Step Up - Hematologic Diseases and Neoplasms Flashcards
Anemia - Definition:
A reduction in Hct or Hb concentration.
When red cell mass decreases, several compensatory mechanisms maintain O2 delivery to the tissues. These include:
- UP CO.
- UP extraction ratio.
- Rightward shift of the oxyhemoglobin curve (Incr. 2,3-DPG).
- Expansion of plasma curve.
As a general rule, blood transfusion is NOT recommended UNLESS either of the following is true:
- Hb <7 OR
2. Patient requires incr. O2-carrying capacity - patients with CAD or some other cardiopulmonary disease.
Symptoms of anemia are highly variable, depending on:
- How rapidly the Ht drops.
- Underlying condition of the patient.
- Ht level the patient typically lives on.
Pseudoanemia:
Refers to a decrease in Hb and Ht 2o to dilution (ie 2o to acute volume infusion or overload).
If Ht and Hb reveals anemia, next tests to obtain to determine the cause of anemia are:
- Reticulocyte count
2. MCV
All anemias are initially?
Normocytic - it takes some time for the abnormal-sized RBCs to outnumber the normal-sized ones.
Anemia of liver disease:
MCV up to 115 - due to altered metabolism of plasma lipoproteins into their membranes, altering RBC shape (and incr. volume).
Normocytic anemia - DDX:
- Aplastic anemia
- Bone marrow fibrosis
- Tumor
- Anemia of chronic disease
- Renal failure
If the reticulocyte index is >2, do the following:
- Suspect blood loss –> Look for the source of bleeding.
2. Suspect hemolysis.
In an anemic patient, 1st step is:
To assess the volume status + hemodynamic stability.
If unstable, transfuse PRBCs BEFORE attempting to find the cause of anemia.
Dietary deficiency/incr. iron requirements - primarily seen in:
- Infants and toddlers.
- Adolescents.
- Pregnant women.
Microcytic anemias - Serum ferritin:
Fe def. –> Low.
Beta thal –> Normal/high.
ACD –> Normal/high.
Microcytic anemias - Serum Iron:
Fe def –> Low.
Beta thal –> Normal/high.
ACD –> Low.
Microcytic anemias - TIBC:
Fe def. –> High.
Beta thal –> Normal.
ACD –> Normal/low.
Microcytic anemias - RDW:
Fe def. –> High.
Beta thal –> Normal/high.
ACD –> Normal.
Treatment of iron def. anemia:
- Oral iron replacement (ferrous sulfate).
- Parenteral iron replacement (iron dextran IV, IM).
- Blood transfusion is NOT recommended unless anemia is severe or the patient has cardiopulmonary disease.
What is the main pathogenetic mechanism in beta thal?
Excess ALPHA-chains bind to and damage the RBC membrane.
Cooley’s anemia - another name?
Beta thal major.
Diagnosis of beta thal major:
- Hb electrophoresis –> HbF + HbA2 UP.
2. Peripheral smear –> Microcytic/hypochromic, TARGET cells may be seen.
Sideroblastic anemia - Clinical findings:
- Incr. serum iron + ferritin.
- Normal TIBC.
- TIBC sat is normal/elevated –> Distinguishes it from Fe def.
- Ringed sideroblasts in bone marrow.
Sideroblastic anemia - Treatment:
Remove offending agent - Consider pyridoxine.
Aplastic anemia - Can transform into a leukemia?
Yes - Into acute leukemia.
Aplastic anemia - Diagnosis:
- Normocytic/chromic anemia.
- Perform a bone marrow biopsy for definitive diagnosis - This reveals HYPOCELLULAR marrow and the absence of progenitors of all 3 hematopoietic cell lines.
Aplastic anemia - Treatment:
- Bone marrow transplantation.
- Transfusion of PRBCs + platelets, if necessary.
- Treat any known underlying cause.
VitB12 is involved in 2 important reactions:
- As a co-factor in conversion of homocysteine to methionine.
- As a co-factor in conversion of methylmalonyl CoA to succinyl CoA.
B12 def. due to how much ileac resection?
Approx. the last 100cm.
Other organisms competing for B12:
- Diphyllobothrium latum infestation - Fish tapeworm.
2. Blind-loop syndrome - Bacterial overgrowth.
B12 neuropathy:
- Demyelination in POSTERIOR columns + Lateral corticospinal + Spinocerebellar tracts –> Loss of position/vibratory sensation in lower extremities + Ataxia and UMN signs.
- Can lead to urinary/fecal incontinence, impotence.
- Dementia - Investigate in the workup for dementia.
Test that provides info regarding the cause of vitB12 def:
Schilling test.
B12 def - Treatment:
B12 IM once per MONTH.
What is elevated ONLY in B12 but NOT IN FOLATE def.?
Serum MMA!!!
Treatment of folate def. :
DAILY oral folate replacement.
The following are relevant in the history of a patient with hemolytic anemia:
- Ethnic background.
- Family history of jaundice/anemia.
- Medications.
Lab tests in hemolytic anemia:
- Elevated reticulocyte count.
- Elevated LDH.
- Decr. haptoglobin and Hb/Ht..
Dark urine color in intravascular hemolytic anemia:
Due to Hburia, NOT bilirubin.
Spherocytes or helmet cells suggest intra- or extra-vascular hemolysis?
Extra
Heinz bodies are seen in?
G6PD def.
Haptoglobin binds to?
Hb
LDH is elevated in hemolytic anemias because?
LDH is released when RBCs are destroyed.
Hemolytic anemias - General Treatment:
- Treat the underlying cause.
- Transfusion of PRBCs if severe anemia is present or patient is hemodynamically compromised.
- Folate supplements - folate is depleted in hemolysis.
Almost every organ can be affected in SCA:
- Blood –> Chronic hemolytic anemia, aplastic crises.
- Heart –> High-output HF due to anemia.
- CNS –> Stroke.
- GI tract –> Gallstones, splenic infartions, abdominal crises.
- Bones –> Painful crises, osteomyelitis, avascular necrosis.
- Lungs –> Infections, acute chest syndrome.
- Kidneys –> Hematuria, papillary necrosis, renal failure.
- Eyes –> Proliferative retinopathy, retinal infarcts.
- Genitalia –> Priapism.
SCA - Prognosis:
- Survival correlates with the frequency of vaso-occlusive crises - more frequent crises are associated with a shorter lifespan.
- If >3 crises per year –> Median age of death is 35.
- In general –> Life expectancy is reduced by 25-30yrs.
SCA - Does it require transfusions?
The anemia is well compensated and is RARELY transfusion dependent.
SCA - Aplastic crisis - Cause:
Usually provoked by a viral infection such as B19 –> Reduces the ability of bone marrow to compensate.
SCA - Aplastic crisis - Treatment:
Blood transfusion –> Recovers in 7-10d.
SCA - Painful crises involving bone - How long do they last?
2-7days.
SCA - Hand-foot syndrome (dactylitis):
Painful swelling of dorsa of hands and feet seen in infancy and early childhood - usually 4-6months.
SCA - What is often the 1st manifestation of SCA?
Hand-foot syndrome (dactylitis).
SCA - Hand-foot syndrome - Cause:
By avascular necrosis of the metacarpal and metatarsal bones.
SCA - Acute chest syndrome:
- Repeated pulmonary infarctions.
- Clinical presentation is similar to pneumonia.
- Associated with chest pain, respiratory distress, pulm. infiltrates, and hypoxia.
SCA - Priapism - How long does it last?
Usually 30min to 3hrs.
SCA - Priapism - How does it pass?
Usually subsides spontaneously, after urine is passed, after light exercise, or after a cold shower.
Sustained priapism is a?
Medical EMERGENCY - Rarely, priapism lasts >3hr.
SCA - Why predisposition for salmonella osteomyelitis?
Also due to splenic malfunction.
SCA - Diagnosis:
- Anemia is the MC finding.
- Peripheral smear - sickle-shaped RBCs.
- Hb electrophoresis is REQUIRED for diagnosis. In most cases, diagnosis is made from newborn screening tests.
SCA - Advise the patient as follows:
- Avoid high altitudes (also avoid airplanes).
- Maintain fluid intake.
- Treat infections properly.
SCA - Management of painful crises:
- Hydration
- Morphine
- Keep the patient warm
- Supplemental O2 if hypoxia is present
SCA - Treatment - Role of hydroxyurea:
- Enhances HbF levels - which interferes with the sickling process.
- Results in reduced incidence of painful crises.
- Accelerates healing of leg ulcers and may reduce recurrence.
SCA - Blood transfusion?
- Not used unless absolutely necessary.
- Not based on Hb levels.
- Should be considered in acute chest syndrome, stroke, priapism that does not respond to fluids/analgesia, and cardiac decompensation.
Causes of spherocytosis:
- Hereditary spherocytosis
- G6PD def.
- ABO incompatibility (but not Rh incompatibility).
- Hyperthermia.
- Autoimmune hemolytic anemia.
Hereditary spherocytosis - Diagnosis:
RBC osmotic fragility to hypotonic saline.
Also, COOMBS (-) –> Helps to distinguish from AHA, in which spherocytes are also seen!
Mechanism of Heinz bodies formation in G6PD def.?
Def. of G6PD –> Accumulation of unneutralized H2O2 –> Denatures Hb –> Precipitates Heinz body formation within RBCs.
Problem with the Heinz bodies?
They attach to RBC membranes, reducing their flexibility and making them prone to sequestration by the spleen.
G6PD def. Diagnosis:
- Peripheral blood smear –> Bite cells, Heinz bodies.
- Deficient NADPH formation on G6PD assay.
- Measurement of G6PD levels is diagnostic –> HOWEVER, G6PD levels may be NORMAL during the hemolytic episode because the RBCs that are most deficient in G6PD have already been destroyed.
G6PD def - Treatment:
- Avoid drugs that precipitate hemolysis.
- Maintain hydration.
- Perform RBC transfusion when necessary.
AHA - Main mechanism:
Production of autoantibodies toward RBC membrane antigen(s) which leads to destruction of these RBCs.
AHA - What determines the prognosis, site of RBC destruction, and response to treatment?
The type of antibody produced (IgG or IgM).
AHA - Course:
Variable - More fulminant in children than in adults.
AHA - Diagnosis - Warm or cold?
Direct Coombs test:
If RBCs are coated with IgG –> WAHA.
If RBCs are coated with COMPLEMENT alone –> CAHA.
AHA - Treatment:
Often NO TREATMENT is necessary in either type of AHA, because the hemolysis is mild. If it is more severe, the therapeutic approach depends on the type of autoantibody causing the hemolysis.
Warm AHA - Treatment:
- Mainstay of therapy –> Glucocorticoids.
- Splenectomy.
- Immunosuppression –> Azathioprine or cyclophosphamide.
- RBC transfusions - If absolutely necessary.
- Folate supplements.
CAHA - Treatment:
- Avoid exposure to cold.
- RBC transfusion - if absolutely necessary.
- Various chemo agents.
- Steroids ARE NOT beneficial.
Paroxysmal nocturnal hemoglobinuria (PNH) - What is it?
Acquired disorder that affects hematopoietic stem cells and cells of ALL blood lineages.
PNH - Mechanism:
Caused by a deficiency of anchor proteins that link complement-inactivating proteins to blood cell membranes.
–> Unusual susceptibility to complement-mediated lysis of RBCs, WBCs, and platelets.
PNH - Thrombosis?
YES - of venous systems –> Budd-Chiari syndrome.
PNH - May evolve into?
- Aplastic anemia.
- Myelodysplasia
- Myelofibrosis.
- Acute leukemia.
PNH - Diagnosis:
- Ham’s test.
- Sugar water test.
- Flow cytometry (CD55, CD59).
PNH - Treatment:
- Glucocorticoids (prednisone) are the usual initial therapy - Many patients do NOT respond.
- Bone marrow transplantation.
Heparin-induced thrombocytopenia (HIT) - How many types?
2
HIT type 1:
Heparin directly causes platelet aggregation - Seen in <48hrs, after initiating heparin - No treatment is needed.
HIT type 2:
Heparin induces antibody-mediated injury to platelet - Seen in 3-12days.
Heparin should be discontinued immediately.
Severity of thrombocytopenia and associated risk - >100.000:
Abnormal bleeding (even after trauma or surgery) is unusual.
Severity of thrombocytopenia and associated risk - 20.000-70.000:
Incr. bleeding hemorrhage during surgery or trauma.
Severity of thrombocytopenia and associated risk - <20.000:
Minor spontaneous bleeding, easy bruising, petechiae, epistaxis, menorrhagia, bleeding gums.
Severity of thrombocytopenia and associated risk - <5.000:
Major spontaneous bleeding, intracranial bleeding, heavy GI bleeding.
Immune (idiopathic) thrombocytopenic purpura - What happens?
Results from autoimmune antibody formation against host platelets. These antiplatelet antibodies (IgG) coat and damage platelets, which are then removed by splenic macrophages.
Immune (idiopathic) thrombocytopenic purpura - 2 forms:
Acute and chronic.
Immune (idiopathic) thrombocytopenic purpura - Acute form:
- Seen in children.
- Preceded by viral infection (in most cases).
- Usually self-limited - 80% resolve spontaneously within 6 months.
Immune (idiopathic) thrombocytopenic purpura - Chronic form:
- Usually seen in adults, most commonly in women between 20-40yrs of age.
- Spontaneous remissions are rare.
ITP - Clinical features:
- Petechiae and ecchymoses on the skin - many patients will have only very minimal bleeding symptoms despite extremely low platelet counts (<5.000).
- Bleeding of the mucous membranes.
- No splenomegaly.
ITP - Diagnosis:
- Platelet count is frequently <20.000.
- Peripheral smear shows decreased platelets.
- Bone marrow aspiration shows incr. megakaryocytes.
- There is an incr. amount of platelet-associated IgG.
ITP - Treatment:
- Corticosteroids.
- IVIG –> Saturates reticuloendothelial system binding sites.
- Splenectomy –> Remission in 70-80% of cases.
- 2 new drugs –> Romiplastim, eltrombopag for splenectomy-resistant patients.
Thrombotic thrombocytopenic purpura (TTP) - Mechanism:
Rare disorder of platelet consumption. Cause is unknown.
- -> Hyaline microthrombi (mostly platelet thrombi) occlude small vessels - any organ may be involved.
- -> Mechanical damage to RBCs –> Schistocytes on peripheral smear.
TTP is a?
Life-threatening EMERGENCY that is responsive to therapy. If untreated, death occurs within a few months.
TTP - PT and PTT?
There is no consumption of clotting factors, so PT/PTT are normal.
TTP and HUS?
TTP = HUS + fever + altered mental status.
HUS is?
HUS = Microangiopathic hemolytic anemia + Thrombocytopenia + Renal failure.
TTP - Treatment:
- Plasmapheresis (large volume) –> ASAP!!!
- Corticosteroids and splenectomy - may be of benefit in some cases.
- Platelet transfusions are CONTRAindicated.
HIT - Main complications:
- Pulm. embolism
2. DVT.
What suggests HIT?
Decr. in platelet count by 50%.
HIT - Diagnostic tests:
Antiplatelet factor IV antibody or serotonin release assay.
HIT treatment:
- Stop heparin.
2. If anticoagulation is indicated (venous thrombosis), give a thrombin inhibitor such as lepirudin.
Bernard-Soulier syndrome - Inheritance pattern:
AR
B-S syndrome - Problem:
Disorder of platelet adhesion (to subendothelium) due to deficiency of platelet glycoprotein (GPIb-IX).
B-S syndrome - Peripheral smear:
Platelets are abnormally large.
B-S syndrome - Platelet count:
Mildly low.
Glanzmann’s thrombasthenia - Inheritance pattern:
AR
Glanzmann thrombasthenia - Problem:
Disorder of platelet aggregation –> Due to deficiency in platelet glycoprotein GPIIb-IIIa.
Bleeding time is prolonged.
Platelet count is normal.
The ristocetin assay can be used to test for?
vWD.
Factor VIII has 2 portions:
- The coagulant portion - Factor VIII coagulant protein.
2. The antigenic portion - Factor VIII antigenic protein –> Synonymous with vWF.
vWD - What happens?
AD disorder characterized by DEFICIENCY or DEFECT of factor VIII-related antigen (vWF).