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What 3 categories of disease cause anemia?
- 1. blood loss
- 2. RBC production
- 3. destroy RBC
What are tests for anemia?
- Hematocrit: low 40's (lower for females)
- erythrocyte 5M/uL
- evaluate Hg
What are 3 classes of anemia?
- normo: loss/decrease prod
- micro: Fe (hypochrom)
- macro: (B12, folate)
What are the intraoral signs of anemia?
- red, sore, smooth tongue(atrophy papillae)
- esophageal webs and dysphagia
- oral mucositis
What are therapies for microcytic anemia?
Fe replacement: ferrous sulfate(uncomplicated, 3-8weeks), deferoxamine(chelating, acute)
What enzyme converts homocysteine to methionine?
- hydroxocobalamin to methylcobalamin
- methionine synthase
What enzyme is necessary for folates role in DNA synthesis?
DHF reductase (DHF->THF) (di->tetra)
What is diff in clinical presentations of B12 and folic acid def?
- Both: pallor, anemia, fatigue, glossitis
- B12: neuro (myelin synthesis)
Exposure to what compound results in megaloblastic anemia?
NO: inhibit methionine synthase
What are the causes of folic acid deficiency?
- malabsorption, overcooking, maternal, hepatic(alcohol)
- drugs: phenytoin, oral contraceptives, antimalarials
- DHF reductase inhibitors(cancer, autoimmune): methotrexate, trimethoprim
- leucovorin counteracts DHF reductase inhibitors
What are the classes of antithrombic drugs?
- 1. anticoagulants: warfarin(coumadin), pradaxa, heparin (thrombin inhibitor)
- 2. antiplatelet: aspirin, clopidogrel, dipyridamole
- 3. thrombolytic (fibrinolytic):
What is the difference between low and high conc of heparin?
- low: accelerate antithrombin III (1000x) inactivating 9,10,12
- high: hep/antithrIII binds thrombin itself
- all parenteral admin
What is the heparin antagonist?
What are the indirect anitcoags?
- coumadin (warfarin)
- inibit reduction of Vit K (necessary for gamma carboxylation of 2,7,9,10)
- SE: hemmorhage
- Int: antimicrobials, barbituates (inc met), NSAIA (sensitize)
what does vit K do?
cofactor in gamma carboxylation of glutamic acid residues of clotting factors 2,7,9,10
What drugs are platelet inhibitors?
- Aspirin: (cyclooxygenase)TXA2 inhibitor
- Clopidogrel: ADP receptor antagonist (no agg)
- Dipyridamole: vasodilation, PDEase inhib->inc CAMP, less agg
What are fibronolytic drugs?
- plasmin: lyses fibrin, degrades factors 5,8
- plasminogen activators: t-PA (3 hour window) adheres fibrin, absorbs and cleaves plasminogen
- urokinase: activates circualting plasminogen
- steptokinase: (exotoxin) binds and kinda activates plasminogen
- anistreplase: streptokinase & acylated plasminogen
- uses: MI, pulm emb, DVT
How long should pt on aspirin or coumarin stop b4 procedure?
- aspirin: 5 days, start 1 day after
- coumarin: INR (international normalized ratio) 2.5 (5 bad, 1 avg)
- heparin: 6 hours or reverse w protamine, restart after clot formed
Which blood disorder pts are of particular concern for dentist?
- leukopenia: drug, chemo, cyclic neutropenia
- lekemias & lymphomas: dysfunctional WBC
What are important lab values to asses hematologic status?
- RBC: stress
- WBC: infection (osteomyleitis after extractions, antibiotic prohy)
- Platelets: hemostasis
What precautions should be done for pt on chemo?
- done befor chemo/radio
- CHX, antifungal rinses
- treat during intervals
- early after diagnosis
What does aPTT assess?
- partial thromboplastin time (30+-5 seconds)
- Intrinsic: 1,2,5,8,9,10,11,12 (8 most imp)
- heparin levels
What test is used to assess LMWH levels?
What are thrombophila causes?
- V mutation
- prothrombin mutation
- def of protein C, S or antithrombin
- acquired: inflammation (TF)
Consequences of DIC?
- bleeding: depleted factors, platelets
- thrombosis: organ failure (infarcs)
What does PT assess?
- prothrombin time: 13 secs+-1
- Extrinsic: 1,2,5, 7*, 10
- INR: international normalized ratio = pt PT/mean lab PT adj w/ international sensitivity
- warfarin/coumadin levels
Describe platelet ranges.
- <5,000 GI or cerebral hemmorhage
- <20,000 spontaneous bleeding
- >50,000 needed for surgical hemostasis
- <100,000 thrombocytopenia
- 150,000-300,000 normal
- life span 10 days
What is bleeding time evaluate?
- qualitative platelet function & vascular integrity
- 40mm Hg BP cuff and incision blotted every 30 secs
- 5 min +- 2 (longer 9.5 if aspirin)
What is PFA-100?
main test: platelet ability to aggregate to collagen-epi & collagen-ADP
What is are other qualitative platelet tests?
- platelet aggrometry: agg w/ ADP, collagen, Arachidonic acid, or EPI
- ultegra: bind fibrinogen
Heriditary coagulation disorders?
- Hemophilia A/B
- vWF disease
- v, VIII def
- hemorrhagic telangicastia
- Protein C def
- antithrombin III def
- intravascular activation
- cellular procoags: TF, cell lysis
- vascular factors: endothelial damage, hypotension/stasis shock
Acquired coag disorders?
- Vit K def
- drug-induced hemmorhage, platelet
- blood transfusion
- post bypass
- idiopathic or thrombotic thrombocytopenic purpura
- vWF is carrier for Factor VIII (inc half life and conc)
- low plasma vWF released from endothelium and platelets
- types (I, IIA, IIB, III)
- bleeding persists (usually diagnosed via dental)
- mild tx: desmopressin (DDAVP)
- moderate: viral factor VIII-vWF, cryoprecipitate(disease tx), antifibronlytics
- no aspirin/NSAIDS, acetomenophin& opiods OK
- coagulation adjuncts should be available
What are some antifibrinolytics?
- plasminogen activator inhibitors
- rinses of tranexamic acid
Is aspirin a dental procedure concern?
not really, NEVER stop for pts w/ Coronary artery stents
How many half lifes will NSAIDS be cleared?
4: 94% clearance
What are plavix(clopidogrel) and prasugrel(effient) dental concerns?
- active metabolites
- less bleeding problems than aspirin
- do not D/C
- never for stents
- if D/C need 6 days
- X linked recessive (males only, female carriers)
- Hemophilia A: (VIII def) 80%
- Hemophilia B: (IX def) 15%
- early hemostasis may bleed late
- watch out for Deep IM injections (IAN)
- tx: replace factors & antifibrinolytics, no aspirin/NSAIDs
For hemophilia what levels of VIII do you need for dental surgery?
- >40% general
- 80-100% for major oral
- use advate or cryoprecipitate
What does coumadin do?
- warfarin: competitive antagonist of vit K (epoxide reductase) 2, 7, 9, 10
- many interactions
- uses: DVT, post pulm emb, A-fib, Post MI/CVA, prosthetic valves
- asses PT/INR usually ok <3
What are the aids to coagulation?
- pressure packs
- aggregation promoters: geleini, collagin, collagen-like
- coagulation promoters: thrombostat
What should acetaminophen be limited to for pts on coumadin?
What are the dental concerns for heparin and LMWH?
- won't typically see hep
- LMWH: against Xa (enoxaparin) DVT, pulmonary embolus
- delay dental tx if possiible, consult MD
- useful as bridge D/C coumadin and start lovenox
NHL is what % of new cancers?
- 6th most common cause cancer death
- increasing incidence/mortality
What are the mechanisms of lymphomagensis?
- genetic alterations:
- infection: (H. pylori, Chlamydia psittaci, EBV(burkitts), HTLVI (Tcell) HTLV-V (cutaneous T-cell), Hep C
- antigen stim: Sjogrens
- immunosuppression: wiskott-aldrich, organ, AIDS, age
Clincal behavior classifications of lymphoma?
- low grade: indolent, incurable, years life expectancy (CLL,hairy cell)
- intermediate: aggressive
- high grade: very aggressive, potentially curable, weeks life expectancy (ALL, burkitts)
Clinical features of lymphomas?
lymphadenopathy (may fluctuate), cytopenia, hepatosplenomegaly, fever, night swears, weight loss
What is a waldeyer's ring a sign of?
What does a biopsy for NHL evaluate?
- morphology and nodal architecture
- immunohistochemistry: reveal monoclonal
What are important chromosomes involved with NHL?
- bcl-2 (14,18 trans follicular lymphoma)
- c-myc (Burkitts)
- cyclin D1 (mantle cell)
What is counterintuitive about indolent lymphoma treatement?
- stage III (both sides diaphragm) and IV(marrow) are highly curable
- wait til symptomatic to treat
What is the most common indolent lymphoma?
- follicular (bcl-2 absent) germinal center B-Cell
- translocation (14,18) fuses bcl-2 and IgH constitutively expressed
What is rituximab?
immunotherapy- monoclonal CD20 (B-cells) Ab
Does immediate treatement prolong survival of Follicular cell lymphoma?
What is Diffuse large B-cell lymphoma(DLBCL)?
- most common aggressive lymphoma
- usually symptomatic, extranodal, germinal center B-cell
- curable 60-75%
- rapidly enlarging mass(nodal)
- elevated LDH
What is the treatment course for DLBCL?
What is Burkitt's lymphoma?
- EBV associated
- abdominal, rapidly growing mass/tumor
- c-myc oncogene linked with Ig genes
What is hodgkin's disease?
- highly curable, not as common, Reed-Sternberg cells(giant B cells (popcorn), some w/EBV genomes)
- more common for rich, young(>50 bimodal)
- Pel-Ebstein fever(relapsing high-grade)
- painful to drink alcohol
- Predictable: cervical->mediastinum or axilla
- tx: ABVD, BEACOPP
- ABVD: adriamycin, bleomycin, vinblastine, dacarbazine
- sensitive to Radiation
What is a thick buffy coat a sign of?
too many WBCs and platelets
- neoplastic, unregulated accumulation or proliferation of WBCs
- assess: cell line, maturatation, chronic, acute
What are the granulocytes?
- myeloid progenitor
- BEN, baso, eosin, neutro
What are the agranulocytes?
- lymphoid progenitor
- lymphocyes, monocytes
- philly chromosome
- active tyrosine kinase
- anemic symtpoms (splenomegaly)
- all stages of myeloid(B,E,N), giant platelets
- low leukocyte alkaline phosphotase
- high B12 binding
What is philadelphia chromosome?
- abnormal 9-22 translocation
- BCR-ABL on 22 w always active tyrosine kinase
What are CML treatments?
- imantinib, (-inibs)
- marrow transplants, chemo
- no tx for blast crises
What are features of acute leukemias?
- generally unknown causes
- block of maturation, many immature blasts
- blasts in periphery, inc buffy coat, pancytopenia (mature) hypercellular, monotonous marrow
- AML increase w/age, ALL decrease then increase
- myeloblasts ubiquitous
- anemia, thrombo, neutorpenia
- leukemic infiltration
- 3-6 months survival
- translocation are favorable
- diploid, -Y is most common (intermediate prognosis)
Which leukemia presents w gum hyperplasia?
- M5- monoblastic
induction: cleared but could come back, follow w/ consolidation or transplant
- M3- acute promyelocytic
- DIC (from granules release)
- t(15,17) 90% treatable w/ vitamins
What are the features of ALL?
- most common of children (peak 3-4 yr old)
- adults usually relapse
- marrow and blood lymphoblasts
- CNS involvement
- 70% cureable in children(chemoradiation)
- L1: big no cytoplasm
- L2: large w/more cytoplasm
- L3: burkitts, big w/ vacuoles
What are oral complications of acute leukemias?
- leukemic infiltration-> gum hyperplasia: moncytic leukemias
- mucositis: chemo, radiation, neutropenia
- infections: abcess, herpes, candida
- bleeding: peticea, gingival
- graft vs host: mucostis, infection, secondary tumors
- small mature lymphocytes in blood
- hypercellullar marrow w mature small lymphocytes
- treat only if symptomatic
- Painless lymph nodes
- proliferating neoplastic PLASMA cells (crowds out other cells->pancytopenia)
- clonal and produce monoclona Abs (found in blood and urine)
- proliferate in marrow and cause skeletal destruction (radiolucent xrays)
- Rouleaux formation of RBCs (stuck in rows)
- excess bleeding light chains
Multiple myeloma tx?
- thlidomide, lenaldomide
Which marker indicates stem cells?
What is usually the most histocompatible relative?
- class I: A,B,C
- Class II: DR
What endothelial secretions inhibit platelet aggrigation?
what is the catalyst of fibrinogen?
Describe the intrinsic pathway.
- 12, 11, 9 (8) 10, V (prothrombin), 1 fibrinogen 13
- all factors in blood
- activation: damaged surface
What sets off the extrinsic pathway?
- tissue factor from fibroblast membranes (trauma)
- initiatesclotting transient because VIIa is inhibited
What factor is typically used to speed clottiing?
what does thrombin do?
- activates fibrinogen
- cleave thrombin receptor (activates platelets)
- cleave V adn VIII
- limit by cleaving Va and VIIIa
what else do platelets do?
release growth factors that facilitate healing
what are the natural clotting limiters?
- thombomodulin (protein C & S) hydolize Va, VIIIa
- antithrombin & 2a and 10a & heparin- antithrombin inactive protease complex
Role of vit k?
- 2,7,9, 10, C, S
- glutamate residues (gamma carboxylation)
- coumadin (oral) (K blocker)
what is a tPA drug name?
What are D-dimes?
- biproducts of plasmin breakdown of clots
What are some embryological milestones of hematopoiesis?
- 3 wks: yolk sac stem cells
- 3 months: migrate to liver (some in spleen, lymphoid dev in nodes and thymus
- 4 months: migrate to bone marrow (func after 7 mo)
- birth: cord blood w/hematopoietic stem cells
- 2 wks postpartum: hematopoiesis shifts to marrow
What hormone controls RBC production?
- erythropoietin: kidney, O2
- nutrients: Fe, B12, Folate
- normal bone marrow
- proerythroblast->basophilic eb->polychromatic eb-> normoblast
What is a reticulocyte?
immature RBC, no nucleus, reticular(mesh) rRNA (methylene blue)
What is the protein of the cytoskeleton of RBC?
What are normal lab ranges for erythron for males and females?
- name, male, female (lower numbers)
- RBC: 4.4-5.9, 3.8-5.2
- Hemoglobin: 13-18, 12-16
- hematocrit: 40-52, 35-47
- reticulocytes: 0.5-1.5%, 0.025-0.105/mm3
What are the normal ranges of RBC indices?
- MCV: avg volume 80-100
- MCHC= avg Hg/volume 31-36
- MCH: avg weight 27-34
What are the presentations of iron deficiency anemia?
- hypochromic, microcytic
- most common (cause chronic blood loss, menorrhagia, intesinal)
- Fe absorbed in duodenum (malabsorbtion sprue, celiac)
- transferrin: transport protein
- no active Fe excretion
- ferritin(best indicator) & hemosiderrin: storage protein
- dimple is 1/2 cell when should be 1/3rd
- pica: desire to eat nonedible
What is pica?
desire to eat non-edible, consequence of Fe def anemia
What are oral presentations of anemia?
- sore tongue
- angular chelitis
- aphtous ucerations
- atrophic mucositis of upper aero-digestive tract
What are the causes of anemia of chronic disease?
- infection: TB, osteomyelitis
- immune disorders: rheumatoid arthritis, regional enteritis
- neoplasms: lymphoma, carcinoma
- All increase IL which inhibit rls of Fe from stores and decrease erythropoeitin response
What are the causes of megaloblastic anemia?
- B12 and folic acid deficiency
- req for DNA synth, delay nuclear maturation w respect to cytoplamic elements
- (hypercelluar) megaloblasts in marrow, macrocytic RBC & hypersegmented neutrophils in blood
What is the function of folic acid?
- C1 fragment tranfer
- rate limiting: deoxyurdilate+ c1 frag--> thymidilate
What causes folic acid deficiency?
- diet, alcohol, metabolic needs, drugs (anticonvulsants, antimicrobials, methotrexate)
- malabsorbtion: celiac, sprue
What is the function of B12?
cofactor in thymidilate synthesis, cofactor in methylmalonyl CoA to Succinyl CoA
What is required to absorb B12?
- intrinsic factor: cofactor of gastric parietal cells)
- receptor in terminal ilial
- transcobalamin: transport protein
What is pernicious anemia?
deficient(autoimmune) intrinsic factor (B12)
What are some causes of B12 deficiency?
- pernicious, malabosbtion, competition (tapeworm), diverticulosis
- rarely dietary or hereditary
- poikilocytes & megoblastc marrow
Describe the classifications of hemolysis.
- extravascular: spleen
- intracorpuscular: intrinsic deficient
What are the byproducts of hemoglobin after hemolysis?
- Fe: transerrin back to bone marrow
- porphyrin: indirect, unconjugated bilirubin
- globin: digested to AA