Hematology - 5% Flashcards
Acute Lymphocytic Leukemia (ALL)
MC in children 3-7yo and MCC childhood cancer
highly responsive to chemotherapy
Sxs
- lymphadenopathy
- Bone pain
- bleeding from nose and gums, diffuse ecchymosis
Dx:
- bone marrow > 20% blasts
Tx
- chemotx - Imatinib (+philly) or methotrexate (CNS dz)
- relapse = transplant
Acute Myeloid Leukemia (AML)
MC Adults >50yos
RF toxin exposure - benzene, radiation (organic chemist)
Sxs:
- gingival hyperplasia, bone pain, pallor, bleeding
Dx:
- bone marrow with Auer Rods
- >20% blasts + Pancytopenia
Tx
- Induction chemo (short) => transplant, better prognosis if <60yo
- Tumor lysis syndrome - 48-72 hrs after tx, incr in uric, K, phostphate and decr in Ca –> treat with allopurinol and IV fluids
Anemia of Chronic Dz
Eti - older patients w/ inflammation, cancer, RF, liver
MCC - chronic renal failure - impaired EPO production
Dx:
- Normal or microcytic MCV
- low TIBC and Fe
- High Ferritin stores (nl to 3x)
- low Serum EPO
Tx
- IV EPO
- Tx underlying dz
Antiphospholipid Antibody Syndrome
Hypercoaguable State
Autoimmune, often a/w SLE
AutoABs attack platelet membranes, activates endothelial cells + plts - breaks down platelets
Sxs
- thromboses and recurrent spont abortions
Dx:
- lupus anticoag
- prolonged Dilute Russell viper Venom Time (DRVVT)
- Prolonged PTT
- anti-B2 glycoprotein
- anticardiolipin
Tx
- high dose IV hep w/ thrombic event, PO Anticoag indef
Antithrombin III Deficiency
Hypercoaguable State
Recurrent venous thrombosis and PE, Repetitive IU fetal death
AT III - is a natural anticoag; inhibits thrombin (IIa), and Xa, and other proteases
- a/w VTE - 1st ep during 20-30yo
Tx
- asymptomatic - anticoag before sx
- w/ acute thrombotic event = high dose IV Hep, PO Anticaog indefinitely
Aplastic Anemia
All three cell lines decreased - LOW WBC, RBC, Plts Pancytopenia
eti - chemicals, drugs, radiation (ACE-I, gold, sulfa, phenytoin, chemo, XRT)
Sxs:
- severe pallor, weakness
- petechiae
- ecchymosis
- mucosal bleeding
- severe infx
Dx:
- pancytopenia
- BM bx - gold
Tx - stop causative agent, RBC transfusion, BMT
Chronic Lymphocytic Leukemia (CLL)
MCC leukemia in adults; esp B cell type
Middle age pt - peak at 50yo
asymptomatic - incidental finding
Sxs:
- recurrent infections*** - pna, renal infx,
- splenomegaly, lympadenopathy
Dx:
- Smudge cells - lymphocytosis - on perip smear, mature lymphocytes
Tx:
- chemo or allogenic stem cells - cure
- younger = more aggressive in patients
- Fludarabine - IV 5d/wk x4-6 mo = not cure
Chronic Myelogenous Leukemia (CML)
>50yo, AA descent has poorer prognosis
Sxs:
- Usu asymptomatic until blast crisis (acute leukemia)
- fever, nt swts, anorexia (gradually)
- Hyperuricemic
Dx:
- Incr LDH, uric acid
- WBC > 150,000 in the setting of + Philadelphia chromosome
- left myeloid shift on perip smear
Tx
- Imatinib/Gleevac - Tyrosine kinase inhibitor = not cure
- BM or stem cell transplant - better prognosis if younger
Disseminated Intravascular Coagulation
Thrombocytopenia
Abnormal activation of coagulation sequence
- microthrombi throughout microcirculation
- consumption of plts, fibrin, coag factors
- Bleeding and thrombosis occurs simultaneously
- Burn, trauma, OBGYN patients
Dx:
- ↓ Platelets,
- ↑ bleeding time, ↑ PT, ↑ PTT
- D-Dimer (fibrin degradation product)
Tx:
- Supportive
- cryoprecipitate, FFP
- plt transfusion if < 30,000
- Heparin
- tx cause
Factor V Leiden
Hypercoaguable State
MCC hypercoaguable state, Autosomal dominant
Mutated factor V resistant to breakdown by Protein C - amplifies production of thrombin causing more clot formation
- increased risk of DVT and PE in young pts
Dx
- activated protein C resistance assay - if +, confirm with DNA testing for factor V Leiden
- normal PT/PTT
Tx
- LMWH bridge to warfarin
- long term antithrombic tx not rec’d
Hemolytic Anemia - G6PD
hemolytic anemia - premature breakdown of RBCs,
AA and Mediterranean; Autosomal Recessives
Oxidant sensitivity - after infection or medication causing oxidative stress
- Fava beans
- sulfonamides
- antimalarials
- analgesics - phenacetine - acetylsalicyclic acid
Dx - Bite cells, Heinz body** on smear
Tx - avoid drugs,
acute - blood transfusion
Hemolytic Uremic Syndrome (HUS)
Thrombocytopenia
Low platelets + anemia + renal failure (a/w E.coli O157:H7 and diarrheal illness in a child
post infection - E coli or shigella
Children
Severe kidney problems
Hemophilias A and B
Clotting Factors Disorder
hereditary bleeding disorder - two forms
- Hemophilia A - Factor VIII/8 Deficiency - More common
- Hemophilia B - Factor IX/9 Deficiency (Christmas Disease)
Sxs:
- Spontaneous Hemarthrosis - bleeding into joint space
- Bruising and bleeding easily
Dx:
- ↑ aPTT
- normal PT and plts
- Low Factor 8 or 9 on assay
Tx - replace factor 8 or 9
Hodgkin Lymphoma
Bimodal - peaks in 20s then 50s ; a/w EBV
Sxs:
- B constitutional sxs - cyclical fever, wt loss, chills, drenching, nt swts up/down 2 wks period
- painless enlarged posterior cervical chain (neck)
- MC supraclavicular LNs (Virchow’s Nodes)
Dx
- excisional bx - Reed Sternberg Cells (owl eyes)
Tx
- 5 year prog - excellent
- Combo chemo
- Adriamycin
- Bleomycin
- Vinblastine
- Dacarbazine
Hypercoaguable State:
Eti
Platelets - too many or overactive
- TTP
- HIT
- HUS
- HELLP
Vascular injury - plaques, trauma, or burns
Clotting factors - anti clotting factors
- Protein C
- Protein S
- Antithrombin III deficient
Stasis and Surgery
Idiopathic Thrombocytopenic Purpura
Thrombocytopenia
Autoimmune rx to platelets usu after viral illness (1-2 wks)
Chronic in adults, self limited in children
A/w HIV, HCV, SLE, CLL
Sxs
- well appearing, mucosa, skin purpura
- no hemarthrosis
Dx of exclusion
- +Direct Coombs Test
- isolated thrombocytopenia (low plts) - normal CBC and peripheral blood smear
- normal coag studies
Tx
- Self limited - no tx
- IVIG = platelets < 50,000 w. C/I to CS, refractor to CS tx, bleeding or will be bleeding
- Splenectomy - 2nd line tx for pts w/ refractory ITP
Iron Deficiency Anemia
MC anemia in US, MCC menstrual bleeding, GI bleeding
Sxs:
- fatigue/weakness, Splenomegaly
- glossitis, angular chelitis, pica
- koilonychia - spoon nails
Dx:
- Low MCV < 80, low MCH (hypochromic)
- High TIBC
-
low ferritin (low Fe stores)** < 15ng/mL
- Females - Hgb < 12/ Hct < 37%
- Males - <13.5 / < 39%
- target cells
Tx
- PO Fe TID 325mg - empty stomach, Vit C for absorption
- 6 wks to correct
- 6 mos to restore Fe stores
- IV Fe infusion - need a skin test first
Folate Deficiency
Cofactor in DNA synthesis = contributes to neural tube bifida
eti - etoh or malnourished, or pregnant women
Sxs
- same as B12 but no neuropathy sxs
Dx:
- low folate
- incr MCV - looks like B12 but no neuro sxs
- Hypersegmented PMNs
- elevated homocysteine; normal MMA levels
- Howell-Jolly bodies**
Tx - PO Folic acid 1-5mg/d
green veggies
Myelodysplastic Syndrome
Older pop - previous chemo/XRT
Sxs
- transition to AML leukemia is common
*
Non-Hodgkin’s Lymphoma
Diffuse large B lymphocytes, patients > 50yo
increased IMC risk
Sxs
-
painless peripheral lympadenopathy [more disseminated] (axillary, abd, pelvic, inguinal, femora)
- common spread to stomach
- B const sxs not common
- Non-contiguous extranodal spread - GI and skin most common
Dx
- Excisional bx
- Staging with CT
Tx
- Variable cure rates with chemo
- R-CHOP
- Rituximab
- Cyclophosphamide
- Hydroxydaunomycin
- Oncovine
- Prednisone
Polycythemia Vera (primary)
Primary - Inherited & malignancy of BM - increased production of RBCs (can affect WBC and plts); M>60yo
Sxs
- Pruritis after hot baths
- Swelling, blurred vision, ringing in ear, headache
- rubor on hands and feet, burning pain
Dx:
- 4 H’s
- Hypervolemia - incr RBC, Hct > 30
- Histaminemia - incr histamine d/t release frm mast cells
- Hyperviscosity - incr Hct = incr viscosity
- Hyperuricemia
- Serum EPO lvls reduced
- ele Vit B12 levels
- Positive JAK2** tyrosine kinase mutation
- BM bx
Tx
- repeated phlebotomy until Hct < 42%
- Hydroxyurea, ASA
Secondary Polycythemia - acquired dz
- 2/2 d/t low O2 - (OSA, COPD, CO levels (toll booth)
- compensatory release of EPO from kidneys - abs of splenomegaly
- tx - with O2 treatment
Protein C and S Deficiency
Hypercoaguable State
Protein C - cleaves/inhibits factor V and VIII (coag factors)*
Protein S - inhibits Factor Va and VIIIa, cofactor of Protein C –> reduces thrombin generation
Vitamin K dependent anticoag liver protein - stimulates fibrinolysis and clot lysis (inactivates factor V and VIII)
- recurrent DVT and PE risk
Dx
- Protein C/S functional assay
- decreased C and S activity levels
Tx
- Heparin and PO anticoag for life
- Protein C deficiency - risk of skin necrosis while on warfarin
Sickle Cell Anemia
AA, fam hx, B-globin mutation - hemolytic anemia; Autosomal Recessive
Heterozygous - sickle cell anemia, homozygous - sick cell trait
sxs:
- Priapism, bone pain, stroke, hypoxia, deH2O
- Acute chest syndrome
- Jaundice, pigmented gallstones, splenomegaly
- Delayed physical development
Dx:
- Hemoglobin electrophoresis - Hemoglobin S
- Hct 15-30%
- Sickle RBCs, Howell-Jolly bodies, target cells
- Regular slit exam for retinopathy
Tx
- Hydroxyurea
- vigorous H2O
- Morphine - RBC tranfusion
- Cure - stem/bone marrow transplant
Hemolytic Anemia - Thalassemia
Genetic - microcytic; Lowest MCV; hypochromic
only 2 B globin genes instead of 4 - change stability of Hgb = hemolysis
Beta Thalassemia Mino
- Most severe, Mediterrean, Italian, greek AA, - lifelong microcytic anemia + folic acid supp FTT
- HgB A2 and F
Beta Thalassemia Major
- Cooleys anemia - facial malformation, cog delays, bone dz/osteopenia
- BM transplant, iron chelation to liv e>30 yo
Alpha Thalassemia
- Silent > Mild > Major
- Chinese and SE Asians - blood transfusion, folic acid supp
- Major - hemoglobin Bart’s (Hydrops fetalis)
Dx - periph smear - Target cells and basophilic stippling
Tx
- acute - blood transfusion
- Asymp - PO Fe repletion
- Poor prognosis - most die In 20-30s from Infx, liver or heart failure
Thrombotic Thrombocytopenic Purpura (TTP)
Thrombocytopenia
low Platelets + anemia + schistocytes on smear; 20-50 yo
Hemolytic Uremic Syndrome (HUS) if childe w/ Low platelets + anemia + renal failure (diarrhea)
Eti - after drugs - quinidine, cyclosporine, pregnancy, estrogen, plavix
inhibition of ADAMTS13
Sxs:
- Purpura + FAT RN
- Fever
- Anemia
- Thrombocytopenia
- Renal failure
- Neurological symptoms
Dx:
- CBC - ↓ Platelets
- Schistocytes (RBC fragments)***
- neg Coombs test
Tx
- Emergent plasmapheresis** until plts are back to normal
- Corticosteroids
Vitamin B12 deficiency
Cobalamine - autoimmune destruction of gastric parietal cells => atrophic gastritis => no Intrinsic Factor (IF) = no Vit B12 absorption
Pernicious Anemia - autoimmune, a/w gastric cancer & IF antibodies
2/2 causes - gastric bypass sx, celiac dz
Sxs:
- Weakness
- gums bleeding
- sore tongue - Glossitis
- peripheral neuropathy/ paresthesias*
- Depression, Dementia
- Late - AMS, neurological deficients = irreversible
Dx:
- MCV > 100, low B12, high
- Hypersegmented neutrophils
- MMA and homocysteine elevated (not in folate)
- positive Schillings test*** for pernicious anemia
- IF antibodies = pernicious anemia
Tx
- IM B12 1000mg q 5 wks lifelong
- years to replete stores
Von Willebrand’s Disease (vWD)
Clotting Factors Disorder
MC genetic bleeding disorder, Autosomal Dom
plts can’t adhere to vessel wall = bleeding doesn’t stop as quickly
Sxs/ Dx
- Hx of bleeding post cut or incr menstrual bleeding, no hemathrosis
- petechia, small amt of superficial bleeding
- ↑ PTT, prolonged bleeding time (extrinsic)
- low vW Factor
- low Factor 8
Tx:
- Desmopressin/DDAVP
- avoid ASA or NSAIDs
Thrombocytosis
Sustained platelet production;
Uncommon (50-60), Platelet count >500k
Sxs
- PE and DVT** = main COD
- Headache as 1st presenting sx
- Splenomegaly
- Burning of palms and soles => ASA relieves
Tx
- Hydroxyurea - suppresses plt count
Multiple Myeloma
>65yo AA Men; Plasma cell proliferate
Sxs
- osteolytic bone lesions
- bone pain, hyperCa, renal failure
- Cord compression, bone fractures
- new ARF + compression fractures **
Dx
- Bence jones proteins - clonal spike on plasma electrophoresis
- NO FEVER, incr alk phos, splenomegaly
Tx
- Stem cell transplant
- Chemo - thalidomide
Sideroblastic Anemia
Lead exposure in kids
Sxs
- abd pain, diffic concentrating
- low IQ, gait ataxia
- episodic paralytic ileus***
Dx
- Basophilic stippling*** on smear
- serum Fe nl
- Bone marrow - ringed sideroblasts on prussian blue stain
Tx
- chelation therapy
- remove
Hereditary Spherocytosis
Mild hemolytic anemia - Autosomal Dom
Defect in RBC surface membrane
Sxs
- abn, oval shaped hgb- dense and lack central pallor
- Hemolysis in body is in state of stress
- Malaise, jaundice, high # of gall stones - cholecystectomy
Dx - periph smear osmotic fragility test
high RDW
Tx - splenectomy, folate replacement
Hemochromatosis
Autosomal recessive = excess Fe absorption => accumulation of Fe in organs => fibrosis d/t hydroxyl free radicals
Sxs
- Liver - main organ - Cirrhosis & HCC x 200x
- Pancreas - DM (fe deposits in pancreas)
- Heart - CMO, CHF, arrhythmias
- Joints - arthritis - 2nd/3rd metacarpo joints, hips, knees
- Skin - bronzeline
Dx
- ↑ Elevated ferritin (may be >1,000 ng/mL)
- ↑ Elevated fasting serum transferrin
- ↓ Decreased total iron binding capacity
- Prussian blue stain - brown spots inside hepatocytes
Tx - Phlebotomy or deferoxamine
