Exam 3 Flashcards
Transferrin
Absorbed iron is carried by this
Ferritin
Stores excess iron
Patho/mechanism of disease of iron deficiency anemia
Blood loss, reproduction and growth, inadequate iron intake
Symptoms of anemia’s
Fatigue
Tachycardia
Palpitations
Dyspnea or tachypnea on exertion
Pica
Common in iron deficiency patients
Craving for specific food, even if it doesn’t contain iron
Cheilitis
Irritation at corners of mouth
Seen in iron deficiency anemia
Glossitis
Smooth red tongue, common in anemia’s
Koilonychia
Spoon nails, common in iron deficiency anemia
Plummer Vinson syndrome
Dysphagia due to esophageal webs, seen only in severe disease of iron deficiency anemia
Lab eval for iron deficiency anemia
Microcytic, hypochromic
May see elevated RDW early in disease
Ferritin levels in iron deficiency anemia
Decreased
**will be falsely elevated in inflammation
B12 characteristics
Cobalamin Produced in microbes 100% needed from diet Stores well in tissues Takes years to deplete stores
B12 deficiency anemia causes
Nutritional deficiency
Inadequate absorption
Pernicious anemia
Large prevelance in patients 60+
Autoimmune destruction of gastric mucosa
Decreased instrinsive factor, causing severe b12 malabsorption
General cobalamin metabolism
Made into transcobalalmin, goes into cells, bings to MMcoA, donates methyl to DNA RNA, proteins, etc.
Why does b12 deficiency cause macrocytic anemia?
Accumulation of genetic material
B12 deficiency anemia signs and symptoms
Can cause leukopenia/thrombocytopenia
Glossitis, anorexia, diarrhea
**neuropathy! Stocking/glove distribution
B12 anemia lab testing
Low cobalamin
MMA and/or homocysteine levels elevated
Macrocytosis
Folic acid deficiency general characteristics
Neural tube defects (spina bifida) in pregnancy, congenital heart disease
Abundant in citrus and leafy greens
2-3 month store
Folic acid deficiency causes
Increased demand, dietary deficiency, drugs
Folic acid deficiency anemia signs and symptoms
Similar to b12, often simultaneous
**no neural abnormalities!!!
Lab testing for folic acid deficiency
Low serum folic acid
Cobalamin to rule out b12 deficiency
Thalassemias pathophysiology
Defective globin synthesis
Leads to microcytic, hypochromic anemia
Asian, black, Mediterranean patients
Alpha thalassemia pathophysiology
Gene deletion reduces alpha globin chain synthesis
Beta thalassemia pathophysiology
Point mutation, decrease or absent beta chain synthesis
How can you distinguish alpha and beta thalassemia?
Beta has basophilic stippling (also seen in lead poisoning)
Severe thalassemia, consider…
Splenectomy
Autoimmune hemolytic anemia
Autoantibodies form against RBC membrane causing hemolysis
IgG binds at body temp- autoimmune hemolytic anemia, warm auto Abs
IgM binds at cooler temps- cold agglutinin disease
Coombs test diagnoses…
Autoimmune hemolytic anemia
Sickle cell disease general characteristics
Autosomal recessive, amino acid substitution on beta globin chain
Hb S is unstable and prone to polymerization with other Hb S, leads to suckling
What are common triggers of sickling?
Hypoxemia and acidosis, deoxygenated Hb S
Heterozygous sickle cell…
Are typically hematologically normal
Homozygous sickle cell disease…
Causes the disease
Sickle cell disease diagnosis
Chronic hemolytic anemia
Sickle D cells visible on smear
Elevated acute phase reactants
Hemoglobin electrophoresis** confirmatory test
Sickle cell disease manifestations
Vaso-occlusive episodes/ crises
Acute chest syndrome- respiratory failure due to emboli, thrombosis, sometimes infection
Sickle cell and the spleen
Spleen is very active in removing old RBC and RBC fragments
Splenomegaly, splenic sequestration, can lead to hypocalcemia shock
Can cause auto splenectomy
Sickle cell disease traetment
Stem cell transplant for kids
**pain management
Hydroxyurea
Paroxysmal nocturnal hemoglobinuria General
Rare
Gene on X chromosome, but not X linked
Abnormal RBC vulnerability to complement (Coombs negative)
PNH symptoms/signs
Hemoglobinuria, jaundice, bone marrow suppression, increases at night
PNH labs
Flow cytometry, sorts and identifies cell types
**severe disease needs to be treated
Aplastic anemia
Injury or suppression of heme stem cell- marrow failure and inability to make mature blood cells
Hereditary Spherocytosis
RBC membrane protein defect, leads to hemolysis due to membrane fragility
Spherocytosis diagnosis
Osmotic fragility testing
Spherocytes in peripheral smear
G6PD deficiency
G6PD decreases oxidative stress, so a deficiency leads to denatured proteins
G6PD deficiency RBC presentation
Heinz bodies
RBC membrane damaged
Bite cells in peripheral smear
**enzyme assay confirms low G6PD
Anemia of chronic disease
Microcytic
Commonly from inflammation, organ failure, old age
Extrinsic pathway general
Triggered by tissue damage, started from exposure to tissue factor
Quick, small steps to form thrombin, positive feedback loop
Prothrombin time evaluates this pathway
Intrinsic pathway general
Trauma to blood or exposed collagen, less potent enough than extrinsic pathway
PTT evaluates this pathway
Plasminogen is activated to…
Plasmin, which does fibrin degredation
Platelet range indicative of platelet transfusion
<10-20 k
Petechiae
No blanching, erythematous or violaceous lesion
<3 mm
Purpura
3-10 mm
Ecchymosis
> 10 mm
Hemorrhagic bullae
Fluid filled lesion >10 mm
Vasculitis, necrotizing infections, etc
Thrombocytopenia in pregnancy
Often due to expanded plasma volume, HELLP
Hemolysis, elevated liver enzymes, low platelets
Pseudo thrombocytopenia
Platelet clumping can occur in lab testing, but citrated platelet count can verify true vs. pseudo thrombocytopenia
Immune Thrombocytopenia general
Dz of young women
Circulating antiplatelet autoantibodies, insufficient platelet production
Thrombopoietin levels low
Immune thrombocytopenia manifestations
Some asymptomatic
Mucocutaneous bleeds, mild nosebleeds
Some severe bleeds
ITP work up/treatment
Isolated thrombocytopenia on CBC
Thrombotic microangiopathy
2 forms, thrombotic thrombocytopenic purpura and hemolytic-uremic syndrome
Thrombotic thrombocytopenic purpura general
Deficiency of ADAMTS13
Causes huge multimers and then thrombus formation
Thrombotic thrombocytopenic purpura manifestations
Classic Pentad- Thrombocytopenia Anemia Fever Neurological problems Renal abnormalities
**rare
More likely to see thrombotic complications
Hemolytic uremic syndrome
Very similar to TTP, kids, endemic HUS usually caused by bacterial diarrhea
Heparin induced thrombocytopenia
IgG antibodies formed to heparin-platelet factor 4 complex
Usually asymptomatic, within 5-10 days starting heparin
Disseminated intravascular coagulation
Uncontrolled coagulation
Depletes the clotting system, causing lots!! Of bleeding and ischemic events
Disseminated intravascular coagulation related conditions
HELLP syndrome and sepsis
Hemoch- schonlein purpura
Systemic vasculitis in kids
Palpable purpura, arthritis, hematuria, maybe abdominal pain
Hemophilia A
Deficiency of factor VIII
Hemophilia B
Deficiency of factor IX
Genetics of hemophilia
X linked recessive, affects males and females will be carriers
Hemophilia clinically
Severe cases develop spontaneous hemarthroses and soft tissue bleeds
Hemophilia C
Factor XI deficiency
Mild bleeding risk, usually detected in surgery or trauma
Can supplement factor XI
Von willebrand disease general
Most common inherited bleeding disorder
Type 1- mild to moderate platelet type bleeding, epistaxis >10 and bleeding after dental work
Type 2,3- moderate to severe bleeding in childhood, may look like hemophilia
VWD diagnosis and treatment
Ristocetin cofactor activity
Type 1 traetment- DDAVP (des oppression)
Vitamin K deficiency
Vitamin K needed to activate 1971
Antiphospholipid antibody syndrome general
Autoantibodies to phospholipids (not SLE)
Phospholipids involved in much of the coag cascade
Anti phospholipid antibody syndrome symptoms
Venous or arterial conclusions, recurrent fetal loss
Need to rule out SLE
Factor V Leiden mutation
Most common inherited cause of hypercoagulability
Resistance to activated protein C, more common for DVT with homozygous
Suspect factor V Leiden mutation if….
Thrombosis on OCP
Cerebral vein thrombosis
DVT/PE in white patients
MGUS general
Asymptomatic premalignant clonal proliferation
Absence of end organ damage
Variable risk of progression
Non-igm MGUS
igm mgus
Light chain mgus
Abnormality on testing should prompt a …
Bone marrow biopsy
When MGUS is found, what is the course of action?
WATCH, multiple myeloma is preceded by this.
MGUS complications
Fracture
Thromboembolism
Secondary cancer
MM general
Heme malignancy, stem cells that differentiated into plasma cells
In elderly
MGUS and end organ damage*
Malignant plasma cells can form tumors, bone dz means increased osteoclast activity
Bence jones proteins
In multiple myeloma, M proteins/globulin found in the urine
Amyloidosis
Found in multiple myeloma
Light chain fragments that aggregate into tangles, common cause of renal impairment and proteinuria
Multiple myeloma presentation
Anemia Bone pain Infection (pancytopenia) Renal dz Hyperviscosity
Multiple myeloma diagnosis
Pancytopenia
Anemia
**rouleaux, bundles of RBCs suggesting para proteins
Bone marrow biopsy to confirm dx
Smoldering myeloma
Meets hematologic criteria for multiple myeloma, but has no end organ damage
**just observe, like MGUS
Neutropenia
Absolute neutrophil count <1800
Greatest risk of infection if < 500
Congenital neutropenia
Genetic disruption of neutrophil development
High risk of infection, heme cancers in adolescence, early onset osteopenia and osteoporosis
Neutropenic fever
Hematologic emergency!!
Someone with neutropenia that develops a fever is treated very aggressively
Bone marrow transplant general
Allogenic-from an outside source
Recipient needs chemo before to clear out abnormal marrow cells
Myeloproliferative neoplasms general
Acquired clonal abnormality of heme stem cell
Shift into different types, but any can progress to acute myeloid leukemia
Polycythemia vera general
Overproduction of all 3 hematopoietic lines
EPO is low, yet RBCs still being produced
JAK2 mutation
Signs/symptoms of polycythemia vera
Hypervolemia/increased blood viscosity
Pruritus after a warm shower
Epistaxis
Polycythemia vera complications
Splenomegaly!!
Hallmark: elevated Hct
Primary myelofibrosis general
Fibrosis of the bone marrow, extramedullary hematopoiesis takes place in the liver, spleen and lymph nodes
JAK2 or MPL gene mutations common
Primary myelofibrosis presentation
Fatigue, splenomegaly, bleeding, bone pain
Primary myelofibrosis diagnosis
Anemia
Bone marrow biopsy is a dry tap or collagen
Essential thrombocytosis general
Proliferation of megakaryocytes and a rise in platelet counts
JAK 2 mutation
Essential thrombocytosis presentation
Asymptomatic thrombocytosis, splenomegaly, VTE
Rare: erythromelalgia (painful burning of hands with erythema)
Essential thrombocytosis bone marrow biopsy
Increased megakaryocytes
Myelodysplastic syndrome
Cluster of acquired clonal disorders of heme stem cells
Hyper or hypo cellular marrow, cell abnormalities
Preleukemia
Myelodysplastic syndrome presentation
> 60 years old
Usually asymptomatic
Fatigue, infection, or bleeding
Splenomegaly
Paraneoplastic syndromes
Rare disorders triggered by an altered immune system response to a neoplasm
Symptoms that result from substances produced by the tumor or antibodies against cancer
What is leukemia?
Neoplastic disorders of white blood cells with the origin of the problem in the stem cell
Lymphoid or myeloid cell lines at any stage
As population of cells expands, bone marrow starts to fail
Acute lymphoblastic leukemia general
Lymphoblasts arrest in early development, then proliferate
Replaces normal marrow, circulating blasts, effects b and t cells
Most common childhood malignancy
Acute lymphoblastic leukemia manifestations
Fever without infection
Fatigue
Bone pain (marrow replacement)
Confirm acute lymphoblastic leukemia with…
Bone marrow biopsy with 20% or more blasts
Also, Ph chromosome means poor prognostic factor
Tumor lysis syndrome
Oncologic emergency!!
Metabolic abnormalities caused by release of intracellular contents
Renal failure, hypocalcemia, hyperkalemia, hyperuricemia, hyperphosphatemia
Chronic lymphoblastic leukemia general
Older patients, ~70
Incidentally discovered lymphocytosis, may be >100K
Chronic lymphoblastic leukemia presentation
Fatigue
LAD
HSM
Hypogammaglobulinemia
Low CD4 count, t cell deficiency
Hairy cell leukemia
Subtype of chronic lymphoblastic leukemia
Need:
Pancytopenia
Splenomegaly
Hair cells present on blood smear or BMbx
MEN around 50 years old
Acute myeloid leukemia general
Arrest of maturation in marrow cells, pancytopenia
20% or more blasts
Acute myeloid leukemia presentation
Related to cell deficiencies, like bleeding, fatigue and infection
Organ infiltration
Leukostasis
Acute myeloid leukemia pathognomonic finding
Auer rods in cytoplasm
Pancytopenia + blasts
Acute promyelocytic leukemia general
Differentiation stops at promyelocytes
Hyperacute but highly curable
Acute promyelocytic leukemia presentation
Presents like acute myeloid leukemia, but with coagulopathy
~40
Chronic myeloid leukemia general
Disorder of middle age
Hypermetabolic state, overproduction of white blood cells
Chronic myeloid leukemia presentation
Fatigue, night sweats and low grade fever
Splenomegaly
Myelocyte buldge
What is the myelocyte buldge?
Myelocytes outnumber more mature metamyelocytes in peripheral blood
Seen in chronic myeloid leukemia
What leukemia is prone to blast crisis?
Chronic myeloid leukemia
Leukemia cutis
Single or multiple nodules in the absence of systemic findings
Often asymptomatic lesions, but could have other signs of leukemia
Lymphoma general
Solid cancers of lymphocytes
Non hodgkin lymphoma general
Peak between 20-40 years
Mostly B cell
Non Hodgkin lymphoma presentation
Painless LAD, local or widespread
“B” symptoms
-fever, drenching night sweats, weight loss >10%
Non hodgkin lymphoma diagnosis
Lymph node biopsy
Peripheral blood often normal, CBC will NOT make diagnosis, need the biopsy
Indolent non hodgkin lymphoma
Follicular, marginal zone, little node thing
Waldenstroms macroglobulinemia
Monoclonal IgM paraprotein, low grade non hogdkin lymphoma
B cells that are hybrid of lymphocytes and plasma cells
Waldenstroms macroglobulinemia presentation
Rouleaux
Fatigue/anemia
Hyperviscosity
Cold agglutinin dz!
Aggressive non hodgkin lymphoma
Sezary syndrome, Burkitt lymphoma, cns lymphoma, peripheral t cell, mantle cell lymphoma
Non hodgkin lymphoma staging
Ann arbor staging
1- one node region
2- two+ node regions on same side of diaphragm
3- node regions on both sides of diaphragm
4- disseminated dz
Mycosis fungoides
Slowly progressive cutaneous t cell lymphoma
Can present just in skin for decades
Hodgkin lymphoma general
Reed stern berg cells! (Abnormal B cell precursor)
EBV most common cause
Usually localized to single group of nodes
Where do you see schistocytes?
Microangiopathic hemolytic anemia
**TTP and HUS
What is the cornerstone of therapy for TTP?
Plasmapheresis/plasma replacement
HIT is more common in what type of heparin?
Unfractionated
What is the diagnostic test for HIT?
ELISA
Serotonin release assay**gold standard
Presentation of heparin induced thrombocytopenia
Usually asymptomatic
Thrombosis!
What substance is decreased in PNH?
Nitric oxide
What is the likely diagnosis if PNH causes bone marrow suppression?
Aplastic anemia
What 2 diseases that have mild bleeds can be treated with desmopressin?
Hemophilia A and wonvillebrand disease
What is the most common inherited thrombophilia?
Factor V Leiden mutation
What is the diagnostic test for MGUS?
SPEP
What are the two best tests for diagnosing leukemia?
Bone marrow biopsy and flow cytometry
Philadelphia chromosome is commonly found in…and sometimes in…
Chronic myeloid leukemia
Acute lymphoblastic leukemia
