Hematology Flashcards
Fetal erythropoiesis occurs in: • Yolk sac (?-?) • Liver (?- ?) • Spleen (?- ?) • Bone marrow (?-?)
Fetal erythropoiesis occurs in:
• Yolk sac (3- 8 weeks) - yolk opens from 8-3pm
• Liver (6 weeks- birth) 6iver - living
• Spleen (10- 28 weeks) spleen in between
• Bone marrow (18 weeks to adult) 18 y.o.-adult
ABO classification
AB -?
O -?
AB -Universal recipient of RBCs; universal donor of plasma.
O - Receive any non-O -> hemolytic reaction.
Universal donor of RBCs; universal recipient of plasma.
Neutrophils - Specific granules contain:
Mafia bullies: “Break, Burn, take money and get lap dances.”
leukocyte alkaline phosphatase (LAP) -“Lap dances”
Collagenase - Break
Lysozyme - Burn
Lactoferrin - “take money (Iron)”
Azurophilic granules (lysosomes) contain: Break, break burn and take proteinases - break acid phosphatase - take myeloperoxidase - burn beta-glucuronidase break
Important neutrophil chemotactic agents:
P - platelet-activating factor. L - LTB4 I - IL-8 C - C5a K - kallikrein
Anisocytosis = ?
Poikilocytosis =?
Reticulocyte = ?
Anisocytosis = varying sizes.
Poikilocytosis =varying shapes.
Reticulocyte = immature RBC; reflects erythroidproIiferation.
Thrombocytes dense granules contain:
ADP, Ca2+
Thrombocytes alfa granules contain:
4 F’s:
vWF
fibrinogen
fibronectin
platelet factor 4
Eosinophils - Causes of eosinophilia
PACA-MAN:
Parasites Asthma Churg-Strauss syndrome Adrenal insufficiency (Chronic) Myeloproliferative disorders Allergic processes Neoplasia (eg, Hodgkin lymphoma)
Eosinophils - Produce
N - neurotoxin y M - major basic protein (MBP, a helminthotoxin) P - peroxidase H - histaminase i C - cationic protein
Basophils - Densely basophilic granules contain:
heparin (anticoagulant)
histamine (vasodilator)
Leukotrienes synthesized and released on demand.
Mast cells Activated by
Activated by TEC
T - tissue trauma
E - surface IgE cross-linking by antigen (IgE receptor aggregation)
C - C3a and C5a
Mast cells degranulation ->
release of histamine heparin tryptase eosinophil chemotactic factors.
Plasma cells Found in_________ and
normally do not______.
Plasma cells Found in the bone marrow and
normally do not circulate in peripheral blood.
Coagulation factors that require Ca+ and phospholipid
Activation of 7,9 -> 2
factor IIa activates
XIa, VIIIa, Va, XIIIa
factor XIII purpose
crosslinks fibrin
Anticoagulation pathways:
Antithrombin pathway (heparin-like molecule - enhances ATlll activity) Inhibits IIa, VIIa, IXa. Xa, XIa, Xlla
Protein C pathway - C->S
Inhibits Va, VIIIa
Shortest and Longest factor half lives
Seven - Shortest
Two - Tallest (longest)
Basophilic stippling
Aggregation of ribosomal precipitates.
Do not contain iron.
Heinz bodies
Hb denatures and precipitates
Howell-Jolly bodies
Basophilic nuclear remnants found in RBCs.
Pappenheimer bodies
Siderocytes containing basophilic granules of iron in sideroblastic anemias.
Ringed sideroblasts
Excess iron in mitochondria - Seen inside bone marrow smear with special staining
Microcytic anemia
Hemoglobin affected (TAIL): Defective globin chain: • Thalassemias Defective heme synthesis: •Anemia of chronic disease •lron deficiency •lead poisoning
Normocytic - Nonhemolytic anemia
- Iron deficiency (early)
- Anemia of chronic disease
- Aplastic anemia
- Chronic kidney disease
Normocytic - Hemolytic - Intrinsic anemia
INSIDE the cell you have (enzymes, Hb, membrane)
Membrane defects:
Hereditary spherocytosis
Paroxysmal nocturnal hemoglobinuria
Enzyme deficiencies:
G6PD deficiency
Pyruvate kinase deficiency
Hemoglobinopathies:
Sickle cell anemia
HbC disease
Normocytic - Hemolytic - Extrinsic anemia
- Autoimmune
- Microangiopathic
- Macroangiopathic
- Infections
Macrocytic - Megaloblastic anemia
DNA affected: Defective DNA synthesis •Folate deficiency •Vitamin B12 deficiency •Orotic aciduria
Defective DNA repair:
•fanconi anemia
Macrocytic - Nonmegaloblastic anemia
Diamond-Blackfan anemia
Liver disease
Alcoholism
Iron-deficiency anemia progression:
- dec ferritin. inc TIBC
- dec. serum iron, dec saturation.
- Normocytic anemia
- Microcytic anemia
Iron-deficiency anemia Causes:
Losing - chronic bleeding
Not getting - malnutrition, absorption disorders, GI surgery
Need more - inc demand (eg, pregnancy)
alfa thalassemia types
a -thalassemia minima
a -thalassemia minor
Hemoglobin H disease (HbH);
Hemoglobin Barts disease;
Beta -thalassemia types
beta - thalassemia minor - HbA2 (> 3.5%) on electrophoresis.
beta - thalassemia major
HbS/beta-thalassemia heterozygote
beta-thalassemia major results in
H - hemochromatosis (2° to blood transfusion)
E - Extramedullary hematopoiesis -> hepatosplenomegaly.
P - Parvovirus Bl9-induced aplastic crisis risk.
A - anemia (severe microcytic, hypochromic)
T - target cells
o
M - Marrow expansion: “crew cut” skull x-ray, “chipmunk” facies
A - anisopoikilocytos (increased)
Sideroblastic anemia causes
R - reversible
A - acquired (myelodysplastic syndromes)
G - genetic (eg, X-linked defect in ALA synthase gene),
Reversible Sideroblastic anemia causes
C - copper deficiency
A - alcohol, is the most common
L - lead
B - B6 deficiency
D - drugs: isoniazid, linezolid
o
g
Symptoms of LEAD poisoning:
- Lead Lines on gingivae (Burton lines) and on metaphyses of long bones on x-ray.
- Encephalopathy and Erythrocyte basophilic stippling.
- Abdominal colic and sideroblastic Anemia.
- Drops- wrist and foot drop.
Anemia of chronic disease associations
A - autoimmune diseases (eg, SLE, rheumatoid arthritis).
I - infections
N - neoplastic disorders
K - kidney disease
Aplastic anemia
Fan DRIVe
F - Fanconi anemia
D - drugs (ABC eg, alkylating agents/antimetabolites, benzene, chloramphenicol)
R - Radiation
I - Idiopathic (immune-mediated, primary stem cell defect)
V - Viral agents (EBV, HIV, hepatitis viruses)
e
Fanconi anemia vs. Diamond-Blackfan anemia
Both have Short stature and limb defects.
Diamond-Blackfan anemia - defect in erythroid progenitor cells.
Fanconi anemia - DNA repair defect causing bone marrow failure.
Fanconi anemia also presents with tumors/ leukemia, cafe-au-lait spots
Aplastic anemia vs aplastic crisis
Dec. reticulocyte count, Inc. EPO.
Normal cell morphology, but hypocellular bone marrow with fatty infiltration
Pancytopenia characterized by anemia, leukopenia, and thrombocytopenia.
aplastic crisis - causes anemia only.
Hereditary spherocytosis
defect in proteins interacting with RBC membrane skeleton and plasma membrane (eg, ankyrin, band 3, protein 4.2, spectrin).
Mostly autosomal dominant inheritance.
Hereditary spherocytosis Labs:
Labs:
Dec. mean fluorescence of RBCs in eosin 5-maleimide (EMA) binding test
Inc. fragility in osmotic fragility test.
Normal to dec. MCV with an abundance of RBCs.
Small, round RBCs with less surface area and no central pallor (inc MCHC) -
premature removal by the spleen.
Paroxysmal nocturnal hemoglobinuria Triad:
Triad:
Coombs (-) hemolytic anemia
pancytopenia,
venous thrombosis (eg, Budd Chiari syndrome).
Sickle cell anemia - Vaso-occlusion:
Complications in sickle cell disease:
Vaso-occlusion:
1.dactilits/priapism
2.Autosplenectomy (Howell-Jolly bodies) - risk of infection by encapsulated
organisms (eg, S pneumoniae, Salmonella osteomyelitis)
3.Acute chest syndrome
4.Sickling in renal medulla (dec Po2) -> renal papillary necrosis -> hematuria.
5. avascular necrosis, stroke.
Sickle cell anemia other complications:
Intravascular -> dec. haptoglobin, Target cells
Extravascular -> anemia, jaundice, gallstones.
- Aplastic crisis (transient arrest of erythropoiesis due to parvovirus Bl9).
- Splenic infarct/sequestration crisis.
Sickle cell anemia Dx
Metabisulphite screen -> Sickels with any amount.
Disease - 90% HbS, 8% HbF, 2% HbA2 (no HbA)
Trait - 55% HbA, 43% HbS, 2% HbA2
Hemoglobin electrophoresis
Autoimmune hemolytic anemia - IgM vs. IgG
Warm (lgG)- chronic anemia seen in SLE and CLL and with certain drugs (eg, alfa-methyldopa)
Cold (lgM AND COMPLIMENT)- acute anemia triggered by cold; seen in CLL, Mycoplasma pneumoniae infections, and infectious Mononucleosis.
Many warm and cold All IAs are idiopathic.
Both have CLL.
Direct vs Indirect Coombs test.
Direct Coombs test - anti-lg antibody (Coombs reagent) added to the patient’s RBCs.
RBCs agglutinate if RBCs are coated with lg.
Indirect Coombs test - normal RBCs added to the patient’s SERUM. If serum has anti-RBC surface lg, RBCs agglutinate when Coombs reagent added.
Lead poisoning
AFFECTED ENZYME
ACCUMULATED SUBSTRATE
AFFECTED ENZYME: Ferrochelatase and ALA dehydratase
ACCUMULATED SUBSTRATE: PORTOporphyrin, ALA
Acute intermittent porphyria
AFFECTED ENZYME
ACCUMULATED SUBSTRATE
AFFECTED ENZYME: Porphobilinogen Deaminase
ACCUMULATED SUBSTRATE: PorphoBILInogen, ALA
Autosomal dominant
“call the P.D (Porphobilinogen Deaminase), because of Billi Domino, that like sweet ham”
Porphyria cutanea tarda
AFFECTED ENZYME
ACCUMULATED SUBSTRATE
AFFECTED ENZYME: Uroporphyrinogen decarboxylase
ACCUMULATED SUBSTRATE: Uroporphyrin (teacolored urine)
Autosomal dominant
Uri D Carbi is an alcoholic vampire with Hep C”
Acute intermittent porphyria Symptoms
(5 P's): • Painful abdomen • Port wine-colored urine • Polyneuropathy • Psychological disturbances • Precipitated by drugs (eg, cytochrome P-450 inducers), alcohol, starvation Treatment: hemin and glucose.
“call the P.D (Porphobilinogen Deaminase), because of Billi Domino, that like sweet ham”
Porphyria cutanea tarda Symptoms
Blistering cutaneous photosensitivity and hyperpigmentation
Most common porphyria. Exacerbated with alcohol consumption.
Associated with hepatitis C.
Treatment: phlebotomy, sun avoidance, antimalarials (eg, hydroxychloroquine).
Uri D Carbi is an alcoholic vampire (phlebotomy, sun avoidance, antimalarials) with Hep C”
Heme and ALA synthase activity
Dec heme ->Inc ALA synthase activity
Inc heme -> Dec. ALA synthase activity
Coagulation disorders can be due to…
clotting factor deficiencies or acquired inhibitors.
Coagulation disorders - mixing study
Diagnosed with a mixing study, in which normal plasma is added to the patient’s plasma. Clotting factor deficiencies should correct whereas factor inhibitors will not correct.
Bernard-Soulier
syndrome
Defect
Defect in adhesion
Glanzmann
thrombasthenia
Defect
Defect in aggregation
Immune thrombocytopenia
Destruction of platelets in spleen. Anti-Gpllb/ Illa antibodies
Maybe idiopathic or 2° to autoimmune disorders (eg, SLE)
OR
D - drug reactions
M - malignancy (eg, CLL)
V - viral illness (eg, HIV, HCV)
The atypical form of HUS (aHUS)
Atypical form (aHUS) is caused by complement gene mutations or autoimmune response.
(common form caused by Shiga-like toxin from EHEC- serotype 0157:H7 infection)
Disseminated intravascular coagulation
S - Sepsis (gram-negative)
T - Transfusion
O - Obstetric complications
P - Pancreatitis (acute)
Making - Malignancy
New - Nephrotic syndrome
ThrombuS -Trauma and Snake bites
Antithrombin
deficiency
Inherited deficiency of antithrombin: has no direct effect on the PT, PTT, or thrombin time but diminishes the increase in PTT following heparin administration.
Factor V Leiden
Production of mutant factor V that is resistant to degradation by activated protein C
(guanine ->adenine DNA point mutation - >Arg506Gln mutation near the cleavage site)
“G->A make you Argue with Glen 506 times”
Protein C or S
deficiency
Dec ability to inactivate factors Va and VIIIa
Risk of thrombotic skin necrosis with hemorrhage after administration of warfarin. If this occurs, think protein C deficiency
Prothrombin gene
mutation
Mutation in 3’ untranslated region - inc production of prothrombin - inc plasma levels and venous clots
X3 Clots
Cryoprecipitate Contains
fibrinogen, factor VIII, factor XIII, vWF, and fibronectin
Blood transfusion risks include
T -transfusion reactions
H - hemochromatosis 2° iron overload
I - infection transmission (low)
C - Ca2+ - hypocalcemia (citrate is a Ca2+ chelator)
K - K+ - hyperkalemia (RBCs may lyse in old blood units).
Fresh frozen plasma/prothrombin complex concentrate clinical use:
Cirrhosis, immediate anticoagulation reversal
Hodgkin lymphoma subtypes:
Nodular sclerosis - Most common
Lymphocyte rich - Best prognosis
Mixed cellularity - Eosinophilia, seen in immunocompromised patients
Lymphocyte deleted - seen in immunocompromised patients
Adult T- cell lymphoma
Adults present with cutaneous lesions
Lytic bone lesions, hypercalcemia.
common in Japan, West Africa, and the Caribbean.
Mycosis fungoides/
Sezary syndrome
skin patches and plaques (cutaneous T-cell lymphoma),
characterized by atypical CD4+ cells with “cerebriform” nuclei and intraepidermal neoplastic cell aggregates (Pautrier microabscess).
May progress to Sezary syndrome (T-cell leukemia).
Multiple myeloma
Think CRAB:1,2,2,3
C - HyperCalcemia
R - Renal involvement/ Rouleaux formation
A - Anemia/ Primary amyloidosis (AL)
B - Bone lytic lesions/Back pain/ Bence Jones protein (urine dipstick is negative)
Multiple Myeloma: Monoclonal M protein spike
Myelodysplastic
syndromes
Stem cell disorders involving ineffective hematopoiesis - defects in cell maturation
of nonlymphoid lineages.
Caused by de novo mutations or environmental exposure (eg, radiation, benzene, chemotherapy).
Risk of transformation to AML.
Pseudo-Pelger-Huet anomaly
Neutrophils with bilobed (“duet”) nuclei . Typically seen after chemotherapy.
Acute lymphoblastic
leukemia/lymphoma
Peripheral blood and bone marrow have INC (!) lymphoblasts
T-cell ALL can present as mediastinal mass (presenting as SVC-like syndrome).
TdT+ (a marker of pre-T and pre-B cells), CDI0+ (a marker of pre-B cells).
May spread to CNS and testes.
t( l2;21) - better prognosis.
Chronic lymphocytic
leukemia/small
lymphocytic
lymphoma
Age> 60 years.
CD20+, CD23+, CD5+ B-cell neoplasm.
smudge cells in peripheral blood smear;
autoimmune hemolytic anemia.
Richter transformation- CLL/SLL transformation into an aggressive lymphoma, most commonly diffuse large B-cell lymphoma (DLBCL).
Hairy cell leukemia
Adult males.
Mature B-cell tumor - Cells have filamentous, hair-like projections
Peripheral lymphadenopathy is uncommon.
Causes marrow fibrosis - dry tap on aspiration. Patients usually present with massive splenomegaly and pancytopenia.
Stains TRAP - largely replaced with flow cytometry. Associated with BRAF mutations.
Treatment: cladribine, pentostatin.
Acute myelogenous
leukemia
Median onset of 65 years.
Auer rods; myeloperoxidase(+) cytoplasmic inclusions seen mostly in APL (formerly M3 AML); INC circulating myeloblasts on peripheral smear.
Chronic myelogenous
leukemia
Median age at diagnosis 64 years.
Defined by the Philadelphia chromosome (t[9;22), BCR-ABL) and myeloid stem cell proliferation.
Presents with dysregulated production of mature and maturing granulocytes (eg, neutrophils,
metamyelocytes, myelocytes, basophils) and splenomegaly.
May accelerate and transform to AML or ALL (“ blast crisis”).
Acute myelogenous leukemia
Risk factors:
Risk factors: DRAMa D - Down syndrome. R - radiation A - alkylating chemotherapy M - myeloproliferative disorders, a
APL: t(15;17), responds to all-trans retinoic acid (vitamin A) and arsenic, which induce differentiation of promyelocytes; DIC is a common presentation.
Polycythemia vera Tx
Treatment: phlebotomy, hydroxyurea, ruxolitinib (JAK1/2 inhibitor).
JACK rocks a lot! - ruxolitinib (JAK1/2 inhibitor)
erythromelalgia
Rare but classic symptom of Polycythemia Vera and Essential thrombocytopenia
Severe, burning pain and red-blue coloration) due to episodic blood clots in vessels of the extremities.
Polycythemia vera presents with
Inc in RBC, WBC, Platlets
JAK2 MUTATIONS are present in:
Polycythemia vera (+)
Essential thrombocythemia and Myelofibrosis - 30-50%
t(9;22) (Philadelphia chromosome) ASSOCIATED DISORDER
CML (BCR-ABL hybrid)
ALL (less common, poor prognostic factor)
t(11;14) ASSOCIATED DISORDER
Mantle cell lymphoma (cyclin D1 activation)
t(11;18) ASSOCIATED DISORDER
Marginal zone lymphoma
t(14;18) ASSOCIATED DISORDER
Follicular lymphoma (BCL-2 activation)
t(8; 14) ASSOCIATED DISORDER
Burkitt (Burk-8) lymphoma (c-myc activation)
t(15;17) ASSOCIATED DISORDER
APL (M3 type of AML; responds to all-trans retinoic acid)
Langerhans cell histiocytosis
proliferative disorders of Langerhans cells
Presents in a child as lytic bone lesions and skin rash or as recurrent otitis media with a mass involving the mastoid bone.
Cells express S-100 (mesodermal origin) and CD1a. Birbeck granules (“tennis rackets”)
The lg heavy chain genes is on
on chromosome 14 are constitutively expressed. When other genes (eg, c-myc and BCL-2) are trans located next to this heavy chain gene region, they are overexpressed.
Hemophagocytic lymphohistiocytosis
Systemic overactivation of macrophages and cytotoxic T cells - fever, pancytopenia, hepatosplenomegaly.
Bone marrow biopsy shows macrophages phagocytosing marrow elements .
INC (!) serum ferritin levels.
Hemophagocytic lymphohistiocytosis causes
Can be inherited or 2° to strong immunologic activation (eg, after EBV infection, malignancy)
Tumor lysis syndrome - Electrolytes affected
Electrolytes affected: PUKe Calcium P - inc Po4- U - inc Uric acid K - inc K+ e
Calcium - dec Ca2+
Tumor lysis syndrome results in
M - Muscle weakness (K+) A - Arrhythmias, ECG changes (K+, Ca2+) S - Seizures (Ca2+) T - tetany (Ca2+) S (x2) - Stones (uric acid/ Calcium-phosphate)
Procarbazine
Cell cycle phase- nonspecific alkylating agent, mechanism not yet defined.
Hodgkin lymphoma, brain tumors.
Bone marrow suppression, pulmonary toxicity, leukemia, disulfiram-like reaction.
Cetuximab, panitumumab
Monoclonal antibodies against EGFR.
Stage IV colorectal cancer (wild-type KRAS), head and neck cancer.
Rash, elevated LFTs, diarrhea.
Earl has a C-TUX and panties for colon an head and neck
Dabrafenib, vemurafenib
BRAF inhibition. Often co-administered with MEK inhibitors (eg, trametinib).
VEmuRAF-enib is for V600Emutated
Devra Vemura wants to make it to the TRAM
