Hematology Flashcards
Three basic pathophysiological causes of anemia
- Decreased RBC production - bone marrow, renal failure, low B12 or folate
- RBC loss - hemorrhage, hemolysis
- Production of defective RBCs
Clinical definition of anemia
Hemoglobin less than 12 in women and 13 in men
Symptoms of anemia
fatigue, dizziness, tachycardia, pallor, orthostatic HTN, exertional dyspnea
What are reticulocytes?
immature RBCs
What is MVC measure?
volume of average RBC in sample
MCV of microcytic and macrocytic anemia?
Microcytosis = MCV less than 80 (small cells) Macrocytosis = MCV +100 (big cells)
How to determine blood cell morphology?
peripheral blood smear
What measures are included in CBC?
WBC, RBC, hematocrit, platelet count, retic count, MCV, RDW, MCHC
basophil, eosinophil, lymphocyte, monocyte, neutrophil %s
What is the significance of low reticulocyte count?
means poor RBC production
seen in all microcytic anemias
Most common cause of microcytic anemia
iron deficiency
Causes of iron deficiency
GI bleeds (think NSAIDs) Decreased iron intake Decreased iron absorption
Signs of iron deficiency anemia
fatigue mouth ulcers palpitations pallor brittle nails angular cheilitis dysphagia pica
What is ferritin and transferrin?
Ferritin = iron stores
Transferrin = transport protein for iron or iron binding capacity
What lab is diagnostic of iron deficiency anemia?
plasma ferritin < 10 in women and < 30 in men
Treatment of iron deficiency anemia
ferrous sulfate 325 TID x 6 months
Side effects of iron supplementation
lots of GI issues
Epidemiology of alpha and beta thalassemia
alpha - Southeast Asia, Middle East, African
beta - Mediterranean
minor vs major thalassemia
Minor = gene inherited from one parent; few or no symptoms
Major = gene inherited from both parents
- Alpha major = Bart’s Hgb
Still born or death soon after birth (hydrops fetalis typical outcome)
- Beta major = Cooley’s anemia
Born without a problem, but develop severe anemia over the first year and typically don’t survive past 30 yo
Symptoms of thalassemia
bone issues, splenomegaly, jaundice, severe anemia, osteopenia, fatigue
How to definitively dx thalassemia
HgB electrophoresis
Treatment of thalassemia
Folic acid
Serial blood transfusions but watch for iron overload
Genetic counseling
Splenectomy
Basophilic stippling on peripheral blood smear seen in what 3 hematologic diseases?
beta thalassemia
lead poisoning and sideroblastic anemia
Diagnostic test of choice for sideroblastic anemia
Prussian blue staining of bone marrow - shows ringed sideroblasts
How can sideroblastic anemia be acquired?
alcoholism
lead poisoning
myelodysplasia
Heinz bodies seen in what anemia?
alpha thalassemia
G6PD deficiency anemia
What are Howell-Jolly bodies? in what diseases?
DNA remnants seen with macrocytic anemia or damaged spleen
B12 or folate deficiency anemia, sickle cell anemia, celiac disease
Hemolysis of macrocytic anemia can progress to ______ dysfuction.
spleen
Microcytic anemias
iron deficiency
thalassemia
lead poisoning
Macrocytic anemias
folic acid deficiency
B12 deficiency
Sickle cell
G6PD deficiency
hypersegmentation of PMN nuclei on peripheral blood smear =
folic acid or B12 deficiency
stocking glove paresthesias =
B12 deficiency or diabetic neuropathy
bite cells =
G6PD deficiency
Clinical presentation of folic acid deficiency
sore/swollen tongue
GI issues - diarrhea
mouth and peptic ulcers
anemia sx’s
Pathophysiology of pernicious anemia
inability of GI tract to absorb B12 due to missing transport protein called intrinsic factor
Causes of B12 deficiency
- Pernicious anemia (#1 cause)
- Vegan diet
- Bowel surgery
- Crohn’s disease
B12 absorbed where in body?
terminal ileum
Clinical presentation of B12 deficiency
neuro sx’s: stocking glove paresthesias, ataxia, dementia, depression
anemia sx’s
How is B12 deficiency differentiated from folic acid deficiency?
Neurologic sx’s
Low LDH
Low indirect bilirubin
- Low serum B12 is NOT diagnostic
Schilling test
Determines cause of B12 deficiency; pernicious anemia or terminal ileum disease (bacteria Crohns, sprue)
- IM B12 injection to saturate B12 receptors in ileum
- Patient given oral radioactive B12
Normal = B12 in urine; B12 binds to intrinsic factor and absorbed into bloodstream
Pernicious anemia = B12 in urine only if patient also given intrinsic factor
B12 deficiency treatment
Treat underlying cause if possible
Intramuscular B12
High dose of oral B12 will allow some to pass through small intestine by passive diffusion without intrinsic factor
Oral intrinsic factor may be given, but if patient has intrinsic factor antibodies this method will not be effective.
Neurological symptoms which are treated within the first 6 months do well. Starting treatment after 6 months of symptoms may result in permanent damage.
Etiology and Epidemiology of Sickle cell anemia
autosomal recessive
predominantly African American
What is a sickle cell crisis?
Life-threatening; acute painful episode due to ischemia somewhere in body
Increased risk associated with dehydration, acidosis, and hypoxemia
How do carriers of sickle cell trait present?
Asymptomatic unless under stress (dehydration, acidosis, hypoxia)
Sickle cell anemia makes patients at increased risk for what other conditions?
splenomegaly (pneumococcal infections), non-healing ulcers, strokes, retinopathies, osteomyelitis, necrosis of femoral head
Elevated retic count anemia
Sickle Cell G6PD deficiency (during hemolytic episode)
Definitive diagnosis method for Sickle cell anemia
electrophoresis - HbS in red blood cells
Sickle cell treatment
No specific treatment
Folic acid supplement and pneumococcal vaccination
Acute painful episode – fluids, pain meds, and oxygen
Exchange transfusion may be necessary in severe crisis
Drugs that increase risk of hemolytic episode
Antimalarials Sulfonamides Methylene blue Aspirin Fava beans Menthol
I came in to see my physician assistant because of…
Prolonged jaundice
Hemolytic crises secondary to illness, certain medications or foods.
G6PD deficiency anemia
Treatment of G6PD deficiency anemia
Supportive; episodes are self-limiting
Prevention is key
Inheritance of G6PD deficiency anemia
X-linked recessive
Signs of anemia + thrombocytopenia + decreased WBCs =
Normocytic anemia
Normocytic anemia treatment
Treatment of underlying disease Bone marrow transplant Immunosuppression Erythropoietin Blood transfusions
Define hemophilia
a clotting factor deficiency
Utility of measuring PTT and aPTT
- Assess intrinsic (12, 11, 9, 8) and common coagulation pathways (10, 5, 2, 1)
- Monitor Heparin therapy
*PTT longer name than PT, and intrinsic pathway more coagulation factors
Causes of delayed PTT include…
Heparin use, hemophilia, sepsis secondary to coagulation factor consumption
Utility of measuring PT and INR
- Assess extrinsic pathway of coagulation (VII = tissue factor)
- Monitor Warfarin therapy
- Check for liver damage
Causes of delayed PT/INR
Warfarin use, liver damage
Bleeding time used to assess _______.
platelet function
Most common inherited clotting disorder
von Willebrand disease
Functions of von Willebrand’s factor (vWF)
Helps platelets stick to blood vessel wall and bind to factor VIII
Increases half-life of circulating factor VII
Symptoms of bleeding disorders
easy bruising/bleeding
frequent bloody noses
bleeding gums
heavy menses
Results of following tests for von Willebrand disease:
PT/INR
PTT
PT/INR normal
PTT usually prolonged
von Willebrand disease treatment
Desmopressin
Factor VII concentrate
Platelet concentrates may be given in severe cases
Hemophilia A is deficiency in factor ____ and Hemophilia B is deficiency in factor ____.
VIII
IX
Inheritance of hemophilia A and B
X-linked recessive
Results of following tests for Hemophilia A and B:
PT/INR
Bleeding time
PTT
PT/INR are normal
Bleeding time is normal
PTT is prolonged
What type of hemophilia primarily occurs in Ashkenazi Jews?
Hemophilia C
Hemophilia C is deficiency in what?
coagulation factor XI
Treatment of Hemophilia A, B, and C
Mild cases of A and B: Desmopressin to encourage factor VII release
Severe cases of A and B: factor concentrate 2-3x/week; patients may develop antibody to factor VIII and IX with treatment
C: tx usually unnecessary unless severe trauma or surgery; fresh frozen plasma, platelets, Desmopressin
Congenital cause of hypercoagulable states
Factor V Leiden
Acquired causes of hypercoagulable states
Antiphospholipid syndrome (autoimmune disease where antibodies against cell membranes) Poor blood flow (sedentary, Afib, Sickle cell disease, Polycythemia vera) Cancer Pregnancy Nephrotic Inflammatory bowel diseases Estrogen/birth control Obesity Recent surgery
What is Polycythemia vera?
excess production of red blood cells
type of clots
DVT
Pulmonary embolism
Superficial vein thrombosis (SVT)
How to manage a hypercoaguble state?
Treat underlying cause if possible
Long term warfarin – risk of major bleed is 3% per year
How should pregnant woman with hypercoaguability be treated?
Warfarin is teratogenic so women who may become pregnant should use low molecular weight heparin
________ defined as platelet count less than 50,000.
thrombocytopenia
What distinguishes petechia and purpura from other rashes?
do not blanch
Megathrombocytes
immature platelets recently released from bone marrow
Petechiae and purpura are found on the skin and mucous membranes
Low platelet count with no apparent cause
ITP
ITP treatment
Avoid aspirin and NSAIDS
Typically no treatment is necessary for either acute or chronic disease
Steroids
Splenectomy
Platelet transfusion in cases of severe trauma
Petechiae and purpura
Low platelets
Labs tests showing less than 5% normal ADAMTS13 protein
DX?
TTP
Symptoms of TTP
Petechiae and purpura Malaise Fever Bleeding from the nose and gums Neuro sx's including hallucinations and altered mental status Kidney failure
TTP treatment
Plasma exchange
Steroids
Without treatment 95% of patients will not survive. With treatment this number drops to around 10%
Similarities and differences between TTP and DIC
Both have hemolysis and thrombocytopenia
TTP has abnormal renal function but normal PT/PTT
DIC has normal renal function but prolonged PT /PTT causing increased clotting
DIC treatment and prognosis
Platelet transfusion
Fresh frozen plasma
Anticoagulation may be necessary??
10-50% of patients will not survive
Disease characterized by overproduction of WBCs
leukemia
What are PE findings of leukemia?
swollen lymph glands, enlarged spleen
How is chronic and acute leukemia differentiated in lab?
acute - cells immature from fast increase in WBC production
chronic - slower buildup of WBC so mature cells; cells still abnormal and non-functioning
Myelogenous vs lymphocytic leukemia
Lymphocytic - overproduction of lymphocytes
Myelogenous- overproduction of RBCs as well as some WBCs and platelets
Symptoms of leukemia
Symptoms of anemia Weakness Fatigue Fever/infection Decrease in appetite Bone and joint pain Enlarged lymph nodes Petechia
Leukemia in ages 2-5 with excessive lymphoblasts
ALL
Bone marrow biopsy of ALL and AML
hypercellular
Most common type of leukemia, majority of men over 50 yo
CLL
Auer rods are pathonomonic for ______.
ALL
Leukemia treatment
Chemotherapy
Radiation
Steroids
Bone marrow transplant
Which leukemias can present as asymptomatic?
CLL, CML
Which leukemia can be managed with tyrosine kinase inhibitors?
CML
Unlike leukemia, __________ is a solid tumor.
Hodgkins lymphoma
Staging 1-4 for lymphoma
Stage 1: single site
Stage 2: two or more lymph nodes on same side of diaphragm
Or one extralymphatic site and one lymph node on same side
Stage 3: Affected lymph nodes on both sides of diaphragm and involvement of spleen or another extralymphatic site
Stage 4: Presence of B symptoms (fever, weight loss, night sweats) or diffuse extra lymphatic involvement
Lymph node biopsy showing ________ is diagnostic for Hodgkins lymphoma.
Reed-Sternberg cells
Differences between Hodgkins and non-Hodgkins lymphoma?
- Both cancer of WBCs (lymphomas)
- Non Hodgkins more common
- Hodgkins has Reed-Sternberg cell on microscopy
Build up of plasma cells in the bone marrow interfering with normal production
Multiple Myeloma
Findings of Multiple Myeloma on skeletal survey
XR of skull shows punched on lesions
Lytic lesions
Why is hypercalcemia seen in multiple myeloma?
excessive bone resorption
Multiple Myeloma treatment and prognosis
No treatment other than treating end organ damage
Chemo with stem cell transplant
5 yr survival rate 35%
Philadelphia Chromosome is pathognomonic for _____.
CML
Bence-Jones proteins and rouleaux formation on peripheral smear
multiple myeloma
hematopoiesis
development of blood cells
How is fetal hemoglobin different than adult?
greater affinity for oxygen
What is hematocrit measure?
percent of blood volume composed of RBC
Normal range for WBC
4.5K to 11K
Normal range for platelets
150K to 400K
What is the spleens role in hematologic system?
- filters out malformed, damaged, or old RBCs
- hematopoiesis in fetal period
Site of hematopoiesis
bone marrow in adults
spleen in fetus
What is aplastic anemia?
loss of hematopoietic cells leading to pancytopenia (decrease in all blood cell types)
Pathologies of the hemoglobin
Sickle cell
Thalassemias
Lab findings of hemolysis
increased indirect bilirubin increased LDH increased reticulocytes decreased free haptoglobin schistocytes
Type I hypersensitivity reaction
Anaphylaxis
IgE mediated
Allergies (food, dust, insects)
Type II hypersensitivity reaction
Cytotoxic
mediated by IgG, IgM antibodies
Hypersensitivity reaction with antigen-antibody complexes
Type III
Cell mediated or delayed hypersensitivity reaction
Type IV
What cells produce antibodies?
lymphocytes
_________ is proliferation of WBCs in bone marrow and _________ is proliferation in lymphatic tissue.
Leukemia
Lymphoma
Where is lymphatic tissue?
lymph nodes and spleen
Causes of elevated WBC
infection or inflammation autoimmune disease hematologic malignancy (leukemia, lymphoma)
Cells that arrive at site of inflammation first
neutrophils
Coagulation factors that need Vitamin K for synthesis?
Mneumonic: 1972
X, IX, VII, II
What does abnormal PT and normal PTT mean?
problem with extrinsic pathway of clotting cascade
MOA of Coumdadin and how is it monitored
anticoagulation; interferes with Vit K-dependent clotting factors (10, 9, 7, 2)
monitored by PT
MOA of Heparin and how is it monitored
anticoagulation; increases antithrombin III activity and decreases amount of fibrin
monitored by PTT (intrinsic)
What helps platelets stick together when forming a clot?
fibrinogen (factor I)
Pathologies that cause platelet loss or destruction?
ITP
TTP
HUS
DIC
Byproduct of RBC breakdown
Bilirubin, iron, and amino acids
When _____ is negative, this rules out PE in a low risk patient.
D-dimer
