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Heme/Lymph > Exam 1 > Flashcards

Exam 1 Flashcards

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1
Q

What is the myeloid tissue and the derivatives?

A

RBCs, platelets, granulocytes, megakaryoblasts, monocytes, etc.
tissue is BM

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2
Q

What are the lymphoid tissues and derivatives?

A

thymus, spleen, lymph nodes

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3
Q

Where do plasma cells and memory lymphocytes reside?

A

bone marrow

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4
Q

When is the liver important in blood cell production?

A

month 3 of development until shortly before birth

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5
Q

Why are placental HSCs important?

A

they can be used in future therapy via transplantation

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6
Q

What is the earliest fetal site of blood cell production?

A

mesonephros

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7
Q

What is the final developing site of fetal blood cell production?

A

bone marrow

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8
Q

What general area is hematopoietically active in post-pubertal adults?

A

axial skeleton

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9
Q

What are hemtopoietic stem cell markers?

A

cKIT+, Sca-1+, LIN-

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10
Q

Why are differentiated cells easier to identify than stem cells based purely on markers?

A

they become more specific with differentiation

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11
Q

What are the two essential features of hematopoietic stem cells?

A

pluripotency and capacity for self renewal

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12
Q

What can stress and G-CSF do to stem HSCs?

A

mobilize them into peripheral blood

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13
Q

How can unregulated clonal expansion occur?

A

lack of GF dependence and inability to mature

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14
Q

What is the normal morphology of the bone marrow?

A

thin-walled sinusoids lined with endothelial cells, the interstitium is filled with HSCs and fat cells

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15
Q

Where are megakaryoblasts found in in normal BM?

A

next to sinusoids and extend cytoplasmic processes into blood stream to elaborate platelets, also have surrounding precursor RBCs “nurse cells” can give iron to help with Hg synthesis

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16
Q

What is leukoerythroblastosis?

A

abnormal release of immature precursors into the peripheral blood

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17
Q

What are immature WBCs in the peripheral blood known as and what should be done?

A

they are called blasts and should be worked up for neoplasia, can be differentiated with cell markers

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18
Q

How is bone marrow fat useful in identifying hematopoietic tumors?

A

ratio is normally 1:1 fat to hematopoietic elements, this decreases with tumors

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19
Q

What are the two broad categories of WBC disorders?

A

proliferative is increased which can be reactive or neoplastic and leukopenias are decreases,

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20
Q

What causes reactive proliferation of WBCs?

A

infections and inflammation

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21
Q

What are the common causes of lymphopenias?

A

HIV infections, glucocorticoid or cytotoxic drug therapy, malnutrition, acute viral infections

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22
Q

How do viral infections cause lymphopenia?

A

redistribution phenomenon where T cells are sequestrated in the lymph nodes

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23
Q

What are neutropenia and agranulcytopenia?

A

low and nearly absent neutrophils, respectively

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24
Q

What are the main mechanisms by which neutropenia is caused?

A

inadequate/inaffective granulopoiesis or increased destruction/sequestration in the periphery

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25
Q

In what settings is inadequate granulopoiesis observed?

A

suppression of HSCs(aplastic anemia),
suppression of committed granulocytic precursors(drugs),
ineffective hematopoiesis(megaloblastic anemias),
congenital conditions(gene impairment)

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26
Q

In what settings is accelerated destruction/sequestration of neutrophils seen?

A

immunologically mediated injury(SLE), splenomegaly(cells are held inside), increased peripheral utilization(overwheming infections)

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27
Q

What is the most common cause of agranulocytosis?

A

drug toxicity, frequently cancer Tx, either by direct toxic effects or by antibody formation

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28
Q

How do LGL leukemias occur?

A

casue agranulocytosis via unknown cytotoxic T cell mediated neoplasm

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29
Q

What histologic BM changes are seen in leukopenia?

A

hypercellularity to replace lost cells in peripheral destruction, hypocellularity is seen if the precursors are suppressed

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30
Q

What is the morphology of infections due to agranulocytosis?

A

oral cavity necrotizing lesions, deep, with necrotic membranes covering bacteria or fungi, ulcerations can occur on skin, GI mucosa and perineal area, if any occur in the kidney or lungs they are life-threatening, these sites show massive growth of organisms in colonies(botryomycosis)

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31
Q

What species of fungal infections are neutropenic patients at risk for>

A

candida and aspergillus

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32
Q

What are some signs and symptoms of neutropenia?

A

infection, malaise, chills, fevers, weakness and fatigability, infections in agranulocytosis can cause death in days

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33
Q

What is a treatment for neutropenia?

A

G-CSF

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34
Q

What is leukcoytosis?

A

increase in WBCs, common in inflammation

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35
Q

On what factors does peripheral leukocyte count depend?

A

lymphoid/myeloid precursor size and storage cells in tissue,
rate of release of storage,
porportion of cells adhered to vessel walls(marginal),
rate of extravasation from blood into tissue

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36
Q

What can decrease WBC margination and extravasation?

A

exercise/catecholamines and glucocorticoids respectively

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37
Q

What factors lead to egress of WBCs due to infection?

A

IL-1 and TNF, if chronic these cause HSC growth factors to enhance proliferation, leading to left shift and leukocytosis

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38
Q

What are toxic granules and Dohle bodies and their association?

A

TG-coarse, dark granules, abnormal azurophilic
DB-dilated ER appear as sky blue puddles,
seen in sepsis or severe inflammation

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39
Q

What is a leukomoid reaction?

A

severe infections causing release of immature granulocytes into blood which resemble myeloid leukemia

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40
Q

What are the primary and secondary lymphoid tissues?

A

primary: thymus(t cells) and BM(b cells)
secondary: LN, spleen, Peyer patches, tonsils, adenoids

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41
Q

What occurs in germinal center?

A

B cells acquire ability to produce Abs against Ags

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42
Q

What typically causes acute nonspecific lymphadenitis?

A

drainage of microbes and their products from infection into the regional nodes, systemic viral infections and bacteremia can cause generalized lymphadenopathy

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43
Q

What is seen in lymph node with acute nonspecific lymphadenitis?

A

swollen, red, gray, large germinal centers with mitoses, dead bacteria or necrotic cells inside macrophages, pyogenic organisms can lead to prominent neutrophils and necrosis of follicles, hyperplastic endothelial cells

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44
Q

How does acute nonspecific lympahdenitis cause scarring?

A

abscesses that rupture the LN capsule cause skin redness and this can track to the skin to drain, leaving a scar on healing

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45
Q

What causes follicular hyperplasia?

A

stimuli that activate humoral immune responses, presence of oblong GC(secondary follicles), can be caused by RA, toxoplasmosis and early HIV infections

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46
Q

What do GC normally contain?

A

dark zone of proliferating B cells and light zone of B cells with irregular nuclear contours, as well as central DC and macrophages, surrounded by a collar of naive B cells(mantle)

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47
Q

What is special about GC macrophages?

A

they are known as tingible body to the refraction of light and they contain debris of B cells who failed to mature with proper Ab

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48
Q

What findings favor a reactive(nonneoplastic) follicle?

A

maintained architecture, variation in size and shape of follicles, frequent mitotic figures, light/dark zones and macrophages

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49
Q

What causes paracortical hyperplasia?

A

stimuli that trigger T cell response(viral infections),

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50
Q

What is the morphology of paracortical hyperplasia?

A

T cell zones contain blasts, T cells 3-4 times normal size with large round nucleus, prominent nucleoli and moderate cytoplasm, T cell zone encroaches on the B cell follicles can look similar to lymphoid neoplasm, endothelial cell hypertrophy with macrophages and eosinophils

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51
Q

What is sinus histiocytosis?

A

reticular hyerplasia, increase in number and size of cells lining lymphatic sinusoids, can occur with CA drainage, macrophages are increased and thy hypertrophy can cause sinusoidal distension

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52
Q

What are the patterns of chronic nonspecific lymphadenitis?

A

follicular hyperplasia, paracortical hyperplasia, sinus histiocytosis

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53
Q

What factors can lead to tertiary lymphoid organs?

A

these are collections of immune cells in nonlymphoid tissue, H. pylori casuing chronic gastritis and RA can lead to these collections and its thought a certain cytokine also plays a role

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54
Q

What is hemophagocytic lympohistocytosis?

A

HLH is a reactive condtion marked by cytopenias and systemic inflammation related to macrophage activation, aka macrophage activation syndrome, sporadic and familial

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55
Q

What is common to all forms of HLH?

A

systemic activation of macrophages and CD8+ CTLs

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56
Q

How does HLH occur?

A

macrophages phagocytose blood cell precursors in BM and release mediators which can cause a cytokine storm or SIRS, with symptoms of systemic inflammation

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57
Q

How do familial forms of HLH interact with T cells and NK cells?

A

they have several different mutations that impact the ability of these cells to properly form or deploy cytotoxic granules

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58
Q

What idea is given as to why familial HLH occur as it does?

A

CTLs keep immune responses in check by lysing AG carrying cells, if this cannot occur immune hyperactivity occurs and extremely high levels of inflammatory cytokines are reached

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59
Q

What is the most common trigger for HLH?

A

EBV

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60
Q

How do patients with HLH present?

A

febrile, hepatosplenomegaly, anemia, thrombocytopenia, high plasma ferritin and IL-2R; elevated liver enzymes and triglyceride levels secondary to hepatitis, this can lead to MOF, shock and death,

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61
Q

How is HLH treated?

A

immunosuppression and mild chemo, maybe HSC transplant, without Tx familial HLH prgnosis is 2 months, with Tx half survive but with sequelae(renal damage in adults & growth stunting and MR in kids)

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62
Q

What cells make up lymphoid neoplasms?

A

B cell, T cell and NK cell

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63
Q

What cells make up myeloid neoplasms?

A

early hematopoietic progenitors

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64
Q

What are the 3 myeloid neoplasm categories?

A

acute myelogenous leukemias, myeloproliferative disorders, myelodysplastic syndromes

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65
Q

To what does histiocytoses refer?

A

macrohpages and dendritic cells, specifically langerhans cell histiocytoses

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66
Q

What type of chromosomal abnormality is commonly seen in the majoroty of WBC neoplasms?

A

translocation

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67
Q

In what stage do oncoproteins typically arrest cells?

A

highly proliferative phases, oftern prior to diferentiation

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68
Q

How can oncoproteins cause enhanced self-renewal?

A

constitutively activated RTK, activates RAS and PI3/AKT as well as MAPK

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69
Q

What are the 3 main mechanisms by which WBCs become malignant?

A

increased cell division, Warburg metabolism;
decreased apoptosis;
increased self renewal

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70
Q

What is AID used for in B cells?

A

class switching and somatic hypermutation; these allow for increased affinity for Ag;
due to its DNA cleavage it is sufficient to cause translocations of MYC/Ig or BCL6;
(activation-induced cytosine deaminase)

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71
Q

How can VDJ recombinase cause mutations?

A

similar to AID it can cut and join AG receptors to other DNA

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72
Q

What genetic diseases are linked to WBC neoplasms?

A

Bloom, Fanconia anemia and ataxia telangectasia are at increased risk of acute leukemia;
Down syndrome and NF1 are at increased risk of childhood leukemias

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73
Q

What viruses are linked to WBC neoplasms?

A

HTLV-1 can cause adult T cell leukemia/lymphoma;
EBV can cause Burkitt lymphoma, HL, NK lemphomas and B cell lyphomas in the setting of T cell immunosuppression;
kaposi sarcoma(KSHV) is associated with B-cell lymphoma with malignant pleural effusion;
HIV linked to B-cell lymphomas in any organ system;

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74
Q

What inflammation disorders can lead to WBC neoplasia?

A

H. pylori can lead to B-cell lymphomas;
gluten senstive enteropathy and intestinal T-cell lymphomas;
breast implants can cause T cell lymphoma

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75
Q

How does HIV lead to an increased risk of lymphoid neoplasias?

A

T cell dysregulation leads to GC hyperplasia leading to lymphomas;
AIDS further increases B cell lymphoma risk assocaite with EBV, KSHV/HHV8

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76
Q

What WBC neoplasia can smoking cause?

A

1.3-2x increase of AML

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77
Q

How are leukemia and lymphoma different?

A

leukemia is typically systemica and primarily blood borne while lymphomas typically are tissue tumors

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78
Q

What are causes of neutrophilic leukocytosis?

A

acute bacterial infection(pyogenic), tissue necrosis

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79
Q

What are causes of eosinophilia?

A

allergies, drug reactions, malignancies, autoimmune disorders, vasculitidies

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80
Q

What are causes of basophilia?

A

rare, indicative of myeloproliferative diseases

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81
Q

What are causes of monocytosis?

A

chronic infections, bacterial endocarditis, rickettsiosis, malaria, autoimmune disorders, IBD

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82
Q

What are causes of lymphocytosis?

A

accompanies monocytosis associated with immunologic stimulation, viral infections, B. pertussis

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83
Q

How do many HLs and NHLs present?

A

nontender lymphadenopathy the others present with extranodal involvment

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84
Q

how can you define precursor, peripheral and NHLs?

A

immature, mature and Reed-Sternberg cells, respectively

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85
Q

How can receptors lead to differentiation between reactivity and neoplasms?

A

reactive cells will be polyclonal while malignancies have a monoclonality due to being exactly like the progenitor with the mutation

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86
Q

How are neoplastic B and T cells similar to the normal counterpart?

A

they tend to perform the same activities, go to the same locations, etc

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87
Q

What are the broad immunologic abnormalities seen in lypmhoid neoplasms?

A

loss of protective immunity and breakdown in tolerance

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88
Q

What are the primarily T cell associated CDs?

A 
CD1-thymocytes, langerhans cells; 
CD3-thymocytes, mature T cell;
CD4- Th cells
CD5- T cells and some B cells
CD8- CTLs and some NK
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89
Q

What are the primarily B cell associated CDs?

A

CD10-pre-B cells and GC B cells
CD19- B cells other than plasma cells
CD20-after CD 19 on B cells but not plasma cells
CD21-EBV receptor, follicular DCs and mature B cells
CD23-activated B cells
CD79a-marrow pre B cells and mature B cells

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90
Q

What are the primarily monocyte/macrophage associated CDs?

A 
CD11c-granulocytes, monocytes, macrophages, hairy CL;
CD13-monocytes and granulocytes
CD14-monocytes
CD15-granulocytes, Reed-Sterneberg cells
CD33-myeloid progenitors and monocytes
CD64- mature myeloid cells
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91
Q

What CDs are primarily NK associated?

A

CD16-NK cells and granulocytes

CD56-NK cells and come T cells

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92
Q

What is CD43?

A

pluripotent HSCs

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93
Q

What is CD30?

A

activation marker of B cells, T cells and macrophages, as well as RS cells

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94
Q

What is CD45?

A

all leukocytes, aka LCA(leukocyte common antigen)

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95
Q

How do NHL and HL tend to spread>

A

HL spreads in an orderly fashion will NHLs spread widely, early in their course

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96
Q

What are the neoplasms of immature B and T cells?

A

B cell ALL and T cell ALL

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97
Q

What are the mature B cell neoplasms?

A

burkitt lymphoma, diffuse large B cell lymphoma, extranodal marginal zone lymphoma, follicular lymphoma, hairy cell leukemia, mantle cell lymphoma, multiple myeloma, SLL/CLL

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98
Q

What are the neoplasms of mature T cells or NK cells?

A

adult T cell leukemia, peripheral T cell lymphoma, unspecified, anaplastic large cell lymphoma, extranodal NK/T cell lymphoma, mycosis fungoides/Sezary syndrome, large granular lymphocytic leukemia

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99
Q

What cell, genotype and clinical features are involved in B cell ALL?

A

bone marrow precursor B cell;
t(12;21) involving RUNX1 and ETV6 in 25%;
mostly children, aggressive, pancytopenia

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100
Q

What cell, genotype and clinical features are involved in T cell ALL?

A

precursor T cells(thymic origin);
chromosomal translocations, NOTCH1 mutations over 50%;
adolescent males mostly, aggressive, thymic masses, BM involvement

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101
Q

What cell, genotype and clinical features are involved in burkitt lymphoma?

A

GC B cells;
MYC and Ig loci translocations, t(8;14), EBV associated;
adolescents or young adults, aggressive, extranodal masses(leukemia presentation at times)

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102
Q

What cell, genotype and clinical features are involved in diffuse large B cell lymphoma?

A

GC or post GC B cells;
chromosomal rearrangements BCL6, BCL2 and MYC;
all ages, mostly older adults, aggressive, usually rapidly growing mass

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103
Q

What cell, genotype and clinical features are involved in extranodal marginal zone lymphoma?

A

memory B cells;
t(11;18)-MALT-IAP2, t(1;14)-BCL-10-IgH, and t(14;18)-MALT-IgH;
extranodal sites in adults with chronic inflammatory disease, indolent, may remain localized

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104
Q

What cell, genotype and clinical features are involved in follicular lymphoma?

A

GC B cell;
t(14;18)-BCL2-IgH;
older adults with generalized LAD and marrow involvement, indolent

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105
Q

What cell, genotype and clinical features are involved in hairy cell leukemia?

A

memory B cell;
activating BRAF mutation;
older males with pancytopenia/splenomegaly, indolent

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106
Q

What cell, genotype and clinical features are involved in mantle cell lymphoma?

A

naive B cells;
t(11;14) CyclinD1-IgH ;
older males with disseminated disease; moderately aggressive

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107
Q

What cell, genotype and clinical features are involved in multiple myeloma/solitary plasmacytoma?

A

post GC BM homing plasma cell;
rearrangements involving IgH and 13q deletions;
myeloma: older adults with lytic bone lesions, fractures, hypercalcemia, renal failure, moderately aggressive;
plasmacytoma: plasma cell masses in bone or soft tissue, indolent

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108
Q

What cell, genotype and clinical features are involved in small lymphocytic lymphoma/chronic lymphocytic lymphoma?

A

naive B cells/memory B cells;
trisomy 12, 11q/13q/17p deletions;
older adults with BM, LN, spleen and liver disease, minority with autoimmune hemolysis and thrombocytopenia, indolent

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109
Q

What cell, genotype and clinical features are involved in adult T cell leukemia?

A

helper T cell;
HTLV-1 provirus in tumor cells;
adults with cutaneous lesions, marrow involvement, and hypercalcemia, mainly in Japan, West Africa, and Caribbean, aggressive

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110
Q

What cell, genotype and clinical features are involved in peripheral T cell lymphoma, unspecified?

A

helper or cytotoxic T cell;
no chromosomal abnormality;
older adults, LAD, aggressive

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111
Q

What cell, genotype and clinical features are involved in anaplastic large-cell lymhpoma?

A

cytotoxic T cells;
ALK rearrangements;
children/young adults, LN and soft tissue disease, aggressive

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112
Q

What cell, genotype and clinical features are involved in extranodal NK/T cell lymphoma?

A 
NK cell(common) or CTL(rare);
EBV associated, no chromosomes;
adults with destructive extranodal masses, commonly sinonasal, aggressive
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113
Q

What cell, genotype and clinical features are involved in mycosis fungiodes/Sezary syndrome?

A

helper T cells;
no chromosomes;
adults with cutaneous patches, plaques, nodules, or generalized erythema, indolent

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114
Q

What cell, genotype and clinical features are involved in large granular lymphocytic leukemia?

A

two types: CTLs and NK cells;
point mutations in STAT3;
adults with splenomegaly, neutropenia, and anemia, sometimes autoimmune disease

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115
Q

What are lymphoblasts and what cancers are they commonly seen in?

A

immature B/T cells (pre-B/T cells), they make up ALLs, 85% are B cell ALLs

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116
Q

How does B-ALL uncommonly present?

A

skin or bone masses

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117
Q

What is the most common form of cancer in children?

A

ALL

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118
Q

In what ethnicities and ages are ALLs common?

A

boys>girls
hispanics>whites>blacks
B-ALL peaks at 3yo
T-ALL in adolescence

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119
Q

Is hyperploidy or hypoploidy more common in ALLs?

A

hyperploidy(>50 chromsomes)

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120
Q

What is the morphology seen in leukemic presentations of ALLs?

A

lymphoblasts in the marrow with hypercellularity

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121
Q

What is TdT?

A

present on all pre-B/T cells

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122
Q

On what cell is PAX5 seen?

A

B-ALL lymphoblasts

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123
Q

How do myeloblasts differ from lymphoblasts?

A

lymphoblasts have more condensed chromatin, less conspicuous nucleoli, smaller amounts of agranular cytoplasm, and are also MPO negative with PAS+ material

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124
Q

What markers do late pre-T cells show?

A

CD3, CD4 and CD8

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125
Q

What are common clinical features between AMLs and ALLs?

A

abrupt stormy onset(days to weeks after Sx); Sx including fatigue, fever, neutropenia, thrombocytopenia; mass effect from neoplastic infiltration; CNS manifestations

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126
Q

What is the prognosis for pediatric ALL?

A

95% remission and 75-85% cure rate

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127
Q

What factors are associated with worse prognosis of ALL?

A

younger than 2, due to MLL gene; presentation in adolescence or adulthood; peripheral blast counts over 100,00;

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128
Q

What factors are assocaited with good ALL prognosis?

A

age between 2-10yo; low WBCs; hyperdiploidy; trisomy of 4, 7, 10; presence of t(12;21)

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129
Q

What is the Philadelphia translocation?

A

t(9;22) BCR-ABL, RTK constituently active and stronger in ALL than AML, treatment in children with ALL is very effective

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130
Q

How do SLL and CLL differ?

A

lypmhocytosis count, CLL over 5000 WBCs

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131
Q

What is the most common leukemia in adults in the Western world?

A

chronic lymphoblastic leukemia(CLL)

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132
Q

What patients have CLL?

A

60yo is median with 2:1 M:F ratio

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133
Q

What is the gneotype of CLL?

A

deletions of 13q14.3, 11q and 17p along with trisomy of 12q;

the 13 deletion includes miR-15a and 16-1 which are tumor suppressor genes

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134
Q

What treatment has seen somes success in CLL?

A

BTK inhibitors, similar to the pathophysiology of X-linked agammaglobulinemia

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135
Q

What morphology is pathognomonic for CLL?

A

proliferation centers which are loose aggregates of larger activated lymphocytes

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136
Q

How do LNs appear in CLL?

A

effaced architectures, homogenous appearance at low mag, but at high mag there are small round lymphocytes

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137
Q

What is a smudge cell?

A

small round lymphocytes that have been destroyed on blood smear, look like smudges, in CLL

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138
Q

What is the SLL/CLL immunophenotype?

A

CD19, 20, 23 and 5, low Ig expression(typically M or D)

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139
Q

What physical exam findings and Sxs are present in SLL/CLL?

A

fatigue, weight less, anorexia, generalized LAD, hepatosplenomegaly, leukopenia in SLL or WBCs over 200,000 have been seen in CLL

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140
Q

How does CLL/SLL contribute to normal immune disruption?

A

unknown mechanisms, with hypogammaglobulinemia leading to infections by bacteria, or Abs from neoplastic B cells that attack platelets and RBCs

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141
Q

What leds to a poor outcome in SLL/CLL?

A

11q and 17p deletions; lack of somatic hypermutation; ZAP-70 expression; NOTCH1 mutations

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142
Q

How is CLL/SLL treated?

A

gentle chemo, immunotherapy with Abs against CD20; HSC transplantation; BTK inhibitors

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143
Q

What is Richter syndrome?

A

SLL/CLL transformation to diffuse large B cell lymphoma, occurs with rapidly enlarging mass in spleen or LNs, ominous leading to death in 1 year

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144
Q

What is the most common form of NHL in the US?

A

follicular lymphoma

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145
Q

What type of patients get follicular lymphoma?

A

middle age females and males equally, less common in European an especially Asian populations

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146
Q

What cell and translocation lead to follicular lymphoma?

A

GC B cells, t(14;18) which attaches BCL2 with IGH which overexpresses BCL2(anti-apoptosis protein)

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147
Q

What does MLL2 encode for and what cancer is it highly associated with?

A

histone methyltransferase is commonly upregulated in follicular lymphoma

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148
Q

How is therapy influenced in follicular lymphoma?

A

the microenvironment affects treatment which includes reactive follicular DCs with macrophages and T cells

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149
Q

What morphology is seen in follicular lymphoma?

A

nodular pattern in LNs, centrocytes(small cleaved cells) and centroblasts(large cells with open chromatin, several nucleoli and modest cytoplasm; 85% have para trabecular lymphoid aggregates; involvement of splenic white pulp and hepatic portal triads

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150
Q

What is the immunophenotype of follicular lymphoma?

A

GC cells with CD 19, 20, and 10, surface Ig and BCL6;
different from CLL/SLL and mantle cell lymphoma by lacking CD5;
90% express BCL2, normal folicular B cells do not express BCL2

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151
Q

How does follicular lymphoma present in patients?

A

painless LAD, extranodal site involvement is uncommmon(GI, CNS, testis), indolent waxing/waning course;

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152
Q

How is follicular lymphoma treated?

A

pallaitive care with low dose chemo or immunotherapy when symptoms occur; does not affect survival of 7-9yrs

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153
Q

Into what does follicular lymphoma have histologic transformation?

A

large diffuse B cell lymphoma or Burkitt lymphoma with MYC translocations, median survival is 1 yr after transformation

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154
Q

What is the most common form of NHL?

A

Diffuse large B cell lymphoma(DLBCL)

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155
Q

What type of patients have DLBCL?

A

males slightly more than females with a median age of 60 but young adults and children do get this cancer

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156
Q

How do BCL6 mutations lead to DLBCL?

A

BCL6 mutations occur as byproducts of somatic hypermutation as well as occasional MYC oncogenes, this typically inhibits growth of B cells and apoptosis, it is a zinc finger transcriptional repressor

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157
Q

How does t(14;18) lead to DLBCL?

A

typically arise from follicualr lymphomas leading to two classifications of DLBCL

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158
Q

What morphology is seen in DLBCLs?

A

large cell size 4-5 times larger than normal, and diffuse pattern of growth;
large nuclei, open chromatin, prominent nucleoli

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159
Q

What is the immunophenotype of DLBCL?

A

CD19/20 as well as CD10 and BCL6, most have surface Ig

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160
Q

What is the immunodeficiency-associated LBCL?

A

occurs with severe T cell depletion(HIV/BM transplant), the neoplastic B cells are usually infected with EBV, restoration of T cells causes regression of cancer

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161
Q

What is primary effusion lymphoma?

A

malignant pleural/ascitic effusion in older patients or those with HIV;
anaplastic tumor cells without T or B cell surface markers, but with clonal IgH rearrangements, tumor cells are infected with KSHV/HHV8

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162
Q

How does DLBCL present?

A

rapidly enlarging mass at extranodal or nodal sites, commonly Waldeyer ring, can involve liver/spleen causing destructive masses; no BM involvement usually

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163
Q

What is the prognosis of DLBCL?

A

60-80% achieve complete remission with intensive chemotherapy and 40-50% are cured, anti-CD20 Ab is a helpful adjuvant therapy, limited is better than diffuse, DLBCL with MYC translocations are worse than those without, treat as Burkitts

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164
Q

What are the categories of Burkitt lymphoma?

A

African(endemic), sporadic(nonendemic) or American and immunosuppression(HIV)

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165
Q

What translocation is involved in Burkitt lymphoma?

A

MYC on chromosome 8, regulates aerobic glycolysis, can be combined as t(8;22) or t(8;14) or t(2;8) depedning on the Ig chain(lambda, heavy or kappa, respectively)

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166
Q

What is the Warburg effect?

A

use of glutamine and glucose to build all building blocks of cells, seen in Burkitt lymphoma due to MYC mutation making it very fast growing

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167
Q

Which Burkitt lymphomas are infected with EBV?

A

all in the endemic form, 25% of HIV related and 15-20% of sporadic

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168
Q

What is the morphology of Burkitt lymphomas?

A

high mitotic index and multiple apoptotic cells, interspersed between macrophages leading to a “starry night” due to clear cytoplasm of phages, the BM can show royal blue cytoplasm clumped cells with clear cytoplasmic vacuoles

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169
Q

What is the immunophenotype of Burkitt lymphoma?

A

IgM, CD20, 19, 10 and BCL6, never has BCL2

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170
Q

How does Burkitt lymphoma present?

A

children and young adults, 30% of childhood NHL in US; extranodal sites, endemic has a mandibular mass or predilection for abdominal viscera(kidneys, ovaries, adrenals), sporadic appears in ileocecum or peritoneum, no BM or blood involvement usually;

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171
Q

What is prognosis of Burkitt lymphoma?

A

aggressive but responds well to intensive chemotherapy, young can be cured while older patients have guarded outcomes

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172
Q

What do plasma cell dyscrasias nearly always secrete?

A

monoclonal Ig or fragments

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173
Q

What are light chains excreted in the urine called

A

Bence-Jones proteins

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174
Q

Define multiple myeloma, solitary myeloma and smoldering myeloma.

A

MM-most important plasma cell neoplasm, tumorous masses in the skeleton(plasma cell myeloma)
SolM-single mass in tissue(plasmacytoma)
SmolM- high plasma M component without symptoms

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175
Q

What is Waldenstrom macroglobulinemia?

A

high levels of IgM lead to symptoms related to hyperviscosity of the blood, older adults, LPL association

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176
Q

What is heavy chain disease?

A

rare monoclonal gammopathy associated with LPL and small bowel marginal zone lymphoma in malnourished populations(mediterranean lymphoma), synthesis and secretion of heavy chain frags

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177
Q

What is primary or immuno-associated amyloidosis?

A

monoclonal proliferation of PC secreting light chains deposited as amyloid

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178
Q

What is MGUS?

A

monoclonal gammopathy of undetermined significance small to large M components without Sx, older adults and low but constant rate of MM conversion

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179
Q

With what is MM associated?

A

lytic bone lesion, AKI, hypercalcemia, acquired immune abnormalities

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180
Q

What patients get MM?

A

older adults 65-70yo, men and African descent

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181
Q

What are the common translocations of MM?

A

IGH(14) with cyclin D1(11) and cyclin D3(6); TP53 and 17p deletions indicate poor prognosis; late stages can have MYC mutations

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182
Q

What leads to the growth of MM?

A

IL-6, produced by the tumors and resident stromal cells, poor prognosis

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183
Q

How does MM cause lytic bone lesions?

A

RANKL is upregulated activating osteoclasts and inhibition of osteoblasts by Wnt cause increased bone resorption, hypercalcemia and pathologic fractures

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184
Q

What morphology is seen in MM?

A

destructive plasma cell tumors in the axial skeleton; punched out 1-4cm in diameter lesions(soft, gelatinous, red tumor masses), plasmablasts or bizzare multinucleated cells;
variants include flame cells(red cytoplasm), Mott cells with grape like cytoplasmic droplets with fibrils, crystalline rods and globules, the latter are referred to as Russell bodies in cytoplasm and Dutcher bodies in the nucleus; RBCs are seen in rouleaux formations; BJ proteins in the kidney cause renal disease called myeloma kidney

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185
Q

What is the immunophenotype of MM?

A

CD138, syndecan-1 and CD56, secrete IgG and IgA mostly

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186
Q

What three things cause the Sx in MM?

A

PC growth in tissue(bones), Ig excessive production and humoral immunity suppression

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187
Q

What are the Sx/findings of MM?

A

hypercalcemia, pathologic fractures, chronic pain, bacterial infections, renal insufficiency, Bence-Jones proteinuria, amyloidosis

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188
Q

What levels of light chains are common in MM?

A

3gm/dL in the serum and 6gm/dL in the urine

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189
Q

What is the prognosis in MM?

A

variable, 4-7 year survival, bony lesions result in 6-12 month lifespan, good outcomes with cyclin D translocation but worse with 13q and 17p deletions as well as t(4;14)

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190
Q

What treatments exist for MM?

A

proteosome inhibitors can cause buildup of misfolded and unpaired Ig chains leading to apoptosis of the cell;
thalidomide which ubiquinizes proteins for degradation; bisphosphonates inhibit bone resorption; and HSC transplants

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191
Q

What occurs in solitary myelomas?

A

single lesion in bone or ST, lungs, oropharynx and sinuses, osseus lesions almost inevitably progress to MM in 10-20 years , extraosseus are amenable to resection

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192
Q

What occurs in smoldering myleomas?

A

middle ground between MM and MGUS, 10-30% of marrow is PC, patients are asymptomatic; 75% progress to MM in 15 years

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193
Q

What occurs in MGUS?

A

most common plasma cell dyscrasias especially in older patients; patients are asymptomatic with serum M protein less than 3gm/dL; 1% develop CA or MM every year; same mutations as MM

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194
Q

What is lymphoplasmacytic lymphoma?

A

B cell neoplasm of older adults in 6th-7th decades, different than CLL due to PC differentiation, IgM secretion unlike IgG in MM, no kidney or bone involvement

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195
Q

What mutation is relate to LPL?

A

MYD88, activates NF-kB and promotes growth of tumor cells

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196
Q

What morphology is seen in LPL?

A

PC infiltrates in the marrow, PAS staining receals nuclear Dutcher bodies and cytoplasmic Russell bodies

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197
Q

What is the immunophenotype of LPL?

A

CD 20 and Ig, secretion of IgM mostly but also IgA or IgG

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198
Q

What is the presentation of LPL?

A

weakness, fatigue and weight loss, LAD, HSM, anemia is common, cold agglutinin medaite anemia by IgM, these Abs bind RBCs at temps lower than 37C

199
Q

What does the hyperviscosity of LPL cause?

A

visual impairment, neurologic problems, bleeding, cryoglobulinemia

200
Q

What is cryoglobulinemia and what does it cause?

A

precipitation of macroglobules at low temps producing Sx of Raynaud phenomenon and cold urticaria

201
Q

What is the prognosis of LPL?

A

no cure, 4 years after Dx, treat with plasmaphoresis of low dose chemo and CD20 Ab immunotherapy

202
Q

Who gets mantle cell lymphoma?

A

50-60s, men slightly more than women

203
Q

What is the mutation in mantle cell lymphoma?

A

t(11;14) involving IgH and cyclin D1

204
Q

What morphology is seen in mantle cell lymphoma?

A

GI preference, homogenous population of small lymphocytes with irregular to occasionally deepy clefted(cleaved) nuclear contours;
different from follicular lymphoma and CLL based on centroblasts and absent proliferation centers

205
Q

What is the immunopheotype of mantle cell lymphoma?

A

CD19, CD20, cyclin D1, Ig;
CD5+ and CD 23-(different than CLL/SLL);
lacks somatic hypermutation

206
Q

How does mantle cell lymphoma present? Prognosis? Tx?

A

painless LAD, splenic Sx and gut Sx;
poor prognosis, 3-4 yr survival;
no cure, treated with HSC transplant and proteasome inhibitors

207
Q

What is marginal zone lymphoma?

A

comes from memory B cells, considered MALTomas,

208
Q

Where do marginal zone lymphomas tend to arise?

A

areas of chronic inflammation, infection or autoimmune targets;
localized for long periods, spreading late in their course;
regress if inciting agent is resolved

209
Q

What mutations in seen in marginal zone lymphomas?

A

they are a continuum between reactive lymphoid tissue and lymphoma; can gain t(11;18), t(14;18), t(1;14), which upregualte BCL10 and MALT1 expression;
DLBCL mutation can occur

210
Q

Who gets hairy cell leukemia?

A

middle aged(55) white males 5:1 to females

211
Q

What mutation is seen in hairy cell leukemia?

A

point mutation in BRAF, valine to glutamate substitution

212
Q

What is the morphology of hairy cell leukemia?

A

fine hair like projections from leukemic cells on phase contrast microscopy; BM results in “dry tap”

213
Q

What is the immunophenotype of hairy cell leukemia?

A

CD19, CD20, surface Ig, CD11c, CD25, CD103 and annexin A1

214
Q

How does hairy cell leukemia present?

A

HSM, pancytopenia, infection related due to BM, liver and spleen infiltration

215
Q

What is the prognosis and Tx of hairy cell leukemia?

A

indolent course, sensitive to gentle chemo, producing long lasting remission, relapse after 5 years but responds to initial therapy again; BRAF inhibitprs work in failed response to chemo; excellent prognosis

216
Q

What is peripheral T cell lymphoma, unspecified

A

wastebasket diagnosis of those disease that do no fall into WHO classifications; typically have effaced LNs with variable sizes of tumor cells; many reactive eosinophils and macrophages

217
Q

What is the immunophenotype of peripheral T cell lymphoma, unspecified?

A

CD2, CD3, CD5 and T cell receptors, possibly CD8 or CD4

218
Q

How do patients present with peripheral T cell lymphoma, unspecified?

A

generalized LAD, eosinophilia, pruritus, fever, and weight loss; worse prognosis than comparable mature B cell lymphomas(DLBCL)

219
Q

What is the mutation in anplastic large cell lymphoma?

A

ALK rearrangements on chromosome 2 forming constitutive RTK

220
Q

What is the morphology of anaplastic large cell lymphoma?

A

large anaplastic cells with horseshoe shaped nuclei with voluminous cytoplasm(hallmark cells);
infiltrate sinusoids and venules mimicking metastatic carcinoma

221
Q

Who gets anaplastic large cell lymphoma?

A

children and young adults in soft tissue;

222
Q

What is the prognosis of anaplastic large cell lymphoma? treatment?

A

very good prognosis, cure rate of 75-80% with chemo; ALK inhibitors;
adults get ALK- tumors with worse prognosis

223
Q

What is the immunophenotype of anaplastic large cell lymphoma?

A

CD30, ALK+/-

224
Q

What is the mutation of adult T cell leukemia?

A

HTLV1 infection of CD4+ cells

225
Q

Who gets adult T cell leukemia?

A

endemic in Japan, West Africa and Carribean basin

226
Q

What are the symptoms of adult T cell leukemia?

A

skin lesions, generalized LAD, HSM, hypercalcemia, peripheral lymphocytosis; can lead to demyelination of CNS

227
Q

What is the morphology of adult T cell leukemia?

A

multilobulated cells called cloverleaf cells

228
Q

What is the prognosis and treatment of adult T cell leukemia?

A

rapidly progressive, fatal within moths to 1 year even with chemo;
tumors only in the skin are indolent

229
Q

What is mycosis fungoides/sezary syndrome?

A

different manifestation of CD4+ tumors that home to the skin

230
Q

How does mycosis fungoides present?

A

sking lesions with 3 phases, premycotic, plaque and tumor; T cells are found in the epidermis and dermis; late disease is characterized by spread to LN and BM

231
Q

How does Sezary syndrome present?

A

generalized exfoliative erythorderma; there are usually no tumors like MF but there can be leukemic phases with Sezary cells

232
Q

What is immunophenotype of MF/SS?

A

CLA(cutaneous leukocyte Ag), CCR4, CCR10, which contribute to homing to the skin

233
Q

What is the prognosis for MF/SS?

A

8-9 year survival; T cell lymphomas can occur as terminal events

234
Q

What is the mutation in large granular lymphocytic leukemia?

A

STAT3 activation

235
Q

What are the symptoms in large granular lymphocytic leukemia?

A

T cell disease showsmoderate lymphocytosis and splenomegaly; usually no hepatomegaly or LAD; NK versions are even more subtle

236
Q

What is the morphology of large granular lymphocytic leukemia?

A

large lymphocytes with abundant blue cytopalasm;

BM shows sparse interstitial lymphocytic infiltrates as well as in spleen and liver

237
Q

What is the immunophenotype of large granular lymphocytic leukemia?

A

CD3+ in T cell versions and CD3- and CD56 positive in NK types

238
Q

How does large granular lymphocytic leukemia present?

A

neutropenia and anemia, increased rheumatologic disorders

239
Q

Which leukemia is associated with Felty syndrome and what is the syndrome?

A

large granular lhmpcoytic leukemia is associated with the syndrome of RA, splenomegaly and neutropenia

240
Q

How does extranodal NK/T cell lymphoma present?

A

destructive nasopharyngeal mass; or the testis and skin;

caused by small vessel invasion leasing to necrosis

241
Q

What virus is extranodal NK/T cell lymphoma associated with?

A

EBV although the tumor does not express CD21

242
Q

What is the immunophenotype of extranodal NK/T cell lymphomas?

A

CD3- and have NK markers, suggestiong NK origin; also CD21-

243
Q

What is the prognosis of extranodal NK/T cell lymphoma

A

highly aggressive but responsive to radiation and not chemo; poor prognosis in advanced disease

244
Q

What is the prognosis of large granular lymphocytic leukemia?

A

indolent course in T cell tumors and aggressive in NK tumors

245
Q

What are characteristics of HL and NHL?

A

HL: localized to single group of nodes, spreads contiguously, rarely involves mesenteric nodes or Waldeyer ring, rarely extranodal

NHL: multiple peripheral nodes, noncontiguous spread, waldeyer ring and mesenteric nodes are frequently involved, commonly extranodal

246
Q

What is HL characterized by on morphology?

A

Reed-Sternberg cells or variants

247
Q

What are the 5 subtypes of HL and which are classical?

A

classic: nodular sclerosis; mixed cellularity; lymphocyte rich; lymphocyte depleted;

non-classic: lymphocyte predominance

248
Q

What are RS cells?

A

come from GC B cells or postgerminal B cells; have undergone somatic hypermutation and V(D)J recombination; they don’t express many B cell markers such as Ig genes

249
Q

What is the mutation in HL?

A

NF-kB; through separate mechanisms
EBV infection and LMP signal to NK-kB
EBV infection causing LOF in TNFAIP3
or NK-kB activated by EBV cripples GC B cells so they cannot express Igs

250
Q

What morphology is seen in HL?

A

RS cells have owl eye appearance; can also have mononuclear variant with a single nucleus and many inclusions; lacunar cells are seen with pale cytoplasm as a variant and finally lympohistiocytic variants in the lymphocyte predominance type

251
Q

What is seen in nodular sclerosis HL?

A

lacunar cells and RS cells on background of myeloid cells and PC; fibrous bands dividing into nodules; RS cells CD15+, CD30+ and no EBV; most common subtype

252
Q

What is seen in mixed cellularity HL?

A

mononuclear cell and RS cells on myeloid and PC background: RS cells CD15+, CD30+ and EBV+ in 70%; second most common

253
Q

What is seen in lymphocyte predominance HL?

A

popcorn RS cells with pale cytoplasm on background of DC and B cells;
RS cells CD20+, CD15- and CD30-, also EBV-

254
Q

How does HL present?

A

painless LAD, NS/LP types are asymptomatic systemically due to low stage disease, while MC and LD subtypes have B symptoms; anergy in many cases

255
Q

What is the common stepwise involvement of HL?

A

nodal to begin moving to splenic disease then hepatic and finally BM and other tissue

256
Q

How is HL treated?

A

radiotherapy and less toxic chemo with 60-70% survival at 5 years with lows stag disease the cure rate is 90%

257
Q

What are the 3 broad categories of myeloid neoplasias?

A

AML, myelodysplastic and myeloproliferative diseases

258
Q

What does the increased production of blasts lead to in AML?

A

anemia, thrombocytopenia and neutropenia due to replacement of BM with blasts

259
Q

What are the four classifications of AML?

A

type I is genetic; Type II is MDS-like; Type III is therapy related: Type IV is NOS

260
Q

What are the genetic alterations in AML?

A

t(8;21) involving RUNX1and inv(16) involving CBFB are most common; APL is caused by t(15;17) involving PML-RARA

261
Q

What do all AMLs frequently have in common leading to mutations?

A

epigenetic modifications via methylation and histone modification

262
Q

What is the immunophenotype of AML?

A

CD34+, CD33+. CD15+ in subsets and CD 64-; confirmed with myeloid specific antigen staining

263
Q

What is the diagnosis of AML based on?

A

20% blasts in the BM

264
Q

What morphology is seen in AML?

A

myeloblasts, auer rods in cytoplasm, monoblasts; aleukemic leukmia can have no blasts at all

265
Q

What leads to bad abberations of AML in adults?

A

deletions of 5q and 7q

266
Q

How does AML present?

A

anemia, neutropenia and thrombocytopenia; fever, fatigue and spontaneous mucosal bleeding; petechiae and bruising

267
Q

What is the prognosis in AML?

A

poor with MDS features and MLL fusion genes, worse if therapy related; intermediate if NOS or t(15;17) and favorable for the common types

268
Q

Which MDS most often progresses to AML?

A

t-MDS, therapy related

269
Q

What causes MDS?

A

epigenetic factors, RNA splicing factors, and transcription factors, 10% have loss of TP53, loss of RPS14 decreases effecting erythrpoiesis

270
Q

What is the morphology of MDS?

A

ring sideroblasts(iron laiden macrophages); megaloblastoid maturation, nuclear budding abnormalities; Psuedo-Pelger-Huet cells(bilobed neutrophils or no segmentation at all); myeloid blasts and pawn ball megakaryocytes with multiple nuclei

271
Q

Who gets MDS?

A

70 years is median age

272
Q

How does MDS present?

A

weakenss, infections, hemorrhages due to pancytopenia

273
Q

What is the prognosis is MDS?

A

9-29 months(over 2 years); 4-8 months in t-MDS

274
Q

How is MDS treated?

A

ABx, blood products and thalidomide drugs can improve blood production

275
Q

What mutations leads to MPD?

A

JAK2 mutations or BCR-ABL in CML

276
Q

What are the features of MPD?

A

increasing proliferative drive in BM, extramedullary hematopoiesis, marrow fibrosis and cytopenias in spent phase, acute leukemia transformation possibility

277
Q

What is the skin related MPD?

A

systemic mastocytosis caused by KIT mutation

278
Q

What is the mutation in CML?

A

BCR-ABL, t(9;22) or philadelphia chromosome up regulating JAK/STAT and RAS

279
Q

What morphology is seen in CML?

A

hypercellularity in BM, leukocytosis over 100,000, all myeloid cell lines; sea-blue histiocytes are macrophages with blue-green cytoplasm; massive splenomegaly

280
Q

Who gets CML?

A

older adults primarily 50-60s but also young adults and children

281
Q

How does CML present?

A

weight loss, weakness, fatigue, anorexia, or heavy sensation in abdomen due to splenomegaly(biggest ever) or acute infarct of spleen

282
Q

What is the prognosis of CML?

A

3 years; worse with blast crisis or accelerated phase

283
Q

What are the stages of CML?

A

accelerated phase with increasing anemia and thrombocytopenia with increased basophils in blood ending in blast crisis with increased myeloid of lymphoid blasts in BM

284
Q

What CA can CML become?

A

B-ALL

285
Q

How is CML treated?

A

BCR-ABL inhibitors or 2nd and 3rd gen RTK inhibitors; the former has 90% remission and tolerable side effects

286
Q

What is the mutation in polycythemia vera?

A

JAK kinase

287
Q

What happens in PCV?

A

increased in myeloid cells and RBCs, RBCs cause the Sx; low EPO due to constitutive activation of RTKs; blood is thick and sludgy leading to thrombosis and bleeding due to abnormal platelets

288
Q

What morphology is seen in PCV?

A

increase in red cell progenitors as well as megakaryocytes and granulocytes; marrow fibrosis can occur during spent phase leading to extramedullary hematopoiesis

289
Q

Who gets PCV?

A

late middle age adults

290
Q

How does PCV present?

A

Sx related to increased red cell mass and Hct as well as blood volume; can be plethoric and cyanotic due to blood stagnation, HA, dizzy, HTN, GI symptoms; pruritus and peptic ulcers can occur due to histamine from basophils; gout is seen in 5-10% of cases due to hyperuricemia from RBC turnover

291
Q

What does the thick blood in PCV lead to?

A

thrombosis and bleeding; 25% come in with DVT

292
Q

How can Hct be normal in PCV?

A

elevated Fe counteracts the erythropoiesis that is occuring

293
Q

What happens to WBCs and platelets in PCV?

A

both are increased to 12,00 and 500,000 respectively while the platelets are usually large and cannot function correctly

294
Q

What is the prognosis of PCV?

A

death within months from clots and bleeding if not treated; 10 yrs with regular phlebotomy

295
Q

What is the mutation in essential thrombocytosis?

A

JAK kinase or MPL which is normally activated by thrombopoietin; the others are calreticulin

296
Q

How is ET different than PCV?

A

no RBC involvement or marrow fibrosis

297
Q

What is the morphology of ET?

A

large megakaryocytes similar to RBCs, multiple platelets on PS; mild leukocytosis

298
Q

Who gets ET?

A

after age 60 usually but also young adults

299
Q

How does ET present?

A

hemorrhages and thrombosis due to number and qualitative abnormalities in platelets; DVT, portal/hepatic vein thrombosis; burning of hands and feet called erthromyalgia due to small arteriole occlusion

300
Q

What is the prognosis and treatment of ET?

A

12-15 years; gentle chemo

301
Q

What is the mutation in primary myelofibrosis?

A

JAK2 kinase

302
Q

What morphology is seen in primary myelofibrosis?

A

fibrotic hypocellular marrow, splenic extramedullary hematopoiesis, leukoerythroblastosis which are RBCs with nuclei and granulocyte progenitors; teardrop shaped red cells are seen due to damage from the fibrosis

303
Q

What causes primary myelofibrosis?

A

collagen deposition in the BM by non-neoplastic fibroblasts;due to PDGF and TGF-B; this leads to extramedullary hematopoiesis

304
Q

Who gets primary myelofibrosis?

A

60 years and older

305
Q

How does primary myelofibrosis present?

A

usually with anemia and splenomegaly unless it is the spent phase of another MPD, fatigue, weight loss, and nnight sweats due to increased metabolism

306
Q

What do the labs in primary myelofibrosis look like?

A

n/n anemia, WBCs normal or low, low to elevated platelets; need BM biopsy for diagnosis

307
Q

What mutations causes Langerhans cell histiocytosis?

A

BRAF mutations as well as TP53, RAS and MET RTK

308
Q

What is the morphology of LCH?

A

adbundant macrophages/DCs with vacuolization of the cytoplasm and linear grooves in the nuclei; Birbeck granules in the cytoplasm are characteristic and look like tennnis rackets

309
Q

What is the immunophenotype of LCH?

A

Birbeck granules contain langerin, and the cells express HLA-DR, S-100, and CD1a

310
Q

What is multifocal multisytem LCH?

A

before age 2, with cutaneous lesions on the back, trunk and scalp; most have HSM, LAD, pulmonary lesions and osteolytic bone lesions, can turn into Langerhans cell sarcoma

311
Q

What is unifocal and multifocal LCH?

A

“eosinophilic granuloma”; LCs mixed with granulocytes, lymphocytse, PCs; arises within bones in skull, ribs or femur; unifocal mostly in older children/adults; multifocal is commonly in children with erosive bony masses; pituitary stalk involvement causes DI in 50%

312
Q

What is the Hand-Schuller-Christian triad?

A

found in LCH(eosinophilic granuloma); refers to calvarium lesions, diabetes insipidus and exopthalmos

313
Q

What is pulmonary LCH?

A

seen in heavy smokers with BRAF mutations

314
Q

What CCR are involved in LCH?

A

CCR6/7; CCR6 binds CCL20 in the skin and CCR7 binds CCL19/21 in the lymphoid organs

315
Q

What are the four functions of the spleen?

A

phagocytose RBCs and particulate matter;
antibody production;
hematopoiesis;
sequestration of formed blood elements

316
Q

What should asplenic patients be vaccinated against?

A

pnuemococci, meningococci and Haemophilus influenzae

317
Q

What is hypersplenism?

A

anemia, leukopenia, thrombocytopenia, alone or in combination; this occurs with splenomegaly

318
Q

What causes congestive splenomegaly?

A

chronic venous outflow obstruction; seen in RHF or LHF or vavlular issues; cirrhosis is the main cause; spontaneous portal vein thrombosis or inflammation

319
Q

What congenital abnormalities involve the spleen?

A

hypoplasia or asplenia in situs inversus;

accessory spleens are important in blood dyscrasias

320
Q

What can happen in splenic rupture?

A

hemorrhage and death

321
Q

What cell types make up the thymus?

A

T lymphocytes and epithelial cells

322
Q

What are Hassall corpuscles in the thymus?

A

whorls of medullary epithelial cells with keratinized cores

323
Q

What developmental disorders involve the thymus?

A

hypoplasia or aplasia as in DiGeorge syndrome;

thymic cyst

324
Q

What occurs in thymic hyperplasia?

A

B cell germinal centers in the thymus known as thymic follicular hyperplasia-frequent in myasthenia gravis; also Graves, SLE, sleroderma, RA and othe autoimmune disorders

325
Q

What is a thymoma?

A

tumors of thymic epithelial cells; 3 categories: noninvasive/benign, invasive/benign and malignant

326
Q

What is the morphology of noninvasive thymomas?

A

normal but large tissue

327
Q

What is the morphology of invasive thymomas?

A

benign but extending through the capsule

328
Q

What is the morphology of thymic carcinoma?

A

SCC is common; next is lymphoepithelioma-like carcinoma; EBV related

329
Q

What is hematocrit?

A

ratio of pRBCs to total blood volume

330
Q

What does MCV, MCH, MCHC and RDW stand for?

A

mean cell volume, mean cell hemoglobin, mean cell hemoglobin concnetration, and red cell distribution width

331
Q

How can hypoxia affect the heart, liver and kidneys?

A

causes fatty changes

332
Q

What are the general symptoms of anemia?

A

hypoxia, pallor, weakness, malaise, fatigability, dysonea on exertion

333
Q

What can occur with acute blood loss?

A

CV collapse, shock and death

334
Q

What cellular changes aoccur in the face of acute blood loss?

A

lymphocytosis to restore volume, reticulocytosis to restore RBCs, shows up as large nucleated RBCs; finally thrombocytosis occurs due to increased platelet production

335
Q

What three factors are seen in hemolytic anemias?

A

RBCs lasting less than 120 days;
high EPO and increase in erythropoiesis;
accumulation of Hb degradation products

336
Q

What is seen in extrravascular hemolysis?

A

anemia, splenomegaly, jaundice and decrease in haptoglobin(binds alpha-Hgb to prevent excretion in urine)

337
Q

How is intravascular hemolysis manifested?

A

anemia, hemoglobinemia, hemoglobulinuria, hemosiderinuria and jaundice

338
Q

What occurs in the kidneys with intravascular hemolysis?

A

as haptoglobin is depleted, the free hgb is oxidized to methemoglobin which is excreted causing brown urine;
hgb can accumulate in the tubular cells leading to renal hemosiderosis

339
Q

How does hemolysis affect the GB?

A

leads to pigmented gallstones

340
Q

What morphology is seen in hemolytic anemia?

A

increased erythroid precursors, prominent reticulocytosis, hemosiderin in lymphoid organs(hemosidereosis), extramedullary hematopoiesis, unconjugated bilirubin and urobilin

341
Q

What proteins are most commonly affected in HS?

A

ankyrin, band 3, band 4.2 and spectrin

342
Q

What is the type of DNA mutation and inheritance of HS?

A

stop codon; autosomal dominant

343
Q

What leads to hemolysis in HS?

A

the defect decreases membrane stability, increasing loss of membrane, making spherocytes small and less deformable, the RBCs are trapped in the spleen leading to erythrostasis causing low pH and glucose; this ruptures the membrane more and the cells breakdown

344
Q

What morphology is seen in HS?

A

spherocytosis, cholelithiasis occurs in 40-50% as well as moderate splenomegaly

345
Q

What are the findings in HS?

A

positive FHx, lab evidence showimg spherocytes, RBCs are sensitive to osmotic lysis in hypotonic solution due to little margin for expansions in the cell, incerased MCHC due to dehydration

346
Q

How do patients present with HS?

A

anemia, splenomegaly and jaundice, some asymptomatic

347
Q

What infection causes aplastic crisis?

A

parvovirus

348
Q

How do you treate anemia in HS?

A

splenectomy

349
Q

How does heriditary G6PD deficiency cause hemolysis?

A

G6PD allows for production of NADPH by reducing NADP+; NADPH can then be used to reduce glutathione in order to neutralize free radicals(H2O2)

350
Q

How is G6PD deficiency inherited and who gets it?

A

X-linked recessive and its common in males

351
Q

What causes G6PD flares?

A

oxidative stress such as from infections, as well as sulfa drugs and food such as fava beans

352
Q

What morphology is seen in G6PD deficiency?

A

bite cells due to splenic phagocytosis, heniz bodies ae inclusions in RBCs from denatured globin; Heinz bodiescan cause membrane lysis and intravascular hemolysis of RBCs

353
Q

Whicj variant of G6PD is worse?

A

mediterranean

354
Q

What is the mutation found in sickle cell disease?

A

beta-globin point mutation from glutamate to valine causing polymerization of deoxygenated Hb leading to deformed sickled cell shapes(aka HbS)

355
Q

What issues does HbS cause?

A

hemolytic anemia, microvascular obstruction, and ischemic tissue injury

356
Q

What is HbA, HbA2 and HbF cosntructed of?

A

A:(alpha, beta)
A2:(alpha, delta)
F:(alpha, gamma)

357
Q

What is sickle cell trait?

A

heterozygous for sickle cell allele

358
Q

Why do RBC dyscrasias stay in populations?(SSD, G6PD deficiency and thalassemias)

A

they offer resistance to falciparum malaria due to frequent lysis of RBCs from splenic phagocytosis and low pH; secondly, membrane knobs do not form in SSD so cerebral malaria is less likely since the knobs allow endothelial adhesion

359
Q

When does SST cause sickling in RBCs?

A

extreme hypoxia due to HbS interference by HbA

360
Q

How does MCHC, pH and transit time of cells affect patients of SSD?

A

increased MCHC from dehydration leads to increased sickling, as pH drops Hb deoxygenates leading to increased sickling, slow moving capillary beds and inflammed beds lead to increased sickling

361
Q

What is the pathophysiology of SSD?

A

repeat bouts of sickling lead to holes in the cell memebranes allowing Ca influx, leading to dehydration due to efflux of potassium, this all causes dehydration and rigidity of the cells; they then get stuck in slow flow areas; NO depletion also plays a role due to vasoconstriction

362
Q

What morphology is seen in SSD?

A

irreversibly sickled cells, Howell-Jolly bodies and autosplenctomy due to splenic infarction from erythrostasis

363
Q

What are vaso-occlusive crises in SSD?

A

aka pain crises, are caused by hypoxic injury and infarction; typically not caused by any triggers; but the triggers can be infection, dehydration and acidosis; most common sites of pain are brain, liver, spleen, penis, lungs and bones; can cause CVA, priapism, and loss of visual acuity

364
Q

What is hand-foots syndrome in SSD?

A

pain in the feet and hands or dactylitis

365
Q

What is acute chest syndrome in SSD?

A

vaso-occlusive crisis in the lungs which presents with fever, cough, CP, and infiltrates on XR

366
Q

What test can be administered for SSD?

A

metabisulftite will beind oxygen causing sickling of cells in SSD

367
Q

What is the treatment for SSD?

A

hydroxyurea, increases HbF, antiinflammatory

368
Q

What are the thalassemia syndromes?

A

defects in alpha or beta globin chains leading to anemia, tissue hypoxia ad RBC hemolysis related to imbalance in globin chain synthesis

369
Q

What two mutations lead to B-thalassemia?

A

B+ mutations, which arereduced but still detectable and B0 mutations which lead to no B globin chains

370
Q

What types mutations lead to B-thalassemia?

A

splicing mutations, promoter region mutations, which lead to B+ and chain terminator mutations which insert stop codons leading to B0

371
Q

By what two mechanisms does B-thalassemia lead to anemia?

A

underhemoglobinized RBCs and decreased survival of these RBCs

372
Q

How does ineffective erythropoiesis occur in B-thelassemias?

A

the insoluble alpha chains that unpaired lead to RBC inclusions causing membrane rupture of RBC precursors as well as increased sequestration; in the severe cases this leads to extramedullary hematopoiesis and increased RBC production in the marrow and causing bone erosion and skeletal abnormalities

373
Q

How can B-thalassemias cause secondary hemochromatosis?

A

ineffective erythropoiesis causes excessive iron absorption due to hepcidin suppression; combine this with blood transfusions can lead to iron loverload and organ injury i.e. liver

374
Q

What are the forms of B-thalassemias?

A

homozygous B0 and B+ is BT major;
heterozygous B+/B or B0/B is BT minor or trait;
milder variants similar to the homozygous is BT intermedia

375
Q

How can BT be reduced or worsened in severity in some cases?

A

a concurrent alpha chain mutation which balances out the mismatch of chains; worsend if an extra alpha chain gene is expressed which increases the imbalance

376
Q

What are the Hb levels in BT major?

A

HbA2 is elevated at times but usually normal; HbA is low and HbF is markedly elevated to compensate

377
Q

What morpholoy is seen in BT major?

A

anistocytes(variation in size) and poikliocytes(shape variation); microcytic and hyopchomic RBCs; target cells are vizualized due to excessive membrane fold oveor

378
Q

What is the prognosis of BT major?

A

brief course unless transfusions are given; untreated children do not grow and then die; good cases that are treated can liver into the 3rd decade

379
Q

How does BT major present?

A

those who live longer have prominent bony areas due to enlagement; cardiac disease from iron overload causes death; heavily transufsed patients must be chelated

380
Q

Does BT minor have symptoms?

A

not typically; but can have elevated HbA2 due to gamma to delta ratio change

381
Q

Why is it important to recognize BT minor?

A

it resembles iron deficiency anemia and has genetic testing implications

382
Q

How many alpha-chain genes are normal?

A

4

383
Q

What do the unpaired globin chains lead to in newbrosn versus older children?

A

hemoglobin barts is due to gamma chain tetramers

hemoglobin H is due to beta tetramers

384
Q

What is the silent carrier state of AT?

A

one alpha chain gene deletion; asymptomatic with slight microcytic anemia

385
Q

What is the AT trait?

A

deletion of 2 alpha chain genes; both on one chromosome is found in Asian populations while one chain from each chromosome is common in African populations; this is worse for the children due to possibility of Hb Barts or HbH; resembles BT minor

386
Q

What is HbH disease?

A

deletion of 3 alpha globin genes; common in Asians; HbH is a tetramer of beta chains which has an extremely high affinity for oxygen and therefore is not a good delivery mechanism leading to hypoxia despite hemoglobin level being normal; HbH can be oxidized and precipitate leading to inclusions of RBCs: resembles BT intermedia

387
Q

What AT causes hydrops fetalis?

A

deletion of all alpha globin chains; leading to gamma chain tetramers and have extremely high affinity for O2 so tissues get no oxygen; this can be treated with transfusions

388
Q

What mutation causes PNH?

A

phophatidylinositol glycan complementation group A or PIGA, essential enzyme for complement regulatio

389
Q

Why does lyonization lead to PNH?

A

women block one X chromosome nad if the good one has a PIGA mutation then all progeny of that HSC will be missing GPI

390
Q

What 3 GPI-linked proteins are deficient in PNH?

A

CD55 or DAF;
CD59 or membrane inhibitor of reactive lysis;
C8 binding protein

391
Q

What is the pathology of PNH?

A

MAC complex formation due to lack of the inhibitors of MAC, leading to intravascular hemoylsis; it only presents at night in 25% most show chronic hemolysis; the night tendency is due to decreased pH at night

392
Q

What leads to death commonly in PNH?

A

thrombiosis in about 40% involving cerebral, hepatic or portal vv.

393
Q

How is PNH treated?

A

Eculizumab which inihibits conversion to C5a and decreasing thrombosis by 90%

394
Q

What causes immunohemolytic anemias?

A

Abs to RBCs leading to destruction

395
Q

Know the direct and indirect Coombs tests.

A

Ok done

396
Q

What is warm antibody type immunohemolytic anemia?

A

most common form; 50% are idiopathic the others are drug or predisposing conditions;
typically IgG related, membrane is removed by phagocytosis causing spherocytes which are destroyed in the spleen

397
Q

How do antigenic drugs lead to warm antibody hemolysis?

A

1-2 weeks after large dose of IV drugs like penicillin or cephalosporins binding to RBCs

398
Q

How do tolerance breaking drugs cause warm antibody hemolysis?

A

drugs such as alpha-methyldopa produce Abs against RBC Ags like Rh Ag

399
Q

What is cold agglutinin type of hemolysis?

A

caused by IgM bdinding RBCs at low temps(0-4C); less common than warm and can be brought on by viral infections(EBV, HIV, CMV, influenzae, mycoplasma); can lead to binding of IgM in fingers and toes causing Reynauds syndrome and opsonization and destruction of RBCs in spleen

400
Q

What is cold hemolysin type hemolysis?

A

paraxysmal cold hemoglobinuria; IgG Abs to P blood group Ag in cool regions of the body then in warmer areas the cells are lysed with complement, caused by viral infections and recover after 1 month

401
Q

how are RBCs lysed due to trauma?

A

RBCs flowing by artifical heart valves are lysed by shearing forces; migroangiopathic hemolytic anemia is seen with DIC, TTP, HUS, malignant hypertension and SLE; RBCs hit fibrin meshwork and lyse: schistocytes are seen on PS

402
Q

What causes megaloblastic anemias?

A

DNA synthesis impairment leading to abnormally large cells due to inability to divide

403
Q

What morphology is seen with megaloblastic anemias?

A

macro-ovalocytes(RBCs); nuetrophil nuclear hypersegmentation;
giant metamyelocytes and band forms

404
Q

How is pernicious anemia caused?

A

autoimmune gastritis impairing production of If which is required for B12 uptake in the intestines; also caused by veganism without supplementation

405
Q

How does B12 absorption occur?

A

B12 is ingested bound to protein; haptocorrin is secreted from salivary glands; B12 is removed by degradation in the stomach and is bound to haptocorrin: IF is released from parietal cells; as the H-B12 complex meets proteases the compound is cleaved and B12 binds IF which can bind to receptors in the ileum(cubulin) and be absorbed; it is then transferred to the liver via transcobalamin II

406
Q

What is B12 needed for in the body?

A

turning homocysetine into methionine; as well as conversion of methlymalonic acid which is needed for neuronal myelination;
thus both of these substrates build up in the blood and urine

407
Q

How does pernicious anemia occur?

A

autoimmune attack on gastric mucosa leading to loss of parietal cells(and IF), destruction is caused by auto reactive T cells

408
Q

What morphology is seen in pernicious anemia?

A

lymphoctes and plasma cells and megaloblastic changes in mucosal cells;
fundic gland atrophy, instestinalization, beefy tongue(atrophic glossitis), demyelination of dorsal and lateral spinal tracts

409
Q

What Abs are present in pernicious anemia?

A

Type I Abs, block B12 binding to IF;
Type II Abs, prevent binding of B12-IF complex to the receptor(cubilin);
Type III Abs, recognize the alpha and beta subunits of the proton pump;
IF Abs are highly specific for PA

410
Q

What other disease can lead to pernicious anemia?

A

gastrectomy, achlorydia and loss of pepsin, loss of pancreatic function, ileal resection

411
Q

How does pernicious anemia present?

A

insidious onset, moderate to sever megaloblastic anemia, low B12 in serum, elevateds erums levels of homocyteine and MMA; diagnosis made with increased reticulocytes with B12 administration

412
Q

Why is folate important in the body?

A

purine synthesis, converting homocysteine with B12, dTMP production

413
Q

Why does folate or B12 deficiency cause megaloblastosis?

A

DNA synthesis ceases and the cytoplasm cannot separate but has already increased so the RBCs are large

414
Q

What can cause a deficiency in folic acid?

A

decreased intake, increased need, impaired utilization

415
Q

How do alcoholics gain a deficiency in folate?

A

poor diet along wit liver trapping, abnormal metabolism, excessive urinary loss

416
Q

How is folate deficiency diagnosed?

A

decreased folate levels, high homocyteine levels, although normal MMA levels; make sure to rule out B12 deficiency before giving folate or it could worsen the imbalance of high folate and low B12

417
Q

What is the most common nutritional deficiency in the world?

A

iron deficiency

418
Q

What is the basis of the prussian blue stain?

A

iron in hemosiderin turns blue-black when exposed to potassium ferrocyanide

419
Q

What regulates iron storage?

A

hepcidin made in the liver with low iron levels, if iron is high hepcidin decreases; hepcidin binds ferroportin to inhibit iron transfer into the blood

420
Q

Who is most at risk for iron deficiency anemia?

A

infants, impoverished, adults without good diets, teenagers without good diets

421
Q

When does anemia appear in iron deficiency?

A

when iron, ferritin, and transferrin saturation levels are low

422
Q

What morphology is seen in iron deficiency anemia?

A

disappearance of stainable iron from BM macrophages, microcytic, hypochromic RBCs

423
Q

What is the triad of Plummer-Visnson syndrome?

A

esophageal webs, microcytic hypochromic anemia and atrophic glossitis

424
Q

What is the most common cause of anemia in hospitalized patients?

A

anemia of chronic disease

425
Q

What groups of chronic disease lead to anemia?

A

chronic microbial infections like osteomyelitis, endocarditis, lung abscess;
chronic immune disorders like RA and enteritis;
neoplasms like carcinoma of lung/breasts and HL

426
Q

What are the labs in AOCD?

A

high ferritin, high hepcidin, low iron, low TIBC, low transferritin

427
Q

What is aplastic anemia?

A

chronic primary hematopoietic failure and pancytopenia

428
Q

What agents can cause aplastic anemia?

A

idiopathic, immune mediated, dose related drugs, irradiation, viral infections from VMC, Hep viruses, EBV, herpex zoster, fanconi anemia, telomerase defects

429
Q

What is fanconi anemia?

A

AR disease caused by defects in multiprotein complex for DNA repair; seen with kidney and spleen hypoplasia and bone anomalies of thumb/radii

430
Q

What two etiologies have been attributed to aplastic anemia?

A

extrinsic immune mediated suppression of BM and intrinsic abnormality of stem cells; cytokines like IFN-y and TNF are secreted to kill hematopoietic progenitor cells

431
Q

How does aplastic anemia present?

A

weakness, pallor, infection due to pancytopenia; not usually splenomegaly

432
Q

What is pure red cell aplasia?

A

primary marrow disorder where only erythroid progenitors are suppressed

433
Q

What does infectioen with Parvovirus B19 cause?

A

specific RBC aplasia

434
Q

What can be done to treat pure red cell aplasia?

A

thymoma resection if causative or immmunosuppressive therapy if not thymoma

435
Q

What is myelophthistic anemia?

A

failure of marrow due to space occupying lesions replacing normal marrow; usually metastatic cancer; tear drop RBCs seen on PS and leukoerythroblastosis

436
Q

How does chronic renal failure lead to anemia?

A

decreased EPO made by kidneys

437
Q

What other disorders lead to anemia?

A

hypothyroidism and hepatocellular liver disease

438
Q

What are the causes of polycythemia?

A

high red cell count with high Hb; relative occurs with dehydration whileabsolute it primary with an intrinsic mutation in progenitor cells, secondary is caused by increased EPO; PCV is a JAK2 mutation

439
Q

What can cause excessive bleeding?

A

vessel fragility, platelet decrease or dysfunction, coagulation derangements

440
Q

What is PT measuring?

A

extrinsic and common pathways; prothrombin time; measured with addition of tissue thromboplastin and Ca; plasma clotting is measured in seconds; involves factor V, VII, X, prothrombin or fibrinogen

441
Q

What does PTT measure?

A

partial thromboplastin time; assess instrinsic and common pathways; factors V, VIII, IX, X, XI or XII and fibrinogen and prothrombin; clotting measurement after addition of koalin, cephalin and Ca

442
Q

What vessel wall abnormalities are seen in bleeding disorders?

A

infections causing septicemial, endocarditis and rickettsioses;
hypersensiticity drug reactions;
scurvy and Ehloers-Danlos syndrome due to collagen weakness in vessels(also Cushing syndrome);
Henoch-Schonlein purpura due to circulating Ab deposition;
hereditary hermorrhagic telangiectasia casued by TGF-B mutations leading to mucosal bleeding;
fianlly, perivascular amyloidosis from AL chain depostion

443
Q

What does thrombocytopenia look like?

A

PT, PTT normal, worrisome for IC hemorrhage; mostly petechiae and ecchymoses

444
Q

What can cause thrombocytopenia?

A

decreased production from marrow issues, decreased survival due to destruction or Abs, sequestration in spleen and dilution from blood products not including platelets

445
Q

What causes chronic immune thrombocytopenic purpura?

A

Abs to platelets mediate destruction, Abs are against IIb-IIIa or Ib-IX typically IgG class; Abs can also bind megakaryocytes leading to further thrombocytopenia

446
Q

How is CITP treated?

A

splenectomy decreases destruction of platelets by macrophages and by Ab production of PC in spleen

447
Q

What morphology is seen in CITP?

A

found in spleen, BM, and blood but not specific, moderately increased megakaryocytes as well as abnormally large platelets

448
Q

Who gets CITP?

A

adult women under 40 years old 3:1 females to males

449
Q

How does CITP present?

A

insidiously, bleeding into skin and mucosa known as petechiae or ecchymoses, melena and hematuria can occur and move on towards IC bleeding

450
Q

How is CITP treated?

A

steroids, if that does not help then splenectomy or anti-CD20 abs(rituximab)

451
Q

What is acute immune thrombocytpenic purpura?

A

also caused by auto Abs to platelets; occurs in childhood typically after a viral illness and resolves in around 6 months; can be childhood CITP is not resolved alone or with steroids

452
Q

What is drug induced thrombocytopenia?

A

direct effects on platelets by drugs and through immune mediation; quinine, quinidine and vancomycin are culprits; HIT is a common cause

453
Q

What is heparin induced thrombocytopenia?

A

Type I is from platelet aggregating effects of herpain and resolves with d/c;
Type II leads to life threatening thombosis, Abs recognize heparin and PF4 these bind together initiating thrombosis even in thrombocytopenic states; LMWH is better but still can cause HIT

454
Q

What is HIV associated thrombocytopenia?

A

most common hematologic manifestations of HIV infections, CD4 and CXCR4 are found on megakaryocytes allowing for their infections by the virus; B cell hyperplasia can lead to auto-Abs against IIb-IIIa on platelets

455
Q

What are TTP an HUS grouped as?

A

thrombotic microangiopathies; leads to excessive activation of platelets and deposit thrombi in small vessels

456
Q

What is the pentad of TTP?

A

fever, thrombocytopenia, MAHA, neuro deficits and renal failure

457
Q

What is the triad of HUS?

A

thrombocytopenia, MAHA, and AKI, commonly in children

458
Q

What are the albs in TTP/HUS?

A

PT, PTT are normal, unlike DIC

459
Q

What are the types of HUS?

A

typical: EHEC;
atypical: autoantibodies or complement deficiency
miscellaneous: drugs, radiation, infections, autoimmune diseases

460
Q

What is the mutation in TTP?

A

ADAMTS13 which normally degrads vWF; without it the factors aggregate causing platelet usage and clots

461
Q

How is TTP treated?

A

plasmaphoresis to remove the Abs

462
Q

What is seen in Bernard-Soulier syndrome?

A

deficiency in Ib-IX(GP-Ib) which binds platelets to vWF on subendothelial ECM

463
Q

What is seen in Glanzmann thrombathenia?

A

deficiency in IIb-IIIa which binds platelets to fibrinogen in response to ADP, collagen, epi or thrombin

464
Q

What are acquired defects of defective platelet bleeding?

A

aspirin/NSAIDs which inhibit COX and therefore thromboxane A2 and prostaglandins which are important for platelet aggregation;
uremia also causes plaetelet dysfunction

465
Q

What type of bleeding is see in inherited coagulopathy diatheses?

A

large posttraumatic hemorrhage or hematomas or prolonged bleeding; also into GI, joints and urinary tract

466
Q

What factors are related to Viatmin K deficiency?

A

II, VII, IX, X and Protein C

467
Q

What is the ristocetin test?

A

activates vWF to bind Gp-Ib and agglutinate; negative in BS syndrome and vWF disease but positive in GT

468
Q

What is the most common bleeding disorder in humans?

A

vWF disease

469
Q

What are they types of vWF disease?

A

type 1 and 3 are quantitative, although type 3 is AR and worse;
type 2 is qualitative and AD

470
Q

How is vWF disease treated?

A

desmopressin which releases stores of vWF or plasma infusions of factor VIII and vWF

471
Q

What is a common type of bleeding in hemophili A?

A

into joints and spontaneous bleeding

472
Q

What is deficienct in hemophilia A?

A

Factor VIII

473
Q

How is hemophilia A treated?

A

recombinant factor VIII or transfusion before this

474
Q

What is Hemohpilia B a deficit of?

A

factor IX(christmas disease)

475
Q

How is HB treated>

A

recombinant factor IX

476
Q

Waht is DIC?

A

acute, subacute or chronic thrombohemorrhagic disorder with excessive activation of coagulation and formation of thrombi in microvasculature

477
Q

What two major mechanisms trigger DIC?

A

release of TF into circulation and widespraed injury to endothelial cells

478
Q

What does TNF do in DIC?

A

inhibits thrombomodulin and increases TF expression;

upregulates adhesion molecules

479
Q

What most often predisposes to DIC?

A

neoplasms, pregnancy, trauma and sepsis

480
Q

What are he consequences of DIC?

A

widespread fibrin deposition and MAHA due to RBCs being shredded;
consumption of platelets and clotting factors leads to hemorrhagic diatheses

481
Q

What morphology is seen in DIC?

A

thrombi are most often found in brain, heart, lungs, kidneys, and liver; kidneys show bilateral renal cortical necrosis

482
Q

What two syndromes is DIC associated with?

A

waterhouse-friderichsen causing massiave adrenal hemorrhage and Kasabach-Merritt syndrome where thrombi form in giant hemangioma neoplasmsdue to stasis and trauma to blood vessels

483
Q

What do most people in DIC present with as cause?

A

50% obstetric(bleeding diatheses) and 33% with carcinoma(thrombic complications)

484
Q

How do DIC patients present?

A

MAHA due to fibrin clots, cyanosis, dyspnea, repsiratory/ circulatory failure and shock

485
Q

How is DIC diagnosis made?

A

laboratory studies and clinical observation

486
Q

What is a febrile nonhemolytic reaction after transfusion

A

feve and chills, mild dyspnea within 6 hours of platelets or pRBCs

487
Q

What allergic reactions are associated with transfusions?

A

certain antigens that the recipient is already sensitized to; commonly in pts with IgA deficiency when given IgA in transfusions; urticarial reactions occur when IgE recognizes an Ag in the transfused blood

488
Q

What causes acute hemolytic transfusion reactions?

A

preformed IgM abs against donor RBCs due to ABO incompatability; presents as fever, chills, shaking and flank pain rapidly due to complement formation; can progress to shock

489
Q

What is delayed hemolytic transfusion reaction?

A

caused by reaction to previously sensitized Ag through prior blood transfusion(Rh, Kell, Kidd)

490
Q

What is Transfusion related acute lung injury?

A

TRALI is severe and frequently fatal where blood products trigger activation of neutrophils in the lung microvasculature; occurs more often in those with lung issues

491
Q

What causes TRALI with the “two hit” hypothesis?

A

sequestration of neutrophils in the lungs and then the trasnfusion products activate the cells: Abs to MHC class I ags

492
Q

How does TRALI present?

A

acute respiratory failure during or soon after transfusion, b/l pulmonary infiltrates; fever, hypoxemia, hypotension

493
Q

What infectious events can occur with transfusion?

A

viral exposure like HIV or Hep B/C or simple bacterial infections from skin puncture

Heme/Lymph (2 decks)

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