Hemonc Flashcards

Question

Microcytic, hypochromic (MCV< 80 fL) anemia

Answer 1

Iron deficiency-most common Decreased iron due to chronic bleeding (GI loss, menorrhagia), malnutrition, gastrectomy (acids promotes Fe2+ form which is more readily absorbed) increased demand (pregnancy), hookworm (developing world) Findings: decreased iron and ferritin, and increased TIBC. Fatigue, conjunctival pallor, pica (consumption of nonfood substances), spoon nails (koilonychia) May manifest as Plummer-Vinson syndrome (triad of 1. iron deficiency anemia, 2. esophageal webs, and 3. atrophic glossitis) Central pallor > 1/3 of RBC diameter is a marker of hypochromia

Answer 2

``` Iron deficiency: Serum iron - decreases TIBC - increases Ferritin - storage form) - decreases % transferrin sat - really decreases ``` ACD Serum iron - decreases TIBC - decreases Ferritin - storage form) - increases % transferrin sat - normal (not iron deficiency) -inflammation of the liver, IL stimulate the liver to make hepsiden - blocks ferroportin which means iron can’t get out of the enterocyte, sloughs and lose in the stool. You block ability of iron to get in. Hepsiden also blocks transport of liver outside. You have iron trapped in these organs. TIBC reciprocal is low ``` Hemochromatosis Serum iron - increases TIBC - decreases Ferritin - storage form) - increases % transferrin sat - really increases -high iron, very high ferritin, high saturation. You can set off the metal detector. ``` ``` Pregnancy Serum iron TIBC - increases Ferritin - storage form) - N/A % transferrin sat -decreases ``` Iron deficiency has low iron stores (ferritin) with a compensatory increase in TIBC •  Anemia of chronic disease (ACD) due to inflammation has ferritin trapped in cells and a low TIBC.

Answer 3

α-thalassemia Two genes on each chromosome 16, four genes total α -globin gene deletions > decreased α-globin synthesis. Cis deletion prevalent in Asian populations; trans deletion prevalent in African populations. 1 allele deletion no anemia 2 allele deletion- mild microcytic anemia 3 allele deletion – HbH disease. Very little α-globin. Excess β-globin forms β4 (HBH) - microcytic anemia 4 allele deletion- No α-globin. Excess γ-globin forms γ4 (causes fatal hydrops fetalis). More likely in Asians

Answer 4

β -thalassemia One beta gene on each chromosome 11, two total. β+ mutant, β0 absent Prevalent in Mediterranean and AA populations β-thalassemia minor (heterozygote): β/β+ Diagnosis confirmed by increased HbA2 (alpha2delta2)>2.5% ) and/or HbF (α2γ2, >1.0%) on Hb electrophoresis β-thalassemia major (homozygote): β0/β0 (β chain is absent, >95% HbF); β+/β+ (>70% HbF) - means if both are mutated as opposed to both absent Severe anemia with target cells requiring blood transfusion. Marrow expansion (crew cut on skull x-ray). Chipmunk facies. Increased risk of parvovirus B19-induced aplastic crisis - it wipes out this hyperplastic bone marrow. HbF is protective in the infant and disease only becomes symptomatic after 6 months. (something important I realized, in alpha thal you can still make tetramers of beta and make RBCs, in beta thal major, alpha globins can’t make tetramers, you make precipitates, and its toxic killing RBC precursors. This is why you have the associated target cell (low hemoglobin), extramedullary hematopoiesis, and aplastic crisis due to PARVO

Answer 5

Sideroblastic anemia Defect in heme synthesis: in forming the protoporphyrin ring (the first step) most common cause alcohol (acquired), myelodysplastic syndrome, genetic X-linked defect in δ-ALA synthase, vitamin B6 deficiency, copper deficiency Findings: high serum iron (not used), high ferritin, low TIBC, high saturation, basophilic stippling (retained rRNA) Treatment: Pyridoxine (B6, cofactor for delta ALA synthase) - minor enzymatic defect may respond

Answer 6

Lead inhibits *ferrochelatase and δ-ALA dehydratase, ringed sideroblast and basophilic stippling Symptoms: (LEAD) Lead Lines on gingivae (Burton Lines) and long bones. Encephalopathy and Erythrocyte basophilic stippling. Abdominal colic and sideroblastic anemia. Drops- wrist and foot drop. (these are severe chronic lead poisoning and are not that useful) - usually just have suspicion and test positive for lead Treatment: Chelation with dimercaprol and EDTA

Answer 7

A) malignancy This patient has microcytic anemia - MCV is low first thing to think about is blood loss > occult malignancy in the colon. this patient has microcytic anemia which is typical of iron deficiency. Iron deficiency is the most common form of anemia worldwide. The lack of iron impairs heme synthesis. The marrow response is to downsize the RBCs eventually resulting in a microcytic and hypochromic anemia. At this patient’s age, bleeding from an occult malignancy should be strongly suspected as the cause of iron deficiency.

Answer 8

C) The infant had alpha- thalassemia major, which is most likely to occur in individuals of Southeast Asian ancestry, each of whose parents could have two abnormal alpha-globin genes on chromosome 16. A complete lack of alpha-globin chains precludes formation of hemoglobins Alpha1, Alpha 2 and F. ONly a tetramer of gamma chains (bart’s hemoglobin can be made leading to severe fetal anemia, Inheritance of three abnormal alpha globin chains leads to hemoglobin H disease with tetramers of beta chains;survival to adult hood is possible. Hemoglobin C and E produce mild hemolytic anemias

Answer 9

Inflammation > increased hepcidin from the liver > inhibits iron transport > decreased release of iron from macrophages and decreased iron absorption from gut. Associated with conditions such as rheumatoid arthritis, SLE, neoplastic disorders and chronic kidney disease Decreased serum iron and TIBC; increased ferritin Can become microcytic like iron deficiency anemia. Iron can’t reach the bone marrow where it is needed to make erythrocytes Treatment: EPO (chronic kidney disease only)

Answer 10

Aplastic Anemia Caused by destruction of myeloid stem cells due to: - radiation and drugs (benzene, chloramphenicol, alkylating agents, antimetabolites), - viruses (parvovirus B19, EBV, HIV, HCV), - Fanconi anemia (DNA repair defect), - idiopathic primary stem cell defect Pancytopenia: all cell types are down, RBC, WBC, platelets. Normal cell morphology, but hypocellular bone marrow with fatty infiltration (dry bone marrow tap) Symptoms: Fatigue, malaise, pallor, purpura (low platelets-bleeding), mucosal bleeding, petechiae, infection Treatment: immunosuppressives, allogenic bone marrow transplantation, RBC and platelet transfusion, bone marrow stimulation with colony stimulating factors. You can’t transfuse WBC as they have MHC class 1.

Answer 11

*Parvovirus B19, EBV, HIV, HCV

Answer 12

Intravascular hemolysis Findings: decrease haptoglobin, increased LDH and some increase in unconjugated bilirubin, hemoglobinuria, and hemosiderinuria, Causes: paroxysmal nocturnal hemoglobinuria, G6PD deficiency, micro/macro angiopathic anemia, malaria Extravascular hemolysis Findings: macrophage in spleen clears RBCs - outside the blood circulation. Increased LDH plus large (breakdown if much more effective) increase in unconjugated bilirubin (from heme breakdown in macrophages), which causes jaundice but NO hemoglobinuria/hemosiderinuria. (most of the breakdown goes right into the blood) Causes: RBC membrane defect, RBC enzyme defect, hemoglobinopathies (S and C), autoimmune

Answer 13

``` Intravascular: Serum Haptoglobin- absent urine hemoglobin - present urine hemosiderin - present Unconjugated bilirubin - elevated Serum LDH - elevated ``` ``` Extravascular: Serum Haptoglobin - mildly reduced - minimal spilling of heme urine hemoglobin - absent urine hemosiderin - absent Unconjugated bilirubin - very elevated Serum LDH - elevated ```

Answer 14

1. Hereditary spherocytosis: Defect in proteins interacting with RBC membrane skeleton and plasma membrane causes premature removal of RBCs by spleen. - vertical posts interact with spectrin allows an RBC to be biconcave. Spherocyte exposed to macrophage chews on it, gets some cell membrane off forming a spherocyte. - spleen is taking this out, its extravascular predominantly but intrinsic defect. Findings: Splenomegaly, aplastic crisis (parvovirus B19) Labs: Osmotic fragility test Treatment: Splenectomy which resolves hemolysis but Howell-Jolly bodies appear 2. G6PD deficiency: Most common enzymatic disorder of RBCs. X-linked recessive so disease of males. Increased RBC susceptibility to oxidant stress (no reduced glutathione) when exposed to sulfa drugs, anti-malarials, infections, fava beans. Heinz bodies and bite cells - from splenic macrophages . 3. Pyruvate kinase deficiency: Defect in pyruvate kinase > decreased ATP > rigid RBCs > extravascular hemolysis. Newborn hemolytic anemia - it only uses glycolysis - terminal enzyme is pyruvate kinase. RBC can’t form the biconcave shape, taken out vascularly. 4. HbC:Glutamic acid-to-lysine mutation in β-globin. Patients with HbSC (1 of each mutant gene) have milder disease than have HbSS patients Labs (homozygotes) target cells - valine is uncharged allowing hemoglobin to stick together. glutamic acid is negative charge but this is why hemoglobin sickles when sticking together .IN contrast, glutamic acid is negative, lysine is positive. You’ve changed a negative to positive. You get target cells with HbC.

Answer 15

Sickle Cells Anemia: HbS point mutation (substitution of glutamic acid with valine) at position 6. 8% of African Americans carry the HbS trait. Low O2, dehydration or acidosis precipitates sickling > anemia, and vaso-occlusive disease. This gives the Hb a new ability to polymerase when deoxygenated HbS/β-thalassemia heterozygote: mild to moderate sickle cell disease depending on amount of β-globin - sickle trait has one normal beta and one sickle. Sickle beta thal would have even less beta. More likely to sickle. Findings: Newborns are initially asymptomatic because of increased HbF and decreased HbS. “Crew Cut” on skull x-ray due to marrow expansion from increased erythropoiesis (also in thalassemias). Sickle cells on smear. Crew cut: Bone marrow expansion in the calvara. Anytime bone marrow is hyperactive is going to produce an aplastic crisis by effecting the stem cells. Complications: -Aplastic crisis (Parvovirus B19), -Autosplenectomy (Howell-Jolly bodies)> increased risk of infection with encapsulated organisms (common cause of death in children), -Salmonella osteomyelitis, -Extramedullary hematopoiesis, -Dactylitism (swollen fingers from vaso- occlusion), -Acute chest syndrome (common cause of death in adults), -Renal papillary necrosis (due to low O2 in papilla. Treatment: hydroxyurea (increased HbF) and hydration

Answer 16

Paroxysmal Nocturnal Hemoglobinuria Acquired mutation in a hematopoietic stem cells. Increased complement- mediated RBC lysis (impaired synthesis of GPI anchor for decay accelerating factor that protects RBC membrane from complement). Mild respiratory acidosis at night triggers hemolysis. 10% of patients > acute leukemia. Triad: Coombs (-) hemolytic anemia, pancytopenia, and venous thrombosis (cause of death) Labs: CD55/59 (-) RBCs on flow cytometry, low or no haptoglobulin. Treatment: Eculizumab (complement pathway inhibitor) Only pure cause of intravascular hemolysis due to an intrinsic RBC defect.

Answer 17

Autoimmune hemolytic anemia (AIHA) Warm agglutinin (IgG)- chronic anemia seen in SLE (most common), CLL, α-methyldopa, pencillin. Cold agglutinin (IgM)- acute anemia triggered by cold; seen in CLL, Mycoplasma and Mononucleosis. RBCs agglutinate and may cause painful, blue fingers and toes with cold exposure. Many warm and cold AIHA are idiopathic but most are Coombs (+) Microangiopathic anemia: RBCs are damaged when passing through obstructed or narrowed vessel lumina. DIC, TTP-HUS, SLE, and malignant hypertension. Schistocytes (helmet cells) due to mechanical destruction of RBCs Macroangiopathic anemia: Prosthetic heart valves and aortic stenosis may also cause hemolytic anemia secondary to mechanical destruction. Schistocytes on peripheral blood smear Infections: Malaria, Babesia invade RBCs and cause lysis

Answer 18

C) portal vein thromboses is odd. WBC count: low Paroxysmal nocturnal hemoglobinuria is an acquired disorder in the myeloid stem cell membrane produced by a mutation in the PIGA gene. Mutation in this gene prevents the membrane expression of certain proteins that require a glycolipid anchor. These include proteins that protect cells from lysis by spontaneously activated complement. As a result, RBCs, granulocytes, and platelets are exquisitely sensitive to the lytic activity of complement. The RBC lysis is intravascular, patients can have hemoglobinuria (dark urine. Defects in platelet function are believed to be responsible for venous thrombosis

Answer 19

Function: Cofactor for methionine synthase (transfers CH3 groups) and methylmalonyl-CoA mutase (metabolizes methylmalonyl-CoA). Found in animal products and only synthesized by microorganisms. Folate works with B12 to form methionine from homocysteine. Folate (THF) required for many synthetic pathways including nucleotide synthesis. B12 deficiency- Methylmalonyl CoA accumulates and causes CNS damage - to make B12 you must have animal byproducts - folate comes from greens. THF (folate) + B12 + homocysteine= methionine. If they don’t make methionine you have increase of homocysteine. Elevated homocysteine leads to damage to blood vessels, thrombosis. If you dont have B12, all of the folate is trapped as methyl tetrahydrofolate but you need THF in other areas to make DNA. Nucleus sitting there that can’t replicate its DNA< nucleus is immature. B12 also converts methymalonyl coA > succinyl-coA - leads to CNS damage dorsal and lateral corticospinal columns (differs it from folate). Even chain fatty acids are broken down to acetyl coA, odd chain fatty acids is the only time you have methylmalonyl coA- without B12 you can’t further metabolize it. Its the one example where fatty acids can be converted into glucose via succinyl coA. (ONE EXCEPTION)

Answer 20

Megaloblastic Anemia Impaired DNA synthesis> delayed maturation of nucleus of precursor cells in bone marrow is delayed relative to cytoplasm. Macrocytosis, hypersegmented neutrophils, glossitis Folate Deficiency- takes months to develop Causes: malnutrition (alcoholics), malabsorption, antifolates (methotrexate, trimethoprim, phenytoin), increased requirement (hemolytic anemia, pregnancy). B12 deficiency- takes years to develop Causes: insufficient intake (strict vegans), malabsorption (Crohn disease), pernicious anemia (no intrinsic factor), Diphyllobothrium latum (fish tapeworm), gastrectomy. Pancreatic disease (need enzymes to release B12 so it can bind to IF) Neurologic symptoms: subacute combined degeneration (due to involvement of B12 in fatty acid pathways and myelin synthesis. spinocerebellar tract, lateral corticospinal tract, dorsal column dysfunction. Accumulated methymalonic acid - Subacute combined degeneration Diagnosed with Schilling test: Schilling Test- Give oral radioactive B12 without (Part 1) and then with intrinsic factor (IF, Part 2). Measure radioactive B12 in urine - ileum - chrons disease (folate is absorbed, duodenum and jejunum. B12 and IF together are used for absorption. Say you don’t have B12 in urine, then you add IF and you do, then you know you have pernicious anemia Orotic aciduria: Inability to convert orotic acid to UMP (de novo pyrimidine synthesis pathways). AR. **megaloblastic anemia that cannot be cured by folate or B12. Treatment: UMP to bypass mutated enzyme

Answer 21

Non-megaloblastic macrocytic anemias: Macrocytic anemia in which DNA synthesis unimpaired. Caused by liver disease, alcoholism. RBC Macrocytosis w/o hypersegmented neutrophils These conditions are likely precursors to megaloblastic.

Answer 22

There are two important points I think- about platelet size. Some disorders associated with thrombocytopenia, like ITP, are caused by platelet destruction. In all other ways, however, we can presume the bone marrow and the platelets themselves are normal. The bone marrow will ramp up to make new platelets (as free circulating TPO will increase) and newly formed "young" platelets will come into the blood stream- immature platelets are larger sized. You would expect the mean platelet volume (an indicator of platelet size) to be higher. This is analogous to what happens with immune-mediated destruction of RBCs (as well as other causes of anemia when the bone marrow is capable of responding) when young, immature RBCs (reticulocytes) enter the blood stream in larger numbers and these are also LARGER than normal RBCs. Bottom line: platelets are larger than expected-they are normally 1/5th the size of an RBC so maybe some will be 2X normal . This is distinct from Bernard-Soulier Syndrome (BSS). With BSS- the platelet receptor that is absent or decreased in expression (GPIb/IX/V) mediates platelet adhesion to vWF- so basically- the platelets can't adhere when and where they need to (e.g. at sites of vascular injury). HOWEVER, because the GPIb/IX/V complex is located in the platelet cytoskeleton, it is also essential to the production of platelets from the megakaryocytes in the bone marrow. The altered receptor expression directly affects how the platelets are made- leading to the large size and decreased numbers of platelets in this syndrome. With regard to size- we are talking GIANT platelets !!! these platelets can be the size of RBCs so this is 5X the normal size- WAYYYYY bigger than normal. Another congenital platelet disorders that does this-is a deficiency of platelet alpha granules (eg, gray platelet syndrome). Inherited platelet disorders with giant platelets are quite rare.......so you know- stick it on your bulletin board for step 1

Answer 23

First Aid is right- but in the lecture - I specified that Follicular Lymphoma was the most common INDOLENT (slow growing) lymphoma- not most common overall- Overall, most common is DLBCL- but the behavior of this tumor is different, it is faster growing and thus more aggressive- so I separate the diseases out in terms of their behaviors so you can think about this for the vignettes. What about molecules? FA also lists BCL2 as being important to DLBCL- this is also correct but I do not think it is as important to know as the association with BCL6 Important summary points: Follicular lymphoma : 85-90% have t(14;18) and remember that this is necessary (but not sufficient) for transformation. DLBCL: I emphasized the BCL6 translocation [t(3;14)] but also pointed out that when all DLBCL patients are considered, 30-40% have the BCL6 translocation- and the rest have mutations causing BCL6 to be overexpressed via another mechanism. In other words- BCL6 is the BIGGER problem. BCL2 translocation typical of follicular lymphoma can also be found in 20-30% of DLBCL patients- some people think that part of this population represents people with follicular lymphoma that has transformed and become more aggressive.

Answer 24

Burkitt lymphoma (c-myc activation)

Answer 25

CML (BCR-ABL hybrid) ALL (less common with poor prognostic factor) * Philadelphia CreaML cheese. The Ig heavy chain genes on chromosome 14 are constitutively expressed. When other genes (eg, c-myc and BCL-2) are translocated next to this heavy chain gene region, they are overexpressed.

Answer 26

Mantle cell lymphoma (cyclin D1 activation)

Answer 27

APL (M3 type of AML) responds to all-trans retinoic acid

Answer 28

Follicular lymphoma (BCL-2 activation)

Answer 29

Collective group of proliferative disorders of dendritic (Langerhans) cells. Presents in a child as lytic bone lesions and skin rash or as recurrent otitis media with a mass involving the mastoid bone. Cells are functionally immature and do not effectively stimulate primary T cells via antigen presentation. Cells express S-100 (mesodermal origin) and CD1a. Birbeck granules (“tennis rackets” or rod shaped on EM) are characteristic

Answer 30

Burkitt lymphoma Adolescents or young adults t(8;14)—translocation of c-myc (8) and heavy-chain Ig (14) “STARRY 🤩sky” appearance: “lymphoid cells with numerous mitotic figures”, sheets of lymphocytes with interspersed “tingible body” macrophages Associated with EBV. Jaw lesion in endemic form in Africa; pelvis or abdomen in sporadic form. *HIGHLY aggressive B cell non-Hodgkin lymphoma, rapidly growing tumor with VERY SHORT doubling time (25 hrs)

Answer 31

Usually older adults but 20% in children Alterations in Bcl-2, 6 Most common type of non-Hodgkin lymphoma in adults BcL-6 association is more important to know: zinc finger transcriptional repressor This mutation: prevents cells from undergoing apoptosis in response to DNA damage, suppresses normal DNA damage response, damaged cells progress through the cell cycle, encourages somatic hypermutation

Answer 32

Adults t(14;18) - heavy chain ig (14) and BCL-2 (18) Indolent course; Bcl-2 inhibits apoptosis. Presents with painless “waxing and waning” lymphadenopathy. Follicular architecture: small cleaved cells (grade 1), large cells (grade 3), or mixture (grade 2). Arises from germinal center B cells BCL2 is an antiapoptotic protein. Mature lymphocyte population expands!

Answer 33

adult males t(11;14)—translocation of cyclin D1 (11) and heavy-chain Ig (14), CD 5+ Very aggressive, patients typically present with late-stage disease Promotes G1-to-S phase transition

Answer 34

adults t(11,18) Associated with chronic inlammation (eg, Sjögren syndrome, chronic gastritis [MALT lymphoma]).

Answer 35

Adults Most commonly associated with HIV/AIDs; pathogenesis involves EBV infection Considered an AIDS-deining illness. Variable presentation: confusion, memory loss, seizures. Mass lesion(s) on MRI needs to be distinguished from toxoplasmosis via CSF analysis or other lab tests.

Answer 36

Adults Caused by HTLV (associated with IV drug abuse) Adults present with cutaneous lesions; common in Japan, West Africa, and the Caribbean. Lytic bone lesions, hypercalcemia.

Answer 37

Adults Mycosis fungoides: skin patches/plaques (cutaneous T-cell lymphoma), characterized by atypical CD4+ cells with cerebriform nuclei and intraepidermal neoplastic cell aggregates. (Pautrier microabscess). May progress to Sézary syndrome (T-cell leukemia).

Answer 38

Both Hodgkin and non-Hodgkin lymphoma are malignancies of a family of white blood cells known as lymphocytes, which help the body fight off infections and other diseases. Hodgkin lymphoma is marked by the presence of Reed-Sternberg cells, which are mature B cells that have become malignant, are unusually large, and carry more than one nucleus. The first sign of the disease is often the appearance of enlarged lymph nodes. Non-Hodgkin lymphoma, by contrast, can be derived from mature B cells or T cells and can arise in the lymph nodes as well as other organs. (B cells and T cells play different roles in the body’s immune response to disease.) Both diseases are relatively rare, but non-Hodgkin lymphoma is more common in the United States, with more than 70,000 new cases diagnosed each year, compared to about 8,000 for Hodgkin lymphoma. The median age of patients with non-Hodgkin lymphoma is 60, but it occurs in all age groups. Hodgkin lymphoma most often occurs in people ages 15 to 24 and in people over 60. There are more than 60 distinct types of non-Hodgkin lymphoma, whereas Hodgkin lymphoma is a more homogeneous disease. The two forms of lymphoma are marked by a painless swelling of the lymph nodes. Hodgkin lymphomas are more likely to arise in the upper portion of the body (the neck, underarms, or chest). Non-Hodgkin lymphoma can arise in lymph nodes throughout the body, but can also arise in normal organs. Patients with either type can have symptoms such as weight loss, fevers, and night sweats. The diseases often follow different courses of progression. Hodgkin lymphoma tends to progress in an orderly fashion, moving from one group of lymph nodes to the next, and is often diagnosed before it reaches an advanced stage. Most patients with non-Hodgkin lymphoma are diagnosed at a more advanced stage. Treatments for lymphoma vary depending on the type of disease, its aggressiveness, and location, along with the age and general health of the patient. As a general rule, however, Hodgkin lymphoma is considered one of the most treatable cancers, with more than 90 percent of patients surviving more than five years. Survival rates for patients with non-Hodgkin lymphoma tend to be lower, but for certain types of the disease, the survival rates are similar to those of patients with Hodgkin lymphoma. New treatment approaches, including the use of therapies that spur the immune system to attack cancerous lymphocytes, are showing considerable promise.

Answer 39

Endothelial cells constitutively synthesise and release von Willebrand factor (vWF) into blood, which serves two functions (at least). Firstly, vWF stabilises coagulation factor VIII and protects it from proteolytic degradation in plasma. Secondly, vWF binds avidly to collagen and activates platelets when it does so. Now, blood and collagen don’t usually come into contact with each other unless the endothelium is damaged. When the endothelium is disrupted – say by a cut through a vessel – vWF immediately binds to collagen ready to activate the first platelet that comes along.

Answer 40

Bax and Bak promote pore formation; release of cytochrome c and APAF1 initiates apoptosis Bcl-2 binds Bax/Bak and prevents pore formation; anti-apoptotic Bid, Bad, and PUMA promote apoptosis: tie up Bcl-2 and free Bax/Bak.

Answer 41

Occurs across the age spectrum with peak incidence 45–85 years, median age at diagnosis 64 years. Deined by the Philadelphia chromosome (t[9;22], BCR-ABL) and myeloid stem cell proliferation. c-Abl is a tyrosine kinase that promotes proliferation and survival- gains a domain from BCR that facilitates dimerization - constitutively active and trapped in cytoplasm. Presents with dysregulated production of mature and maturing granulocytes (eg, neutrophils, metamyelocytes, myelocytes, basophils) and splenomegaly. May accelerate and transform to AML or ALL (“blast crisis”). Very low LAP as a result of low activity in malignant neutrophils (vs benign neutrophilia [leukemoid reaction], in which LAP is increased). Responds to bcr-abl tyrosine kinase inhibitors (eg, imatinib).

Answer 42

Median onset 65 years. Auer rod, myeloperoxidase ⊕ cytoplasmic inclusions seen mostly in APL (formerly M3 AML); SUPER INCREASE in circulating myeloblasts on peripheral smear; adults. -FTL3 (receptor tyrosine kinase) mutation: expressed by immature hematopoietic cells, poor prognosis, found in 30% of AML Risk factors: prior exposure to alkylating chemotherapy, radiation, myeloproliferative disorders, Down syndrome. APL: t(15;17), responds to all-trans retinoic acid (vitamin A), inducing differentiation of promyelocytes; DIC is a common presentation. PML-RAR alpha fusion protein accumulates - activates transcription. So what happens is that RA usually binds to RAR and relieves repression allowing transcription to activate. This leads to proliferation of immature myeloid cells because self-renewal activity is enhanced. If you give pharmacologic doses of RA, you can bypass and force the cells to mature

Answer 43

ALK (anaplastic lymphoma kinase) - nonreceptor tyrosine kinase located on chromosome 2 t (2;5) translocation is most common. T cell lymphoma ALK fusion is constitutively active

Answer 44

both are hematopoietic transcription factors RUNX1 (AML) -t(8;21) RUNX-RUNXT1 - AML-ETO blocks RUNX function RUNX1 (ALL) -t(12;21) ETV6-RUNX - TEL-AML Activation of transcrption *both good prognosis

Answer 45

MLL (KMT2A - histone methyltransferase) associated with both ALL and AML most common cytogenetic abnormality in infants with acute leukemia) ALL vs AML lymphocytic vs other blood cell types found in bone marrow poor prognosis

Answer 46

Unregulated growth and differentiation of WBCs in bone marrow > marrow failure > anemia (decreased RBCs), infections (decrease mature WBCs), and hemorrhage (decrease platelets). Usually presents with increase circulating WBCs (malignant leukocytes in blood); rare cases present with normal/decrease WBCs. Leukemic cell iniltration of liver, spleen, lymph nodes, and skin (leukemia cutis) possible.

Answer 47

Most frequently occurs in children; less common in adults (worse prognosis). T-cell ALL can present as mediastinal mass (presenting as SVC-like syndrome). Associated with Down syndrome. Peripheral blood and bone marrow have SUPER INCREASED lymphoblasts. TdT+ (marker of pre-T and pre-B cells), CD10+ (marker of pre-B cells). Most responsive to therapy. May spread to CNS and testes. t(12;21)> better prognosis.

Answer 48

Age: > 60 years. Most common adult leukemia. CD20+, CD23+, CD5+ B-cell neoplasm. Often asymptomatic, progresses slowly; smudge cells in peripheral blood smear; autoimmune hemolytic anemia. CLL = Crushed Little Lymphocytes (smudge cells). *Richter transformation—CLL/SLL transformation into an aggressive lymphoma, most commonly diffuse large B-cell lymphoma (DLBCL).

Answer 49

Age: Adult males. Mature B-cell tumor. Cells have filamentous, hair-like projections (fuzzy appearing on LM). Peripheral lymphadenopathy is uncommon. Causes marrow fibrosis > dry tap on aspiration. *even though hair cell leukemia affects the white cells, the lymph nodes usually don’t enlarge and they tend to accumulate in bone marrow, liver and spleen. 100% have a BRAF mutation Patients usually present with massive splenomegaly and pancytopenia. Stains TRAP (tartrate-resistant acid phosphatase) ⊕. TRAP stain largely replaced with low cytometry. Treatment: cladribine, pentostatin.

Answer 50

Primary polycythemia. Disorder of increased RBCs. 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 *JAKV617F mutation - nonreceptor tyrosine kinase which leads to constitutive activation Decreased EPO (vs 2° polycythemia, which presents with endogenous or artiicially increased EPO). Treatment: phlebotomy, hydroxyurea, ruxolitinib (JAK1/2 inhibitor).

Answer 51

Characterized by massive proliferation of megakaryocytes and platelets. Symptoms include bleeding and thrombosis. Blood smear shows markedly increased number of platelets, which may be large or otherwise abnormally formed. Erythromelalgia may occur.

Answer 52

Obliteration of bone marrow with fibrosis due to increased fibroblast activity. Often associated with massive splenomegaly and “teardrop” RBCs. “Bone marrow is crying because it’s fibrosed and is a dry tap.”

Answer 53

•  Arachidonic acid: used to assess the viability of the thromboxane pathway. •  Thrombin: Most potent physiologic agonist of platelets. Reacts with several membrane sites to induce full aggregation and secretion of organelle contents independent of the prostaglandin or ADP pathways. •  Collagen: Important for platelet adhesion and activation of the ECM of the endothelium. Depends on intact membrane receptors, membrane phospholipase pathway integrity and normal cyclooxygenase and thromboxane pathway function. •  ADP: Mild platelet agonist. Binds to a specific platelet membrane receptor and causes platelet activation and release of dense granule stored ADP. •  Epinephrine: Mild platelet agonist. Binds to specific receptor and causes ADP secretion. •  Ristocetin: requires vWF and intact surface membrane including a functional vWF receptor site (GPIb).

Answer 54

•  Immune thrombocytopenic purpura (ITP) •  Acquired thrombocytopenia secondary to autoantibodies against platelet antigens: usually it is an IgG made by patient that acts on glycoprotein receptors in platelets •  Primary: Autoimmune platelet destruction •  Secondary: Associated with underlying condition component of impaired production) Pathogenesis: •  Reduced platelet lifespan secondary to antibody-mediated destruction (also •  Triggers •  Infection (more often viral): viral like symptoms, all of a sudden the yhave massive bruising •  Immune alteration: lupus, RA Manifestations - Petechiae, purpura, epistaxis, severe bleeding (<1% of patients) Diagnosis: •  Thrombocytopenia •  Mild (>100,000/ul) to severe (>10-20,000/ul) •  Increased MPV/giant platelets •  Absence of other abnormal findings (Rest of CBC normal, normal coags) •  Bone marrow exam: Normal cellularity, normal or increased number of megakaryocytes, normal hematopoiesis ``` Treatment •  Immunosuppression •  Steroids •  Rituxan •  Splenectomy •  TPO agonists ``` Keywords - thrombocytopenia, large platelets, Hb is normal, WBC is normal, normal CoAgs , normal PT, PTt, fibrinogen.

Answer 55

(as with all MAHA), RBC is down (excludes ITP), you see schistocytes Dissemintated intravascular coagulation (DIC) •  Activation of the coagulation cascade unnecessarily leading to excessive fibrin in vessels, combines with platelets, making thrombi •  Consumption of platelets and coagulation factors •  Manifests as bleeding and clotting; multi-organ disease Causes: •  Obstetric (relating to childbirth) complications, adenocarcinomas, APL (acute promyelocytic leukemia), snake bites •  Sepsis, trauma, thermal burns, vasculitis •  Acute or chronic ``` DIC Diagnosis: •  Prolonged PT/INR, PTT, and TT •  Decreased fibrinogen, increased FDPs and dd-dimer •  Thrombocytopenia •  Smear: schistocytes ``` Treatment: •  Treat underlying disorder •  Transfusion support Keywords: overactive coagulation cascade, multi-organ disease, thrombocytopenia, decreased fibrinogen, prolonged PT/INR, PTT, and TT, anemia you have thrombocytopenia with clots going on everywhere (which is why all clotting factors are going down)

Answer 56

Simultaneous occurrence of microangiopathic hemolytic anemia, thrombocytopenia, and ACUTE SEVERE kidney injury   Classification •  Primary: Complement dysregulation: Mutations in complement gene, antibodies against complement factor H ``` Secondary: •  Infection: Shiga toxin producing E.Coli, Strep pneumo, HIV •  Drug toxicity •  Pregnancy •  Autoimmune disorders ``` Diagnosis •  Microangiopathic hemolytic anemia, thrombocytopenia •  Schistocytes on smear •  Normal coags, Coombs negative •  Acute kidney injury: range from hematuria/proteinuria to severe renal failure •  Cultures, viral studies, complement studies Treatment •  Supportive care, transfusions, dialysis •  Plasmapheresis •  Eculizumab: inhibits complement

Answer 57

Mechanism •  Deficiency of ADAMTS13 •  ADAMTS13 cleaves ultra large VWF multimers •  Increases large multimers in circulation, adhere to platelets, thrombocytopenia and primary thrombi formation (but NOT coagulation) -  Acquired or inherited Presentation •  Thrombocytopenia and hemolytic anemia in previous healthy pt •  PENTAD: Fevers, Anemia, Thrombocytopenia, Renal, Neuro ``` Diagnosis •  Evidence of MAHA on smear/labs •  Coombs negative •  Normal coags •  ADAMTS13 activity <5-10%: Reflex to inhibitor ``` Treatment-Medical Emergency •  Plasmapheresis - FFP: fresh frozen plasma Immunosuppression •  Steroids +/- Rituxan •  Avoid transfusion - if you just give more platelets it will just bind to the multimers and cause more clotting Keywords - sudden onset low platelet and anemia, NORMAL PTT, NORMAL Fibrinogen, NORMAL COAGS (differs from DIC)

Answer 58

Occurs in 5% of exposed patients •  Autoantibody against endogenous platelet factor 4 (PF4) - the protein in alpha granules - in complex with heparin •  Activates platelets •  Catastrophic arterial and venous thrombosis Risk factors: •  Unfractionated heparin > LMWH, increased dose of heparin, female sex, surgery, age Presentation •  Thrombocytopenia •  Timing of drop 5-10 days after heparin exposure •  Thrombosis: arterial or venous, thrombotic sequelae •  Anaphylaxis ``` Treatment •  Discontinuation of all heparin products •  Evaluation for thrombosis •  Alternative anticoagulation Long term •  Transition to coumadin •  Lifetime avoidance of heparin ``` *if someone on heparin develops a clot you should go “hmmmmmm”

Answer 59

Splenic sequestration •  1/3 of platelet mass is sequestered in spleen •  Can increase to 90% with severe splenomegaly - Total platelet mass is normal -  Rarely with clinical bleeding •  Cirrhosis, portal hypertension, splenomegaly

Answer 60

-normal platelet number but these platelets aren’t working Medications •  ASA •  NSAIDS •  Dipyridamole •  P2Y12 receptor antagonists •  Miscellaneous: Antibiotics, SSRIS, antiepileptics, fish oils Uremia •  Associated with chronic renal failure •  Increased clinical bleeding: ecchymoses, epistaxis, GI/GU bleeding •  Mechanism: intrinsic platelet metabolic defects, deficiencies in platelet endothelial interaction, associated anemia •  Severity of renal failure does not correlate with bleeding *   Liver disease *   Cardiopulmonary bypass *   Dysproteinemia Congential •  Bernard-Soulier •  Glanzmanns thombasthenia •  Storage pool disorders

Answer 61

Bernard-Soulier Syndrome Glycoprotein Ib/IX/V Deficiency •  Plays a major role in platelet adhesion to the subendothelium. •  Mediates the binding of VWF to platelets •  Characterized by prolonged bleeding time, large platelets, and thrombocytopenia Extremely rare: •  Autosomal recessive - Often associated with consanguinity •  Populations of Europe, North America, and Japan Clinical Manifestations •  Evident from early childhood.- Symptom severity may vary through life •  Frequent episodes of epistaxis •  Gingival and cutaneous bleeding •  Spontaneous ecchymoses •  Hemorrhage associated with trauma/surgery/dental extractions •  Menorrhagia and pregnancy manifestation may be variable Diagnosis •  Prolonged bleeding time •  Morphologically Enlarged platelets •  Thrombocytopenia (?) •  Platelet aggregation: an isolated defect in ****ristocetin-induced aggregation - which is vWF used as an agonist Confirmation: •  Flow cytometry: assessment of platelet surface glycoprotein expression •  Immunoblotting of platelet lysates with specific antiplatelet glycoprotein antibodies. •  Genotype Management •  General measures: •  Avoiding even relatively minor trauma •  Advise against the use of antiplatelet medications •  Adequate dental hygiene-to prevent gingival disease and minimize procedures •  Iron supplementation as needed •  Hormonal control of menses Bleeding episodes or prophylaxis: •  *Transfusion of blood and/or platelets •  Use of antifibrinolytic drugs may or may not be beneficial •  DDAVP may shorten the bleeding time in some (this drug increases the amount of platelets you have) •  Novo-7 •  Hematopoeitic stem cell transplant

Answer 62

GPIIb/IIIa Deficiency (the protein that binds to fibrinogen and links platelets) •  Characterized by a prolonged bleeding time, normal platelet count, absent macroscopic platelet aggregation •  Relatively more severe mucocutaneous bleeding manifestation than most platelet function disorders •  Autosomal recessive Presentation: •  Mucocutaneous bleeding during neonatal period or infancy (ex. Circumcision) •  Spontaneous petechiae uncommon •  Epistaxis •  Gingival bleeding •  Menorrhagia •  GI/GU bleeding •  Severity of hemorrhage unpredictable, even within families, does not correlate with deficiency Diagnosis •  **Platelet counts and morphology normal •  Bleeding time: markedly prolonged •  Platelet aggregation: absent agonist-stimulated platelet aggregation: only ristocetin works so the complete opposite of Bernard-Soulier •  Platelet secretion by strong agonist normal •  (Weak agonists ADP/epinephrine absent) •  Flow cytometry: decreased platelet expression of GPIIb/IIIA complex Treatment •  General measures: •  Avoiding even relatively minor trauma •  Advise against the use of antiplatelet medications •  Adequate dental hygiene-to prevent gingival disease and minimize procedures •  Iron supplementation as needed •  Hormonal control of menses Bleeding episodes or prophylaxis: •  Transfusion of platelets •  Use of antifibrinolytic drugs, such as ε-aminocaproic acid or tranexamic acid •  DDAVP may shorten the bleeding Novo-7 •  Hematopoeitic stem cell transplant

Answer 63

``` Thrombin Time (TT) •  Measures final step of coagulation, conversion of fibrinogen to fibrin ``` •  Prolonged if fibrinogen levels are low or inhibiting anticoagulant is present *   Used if: *   Prolonged PT/aPTT *   Evaluation of inherited fibrinogen disorder *   Detection of heparin

Answer 64

abnromal pTT and PT- take patients plasma, give them additional plasma and do test again. If they have factor deficiency, it should correct, because the plasma would contain all the factors. Give them back the factors and if it doesn’t work, there is an inhibitor If an inhibitor is present, mixing studies can also be used to determine the titer of the inhibitor •  Serial dilutions of patient plasma are mixed with normal plasma until the proportion of patient plasma is reduced to the point that the mixing study does correct •  Reported in Bethesda units (BU)

Answer 65

X-linked recessive diseases that present in male children of carrier females •  Hemophilia A (factor 8)- Occurs 1:5000 live male births, 2/3 will have severe disease •  Hemophilia B (factor 9)- Occurs in 1:30,000 live male births, ½ will have severe disease •  Severe hemophilia is almost exclusively a disease of males Initial presentation Severe disease: •  Present within the first year to one and a half years of life •  Average age of diagnosis is 8-36 months •  Majority undergo delivery without significant bleeding •  Easy bruising, hemarthrosis, bleeding due to oral injury, invasive procedures •  Majority present with a known family history* : Although there will be some that present with a de novo gene mutation transmitted from the mother •  Mild disease •  May go undetected for significant period of time until significant hemostatic challenge •  Average age of diagnosis 14-62 years •  1/3 have minimal bleeding Initial site of bleeding Infants •  CNS •  Sites of medical interventions Children •  Bruising, joint bleeds, and other sites of musculoskeletal bleeding •  More common once children begin walking Older children and adults •  Joints and muscles Laboratory findings •  Prolonged PTT (because factors 9 and 8 are intrinsic) •  May be normal in mild disease (factor activity >15%) •  Normal PT and platelet count •  Measurement of the factor activity •  Normal VWF antigen- Should be checked with all decreased FVIII A: Confirmation FVIII activity <40% or identification of a known a pathogenic factor VIII gene mutation •  Documented normal VWF antigen B: Confirmation FIX activity <40% or identification of a pathogenic factor IX gene mutation •  Newborns have a lower normal range of factor IX activity Clinical severity correlates well with assayed factor levels. •  <1% factor activity defined as severe disease •  1 to 5% defined as moderate disease •  >5% of normal defined as mild disease •  Prophylactic treatment over “on demand” treatment •  The goal to maintain the factor VIII above 1 percent

Answer 66

Factor XI Deficiency •  Incidence is 1 in 1,000,000 •  Autosomal bleeding disorder common among Ashkenazi Jews •  Heterogeneous phenotype, with a poor correlation between plasma FXI levels and bleeding •  Most do not suffer from spontaneous bleeding •  Do not need prophylaxis for routine daily activity •  At risk of bleeding following trauma or surgery •  Higher, variable risk for menorrhagia and postpartum hemorrhage Management •  Do not need prophylaxis for routine daily activity •  Treatment indicated for dental extraction, major surgery, trauma, childbirth •  Surgery or injury involving tissues with high fibrinolytic activity associated with higher bleeding risk •  Antiplatelet agents, aspirin, and other NSAIDs are absolutely contraindicated before surgery, as their presence may increase the risk of bleeding. •  At other times, these agents are relatively contraindicated.

Answer 67

Spontaneously acquired inhibitors of blood coagulation •  Antibodies that either inhibit the activity or increase the clearance of a clotting factor. •  May be secondary to transfusion of plasma or recombinant factor infusion, or arise de novo in previously normal patients •  Most common against FVIII Clinical Setting •  Alloantibodies in congenital hemophilia •  Postpartum •  Associated with immunologic disorders (SLE, RA) •  Associated with malignancies (solid tumors or lymphoproliferative) •  Drug Reactions (PCN) •  Spontaneous development (50%) Demographics •  Gender: equal •  Age: >50 yo Course •  Mortality 22% •  Spontaneous remission 38% Presentation •  Severe bleeding diathesis •  Skin, mucous membrane, soft tissue bleeding •  Sudden large hematomas or hemarthroses •  Fatal GI, retroperitoneal, or intracranial bleeding Ex. SEVERE bruising, Hb of 4, happens rapidly, they are in their 80’s and never had bleeding before, prolonged PTT, bleeding everywhere Evaluation •  Repeat all tests •  Exclude heparin affect with dilute thrombin time and reptilase time •  Inhibitor screen (mixing test), with incubation studies •  Correction of the prolonged aPTT suggests a deficiency, while persistent prolongation of the aPTT indicates the presence of an inhibitor. •  Phospholipid: Adding source of phospholipid to the mixed plasma. Correction of the aPTT suggests the presence of antiphospholipid antibodies. •  Factor activity assay and inhibitor screen -  Establishes diagnosis and quantifies inhibitor ``` Management •  Acute bleeding - Careful nursing care •  No IM injections, fall precautions •  Transfusion support •  Bypassing agents: First line therapy - Recombinant FVIIa - aPCC •  Factor replacement - Potential option if antibody titer is low (<5BU) ``` Elimination of the autoantibody Immunosuppression •  Prednisone plus cyclophosphamide (CR 70%) •  Rituximab •  Single agent prednisone, cyclophosphamide, azathrioprine •  Some resolve spontaneously (postpartum, drug induced) ê •  Plasmapheresis has also been studies in combination with immunosuppression

Answer 68

Von Willebrand factor (VWF) •  Binds both platelets and endothelial components, forming bridge between platelets and vascular subendothelial structures at sites of endothelial injury and between adjacent platelets •  Carrier protein for FVIII •  Synthesized by megakaryocytes and endothelial cells •  Require extensive post-synthetic processing •  VWF is sufficiently decreased in the plasma or when a qualitative defect in VWF bleeding occurs •  Affect platelet plug formation during the primary hemostatic response. *#**no enlarged platelets because no decreased platelet count either! (seen in Bernard Soulier) ``` Clinical Manifestations •  Easy bruising •  Skin bleeding •  Prolonged bleeding from mucosal surfaces (eg, oropharyngeal, gastrointestinal, uterine •  Bleeding more serious and earlier in life in patients with VWD variant (type 2N) or type 3 VWD •  Type 3 patients often have symptoms in infancy (eg, with circumcision) or when they begin to be mobile ``` Types 1 and 3 are quantitative, Type 2 is qualitative, you make enough but activity is very low. Desmopressin (DDAVP) •  Overview of DDAVP administration •  Can be administered intravenously or by intranasal spray •  Increase secretion of intrinsic VW factor •  3-5X increase in baseline levels of VWF and FVIII expected 30-60 minutes after infusion •  Response lasts 6-12 hours •  Limited by tachyphylaxis and hyponatremia •  Intranasal administration favored choice for minor bleeding not requiring a hospital visit or prior to planned minor invasive procedure Treatment Options *   Antifibrinolytic therapy — Aminocaproic acid and tranexamic acid *   Especially good for mucosal bleeding (dental, menorrhagia) *   Can be given orally or intravenously *   Prolonged use carries a risk of thrombosis if underlying hypercoagulable state *   Contraindicated if gross hematuria •  Topical agents — Topical thrombin •  Nasal or oral bleeding •  Gelfoam or Surgicel are soaked in topical thrombin and applied to areas of bleeding *   Estrogen *   Increases synthesis of VWF •  Recombinant factor VIIa •  Can be used in patients with Type 3 disease who develop antibodies to replacement therapy •  Bypasses need for FVIII in coagulation pathway, binds activated platelets, initiates the extrinsic clotting cascade ``` VW factor replacement •  Plasma derived •  Contain VWF and Factor VIII •  Dosed based on ristocetin cofactor activity •  Examples •  Wilate •  Humate P •  Recombinant •  Vonvendi •  Does not contain factor VIII ``` Complete diagnosis of VWD performed •  DDAVP can be used in patients with Type I and mild Type 2A/M but not Type 2B or Type 3 •  Response trial should be documented •  Avoid in young patients, pregnant, history of cardiovascular disease •  Von Willebrand factor concentrate is given to patients with major bleeding or major surgery •  Ex. involving vital organs not accessible to direct observation, requiring more tissue dissection or for which greater-than-expected bleeding would adversely affect the outcome •  Risk of delayed bleeding in certain circumstances

Answer 69

Conversely, when hepcidin levels are low (as occurs in hemochromatosis), basolateral transport of iron is increased, eventually leading to systemic iron overload. The HFE gene, which is defective in hemochromatosis, regulates hepcidin production in the liver (HFE mutated leads to low hepcidin)

Answer 70

- Pancytopenia - tartrate-resistant acid phosphatase (TRAP) - massive splenomegaly (red pulp infiltration) - hairy cells - treatment is 2-chlorodeoxyadenosine, cladribine - dry tap - middle aged, caucasian men, indolent course.

Answer 71

1. gram negative sepsis (ex klebsiella in alcoholics) 2. trauma 3. pregnancy complications 4. malignancy 5. pancreatitis 6. kidney complications

Answer 72

- decreased fibrinogen levels - elevated fibrin degradation products (plasmin mediated degradation of circulating fibrinogen or fibrin) - D dimers (only from fibrin within blood clots) - prolonged bleeding time (from the thrombocytopenia, consumption of platelets)

Answer 73

CD8+ T cells (reactive atypical) - viruses naturally activate cytotoxic CD8 cells

Answer 74

Vivax or ovale - Schuffner dots - oval body - capable of causing relapse - both leave dormant forms in liver called hypnozoites Vivax: Western hemisphere P. falciparum, malariae -do not possess dormant forms and can’t cause relapses

Answer 75

``` fever thrombocytopenia neurologic alterations (microthrombi) Renal dysfunction (microthrombi) Schistocytes ``` PT, pTT normal -thrombocytopenia causes petechiae, ecchymoses, purpura, and prolonged bleeding time. Treatment is plasmapharesis frequently seen in women. also see elevated indirect bilirubin and lactate dehydrogenase characteristic of microangiopathic hemolytic anemia.’ Similar presentation to HUS except no mental status change, commonly in children, following E.coli O157:H7 infection.

Answer 76

Erythrocyte sedimentation rate - rate what which red cells settle in blood Decreased (slow rate) - sickle cell anemia (altered shape) - Polycythemia vera (many cells) - CHF (unknown) Increased (fast) - inflammation - increased antibodies, make RBCs stick better to each other (CRP is another marker of inflammation, rises more rapidly in inflammatory conditions and is not as affected by other shit so its better, ESR is just cheap and easily performed.

Answer 77

``` CLL -small round lymphocytes and smudge cells, neoplastic B cells, CD19, 20, CD5 (anomaly) -hypogammaglobulinemia -autoimmune hemolytic anemai 0transformation to DLBL (richter) ```

Answer 78

Glanzmann thrombasthenia - defective or decreased levels of CPiib/iiia Von Willebrand disease, Bernard Soulier (GPIb)

Answer 79

Ex 35 yr old with painful palpable masses in the groin. Multiple enlarged abscessed lymph nodes draining through the skin through indolent sinuses. - primary lesion is a self-healing papule or shallow ulcer - painful enlarged abscessed lymph nodes termed "buboes" with stellate abscesses - causative organism is C.trachomatis - granuloma inguinale caused by Klebsiella is PINLESS.

Answer 80

ITP - acquired autoantibody G6PDH deficiency - X linked recessive TTP - acquired or inherited deficiency in ADAMTS13 HIT - autoantibody against PF4 Bernard Soulier - autosomal recessive, extremely rare Glanzmann Thromboasthenia- GPIIb/IIIa deficiency - autosomal recessive Von Willebrand - autosomal dominant Hemophilias - X linked recessive (usually in males) - PTT PNH -acquired Hemophilias - X linked recessive

Answer 81

Acetaminophen - especially if its lack of gastric distress and cardiovascular risk matter. It has no effect on reducing inflammation Poisoning: hepatotoxicity - asymptomatic for the first 24-48 hrs, end organ toxicity manifests. N-acetylcysteine is antidote for acetaminophen toxicity .

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