Heme Flashcards
1
Q
Hemophilia
A
X-linked recessive inheritance clotting factor disorder
- Hemophilia A: factor VIII decrease → “Aight”
- Hemophilia B: decreased clotting factor IX
- Normal Factor Activity: 50-150%
- mild: 6-49% (Bleeding during surgery)
- moderate: 1-5% (occasional bleeding)
- Severe: <1% (spontaneous bleeding)
-
S/sxs:
-
hemarthrosis (bleeding in joint)
- main sxs = excessive bleeding
-
hemarthrosis (bleeding in joint)
-
Diagnosis: increased PTT, normal PT, normal platelets and function
- → corrected with mixing study
- if PTT is NOT corrected with mixing studies = indication of lupus anticoagulant or factor inhibitor
- most specific test: functional assay for factor VIII or IX
- → corrected with mixing study
-
Tx: replacement for depleted factors
- avoid situations that cause bleeding
- avoid certain drugs that interfere with platelet function (NSAIDs and aspirin)
2
Q
Von Willebrand Disease
A
Autosomal Dominant → most common genetic bleeding disorder clotting factor disorder
- missing protein for platelet function (usually hangs out in the endothelium of the blood vessels and is important for factor VIII transport → platelets cannot adhere to vessel at site of injury → bleeding doesn’t stop as quickly as it should
- hormonal changes, stress, pregnancy, inflammation, and infection can stimulate vWF production
- S/sxs: hx and family hx of bleeding, bruising easily, increased menstrual bleeding, no hemarthrosis, petechiae, bleeding with minor injury
-
Dx:
- decreased vWF and decreased Factor VIII
- normal CBC, normal platelet count, and increased bleeding time
- → normal or prolonged PTT with normal PT
-
Tx: DDVAP (desmopressin)
- if excessive bleeding → transfusion of concentrated blood clotting factors containing vWF
3
Q
Vitamin K Deficiency
A
Clotting Factor Disorder
Vitamin K does not cross the placenta and it is a fat soluble vitamin for bone calcification and activation of coagulation factors
- Vitamin K activates: factors II, VII (half-life = 4-6 hours), IX, X, Protein C and Protein S
- prolonged PT
- causes: malnutrition, abx, fat malabsorption, hemorrhagic disease of the newborn
-
S/sxs:
- bleeding, mucosal bleeding, epistaxis, GI hemorrhage, menorrhagia, and hematuria
-
Dx:
- prolonged PT or elevated INR that improves with phytonadione (generic name for vitamin K1)
- Tx: Oral or SQ phytonadione
4
Q
What causes a high aPTT?
A
activated partial thromboplastin time
measures the intrinsic pathway (slower)
- Intrinsic Pathway Factors: XII, XI, IX, VIII
- aPTT is the time in seconds for a fibrin clot to form: measures the function of factors VIII, IX, and XI
-
Causes of a high aPTT:
- heparin
- decreased factor (VIII, IX, XI), vitamin K, liver disease
- consumption: inhibitor, DIC
5
Q
What causes a high PT?
A
Prothrombin Time: measured in INR
measures the extrinsic pathway (faster pathway)
-
PT is the time in seconds for the fibrin clot to form: measures the function of tissue factor and Factor VII
- Warfarin
- NOACS
- decreased factors: VII, liver disease, Vitamin K
- overconsumption: DIC
6
Q
Heparin-Induced Thrombocytopenia
A
hypercoagulable state
- ≥ 50% reduction in platelet count within 7-10 days of exposure to heparin; results in global thrombocytopenia and thromboembolism due to immune rxn with platelet factor
- S/sxs: hx of multiple DVTs, CBC is normal, PT and PTT is normal
- Dx: HIT assay
-
Tx:
- to prevent thrombotic stroke or MI use antiplatelet therapy: aspirin, clopidogrel, prasugrel or dipyridamole/aspirin combo
- stop the heparin but still need an anticoagulant → must use a direct thrombin inhibitor (dabigatran)
7
Q
Antiphospholipid Syndrome
A
Hypercoagulable State
Dx & Tx trick: CardiB goes to War → Cardiolipin, anti-beta 2, tx with warfarin
certain membrane phospholipids are normally prevented from activating the coagulation cascade by binding to circulating phospholipid-binding proteins; antibodies to these binding proteins block this protective measure and predispose the pt to thrombosis → associated with lupus and PREVIOUS MISCARRIAGES
-
S/sxs:
- hx of multiple DVTs
- CBC is normal, PT and PTT are normal
- hx of multiple DVTs
-
Dx: ANA and CRP in SLE
- Russell’s Viper Venom time is specific to detect lupus anticoagulant
- (+) anticardiolipin antibody
- (+) anti-beta 2 glycoprotein I ELISA
-
Tx:
- Prednisone (for Lupus) and Warfarin
8
Q
Factor V Leiden Mutation
A
Most common genetic hypercoagulable state
mutations in factor V (of the common pathway) make it resistant to normal inactivation by activated protein C and predispose the pt to venous thrombosis
- have high suspicion in pts with recurrent thromboembolic events, thromboembolism in young pts, or in pts with NO risk factors; previous miscarriages
- S/sxs: hx of multiple DVTs, CBC is normal, PT and PTT are normal
-
Dx:
- Factor V leiden Assay
- Protein CC
-
Tx: anticoagulation
- antiplatelet therapy: aspirin, clopidogrel, prasugrel or dipyridamole/aspirin
- oral anticoagulant: Vitamin K antagonist, warfarin, direct thrombin inhibitor (dabigatran) or factor Xa blocker (rivaroxaban)
9
Q
Normal Platelet Range
A
130-400K
10
Q
Idiopathic Thrombocytopenic Purpura
A
aka immune thrombocytic purpura
- Epidemiology: autoimmune rxn to platelets usually after a viral illness → splenic platelet destruction often after an acute infx
- Caused by: viral infx, SLE, lymphoma, medications
-
s/sxs:
- mucosal bleeding, purpura, rashes, easy ecchymosis, petechial rashes
- chronic in adults, self-limiting in children (usually)
-
dx:
- diagnosis of exclusion (clinical diagnosis)
- isolated thrombocytopenia (very low) with a normal CBC and normal peripheral blood smear
- (+) Direct Coombs Test
- Normal PT and aPTT
- Primary ITP: isolated thrombocytopenia (<100K) without a known cause
- Secondary ITP: isolated thrombocytopenia (<100K) with an underlying condition (e.g. HIV)
-
Tx:
- steroids (prednisone) → blocks production of antibody
- IVIG (IV Immune globulin)
- Rituxan (Rituximab) → thrombopoietin receptor agonist
- Splenectomy → reserved for pts with severe thrombocytopenia (<15K)
11
Q
Thrombotic Thrombocytopenic Purpura
A
acute febrile disease with multi-organ thrombosis
-
caused by: deficiency or inhibition of metalloproteinase ADAMTS13 → most commonly disabled by autoantibody
- ADAMTS13 normally degrades (cuts up) vWF multimers; so with deficiency have increased platelet adhesion → platelet thrombosis = damages brain and kidneys
- Triggers: after drugs: quinidine, cyclosporine, clopidogrel, ticlopidine
- Risk Factors: female, AA, use of desmopressin (DDVAP), pregnancy
- Hemolytic uremic syndrome
-
S/sxs:
- adults = purpura and FAT RN → Fever, anemia, thrombocytopenia, renal failure, neurological symptoms
-
Dx: CBC = normal, except LOW platelets
- schistocytes (RBC fragments on the smear)
- (-) Direct Coombs Test
-
Tx:
- plasmapheresis (plasma exchange) = tx of choice → done daily until evidence of subsiding disease and is indicated by a normal platelet count
- corticosteroids + Rituximab (thrombopoietin receptor agonist)
12
Q
Disseminated Intravascular Coagulation
A
abnormal activation of the coagulation sequence lead to the formation of microthrombi through the microcirculation → causes increased consumption of platelets, fibrin, and coagulation factor
-
S/sxs: bleeding and thrombosis occur simultaneously
- bleeding and oozing at catheter sites, mucosal surfaces, petechiae, and ecchymosis, hypotension, and tachycardia
-
Dx:
-
decreased platelets (slightly), increased bleeding time, increased PT and aPTT, (+) D-Dimer
- SCHISTOCYTES
- Fibrinogen = decreased
-
decreased platelets (slightly), increased bleeding time, increased PT and aPTT, (+) D-Dimer
-
Tx:
- supportive care: cryoprecipitate, FFP, platelet transfusions if <10K, heparin for thrombosis, tx the cause
13
Q
A
Schistocyte
14
Q
Microcytic Anemia
A
Low MCV (<80): a Tic is small (microcytic)
- Thalassemia
- Iron Deficiency
- Chronic Disease
- Lead poisoning
15
Q
Iron Deficiency Anemia Pathophys, Etiology, & Risk Factors
A
Microcytic Anemia: most common cause of anemia worldwide
- Pathophys: decreased RBC production due of lack of iron and decreased iron stores (ferritin) normally stored in the bone marrow, liver and spleen
-
Etiology:
- chronic blood loss = most common cause in the US, excessive menstruation, occult GI blood loss, decreased absorption: diet, celiac, bariatric surgery, H.pylori
-
Risk Factors:
- increased metabolic requirements → children, pregnant and lactating women
- → cow milk ingestion in young children: infants fed cow’s milk <1 yr of age, toddlers fed large quantities of cow’s milk
16
Q
Iron Deficiency Anemia S/sxs, PE, Dx, & Tx
A
Microcytic (<80) anemia
-
S/sxs: weakness, fatigue, exercise intolerance, dyspnea
- pagophagia→ craving for ice
- Pica: appetite for non-foods (clay, starch)
-
PE: koilonychia: spooning of the nails
- angular cheilitis : inflammation of the corner of the mouth
- tachycardia, glossitis (smooth tongue), signs of anemia (pallor)
-
Dx:
- CBC: microcytic hypochromic anemia = CLASSIC
- Increased RDW, decreased reticulocytes
- Iron Studies: decreased ferritin (pathognomonic), increased TIBC (transferrin), decreased transferrin saturation
- CBC: microcytic hypochromic anemia = CLASSIC
-
Tx: iron replacement: results in increased reticulocytes (within 5-10days), correction of anemia (6-8weeks), repletion of iron stores (1-3 months)
- increased absorption: take iron replacement with vitamin C (ascorbic acid) with water or orange juice on an empty stomach
- severe life threatening anemia tx: rbc transfusion (e.g.myocardial ischemia)
17
Q
Intrinsic vs Extrinsic Hemolytic Anemia
A
-
Intrinsic: (inherited Disorders)
- sickle cell anemia, thalassemia (microcytic), G6PD deficiency, hereditary spherocytosis
-
Extrinsic: (Acquired Disorders)
- autoimmune hemolytic anemia, DIC, TTP, HUS, paroxysmal nocturnal hemoglobinuria, hypersplenism
18
Q
Hemolytic Anemia S/sxs & Dx
A
- acute onset of pallor from anemia
-
splenomegaly
- jaundice with high indirect bilirubin → too much RBC breakdown for the liver to keep up with
-
splenomegaly
- increased LDH: hemolytic anemias will have increased LDH b/c it is part of the RBC membrane
- increased reticulocytes
-
Dx:
- positive Coombs test if autoimmune etiology
-
G6PD deficiency:
- episodic hemolytic anemia associated with sulfa drugs, fava beans, infx
- HEINZ BODIES
-
Hereditary Spherocytosis:
- (+) osmotic fragility test: mixes RBCs with varying saline, abnormally shaped RBCs will be fragile and fall apart
- Thalassemia: very low MCV + normal TIBC and ferritin
- Sickle Cell Anemia: very high reticulocyte count + pain
19
Q
Autoimmune Hemolytic Anemia Tx
A
1st line = steroids; more severe and persistent may need a splenectomy and/or blood transfusions
20
Q
Hereditary Spherocytosis Tx
A
Hemolytic anemia
splenectomy after appropriate IZs
21
Q
Two types of Autoimmune Hemolytic Anemia
A
-
warm antibody type: autoantibodies attach to and destroy RBCs at temperatures equal to or in excess of normal body temp
- medications: penicillins, cephalosporins, rifampin
-
Cold antibody Type: autoantibodies become most active and attack RBCs only at temperatures below normal body temp
- IgM antibodies
22
Q
Anemia of Chronic Disease Etiology &
Pathophys
A
Microcytic or Normocytic Anemia
due to decreased RBC production in setting of chronic disease
- Etiology: chronic infection, inflammation, autoimmune disorders, malignancy
-
Pathophys: 3 main factors that decrease serum iron:
- increased hepcidin: acute phase reactant that blocks the release of iron from macrophages, blunts EPO, and reduces GI absorption
- increased ferritin: acute phase reactant that sequesters iron into storage
- erythropoietin inhibition via cytokines
23
Q
Anemia of Chronic Disease common causes, Dx, & Tx
A
Microcytic or Normocytic Anemia
-
Most common causes:
- CKD (stage 4 and 5), anemia from connective tissue disorders, other diseases → RA, SLE, HIV, CA, cirrhosis, chronic infx
-
Dx: normocytic or decreased MCV
- decreased TIBC, and normal or increased ferritin
- CBC, serum iron, ferritin, transferrin
-
Tx:
- tx the underlying disorder
- recombinant EPO and iron supplements if HGB <10gm/dl → need to stop once hgb >11 gm/dl due to increased risk of MI and stroke
24
Q
Aplastic Anemia
A
Normocytic, normochromic anemia
- only anemia where all 3 cell lines are decreased: decreased WBCs, decreased RBCs, decreased platelets
- ***will have normal MCV, decreased reticulocytes***
-
Etiology:
- often idiopathic but can be caused by chemicals, drugs, or radiation → ACE inhibitors, sulfonamides, phenytoin, chloramphenicol, chemo, methimazole, and radiation
-
PE: severe pallor, petechiae, ecchymosis, mucosal bleeding
- → severe infx with decreased RBCs, WBCs, and platelets but no reticulocytosis
-
Dx: suspect in pts with pancytopenia (WBC < 1500, ****platelets <50K****)
- decreased reticulocytes (helps to differentiate aplastic anemia in sickle cell patients who usually have a high baseline reticulocyte count)
- serum iron = elevated
- Most accurate test = bone marrow biopsy → normal cell morphology, hypocellular bone marrow with fatty infiltrate
-
Tx:
- d/c offending drug, RBC transfusion
- curative = bone marrow transplant (for pts <50 yo)
- immunosuppression agents for pts >50 yo or with comorbidities
-
Filgrastim (hematopoietic growth factor: G-CSF)
- reduces infx but does not change the course of the disease
25
Q
Folate Deficiency Anemia Etiology
A
Megaloblastic Macrocytic Anemia
Folate needed for DNA synthesis: decreased folate → abnormal synthesis of DNA, folate stores last 2-4 months
-
Etiology: most common: inadequate intake (alcohols, unbalanced diet)
- → increased requirements: pregnancy, infancy, hemolytic anemias, psoriasis (increased skin turnover)
- → impaired absorption: celiac disease, inflammatory bowel disease, chronic diarrhea, anticonvulsants (phenytoin, phenobarbital, carbamazepine)
- → impaired metabolism: methotrexate, trimethoprim
- → Loss: dialysis
26
Q
Folate Deficiency Anemia S/sxs, Dx, & Tx
A
Megaloblastic Macrocytic (>100) Anemia
-
S/sxs: anemia sxs similar to B12 deficiency but without neurologic abnormalities
- fatigue, exercise intolerance, pallor, chlorosis (pale, faintly green complexion)
- Glossitis, aphthous ulcers, diarrhea
- Maternal Deficiency = risk of neural tube birth defects
-
Dx: decreased Folate, increased MCV
- what to order: CBC, serum vitamin B12, and folate
-
CBC with peripheral smear:
- increased MCV + megaloblastic anemia (hypersegmented neutrophils, macroovalocytes), low reticulocytes
- decreased serum folate (<3), increased LDH, increased homocysteine, normal methylmalonic acid (distinguishes from B12 deficiency)
-
Tx:
- folate supplements (oral folic acid): 400-1000 micrograms PO daily
- d/c offending med and limit alcohol consumption
- CDC recommendation and pregnancy: 4000 mcg each day 1 month before becoming pregnant, and during 1st 3 months of pregnancy
- folate supplements (oral folic acid): 400-1000 micrograms PO daily
27
Q
Vitamin B12 Deficiency Anemia Pathophys and Etiology
A
Sources of B12: mainly animal products (meats, eggs, dairy)
- Absorption: B12 is released by the acidity of the stomach & combines with intrinsic factor where it is mainly absorbed in the distal ileum
- Pathophys: B12 deficiency → abnormal synthesis of DNA ; B12 normally needed to convert homocysteine to methionine for DNA synthesis.
-
Etiology:
- Pernicious Anemia = most common cause → lack of intrinsic factor due to parietal cell antibodies leading to gastric atrophy (parietal cells secrete acid and intrinsic factor)
- Crohn’s Disease, gastric bypass, chronic alcohol use, celiac disease, pancreatic insufficiency
- Meds: H2 blockers, PPIs (decreased acidity of stomach = less absorption); metformin (decreased nucleic acid synthesis)
- Vegans → decreased intake
28
Q
Vitamin B12 Deficiency Anemia S/sxs, Dx, & Tx
A
Megaloblastic macrocytic (>100) anemia
-
S/sxs: anemia sxs similar to folate deficiency → fatigue, exercise intolerance, pallor, weight loss, glossitis, diarrhea
- neurologic sxs: symmetric paresthesias = most common initial sxs (especially the legs)
- lateral and posterior spinal cord demyelination and degeneration: ataxia, weakness, vibratory, sensory and proprioception deficits, decreased deep tendon reflexes, + babinski
-
Dx:
- CBC with peripheral smear:
- increased MCV + megaloblastic anemia (hyper segmented neutrophils), low reticulocytes
- increased homocysteine levels and methylmalonic acid → distinguishes B12 from folate deficiency
- CBC with peripheral smear:
-
Tx:
- B12 replacement
- for symptomatic anemia or neuro findings: start with IM B12, if adult IM = cyanocobalamin injection weekly until deficiency is corrected then once monthly)
- pts with pernicious anemia require lifelong monthly IM therapy (or high dose oral therapy)
- dietary deficiency = oral B12 replacement
- B12 replacement
29
Q
G6PD Deficiency Anemia Risk Factors, Pathophys, & Exacerbating Factors
A
Hemolytic Anemia
- X-linked recessive that can cause episodic hemolytic anemia
- Risk Factors: primarily males (x-linked), 10-15% of African-American males
-
Pathophys:
- G6PD catalyzes NADP to NADPH, which protects RBCs from oxidative injury
- → loss of the NADPH causes the oxidative injury to the RBCs which leads to denatured HGB that will then precipitate as a Heinz Body
-
Exacerbating Factors:
- infection = most common cause
- fava beans
- Medications: dapsone, primaquine, methylene blue, nitrofurantoin, phenazopyridine
- G6PD catalyzes NADP to NADPH, which protects RBCs from oxidative injury
30
Q
G6PD Deficiency Anemia S/sxs, Dx, & Tx
A
X-linked recessive episodic Hemolytic Anemia
-
S/sxs: most pts are asymptomatic until times of oxidative stress
- sxs begin 2-4 days after exposure → back or abd -pain, sxs of anemia, jaundice, transient splenomegaly
- neonatal jaundice
-
Dx: G6PD assay
- Heinze bodies + bite cells
- increased LDH, increased indirect bilirubin, decreased haptoglobin
-
Tx:
- avoidance of trigger and supportive care
- during acute hemolysis, tx is supportive; transfusion is rarely needed
- neonatal jaundice: phototherapy
31
Q
Hemochromatosis
A
Autosomal recessive hemoglobinopathy caused by excess iron absorption
- excessive iron absorption in the intestine leads to increased accumulation of iron (as ferritin and hemosiderin) in various organs → leads to organ fibrosis
-
S/sxs:
- Classic Triad: cirrhosis, DM, & Skin Pigmentation
- affected organs:
- Liver (primary organ): cirrhosis → increased risk of hepatocellular carcinoma
- pancreas → diabetes due to iron deposition
- heart → cardiomyopathy, CHF, arrhythmias
- Joints: arthritis of the phalangeal joints, hips and knees
- skin: hyperpigmentation → “Bronze-like”
-
Dx: screen patient’s siblings
- high levels of serum iron, increased elevated fasting serum transferrin saturation and ferritin
- decreased total iron binding capacity (TIBC)
- Liver biopsy to determine degree of fibrosis
- HFE gene testing
-
Tx:
-
phlebotomy → usually weekly at first then lifelong maintenance phlebotomy Q2-4 months
- avoid iron supplements, vitamin C or excessive alcohol consumption
- Deferoxamine (medication): chelation of iron → used if the patient is unable to undergo phlebotomy
-
phlebotomy → usually weekly at first then lifelong maintenance phlebotomy Q2-4 months
32
Q
Sickle Cell Trait
A
Autosomal Recessive → causes defective beta chain that leads to RBCS to sickle under conditions of low oxygen
- HbA + HbS; HbSA = trait
- avoid hypoxia and dehydration
- no anemia, resistance to malaria
- Hematuria
- Dx: sickled cells on peripheral smear + HbS + HbA on hgb electrophoresis
33
Q
Sickle Cell Disease
A
Autosomal Recessive Normocytic Anemia
HbSS = disease, causes a defective beta chain
- almost exclusively in AAs, caused by homozygous inheritance of HbS → sickle-shaped RBCs clog capillaries, causing organ ischemia and infarcts
-
S/sxs: anemia, jaundice, arthralgias, fever, painful (severe abd and joint pain)
- slow healing ulcers, N/V, cranial nerve palsies, hepatosplenomegaly, cholelithiasis
-
Dx:
- (+) HgbS on hemoglobin electrophoresis = Definitive (no Hgb A)
-
normochromic, normocytic cells, increased bili, and LDH
- hgb: approx 8-10, HCT 20-30%
- reticulocytosis (increased reticulocytes)
- sickle cells
- Howell Jolly Bodies (nuclear remnants that have not been phagocytosed due to reduced splenic function)
-
Tx:
-
crises are tx with analgesics and other supportive measures (oxygen, hydration)
- folic acid (penicillin prophylaxis in children)
- vaccines prolong survival
-
antisickling agents:
- Hydroxyurea may decrease the frequency of crises
- voxeolotor: increased oxygen affinity of HbS
- Crizanlizumab: prevents cell adhesion
- RBC transfusion to minimize hypoxia → Hgb >10
- Stem cell transplant and gene therapy = curative
- Median survival 60yo: infx, CVA, renal failure, pulm HTN
-
crises are tx with analgesics and other supportive measures (oxygen, hydration)
34
Q
Alpha-Thalassemia
A
Autosomal Recessive hemoglobinopathy
Hypochromic microcytic anemia
-
S/sxs:
- carrier: 1 deletion = asymptomatic
-
alpha thalassemia minor: 2 deletions = mild anemia, microcytic hypochromic
- cis deletion for asians
- trans deletions for AAs
- alpha thalassemia major: 3 deletions: symptomatic → SPLENOMEGALY, MCHC, anemia, some need transfusion periodically
- Hemoglobin Bart’s Hydrops Fetalis: 4 deletions = incompatible with life
-
Dx: decreased MCV, low hgb, HIGH RBC, normal ferritin, normal TIBC and a (+) HgB electrophoresis
- peripheral smear: target, heinz bodies “Golf ball” looking cells and teardrop cells, microcytic
- hgb electrophoresis: normal hgb rations in adults with 1-2 gene deletions, detects hgbH with 3 gene deletion
-
Tx: for alpha thal minor → no tx
- for alpha thal major → can do splenectomy if severe anemia or splenomegaly
35
Q
Beta-Thalassemia
A
Autosomal recessive hemoglobinopathy
hypochromic microcytic anemia
- Beta Thal major: 2 of 2 beta genes damaged = significant organ damage, transfusion dependent anemia, excess alpha chains, stable as monomers, no precipitation in RBC
- Beta Thal Minor: 1 of 2 beta genes are damaged = mild-mod anemia
-
S/sxs:
- thrombosis = vascular disease
- ineffective erythropoiesis → splenomegaly, hepatomegaly, bone pain
- hemolysis = iron deposition and gallstones → endocrine dysfunction, cirrhosis, heart failure
-
Dx:
- very high RBC, low MCV, very hypochromic, normal ferritin, normal to low reticulocyte count, normal RDW
- peripheral smear: target and teardrop cells, basophilic stippling; nucleated RBCs → suspect thalassemia in pts with microcytosis and normal iron with increased RBC count
-
hgb electrophoresis:
- trait (minor): increased HgA2 or increased HgbF and decreased HgbA
- Major (Cooley’s): increased HgA2 or increased HgbF (up to 90%) and little to no HgbA
-
Tx:
- beta thal major: transfusion hgb 11-12
- folic acid daily
- luspatercept: RBC maturation agent
- splenectomy
- bone marrow transplant (for severe cases)
- iron chelation daily (need to prevent iron overload)
- beta thal major: transfusion hgb 11-12
36
Q
Neonatal Switch to Adult HbAA
A
alpha and gamma hemoglobin most prevalent just before birth, beta hgb rises just before birth
4 alpha, 2 beta in normal HgbA
45
Q
Acute Lymphocytic Leukemia
A
- Population: children, boys>girls, hispanics, 2-5yo
- Pathophys: overpopulation of immature WBCs (lymphoblasts) overtake normal hematopoiesis
- Pearl: CHILD+Lymphadenopathy + bleeding + fever + bone marrow > 20% blasts
- S/sxs: Pancytopenia → fever & infx (leukopenia); bleeding, petechiae, purpura (thrombocytopenia); Pallor & fatigue (Anemia)
-
Dx: bone marrow aspiration >20% blasts
- flow cytometry test: tells you subtype of leukemia
- WBCs 5-100K, decreased hgb and platelet
-
Tx: combination chemo → highly responsive with a remission >90%
- can do stem cell transplant if relapse
46
Q
Chronic Lymphocytic Leukemia
A
- Population: adults: most common form of leukemia in adults (~50yo; men > women) Mature B cell clonal malignancy → lymphocyte normal range 20-40%
-
S/sxs: often asymptomatic, fatigue, weight loss, sxs related to pancytopenia
- → lymphadenopathy, splenomegaly
-
Dx: peripheral blood smear: Lots of B-cells, limited other leukocytes. “smudge cells”
- WBC > 20K
- Absolute lymphocyte count > 5000 (5K)
- Tx: chemo, observation if indolent
47
Q
Myelodysplasia
A
- Pre-malignant, leukemic disorder
- Risk factors: age >65, radiation therapy, chemo, tobacco, mercury/lead exposure
- S/sxs: often asymptomatic: pancytopenia → easy bruising, bleeding, frequent infx & fatigue
- Dx: bones marrow biopsy → dysplastic bone marrow = hallmark → increased myeloblasts <20%
-
Tx: goals are sx improvement and prevention of progression to AML (blasts >20% in bone marrow)
- some may need intermittent blood or platelet transfusions and EPO
48
Q
Acute Myelogenous Leukemia
A
-
Pearls: most common presentation → blasts + Auer rods in adult pts t(15:17)**
- major of pts > 50yo
- Auer rods associated with DIC
-
S/sxs: anemia, bleeding, bruising, bone pain, thrombocytopenia, neutropenia
- TUMOR LYSIS SYNDROME
- PE: splenomegaly, gingival hyperplasia
-
Dx: >20% of myeloblasts in bone marrow = GOLD STANDARD, + myeloblasts with auer rods
- CBC: normocytic, normochromic anemia with normal or decreased reticulocyte count
-
Tx: combo of chemo + bone marrow transplant
- tumor lysis syndrome → allopurinol or rasburicase
49
Q
Chronic Myelogenous Leukemia
A
BCR-ABL translocation t(9:22)(Philadelphia gene)
-
S/sxs: fatigue, abdominal pain, night sweats, weight loss
- → splenomegaly
-
Dx: CBC full spectrum of WBCs, hgb and MCV = normal, platelets = slightly elevated
- BCr-abl fusion
-
Tx:
- imatinib = tyrosine kinase inhibitor for philadelphia + → they inhibit philadelphia chromosome tyrosine kinase activity and myeloid leukemic cell proliferation
- hematopoietic stem cell transplant = most effective cure
50
Q
Hodgkin’s Disease
A
- general: most common type of lymphoma, age: bimodal 20s & 50s, associated with EBV infx
-
S/sxs: B-cell sxs are NOT common→ fever, night sweats, weight loss, fatigue (sxs due to cytokine release from B-cells)
- Pel-Ebstein Fever: cyclical high fever q 1-2 weeks
-
PE: painless lympha, especially of upper body lymph nodes (but may worsen with EtOH ingestion)
- if solitary lymph node present > 30 days with no pain and no change → needs to be biopsied
- contiguous spread (owls fly to the next tree)
-
Dx: Reed-Sternberg cells = Pathognomonic → B-cell proliferation with bilobed or multilobed nucleus “Owl Eyes” -→ OWL’s HOOT
- Excisional biopsy of lymph node, may need bone marrow
-
Tx: excellent 5 year cure rate (60%)
-
chemo + radiation
- ***stage predicts outcome***: Ann Arbor Staging: stage I-II single side of diaphragm; stage III-IV both sides of diaphragm
- SEs of tx: cardiac disease if mediastinal radiation
-
chemo + radiation
51
Q
Burkitt Lymphoma
A
high grade non-hodgkin lymphoma
-
Pearls: CD20+, t(8:14), very aggressive, associated with EBV, HIV
- pediatric/adolescents.
- endemic to Africa
-
S/sxs:
- B-cell sxs common,
- usually involves the jaw and facial bones
- B-cell sxs common,
- “starry sky” appearance of bone marrow biopsy
-
Tx: African type Burkitt lymphoma = easily curable with chemo
- Sporadic & HIV associated Burkitt Lymphoma = curable with multiagent chemo
- Rituximab = anti-CD20 antibody
52
Q
Follicular Lymphoma
A
low grade non-hodgkin lymphoma
- Pearls: small cell proliferation in follicles, CD20+, t(14:18), usually indolent but hard to cure; can progress to diffuse large cell
-
S/sxs: B-sxs common, rapid onset, SOB, intussusception, bowel obstruction and abdominal mass = more common
- → non-contiguous, extranodal spread → GI & Skin = most common
-
Dx: r/o other causes of lymphadenopathy
- persistent, unexplained, enlarged lymph nodes should be biopsied
- staging: should be done with CT of abdomen and pelvis
- Tx: pts with indolent lymphoma with one or two nodes can be treated with radiation alone, incurable***
53
Q
Diffuse Large B Cell Lymphoma
A
intermediate grade non-hodgkin lymphoma
- Pearls: CD20+, rapidly enlarging nodes, most common type of NHL, ave age - 70yo
-
S/sxs: B-sxs common
- SOB, intussusception, bowel obstruction, and abdominal mass = more common → non-contiguous, extranodal spread → GI & skin = most common
- Painless lympha, of multiple peripheral lymph nodes
-
Dx: r/o other causes of lymphadenopathy
- persistent, unexplained, enlarged lymph nodes should be biopsied
- staging: should be done with CT of abdomen and pelvis
- Tx: chemo + immunotherapy (rituxan : anti-CD20 antibody), and stem cell transplant
54
Q
Multiple Myeloma
A
- most common primary tumor of the bone/bone marrow in pts >50
- all myeloma has prior MGUS stage, but only 1%/yr of MGUS pts develop myeloma
- Malignant clonal disorder of ***plasma cells*** → overproduction of IgG or IgA
-
S/sxs: CRAB:
- hypercalcemia
- Renal failure
- Anemia
- Bone pain (atraumatic fractures
- Pe: punched-out lytic bone lesions
-
Dx: serum protein electrophoresis → to determine clonality: monoclonal immunoglobulin
- urine protein electrophoresis → Ig light chains (Bence Jones Protein)
- RBC rouleaux formation
-
Tx: median survival = 10 years
- complications of infx, renal failure, spinal cord compressionb
- chemo +/- stem cell transplant
- 3 med combo: revlimid (oral) + decadron (oral) + bortezomib (SQ) → disrupts protein production
- complications of infx, renal failure, spinal cord compressionb
56
Q
Waldenstrom Macroglobulinemia
A
Lymphoplasmacytic B-cell lymphoma that produces excess IgM
-
S/sxs: NOT myeloma → no renal, bone disease nor hypercalcemia
- hyperviscosity (caused by large protein: IgM) → bleeding, vision changes, and headache
- nephropathy: IgM protein acts as auto-antibody and causes immune disorder of the nerves
- “OVA”: organomegaly, viscosity, anemia
- anemia due to bone marrow failure
-
Dx: IgM on serum protein electrophoresis
- bone marrow: shows plasmacytoid lymphocytes → look luke plasma cells and lymphocytes >10% lymphoplasmacytic infiltrate
- Tx: plasmapheresis → to eliminate IgM and to tx the severe hyperviscosity
- immunochemotherapy → rituximab (Rituxan)
- Outcome: ****INCURABLE*** but course is indolent
