear)
chronic lymphocytic leukemia
General info:
- most common form of leukemia in adults in western world
- medial age: 62 yrs
- therapy only initiated if sxs warrent
chronic myelogenous leukemia (CML)
chromosome 22 translocation mutation - Philadelphia chromosome
- raised WBC count
- lifelong treatment but can make life-expectancy years
multiple myeloma
accumulation of plasma cells in bone marrow or visceral/soft tissue
s/sx: CRAB
C: calcium-elevated from osteolytic bone destruction
R: renal-insufficieny from damage of protein deposition’
A: anemia: BM suppression
B: bone: lytic lesions (PUNCHED OUT LEASIONS)
- found after eval for anemia, back pain, renal insufficiency, and large protein/albumin
- rouleaux: stacking of RBCs
- Dx: hallmark of MM is the finding of a monoclonal spike on serum protein electrophoresis
tx: incurable
- stem cell transplant
- immunosuppression
non-hodgkins lymphoma - risks, s/sx,
6th most common cancer
- many types
- 85% of lymphomas
risks: - male, older - chronic immunosuppression - chromic autoimmune dz chronic infections
s/sx:
- weight loss
- painless nodes
- night sweats
- fevers
- pruritus
- chest or abd pain
Hodgkins lymphoma
General
- bimodal: 15-30, >55 y/o, FH (HLA link)
- very curable
s/sx:
- weight loss
- painless nodes
- night sweats
- fevers
- pruritus
- mediastinal mass
- PAIN after ETOH consumption
d/dx:
- biopsy with Reed Sternberg cells (multinucleate)
- inc. LDH
