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Emory University Physician Assistant Program
Heme 101
Allan Platt PA-CEmory PA Program
Atlanta [email protected]
Emory University Physician Assistant Program
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BloodBlood has red cells(erythrocyctes)White cells (leukocytes)Platelets (thrombocytes)
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Blood Components
Plasma 54%
White cells and platelets 1%
Red Cells 45%
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White Blood CellsWhite Blood CellsFight infectionsAre increased in infectionsMove inside and outside of blood vesselsAre made in the bone marrow
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White Blood CellsWBC - White Blood Cells 4.5 - 11.0 K/uL
Low = Leukopenia High = Leukocytosis
WBC Differential
Neutrophils - Segs 54 -62%
Neutrophils - Bands 3 -5 %
Lymphocytes - Lymphs 25 - 33%
Monocytes - Monos 3 - 7%
Eosinophils - Eos 1 - 3%
Basophils - Basos 0 - 0.75%
Atypical Lymphs 0
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PlateletsPlug holes in the body to stop bleedingCan help cause blood to clotMade in the bone marrow
FibrinFibrin
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Red Blood Cells Carry oxygen from the lungsCarry carbon dioxide back to the lungsNormally live 120 daysContains the protein hemoglobinMade from iron, folic acid, vitamin B12Made in the bone marrow
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Red Blood Cells
Red cells look like Red cells look like doughnuts that are doughnuts that are very flexiblevery flexible
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Microscope View
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Red Blood Cells - Shape
Red cells travel through Red cells travel through very narrow blood vesselsvery narrow blood vessels
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Red Blood Cells Red Cell Flow
Blood VesselBlood Vessel
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Red Blood Cells - Hemoglobin
OxygenOxygen
Hemoglobin, the Hemoglobin, the main protein in main protein in red cells holds red cells holds four oxygen four oxygen moleculesmolecules
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Red Blood Cells - Hemoglobin
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Red Blood Cells - Marrow Red cells, white cells and platelets are made in the bone marrow
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Red Blood Cells - Retics
Reticulocytes, or Retics are young red cells just released from the bone marrow. The Retic count is the best indicator about how the marrow factory is doing.
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Red Blood CellsRed Blood Cells
Red cells live 120 days in the circulation
Food with iron and vitamins is digested
Red cells are made in the bone marrow
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Red Blood Cells Red Blood Cells -- RecycledRecycledRed cells are recycled in the spleen and liver. Red cells are recycled in the spleen and liver. The iron and protein are stored and bilirubin The iron and protein are stored and bilirubin is released.is released.
SpleenSpleen
LiverLiver
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Red Blood CellsRed Blood Cells - The KidneyErythropoietin is made by Erythropoietin is made by the kidney as a signal to the the kidney as a signal to the bone marrow to make more bone marrow to make more red cellsred cells
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The History
WeaknessTiredness - FatigueDyspneaDizzy – non vertigoPalpitationsNew angina
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The History -2- History of melena, abdominal pain, Aspirin or non-steroidal anti-
inflammatory agents (NSAIDs) use, past peptic ulcer disease , then consider GI bleeding, platelet dysfunction.
- In females the menstrual history quantifying the amount of bloodloss ,or possible pregnancy should be obtained.
- History of pica or abnormal craving for ice, clay, starch...; dysphagia then consider iron deficiency.
- Poor diet, then consider iron or folate deficiency, and generalmalnutrition
- History of gastric surgery, distal paresthesias, gait problems -consider B12 deficiency
- History of alcohol abuse - consider folate deficiency or liver disease. If moonshine use or lead paint/pipe exposure, consider lead toxicity.
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The History -3- Family history of blood cell or bleeding disorder: consider Sickle
Cell disease, G6PD,Thalassemia, Hemophilia, von Willebrand- History of jaundice, transfusion, new medication, infection -
consider hemolytic process- History of weight loss, Cancer, HIV, rheumatoid arthritis, thyroid
disease, renal disease -then consider secondary cause- History of fever and chills, cough, dyspnea, then consider
Infection.
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Physical Exam
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Sclera
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Spoon Nails – Fe Def.
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Glossitis and Chelosis –Fe and B12
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Physical ExamGENERAL INSPECTION- clubbing in TB or lung cancer
Skin- Hypothyroid, SLE, Bruises, lesions, petechiae or purpura.Weight - Loss in Cancer, HIV, Chronic disease, gain in hypothyroid
VITAL SIGNS- Pulse: Tachycardia from increased cardiac outputRespirations: Tachypnea from decreased oxygen transportBP: Orthostatic if volume depletedTemp: Fever in infections and drug or transfusion reactions,
HEENT- Eye: Jaundice if hemolysis, pallor in palpebral conjunctivaMouth: Glossitis and angular stomatitis in iron or B12 deficiency
NECK- Thyroid enlargement or nodules, lymph nodesHEART- Increased output/murmur- consider high output failureLUNG- consider infection, lesionABDOMINAL- Liver/spleen size, masses, tenderness, surgical scarsRECTAL- Stool guaiac, prostate exam in menPELVIC/BREAST- Uterine abnormality, Pap smear, Breast noduleLYMPHNODES- consider lymphoma,leukemia,infection,connective tissue DiseaseNEUROLOGIC- Decreased vibratory and position sense in B12 deficiency
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LAB- INITIAL SCREENING TESTS
Urinalysis- Hematuria/proteinuria in renal disease ,hemoglobinuria in hemolysis. CBC, red cell morphology and white
blood cell differential, Reticulocyte count,Chemistry profile (LDH, Bilirubin- Direct and Indirect, BUN, Creatinine, GOT),Hemoglobin Electrophoresis if hereditary hemoglobinopathy is suspectedIF BLEEDING - Platelet Count, PT, aPTT
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CBC- Red Cell Measures
PARAMETER NORMAL ADULT COMMENTS
HB - Hemoglobin Male= 15.5 +/- 2 mg/dl Low = Anemia
Female = 13.5 +/- 2 High = polycythemia
HCT - Hematocrit Male= 46.0 +/- 6% "
Female= 41.0 +/- 6% "
RBC - Red Blood Male = 4.3 - 5.9 Million/uL "
Cell Count Female = 4.0 - 5.2 " "
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Red Cell Indices MCH, MCHC
MCH - Mean Corpuscular 27 -32 pg Low = Hypochromic
Hemoglobin High = Hyperchromic
MCHC - Mean Corpuscular 30 - 36 gm/dl Low = R/O Fe def.
Hemoglobin Concentration High = Spherocytosis
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Red Cell Indices MCV - RDWMCV - Mean Corpuscular Volume 80 - 94 fl
Low = Microcytosis High = Macrocytosis
RDW - Red Cell Distribution Width 11.5 - 14.5Variation in RBC size
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PlateletsPlatelet Count 150 - 400 K cell/uL Low = ThrombocytopeniaHigh = Thrombocytosis
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Retics or Reticulocyte countRetic - Reticulocyte Count 0.5 -1.5 %Low in anemia = low marrow output High = RBC loss
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Corrected Retic CountCorrected Retic Raw Retic Pt's HematocritPercentage = Percentage X 45
Corrected Retic Raw Retic Pt's HemoglobinPercentage = Percentage X 14
An example would be if the raw retic percentage reported on the CBC was 6% and the patient's hematocrit is 23 then:
The corrected retic percentage = 6% x 23/45 or 3%.
The normal corrected reticulocyte percentage is 1 - 2%.With severe anemia and marked marrow response, other corrections may be necessary.
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RBC MorphologyRed Cell Morphology SIGNIFICANCE
Burr Cells Uremia, Low K, artifact, Ca stomach, PUD
Spur Cell Post-splenectomy, Alcoholic liver disease
Stomatocyte Hereditary, Alcoholic liver disease,Spherocyte Hereditary, Immune hemolytic anemia,
water dilution, post-transfusionShistocyte - helmet TTP, DIC, vasculitis, glomerulonephritis,
heart valve, burnsEliptocyte - Ovalocyte Hereditary, Thalassemia, Fe Def.,
Myelophthistic, megaloblastic anemiasSickle Cells Sickle cell diseaseTarget Cells Thalassemias, hemoglobinopathiesMicrocytes Thalassemia, Iron Def., Lead Toxic,
Macrocytes B12 of Folate Def.Parasites Malaria, Babesiosis
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Diagnostic PathwayReticulocyte Production Index
<2 Decreased Production >2 Increased Loss
Red Cell Indicies MCV Hemolysis Bleeding
>94 80-94 <80Macro Normo Micro Extrinsic Intrinsic
Coombs CoombsPositive Negative
Drug Warm ColdAntibody Antibody
Membrane Hb Enzyme
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MicrocyticMICROCYTIC = "TICS"
T-Thalassemias I-Iron DeficiencyC-Chronic InflammationS-Sideroblastic - lead, drug, or hereditary
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Microcytic TestsTESTS TO ORDER:Serum Iron
TIBC = Transferrin binding sites
% Saturation = Transferrin saturation with Iron
Ferritin = Storage Iron
HBELP = Hemoglobin Electrophoresis
Lead level if exposed
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Thalassemia Syndromes.Hereditary – Alpha or Beta chainDecrease Hemoglobin AHemoglobin ELP and normal Iron are diagnosticSupportive therapy or BMT Target Cells
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Iron deficiencyLow Serum iron, Low Ferritin, High TIBCFind out why –GI bleed, menses, dietTreat FeSO4 300mg tid
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Chronic Inflammation
Block of normal iron stores transport to bone marrow factoryNormal Ferritin, serum iron and TIBC are low with a low saturationHigh Sed rate or c-reactive proteinTreat inflammation – RA, SLE, HIV….
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SideroblasticRing sideroblasts in bone marrowSerum iron is increased and TIBC normal resulting in a high saturation. Serum ferritin is increasedBasophillic stipplingLead toxicity is suspect
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Normocytic AnemiaNORMOCYTIC = "NORMAL SIZE"
N-Normal PregnancyO-Over hydrationR-Renal DiseaseM-MyelophthisticA-Acute Blood LossL-Liver Disease
SI-Systemic InfectionZ-Zero Production- Aplastic anemiaE-Endocrine:Hypothyroid, hypoadrenal, hypoandrogen
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Normocytic Tests
Blood Urea Nitrogen (BUN), Creatinine, SGOT, Alkaline Phosphatase, Bilirubin, Erythrocyte Sedimentation Rate (ESR), Urinalysis, and Thyroid profileBone Marrow Biopsy
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Macrocytic AnemiaMACROCYTIC = "BIG FAT RED CELLS"
B-B12 MalabsorbtionI-InheritedG-Gastrointestinal disease or surgery
F-Folic Acid DeficiencyA-AlcoholismT-Thiamine responsive
R-Reticulocytes miscounted as large RBCsE- Endocrine - hypothyroidD-Dietary
C-Chemotherapeutic DrugsE-Erythro LeukemiaL- Liver DiseaseL- Lesch-Nyhan SyndromeS-Splenectomy
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Macrocytic TestsThe peripheral blood changes include: -Anemia with decreased reticulocyte count, -Increased MCV-Neutropenia with hypersegmented
Neutrophils-Thrombocytopenia with large platelets.
LABS to order:B12, Serum Folate, RBC Folateif all normal, consider TSH, and a Bone Marrow Bx.
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B12 Cobalamin Deficiency. Physical signs include
edema, pallor, jaundice, smooth tongue, decreased vibratory and position sensation
Hypersegmented polysLow B12pernicious anemia - anti-
intrinsic factor antibodies Schilling's testRx - cobalamin 1000 mg I.M.
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Folate DeficiencyCauses - liver disease, diet vitamin B12 deficiency, and drugs such as methotrexate, ethanol, and dilantin.Lab – low serum and RBC FolateRx – Folate 1mg po qD
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Hemolytic AnemiaHEMOLYTIC = "HEMATOLOGIST"
H-Hemoglobinopathy: sickle cell disease- Hemoglobinuria: Paroxysmal Nocturnal Hemoglobinuria
E-Enzyme DeficiencyM-Medication - drug induced: aldomet, INHA-Antibodies - Immune attackT-Trauma to the red cells: D.I.C , artificial heart valvesO-OvalocytosisL-Liver diseaseO-Osmotic fragility in Hereditary spherocytosis
and in Hereditary EliptocytosisG-G6PD Glucose-6-Phosphate Dehydrogenase DeficiencyI-Infection: malaria, babesiosisS-Splenic destruction in hypersplenismT-Transfusion- Thalassemias
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Hemolytic Signs1. Elevated reticulocyte count, with stable or falling hemoglobin.2. Elevated indirect bilirubin -3. Eevated serum lactate dehydrogenase (LDH)-4. Decreased Haptoglobin levels - Haptoglobin binds hemoglobin released in the plasma from red cell breakdown. 5. Hemoglobinemia and hemoglobinuria6. Erythroid hyperplasia in bone marrow 7 Abnormal Hemoglobin Electrophoresis
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Hemolytic Tests1. The direct antiglobulin (Coombs') test Direct Coombs test looks for antibody on the red cells. The Indirect Coombs looks for antibody in the serum.2. Hemoglobin electrophoresis3. Heinz body stain4. Osmotic fragility 5. Blood smear
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HemoglobinopathySickle Cell Disease – SS, SC, SD, SE, SOarab, S beta Thal
Newborn Screening or HbELP
Daily Penicillin –birth -6yo
Hydroxyurea
Hydration, Oxygen, Temperature, and Folate
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G6PD - Glucose - 6 - Phosphate Dehydrogenase Deficiency
X linked genetic
Precipitated by oxidant drugs
Heinz body stain show denatured Hb
Avoid medications such as antimalarials, aspirin, sulfa drugs, and avoid eating favabeans.
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Parasites – Malaria -Babesiosis
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Spherocytosis and Ovalocytosis
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To Clot or NotCoagulopathies
Allan Platt, PA-CFaculty, Physician Assistant ProgramEmory University School of Medicine
Atlanta, [email protected]
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Clotting Needs
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Clotting Steps
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Clotting system activated
Normal Blood FlowNormal Blood FlowClotClot
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Clot
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Platelet Activation
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Clotting Cascade
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Inhibitors of Clotting
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Vitamin K Factors
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Increased Bleeding PresentationBleeding gums
Easy Bruising
Prolonged Post-op Bleeding
Prolonged Bleeding post dental work
Petechiae or Purpura
Increased Menstrual Bleeding
Lab Finding of Low Platelets or Abnormal PT, aPTT
G.I. Bleeding
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Increased Clotting Presentation
Deep Vein Thromboplebitis (DVT)
Calf swelling, pain
Pulmonary Embolus (PE)
Myocardial Infarction, Angina
Stroke, or Transient Ischemic Attacks (TIAs)
High Risk – post operative, pregnancy, atrialfibrilation, congestive heart failure
Elevated platelets
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Bleeding History
1. Abnormal bleeding from the mucus membranes such as the mouth, nose or vagina suggests platelet defects or von Willebrand’sdisease (vWD). 2. Abnormal bleeding into joint spaces and soft tissues implies a defect in the clotting factors.3. Purpuric lesions are usually caused by vascular wall defects.
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Bleeding History
HX - History of melena, abdominal pain, Aspirin or non-steroidal anti-inflammatory agents (NSAIDs) use, past peptic ulcer disease , then consider GI bleeding, platelet dysfunction.
- In females the menstrual history quantifying the amount of bloodloss ,or possible pregnancy should be obtained.
- History of alcohol abuse - consider liver disease.- Family history of blood cell or bleeding disorder:
consider Hemophilia, von Willebrand Disease
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Bleeding History- History of weight loss, Cancer, HIV, rheumatoid
arthritis, thyroid disease, renal disease -then consider secondary cause
- History of fever and chills, cough, dyspnea, then consider Infection.
- History of prolonged bleeding after dental extractions, epistaxis, gum bleeding, easy bruising, then consider low or dysfuctional platelets.
- History of bleeding into joints, then consider hemophilia.
- History of Lupus - Lupus anticoagulant
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Increased Clotting History
History of recurrent clots, PEs... consider protein S,C, or Antithrombin III deficient Pregnancy - Increased blood viscosity, fibrinogen and factor VIII. Post Partum -Hypercoaguable statePolycythemia vera - increased viscosity
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Increased Clotting History
Smoking, Resent Surgery, Diabetes, Congestive Heart Failure, Cancer, AtrialFibrillation are all high riskAutoimmune diseases such as systemic lupus erythematosis, and medications such as procainamide, chlorpromazine, and quinidine. Oral contraceptives - Estrogen
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Physical ExamPHYSICAL EXAMGENERAL INSPECTION- clubbing in TB or lung cancer
Skin- Hypothyroid, SLE, Bruises, lesions, petechiae or purpura.
Weight - Loss in Cancer, HIV, Chronic diseaseVITAL SIGNS- Pulse: Tachycardia from increased cardiac output
Respirations: Tachypnea from decreased oxygen transportBP: Orthostatic if volume depletedTemp: Fever in infections and drug or transfusion reactions,
HEENT- Eye: Jaundice if hemolysis, pallor in palpebralconjunctiva
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Physical Exam 2
HEENT- Eye: Jaundice if hemolysis, pallor in palpebralconjunctivaLUNG- consider infection, lesion, rubCV - new murmer or CHF , Listen for BruitsABDOMINAL- Liver/spleen size, masses, tenderness, surgical scarsRECTAL- Stool guaiac,PELVIC/BREAST- Uterine abnormality, Pap smear, Breast noduleLYMPHNODES- consider lymphoma, leukemia, infection, connective tissue diseaseEXTR- Homan’s or calf tenderness/swelling
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Platelet Problems or Von Willebrand Disease (vWD)
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Clotting Factor Disorders
Hemarthrosis
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Vascular Wall Defects
Purpura
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Tests to Order
-CBC, Differential, Cell Morphology-Platelet Count - 150,000 - 350,000 cu/mm Bleeding can occur if < 50,000 if > 500,000 Clotting too much-Chem 18 (Hepatic profile, Indirect Bili in hemolysis, Renal)-Bleeding Time - (normal 3-8 minutes) is a measure of platelet function and an intact coagulation cascade.-PT -Prothrombin Time - +/- 2 of control = 11 - 16 sec. Extrinsic system monitor for coumadin therapy. INR is International Normalization Ratio, 1 is normal, 2- 3 for Coumadin Therapy, 2.5 - 3.5 if heart valve-aPTT - activated Partial Thromboplastin Time- 25 - 38 sec. Intrinsic system. Used to monitor Heparin therapy- Fibrinogen level (normal 100-300 mg/dl). Causes of an abnormally low fibrinogen level include DIC, hereditary dysfibrinogenemia, and hepatic failure.- Fibrin degradation products. Abnormal elevations occur in DIC, primary fibrinolytic states, and hepatic failure.
For Clotting too much: Protein S, C and antithrombin III assay
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Bleeding TimeThe bleeding time: To check platelet functionCheck platelet countNo aspirin X 7 days1. BP cuff inflated to 40 mm.2. Two cuts on volar arm 9mm long 1 mm deep.3. Blot excess blood do not touch cut.4. Normal time until stops is 9 minutes
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Differential DiagnosisC - Cirrhosis/Liver Disease and CoumadinA - Aspirin and other drugs NSAIDsL - Leukemia, Lupus anticoagulant F - Factor Deficiency - Hemophilia
D - Disseminated Intravascular Coagulation I - Idiopathic Thrombocytopenic PurpuraP - Platelet Deficiency (TTP, HUS, DIC, Heparin) or Platelet Dysfunction (vWD)S - Scurvy: Vitamin C Deficiency
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Clotting too muchClotting Too much - Pulmonary Embolus, Deep Vein Thrombophlebitis, Stroke, Myocardial Infarction
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Differential DiagnosisHypercoagulation The mnemonic is: 5 Ps CLOT
P - Pregnancy - Increased blood viscosity, fibrinogen and factor VIII.P - Post Partum - Hypercoaguable stateP - Protien S, C, or Antithrombin III deficient – InheritedP - Polycythemia vera - increased viscosityP - Platlets - Thrombocytosis - too many plateletsS- Smoking, Surgery, Sugar - Diabetes
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Differential DiagnosisHypercoagulation The mnemonic is: 5 Ps CLOT
C - Congestive Heart Failure (CHF), Cholesterol elevation, Cancer - procoagulant effects L - Lipids - Antiphospholipid antibodies - infection, autoimmune diseases such as systemic lupus erythematosis, cancer, and medications such as procainamide, chlorpromazine, and quinidine. O - Oral contraceptives - Estrogen is the main culpritT - Trauma, Travel (immobility) - Stasis of blood flow and release of tissue throboplastin in trauma
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Who ya gonna Call?
Clot Busters
tPA, Streptokinase, Urokinase
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TherapyTo block Clotting-Antiplatelet: Aspirin, NSAIDS, Ticlopidine, ClopidogrelStop Clotting and clot prevention- Heparin and LMW HeparinCoumadin (Reversed with vitamin K)Thrombin inhibitor - bivalirudin - Angiomax, Argatrobanlepirudin - Refludan, Thrombate III
Antithrombin III - AtnativTo Bust Clots - tPA - alteplase, enecteplase
streptokinaseurokinase
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Resources
Aventis http://www.thrombosis-consult.com/home.htmAmerican Heart Association http://www.americanheart.org
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LymphadenopathyL- Lymphoma, LeukemiaY-Yersinia Pestis (Plague)M-Mononucleosis or CMVP-Parasite - ToxoplasmosisH-Hodgkins Disease or HIV infectionN-Neoplasm or metastisisO-Obvious local infection or inflamation-Other systemic infections: Hep B, Rubella, Tularemia, Cat scratch
D-Drug- Procainamide (Pronestyl), Phenytoin (Dilantin)E-Endocrine - Addisons, HypothyroidS- Syphilis
-SLE/Rheumatoid arthritis-Serum sickness-Sarcoid
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Mononucleosis
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Mono - continued
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Hodgkins Disease
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Hodgkins – Reed Sternberg cells
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Multiple MyelomaSymptoms and Signs - Itching, Bone pain, weakness, anemia, lytic bone lesions, increased protein, M - Spike, Bence Jones protein in urine
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Primary - Polycythemia vera
Sx: Pruritis HA, Dizziness, vertigo, visual disturbance, tinnitusPE: Rubor, BP increased, splenomegalyor hepatomegallyLab: HCT >55 lncreased platelets and WBC countRX: Phlebotomy, Hydroxyurea
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Secondary Polycythemia
Increase erythropoietin due to hypoxia (COPD, smokers, high altitude), tumors of kidney, ovary, liver, brain, drugs: steroids, androgen, dehydration, burnsPE: No hepatospenomegaly unless tumor
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Leukemia and LymphomaALL: Acute Lymphocytic Leukemia (Usually in Children)AML: Acute Myelogenous LeukemiaCLL: Chronic Lymphocytic LeukemiaCML: Chronic Myelogenous LeukemiaLymphomas, Hodgkins
HX: Fatigue, anorexia, wt loss, fever, bone pain, headaches, lymphadenopathy, non healing infections, thrush, bleedingPE: Pallor, gingival hyperplasia, Candida infections, lymphadenopathy, hepatosplenomegaly, lung infiltrates, bleeding, bruisingLAB: CBC, WBC Differential, Chem 18, Bone Marrow BiopsyPhiladelphia Chromosome seen in CMLAuer bodies or rods in AMLLymph node BX: Reed -Sternberg cells in Hodgkins DiseaseCT - MRI chest and abdomenCXR - Chest infiltation, pneumoniasRX: Chemotherapy, Bone Marrow Transplant
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ALL - Blasts
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CLL - Blasts
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AML Auer Rod
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CML