Hem Onc Flashcards
Different types of white blood cells
Neutrophils - increased means infection - bands suggest bacterial infection
Lymphocytes: increased means viral infection
Eosinophils: parasites, allergic conditions
What diseases only have spherocytes on a peripheral blood smear?
Spherocytes are spheroid RBCs rather than bi-concave
Autoimmune hemolytic anemia - also has a positive direct Coombs test
—the spleen sees the spherocytes and identifies them as abnormal so it destroys them, therefore causing anemia
What are acanthocytes
RBCs that have a spiked cell membrane due to abnormal thorny projections.
“spur cell”
Usually caused by liver disease
What are schistocytes
RBC fragments as a result of mechanical destruction (fragmentation hemolysis) of a normal RBC.
Occurs when there is damage to a blood vessel and a clot begins to form
What are Howell-Jolly bodies
nuclear remnants in the cytoplasm
indicate splenic dysfunction
What do bands indicate?
These are immature white blood cells that are released when there is an infection
What might metamyelocytes suggest?
These are immature band cells
Indicate very immature WBC being sent out. Likely represents sepsis.
What do smudge cells indicate
remnants of cells that lack any identifiable cytoplasmic membrane or nuclear structure
Associated with chronic lymphocytic leukemia
What do blasts indicate if seen in the peripheral blood?
Usually indicates a leukemia or severe myelodysplastic syndrome
These are cancerous and should raise alarm
What are the three causes of anemia
-Problem with RBC production, usually in bone marrow
-Premature destruction of RBC (hemolysis) faster than new ones can be made
-Loss of blood
What are the three types of anemia
Microcytic: MCV <80
Normocytic: MCV 80-100
Macrocytic: MCV >100
Work up for microcytic anemia
Check iron levels
-If deficient (MOST LIKELY), work up for source of chronic blood loss
-if normal or elevated, consider anemia of chronic disease
Generally is caused by iron deficient anemia
Work up for normocytic anemia
Check a reticulocyte count (immature RBC)
-If low, anemia of chronic disease or bone marrow disease
-If elevated, blood loss or hemolysis
Work up for macrocytic anemia
Check B12/folate levels
-If low, vitamin B12 deficiency - Most likely - Pernicious anemia
-If normal, consider thyroid, ETOH, liver disease
Hemachromatosis: Causes, clinical presentation and treatment
Clinical syndrome of iron overload that is either caused by primary cause (gene mutation) or a secondary cause such as excessive blood transfusions or taking too many supplements.
Presents with interference of organ functions:
-Cirrhosis
-Bronzing of the skin
-CHF, arrythmias
-Endocrine problems
Treatment is phlebotomy to reduce ferritin
In primary gene mutation - can give Deferasirox (Exjade)
Lab findings in Thalassemia
Anemia with microcytosis and hypochromia
(low MCV and low MCHC)
Paroxysmal nocturnal hemoglobinuria - clinical presentation
-First morning urine is often dark or red (hgb)
-Prone to thrombosis especially in the skin (forms nodules), the hepatic and mesenteric veins
-Erectile dysfunction
-Esophageal spasm
Labs show thrombocytopenia, hemoglobinuria
What is autoimmune hemolytic anemia: Causes and presentation include labs
Increased RBC destruction
Intrinsic causes: spherocytes,
-hemoglobinopathies: thalessemia, sickle cell
Extrinsic - immune response, infx (malaria, babeiosis)
-All are caused by hyperbilirubinemia
—Could get GGT which will be normal because LFTs will all be elevated in hemolytic anemia and GGT only elevated in liver disease
-Positive Coombs test
-If you see shystocytes - autoimmune hemolytic anemia
Will present with rapid onset anemia, plus jaundice and splenomegaly
Treatment of autoimmune hemolytic anemia
Prednisone 1-2mg/kg/day
Plasmapheresis
Splenectomy
Transfuse as needed
Treatment of autoimmune hemolytic anemia
Prednisone 1-2mg/kg/day
Plasmapheresis
Splenectomy
Transfuse as needed
Polycythemia Vera - Cause and presentation
Mutation of the JAK2 gene results in the overproduction of all blood cells, causing an expanded blood volume and increased blood viscosity
Patients usually complain about pruritus, headache, dizziness, pulsatile tinnitus
Usually appear ruddy complexion and look swollen
Biggest complication is the blood viscosity and arterial thrombosis
Treatment of polycythemia vera
Regular phlebotomy to keep HCT <45
Hydroxyurea can be used as well if phlebotomy is not tolerate
Ruxolitinib is the only JAK2 inhibitor approved by the FDA
Disorders that cause thrombocytopenia
Immune thrombocytopenia purpura (ITP)
-Diagnosis of exclusion
-Sxs include spontaneous bruising, petechial rash, spontaneous bleeding from the nose, gums, vagina
-Platelet count will be very low
-Caused by decreased production due to destruction of the metakaryocytes
-Treatment can be supportive and it will resolve on its own or can give prednisone
Thrombotic Thrombocytopenic Purpura (TTP)
-Rare, hem emergency
-ITP plus hemolytic anemia
-blood clots form in small vessels throughout the body
-This causes low platelet count, low RBC count, and kidney, heart and brain dysfunction
-Presentation is fevers, AMS, thrombocytopenia, acute renal failure, hemolytic anemia
-Treatment is plasmapheresis and usually Rituximab
—Do not give platelets as this will only fuel the disease
Heparin-induced thrombocytopenia (HIT)
The immune system forms antibodies against heparin when it is bound to a protein called platelet factor 4
If you see platelet counts falling within 5 days of starting heparin, should stop heparin right away and start alternative anticoagulant
–bivalirudin, argatroban, fondaparinux
—This treats the clots that are formed because of the HIT
—Do not start Warfarin
Disseminated Intravascular Coagulation (DIC)
Clotting cascade is activated either locally or systematically
Condition is always secondary to something else
-Sepsis
-Retained products of conception
-Malignancy, often acute leukemia
-Starts with inappropriate activation of the clotting cascade and platelet activation
-As it progresses, clotting factors and platelets are exhausted and spontaneous bleeding begins
Treatment of DIC
Treat the trigger
Establish a baseline with lab parameters
-Platelet count
-PT, PTT
-D-Dimer
Transfuse blood products
Follow the lab parameters every 4 hours
If bleeding persists, consider heparin infusion if the platelets are >50 but contraindicated if the GI or CNS bleeding, placental abruption, need for operative management
Von Willebrand Disease: Cause and Presentation
The most common congenital disorder of coagulation
-Deficiency in the quality or quantity of von Willebrand factor - a protein required for platelet adhesion
Presentation ranges from mild bleeding that often goes undiagnosed because it is so small to severe bleeding with even minor trauma
Treatment of Von Willebrand Disease
For most patients it is DDAVP (Desmopressin)
If more severe bleeding, can give Factor VIII
Hemophilia - Causes and complications
X-linked recessive disorder (therefore only occurs in males)
Hemophilia A is a deficiency of Factor VIII
Hemophilia B is a deficiency of Factor IX
Diagnosis:
Generally done by genetic counseling and diagnosed during pregnancy
Complications:
Deep internal bleeding from minor trauma
Joint damage from hemarthrosis
Spontaneous intracranial hemorrhage
Treatment:
DDAVP for mild cases
Severe cases: regular administration of recombinant factors
Reversal of anticoagulation
Heparin and LMWH - Protamine
Fonaparinux - cannot be reversed with Protamine
Warfarin - Vit K, K centra
DOACs - short half life so usually can just stop it
–Pradaxa - Praxabind
–Xarelto and Eliquis - Andexxa
Difference between acute and chronic leukemias
Acute: Rapid increase in the number of immature blood cells
–Immediate treatment is needed because of the rapid progression and accumulation of blasts which can spill into blood stream and spread to other organs
—Usually easier to treat because the cells are so immature and differentiating so quickly that they are vulnerable
Chronic: Excessive buildup of relatively mature, but still abnormal WBC
–Usually seen in older patients
—Usually monitored for a bit to determine treatment course
Chronic Myeloid Leukemia (CML) - cause, presentation, treatment
-Caused by a chromosomal abnormality at the Philadelphia chromosome*** HALLMARK
-Early stages are asymptomatic and usually picked up incidentally on routine lab studies
-Can present in acute form - rapid progression, low survival rate - “blast crisis”
—spontaneous bleeding, fevers, petechia
In chronic form, presents with fatigue, bone pain, splenomegaly
Labs will show pronounced leukocytosis without obvious infection
–Mature myeloid cell types predominate
—Bone marrow biopsy shows the bcr/abl genotype
Treatment:
-Since often found in the elderly, treatment may be deferred
-If undertaken, usually treated with Tyrosine kinase inhibitors with good prognosis at 5 years
–Curative with bone marrow transplant
Myelodysplastic Syndrome
Acquired clonal disorder of the hemotopoietic stem cell
—These cells are disorder and they make clones of themselves
These cells stay in the marrow and do not leave
Caused by radiation and chemotherapy
Many patients had cancer before, were treated with chemotherapy, went into remission and then develop MDS because of the chemo.
—They then will progress to an Acute Myeloid Leukemia
Treatment is supportive and blood products
-Also hematopoietic growth factors
Prognosis is months to years
Acute Myeloid Leukemia - Presentation and lab findings
More common in adults, specifically males
Presentation is usually fatigue and spontaneous bleeding
Labs: Leukocytosis, severe anemia, thrombocytopenia, blasts appear on the diff
Malignant cell in AML is the myeloblast
Treatment of AML
High dose cytarabine and daunorubicin to stop the massive proliferation of myeloblasts
Then consolidation of doses
Then BMT
Acute Lymphocytic Leukemia - Causes and Presentation (including labs)
In ALL, the lyphoblast is the cancerous cell
Usually presents in children
-Often leptomeningeal spread to the CNS
CBC shows atypical lymphocytes with pancytopenia ***HALLMARK
Chronic Lymphocytic Leukemia - causes, presentation, labs
CLL is a clonal malignancy of the B cell lymphocytes
Usually very slow moving and is an accumulation of long-lived lymphocytes that do not work very well, therefore causing immunosuppression
Presents similar to HIV
More common in elderly patients
CBC shows lymphocytosis - smudge cells present***HALLMARK
What is a Richter Transformation
In CLL, the disease can transform a lymph node into an aggressive large B-cell lymphoma
Hairy Cell leukemia
Similar to CLL however there is pancytopenia on CBC
Treatment is focused on symptom burden and presence of opportunistic infections
Major difference between leukemias and lymphomas
In lymphomas - the CBC is usually normal
Burkitt’s Lymphoma - causes, clinical presentation, treatment
Rapidly growing, invasive tumors of the lymph nodes and have a strong association with immune dysfunction (either post-viral or related to immunosuppression)
Respond quickly to chemotherapy
Spread quickly to the CNS and given that the patient is likely immunocompromised, can have high mortality rate
Hodgkin’s Lymphoma
Presents as painful, tender lymph node, usually in one of the cervical chains
B sxs often present - fatigue, malaise, weight loss
Classic finding is a biopsy showing Reed-Sternberg cells
Treatment is excision of the lymph node and chemotherapy
Plasma Cell Myeloma (formerly known as Multiple Myeloma) - Presentation, Diagnosis and treatment
Presents with CRABS:
C: Hypercalcemia
R: Renal failure
A: Anemia
B: Bony lesions - often moth eaten to long bones - pathologic fractures
Diagnosis made by protein electrophoresis of the urine of blood to identify paraproteins (Bence-Jones Protein)
Disease is incurable but the goal is to drive into remission and treat symptoms:
Lenalidomide - immunomodulator
Bortezomib - Proteasome inhibitor
BMT
Ortho intervention to treat pathologic fxs
Tumor Lysis Syndrome - When is it seen? Lab findings? Treatment
Most commonly seen following a treatment of a hematologic malignancy such as ALL or Burkett’s Lymphoma
Lab findings:
-Hyperuricemia
-Hyperkalemia
-Hyperphosphatemia
Acute renal failure develops shortly after
Most effective treatment is prevention
-Aggressive IVF before, during and after chemotherapy to keep urine output up and prevent the buildup of cellular materials from destroyed cancer cells
Emergency hemodialysis might be needed in severe cases
What is the normal range for Total Iron binding capacity?
250-450
What is the normal range for serum iron
50-150
Normal range for mean corpuscular hemoglobin concentration (MCHC)
32-36
<32 is hypochromic
> 36 is hyperchromic
A higher Total iron binding capacity means the (greater/lower) the need for iron?
Greater need for iron
DDx for low MCV
Iron deficiency anemia (most common) or thalassemia
DDx for high MCV
B12 or folate deficiency, alcoholism, liver failure and drug effects
Most likely is B12 or folic acid deficiency
What is megaloblastic anemia? Lab values?
B12 or folate deficiency
High MCV
What is the DDx for normocytic anemia?
Anemia of chronic disease
Sickle cell
Renal failure
Blood loss
Hemolysis
Cause of iron deficiency anemia and what labs do we see?
Blood loss, inadequate iron intake, impaired absorption of iron
Low H/H
Microcytic, hypochromic
Low serum iron
Low serum ferritin - stores are low
High TIBC - capacity is high
High RDW
Pica is associated with what type of anemia
Iron deficiency anemia
What is the difference between thalassemia minor and thalassemia major
Thalassemia minor: Have only one copy of they beta thalassemia gene and have only mild anemia (may mimic iron-deficiency anemia)
Thalassemia Major (Cooley’s anemia): Have two genes for beta thalassemia
–Anemia presents after a few months of life and becomes progressively severe
—FFT in a child
—Feeding difficulties (due to easy fatigue and lack of oxygen)
—Bouts of fever
—Diarrhea
—Hepatosplenomegaly and jaundice
—Maxillary enlargement
What are the labs associated with thalessemia
Decreased Hgb
Microcytic, hypochromic
Normal TIBC
Normal ferritin
Decreased alpha or beta Hgb chains
Which anemia is known to have decreased alpha or beta hemoglobin chains?
Thalassemia
Management of thalassemia
Usually no management is needed
Might need RBC transfusion/splenectomy for more severe forms
Iron is contraindicated as iron overload can occur
Should consider prenatal testing
Folic Acid deficiency - what are the labs?
Macrocytic, normochromic
HCT and RBC decreased
Serum folate decreased
Symptoms of folic acid deficiency
What is the difference in clinical presentation of folic acid deficiency and B12 deficiency
Folic acid Deficiency:
-Fatigue
-Dyspnea on exertion
-Pallor
-Headache
-Tachycardia
-Anorexia
-Glossitis (Big beefy tongue)
No neurologic signs are seen - this differentiates it from B12 deficiency
Pernicious Anemia - What are the labs?
Deficiency in B12
Macrocytic, normochromic
Anti-IF (intrinsic factor) and anti-parietal cell antibody test
H/H is also low
Serum B12 <200
Clinical manifestations of pernicious anemia
Weakness
Glossitis
Palpitations
Dizziness
Anorexia
BIG ONES:
-PARESTHESIA
-LOSS OF VIBRATORY SENSE
-LOSS OF FINE MOTOR CONTROL
-POSITIVE ROMBERG
-POSITIVE BABINSKI
Positive neuro findings with
Pernicious anemia
Treatment for pernicious anemia
B12 (cyanocobalamin) 100mcg IM daily x1 week
Then monthly for IM injections for life
What are the treatment priorities for sickle cell crisis
Fluids for dehydration (number 1 cause of crisis)
Analgesics for pain
Oxygen for hypoxemia
What is Von Willebrand Disease
A genetic disorder that results in the reduced ability to create blood clots
Caused by mutation of deficiency in von Willebrand factor and clotting factor VIII
Management of von Willebrand Disease
Desmopressin (DDAVP)
What is a lab value that distinguishes Acute Lymphocytic Leukemia (ALL)
Pancytopenia with circulation blasts
What is the most common leukemia in adults?
Chronic Lymphocytic Leukemia (CLL)
What is the hallmark lab value for chronic lymphocytic leukemia
Lymphocytosis
Hallmark lab value of chronic myeloid leukemia (CML)
Philadelphia chromosome seen in leukemic cells
What is required to confirm diagnosis of leukemia?
Bone marrow aspiration
What is tumor lysis syndrome: Clinical presentation and management
Usually caused when chemotherapy starts to break down tumor cells and breaks them apart. This releases all of their toxins.
Clinical presentation:
Hyperuricemia - elevated uric acid in the blood
Hyperkalemia
Hyperphosphetemia
Hypocalcemia
Management is by allopurinol to reduce risk of tumor lysis syndrome
Staging of lymphomas:
Stage 1: Disease localized to single lymph node
Stage 2: More than one lymph node, confined to one side of the diaphragm
Stage 3: Lymph nodes and spleen involved, crossed diaphragm
Stage 4: Live or bone marrow involved
Which disease is more virulent, Non-hodgkins or Hodgkins?
Non-Hodgkins is less predictable and advances quickly
Hodgkin’s Disease is more common in men or women?
Men, average age is 32
How can we distinguish between Hodgkin’s lymphoma and Non-Hodgkins?
Characteristic Reed-Sternberg cells are noted in Hodgkin’s disease
Normal platelet counts
150,000-400,000
How do you confirm a diagnosis of idiopathic thrombocytopenia purpura?
Bone marrow analysis
Low platelet count with other causes of thrombocytopenia ruled out
May be a history of easy bruising or bleeding
Management of idiopathic thrombocytopenia purpura
May not be necessary until platelet count drops below 20,000
High dose corticosteroids or IV Gamma Globulin may help to elevate the platelet count within 2-3 days
Platelet transfusions may be needed
What do you do if you think you might have Heparin-induced thrombocytopenia (HIT)
Immediately stop Heparin
Can give Argatroban or Lepirudin which will reverse the HIT and offer some anticoagulation therapy
How do you differentiate between idiopathic thrombocytopenia purpura and SLE?
Need bone marrow analysis
What causes disseminated intravascular coagulation:
Acquired coagulation disorder which results from the activation of both the coagulation and fibrinolytic systems (thrombin and plasmin are activated) causing simultaneous thrombosis and hemorrhage
Lab results in DIC
Thrombocytopenia
Hypofibrinogenemia (fibrinogen <170)
Decreased RBC
Increased FDP (Fibrin degradation products)
Prolonged prothrombin time (>19 seconds)
Prolonged PTT (>42 seconds)
Elevated D-dimer
Management of DIC
Platelet transfusions, fresh frozen plasma (to replace clotting factors) and cryoprecipitate (to maintain fibrinogen levels)
If you are giving a lot of pRBC, what would be something to consider giving after a 4-6 units?
Fresh frozen plasma - need the clotting factors
