Hematology and Oncology Flashcards
1
Q
Anisocytosis
A
varying sizes
2
Q
Poikilocytosis
A
varying shapes
3
Q
Polychromasia
A
bluish color on wright giemsa stain of reticulocytes represent residual ribosomal RNA
4
Q
Erythrocytes life span? energy source? membrane contains what transporter?
A
120 days
Glucose
Cl-/HCO3 antiporter to expcort HCO3 and transport CO2
5
Q
Thrombocyte life span? derived from? contains? stored?
A
8-10 days
Megakaryocytes (proliferation due to thrombopoietin)
Contains dense granules (ADP and Ca) and alpha granules (vWF,fibrinogen,fibronectin)
Approximately 1/3 of platelet pool is stored in the spleen
6
Q
Thrombocytopenia
A
decreased platelet function results in petechiae
7
Q
receptor for vWF? fibrinogen?
A
vWF is GpIIb
fibrinogen is GPIIb/IIIa
8
Q
Leukocytes
A
two types :
1) granulocytes (neutrophils (60%), eosinophils (3%), basophils (1%), mast cells)
2) mononuclear cells ( monocytes (6%), lymphocytes (30%))
9
Q
Neutrophils
A
acute inflammatory response cells
increases in bacterial infections
phagocytic
multilobed (hypersegmented have 6+ lobes) and are seen in B12/B9(folate) deficiency
10
Q
Neutrophils contain
A
Granules: leukocyte alkaline phosphatase (LAP) collagenase lysozyme lactoferrin
Azurophilic granules(lysosomes): proteinases acid phosphatase myeloperoxidase beta-glucuronidase
11
Q
Increased band cells (immature neutrophils)
A
reflect states of increased myeloid proliferation (bacterial infections, CML)
12
Q
Important neutrophil chemotactic agents
A
C5a IL8 LTB4 Kallikrein platelet activating factor
13
Q
Monocytes
A
macrophage (tissues) but monocytes (blood)
have a large kidney shaped nucleus and frosted glass cytoplasm
14
Q
Macrophages
A
phagocytose bacteria, cellular debris, and senescent RBCs
activated by gamma interferon and can function as APC via MHC II
have different name in different tissues
15
Q
Septic shock is due to what binding
A
Lipid A from bacterial LPS binds CD14 on macrophages to initiate septic shock
16
Q
Eosinophils defend against? produce? lobed nucleus?
A
- Defend against helminthic infections
- Bilobate nucleus
- Produce histaminase, major basic protein (MBP, a helminthotoxin), eosinophil peroxidase, eosinophil cationic protein, and eosinophil derived neurotoxin
17
Q
Causes of eosinophilia
A
parasites Asthma Churg Strauss syndrome (allergic granulomatosis) Chronic adrenal insufficiency Myeloproliferative disorders Allergic processes Neoplasia
18
Q
Basophils
A
Mediate allergic reactions
basophilic granules that contain heparin (anticoagulant) and histamine (vasodilator)
Leukotrienes synthesized and released on demand
basic stains
19
Q
Basophilia
A
uncommon
sign of myeloproliferative disease particularly CML
20
Q
Mast cells
A
mediate allergic reactions in local tissues (type 1 hypersensitivity)
basophillic granules
21
Q
Activation of mast cells
A
bind Fc portion of IgE to membrane
activated by tissue trauma, c3a and c5a, surface IgE crosslinking by antigen (IgE receptor aggregation) –> degranulation –> release of histamine, heparin, tryptase, and eosinophil chemotactic factors
22
Q
Dendritic cells
A
phagocytic antigen presenting cells
link innate and adaptive immune systems
express MHC class II and Fc receptors on surface
called langerhans cells in the skin
23
Q
Lymphocytes
A
refer to B cells, T cells, and NK cells
B and T cells mediate adaptive immunity
NK cells are part of the innate immune response
24
Q
B cells immune response and development
A
Humoral immune response
from stem cells in bone marrow and matures in marrow
migrate to peripheral lymphoid tissue (lymph nodes, white pulp of spleen, unencapsulated lymphoid tissue)
when antigen is encountered, B cells differentiate into plasma cells (which produce antibodies) and memory cells
APC functioning too
25
T cells immune response and development
Mediate cellular immune response
From stem cells in the bone marrow but mature in the thymus
Differentiate into cytotoxic T cells (express CD 8, recognize MHC I) , helpher T cells (express CD 4, recognize MHC II), and regulatory T cells
26
Costimulatory signal necessary for T cell activation
CD28
27
Most circulatory lymphocytes are
T cells (80%)
28
Plasma cells
Produce large amounts of antibody specific to a particular antigen
"clock face" chromatin distribution and eccentric nucleus
abundant RER and well developed Golgi apparatus
found in bone marrow and normally do not circulate in peripheral blood
29
multiple myeloma
plasma cell cancer that accumulates in bones and weakens them
30
Fetal erythropoiesis occurs in? time frame?
yolk sac for 3-8 wks
Liver for 6 weeks to birth
Spleen 10-28 weeks
Bone marrow 18 weeks to adult
31
Embryonic globins?
zeta (ζ) and epsilon (ɛ)
32
Fetal hemoglobin
HbF=α2γ2
33
Adult hemoglobin
HbA1=α2β2
| HbA2 (small amounts)=α2δ2
34
fetal hemoglobin --> adult
Alpha always
Gamma goes
Becomes beta
HbF=α2γ2
HbA1=α2β2
35
Fetal hemoglobin
HbF has higher affinity for O2 due to less avid binding of 2,3-BPG, allowing HbF to extract O2 from maternal hemoglobin (HbA1 and HbA2) across the placenta
36
Blood groups: Group A
type A has antigen A on surface
antibodies in plasma are Anti-B (IgM)
37
Blood groups: Group B
type B has antigen B on surface
anitbodies in plasma are Anti-A (IgM)
38
Blood groups: group AB
type AB has antigens to A and B on surface
no antibodies
universal recipient of RBC
unviersal donor of plasma
39
Blood groups: group O
Type O has no antigens on surface
Antibodies against A and B (IgM and IgG) in plasma
Universal donor of RBCs
Universal recipient of plasma
40
Rh classification: Rh + RBC
antigen on surface is Rh(D)
No antibodies in plasma
can receive Rh+ or Rh- blood
41
Rh classification: Rh - RBC
no antigen on surface
| Anti-D (IgG) antibodies in plasma
42
Rh hemolytic disease of the newborn (erythroblastosis fetalis)
Mom Rh- but fetus Rh+
after first pregnancy mother will form maternal anti-D IgG
Subsequent pregnancy have anti-D igG crosses the placenta causing HDN in fetus (jaundice, kernicterus, hydrops fetalis)
Prevent: treat mother with anti-D Ig during and after each pregnancy to prevent anti-D IgG formation
43
ABO hemolytic disease of newborn (erythroblastosis fetalis)
Type O mothers with type A or B fetus
preexisting maternal anti-A or anti-B IgG antibodies cross placenta --> HDN in the fetus
44
Hemoglobin electrophoresis (movement from negative cathode to positive anode)
HbA (most negative due to glutamic acid) > HbF > HbS>HbC
missence mutations in HbS and HbC replace glutamic acid (-) with valine (neutral) and lysine (+) --> impacts net protein charge
45
Plasmin pathway
Plasminogen becomes plasmin via tPA
plasmin degrades many blood plasma proteins, including fibrin clots. The degradation of fibrin is termed fibrinolysis (cleavage of the fibrin mesh and destruction of coagulation factors)
46
Kinin cascade
HMWK becomes bradykinin via kallikrein
47
What does bradykinin do
increase vasodilation, permeability, pain
48
Extrinsic pathway
external trauma that causes blood to escape from the vascular system
favtor VII --> VIIa
49
Intrinsic pathway
activated by trauma inside the vascular system, and is activated by platelets, exposed endothelium, chemicals, or collagen.
This pathway is slower than the extrinsic pathway, but more important. It involves factors XII, XI, IX, VIII.
XII --> XIIa which is then used to make XI-->XIa etc
50
Combined pathway
Both pathways meet and finish the pathway of clot production in what is known as the common pathway. The common pathway involves factors I, II, V, and X.
note: II is prothrombin which becomes thrombin or IIa
I is fibrinogen which becomes Ia fibrin monomers
51
Vitamin Ks relationship to the coagulation cascade
oxidized vitamin K becomes reduced vitamin K via epoxide reductase
reduced vitamin k acts as a cofactor that activates factors II, VII, IX,X,C,S
52
Where does warfarin act and how do you reverse its effects
warfarin inhibits epoxide reductase and prevents oxidized vitamin k from becoming reduced vitamin k
You can reverse its effects with vitamin k admin, but FFP and PCC are immediate reversal
53
Neonates and vitamin k
neonates dont have enteric bacteria which produce vitamin k
early administration of vitamin k overcomes neonatal deficiency/coagulopathy
54
Which factor has the longest half life? which has the shortest?
factor VII is shortest
| Factor II is longest
55
vWF carriers/protescts factor ____
factor VIII of intrinsic pathway
they together enter the combined pathway where they join factor VII of extrinsic to form Xa of the combined pathway
56
Anticoagulation with protein C
protein C is activated with thrombin-thrombomodulin complex (endothelial cells)
it then acts with protein S to cleave and inactivate Va (combined pathway) and VIIIa (intrinsic pathway)
57
Antithrombin
inhibits activated forms of factors II,VII,IX,X,XI,XII but the principal targets are thrombin (IIa) and factor Xa
activity is enhanced by heparin
58
Factor V leiden mutation
produces a factor V resistant to inhibition by activated protein C
59
Primary hemostasis steps
1) Injury - endothelial damage causes transient vasoconstriction via neural stimulation reflex and endothelin released from damage cell
2) Exposure- vWF (from weibel palade bodies of endothelial cells and alpha granules of platelets) binds exposed collagen
3) Adhesion - platelets bind vWF via GpIb and undergo conformaitional change. They release ADP(helps platelets adhere) and Ca, TxA2.
4) ADP binds P2Y12 receptor and induces GpIIb/IIIa expression on platelet surface
5) aggregation- fibrinogen binds GpIIb/IIIa receptors and links platelets
6) temporary plug --> secondary coagulation cascade
60
where does vWF get released from
vWF (from weibel palade bodies and alpha granules of platelets)
61
Pro aggregation factors?
TXA2
Decreased blood flow
Increased platelet aggregation
62
Anti-aggregation factors?
PGI2 and NO released by endothelial cells
Increased blood flow
Decreased platelet aggregation
63
Thrombogenesis
the formation of insoluble fibrin mesh
64
Aspirin irreversibly binds ____ thereby inhibiting ____ synthesis
cyclooxygenase
| TXA2 synthesis from arachidonic acid
65
Pt presents with low iron, high TIBC, low ferritin, high free erythrocyte protoporphyrin, increased RDW
Iron deficiency anemia
microcytosis and hypochromasia (increased central pallor)
symptoms: conjunctival pallor and spoon nails (koilonychia), glossitis, cheilosis, plummer vinson syndrome (triad of iron deficiency anemia, esophageal webs, and dysphagia)
66
α-thalassemia
α globin gene deletions which causes decreased α globin synthesis
can be cis (same crhomosome) or trans. But Cis is worse
67
Types of α thalassemia
α thalassemia minima (lose only 1) - no anemia, silent carrier
α thalassemia minor (lose 2) - mild microcytic, hypochromic anemia
Hemoglobin H disease (HbH, lose 3) - excess β forms β4. Moderate to severe microcytic hypochromic anemia
Hemoglobin Barts disease (Hb Barts, lose 4) - excess γ forms γ4 which is hydrops fetalis
68
β thalassemia
Point mutations in splice sites and promoter sequences causes a decrease in β-globin synthesis
69
β thalassemia types
β thalassemia minor (heterozygote)- β chain is underproduced. asymptomatic. Increase in HbA2 on electrophoresis
β thalassemia major (homozygous) - β chain is absent causing severe microcytic hypochromic anemia with target cells and increase anisopoikilocytosis requiring blood transfusion. Results in increased HbF and HbA2
HbS/ β thalassemia heterozygote: mild to moderate sickle cell disease depending on amount of β globin production
70
Patient presents with a crew cut appearance on skull xray due to marrow expansion. He also has what is described as a "chipmunk facies"
β thalassemia major
pts also has extramedullary hematopoiesis --> hepatosplenomegaly
Also at increased risk of aplastic crisis due to parvovirus B19
HbF is protective in the infant and disease becomes symptomatic only after 6 months when fetal hemoglobin declines
71
Lead poisoning
lead inhibits ferrochelatase and ALA dehydratase which decreases heme synthesis and increases RBC protoporphyrin. Also inhibits rRNA degradation which results in basophilic stippling in RBCs
72
Symptoms of lead poisoning
L ead lines on gingivae (burton lines) and on metaphyses of long bones on xray
E ncephalopathy and erythrocyte basophilic stippling
A bdominal colic and sideroblastic anemia
D rops-wrist and foot drop
73
Sideroblastic anemia
form of anemia in which the bone marrow produces ringed sideroblasts rather than healthy red blood cells (erythrocytes).
genetic, acquired, or reversible forms
most common reversible form is due to alcohol
74
Pt presents with the following labs: increased iron, low TIBC, increased ferritin. There are ringed sideroblasts with iron-laden prussian blue stained mitochondria seen in bone marrow. Peripheral blood smear has basophilic stippling of RBCs
Sideroblastic anemia
tx: pyridoxine (B6, cofactor for ALA synthase)
75
Pt presents with RBC macrocytosis, hypersegmented neutrophils, glossitis
Megaloblastic anemia
impaired DNA synthesis causes maturation of nucleus of precursor cells in bone marrow delayed relative to maturation of cytoplasm
76
Pt presents with increased homocysteine, normal methylmalonic acid. No neurologic symptoms
Folate deficiency (i.e. due to alcohol, pregnancy, etc)
77
Pt presents with increased homocysteine and increased methylmalonic acid. With neurologic symptoms
Vitamin B12 (cobalamin) deficiency
dx with the schilling test (dietary insufficiency vs malabsorption)
anemia due to insufficiency may take several years to develop due to livers ability to store B12 (as opposed to folate deficiency)
78
Child presents with failure to thrive, developmental delay, and megaloblastic anemia refractory to folare and B12. Pt has orotic acid in urine. No hyperammonemia. What enzyme is defective?
Orotic aciduria due to an inability to convert orotic acid to UMP (de novo pyrimidine synthesis pathway) because of a defect in UMP synthase.
tx with uridine monophosphate or uridine triacetate to bypass mutated enzyme
79
Nonmegaloblastic anemia
macrocytic anemia in which DNA synthesis is unimpaired. RBC macrocytosis without hypersegmented neutrophils
caused by alcoholism and liver disease
80
Pt presents with increased HbF, short stature, craniofacial abnormalities, and UE malformations (triphalangeal thumbs) in up to 50% of cases
Diamond-blackfan anemia - form of nonmegaloblastic anemia
Rapid onset anemia within first year of life due to instrinsic defect in erythroid progenitor cells
81
Pt presents with low haptoglobin, increased schistocytes on blood smear, hemoglobinuria, hemosiderinuria, and urobilinogen in urine. There is also an increase in unconjugated bilirubin
Intravascular hemolysis (normocytic, normochromic anemia)
notable causes are mechanical hemolysis, paroxysmal nocturnal hemoglobinuria, microangiopathic hemolytic anemias
82
Pt presents with macrophages in spleen clearing RBCs. Spherocytes in peripheral smear. No hemoglobinuria/hemosiderinuria. CAn also present with urobilinogen in urine
extravascular hemolysis (normocytic, normochromic anemia)
83
Pt has SLE and now has low iron, low TIBC, increased ferritin. Pt was initially normocytic but is not microcytic anemia.
Anemia of chronic disease ( nonhemolytic, normocytic anemia)
Inflammation causes an increase in hepcidin release from the liver. Hepcidin binds ferroportin on intestinal mucosal cells and macrophages thus inhibiting iron transport
decrease release of iron from macrophages and decrease iron absorption from gut
84
Pt presents with fatigue, malaise, pallor, purpura, mucosal bleeding, petechiae, infection, a drop in reticulocyte count, and increase in EPO (erythropoietin stimulates RBC production)
Aplastic anemia- Body stops producing enough new blood cells due to failure or destruction of myeloid stem cells
Pancytopenia characterized by anemia, leukopenia, and thrombcytopenia
Decrease in reticulocyte count with an increase in EPO
85
Extravascular hemolysis due to defect in proteins interacting with RBC membrane skeleton and plasma membrane. Resulting in small round RBCs with less surface area and no central pallor --> premature removal by spleen causes an increase in MCHC
Hereditary spherocytosis
splenomegaly, aplastic crisis (parvovirus B19 infection)
labs find increased fragility in osmotic fragility test which causes normal to decreased MCV with abundance of cells.
tx with splenectomy
86
G6PD deficiency causes ______ hemolysis and reduced ____ which increases RBC susceptiility to _______ after eating fava beans. Pt presents with back pain and hemoglobinuria after eating fava beans. Blood smear shows RBCs with _____ bodied and _____ cells.
```
extravascular and intravascular hemolysis
glutathione
oxidant stress
Heinz bodies (Hb precipitation)
Bite cells
```
87
This deficiency causes hemolytic anemia in newborns. It causes a drop in ATP which results in the formation of rigid RBC --> _______ hemolysis. There is an increase level of _______ and thus a drop in hemoglobin affinity for O2
Pyruvate kinase deficiency
88
Paroxysmal nocturnal hemoglobinuria
increase complement mediated intravascular RBC lysis
associated with aplastic anemia
triad of Coombs negative hemolytic anemia, pancytopenia, venous thrombosis.
Pts present with red or pink urine due to hemoglobinuria
CD55/59 - RBCs
tx: eculizumab
89
Mutation in paroxysmal nocturnal hemoglobinuria
acquired mutation in PIGA gene causing impaired synthesis of GPI anchor for decay accelerating factor [DAF/CD55] and membrane inhibitor of reactive lysis [MIRL/CD59] that protects RBC membrane from complement
increases incidence of acute leukemias
90
HbC disease
glutamic acid to lyCine (lysine) mutation in beta globin
causes extravascular hemolysis
pt with HbSC is milder than HbSS
hemoglobin crystals inside RBCs, target cells
91
Sickle cell anemia
HbS point mutation causes beta chain AA glutamic acid to become valine
extra and intravascular hemolysis
Like in beta thalassemia, pt can present with a crew cut on skull xray due to marrow expansion from increased erythropoiesis
Pts can also present with dactylitis or painful swelling of hands/feet
sickling in renal medulla (drop in PO2) --> renal papillary necrosis --> microhematuria
tx with hydroxyurea (increases HbF) and hydration
92
In extravascular hemolysis RBCs are phagocytized by macrophages in the _________
in the spleen and liver.
93
In intravascular hemolysis RBCs are due to physical trauma or complement fixation in the _________
in the blood vessels
94
Warm Autoimmune hemolytic anemia
IgG
chronic anemia seen in SLE and CLL and with certain drugs
"WARM weather is Great
95
Cold Autoimmune hemolytic anemia
IgM
Acute anemia triggered by cold; seen in CLL, Mycoplasma pneumo, Mono.
"COLD weather is MMMiserable"
96
Autoimmune hemolytic anemia
Cold and warm type
RBC agglutinated may cause painful blue fingers and toes with cold exposure
Coombs +
97
Anti-Ig antibody added to patients RBC. RBC agglutinate if coated with Ig
Direct coombs test
98
Normal RBCs added to patients serum. If serum has anti RBC surface Ig, the RBCs agglutinate when coombs reagent added
Indirect coombs test
99
Microangiopathic anemia
RBCs are damaged when passing through obstructed or narrowed vessel lumina
forms schistocytes due to mechanical destruction and formation of fragmented RBCS
100
Macroangiopathic anemia
Prosthetic heart valves and aortic stenosis may also cause hemolytic anemia secondary to mechanical destruction of RBCs
schistocyte formation
101
Iron overload
hemochromatosis
increased serum iron, drop in transferrin or TIBC (TIBC indirectly measures transferrin), increase ferritin (storage), and large increase in percent transferrin saturation
102
Leukopenia
Neutropenia
Lymphopenia
Eosinopenia
Leukopenia is a general decrease in WBCs (leukocytes) found in blood which increases risk of infection
Neutropenia (<1500, if <500 then severe infections result)
Lymphopenia (<1500, <3000 in children)
Eosinopenia (<30)
corticosteroids cause neutrophilia, despite causing eosinopenia and lymphopenia
103
Left shift
defines as a shift towards more immature cells in the maturation process
i.e. in infection or inflammation where we get neutrophilia where there is an increase in neutrophil precursors, such as band cells and metamyelocytes, in peripheral blood
104
Leukoerythroblastic reaction
when a left shift is seen with immature RBCs
occurs with severe anemia (physiologic response) or marrow response
105
Porphyrias
Defective heme synthesis that lead to accumulation of heme precursors
lead can inhibit specific enzymes needed in heme synthesis leading to similar condition
106
What enzyme is affected in lead poisoning and what substrate accumulates
- Ferrochelatase and ALA dehydratase
| - Protoporphyrin, ALA in blood
107
What enzyme is affected in acute intermittent porphyria and what substrate accumulates
- Porphobilinogen deaminase
| - Porphobilinogen, ALA
108
What enzyme is affected in porphyria cutanea tarda and what substrate accumulates
- Uroporphyrinogen decarboxylase
| - Uroporphyrin --> tea colored urine
109
Pt presents with microcytic anemia, basophilic stippling in peripheral smear, ringed sideroblasts in bone marrow. Most notable physical symptoms are a headache. memory loss, and demyelination. The pt child also presents with mental deterioration
Lead poisoning
110
Pt presents with painful abdomen, port wine colored urine, polyneuropathy, psychological disturbances. All of which is precipitated by drugs, alcohol, and starvation
Acute intermittent porphyria
111
Pt was dx with Hep c and now presents with blistering cutaneous photosensitivity and hyperpigmentation. It is exacerbated with alcohol consumption.
Porphyria cutanea tarda
112
Pt is a child that presents with nausea, vomiting, gastric bleeding, lethargy, and scarring that has now lead to a GI obstruction. Child mentions eating something that looked like "Candy"
Iron poisoning
cell death due to peroxidation of membrane lipids
tx with chelation
113
PT
common and extrinsic pathway (I,II,V,VII,X)
Play Tennis outside
114
PTT
Play Table Tennis Inside
common and intrinsic pathway
115
INR (internationalized normalized ratio)
1= normal
>1 is prolonged
based on PT for following patients on warfarin
116
mixing study
normal plasma is added to patients plasma
clotting factor deficiencies should correct the PT or PTT
Factor inhibitors will not be corrected
117
Hemophilia? A?B?C?
Hemophilia is the inability to clot blood due to an intrinsic pathway coagulation defect (PTT)
A? factor VIII (A is eight)
B? factor IX ( Bnine)
C? factor XI (Celeven)
tx is desmopressin + whatever factor is missing
118
Hemarthroses
bleeding into joints due to hemophilia
119
Vitamin K deficiency
Bleeding time normal but see both an increase in PT (extrinsic) and PTT (intrinsic)
120
Platelet disorders
Defects in platelet plug formation causes an increase in bleeding time and possibly platelet count
121
Bernard soulier syndrome
Drop in platelet count and rise in bleeding time
Defect in platelet plug formation due to a decrease in GpIb which prevents adhesion to vWF
Large platelets
Does not correct with mixing studies
122
Glanzmann thrombasthenia
Unchanged platelet count and increased bleeding time
Defect in GpIIb/IIIa causing a problem with platelet to platelet aggregation
blood smear shows no platelet clumping
123
Hemolytic uremic syndrome
Decreased platelet count and increased bleeding time
thrombocytopenia, microangiopathic hemolytic anemia, and acute renal failure
In children: diarrhea and EHEC infection
In adults: no diarrhea and does not need EHEC
124
Immune thrombocytopenia
Decrease platelet count and increased bleeding time
Anti-GpIIb/IIIa antibodies cause splenic macrophages to consume the platelet antibody complex
labs show an increase in megakaryocytes on bone marrow biopsy
125
Thrombotic thrombocytopenic purpura
Decrease platelet count and increased bleeding time
Inhibition or deficiency of ADAMTS13 (vWF metalloprotease) which results in degradation of vWF multimers. This causes increase of multimers and increases platelet adhesion and aggregation --> thrombosis
126
Pentad of sx for thrombotic thrombocytopenic purpura
```
Fever
Microangiopathic hemolytic anemia
Thrombocytopenia (low platelet count)
Renal failure
Neurologic symptoms
```
can also see schistocytes
127
Von willebrand disease
Increase in bleeding time and increase in PTT (instrinsic)
vWF acts to carry and protect factor VIII
most common inhereted bleeding disorder
tx with desmopressin which releases the vWF thats stored in endothelium
128
Disseminated intravascular coagulation
DIC: drop in platelet count, Increase bleeding time, increase PT and PTT
widespread activation of clotting which causes a deficiency in clotting factors resulting in a bleeding state
can see schistocytes, increased fibrin degradation products (D-dimers), decrease fibrinogen, decrease factors V and VIII
129
Pt presents with a decrease in the inhibition of factors IIa and Xa
IIa is thrombin
Antithrombin deficiency
main effect seen is that it diminishes the increase in PTT seen with heparin admin
130
In factor V leiden, there is a mutant factor V due to ___ to ____ point mutation resulting in ______ mutation near the cleavage site
G--> A DNA point mutation
Arg506Gln mutation near cleavage site
resistant to degradtion by activated protein C
DVT, cerebral vein thromboses, recurrent pregnancy loss
131
Pt has a decreased ability to inactivate factors Va and VIIIa With an increased risk of thrombotic skin necrosis with hemorrhage after administration of warfarin
Protein C or S deficiency
C cancels and S stops coagulation
132
Prothrombin gene mutation
mutation in the 3' untranslated region --> increased production of prothrombin (II)
this caueses an increase in factor II plasma levels and ultimately clots
133
Fresh Frozen Plasma/ Prothrombin complex concentrate
FFP - Increase coagulation factors and plasma protein
PCC- factors II, VII, IX, X, C, S
134
Cryoprecipitate
contains fibrinogen
factors VIII
factor XIII
vWF
Fibronectin
135
Pt presents with low grade fever, night sweats, weight loss. On biopsy you find that localized single group of nodes are affected. Contiguous spread is noted. You also noticed Reed-sternberg cells on histology.
Hodgkin lymphoma (better than non-Hodgkins)
young adulthood or >55 years old
Men mostly
EBV associated
Reed-sternberg cells are CD15+ and CD30 + B cell origin
136
Patient presents with a low grade fever, night sweats, weight loss. On biopsy you notice multiple lymph nodes are involved with pathology and that there is extranodal noncontiguous spread
Non-hodgkin lymphoma
majority are B cells and a few are T cells
both kids and adults
May be associated with HIV and autoimmune disease
137
Prognosis of different hodgkin lymphoma types
Nodular is most common
lymphocyte rich is best prognosis
Mixed cellularity - eosinophilia seen in immunocompromised pt
lymphocyte depleted seen in immunocompromised
138
"Starry sky" appearance, sheets of lymphocytes with interspersed "tingible body" macrophages
Burkitts lymphoma
adolescents or young adults "B=Big Kids"
139
This lymphoma has a starry sky appearance on histo and is a common cause of jaw lesions (endemic form) and pelvis or abdomen (sporadic form). What is the genetic mutation for this lymphoma?
Burkitss lymphoma
t(8;14) - translocation of c-myc and heavy chain Ig (14)
"BurKIDS=Big kids are 8 and 14. 8 year olds like MYCdonalds but by 14 they are heavy"
140
This is the most common type of non-hodgkins lymphoma in adults with only 20% being in children. What is the genetics behind it
Diffuse large B cell lymphoma
alterations in Bcl-2 and Bcl-6
141
Lymphoma that has an indolent course with "waxing and waning" lymphadenopathy in adults. What is the genetics behind it
Follicular lymphoma
t(14,18) - translocation of heavy chain Ig (14) and BCL-2 (18)
F=Father was heavy by 14 and was a Big CLown for 2 years by 18 yo"
142
Very aggressive lymphoma in adult males that presents with late stage disease. Genetics?
Mantle cell lymphoma
t(11;14) - translocation of cyclin D1 (11) and heavy chain Ig (14), CD 5+
143
Lymphoma that is associated with chronic inflammation in adults. genetics?
Marginal zone lymphoma
genetics: t(11,18)
144
This lymphoma is considered an HIV/AIDs defining illness and pathogenesis incolves EBV. It needs to be distinguished from toxoplasmosis because it may have mass lesions in the brain
Primary central nervous system lymphoma
145
Pts are adults that are commonly from Japan, west africa, and the caribbean. They present with cutaneous lesions, lytic bone lesions, and hypercalcemia
adult T cell lymphoma
caused by HTLV or Human T-cell lymphotropic virus type 1 (associated with IV drug use)
146
Patient presents with plaques and skin patches all over their body. What lymphoma are we worried about
Mycosis fungoides ( T cell lymphoma) which may progress to Sezary syndrome ( T cell leukemia)
It is a cutaneous T cell lymphoma characterized by atypical CD4+ cells with cerebriform nuclei and intraepidermal neoplastic cell aggregates (pautrier microabscess)
147
Monocolonal plasma cell cancer that arises in the marrow and produces large amounts of IgG or IgA.
Multiple myeloma "fried egg appearance"
Most common bone tumor in >40-50 yo
M spike on serum protein electrophoresis
Bence Jones protein - IgG light chains in urine
Rouleaux formation - RBC stacked like poker chips in blood smear
Punched out ytic bone lesions
Clock face chromatin in plasma cells
primary amyloidosis
Intracytoplasmic inclusions containing immunoglobulin
148
multiple myeloma CRAB mnemonic
C-calcemia (hyper)
R-renal involvement
A- anemia
B - bone lytic lesions/back pain
149
________ has no CRAB (calcemia,renal,anemia, bone lytic lesions) findings but may progress to multiple myeloma
Monoclonal gammopathy of undetermined significance (MGUS)
monoclonal expansion of plasma cells (bone marrow <10% monoclonal plasma cells)
150
M spike due to IgM, no hypercalcemia, no renal involvement, no anemia, no bone lytic lesions
Waldenstrom macroglobulinemia
This is a hyperviscosity syndrome with no CRAB findings
must distinguish from multiple myeloma which has M spike due to IgG (55%) or IgA(25%)
151
Stem cell disorder involving ineffective hematopoiesis that results in defects in cell maturation of nonlymphoid lineages. What anomaly is associated with this
myelodysplastic syndrome
risk of becoming AML
Pseudo Pelger Huet anomaly - neutrophils with bilobed "duet" nuclei. Typically seen after chemotherapy
152
Leukemia
unregulated growth and differentiationof WBCs in bone marrow --> marrow failure --> anemia ( drop in RBC), infection (drop in mature WBCs), and hemorrhage (drop in platelets)
increased WBC in blood (malignant leukocytes in blood)
153
Acute lymphoblastic leukemia/lymphoma
lymphoid neoplasm
mostly in children. Worse prognosis in adults
T cell ALL can present as mediastinal mass
Downs syndrome
Blood smear shows increased lymphoblasts
can spread to CNS and testes
154
_________ leukemia/lymphoma is associated with downs syndrome
Acute lymphoblastic leukemia/lymphoma
155
Markers for Acute lymphoblastic leukemia/lymphoma
TdT +
CD10+
t(12;21) has better prognosis
156
leukemia/lymphoma that is CD20+,CD23+,CD5+ B cell neoplasm. See smudge cells in peripheral blood smear. An autoimmune hemolytic anemai
Chronic lymphocytic leukemia/small lymphocytic lymphoma
Age > 60 years (most common adult leukemia)
CLL= crushed little lymphocytes = smudge cells
157
CLL/SLL can under go a _____ transformation into ______
richter transformation
diffuse large B-cell lymphoma (DLBCL)
158
Mature B cell tumor in adult males. Cells have filamentous hair like projections
Hairy cell leukemia
causes marrow fibrosis --> dry tap on aspiration
massive splenomegaly and pancytopenia
159
Hair leukemia requires what stain menthod
TRAP + stain
Tartate resistant acid phosphatase
160
Pt is 65 yo and has Auer rods on his blood smear and a significant increase in circulating myeloblasts on peripheral smear. He is also suffering from DIC
Acute myelogenous leukemia (AML)
if myeloperoxidase + then it is APL ( a type of AML)
161
Risk factors fo acute myelogenous leukemia
```
alkylating chemotherapy
myeloproliferative disorders
Down syndrome
APL: t(15,17)
Responds to all-trans retinoic acid (vitamin A)
differentiation of promyelocytes
```
162
Dysregulated production of mature and maturing granulocytes and splenomegaly. It may accelerate to AML or ALL "blast crisis". Patient has very low Leukocyte Alkaline Phosphatase (LAP)
Chronic myelogenous leukemia
philadelphia chromosome t(9,22) BCR-ABL
myeloid stem cell proliferation
responds to bcr-abl tyrosine kinase inhibitors - imatinib and dasatinib
163
chronic myeloproliferative disorders are associated with ____ mutation
V617F JAK2 mutation
polycythemia vera
essential thrombocythemia
myelofibrosis
164
Patient complains of feeling extremely itchy after a long hot shower. She has also noted severe, burning pain and red-blue coloration in her extremities
Polycythemia vera (primary)- increased RBCs
erythromelalgia (severe burning pain and red blue coloration due to episodic blood clots in vessels of the extremities) is a classic sx
drop in EPO (vs secondary polycythemia vera which has increased EPO due to endogenour or artificially)
165
Patient presents with bleeding and thrombosis. Blood smear shows markedly increased number of platelets, which may be large or otherwise abnormally formed
Essential thrombocythemia
massive prolfieration of megakaryocytes and platelets
166
Patient has massive splenomegaly and you see teardrop RBCs
myelofibrosis
obliteration of bone marrow with fibrosis due to increased fibroblast activity
"bone marrow is crying because its fibrosed and is a dry tap"
167
Relative polycythemia
drop in plasma volume due to dehydration or burns
168
Appropriate absolute polycythemia
increase in RBC mass, drop O2 sat, increased EPO levels
lung disease, congenital heart disease, high altitude
169
Inappropriate absolute polycythemia
increased RBC mass and increased EPO levels
malignancy, hydronephrosis, due to ectopic epo secretion
170
Pt is a child presenting with lytic bone lesions, skinr ash, and recurrent otitis media with a mass involving the mastoid bone. Birbeck granules are seen on EM.
Langerhans cell histocytosis- collective group of proliferative disorders of dendritic (langerhans) cells
cells are functionally immature and do not effectively stimulate primary T cells via antigen presentation
S-100 and CD1a
birbeck granules are the tennis rackets
171
Tumor lysis syndrome
Release of K+ --> hyperkalemia, release of PO4 --> hyperphosphatemia, hypocalcemia due to sequesteration of PO4
this increases nucleic acid breakdown --> hyper uricemia --> acute kidney injury
tx with aggressive hydration, allopurinol, rasburicase
