2025 MSB_Hematology Oncology

Prévia do material em texto

HEMATOLOGY + ONCOLOGY HEMATOLOGY + ONCOLOGY Embryology Thalassemia 318 Sickle Cell Disease 319 Microcytic Anemias 320 Heme Synthesis Pathologies 321 Macrocytic Anemias 322 Macrocytic Anemias Cont. 323 Intrinsic Hemolytic Anemias 324 Extrinsic Hemolytic Anemias 325 Primary Hemostasis & Anti-Platelets 326 Platelet Disorders & Microangiopathies 327 Coagulation Cascade & Anticoagulants 328 Bleeding vs. Clotting Disorders 329 ABO Classification Coombs Test 330 Erythropoiesis (Polycythemia) 331 Thrombopoiesis (Myelofibrosis & Essential Thrombocytopenia) 332 Granulocytopoiesis & Monocytopoiesis 333 Lymphopoiesis (Hodgkin's Lymphoma) 334 Lymphopoiesis (Non-Hodgkin's Lymphoma) 335 Plasma Cell Dyscrasias 336 Lymphopoiesis of Cells & Tumor Lysis Syndrome) 337 Leukemias 338 Notes 339 References LEGEND - PHARMACOLOGY RISK FACTORS MEMORY TRICKS PATHOLOGY Embryology & Thalassemia SITES OF ERYTHROPOIESIS THINK! Liver Supports Blood!" Y YOLK SAC PLEEN BIRTH Fetal Hb (HbF) Decrease 40- Y Increased affinity Fetal (HbF) Increased Adult (HbA) extraction from 30- maternal circulation Adult Hb produced starting at WEEK gestation! 20- Embryonic globins 10- Adult Hb (HbA) Lower affinity than 0 6 12 18 24 30 36 6 12 18 24 30 36 42 HbF promotes O2 ADULT release tissues FETUS (weeks of development) POSTNATAL (months) >> THALASSEMIA GENERAL ASSOCIATIONS OF THALASSEMIA: arget cells Jolly Bodies nisocytosis ow MCV Thalassemia Thalassemia Thalassemia minima minor Hemoglobin H Hemoglobin Barts Alpha-globin gene One deletion Two deletions Excess Excess globins the deletion on silent (cis trans) formation of CHROMOSOME 16 carrier lead to the decreased Symptomatic formation of globin units globin synthesis Asymptomatic anemia globin Leads (No anemia) Increased 80) units HYDROPS FETALIS OUTPUT prevalence among Symtomatic NO TREATMENT NO TREATMENT HEART FAILURE and REQUIRED anemia REQUIRED populations 80) incompatible with Thalassemia Thalassemia Thalassemia minor major absent -> severe NOTE! Point mutation microcytic hypochromic anemia Patients with on CHROMOSOME X with target cells Thalassemia who are decreased electrophoresis Marrow expansion skeletal globin synthesis deformities symptomatic may require term Increased Extramedullary hematopolesis transfusion. prevalence among Usually splenomegaly IRON CHELATION must be Mediterranean asymptomatic Delay immediate presentation administered avoid populations HbF (protective) begins to decline months after birth iron overload! 318Sickle Cell Disease TESTING FOR SICKLE CELL THINK! CHANGE IN AMINO ACIDS Electrophoresis "Val's Sickle Autosomal recessive missense mutation of stays away from her GLUTAMIC ACID to VALINE at the 6th position of Hemoglobin with HbS lacks the acidic Friend Anode!" the beta globin gene (chromosome 11) GLUTAMIC ACID resulting in decreased migration towards the anode Origin AA GLUTAMIC ACID VALINE disease NOTE: with the sickle cell trait/disease will have HbS! disease disease WHY DOES SICKLING OCCUR? Sickling occurs in reponse to triggers CATHODE low O2, acidosis) chain Adult) Hemoglobin chain Fetal) Polymerization of HbS vaso-occlusion Sickle cell MORE COMMON Patients of African descent SYMPTOMS OF "S.I"CKLE CELL Sequestration: As RBCs pass go through the microcirculation they are at risk of sickling and causing vaso occlusive complications. AUTOSPLENECTOMY become Repeated vaso occlusion VASO (early fibrosis OCCLUSIVE Howell SPLENIC COMPLICATIONS RENAL PAPILLARY jolly bodies INFARCTION NECROSIS Glutamic acid Lysine Splenic THINK! decreases IgM Decreased Milder than sickle cell and can lead extravascular hemolysis activation PRIAPISM ACUTE CHEST DACTYLITIS patients more prone NECROSIS SYNDROME Seen in Osteomyelitis! HAEMOPHILUS Infection STREPTOCOCCUS NEISSERIA INFLUENZAE SALMONELLA PNEUMONIAE MENINGITIDIS TYPE Parvovirus APLASTIC CRISIS (temporary decrease RBC production) ENCAPSULATED ORGANISMS TREATMENT Promotes the production SPLENECTOMY Reduces of HbF which decreases sickling of RBCs complications Acute: Focus on adequate pain control Chronic: associated with splenic sequestration Supplemental oxygen requires prophylactic Appropriate hydration vaccinations 319 Microcytic Anemias MCV Microcytic anemia Generally normocytic but can become microcytic CAUSES OF IRON DEFICIENCY: IRON SYNTHESIS: CKD, Autoimmune diseases GAIN IRON FROM DIET 5 Long standing Iron TREATMENT: derived) inflammation causes Deficiency TIL-6 Address underlying . Non based disease state (vegetable based) EPO Hepcidir from (important factor absorption) ABSORBED THE binds DUODENUM ecreased absorption Heme GIT gastritis more absorbed Decreases gut rugs absorption release TRANSFERRIN( PPI, NSAIDs from macrophages synthesized absorbed rain (blood loss) Macrophages GIT bleeding PPH bone and storage emand NOTE! Pregnancy bound Macrophages deter free Hookworms like ANCYLOSTOMA SYMPTOMS & NECATOR AMERICANUS can penetrate bare feet ... migrate intestinal wall -> suck blood cause iron deficiency anemia! PALLOR RESTLESS LEGS KORONYCHIA PICA Severe INTERPRETATION OF IRON STUDIES IRON DEFIECIENCY CHRONIC DISEASE HEMOCHROMATOSIS PREGNANCY OCF USE Serum iron 1 Transferrin TIBC 1 Ferritin 1 - % transferrin saturation 320 J (serum iron/TIBC) Heme Synthesis & Pathologies R ACUTE INTERMITTENT PORPHYRIA X-LINKED SIDEROBLASTIC ANEMIA Defect ALA synthase Autosomal dominant . Basophilic stippling due to iron being trapped in the mutation Porphobilinogen mitochondria, visible via PRUSSIAN BLUE STAIN deaminase . Acquired causes of sideroblastic anemia include: B6 lead THINK! 5 P's myelodysplastic syndromes . Labs: Ferritin Pyridoxine (B6) ain (abdomen) TIBC ort wine pee SUCCINYL COA ALA SYNTHASE olyneuropathy (Rate limiting enzyme) AMINOLEVULINIC ACID sychological turmoil Isoniazid) GLYCINE 450 (Things that increase ALA synthase Alcohol) LEAD POISONING TREATMENT: Hemin glucose Inhibits ALA Dehydratase Ferrochelatase Symptoms "LEAD" poisoning: HEME ALA DEHYDRATASE ead Lines on Longbones of metaphysis PORPHOBILINOGEN ncephalopathy Erythrocyte basophilic stippling bdominal colic PORPHOBILINOGEN OUTSIDE sideroblastic Anemia DEAMINASE MITOCHONDRIA rop (foot and hand drop) HYDROXYMETHYLBILANE EDTA dimercaprol FERROCHELATASE THINK! EdAT lead! INSIDE PROTOPORPHYRIN MITOCHONDRIA UROPORPHYRINOGEN III COPROPORPHYRINOGEN UROPORPHYRINOGEN DECARBOXYLASE PORPHYRIA CUTANEA TARDA Photosensitivity Porphyrinogen builds up on the skin reacts with UV light -> blistering skin lesions hCv causes most acquired cases Triggers (Alcohol) & Tea colored urine THINK! requires Hydroxychloroquine & Phlebotomy 321Macrocytic Anemias MCV > 100 PERIPHERAL SMEARS OF MEGALOBLASTIC ANEMIA MEGALOBLASTIC ANEMIA SHOWS: Hypersegmented neutrophils Caused by faulty DNA synthesis/repair, leading due impaired division of to B12 and folate deficiency granulocytes Enlargement of RBC precursors IMPAIRED DNA SYNTHESIS Anemia Protein Fatty acids AA's THF METHIONINE SAM anabolic pathways METHYLMALONYL COA COBALAMIN Methionine SAM synthase COBALAMIN Methylmalonyl- CoA mutase SUCCINYL COA HOMOCYSTEINE HEME TCA CYSTEINE FOLIC ACID DEFICIENCY (B9) COBALAMIN DEFICIENCY (B12) SMALL RESERVE pool stored in the liver LARGE RESERVE pool stored in the liver DEFICIENCY Increase in HOMOCYSTEINE only DEFICIENCY Increase in METHYLMALONIC CAUSES OF FOLATE DEFICIENCY: CAUSES OF COBALAMIN THINK! "A FOLIC POD" Malabsorption (i.e. Crohn's) Loss Intrinsic factor (i.e Folic acid antagonist pernicious anemia) Oral contraceptive Decreased intake THINK! Pregnancy Alcoholism Low dietary intake NOTE: Folate supplementation MMA MethyMalonic Old age can mask 812 deficiency from Acid MMA fighters Infection (Giardia) Dilantin the hematological perspective kicked the head Celiac sprue but not neurological! (Neurologic Symptoms!) OROTIC ACIDURIA NOTE: Autosomal Recessive deficiency in UMP synthase Buildup of Orotic acid No hyperammonemia unlike Ornithine transcarbamylase THINK! UMP: Unresponsive to B12 Megaloblastic anemia ediatric population deficiency 322 Macrocytic Anemias Cont. IMPAIRED DNA REPAIR Anemia CAUSES APLASTIC ANEMIA: FANCONI ANEMIA THINK! "Really Vicious Development (bone marrow)!" Autosomal recessive mutation of DNA cross link repair Radiation Labs can also show normocytic anemia as well infections (i.e. EBV, HIV, hepatitis) Fanconi anemia diopathic (immune mediated) Drugs (benzene, chloramphenicol, alkylating agents antimetabolites) ABSENT THUMB APLASTIC ANEMIA INTELLECTUAL DISABILITY PANCYTOPENIA SHORT STATURE SKIN FACIAL ANOMALIES ANOMALIES OF MACROCYTIC ANEMIA Hypopigmentation Microcephaly UPPER LIMBS HORSESHOE KIDNEY Hyperpigmentation Small eyes & RENAL ANOMALIES Vitiligo Absent ears spots NON MEGALOBLASTIC ANEMIA Enlargement of RBC's WITHOUT neutrophil hypersegmentation CAUSES: DIAMOND BLACKFAN ANEMIA LIVER DISEASE CHRONIC ALCOHOL CONSUMPTION CLINICAL FEATURES: HbF ADA Microcephaly Webbed neck Triphalangeal thumbs Nonmegaloblastic PURE RED CELL aplasia unlike Fanconi which shows pancytopenia 323 Intrinsic Hemolytic Anemias problem with the RBC itself!" HEREDITARY SPHEROCYTOSIS A. dominant defect of RBC cytoskeleton membrane proteins: includes ankyrin, spectrin, band 3 Membrane protein defects membrane instability spherocytes Spherocytes with loss of central pallor Increased RDW Mean Corpuscular Hemoglobin Concentration (MCHC) pigmented gallstones Increases risk for aplastic crisis (parvovirus B19) Eosin-5 -maleimide (flow cytometry) & COOMBS negative Splenectomy PAROXYSMAL NOCTURNAL HEMOGLOBINURIA Acquired hematopoietic stem cell mutation absent GPI anchor proteins cells susceptible to complement CDSS DAF/CDSS & MIRL/CD59 on blood cells protect against complement mediated destruction THINK! PNH Pancytopenia CD59 SHUNT Negative COOMBs (in cytoplasm) Hibernating (acidosis at night activates complement) Flow cytometry (lack of CD55 on blood cells) Eculizumab (targets complement protein C5) G6PD DEFICIENCY recessive defect in G6PD decreases G6PD decreases G6PD catalyzes the first NADPH decreases reduced glutathione oxidative injury and rate limiting step the HMP pathway FINDINGS THINK! BITES & BODIES!" BEANS: Fava beans, sulfa drugs, infections trigger oxidative stress hemoglobinuria & back pain hours after exposure! BITES: The spleen bites chunks out of the creating bite cells Heinz bodies form inside RBCs due to denatured hemoglobin PYRUVATE KINASE DEFICIENCY recessive defect in pyruvate kinase decreases ATP rigid RBCs extravascular hemolysis Can Burr cells end stage renal disease! Hemolytic anemia of newborn 324 Blood Smear: Burr cellsExtrinsic Hemolysis Anemias "The environment is the problem!" AUTOIMMUNE HEMOLYTIC ANEMIA Antibody mediated or IgM) destruction of RBCs "Warm weather is Good, go outside!" WARM causes extravascular hemolysis SEEN drugs (i.e. methyldopa) "Cold weather is Misery, stay inside!" COLD AIHIA: IgM complement cause agglutination & intravascular hemolysis upon exposure to cold. SEEN IN: Mycoplasma pneumoniae & Mononucleosis Spherocytes & agglutinated RBCs DIAGNOSIS Direct COOMBs POSITIVE (+) MICROANGIOPATHIC HEMOLYTIC ANEMIA Shearing of RBC's schistocyte formation intravascular hemolysis Occurs with: MICROTHROMBI DIC, HELLP) PROSTHETIC HEART VALVES AORTIC STENOSIS Produce schistocytes! Plasmodium Babesia MALARIA: Fever, headache, anemia, BABESIOSIS: Fever & hemolytic anemia splenomegaly Predominantly & vivax/ovale (two for days 48HR CYCLE) FEATURES Northcentral US Dormant form (hypnozoite) liver Increases risk of severe disease in asplenia Falciparum (Fast fevers daily severe) Anopheles mosquito TRANSMISSION Ixodes tick Trophozoite ring within RBC DIAGNOSIS Ring maltese cross Chloroquine primaquine TREATMENT Atavaquone azithromycin 325 Primary Hemostasis & Anti-Platelets Platelet Blood formation (PRIMARY INJURY EXPOSURE ADHESION ACTIVATION AGGREGATION Endothelial binds Platelets bind ADP binding to Fibrinogen binds receptors damage to exposed via Gplb receptor receptor and links platelets transient the site injury induces Balance vasoconstriction from only (specific) Illa expression AGGREGRATION ANTI- AGGREGRATION neural Palade bodies of platelets undergo platelet FACTORS mulation reflex endothelial cells conformational surface (released and NO and endothelin and change (released from by platelets) (released by of platelets endothelial cells) damaged cell) Platelets release ADP and PRIMARY SECONDARY (necessary for HEMOSTASIS HEMOSTASIS coagulation Mucocutaneous Deep muscle/ bleeding joint bleeding Temporary plug stops defective due issue in easily dislodged platelet plug! clotting cascade! Evaluate ADP helps platelets adhere to endothelium Coagulation cascade bleeding time (SECONDARY HEMOSTASIS EPTIFIBATIDE ARACHIDONIC ACID ASPIRIN CLOPIDOGREL TICLOPIDINE Receptor ADP Receptor Fibrinogen Gplb Subendothelial collagen Receptor PHARMACOLOGY DRUG MOA USE SIDE EFFECTS MEMORY TRICK IRreversible ACS, stroke Ulcers, tinnitus, IRreversible COX inhibitor prophylaxis renal injury COX Clopidogrel, Blocks ADP (P2Y12) Same aspirin Prasugrel, receptor (dual antiplatelet Neutropenia Grel, dine PlaY1e Ticlopidine therapy) Tirofiban, Eptifabatide, Blocks Unstable angina, PCI Bleeding TEA 2.30pm! Abciximab Thrombolytics Activates plasminogen Early ischemic Bleeding "plase" to plasmin cleaving stroke, PE active bleeding, Cut this clot "PLeASE" 326 (i.e. alteplase) clots recent surgery, severe HTN) Platelet Disorders & Microangiopathies Platelet Disorders IMMUNE (ITP) Immune, Platelets destroyed by SPLEEN VON WILLEBRAND DISEASE dominant macrophages phagocytose platelets "one" willebrand factor binds GP "one" b (Gp1b) Platelet antibodies Deficiency leads to defect in platelet adhesion INCREASES BLEEDING TIME platelets Also carries/protects factor VIII tiologies (autoimmune, viral, malignancy) Deficiency leads to intrisnic pathway defect INCREASES PTT bleeding time TREATMENT: Desmopressin (releases vWF) Next step Steroids (1st line), IVIG, rituximab or SPLENECTOMY (if refractory) RISTOCETIN TEST Ristocetin normally activates HOWEL-JOLLY BODIES binds on platelets basophilic nuclear platelets fail aggregate with ristocetin remnants (seen in defect (VON WILLEBRAND DISEASE or functional asplenia) Gp1b Bernard-Soulier GLANZMANN THROMBASTHENIA recessive Autosomal recessive There only in Bernard Soulier (Gp There are n's in Glanzmann (Gp2b/3a) Defect platelet adhesion Defect in platelet aggregation Abnormal RISTOCETIN No platelet clumping (on smear) Decreased platelets, increased bleeding time Normal increased bleeding time THROMBOTIC Thrombotic Microangiopathies THROMBOCYTOPENIC PURPURA (TTP) HEMOLYTIC UREMIC Inhibition metalloprote decreases Microangiopathic SYNDROME (HUS) degradation of multimers Hemolytic anemia increases large multimers Schistocytes This SHIGA TOXIN producing coli increases platelet infection (0157:H7 serotype). causes endothelial damage COMMONLY IN: Females hemolysis leading microangiopathy look LOW TREATMENT: Plasmapheresis haptoglobin! COMMONLY IN: Children exchange steroids TRIAD TREATMENT Supportive care TRIAD Thrombocytopenia Acute Kidney TRIAD FEVER Injury BLOODY DIARRHEA NEUROLOGICAL SYMPTOMS to 327Coagulation Cascade & Anticoagulants 30 40s NORMAL 10 12s VALUES PLAY TABLE TENNIS INSIDE PTT PLAY TENNIS OUTSIDE PT Contact activation (damaged surface) INTRINSIC PATHWAY EXTRINSIC PATHWAY Injury XII Tissue Factor (TF) VII XI IXa COMMON PATHWAY XIII Prothrombinase complex PROTHROMBIN THROMBIN CLOT FIBRINOGEN FIBRIN (la) FORMATION Heparin Warfarin Activates ANTITHROMBIN III Decreases Inhibits VITAMIN K EPOXIDE REDUCTASE action of thrombin inhibits y-carboxylation of clotting factors: VII. IX. protein USE: Immediate anticoagulation (i.e acute coronary DVT) THINK! "War of 1972!" PTT ADVERSE EVENTS: Bleeding (reverse with protamine Chronic anticoagulation (i.e. VTE prophylaxis sulfate) & HEPARIN INDUCED THROMBOC (HIT) & atrial HIT occurs due to platelet factor (PF4) MONITOR: PT/INR antibodies, leading to paradoxical thrombosis ADVERSE Bleeding (reverse with vitamin despite low K skin/tissue TREATMENT: Discontinue heparin! interactions metabolism) Low molecular weight heparins enoXaparin) Initial risk of hyper Protein C act mainly on -> administer subcutaneously depletes first (shorter 1/2 life then factors X) and doesn't require monitoring causing temporary pro coagulant state before LOW MWH CI in pts with function! full anticoagulation 328 TREATMENT: Prevent with heparin bridging! Bleeding vs. Clotting Disorders BLEEDING THROMBOPHILIAS Hemophilia Intrinsic pathway coagulation defect PTT). Antithrombin Deficiency "A sounds like eight" Normally inactivated thrombin inhibits deficiency factor VIII coagulation (DEFICIENCY can't inhibit!) recessive Look for MALE child! PTT after heparin DIMINISHED deficiency factor IX deficiency in factor XI Autosomal recessive Factor V Leiden Most common inherited thrombophilia Hemarthrosis (bleeding into joints) Production of mutant factor that Easy bruising resistant to degradation by protein Bleeding after trauma or surgery SYMPTOMS recurrent pregnancy loss TREATMENT: Desmopressin (for Hemophilia A) +/- replace factors Protein C/S Deficiency Normally Protein Cancels protein Vitamin Deficiency Newborns Stops coagulation DEFICIENCY inability to inactivate factors Va Villa General coagulation defect. birth! Hemorrhage (i.e. ecchymoses) Prothrombin Gene Mutation cirrhosis, fat malabsorption, prolonged Point mutation in untranslated region use of antibiotics, warfarin production of prothrombin plasma PT normal bleeding time levels clots DISSEMINATED INTRAVACULAR COAGULATION (DIC) BLEEDING & CLOTTING DISORDER Widespread clotting Deficiency Prolonged factor activation clotting factors bleeding state CAUSES: THINK! STOP Making New Thrombi! LABS: Sepsis bstetric complications ancreatitis PTT alignancy ephrotic syndrome ransfusion reactions ANTICOAGULANTS CONT. DRUG MOA USE SIDE EFFECTS MEMORY TRICK DIRECT THROMBIN INHIBITORS Venous Bleeding (reverse Bivalirudin thromboembolism two bi! Dabigatran atrial fibrillation with idarucizumab) DIRECT FACTOR Xa INHIBITORS Prophylaxis Bleeding (reverse Inhibit and all have Apixaban treatment DVT Rivaroxaban with andexanet alfa) their name! &PE 329 ABO Classification & Coombs Test ABO CLASSIFICATION HEMOLYTIC DISEASE GROUP A GROUP GROUP AB GROUP OF THE NEWBORN Commonly involves either ABO or Rh Red blood incompatability between mother & fetus . cell type Antibodies Anti-A & None Anti-B Anti-B Anti-A Antigens red blood None FIRST BIRTH AFTER cell DELIVERY PREGNANCY A antigen antigens ABO HEMOLYTIC DISEASE RHESUS ANTIGENS MOTHER: Type FETUS: Type A/B Series of antigens that coat RBCs Rh -D subtype is the most immunogenic Preformed cross placenta and RHESUS (+) RHESUS (-) cause fetal RBC hemolysis RHESUS Mild generally self -limiting STATUS Typically negative Rh antigens Lack antigen coat RBC's on their RBC's Phototherapy or No Anti antibodies exchange transfusion COOMBS TEST RH HEMOLYTIC DISEASE MORE SEVERE Laboratory test used to detect antibodies against RBCs If Mother Rh (-), obtains Rh (+) Antigen antigens from first pregnancy DIRECT COOMBS Subsequent pregnancies lead to TEST Erythrocyte anti- crossing the placenta rythrocytes Diffuse RBC hemoylsis Hydrops Fetalis Kernicterus Antibodies serum Positive + INDIRECT COOMBS TEST Via routine antenatal Reagent screening and administration of erythocyte to Rh (-) mothers 330Erythropoiesis RYTHROPOIESIS TOPOIESIS MONOCY TOPOIESIS LYMPHOPOIESIS REDUCTION NUCLEAR COMMON RED BLOOD CELL PARAMETERS CYTOPLASMIC RATIO AS PROGENITOR CELLS DIFFERENTIATE IN THE BONE MARROW PARAMETERS EXPLANATION RBC COUNT Number of red blood cells that are in sample blood HEMOGLOBIN Amount of carrying in RBC HEMATOPOIETIC HEMATOCRIT Concentration of RBC relative to CELL APLASTIC total blood volume ANEMIA MEAN CORPUSCULAR PROERYTHROBLAST Destruction Average volume RBC's VOLUME (MCV) STEM CELLS Pancytopenia MEAN CORPUSCULA BASOPHILIC decreased Average mass of Hb per RBC HEMOGLOBIN (MCH) reticulocyte increased MEAN CORPUSCULAR Hypocellular HEMOGLOBIN Concentration of Hb all RBC's POLYCHROMATIC bone marrow Calculated by: Hb/Hct CONCENTRATION (MCHC) fatty infiltration RETICULOCYTE Measures appropriate bone marrow PRODUCTION INDEX response anemia ORTHOCHROMATIC Insufficient compensation Sufficient compensation maturation APLASTIC ANEMIA RETICULOCYTE CAUSES ERYTHROPOIETIN (EPO) Peripheral circulation PARANEOPL ASTIC CAUSES KIDNEY OF EPO PRODUCTION BONE ERYTHROCYTES Changes RCC, MARROW renal blood HCC, increases Responsible for transporting Ozand Leiomyoma reticulocyte CO2 between the lungs and tissues consumption production Lack of mitochondria means relies stimulates EPO ANEMIA TRIGGER soley on GLYCOLYSIS to generate ATP interstitial cells loss) Life-span roughly 90-120 days POLYCYTHEMIA VERA Subtype chronic Irreversible THROMBOSIS (arterial venous) TREATMENT 1° Clinical SYMPTOMS LABS myeloproliferative increase primarily driver NEUROLOGICAL SYMPTOMS Phlebotomy disorder JAK2 mutation production Hydroxyurea ERYTHROMELALGIA Ruxolitinib APPROPRIATE Physiological response High altitude Obstructive hypoxia sleep Heart failure LABS 2° Endogenous INAPPROPRIATE production outside of Paraneoplastic syndromes, EPO normal EPO 331 Thrombopoiesis ERYTHROPOIESIS THROMBOPOIESIS TOPOIESIS MONOCYTOPOIESIS LYMPHOPOIESIS MEGAKARYOCYTES BONE MARROW HEMATOPOIETIC MEGAKARYOCYTES PROPLATELETS PLATELETS Megakaryocytes reside PROGENITOR STEM CELL Platelets released the bone marrow "PLATELETS are into circulation THROMBOPOIETIN BANK that holds (TPO) stimulates Involved primary MEGOKARYOCYTE THROMBOCYTOPENIA hemostasis last roughly LOW PLATELET count TPO analogs can be ADP days PRESENTS AS: used treatment recycled the autoimmune eratonin liver/spleen! thrombocytopenias! Easy bleeding/bruising MEGAKARYOCYTES signal $ Petechiae JAK/STAT pathway (a receptor tyrosine kinase) UREMIC PLATELET DYSFUNCTION MUTATIONS IN Occurs CHRONIC KIDNEY DISEASE due Purpura THE JAK/STAT to uremia Uremic toxins impair platelet function Isolated prolonged bleeding time MYELOFIBROSIS ESSENTIAL THROMBOCYTHEMIA Neoplastic proliferation of MEGAKARYOCYTES Proliferation of MEGAKARYOCYTES high PLATELETS Neoplastic Increases risk of thromboembolic events and bleeding! megakaryocytes Generally asymptomatic but can present Excessive release Derived Growth Factor TGF activates fibroblasts GOUTY ARTHRITIS ERYTHROMELALGIA (intermittent hyperperfusion BONE MARROW of extremities) FIBROSIS LABS: Pancytopenia Thrombocytosis 450 10^9/L) Megakaryocyte hyperplasia on bone marrow DACROCYTES "Tear shape are seen smears Hypodense platelets on peripheral smear bone fibrosis! 332 Granulocytopoiesis & Monocytopoiesis ERYTHROPOIESIS GRANULOCYTOPOIESIS MONOCYTOPOIESIS LYMPHOPOIESIS EOSINOPHILS CAUSES OF EOSINOPHILIA: Bi-lobed nucleus Contains major basic proteins Key helminth defense Type HS arasites sthma hronic Adrenal Insufficiency CAUSES EOSINOPENIA: yeloproliferative llergic process eoplasia osinophilic disorders granulomatosis Corticosteroids MAST CELLS Localized tissues MASTOCYTOSIS TYPE HYPERSENSITIVITIES Sensitized binding Clonal proliferation of caused degranulation receptors mast cells due of primed mast cells toward Degranulation releases mutation specific leukotrienes Systemic symptoms CROMOLYN stabilizes and cytokines pruritus, mast cells by preventing triggers allergic gastric secretion degranulation (used inflammatory responses asthma prophylaxis!) NEUTROPHILS NEUTROPHILIA Main contributor in acute LEUKEMOID REACTION (reactive) (myeloproliferative) inflammatory responses . fusion phagocytic cell stress LOW score HIGH LAP score LEFT SHIFT Increase immature neutrophils NEUTROPENIA myelocytes) due bone . Corticosteroids (early) Radiation Sepsis (late) marrow stimulation LEFT SHIFT AGRANULOCYTOSIS increased reticulocytes Drugs Can Cause Clozapine REACTION Pretty Major Granulocytes Collapse Colchicine BASOPHILS Contribute to Monocytes Macrophages hypersensitivity . Monocytes circulate the blood differentiate reactions into macrophages upon entering tissues Macrophages function phagocytes Least common tissue healing and circulating WBC remodeling Contain granules Certain racellular pathogens histamine & macrophages evading destruction LEISHMANIA leukotrienes CML notable Kala-azar (Visceral) pancytopenia, intermittent fevers, hepatosplenomegaly cause Cutaneous skin ulcers 333Lymphopoiesis ERYTHROPOIESIS THROMBOPOIESIS GRANULOCY TOPOIESIS MONOCYTOPOIESIS LYMPHOPOIESIS HODGKIN'S LYMPHOMA B CELL CELL REED STERNBERG CELLS Hodgkin's Lymphoma are POSITIVE CD15 and CD30 receptors CD15 CD30 Targeted EBV CD21 KEY POINTS THINK! Neoplasms found single/ REED STERNBERG cluster lymph nodes CELLS: bilobed Class CD40 Spreads contiguously nucleus looks like switching a OWL Histology REED STERNBERG CELLS EYES (eyes) CD15 CD30! ASSOCIATED WITH EBV Co-stimulatory signal T-cell SUBTYPES activation LYMPHOCYTE RICH Increased ratio of normal B-cells: REED STERNBERG CELLS Antigen presentation CD4+ T-cells . NODULAR SCLEROSIS BIMODAL DEMOGRAPHICS Most common type (females males) OF HODGKIN'S LYMPHOMA YOUNG ADULTS MIXED CELLULARITY (20'S) Increased Eosinophils seen in ADULTS immunocompromised populations (50'S) LYMPHOCYTE DELPLETED Decreased ratio of normal B-cells: 334 REED STERNBERG CELLS Lymphopoiesis Cont. ERYTHROPOIESIS THROMBOPOIESIS GRANULOCYTOPOIESIS MONOCYTOPOIESIS LYMPHOPOIESIS NON-HODGKIN'S LYMPHOMA B CELL T CELL CELL CHROMOSOMAL BURKITT LYMPHOMA FOLLIUCLAR LYMPHOMA TRANSLOCTATION Lymphoma and heavy chain [14:18] Has letters! ASSOCIATED EBV infections and higher incidence in children(KIDS) Translocation involves the BCL-2 gene APOPTOTIC gene) Most common low grade Non- Hodgkin's Lymphoma Slow growing commonly presenting as indolent neck mass over several years appearance on with tingible MARGINAL ZONE LYMPHOMA body interspersed within sheets ymphocytes [11:18] Proliferation of -cells in the MANTLE CELL LYMPHOMA marginal zone of lymphoid follicles tell" lymphoma MALT Associated with long can be resolved via erradication Translocation leads to increased NON-MALT Associated expression of cyclin unable with chronic autoimmune diseases halt cell cycle (i.e. Sjogren's) Affects males over females ("MAN") Extremely aggressive with poor prognosis there lymphoma Mantle Cell Lymphoma CDS positive CDS GENETIC MUTATIONS DIFFUSE LARGE PRIMARY CNS B-CELL LYMPHOMA LYMPHOMA Mutations and BCL Subtype Diffuse Large B-Cell MOST COMMON subtype of Lymphoma Hodgkin's Lymphoma MRI reveals ring enhancing lesions Increased incidence in older age ASSOCIATED WITH: EBV AIDS infection KEY POINTS Diffuse lymph node involvement POORER Both Hodgkin's and Non- Spreads contiguously PROGNOSIS Hodgkin's Lymphoma have Majority of Non Hodgkin's involve cells with "B SYMPTOMS' Non specific some cell subtypes constitutional symptoms like ASSOCIATED WITH long-standing autoimmune grade fevers, night sweats, conditions or chronic diseases and weight loss! (H. pylori) also known as 335 Plasma Cell Dyscrasias ERYTHROPOIESIS THROMBOPOIESIS GRANULOCYTOPOIESIS MONOCYTOPOIESIS LYMPHOPOIESIS SERUM PROTEIN ELECTROPHORESIS (SPEP) ABNORMAL IgA PEAK M spike CELL IgG IgM ALBUMIN Y NORMAL MULTIPLE MYELOMA WALDENSTRÖM MULTIPLE MYELOMA MACROGLOBULINEMIA Overproduction of IgA. Overproduction of IgM Sporadic proliferation of plasma cells (>10% in (MACRO IgM largest bone marrow) Serum protein will show M with COMPLICATIONS: Increased infection risk Headache increased concentrations of IgM amyloidosis Increased serum IgM Hyperviscosity phenomenon Blurry vision MANIFESTS CLINICALLY alcemia (hyper): plasma cells stimulate osteoclasts increases bone resorption due to light chain deposition in tubules. BENCE JONES proteins can be found in urine PERIPHERAL RETINAL HYPERVISCOSITY NEUROPATHY HEMORRHAGE SYNDROME due to lymphoid shift & kidney failure MONOCLONAL GAMMOPATHY OF (Decreases EPO production) UNDETERMINED SIGNIFICANCE lytic lesions due to increased osteoclast activity Overproduction of ANY Immunoglobulin. Biopsy of the bone marrow will show 10% plasma Absence of any myeloma defining event (no CRAB). 1-2% risk per year of transforming into MULTIPLE MYELOMA MORPHOLOGY OF PLASMA CELLS Mature and differentiated B-cells expressing antigenic specific antibodies. Rouleaux formation found peripheral "Clock-face" chromatin smears distribution all . Large concentration of RER + PLASMA DYSCRASIAS Golgi bodies 336Lymphopoiesis THROMBOPOIESIS GRANULOCY TOPOIESIS MONOCY TOPOIESIS LYMPHOPOIESIS NATURAL KILLER CELLS Lymphocyte of the innate immune system. CD56 CD16 (FeR) . Destroy antigens via antibody dependent destruction CELL CELL using their CD16 receptors GRANULES Capable of destroying viral and tumor infected cells via binding of non-specific markers on cell surface i.e. cells that do not have MHC on their surface THINK! T-LYMPHOCYTES Responsible for driving adaptive and cellular immunity. T-cells mature Thymus CD4+ "Helper T-cells" CD8+ "Killer T-cells" Aids stimulating cell production as well Cytotoxic capabilities largely as secreting cytokines to drive phagocytosis responsible for defending against viral THINK! rule 8 and other innate inflammatory processes infections and aids tumor surveillance CD4 MHC 8 Stimulated by MHC binding on APC Co stimulation required for activation & CD8 MHC MHC recognition on somatic cells NEOPLASMS OF MATURE T-CELLS Both are subtype of Non-Hodgkins Lymphoma ADULT T-CELL LYMPHOMA CUTANEOUS T-CELL LYMPHOMA Associated with HTLV-1 infections Mycosis Fungoides most common subtype COMMON IN: The Toyko LOOK OUT FOR Erythematous changes Togo (West & Trinidad (Caribbean) on the skin in sun-protected areas! ASSOCIATED WITH: Hypercalcemia and lytic lesions Peripheral smear shows SEZARY CELLS Peripheral smear shows FLOWER CELL Treatment for advanced disease may involve CHEMOTHERAPY Epstein-Barr Virus Highly contagious spread via bodily secretions (Saliva) TUMOR LYSIS SYNDROME ONCOLOGIC EMERGENCY! CAN Rapid tumor cell often triggered by PUKE Calcium! MONONUCLEOSIS leads to the release intracellular Phosphorus . Pharyngitis causing hyperphosphatemia, Elevated Posterior and hyperuricemia K (potassium) lymphadenopathy Rasburicase Hepatosplenomegaly Calcium (decreased) Avoid contact sports until Tumor cell lysis resolution increased risk splenic rupture! MONONUCLEOSIS also associated with Lymphomas: Burkitt's Lymphoma Muscle tetany weakness . Lymphoproliferative disease Nasopharyngeal carcinoma Acute kidney injury 337 Leukemias A group of conditions distinguished by unregulated and undifferentiated growth of white blood cells in the bone marrow. BONE MARROW INFILTRATION ANEMIA + THROMBOCYTOPENIA + NEUTROPENIA Place L's Laterally the AGE M's Medially! ACUTE CHRONIC ACUTE MYELOID CHRONIC LYMPHOBLASTIC MYELOID LEUKEMIA LYMPHOCYTIC LEUKEMIA (ALL) LEUKEMIA (CML) (AML) LEUKEMIA (CLL) MOST COMMON Children THINK! "Crushed Little THINK! Lymphocytes" Slow progressing & most common adult Bone marrow biopsy leukemia (>60yrs) shows 20% blast Auer rods Can transform into cells THINK! . Very responsive to "CML CreaM cheese" (+) Diffuse Large -Cell Lymphoma therapy . Defined by trans retinoic acid Lymphoblasts are TDT PHILADELPHIA POSITIVE! chromosome RISK FACTORS HAIRY CELL Chemotherapy & LEUKEMIA TWO SUBTYPES Presents with basophilia radiation T-CELL ALL splenomegaly Myeloproliferative disorders BCR-ABL gene THINK! "Only T's" Down syndrome fusion activates tyrosine kinase ACUTE TDT (+) and initially unregulated cell PROTMYELOTIC presents Thoracic Filamentous/hairy proliferation mass (mediastinal) LEUKEMIA (APL) projections Also seen Trisomy Imatinib (a Mature -cell tumor in Twenty one (Down tyrosine kinase inhibitor!) Caused adult males transloc Syndrome) retinoic acid receptor Dry tap marrow fibrosis CELL ALL BLAST CRISIS Can present DIC Massive splenomegaly Spontaneous Treatment with All pancytopenia THINK! for Both mation AML Trans Retinoic Acid TDT CD10+ positive" (66%) ALL (33%) (ATRA) induces Stains TRAP (Tartrate Resistant Acid blastocyte maturity Phosphatase) 338 Notes 3391. Hematopathology Poikilocytes Red blood cell types Wikimedia commons.wikimedia.org. Retrieved 2. Krishnan Sharma (2021) macrophages in anemia of chronic disease ASH Image imagebank hematology.or Retrieved from: chronic-disease 3. Occupational Safety and Health Administration (OSHA) (2008). X-ray of lead poisoning Wikimedia Commons commons wikimedia Retrieved 4. James MD Pseudoporphyria Wikimedia Commons Retrieved https:// 5. Ed Uthman Hypersegmented neutrophils - Wikimedia Commons Retrieved from https:// 6. Main droite de Lauranne Wikimedia commons wikimedia Retrieved from: 7. Pathology Student and RDW in hereditary spherocytosis Pathology Student: pathologystudent.com Retrieved 8. CellWiki Erythrocytes Bite cells CellWiki: Retrieved from: 9. Joel Mills (2007). Heinz bodies in cat Wikimedia Commons commons Retrieved from: https://en.wikipedia.org/ 10. Hematopathology (2010) Poikilocytes Red blood cell types Wikimedia Commons Retrieved 11. (2021) Platelet clumping The Blood Retrieved from: platelet-clumping/ 12. Hematology (2007) Poikilocytes Red blood cell types Wikimedia Commons commons wikimedia Retrieved from: 13. Centers for Disease Control and Prevention Plasmodium ovale 01 Wikimedia Commons Retrieved from: 14. Centers for Disease Control and Prevention (CDC) (2017). Maltese cross in Babesia CDC: Retrieved from: https://www. cdc.gov/dpdx/resources/pdf/benchAids/Babesia_benchaid.pd 15. Cynthia Mohs Howell-Jolly body Wikimedia commons wikimedia Retrieved from: 16. StoryMD Primary myelofibrosis blood stain StoryMD: storymd Retrieved from: 17. Szycher Teardrop cells smear Wikimedia Commons commons wikimedia org. Retrieved from: https://en.wikipedia.org/ 18. Bobjgalindo (2007) Eosinophil blood smear Wikimedia Commons commons wikimedia Retrieved from: 19. Vortioxetine (2022) Mast cells in bone marrow Wikimedia Commons Retrieved from: https:// 20. G. (2012) Neutrophils Wikimedia Commons commons wikimedia Retrieved from: File:Neutrophils.jpg 21. G (2016) Granulocyte basophile Wikimedia commons wikimedia Retrieved from: org/wiki/File:Basophile-9.JPG 22. (2023) Reed-Sternberg cells MyPathologyReport.c Retrieved from: https:// 340 References 23. Centers for Disease Control and Prevention (n8). Burkitt's histopathology Wikimedia Commons commons Retrieved 24. in2Med Plasma cell disorders in2med.co.uk Retrieved from: https://in2med.co.uk/lesson/plasma-cell- disorders/ 25. (2025) Plasma cell disorders - in2med.co.uk Retrieved from disorders/ 26. Hellerhoff (2010). Plasmozytom multiple Osteolysen Unterarm Wikimedia commons wikimedia Retrieved from: 27. SpicyMilkBoy Flower cell in mantle cell lymphoma Wikimedia Retrieved from: 28. El*Falaf Wikimedia commons.wikimedia.org Retrieved from 29. Uthman, Infectious Mononucleosis 3 Wikimedia Commons Retrieved from: https:// 30. Animalculist Morphological types of acute lymphoblastic leukemia Wikimedia commons.wikimedia.org. Retrieved 31. Complete Care Community Health Center Chronic myelogenous leukemia Complete Care Community Health Center: Retrieved 32. Armed Forces Institute of Pathology Myeloblast with Auer rod Wikimedia Retrieved 33. Maslak Chronic Lymphocytic Leukemia 1 ASH Image Bank: imagebank.hematology.org Retrieved from: https:// 34. Hairy cell leukemia smear Wikimedia Retrieved from: https:// 341