Hematology Path Flashcards

Question

What is the function of monocytes? What do they look like?

Answer 1

1. Leukemoid reaction – marked granulocytosis and left shift, resembling chronic myeloid leukemia (CML) 2. Reactive morphology (toxic granulation and Döhle bodies are seen) 3. To rule out CML we have to genetically look for Philedelphia chromosome

Answer 2

Defined by left shift and circulating nucleated red blood cells (remember that the only RBCs in circulation are reticulocytes and mature RBCs, both lack a nucleus). This signifies: 1. Bone marrow fibrosis 2. Bone marrow infiltration - can be infectious or neoplastic

Answer 3

Anti parasitic function, allergic reactions and chronic inflammation. Granules contain 1. Peroxidase 2. Major basic protein 3. Eosinophilic cationic protein 4. Eosinophil derived neurotoxin Last 3 are cytotoxic for helminths and protozoas

Answer 4

Neutropenia is defined as absolute neutrophils count (ANC) of less than 1800/microliters. Agranulocytosis is defined as ANC less than 500. It can be due inadequate production or ineffective production: 1. Suppression of hematopoietic stem cells - Aplastic anemia, radiation 2. Suppression of committed granulocytic precursors 1. Drugs 1. Dose dependent –alkylating agents, antimetabolites. **This is often reversible.** 2. Idiosyncratic –chloramphenicol, aminopyrine, sulfonamides, chlorpromazine, phenylbutazone, thiouracil. **This is often non reversible.** 2. Large granular lymphocyte leukemia 3. Congenital 4. Ineffective hematopoiesis - Megaloblastic anemia, myelodysplastic syndromes Or it can be due to increased destruction: 1. Immune mediated - idiopathic, drug-induced. 2. Splenic sequestration 3. Increased margination

Answer 5

Absolute neutrophil count (ANC) \>7000/μL Increased granulopoiesis: 1. Infections –primarily bacterial Immunological inflammatory 2. Neoplasia Myeloproliferative neoplasms Paraneoplastic 3. Drugs –colony stimulating factors Increased release from marrow stores 1. Endotoxemia 2. Infection 3. Hypoxia 4. Decreased margination 1. Exercise 2. Catecholamines 5. Decreased extravasation into tissues 1. Glucocorticoids

Answer 6

1. Follicular hyperplasia 2. Paracortical (interfollicular) hyperplasia 3. Sinus histiocytosis 4. Mixed pattern of hyperplasia

Answer 7

We see a mixed pattern of hyperplasia, there is marked follicular hyperplasia, epitheloid granulomas and sinusoidal dilation with monocytoid B cells. Epitheloid granulomas consists of small and large histiocytic aggregates with germinal centers and interfollicular areas.

Answer 8

* Allergic disorders * Parasitic infections * Malignant neoplasms * Drugs (IL-2) * Collagen vascular disorders

Answer 9

* Neoplasms - CML * Allergic disorders * Inflammation * Endocrine disorders

Answer 10

* Chronic infections * Inflammation * Collagen vascular disorders * Neoplasms * Inflammatory bowel disease

Answer 11

Absolute lymphocyte count \> 4000/μL (adults) or \> 7000/µL (children) or \> 9000/µL (infants)

Answer 12

Aka Downey cells, these are seen in viral infections such as EBV. They have a characteristic appearence. Atypical lymphocytes are clinically seen in a variety of viral illnesses but as far as STEP is concerned it is only associated with EBV.

Answer 13

Blast cells has a much higher nucelus to cytoplasm ratio as shown.

Answer 14

1. Viral infections 2. Acute bacterial infection - only with whooping cough 3. Chronic bacterial infections - only with TB and brucellosis 4. Lymphoproliferative diseases

Answer 15

Increased number of and larger size of secondary follicles * Infection Systemic inflammatory disorders * Rheumatoid arthritis * Drug reaction * AIDS * Differential diagnosis includes follicular lymphoma

Answer 16

BCL2 gene is overexpressed in follicular lymphoma, making the B cells non apoptotic, we can stain for this protein to differentiate between the 2

Answer 17

Aka interfollicular hyperplasia, expansion of paracortex by a heterogeneous reactive cell population * Viral infection –CMV, EBV, measles, varicella * Immunologic disorders * SLE * Drug reaction

Answer 18

Increase in macrophages in sinuses In lymph nodes during infection, cancer Sinus histiocytosis is associated with massive lymphadenopathy

Answer 19

Absolute lymphocyte count \< 1500/μL (adults) or \< 3000/µL (children) Usually due to decrease in CD4+ helper T-cells

Answer 20

1. Decreased production 1. Congenital and acquired immunodeficiency syndromes 2. Hodgkin lymphoma 2. Increased destruction 1. Radiation, chemotherapy 2. Antilymphocyte globulin 3. Steroids, ACTH 4. AIDS 3. Increased loss of lymphocytes 1. Damage to lymphatics and loss of lymph –protein losing enteropathy, Whipple disease, increased central venous pressure

Answer 21

1. Chronic Lymphocytic Leukemia = Small Lymphocytic Lymphoma 2. Acute Lymphoblastic Leukemia = Lymphoblastic Lymphoma

Answer 22

1. Most frequently occurs in children; less common in adults (worse prognosis). 2. T-cell ALL can present as mediastinal mass (presenting as Superior Vena Cava-like syndrome). 3. Associated with Down syndrome. 4. Peripheral blood and bone marrow have increased lymphoblasts. 5. TdT+ (marker of pre-T and pre-B cells), CD10+ (marker of pre-B cells). 6. Most responsive to therapy. 7. May spread to CNS and testes. 8. t(12;21) = better prognosis.

Answer 23

ALL - Most common malignancy of childhood but incidence also increases after 50 y. Etiologic associations * Ionizing radiation * Immunodeficiency states * Trisomy 21 (**L**ater than the age of 5...**L** for A**LL**)

Answer 24

B cell precursors cause ALL by far majority than T cell precursors.

Answer 25

* Anemia * Weakness * Fatigue * Pallor * Fever * Bone pain * Thrombocytopenia - Bleeding * Hepatosplenomegaly * Lymphadenopathy In peripheral smaer we see leukoblastocytosis with blasts or normal WBCs with blasts and bone marrow is hypercellular with sheets of blast cells.

Answer 26

Precursor B-ALL (85%) * **CD10+, CD19+, TdT+, sIg-** Precursor T-ALL (15%) * **CD2+, CD3+, CD5+, CD7+, TdT+** * May co-express CD4 and CD8

Answer 27

ALL is rapidly fatal, if untreated. With chemotherapy, 95% remission rate and 75-85% cure rate if favorable prognostic features

Answer 28

Diffuse large B cell lymphoma and Follicular lymphoma

Answer 29

CLL or SLL

Answer 30

1. Accumulation of **naive B cell**, CLL is mainly in the bone marrow whereas SLL is confined to lymph nodes. 2. Age: \> 60 years. 3. Most common adult leukemia. 4. CD20+, CD5+ B-cell neoplasm. 5. Often asymptomatic, progresses slowly 6. Smudge cells B in peripheral blood smear 7. Complications of SLL/CLL are 1. Autoimmune hemolytic anemia. 2. **Richter transformation**—SLL/CLL transformation into an aggressive lymphoma, most commonly diffuse large B-cell lymphoma (DLBCL). 3. Hypogammaglobulinemia, leading to immunosuppressive state

Answer 31

1. Assymptomatic 2. Anemia 3. Thrombocytopenia 4. Lymphadenopathy 5. Immunologic abnormalities - autoimmune hemolytic anemia, thrombocytopenia, hypogammaglobulinemia.

Answer 32

1. Lymphocytosis - we see smudge cells on peripheral smear 2. In lymph nodes we see **diffuse infiltrate of small round lymphocytes.**

Answer 33

CD19+, **CD20+, CD5+**, CD10-, sIg+ (clonal)

Answer 34

About half of the SLL/CLL cases involve Ig gene rearrangment but no somatic hypermutation in IgVH. Mutated CLL/SLL has Ig gene rearrangment with somatic hypermutation. Other chromosomal abnormalities may involve 13q deletion.

Answer 35

1. Median survival 6 y 1. Worse for U-CLL/SLL (3 y) than for M-CLL/SLL (\>7 y) 2. Prolymphocytic transformation –15-30% 1. \>10% prolymphocytes 2. Increased splenomegaly 3. Mean survival \<2 y 3. Richter transformation –5-10% 1. Large cell lymphoma 2. Increased lymphadenopathy 3. Mean survival \<1 y

Answer 36

1. Age: Adult males. 2. Mature B-cell tumor. Cells have lamentous, hair-like projections. 3. Causes marrow fibrosis, dry tap on aspiration. 4. Patients usually present with massive splenomegaly. 5. Stains TRAP (tartrate-resistant acid phosphatase) ⊕. TRAP stain largely replaced with flow cytometry. 6. Treatment: cladribine, pentostatin.

Answer 37

Hairy Cell Leukemia Clinical Features * Initially asymptomatic * Splenomegaly - May be massive * Hepatomegaly * Pancytopenia * Infections * Indolent course

Answer 38

1. We see 'hairy cells' - lymphocytes with villous cytoplasmic projections. 2. Absolute monocytopenia 3. Bone marrow shows increased reticulin fibrosis 4. Spleen has enlarged red pulp. On immunophenotyping we see **CD11c+. CD25+, CD103+** and **Annexin A1.** Cytochemistry: Tartrate resistant acid phsophatase Genetics - BRAF mutation.

Answer 39

**Mantle zone is markedly diminished or absent.** Genetics - t(14;18), overexpression of BCL2 protein prevents apoptosis Immunophenotyping - CD19+, CD20+, **CD10+, CD5-, sIg+** (clonal)

Answer 40

1. Very common lymphoma in US 2. Middle aged to older adults 3. t(14;18)—translocation of heavy-chain Ig (14) and BCL-2 (18). BCL2 inhibits apoptosis 4. Hepatosplenomegaly 5. Indolent, chronic course –median survival 7-9 y 6. **Presents with painless “waxing and waning” lymphadenopathy** 7. Follicular architecture: small cleaved cells (grade 1), large cells (grade 3), or mixture (grade 2).

Answer 41

1. Usually older adults, but 20% in children 2. Lymphadenopathy and hepatosplenomegaly are observed. 3. Some cases are associated with HHV8 and EBV, although Sketchy specifically said HIV can directly cause diffuse B cell lymphoma. 4. In lymph nodes we see diffuse infiltrate of large, non cleaved lymphocytes. 5. Alterations in BCL2 and BCL6

Answer 42

Diffuse Large B cell Lymphoma, it is the most common non Hodgekin lymphoma in the US

Answer 43

Aberrant proliferation of plasma cells, diseases like multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS) are examples plasma cell neoplasms. Important to know MGUS can develop into MM.

Answer 44

Important to know that death by MM is primarily due to infection or renal involvement.

Answer 45

1. Endemic form of Burkitt lymphoma is in Africa, \>95% is associated with EBV in, presents as jaw lesions 2. Sporadic BL is in the US that involves children and adults, only 20% associated with EBV, this does not present as jaw lesion but instead can have extranodal sites in the abdomen/pelvis. 3. HIV associated BL, 25% associated with EBV.

Answer 46

1. Very aggressive, patients typically present with late-stage disease. 2. Adult males 3. t(11;14)—translocation of cyclin D1 (11) and heavy-chain Ig (14) 4. CD19+, CD20+, **CD10-, CD5+. sIg+** and **Cyclin D1+**

Answer 47

1. Rapidly progressive tumor mass but higher cure rates with aggressive chemotherapy, 90% cure rate in children. 2. Tumor lysis syndrome is common when treatment is initiated 3. “Starry sky” appearance, sheets of lymphocytes with interspersed “tingible body” macrophages 4. t(8;14)—translocation of c-myc (8) and heavy-chain Ig (14) 5. In lymph nodes we see diffuse infilterate of medium-sized, non cleaved lymphocytes 6. CD19+, CD20+, **CD10+, CD5-, sIg+ and TdT-**

Answer 48

1. Can be along anywhere in the GI tract, lung, head & neck, eye, skin. 2. Association with chronic infection (e.g. H. pylori ) and autoimmune disorders (e.g. Hashimoto thyroiditis, Sjögren syndrome) 3. Usually early stage, rarely involves the bone marrow 4. Expanded marginal zone is observed, lymphoepithelial lesions are seen. 5. **t(11:18)**

Answer 49

1. Mycosis fungoides aka CTCL presents with skin patches/plaques, characterized by atypical CD4+ cells with “cerebriform” nuclei. 2. May progress to Sézary syndrome which is lekemia phase of CTCL (T-cell leukemia). 3. Associated with epidermotropism and Pautrier microabscesses. 4. Sezary syndrome causes erythroderma.

Answer 50

1. Caused by HTLV (associated with IV drug abuse) 2. Adults present with cutaneous lesions; especially affects populations in Japan, West Africa, and the Caribbean. 3. Lytic bone lesions, hypercalcemia. 4. Generalized lymphadenopathy with skin lesions 5. Hepatosplenomegaly

Answer 51

1. Consists of large anaplstic cells positive for **CD30+** 2. t(2;5) - rearrangement of ALK gene, this happens in children and younger adults, associated with good prognosis 3. No ALK rearrangement Anaplastic Large B cell lymhoma happens in older adults, associated with poor prognosis

Answer 52

1. Proliferation of mature T-cells 2. Generalized lymphadenopathy 3. Fever, pruritus, weight loss 4. Eosinophilia 5. Generally poor prognosis. 6. Lymph nodes 1. Architectural effacement 2. Vascular proliferation 7. Immunophenotype CD2+, CD5+, CD3+, TCR-αβ or γδ 8. Genetics T-cell receptor gene rearrangement

Answer 53

1. Lymphadenopathy, splenomegaly 2. Constitutional (“B”) symptoms –fever, night sweats, weight loss 3. Immune dysfunction 4. Prognosis –excellent at early stage (90% cure rate) 5. Risk of second malignancy in long-term survivors 1. Myelodysplastic syndromes and acute myeloid leukemia 2. Lung cancer, breast cancer, gastric cancer, sarcoma, melanoma

Answer 54

Classical Hodgekin lymphoma and Nodular lymphocyte predominance Hodgekin lymphoma

Answer 55

Reed Sternberg cells + polymorphous cellular background. Important to know that Reed Sternberg cells are **CD15+** and **CD30+** and they are negative for most B and T cell markers. Genetics: 1. Reed-Sternberg cells arise from germinal center B- cells 2. NF-κB activation 3. Transformed cells escape from apoptotic pathways to proliferate 4. Ig gene rearrangements in most cases 5. No detectable Ig due to 1. “Crippled” rearrangements 2. Upstream mutations 3. Transcriptional inactivation

Answer 56

* Nodular sclerosis * Broad bands of fibrous tissue * **A special type of reed sternberg cells called lacunar cells are seen** * Mixed cellularity - Numerous Reed-Sternberg cells in a mixed cellular background * Lymphocyte depletion * Rare classic Reed-Sternberg cells * Scant lymphocytes * Lymphocyte rich –rare

Answer 57

Anisocytosis = varying sizes. Poikilocytosis = varying shapes. Anisopoikilocytosis = variation in size and shape.

Answer 58

Red Cell Distribution Width, it is a measure of the variation in size of RBCs. Congenital anemias for example have low RDW (they are more consistent in size) whereas acquired anemias such as iron deficiency anemias have high RDWs.

Answer 59

Immature RBCs that are released from the bone marrow that eventually mature to form functioning RBCs, they survive in the circulation for 1 day. In case of increase hematopoiesis the number of reticulocytes increases dramatically which can be seen on peripheral blood smear, this corresponds to an increase in EPO.

Answer 60

Polychromatophilic erythrocytes.

Answer 61

1. Pallor of skin, nail beds, buccal mucosa 2. Fatigue, weakness, malaise 3. Dyspnea on exertion 4. Syncope, headache, visual disturbances 5. Tachycardia 6. Angina 7. Cardiac failure

Answer 62

It is due to either inadequate or ineffective production (aka ineffecitve hematopoiesis). 1. Bone marrow failure due to 1. Aplastic anemia 2. Pure red cell aplasia 3. Iatrogenic 2. Bone marrow infiltration/replacement (myelophthisis) 3. Nutritional deficiency 1. Iron deficiency (microcytic) 2. Megaloblastic anemia (macrocytic) 4. Anemia of chronic disease (microcytic) 5. Myelodysplastic syndromes (macrocytic)

Answer 63

Aplastic anemia

Answer 64

Caused by failure or destruction of myeloid stem cells due to: 1. Radiation and drugs (benzene, chloramphenicol, alkylating agents, antimetabolites) 2. Viral agents (parvovirus B19, EBV, HIV, hepatitis viruses) 3. Fanconi anemia (DNA repair defect causing bone marrow failure); also short stature, incidence of tumors/leukemia, café-au-lait spots, thumb/radial defects 4. Telomerase defects, acquired stem cell defects, potential for acquiring further mutations and tranforming into AML 5. Idiopathic (immune mediated, 1° stem cell defect); may follow acute hepatitis Findings: 1. Decrease in reticulocyte count, **there are high levels of EPO**. 2. Pancytopenia characterized by severe anemia, leukopenia, and thrombocytopenia. Normal cell morphology, but hypocellular bone marrow with fatty infiltration (dry bone marrow tap). Symptoms: fatigue, malaise, pallor, purpura, mucosal bleeding, petechiae, infection. Treatment: withdrawal of offending agent, immunosuppressive regimens (eg, antithymocyte globulin, cyclosporine), bone marrow allograft, RBC/platelet transfusion, bone marrow stimulation (eg, GM-CSF).

Answer 65

Parvovirus inclusion bodies.

Answer 66

1. Disorder of erythroid progenitor cell causing decreased erythropoiesis 2. Incidence –very rare 3. Clinical features: Anemia – pallor, weakness, fatigue Pathogenesis and etiology 1. **Highly associated with Thymoma (paraneoplastic syndrome)** 2. Viral infections (parvovirus B19) 3. Drugs 4. Autoimmune disorders Pathology: 1. Normochromic, normocytic anemia, no poikilocytes 2. There are markedly decreased erythroid precursors in the bone marrow 3. Intranuclear inclusions in erythroblasts in parvovirus B19 infection Treatment: androgens, plasmapheresis, thymectomy, supportive - transfusions.

Answer 67

Decreased erythropoiesis due to bone marrow infiltration or replacement Clinical features 1. Anemia –pallor, weakness, fatigue 2. Features of underlying disease Pathogenesis and etiology 1. Metastatic cancer 2. Fibrosis (primary myelofibrosis or following treatment) 3. Hematopoietic neoplasms Pathology 1. Normochromic, normocytic anemia 2. Teardrop shaped erythrocytes (poikilocytes) 3. Circulating nucleated red blood cells 4. Granulocytic left shift (leukoerythroblastosis) 5. Replacement of normal bone marrow elements is seen on H&E

Answer 68

1. Daily intake – 10-20 mg, poorly absorbed in duodenum (10- 15%) 2. Daily loss – 1-2 mg 3. Total body iron – 6 g (♂); 2.5 g (♀) 4. Functional – Hgb, myoglobin, enzymes 5. Storage – ferritin, hemosiderin 6. There is constant recycling 7. **Hepcidin** inhibits iron uptake from enterocytes to serum 1. Inappropriately low in hereditary hemochromatosis 2. Inappropriately high in anemia of chronic disease

Answer 69

Iron deficiency anemia

Answer 70

Clinical features 1. Pallor, fatigue, weakness 2. Pica 3. Atrophic glossitis, angular stomatitis, koilonychia 4. **Plummer-Vinson syndrome** (Paterson-Brown-Kelly syndrome) that consist of 1. Iron deficiency anemia 2. Atrophic glossitis 3. Esophageal webs Pathology 1. Hypochromic, microcytic anemia 2. Anisocytosis 3. No increase in reticulocytes 4. Decreased serum iron 5. Decreased ferritin 6. Increased transferrin and soluble transferrin receptor 7. Absent storage iron in bone marrow

Answer 71

1. Infammation -\> increase in hepcidin due to inflammatory mediators such as IL-6 (released by liver, binds ferroportin on intestinal mucosal cells and macrophages, thus inhibiting iron transport) -\> decreases release of iron from macrophages and iron absorption from gut. 2. Associated with conditions such as rheumatoid arthritis, SLE, neoplastic disorders, and chronic kidney disease. 3. Decreased iron, decreased TIBC, **increased ferritin (this is what differentiates it from iron deficiency anemia)**. 4. Normocytic, but can become microcytic. 5. Treatment: EPO (chronic kidney disease only).

Answer 72

1. Its associated findings are hypersegmented neutrophils and macrocytic RBCs 2. Folate is required for DNA synthesis to transfer one carbon groups for purine synthesis, impaired DNA synthesis leads to delayed maturation of nuclei of precursor cells in bone marrow relative to maturation of cytoplasm.

Answer 73

1. Hepatocorrin is released in the saliva which binds to vitamin B12 initially. 2. Intrinsic factor is released in the stomach by parietal cells, B12 dissociates from heptocorrin in the duodenum in the presence of proteases and eventially binds to intrinsic factor. 3. B12 bound to intrinsic factor is eventually absorbed in the gut by ileal cells.

Answer 74

Folate deficiency: 1. Causes include malnutrition (eg, alcoholics), malabsorption, drugs (eg, methotrexate, trimethoprim, phenytoin), increased requirement (eg, hemolytic anemia, pregnancy). 2. Increased homocysteine, **normal methylmalonic acid**. No neurologic symptoms (vs **B₁₂ deficiency**).

Answer 75

Periventricular white matter degeneration in the brain and posterior column degeneration in the spinal cord

Answer 76

Vitamin B12 deficiency (Cobalamin): Causes: insuficient intake (eg, veganism), malabsorption (eg, Crohn disease), pernicious anemia, Diphyllobothrium latum (fish tapeworm), gastrectomy. Findings: 1. Increased homocysteine, increased methylmalonic acid. 2. **Neurologic symptoms**: subacute combined degeneration (due to involvement of B12 in fatty acid pathways and myelin synthesis, deficiency leads to demyelination): spinocerebellar tract, lateral corticospinal tract, dorsal column dysfunction. 3. Historically diagnosed with the **Schilling test,** a 4-stage test that determines if the cause is dietary insufficiency vs malabsorption.

Answer 77

Chronic atrophic gastritis due to autoantibodies against parietal cells. This leads to megaloblastic anemia.

Answer 78

1. Acute blood loss 2. Hypovolemic shock 3. No immediate change in hemoglobin level 4. Slow fluid shift from interstitial space to intravascular space leads to low hemoglobin 5. Normochromic, normocytic anemia 6. Reactive leukocytosis and thrombocytosis may occur

Answer 79

Intrinsic anemia refers to the cause of anemia lies within RBC - hemoglobin, enzyme deficiency, membrane defect etc. Extrinsic anemia refers to external factors like antibodies, trauma.

Answer 80

Main thing to note: in extravascular hemolysis, the RBCs are being destroyed outside of the blood vessels, so there will be no Hb in the blood or urine.

Answer 81

Clinical features –depend on etiology, severity, and course 1. Anemia (usually normochromic, normocytic) 2. Extramedullary hematopoiesis 3. Jaundice 4. Splenomegaly –if extravascular and persistent 5. Gallstones 6. Hemosiderosis

Answer 82

Hemoglobinopathy: * Structurally abnormal hemoglobin due to mutation in α or β globin gene * Sickle cell disease Thalassemia: * Decreased production of α or βglobin chains due to mutations * α-thalassemia * β-thalassemia

Answer 83

1. HbS point mutation (SNP), causing a single amino acid replacement in β chain (**substitution of glutamic acid with valine**). 2. Causes extravascular and intravascular hemolysis. 3. Pathogenesis: _low O2, high altitude, or acidosis_ precipitates sickling (**deoxygenated HbS polymerizes**) leads to anemia and vaso-occlusive disease. 4. Newborns are initially asymptomatic because of **increase HbF** and decrease in HbS. 5. Heterozygotes (sickle cell trait) also have resistance to malaria. 6. 8% of African Americans carry an HbS allele. Sickle cells are crescent-shaped RBCs A . 7. “**Crew cut**” on skull x-ray due to **marrow expansion from erythropoiesis** (also seen in thalassemias) 8. Coexistence of **HbA, HbF prevents sickling** 9. Coexistence of **HbC allows sickling**

Answer 84

Complications in sickle cell disease: 1. Aplastic crisis (due to parvovirus B19). 2. Autosplenectomy (Howell-Jolly bodies), increased risk of infection by encapsulated organisms (eg, S pneumoniae). 3. Splenic infarct/sequestration crisis. 4. Salmonella osteomyelitis. 5. Painful crises (vaso-occlusive): Dactylitis (painful swelling of hands/feet), priapism, acute chest syndrome, avascular necrosis, stroke. 6. Renal papillary necrosis (decreased PO₂ in papilla) and microhematuria (medullary infarcts).

Answer 85

Via hemaglobin electrophoresis.

Answer 86

Blood transfusion Hydroxyurea, leads to increased HbF, hydration also helps. Hematopoietic stem cell transplant is potentially curative

Answer 87

Point mutations in splice sites and promoter sequences , leads to decreased β-globin synthesis. Prevalent in Mediterranean populations. β thalassemia minor (heterozygote): 1. β chain is underproduced. 2. Usually asymptomatic. 3. Diagnosis confirmed by increased HbA₂ (\> 3.5%) on electrophoresis. β thalassemia major (homozygote): 1. β chain is absent leads to severe microcytic, hypochromic anemia with target cells and increased anisopoikilocytosis requiring blood transfusion. (2° hemochromatosis). 2. Marrow expansion (“crew cut” on skull x-ray)skeletal deformities. 3. “Chipmunk” facies. 4. Extramedullary hematopoiesis leading to hepatosplenomegaly. 5. Risk of parvovirus B19–induced aplastic crisis. 6. Increased HbF (α2γ2). HbF is protective in the infant and disease becomes symptomatic only after 6 months, when fetal hemoglobin declines. 7. HbS/β thalassemia heterozygote: mild to moderate sickle cell disease depending on amount of β-globin production.

Answer 88

Crew cut sign, in this case it is due to beta thalessemia.

Answer 89

Crew cut sign is observed in X ray due to expansion of facial and cranial bones due to increased hematopoiesis in sickle cell disease and thalessemia.

Answer 90

1. Defect: α-globin gene **deletions**, leads to decreased α-globin synthesis. 2. cis deletion (both deletions occur on same chromosome) prevalent in Asian populations; trans deletion (deletions occur on separate chromosomes) prevalent in African populations. 3. 4 allele deletion: No α-globin. Excess γ-globin forms γ4 (Hb Barts). Incompatible with life (causes hydrops fetalis). 4. 3 allele deletion: inheritance of chromosome with cis deletion + a chromosome with 1 allele deleted leads to **HbH disease**. Very little α-globin. Excess β-globin forms β4 (HbH). 5. 2 allele deletion: less clinically severe anemia. 6. 1 allele deletion: no anemia (clinically silent).

Answer 91

1. An imbalance of Hb chains leads to apoptosis of RBCs and its precursors in bone marrow so there is decreased hematopoiesis. 2. There is also increased destruction of RBCs in spleen leading to extravascular hemolysis.

Answer 92

1. Hypochromic microcytic anemia 2. Target cells 3. Variable reticulocyte count 4. HbH disease (3-gene deletion) - Elevated HbH (β 4 ) 5. HbBarts disease (4-gene deletion) 1. Elevated HbBarts (γ 4 ) 2. Severe anemia 3. Intrauterine death (hydrops fetalis) without intrauterine transfusions

Answer 93

Heinz bodies and bite cells, seen in G6PD deficiency

Answer 94

1. **Autosomal dominant** 2. Extravascular hemolysis due to defect in **ankyrin**, band 3, protein 4.2, **spectrin**). 3. Loss of biconcave shape (spherocytes) and an increase in membrane rigidity. 4. Results in small, round RBCs with less surface area and no central pallor (**increased MCHC**), this leads to premature removal by spleen. 5. Splenomegaly, aplastic crisis (parvovirus B19 infection). 6. Labs: **osmotic fragility test ⊕.** Normal to decreased MCV with abundance of cells. 7. Treatment: splenectomy.

Answer 95

1. Blood transfusion with iron chelation to avoid development of secondary hemachromatosis. 2. Bone marrow transplant is potentially curative.

Answer 96

1. **X-linked recessive.**. 2. Causes extravascular and intravascular hemolysis. 3. Defect in G6PD, leads a decrease in NADPH production and subsequently a decrease in ability to reduce glutathione. There is an increase in RBC susceptibility to oxidant stress. 4. Hemolytic anemia follows oxidant stress (eg, sulfa drugs, antimalarials, infections, **fava** **beans**). 5. Back pain, hemoglobinuria a few days after oxidant stress. 6. Labs: blood smear shows RBCs with **Heinz bodies (denatured Hemoglobin)** and **bite cells**.

Answer 97

1. Variable anemia 2. Spherocytosis 3. Increased MCHC 4. Splenomegaly 5. Gallstones 6. Negative direct antiglobulin (Coombs) test

Answer 98

1. Complement-mediated intravascular RBC lysis (impaired synthesis of GPI (phosphotidylinositol glycan complementation group A) anchor for decay-accelerating factor that protects RBC membrane from complement). 2. Acquired mutation in a hematopoietic stem cell. 3. Increased incidence of acute leukemias. 4. Triad: Coombs ⊝ hemolytic anemia, pancytopenia, and venous thrombosis. 5. Labs: CD55/59 ⊝ RBCs on flow cytometry. 6. Treatment: **eculizumab** (terminal complement inhibitor).

Answer 99

CD 55 = decay accelerating factor CD59 = C3 convertase inhibitor

Answer 100

Clinical features 1. Anemia 2. Hematuria –typical nocturnal hematuria in 25% of cases 3. Venous thrombosis 4. Transformation to acute myeloid leukemia Pathology 1. Normochromic normocytic anemia 2. Positive urinary hemoglobin and hemosiderin I 3. Iron deficiency 4. Flow cytometric evidence of deficiency of CD55 and CD59 on RBCs and leukocytes

Answer 101

It blocks the conversion of C5 to C5a

Answer 102

Hematopoietic stem cell transplant.

Answer 103

Direct Coombs test—anti-Ig antibody (Coombs reagent) added to patient’s blood. RBCs agglutinate if RBCs are coated with Ig. Indirect Coombs test—normal RBCs added to patient’s serum. If serum has anti-RBC surface Ig, RBCs agglutinate when Coombs reagent added.

Answer 104

1. Warm (Ig**G**)—chronic anemia seen in SLE and CLL and with certain drugs (eg, α-methyldopa) (“**w**arm weather is **G**reat”). 2. Cold (Ig**M** and complement)—acute 3. anemia triggered by cold; seen in CLL, **M**ycoplasma pneumonia infections, and infectious **M**ononucleosis (“cold weather is **MMM**iserable”). 4. RBC agglutinates, may cause painful, blue fingers and toes with cold exposure. 5. Many warm and cold AIHAs are idiopathic in etiology. 6. Autoimmune hemolytic anemias are Coombs test +ve.

Answer 105

We see spherocytes in warm AHA, as opposed to cold AHA where we just see agglutinated RBCs. RBCs agglutinate due to pentavalent nature of IgM in cold AHA.

Answer 106

Splenectomy, steroids and rituximab.

Answer 107

Traumatic hemolytic anemia

Answer 108

Paroxysmal Cold Hemoglobinuria 1. IgG antibodies against RBC membrane P blood group antigen (Donath-Landsteiner antibody) 2. Intravascular, extrinsic, acquired Pathogenesis 1. Antibodies bind below 37C in extremities 2. IgG coated RBCs fix complement at 37C in central circulation 3. Complement coated RBCs lyse in circulation (massive intravascular hemolysis) 4. Clearance of hemoglobin in urine (hemoglobinuria) Clinical features * Episodic anemia and hemoglobinuria following cold exposure * Hemolysis only when incubation at 4 C followed by incubation at 37 C

Answer 109

Traumatic Hemolytic Anemia 1. RBC destruction by trauma 2. Intravascular, extrinsic, acquired 3. Etiology and pathogenesis 1. Macroangiopathic –in large vessels Mechanical heart valves 2. Microangiopathic –in small capillaries 1. Disseminated intravascular coagulation 2. Thrombotic thrombocytopenic purpura 3. Hemolytic uremic syndrome An important lab finding here is the presence of schistocytes.

Answer 110

Leads to hyperviscosity syndrome which can cause visual dysfunction such as blurred vision and neurological deficits such as headache, dizziness, deafness, stupor. It can physiologic such as due to lung disease, heart disease, high altitude or it can pathologic such as due to local kidney hypoxia or EPO secreting tumors.

Answer 111

1. Purpura : bleeding within skin or mucous membranes 2. Petechia : pin point bleeding of skin or mucous membranes (a type of purpura) 3. Ecchymosis : large confluent area of bleeding within skin, larger than petechiae (a type of purpura) 4. Hematoma : a collection of blood in an organ, space, or tissue 5. Hemarthrosis : bleeding into the joint space

Answer 112

Petechia are seen in vascular and platelet disorders whereas hematoma/hemarthrosis are seen in coagulation disorder

Answer 113

1. **Autosomal dominant** 2. Aka **Osler-Weber-Rendu syndrome.** 3. Inherited disorder of blood vessels, weak venules lead to recurrent bleeding. 4. Caused by mutation in **endoglin gene** or a**ctivin- receptor-like kinase 1 gene** 5. Thickened smooth muscle layer and absent elastin fibers in venule wall 6. Findings: branching skin lesions (telangiectasias), recurrent epistaxis, skin discolorations, arteriovenous malformations (AVMs), GI bleeding, hematuria.

Answer 114

Henoch-Schonlein Purpura 1. Most common childhood systemic vasculitis. 2. Acquired disorder, often follows URI, viral infection or drugs. 3. Classic triad: 1. Skin: palpable purpura on buttocks/legs 2. Arthralgias 3. GI: abdominal pain 4. Vasculitis 2° to IgA immune complex deposition. 5. Associated with IgA nephropathy (Berger disease). 6. Fibrinoid necrosis of vessel walls.

Answer 115

1. Anti-Gp2b-3a antibodies, leads to splenic macrophage consumption of platelet-antibody complex. 2. Commonly due to viral illness. Can also be due to SLE or lymphoma 3. Excessive bleeding, skin, muscosa, there can be even intracranial bleeding. 4. Increased megakaryocytes on bone marrow biopsy. 5. Treatment: steroids, IVIG, Rituximab, splenectomy (for refractory ITP).

Answer 116

1. Inhibition or deficiency of ADAMTS 13 (vWF metalloprotease), leads to decrease in degradation of vWF multimers. 2. Pathogenesis: increased large vWF multimers platelet, leads to increased platelet adhesion, aggregation and thrombosis. 3. Labs: 1. Schistocytes, 2. Increased serum LDH 3. Hyaline microthrombi are seen within the arterioles and capillaries (this is the cause of renal failure in this disease) 4. Classic pentad: 1. Micrangiopathic hemolytic anemia 2. Thrombocytopenia 3. Fever 4. Neurologic deficits 5. Renal failure 5. Treatment: plasmapheresis, Rituximab, steroids.

Answer 117

Qualitative Platelet Disorders –Inherited Platelet Receptor Defects Bernard-Soulier Syndrome 1. GP Ib/V/IX deficiency 2. Defective platelet adhesion 3. Diagnosed by platelet aggregation testing 4. No platelet aggregation response to ristocetin Glanzmann thrombasthenia 1. GP IIb/IIIa deficiency 2. Defective platelet aggregation 3. Diagnosed by platelet aggregation testing 4. No platelet aggregation response to epinephrine, ADP, collagen, arachidonic acid, thrombin 5. Normal platelet aggregation response to ristocetin

Answer 118

All of them result in an increase in bleeding time and a decrease in platelet count - thrombocytopenia

Answer 119

1. Characterized by thrombocytopenia, microangiopathic hemolytic anemia, and acute renal failure. 2. Typical HUS is seen in children, accompanied by diarrhea and commonly caused by Shiga toxin-producing E coli (STEC) (eg, O157:H7). 3. HUS in adults does not present with diarrhea; STEC infection not required. 4. Same spectrum as thrombotic thrombocytopenic purpura (TTP), with a similar clinical presentation and same initial treatment of plasmapheresis. 1. Hyaline mircothrombi 2. Schistocytosis 3. Elevated serum LDH 4. Thrombocytopenia 5. **NO neurologic symptoms!**

Answer 120

Qualitative Platelet Disorders –Inherited Platelet Granule Defects Alpha Storage Pool Disease 1. Deficiency of alpha granules (protein-rich) 2. Defective platelet aggregation 3. Bleeding is mild to moderate in severity 4. Diagnosed by electron microscopy Delta Storage Pool Disease 1. Decreased or defective delta granules (ADP-rich) 2. Defective platelet aggregation 3. Bleeding is mild to moderate in severity 4. Diagnosed by platelet aggregation testing

Answer 121

1. PT — tests function of common and extrinsic pathway (factors I, II, V, VII, and X). Defect leads to increased PT. 2. INR (international normalized ratio) — calculated from PT. 1 = normal, \> 1 = prolonged. Most common test used to follow patients on warfarin. 3. PTT—tests function of common and intrinsic pathway (all factors except VII and XIII). Defect leads to increased PTT.

Answer 122

1. Hemophilia is defined as intrinsic pathway coagulation defect. 1. A: deficiency of factor VIII ; X-linked recessive. 2. B: deficiency of factor IX; X-linked recessive. 3. C: deficiency of factor XI; autosomal recessive. 2. PTT is increased 3. Platelet count and bleeding time is normal in all hemophilia 4. Macrohemorrhage in hemophilia—hemarthroses (bleeding into joints, such as knee), easy bruising, bleeding after trauma or surgery (eg, dental procedures). 5. Treatment: desmopressin + factor VIII concentrate (A); factor IX concentrate (B); factor XI concentrate (C).

Answer 123

1. Severe (50%), moderate (10%) and mild (40%) 2. In severe there is spontaneous bleeding, mainly due to the development of FVIII inhibitor. 3. Moderate and mild only result from factor VIII deficiency, there is prolong bleeding only after trauma or surgery. 4. Hence blood transfusion will help mild and moderate hemophilia A but not severe. 5. Treatment for severe hemophilia A consists of recombinant FVIII and recombinant FVIIa

Answer 124

1. Intrinsic pathway coagulation defect: decreased vWF leads to increased PTT (vWF acts to carry/protect factor VIII). 2. Defect in platelet plug formation: decreased vWF leads to defect in platelet-to-vWF adhesion. 3. Autosomal dominant. 4. Petechiae are observed. 5. Mild but most common inherited bleeding disorder. 6. Platelet count is normal, bleeding time is increased, PT is normal, PTT is increased. 7. No platelet aggregation with ristocetin cofactor assay.

Answer 125

Factor XIII Deficiency 1. Rare autosomal recessive bleeding disorder 2. Causes defective fibrin cross-linking and an unstable fibrin clot 3. Manifested by bleeding and delayed wound healing 4. Normal PT, normal PTT, normal bleeding time 5. Abnormal urea solubility test (blood clot dissolves in urea, a denaturing agent)

Answer 126

Von Willebrand Disease -Treatment 1. Humate P (VWF concentrate) 2. Cryoprecipitate -good source of VWF 3. Desmopressin (anti-diuretic hormone) -stimulates endothelial cells to release remaining VWF stores

Answer 127

Acquired Factor VIII Inhibitor 1. Pathogenesis 1. Idiopathic (elderly) 2. Secondary (autoimmune disease: SLE, rheumatoid arthritis, postpartum, hemophilia A) 3. specificity against factor VIII 2. Clinical features - mild to severe bleeding, spontaneous resolution or chronic 3. PTT is increased, PT is normal 4. Treatment is immunosuppressive drugs, recombinant FVIIa

Answer 128

Defined as an acquired hemorrhagic and/or thrombotic disorder caused by excessive release of tissue factor into the blood, leading to over activation of the coagulation system and secondary fibrinolysis. 1. Pathogenesis 1. release of tissue factor into the blood 2. risk factors: bacterial sepsis, massive trauma, acute promyelocytic leukemia, carcinoma, placental abruption, retained dead fetus 3. excess thrombin and plasmin generation 4. clotting factor and platelet consumption 2. Clinical features 1. bleeding (venipuncture sites, etc.) 2. thrombosis (arterial and venous; brain, heart, lung, kidney, adrenal gland, spleen, liver, etc.) 3. syndromes (Waterhouse-Friderichsen, Kasabach-Merritt) 3. Pathologic features 1. hyaline microthrombi of microvessels 2. platelet and fibrin rich thrombi 3. thrombocytopenia 4. prolonged PT and/or PTT 5. decreased fibrinogen 6. elevated D-dimer 7. microangiopathic hemolysis (schistocytes on blood smear

Answer 129

Hypercoagulability Venous stasis Vessel damage

Answer 130

Major surgery/trauma and history of thrombosis

Answer 131

Unilateral leg pain, swelling and non specific symptoms Compression ultrasound can be done to confirm the diagnosis. Additionally venography of proximal leg veins can also be done.

Answer 132

Pulmonary Embolism Clinical Features 1. Dyspnea 2. Wheezing 3. Chest pain (pleuritic -infarction) 4. Hemoptysis (infarction with bleeding into airway) 5. Right sided heart failure; cor pulmonale (hypotension, syncope, coma) 6. Hypoxemia 7. These features are nonspecific; objective testing required for diagnosis Diagnostic testing may involve **spiral CT** that has a high positive predictive value and **D dimer test** that has a high negative predictive value. Additionally ventilation perfusion scan or pulmonary angiography can also be done.

Answer 133

1. Production of mutant factor V (G -\>A, DNA point mutation near the cleavage site, Arginine to Glutamine) that is resistant to degradation by activated protein C. 2. Most common cause of inherited hypercoagulability in Caucasians. 3. Complications include DVT, cerebral vein thromboses, recurrent pregnancy loss. 4. Heterozygotes also have increased risk Diagnosis: 1. Activated Protein C (APC) resistance test is used as a screening test. APC causes prolonged PTT in normal individuals, there is less PTT prolongation in people with Factor V Leiden mutation. 2. Mutation analysis PCR can then be done as a confirmatory test.

Answer 134

Protein C and Protein S are vitamin K dependent proteins that play a role in anticoagulation pathway.

Answer 135

Heparin and thrombomodulin is expressed on the surface of endothelial cells whereas antithrombin, Protein C and Protein S are made by the liver and are found in plasma. Heparin binds to antithrombin, causes a conformational change such that antithrombin then inhibits several coagulation factors, most of the anticoagulent effect of heparin comes from inhibition of thrombin (FII). Protein C and Protein S together inactivates FV and FVIII so they have an anticoagulent effect.

Answer 136

Mutation in 3′ untranslated region leading to increased stability of prothrombin mRNA, leads to increased production of prothrombin, causes increased plasma levels and venous clots. High prevalence in Caucasians. Diagnosis is made by checking for mutation via PCR.

Answer 137

1. Decreased ability to inactivate factors Va and VIIIa. 2. Leads to increased risk of thrombotic skin necrosis with hemorrhage after administration of warfarin. If this occurs, think protein C deficiency. 3. Patients have a high risk of DVT 4. Those who are homozygous for the mutation can express this as neonates that have skin thrombosis and necrosis at birth, disease called Neonatal Purpura Fulminans 5. There are decreased levels of Protein C (or Protein S) in the plasma so mutation analysis is not required, other causes of protein C or S deficiency can be warfarin, liver disease, vitamin K deficiency and DIC

Answer 138

1. Inherited deficiency of antithrombin: has no direct effect on the PT, PTT, or thrombin time but diminishes the increase in PTT following heparin administration. 2. Can also be acquired: renal failure/nephrotic syndrome, leads to antithrombin loss in urine, as a result there is a decrease in inhibition of factors IIa and Xa. 3. Hallmark of this disease is that there is resistance to heparin therapy, PTT doesn't increase when heparin is administered. 4. There is decreased plasma levels of anti thrombin III, could be due to other factors such as liver disease, nephrotic syndrome, DIC

Answer 139

1. APS is an acquired disease characterized by the acquisition of one or more thrombosis-promoting autoantibodies called antiphospholipid antibodies. 2. Can be primary or secondary due to lupus 3. Primary antigen is **β2 glycoprotein.** 4. Diagnose based on clinical criteria including history of thrombosis (arterial or venous)or spontaneous abortion along with **laboratory findings** of 1. Lupus anticoagulant 2. Anticardiolipin 3. Anti-β2 glycoprotein antibodies. 5. Treatment is systemic anticoagulation and immunosuppression. 6. Anticardiolipin antibodies and lupus anticoagulant can cause false-positive VDRL/RPR (syphilis test) and prolonged PTT. 7. Viral infections can give a false positive, must give a positive test on 2 occasions 12 weeks apart.

Answer 140

* Causes a prolonged PTT with a noncorrected 1:1 mixed study * Must perform two tests to confirm the diagnosis: * dilute Russell Viper venom time * hexagonal phase phospholipid neutralization test * Lupus anticoagulant is diagnosed if either test is positive * Must show positive test on 2 occasions, 12 weeks apart, to exclude transient lupus anticoagulant due to infection

Answer 141

Heparin Induced Thrombocytopenia Definition: A drug induced thrombotic disorder caused by antibodies directed against the heparin-platelet **factor 4 complex**

Answer 142

They can be divided into myeloid and lymphoid neoplasms, they can be further divided by the types of genetic mutations and chromosomal abnormalities and their respective concequences.

Answer 143

Neoplasms of **hematopoietic stem cells** with proliferation of one or two myeloid lineages. 1. CML 2. Polycythemia vera 3. Primary myelofibrosis 4. Essential thrombocytopenia 5. Mastocytosis Hallmark of these diseases is constitutively activated **tyrosine kinase**.

Answer 144

1. Occurs across the age spectrum with peak incidence 45–85 years, median age at diagnosis 64 years. (disease of older individuals) 2. ***_Philadelphia chromosome (t[9;22], BCR-ABL)_*** 1. ***__***ABL on chromosome 9 goes next to BCR on chromosome 22 2. Chromosome 22 looks extra short 3. Marked **granulocytosis** including all stages of maturation 4. May accelerate and transform to AML or ALL (“blast crisis”). 5. Responds to bcr-abl tyrosine kinase inhibitors (eg, **imatinib)**.

Answer 145

Initially assymptomatic for many years as its a slowly progressing disease, may present with non specific symptoms such as fatigue, fever, malaise, weight loss. Patients often develop massive splenomegaly (early satiety and LUQ discomfort). There can also be thrombosis and bleeding disorders.

Answer 146

1. On blood smear we can see **granulocytes** of all stages of maturity 2. Leukocytosis, defined to be above **20,000/microL.** 3. **Basophilia** 4. Bone marrow is markedly hypercellular 5. Massive splenomegaly due to **expanded red pulp** that carries out _extramedullary hematopoiesis_.

Answer 147

Blast crisis seen in CML.

Answer 148

Looking for the Philedelphia chromosome.

Answer 149

* Chronic phase, lasts from 2 to 8 years * Accelerated phase: * Blasts 10-19% * Increased basophils * Persistent thrombocytopenia or thrombocytosis * Increasing splenomegaly and WBC * **Karyotypic evolution** * Blast crisis –survival \<1 y * Blasts ≥20% * Can progress to ALL of AML kind of illness Only bone marrow transplant is curative, Imatinib is not a long term solution since tumor cells develop resistance by changing the ATP binding site of TK receptors.

Answer 150

1. Disorder of multipotent stem cell with predominant effects in erythroid lineage, leads to 1° polycythemia. Disorder of hematocrit. 2. May present as intense itching after hot shower. Rare but classic symptom is erythromelalgia (severe, burning pain and red-blue coloration) due to episodic blood clots in vessels of the extremities 3. Responds to aspirin. 4. EPO levels are low (vs 2° polycythemia, which presents with endogenous or artifcially high EPO).

Answer 151

* **Point mutation in pseudokinase domain of JAK2**, as a result it is constitutively active as there is a loss of autoinhibition. * This leads to increases phosphorylation of downstream targets including STAT5. * NOT seen in CML or lymphoproliferative disorders. * **Ruxolitinib** can be used to inhibit JAK2, but it is not as widely used to due to higher incidence of toxic effects

Answer 152

Increased RBC mass, it can cause 1. Plethora 2. Dizziness 3. Angina 4. Headache 5. Visual disturbances 6. Intermittent claudification Splenomegaly and thrombosis or bleeding can also occur. Important to know that RBCs are normochromic and normocytic.

Answer 153

Decreased or absent iron in the bone marrow together with hypercellularity and an increase in red pulp with extramedullary hematopoiesis in spleen.

Answer 154

1. Non specific flu-like symptoms 2. Hemorrhage 3. Recurrent infections 4. Hallmark of this disease is massive splenomegaly **Leukoerythroblastocytosis** and **tear-drop RBCs** are 2 important pathological findings.

Answer 155

Reticulin, collagenous fibrosis and osteosclerosis

Answer 156

There is a proliferative phase during which the RBC count can get very high, this is followed by Spent consisting of a stable or decrease in RBC count. Finally the last phase is **post polycythemia myelofibrosis**, consisting of progressive anemia, splenomegaly, myelofibrosis. In 2% of the cases patients with PV can develop AML like disease.

Answer 157

1. Obliteration of bone marrow with fibrosis due to increase in fibroblast activity. Often associated with massive splenomegaly and “teardrop” RBCs. 2. Neoplasm of multipotential hematopoietic stem cell with reactive fibrosis 3. Pro-fibrotic growth factors (PDGF, TGF-β) from megakaryocytes 4. Leukoerythroblastosis and **extramedullary hematopoiesis** 5. Epidemiology Middle aged and older adults 6. Excludes CML and PCV that progress to fibrosis

Answer 158

Genetics * **JAK2** mutation in up to 50% of cases * **Calreticulin** mutations in 35% of cases * **MPL** mutation in 1-5% of cases - this is a thrombopoietin receptor, thrombopoietin is a factor for megakaryocyte growth and development

Answer 159

1. Characterized by massive proliferation of megakaryocytes and platelets. 2. Symptoms include bleeding and thrombosis. 3. Blood smear shows markedly increased number of platelets, which may be large or otherwise abnormally formed B . Erythromelalgia may occur. 4. Epidemiology - middle aged and older adults 5. Genetics - JAK2, Calreticulin mutations and MPL mutation.

Answer 160

Increased and morphologically abnormal mast cells, these are associated with c-KIT mutation. It can be localized mastocytosis which is called **Urticaria pigmentosa** or it can be systemic

Answer 161

1. There is proliferation AND lack of maturation, which requires atleast 2 different mutations. Median onset 65 years. 2. Auer rods (picture below) 3. Myeloperoxidase ⊕ cytoplasmic inclusions seen mostly in APL (acute promyelocytic leukemia, formerly M3 AML) 4. Circulating myeloblasts on peripheral smear. 5. Risk factors: prior exposure to 1. alkylating chemotherapy, 2. topoisomerase II inhibitors 3. radiation, 4. myeloproliferative disorders, 5. Down syndrome. 6. t(15;17) = APL subtype responds to all-trans retinoic acid (vitamin A), inducing differentiation of promyelocytes. 7. DIC is a common presentation.

Answer 162

1. Anemia - can lead to fatigue, weakness, pallor. 2. Thrombocytopenia - bleeding disorders. 3. Hepatosplenomegaly - 1/3rd of the cases 4. In the bone marrow we see increased number of blast cells (of lymphoid lineage unlike ALL), we also see Auer bodies

Answer 163

Leukostasis and granulocytic sarcoma.

Answer 164

1. AML with t(15;17) defines acute promyelocytic leukemia 2. Disrupts retinoic acid receptor (RAR-α) gene 3. Abnormal promyelocytes with multiple Auer rods 4. Frequent association with DIC 5. All trans retinoic acid (ATRA) used for treatment. However, this is not the cure, these patients still have t(15;17), ATRA only makes these immature cells become mature (neutrophils) and eventually die. 6. Favorable to intermediate prognosis

Answer 165

* Neoplastic proliferation of Langerhans cells * BRAF mutations in 60% of cases * Admixed eosinophils, plasma cells, neutrophils * Variable clinical presentation

Answer 166

Langerhan Cell Histiocytosis

Answer 167

By the presence of Birbeck Granules.

Answer 168

* t(8;21) - Favorable prognosis * inv(16) or t(16;16) - Acute myelomonocytic leukemia with abnormal eosinophils (AML –M4Eo), also favorable prognosis

Answer 169

1. Ineffective hematopoiesis together with peripheral cytopenias + hypercellular marrow 2. Etiologic associations 1. Benzene 2. Alkylating chemotherapeutic drugs 3. Ionizing radiation 4. Topoisomerase II inhibitors 3. Clinical features –related to pancytopenia 1. Variable course 2. May smolder for years; some are transfusion dependent 3. 10-40% transform to AML

Hematology Path Flashcards

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