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CBC, Abnormalities of RBC’s & WBC’s

Compete Blood Count(CBC) • Functions – Detection & evaluation of anemia – Detection of inflammatory & infectious processes – Detection & evaluation of leukemia – Evaluation of peripheral blood cell characteristics – Detection & evaluation of polycythemia Red Blood Cell(RBC) Indices • RBC Count – Number of RBC's per unit volume – Measured directly & given in millions per microliter • Adult males-4.50-5.90 x 106/mm3 • Adult females- 4.00-5.20 x 106/mm3 • Hemoglobin (Hgb) – Measured directly & given in grams per deciliter. – Most useful measure of oxygen carrying capacity of blood – Adult males 13.5-17.5 g/dL – Adult females 12.0-16.0 g/dL • Hematocrit (Hct) – Calculated value – RBC count x MCV – Adult males 41.0-53.0 – Adult females 36.0-46.0 • Mean Corpuscular Volume (MCV) – Measured directly; unit is femtoliter(fl) – Measures size of RBC's – Classifies anemias into "macrocytic" with higher than normal MCV &"microcytic" with low MCV. – Normal 78-102 fl • Mean Corpuscular Hemoglobin (MCH) – Calculated Value – Hgb ÷ RBC count – Average mass of Hgb in an individual RBC; – Unit is picogram(pg) – Normal 26.0-34.0 pg/cell • Mean Corpuscular Hemoglobin Concentration (MCHC) – Hgb ÷ Hct – Expressed g/dL – Provides a measure of Hgb concentration in cells. – Normal 31.0-37.0 g/dL • RBC Distribution Width (RDW) – Standard deviation of MCV – Measure of anisocytosis, or variation in RBC size – Normal 13.0( 11.5-14.5) – Measured in femtoliters (fl). • Reticulocyte Count (RC) – Generated manually – Peripheral smear stained with a supravital dye so number of reticulocytes can be enumerated. – Given as a "corrected reticulocyte count" which compensates for falsely elevated RC with anemia: • RC (corrected) = RC x (patient Hct ÷ 45). – Normal RC 0.5-2.5 % RBC’s • Normal Values for WBC’s – Much less numerous than RBC’s – 1 WBC to 600 RBC’s, or about 8,000 per cubic millimeter of blood, with a normal variation from 6,000 to 10,000 – Under pathologic conditions, number may be greatly increased(leukocytosis) or reduced in number(leukopenia) – Leukocytes identified by microscopic appearance on a stained blood smear.

WBC’s may be identified based on their reactions to different dyes in stain Neutrophil • Mean Cells/uL- 3650/ uL • 95% Confidence Limits 1830-7250 cells/uL • Percent total WBC 40-70% • 9 to 10 days from myeloblast to cell death • Pass from BM to peripheral blood & from peripheral blood to tissues • Movement is not reversible • AKA Polys, PMN, or segmented neutrophil – Bands • Percent total WBC 0-10% – Lymphocyte • Mean Cells/uL- 2500/uL • 95% Confidence Limits 1500-4000 cells/uL • Percent Total WBC 22-44 % • RBC about 2/3 size of a normal lymphocyte. – Monocyte • Mean Cells/uL 430/uL • 95% Confidence Limits 200-950 cells/uL • Percent Total 4-11 % • Kidney shaped • Slightly larger than a lymphocyte & has a folded nucleus. • Monocytes can migrate out of bloodstream & become tissue macrophages under influence of cytokines. – Eosinophil • Mean cells/uL 150 cells/uL • 95% Confidence Limits 0-700 • Percent Total WBC 0-8% • Eosinophils can increase with allergic reactions & with parasitic infestations. – Basophil • Mean cells/uL 30/uL • 95% Confidence Limits 0-150 • Percent Total WBC 0-3% • Lobed nucleus (like PMN's) & numerous coarse, dark blue granules in cytoplasm Platelet Count – Included on routine CBC along with mean platelet volume (MPV) – Platelets not true intact cells, but fragments of giant megakaryocyte – Essential part of coagulation process, with direct or indirect influence on a variety of aspects of homeostasis & thrombosis – Normal 150-350 x 103/mm3 – < 50,000 may be considered a critical value in some situations & counts < 20,000 always considered critical – Values > 1,000,000 may also be considered critical – MPV with normal values 7.4 to 10.4 fL – Larger platelets younger with better homeostatic function than older platelets – With a normal platelet count(150,00 to 400,000), a field containing 200 RBC’s should contain 6 to 18 platelets – Giant Platelet • Bleeding tendency significantly less with higher MPV values • MPV correlates with bleeding tendency in patients with thrombocytopenia Normal RBC(Erythrocyte) – 6 - 8 microns in diameter – Appear as circular, homogeneous discs with a center that is paler than periphery – Cells nearly uniform in size & shape. – RBC about 2/3 size of a normal lymphocyte. Nucleated RBC’s – Precursors to mature RBC’s & in healthy adult they are found only in bone marrow(BM) – Occurrence in peripheral blood circulation when there is a increased demand on BM – –

round deeply basophilic nuclear chromatin remnant • Seen when spleen is absent • Also may be seen in • Hyposplenism • Megaloblastic anemia • Hemolytic anemia • Thalassemia – Heinz Body • Spherical inclusions of precipitated Hgb seen as a perimembranous blue dot after supravital staining • Result from abnormal Hgb precipitation & may be a single large body or several small ones • Not seen in normal individuals because they are removed by spleen – Pappenheimer Body • Multiple tiny iron-containing granules composed of mitrochondria & ribosomes resemble basophilic stippling • Post-splenectomy • Lead poisoning • Iron overload • Sideroblastic anemias • Thalassemia • Iron overload • Multiple transfusions – Plasmodium Infection • Malaria • With Plasmodium infection seen as "ring forms". stippling. – Hyperchromia • Cells stain more deeply with less central pallor. loop shaped) – Howell-Jolly Bodies • Small.• Abnormalities of RBC’s • RBC Inclusions – Basophilic Stippling • Fine Basophilic Stippling • Increased production RBC’s • Increased Reticulocytosis • Coarse Basophilic Stippling • Lead Poisoning • Toxic BM damage • Impaired Hgb synthesis • Megaloblastic Anemia • Myelodysplasia • Thalassemia – Cabot Rings • RBC inclusion indicative of abnormal erythropoiesis • Seen in severe hemolytic anemia • Bluish. depending upon species • PBS demonstrates several ring forms of Malaria (Plasmodium vivax) in RBC’s • Staining – Hypochromia • Cells with decreased MCH. & gametocytes. typical of iron deficiency • RBC’s have less hemoglobin • Central pale area becomes larger & paler. thread-like rings or convolutions(figure-of-eight. • Cells are larger & thicker • Increased Hgb content (elevated MCH) • Normal Hgb concentration (MCHC) • Seen in megaloblastic anemia – Polychromasia • RBC that contain residual RNA stain with blue-gray tint .

resembling a “target” • Occurrence • Obstructive jaundice • S/P splenectomy • Hypochromic anemia's • Iron-deficiency anemia • Thalassemia • Hemoglobin C & Hemoglobin SC disease • Hgb. C leads to formation of "target" cells--RBC's that have a central reddish dot. round dense cell without central pallor • Decreased MVC & increased MCHC • Hereditary Spherocytosis • Suggests extravascular hemolysis in previously normal persons • Immunohemolytic anemias • Recent blood transfusion • Size of many RBC's is small. – Anisiopoikiocytosis-Variation in RBC size & shape • PBS from a patient with Hemoglobin H Disease showing target cells. with lack of central zone of pallor • Spherocytes do not survive as long as normal RBC's & need for increased RBC production. • Cells with decreased MCV. – Target cells • Cell with central & peripheral staining with intervening pallor due to increased redundancy of RBC membrane • When stained. hypochromia. • Increased variation in shape termed poikilocytosis.2 days. further decreasing blood flow & O2 tension . & RBC's change shape to long. a peripheral rim of Hgb seen with a dark. typical of megaloblastic anemias • Note size of RBC's to lymphocyte • Etiologies • B 12/Folate deficiency • Cancer chemotherapy • Myelodysplastic syndromes • Liver diseases • Alcoholism • Hypothyroidism – Poikiocytosis-Variation in RBC shape • Some variation in RBC shape normal. banana-shaped cell with pointed ends found in SC disease from aggregation of Hgb S • Shows marked poikilocytosis • PBS in Sickle Cell Crisis • Hgb SS is prone to crystallization when O2 tension low.• • Indicates cell is immature & has only been in blood 1. central Hgb-containing area.Small RBC’s • RBC's are smaller than normal(microcytic) & have an increased zone of central pallor. • A variety of abnormal shapes seen & any abnormally shaped cell is referred as a poikilocyte. • Curved. typical of iron deficiency anemia & thalassemia – Macrocytosis-Large RBC’s • Cells with increased MCV. microcytosis. thin sickle forms that sludge in capillaries. & anisopoikilocytosis – Spherocytosis • Small. • Increased polychromasia implies reticulocytosis or increased RBC production RBC Size & Shape – Anisiocytosis-Variations in RBC Size • Small cells imply a defect in hemoglobin synthesis caused by iron deficiency or abnormal hemoglobin genes • Large cells imply delay in erythroid precursor DNA synthesis caused by folate or B12 deficiency or drug effect – Microcytosis.

granulomatous process) • Myelofibrosis • Polycythemia • Thalassemia (homozygous type) Agglutinated RBC’s in Cold Agglutinin Disease • Cold –active IgM antibodies react against RBC antigens • Fresh blood specimens agglutinate during with drawl into a cooler syringe • Etiology • Infection( viral & Mycoplasma). uremia. RBC volume loss • • • Left Shift • Absolute increase in neutrophils with an increase in bands. & sometimes an increase in immature forms such as metamyelocytes or myelocytes. or stress • Toxic Granulations – Large darkly staining granules resulting from neutrophilic stimulation by foreign antigens – Seen most often with bacterial infections & in association with cytoplasmic vacuolization – Tend to cluster together • Döhle Body . elliptical cell • Up to 10% of RBC’s in normal individuals may be elliptical. or blasts Hypersegmented Neutrophil • PMN leukocytes normally have 3 or 4 lobes. 6 or more lobes indicate hypersegmentation • Seen most often with megaloblastic anemias. uniformly distributed spiny projections • Occur as an artifact from smear preparation or in some disease states. but 5.• – – – – – – – Schistocytes • Fragmented. or following chemotherapy (methotrexate) Toxic Changes of Neutrophils • Toxic Neutrophil & monocyte – Refers to alterations in morphology of neutrophil in response to infection. sometimes with myeloproliferative disorders. inflammation. fibrosis. Rouleaux • Linear aggregation of RBC's that resembles a stack of coins & sediment more readily. TTP). particularly increased fibrinogen or globulin Sideroblast • Non-nucleated RBC with stainable iron Spur Cells • Hemolytic anemia with bizarre-shaped RBC’s • Occurs in some patients with severe hepatocellular disease. • Seen when surface charge is reduced with increased serum protein. • Prosthetic heart valves or severe valvular diseases • Burns • Snakebites Elliptocyte • Elongated. irregularly shaped RBC • A variant called a "helmet cell" appears cut in half • Intravascular hemolysis • Microangiopathic hemolytic anemia(DIC. usually advanced Laennec’s cirrhosis Tear Drop Cell • Also called dacrocytes • Tear shaped but may also be pear shaped with a blunt pointed projection • Myelophthisis-(invasion of BM by tumor. amounts above this are considered abnormal • Hereditary Elliptocytosis-majority of RBC’s are elliptocytes. • Lymphoproliferative disorders(lymphoma) • Idiopathic cold agglutinin disease • Symptoms • Due to vasoconstriction in cold-exposed regions of circulation Artifactual • Echinocytes (Crenated cells or Burr cells) • Have regularly shaped.

myelophthisis • Conditions with decreased WBC survival – Felty’s syndrome. or other trauma & then disappear • Vacuolation of the Cytoplasm – Seen in infections: especially common in septic processes caused by bacteria or fungi – Can be caused by phagocytosis of extracellular material • Chediak-Higashi Syndrome – Rare disorder with large neutrophilic granules representing abnormal lysosomes • Pelger-Huet Anomaly – Autosomal dominant condition with neutrophils that are mostly bilobed in heterozygote (normal function) & unilobate in homozygote (fatal) Atypical (Reactive) Lymphocytes • Larger (more cytoplasm) & have nucleoli in their nuclei. measles. sepsis. • Nucleus may be eccentrically placed & may have irregular borders & indentations • Cytoplasm contains areas that stain a darker blue due to their increased RNA content. • Often associated IM Qualitative Abnormalities of WBCs • Leukocytosis – Increased amount • Leukopenia – Decreased amount • Presence of immature forms in peripheral blood – Erytroleukoblastic Blood Picture – Leukemia's – Leukemoid Reaction Causes of Neutrophilia • Infections (localized and generalized) • Inflammation • Metabolic: uremia.• • • • – Pale or grayish. psittacosis) – Ricketsia infections • Ionizing radiation • Hematopoietic diseases • Severe renal injury Causes of Neutropenia • Drugs and chemicals – Sulfonamides – Antibiotics – Analgesics – Antithyroid drugs • B12 or folic acid deficiency • Myelodysplasia. HepB. miliary TB. SLE. anaplastic anemia. rubella. autoimmune neutropenia. influenza. splenic secquestration/hypersplenism • Neonatal & Infantile causes – Maternal – Inborn defects of metabolism – Immune defects – Disorders of myeloid stem cell proliferation – Benign chronic granulocytopenia in childhood . gout. • Cytoplasm tends to be indented by surrounding RBC's. burn. – Zoonotic infections – Viral infections (EBV. surgery. poisoning • Hemorrhage & acute hemolysis • Myeloproliferative diseases • Tissue necrosis • Physiologic conditions • Steroid administration • Decreased/ineffective production – Severe bacterial infections. round or elongated bodies usually seen close to cell membranes – Usually seen 1 to 3 days after an infection. acidosis.

• • • • • – Pregnancy: progressive decrease. hypereosinophilic syndrome. rickettsial & bacterial infections • UC. Anemia – Hemorrhage & hemolysis • Lymphocytic – Infectious mononucleosis – Pertussis – Varicella – TB – Carcinoma of stomach – Carcinoma of breast – Dermatitis (some types) • Monocytic – TB (miliary form) Leukoerythroblastic Reaction • Similar to leukemoid reaction with addition of nucleated RBC/s & schistocytes. Crohn’s disease. sprue Causes of Eosinophilia • Allergic diseases • Parasitic infestation • Fungal & infectious diseases (some) • Collagen-vascular diseases • Hematopoietic diseases • Immunodeficiency disorders • Endocrine hypofunction • Postradiation • Others (tumors. dacrocytes (tear dropped) • Presence of precursor cells of myeloid & erythroid lineage. particularly monocytic • Malignant lymphomas • Lipid storage diseases • Post-splenectomy • Protozoan. pneumonia. drugs) Causes of Basophilia • Myeloproliferative disorders – CML – Polycythemia • Hodgkin’s disease • Chronic sinusitis • Myxedema • Nephrosis . & polychromasia • Giant platelets • Causes of Leukoerythroblastosis – Myelofibrosis – Metastatic CA • Breast Cancer • Lung Cancer. sarcoidosis. Causes of Leukemoid Reactions • Myelocytic – Infections (endocarditic. Small Cell & Non-Small Cell • Prostate Cancer: Metastatic and Advanced Disease – Sarcoidosis – Tuberculosis – Lipid Storage disorders (Gaucher Disease) Causes of a Monocytosis • Leukemias. poikilocytosis. kidney) – Post treatment of Meg. leptospirosis) – Burns – Eclampsia – Neoplasia (colon. septicemia. • Anisocytosis.

with a characteristic predominance of segmented neutrophils & myelocytes ("myelocyte bulge"). interaction of platelets with a non platelet surface • 2. & venules – Major Events in Primary Hemostasis • 1. – Fibrin strands produced strengthen primary hemostatic plug. immature myeloblasts with many nucleoli. high nuclear/cytoplasmic ratio & absence of cytoplasmic granules. or disease disrupts vascular endothelial lining & blood is exposed to subendothelial connective tissue • Primary Hemostasis – Name given to process of platelet plug formation at sites of injury.• • • • • • • Serum sickness • Radiation Causes of Increased Plasma Cells • Plasma cell leukemia. Platelet activation & secretion. – Requires several minutes for completion. Chronic Myelocytic Leukemia(CML) • Low Powered – Leukocytosis with presence of precursor cells of myeloid lineage. – It occurs within seconds of injury & is of prime importance in stopping blood loss from capillaries. Approach to the Bleeding Patient • • . • WBC’s were nearly all mature appearing lymphocytes. which forms complexes with all of coagulation protein serine proteases except factor VII. Platelet adhesion. • Distinctive feature of these blasts is a linear red "Auer rod" composed of crystallized granules. & thrombocytosis seen • High Powered – WBCs are present in all stages of maturation. multiple myeloma • Lymphomas & certain cancers • Cirrhosis of liver • Collagen-vascular diseases • Bacterial infections (syphilis. – Numbers of basophils & eosinophils) are increased. Coagulation Pathways • Two independent activation pathways – Contact system or intrinsic system – Tissue factor-mediated or extrinsic system. small arterioles. surgery. Platelet Aggregation binding of activated platelets to adherent monolayer • Secondary Hemostasis – Reactions of plasma coagulation system that result in fibrin formation. Chronic Lymphocytic Leukemia (CLL) PBS • Patient presented with a WBC count of 130. • 3. which inactivates factors V & VIII. • Most of WBC’s are small to medium-sized lymphocytes. Acute Lymphoblastic Leukemia (ALL) • Leukemic cells in characterized by round or convoluted nuclei. – Basophilia. & – Protein C & protein-S system. eosinophilia. CLL. – Reactions are regulated by antithrombin. TB) • Parasitic infestation • Viral infections • Serum reaction Auer Rods in AML • Very large. • Many smudged lymphocytes present. – Particularly important in larger vessels & prevents bleeding from recurring hours or days after injury. Hairy Cell Leukemia (HCL) • PBS demonstrating lymphocytosis & absence of any other type of blood cell (pancytopenia).000/ul. • Characteristic cytoplasmic projections are already visible Normal Hemostasis • Divided into primary & secondary components & is initiated when trauma.

factor IX & factor VIII) & proteins of common pathway(factors X. & fibrinogen) – Differential Diagnosis of Prolonged PT Only • Usually indicates factor VII deficiency • May also be seen in patients who have dysfibrinogenemia (abnormal fibrinogen) or a deficiency in coagulation factor X. V. & tissue factor & proteins of common pathway(factors X. • Coagulation Cascade Hypothesis – Intrinsic System • Factor XII • Prekallikren(PK) • High-molecular weight kininogen(NK) • Factor XI • Factor VIII • Factor IX – Extrinsic System • Factor VII • Tissue factor – Common Pathway • Factor X • Factor V • Factor II • Factor I(fibrinogen) Screening Tests for Bleeding Disorders • Activated partial thromboplastin time(aPTT) – Assesses coagulation proteins of intrinsic system & common pathway – Mixture of a negatively charged surface. & fibrinogen) – Normal 20-36 sec – Differential Diagnosis of Prolonged aPTT Only • Disorders associated with bleeding • Factor VIII deficiency or defect is sex-linked & may be congenital or acquired. V.000) • Bleeding time – Forearm is scratched & time until bleeding stops is measured – Assesses platelet number & function – Bleeding time: Normal 2-9 minutes • . phospholipid. factor XI.antiphospholipid antibodies that interfere with coagulation reactions • Prothrombin Time(PT) – Assesses coagulation proteins of extrinsic system & common pathway – Tissue thromboplastin & plasma are incubated for a few minutes – Plasma is recalcified & time required for clot formation is measured – Prothrombin Time(PT): 10-12 sec-test – International Normalized Ratio(INR): standardizes PT from lab to lab – Measures extrinsic system activated factor VII(VIIa). PK. • Congenital factor VIII deficiency(Hemophilia A) occurs only in males • Factor IX deficiency(Hemophilia B) is sex linked • Factor XI deficiency is autosomal recessive • Disorders not associated with bleeding • Factor XII deficiency is autsomal recessive & most common (prolonged aPTT) • Deficiency of Prekallikren(PK) is a autosomal recessive (mildly prolonged aPTT) • Deficiency of High-molecular weight kininogen( HK) is autosomal recessive & extremely rare • Lupus anticoagulants. II. or II • Platelet count – Used to exclude a quantitative platelet defect as cause of a bleeding disorder – Platelet number(150. V.000-450. & plasma is incubated for a few minutes – Calcium chloride added & time required for clot formation is measured – Measures proteins of intrinsic system factor (XII. II.• Merge at point of factor X (Common Pathway) activation & lead to generation of thrombin. HK. which converts fibrinogen into fibrin.

lymphoma.transfusion purpura • Immune thrombocytopenia purpura(ITP) • Results from autoantibodies directed against platelets • May be idiopathic or associated with SLE. or anticoagulant proteins) – 2. Platelet abnormality( a defect in hemostatic cell fragment) – 3 Defect in platelet-endothelial cell interactions( defect in adhesive interactions between platelets & vessel wall)` Platelet Abnormalities • Quanitative Platelet Disorders – Thrombocytopenia • Decreased number of platelets & relatively common disorder • Mechanisms • Decreased production/ineffective production • Increased destruction • Sequestration in spleen • Etiologies of Thrombocytopenia • Decreased Production • Aplastic Anemia • Bone marrow hypoplasia • Radiation • Chemotherapy drugs • Fanconi Syndrome. or HIV • May be acute or chronic disorder • Platelet counts are typically < 50. & IgM Antibodies bound to surface of platelet can be demonstrated in most cases • ITP Diagnostic Findings • .a genetic aplastic anemia • Viral infections • Thrombopoietin deficiency • Leukemia • Metastatic Carcinoma • Ineffective Production • Alcohol abuse • Megoblastic conditions • Severe iron deficiency anemias • Paroxysmal nocturnal hemoglobinuria • May-Hegglin. Wiskott-Aldrich. & Bernard-Soulier syndrome • Increased Destruction/Loss • Non-Immune processes • Sepsis • Extensive Burns • DIC • Severe hemorrhage with extensive transfusion • Drugs • Immune Processes • Neonatal purpura • Result of placental crossing of maternal antibodies directed against antigens on fetal platelets • Post.• • – Affected by ASA Thrombin clotting time (TCT) – Purified thrombin is added to plasma to determine time for clot formation – Direct measure of fibrinogen function Pathogenesis of Bleeding Disorders • All bleeding disorders caused by one of three defects: – 1. fibrinolytic. Plasma protein defects (defect in one or more plasma coagulation.000 with an increased number of large platelets • IgG & less frequently IgA.

transient. fails or patient extremely ill • 2.000-may have spontaneous bleeding • BM Aspirate & Biopsy: Normal with increased numbers of megakaryocytes • Treatment(may not be needed unless platelet count < 20. Definitive Rx. highdose chemotherapy & other drugs • Abnormal increase in vWF activity & endothelial injury results in formation of widespread thrombi in microcirculation • Clinical Findings TTP • Classical pentad(40% ) • Thrombocytopenia & purpura • Hemolytic anemia with schistocytes • Renal failure • Neurologic problems (waxing and waning consciousness. for chronic ITP after initial control of disease Thrombotic thrombocytopenia(TTP) • Etiology • Associated with pregnancy. menorrhagia.anti-Rh-D. Temporary Phagocytic blockade: IV immune globulin. nose bleeds.• CBC-thrombocytopenia(if < 20. Performed if medical Rx. range 2-9 minutes) • Time required for a wound of standardized length & depth to stop bleeding. WinRo) • May be given if steroids don’t work • Expensive and risk of hepatitis C • C. or other bleeding tendencies.000 or bleeding is occurring) • A. but yielding a platelet count that is within or very near normal reference range & abnormal bleeding time – Tests of Platelet Function • Bleeding Time (ref. Initial treatment: glucocorticosteroids • B. but primarily used in evaluation of platelet adhesion . focal neurologic defects) • Fever • Triad of findings( 75%) • Thrombocytopenia with purpura • Neurologic defects • Hemolytic anemia with schistocytes • Treatment • Delay in Rx may result in sudden death. simple test sensitive to abnormalities of both number & function. mortality approaches 100% if not treated • Exchange transfusion(removal of most of patients blood followed by transfusion of equal amount of donor blood) • Intensive plasmapheresis(removal of plasma from patient) coupled with infusion of FFP • Platelet transfusions are CONTRAINDICATED(will promote increased formation of platelet thrombi • • Qualitative Disorders of Platelet Function – May be hereditary or acquired – Occur as a primary process or secondary to another condition – Suspect in a patient presenting with easy bruising. metastatic cancer. Splenectomy • 1.

ADP. thrombin.• Prolonged in thrombocytopenia. ristocetin regent) is added to a substance of platelet .g. Ticarcillin • Alcohol – Disease process • Vitamin B 12 or folate deficiencies • Myeloproliferative disorders • Uremia • Cirrhosis • Dysproteinemias • DIC • Myelodysplastic syndromes • Von Willebrand’s Disease(vWD) – Most common inherited bleeding disorder: 1/800-1/1000 people affected – Deficiency or decreased function of Von Willebrand factor(vWF) results in decreased platelet function & decreased factor VIII activity – vWF attaches platelets to injured endothelium & carries factor VIII in plasma – Diagnostic Findings • Decreased plasma vWF concentration & activity • Prolonged bleeding time • Decreased plasma factor VIII activity • Prolonged aPTT • Because of decreased factor VIII • .thromboglobulin (protein in alpha-granules that can bind heparin) • Platelet Aggregation Test • Standardized concentration of an aggregating substance (e. epinephrine. & other platelet disorders • von Willebrand Factor Assay • von Willebrand factor (vWF) functions to assist in platelet aggregation • Platelet Factor Assays • Platelet factor III (PF3) activity which measures ability of platelets to provide a surface for factor binding • Platelet factor IV (PF4) .. esp plasma & changes in light transmission are measured • Useful aid in DD between hereditary & acquired disorders of platelet function Functional Abnormalities of Platelets • Defects of platelet adhesions – Uremia – DIC • Defects in platelet aggregation – Seen in conditions where fibrinogen is absent or reduced & where glycoprotein complexes are absent or insufficient in number – Afibrinogenemia – Glanzmann”s thrombasthenia • Platelet release defects – Primary • Storage pool disease • Wiskott-Aldrich Syndrome – Secondary • Uremia • Aspirin • Alcohol • Acquired Defects of Platelet Function – Medications • Aspirin • NSAID’s • Dipyridamole • Heparin • Penicillin.beta . severely decreased or absent fibrinogen. von Willebrand’s disease.

as unexplained bleeding during tooth extraction) infrequent bleeding. up to 10 bags bid for 48-72 h depending on severity of bleeding • Desmopressin (DDAVP): a vasopressin analogue-increases level of vWF. • A carrier has equal chances of having a normal (XY) or hemophilic (XhY) son & a normal daughter or a daughter who carries hemophilia gene on one of her X chromosomes XXh) • Of newly diagnosed patients with factor VIII deficiency. 30% have no family history of hemophilia because there is an inherent de novo spontaneous mutation rate of that portion of X chromosome • Bleeding symptoms of factor VIII deficiency may be expressed in females • Turner Syndrome(XhO) • Double heterozygote for factor VIII deficiency(XhXh)-daughter of a mother who is a carrier of factor VIII deficiency & a father who has hemophilia A • Clinical Presentation • Severe Disease(< 1% factor VIII activity) • Presents shortly after birth as cephalohematoma or profuse bleeding at circumcision.autosomal dominant inheritance.g.000 male births • Genetics • Inherited as a sex-linked recessive disorder • Sons of a hemophilic man & a normal woman do not inherit paternal hemophilia(XY) • All daughters of such a union are obligate carriers (XXh). may present with extensive bleeding after moderate trauma • Mild disease( > 5% factor VIII activity) • Presents in adolescence or young adulthood(e. mild to moderate decrease in vWF level • Type 2: vWF does not function properly • Type 3: no vWF. extremely rare – Bleeding Manifestations • Excessive bleeding after minor surgical procedures • Mucocutaneous bleeding with normal platelet count • Superficial brusing (common) • Petechiae(rare) • Gingivial bleeding • Epistaxis • Mennorhagia • GI mucosal bleeding • Immediate bleeding after dental extraction • Postpartum hemorrhage • Spontaneous hemarthrosis rare. given intranasally for pts with type I vWD (mild-moderately severe disease) • Cryoprecipitate: plasma product rich in factor VIII containing vWF Disorders of Intrinsic Coagulation System • Hereditary(single factor deficiency) – Hemophilia A: factor VIII deficiency • Overview • Most common of the hemophilia with an incidence of 1-2 cases per 10. usually in type 3 – Treatment • Factor VIII concentrates with high molecular weight vWF multimers (Humate-P). usually secondary to trauma • Bleeding Manifestations in Hemophilia • Bleeding after circumcision • Delayed oozing from deep lacerations • Protracted bleeding after dental extractions • IM hematomas • Intraarticular hemorrhage – . may present with spontaneous soft tissue or joint bleeding when child crawls or walks • Moderate disease(1-5% factor VIII activity) • Presents when child walks or crawls with spontaneous hemarthrosis or soft tissue bleeding.• • Intrinsic coagulation pathway affected Variants • Type 1: most common.

thrombin clotting time & bleeding time normal • Treatment • Factor IX concentrate (recombinant or highly purified) • FFP • Plasma fraction enriched in prothrombin complex proteins – Factor XI deficiency (Hemophilia C) • Overview • Rare. although 30% of patients may have no other affected family members but instead carry a spontaneous new mutation • Clinical Presentation • Identical to those of factor VIII deficiency • Diseases are indistinguishable without specific factor assays • Laboratory evaluation • Levels of factor IX below 50% result in prolonged aPTT • Specific factor assay for factor IX is diagnostic • PT.000 live male births • Along with factor VIII deficiency. & mennorhagia • Bleeding with dental extractions and urological procedures • Clinical symptoms tend to be similar within affected family members • Laboratory Evaluation • aPTT is prolonged • PT. bleeding time & thrombin clotting time(TCT) are normal in factor VIII deficiency • Treatment of Hemophilia A • Factor VIII concentrate (recombinant or highly purified) • Cryoprecipitate • ½ factor VIII activity as FFP in 1/10 the original volume • Used if factor VIII concentrate is not available – Factor IX deficiency (Hemophilia B) • Overview • Account for 10% of hereditary coagulation factor deficiencies • Incidence is 1 in 30.25%-49%) • PT. thrombin clotting time & bleeding time are normal • Reduced factor XI is diagnostic • Bleeding is most likely to occur in individuals with levels below 10% Disorders of the Common Pathway: Factors V. hematuria. occurring in 1 of 100. & II – Overview • Deficiencies of these proteins are rare disorders of autosomal recessive inheritance • Incidence is < 1 in 1 million – Clinical Presentation • Patients present with soft tissue and spontaneous bleeding.. Only severe factor V and X deficiencies are associated with hemarthrosis .• • CNS bleeding • Hematuria • Laboratory Evaluation Hemophilia A • Factor VIII levels < 30% can be reliably detected using the aPTT as a screening test • Routine aPTT screening alone misses some patients with hemophilia because aPTT is not always prolonged with mildly decreased factor VIII levels(i.e.000 persons • Genetics • Incompletely recessive autosomal trait • High predilection in Ashkenazi Jews of eastern European descent(50% of cases) • Clinical Presentation • Bleeding symptoms are less severe than in moderate or severe factor VIII or IX deficiency • 50% of patients bleed after surgery or trauma. X. remainder have relatively minor symptoms & are identified only by an abnormal PTT • Symptomatic patients typically have spontaneous nosebleeds. is most severe bleeding state that allows for normal gestation & delivery • Genetics • X-linked recessive disorder.

PT aPTT. & thrombin clotting time are all markedly abnormal in afibrinogenemia. XII & kallikren • Prolongs aPTT to a greater degree than PT • Does not dissolve clots • Low-molecular-weight heparin (LMWH) • Smaller more highly purified carbohydrate polymer – .& to a lesser extent in hypofibrinogenemia • In dysfibrinogenemia. MI. and thrombi clotting time are normal • Disorders of Fibrinogen – Hereditary afibrinogenemia • Rare disorder with only 150 cases reported • Autosomal recessive • No clotting or antigenic fibrinogen is detected – Hereditary hypofibrinogenemia • More common than afibrinogenemia • Some cases are actually dysfibrinogenemia with normal amounts of fibrinogen but functionally abnormal – Clinical Presentation • Prolonged umbilical stump bleeding • Intracranial hemorrhage • Intraarticular bleeds • GI and mucosal bleeding frequent • Most patients with dysfibrinogenemia are asymptomatic & diagnosed during lab screening • If concentration of normal fibrinogen is greater than 100 mg/dL there is a decreased tendency to hemorrhage – Laboratory Evaluation • PT.CVA. & to a lesser extent factors IXa. PTT or both • Causes – Anticoagulation defects • Occur in patients who are taking anticoagulant agents to treat venous thrombosis. & others • Management of these pts involves achieving a balance between preventing thrombosis & preventing excessive bleeding • Usually interfere with PT & aPTT but do not prolong the bleeding time • Medications that interfere with coagulation proteins • Heparin • Carbohydrate polymer that forms complexes with antithrombin & other plasma protease inhibitors • Complexes inhibit major enzymes of hemostatic system: thrombin. XIa. aPTT. & thrombin clotting time are variably prolonged with PT & thrombin clotting time being most sensitive screening test Acquired Disorders of Blood Coagulation • Most common forms of bleeding encountered in practice • Often result of medical treatment or a manifestation of an underlying disease state rather than specific abnormalities of the hemostatic system • Usually cause prolongation of PT. factor Xa.• Laboratory Evaluation • PT and a PTT are both prolonged in deficiencies of these factors • Thrombin clotting time is normal • Disorders of the Extrinsic Coagulation System: Factor VII Deficiency – Genetics • Inherited in an autosomal recessive pattern • Heterozygous individuals are usually asymptomatic – Clinical Presentation • Factor VII levels < 1% are associated with severe spontaneous hemorrhage and intraaticular bleeding • Factor VII levels as low as 10% seem to protect against severe bleeding symptoms – Laboratory Evaluation • Factor VII deficiency is the only cause of an isolated prolonged PT • aPTT. bleeding time.

IX. IX. gastritis & hemorrhoids) • Lab Features • Elevated PT • Normal or elevated PTT • Treatment • FFP • Cryoprecipitate DIC • Clinicopathologic syndrome of activated coagulation • Causes bleeding or thrombosis because of loss of balance between clot promoting and clot-lysing systems in vivo • Clinical spectrum ranges from a bleeding state to a prothromic state • Not a specific diagnosis. these preparations do not prolong the PT or aPTT • Warfarin (Coumadine) • Vitamin K antagonist of 2 enzymes that are essential for carboxylation reactions of certain amino acids in coagulation factors VII. S & Z • Prolongs PT more significantly than aPTT Vitamin K Deficiency • Impairs production of factors II(prothrombin). green vegetables). & X • Co-factor in carboxylation of glutamate residues or prothrombin complex proteins • Major source of vitamin K is dietary(esp.& II & proteins C. VII. it always indicates underlying disease • Bleeding associated with DIC is usually result of excessive fibrinolysis • Thrombosis associated with DIC is result of excess thrombin formation • Characterized by presence of thrombin plasmin • Etiologies of Acute DIC • Infectious Causes • Most common cause is sepsis • Gram-positive & gram-negative septicemia • Typhoid fever • Rocky Mountain spotted fever • Viremia • Parasites • Obstetric Causes • Abruptio placentae • Amniotic fluid embolism • Hypertonic saline abortion • Eclampsia • Hemolytic transfusion reaction • Acute promyelocytic leukemia . with minor production by gut bacteria • Etiology • Inadequate dietary intake especially when associated with antibiotic therapy (kills GI bacteria which make Vit K) • Intestinal malabsorption • Cirrhosis (liver makes bile acids to absorb Vit K) • Laboratory features • Elevation of PT & aPTT • Treatment • Vitamin K 10 mg IM or slow IV • FFP if hemorrhage is occuring(has all coagulation factors) Liver Disease • Liver synthesizes all coagulation proteins &clears activated products of coagulation • Results in deficiencies of all clotting factors except VIII • May be factor also in Vit K deficiency • Structural manifestation of liver disease also promote bleeding(portal HTN. X. varices.– – – • Directed primarily at factor Xa • Some preparations also inhibit activity of thrombin • At most therapeutic doses.

platelet count & fibrinogen level • (1) If the findings of two of these tests are abnormal. DIC is a possible diagnosis • (2) If the findings of three of these tests are abnormal.• • • • Major Trauma • Burns Head injury • GSW Frost bite • Crush injuries Heat stroke • Snakebite • Fresh water drowning • Miscellaneous • Homozygous protein C & S deficiency • Factor V Leiden • Severe liver disease • Heparin induced thrombocytopenia & thrombosis syndrome • Necrotizing enterocolitis • Renal homograft rejection • Dissecting aortic aneurysm Etiologies of Subacute DIC • Usually a prothrombic condition resulting from increased thrombin formation • Malignant • Mucinous adenocarcinoma that may manifest as trousseau syndrome (migratory thrombophlebitis. hemorrhage from surgical incisions. venipuncture. DIC is a probable diagnosis • (3) If the findings of all these tests are abnormal. the diagnosis is considered to be DIC until another diagnosis is established • Confirmatory tests for DIC are the D-dimer. fibrin degradation products (FDP). mouthorgan failure may occur • Subacute or Chronic • More typical in cancer patients • Can become symptomatic with surgery or chemotherapy • Thrombosis my dominate clinical picture Diagnostic Findings in DIC • Mechanical fragmentation of RBC • Formation of schistocytes • Hemolytic anemia • Consumption of platelets. marantic endocarditis (fibrin on heart valves). or catheter sites. and arterial embolization • Obstetric • Retained dead fetus • Vascular • Connective disease disorders • Giant cavernous hemangioma • Chronic renal disease • Venous thrombosis • Pulmonary embolus Clinical Presentation of DIC • Acute • May be explosive & life threatening • Most pts: extensive bleeding in skin & mucous membranes. and fibrin monometer assays • D-Dimer Assay • . aPTT. coagulation factors & fibrinogen: • Thrombocytopenia • Prolonged PT & aPTT • Decreased fibrinogen • Fibrinolysis (degradation of fibrin clots) • Increased fibrin degradation(or split) products:FDP(or FSP) • Increased dimers Laboratory Evaluation of DIC • Screening include PT.

or acute leukemia – Massive transfusion(dilutional coagulopathy) • Infusion of more than 1. a retained dead fetus. migratory thrombophlebitis. usually heparin or warfarin Defect in platelet-endothelial cell interactions • Defect in the adhesive interactions between platelets and blood vessel wall • Many causes Hemostatic Disorders due to Blood Vessel Wall Defects • Aging • Drugs – Glucocorticoids(chronic therapy) – Penicillin's – Sulfonamides • Vitamin C deficiency • TTP • Hemolytic Uremic Syndrome • Henoch-Schonlein purpura • Paraproteinemias • Hereditary hemorrhagic telangiectasia(Osler-Rendu-Weber disease) Differential Diagnosis of Prolonged aPTT & PT • Acquired Medical Conditions • . aPTT & thrombin time is prolonged – Hypergammaglobulinemic states • multiple myeloma • Waldenstrom macroglobulinemia • Systemic amyloidosis – Inhibitors to factors X. purpura fulminans. toxic.5 times patient’s blood volume in 24 hours • Acquired coagulopathy can occur as a result of dilution of plasma & platelets. & digital ischemia. II and fibrinogen – Heparinoids. • Plasmin cleaves the insoluble cross-linked monometer to liberate the D.dimer • Fibrin degradation products assay • Measures plasmin-cleaved soluble or insoluble fibrinogen or fibrin • Fibrin monomer assay • Measures thrombin-cleaved fibrinogen only • Least reliable test for DIC and often produces false negative results • Treatment of DIC • Treat underlying disorder first • Antibiotics for sepsis • Delivery of placenta & fetus when cause is obstetrical catastrophe • Supportive blood component therapy • FFP • Platelet concentrates • Cryoprecipitate • Heparin • My be useful for those patients who have acral cyanosis. V. • In addition one ampule of calcium for every 4-6 units of transfused RBC’s or FFP is administered to overcome the anticoagulant effect of sodium citrate – Dysfibrinogenemias • Usually found in patients who have acquired liver disease as a result of alcoholism or immunologic. & depletion of calcium • Acquired coagulopathy can be prevented by administering 1 unit of FFP for every 4-6 units of packed RBC’s.• • • Measures plasmin-cleaved insoluble cross-linked fibrin which is formed when thrombin cleaves fibrinogen and leaves a soluble fibrin monomer. or heparin-like anticoagulants. increased concentration of anticoagulant sodium citrate dextrose. may be produced in patients who have an underlying malignancy – Factitious bleeding disorders most often occur in an individual who is a health care professional & fakes medical illness by self-administering an anticoagulant. or viral causes • PT.

Screening for possible infectious agents that could be transmitted with transfusion Tests Performed on all Blood Collected for Transfusion • ABO group & Rh type • Screening for blood-group antibodies • Serologic test for syphilis*** • Serologic tests for human retroviruses – HIV-1 antibody – HIV-2 antibody – HIV p24 antigen – HTLV I antibodies • Serologic tests for hepatitis – Hepatitis B surface antigen (HBsAg) – Hepatitis B core antibody (HBcAb) – Hepatitis C antibody Transfusion Transmitted Diseases • Hepatitis B – Transmitted through parenteral & sexual exposure. warfarin). – Risk of transmission (RT) = 1/121. only testing for hepatitis C antibody available. vitamin K deficiency. or II) -Rare cases DDx. Ehlers.000 • Human Immunodeficiency Virus (HIV) – First testing of blood products for HIV started in 1985 detects presence of antibody directed against HIV. – Incubation time -mean of 90 days( range of 30. – Testing for HIV p24 antigen mandated in 1996.180 ) – Donor blood is routinely tested for HBsAg & HBcAb – Risk of transmission (RT) = 1/66. • • . liver disease. – A profibrinolytic state occurs as a result • Blood Bank Testing • Tests Performed – 1.• • Transfusion & Pheresis Therapy • – DIC. & massive transfusion Dysfibrinogenemia – Occurs when abnormal fibrinogen molecules do not participate properly in coagulation reactions • Coagulation protein defects of common pathway (factor X. including pseudoxanthoma elasticum. V.000 to 1:200.000 to 1/825. Screening for antibodies that may produce adverse effects if transfused – 3. with lysis of any clots that are formed. with sexual transmission uncommon – Mean incubation time is 6 -8 weeks – Blood Bank testing for HCV started in 1990. – Risk of transmission = 1/563. & scurvy DDx of Bleeding with no abnormality in screening tests • Factor XIII deficiency – May be congenital or acquired. – Can be acquired as a result of consumption in DIC • Plasminogen activator inhibitor-1 deficiency – Deficiency in major serpin inhibitor of plasminogen activators. – Causes increased activation of plasminogen . use of anticoagulants (heparin. – Patients bleed excessively as a result of surgery or trauma • Alpha 2 Antiplasmin deficiency – Absence of major serine protease inhibitor. – Patients have a bleeding disorder that is caused by hyperfibrinolytic state.000) will increase bleeding time • Rare connective tissue disorders. – At present.000 • Hepatitis C – Route of transmission is parenteral. of Prolonged Bleeding Time with Normal platelet count • Von Willebrand factor • Platelet function defect – Quantitative decrease in platelet count(< 100.000 • Human T-lymphocytotrophic Virus (HTLV-1).Danlos syndrome. Determination of blood type with a crossmatch – 2.

• Units which are crossmatched unnecessarily will deplete Blood Bank inventories & can result in blood shortages. such as those which occurred in California after earthquake. • Unit of blood must be properly labeled & label MUST be checked before use. – Implicated as causing adult T-cell leukemia/lymphoma & neurological disorder similar to MS. – Antibody identification can be complicated & take more than a day to complete. Anti “A” antibody in serum • Type AB – Both “A” & “B” antigens on RBC’s – Neither Anti “A” or Anti “B” antibody in serum • Type O – Neither “A” or “B” antigen on RBC’s – Has both “anti A” & “anti B” antibodies in serum • Screen – Looks for unexpected red cell alloantibodies which may form following pregnancy or prior transfusions. – If screen + antibody is identified & 2 units lacking corresponding antigen are crossmatched for patient. – Potential problems in selected patient populations can be prevented by transfusing CMV negative blood or frozen. – Blood contaminated with CMV can cause problems in neonates or immunocompromised patients. – Risk of transmission = 1/641. deglycerolized RBC's.000 (but only 1-3 % of seropositive individuals will develop disease • Cytomegalovirus (CMV) – Prevalence of CMV antibody ranges from 50 to 80% of population. • “Type & Cross” in Emergencies – Blood products may be released without a crossmatch if patient is in danger of dying if transfusion delayed. – Blood is routinely screened for antibodies to HTLV-1. “Type & Cross” • Determines compatibility between patient serum & donor RBC’s • A full crossmatch procedure takes about 45 minutes to complete • Units refrigerated until used. – There are no practical laboratory tests available to test donor blood. so donors travelling to high risk malaria areas are excluded from donating blood for six months. – Alloantibodies -an antibody specific for an alloantigen • “Front type" – Determines which antigens ("flags") in ABO blood group system are on patient's RBC’s • “Back type“ – Identifies isohemagglutinin (naturally occurring antibody) in patient's serum & should correspond to antigens found on RBC’s • In addition.• • – Retrovirus endemic in Japan & Caribbean. • Every unit crossmatched is removed from general inventory reserved for patient for 72 hours. • Blood will ordinarily not be released for transfusion until compatibility testing is completed. . • Blood shortages can result in cancellation of elective surgical procedures. but not in other members of same species. but for which no routine costeffective laboratory testing is available include: • Babesiosis • Lyme disease • Chagas' disease Blood Compatibility Testing (Crossmatch) • Definitions – Alloantigen -an antigen that occurs in some. • Malaria – Rarely transmitted by RBC products. although # of transfusion associated cases of malaria is at an all-time high. RBC's are Rh typed & identified as "D" positive or negative. • Others – Additional diseases which are rarely transmitted by blood products. – Donor blood is not routinely tested for CMV. Anti “B” antibody in serum • Type B – “B” antigen only on RBC’s. • Type A – “A” antigen only on RBC’s.

– Symptoms usually consist of chills & a temperature rise > 1 degree C. • Circulatory Overload – Can occur with administration of blood or any IV fluid. • Prior exposure to non-self HLA antigens (from WBC contamination of red cell products) can result in antibodies that will render future platelet transfusions useless Graft Versus Host Disease (GVHD) • Transfused lymphocytes engraft & multiply in immunocompromised patients (BM transplant patients). future transfusions can be delayed because extended donor blood typing will be required to identify compatible units. increasing capillary permeability & resulting in sudden pulmonary edema. as packed PRBC's in which about 70% of plasma has been removed. such as FFP. & death – Most common cause is a clerical error. • Remaining platelet rich plasma is utilized as a platelet pack Types of RBC Products • Whole blood • Packed red blood cells (PRBC's) • Leukocyte depleted RBC's: – Obtained by filtering blood through leukocyte-specific filters. • Both whole blood & PRBC's can be stored for up to 42 days at 1 . type-specific blood or RBC's of same ABO & Rh group may be released Blood Preservation & Storage • Blood is collected as whole blood • Blood can be stored as whole blood (with all plasma present) or. then group O Rh negative (O neg) blood can be released without compatibility testing. much more commonly. – Granulocyte enzymes are released. such as a mislabeled specimen sent to blood bank. particularly in patients with diminished cardiac function. – Most often occurs with administration of blood products with plasma. – Complications-DIC. – In cases in which patient's blood type is reliably known. – Transfusing a contaminated unit can result in septic shock & death.6 degrees C. • Newly engrafted lymphocytes attack host tissues – . • Transfusion related acute lung injury (TRALI) – Caused when plasma contains HLA or granulocyte specific antibodies which correspond to antigens found on donor WBC's. • Febrile Reactions – Caused by patient antibodies directed against antigens present on transfused lymphocytes or granulocytes. • Bacterial Contamination – Can occur during collection – Bacteria can grow during storage at room temperature & during refrigeration (psychrophilic organisms).• • • • • • If patient's blood type is not known. or not properly identifying patient to whom you are giving blood. deglycerolized RBC‘s Transfusion Reactions • Hemolytic Reactions – Occur when recipient's serum contains antibodies directed against corresponding antigen found on donor RBC’s – Can be an ABO incompatibility or an incompatibility related to a different blood group antigen. • Allergic Reactions to Plasma Proteins – Can range from complaints of hives & itching to anaphylaxis. Platelet Transfusions & Alloimmunization • Contain HLA & A & B antigens. • Frozen. RBC transfusions & Alloimmunization • Can expose patient to RBC antigens not recognized as self. renal failure. • Plasma can be centrifuged heavily a second time to separate platelet rich plasma • Supernatant plasma can be expressed into a third bag & stored as fresh frozen plasma (FFP). • If an antibody is produced. • O negative blood released uncrossmatched in emergencies could result in a hemolytic transfusion reaction if patient has an alloantibody produced after a previous transfusion.

– Hyperviscosity states(Wladenstrom’s macroglobulinemia – TTP – Immune-complex and autoantibody disorders (Goodpasture’s syndrome.• • • Uniformly fatal & untreatable. hemorrhage) – Used to harvest hematopoietic stem cells from peripheral blood of cancer pts – Such cells are then used to promote hematopoietic reconstitution after high-dose myeloablative therapy • Plateletpheresis – Used in some pts with thrombocytosis associated with myeloproliferative disorders with bleeding & /or thrombotic complications – Removal of platelets can help to avoid complications of thrombosis & bleeding.000/uL) of peripheral blast count – Lowers risk of leukostasis(blast-mediated vasoocclusive events resulting in CNS or pulmonary infarction. • Prevented by gamma-irradiating blood products to be transfused Therapeutic Apheresis • Components of whole blood are separated – Plasma (plasmapheresis) – Platelets (plateletpheresis) – Leukocytes (leukapheresis) • Purpose is to remove a component of blood which contributes to a disease state. possibly Guillain-Barre. • Whole blood is introduced into a chamber that is spinning. rapidly progressive glomerulonephritis.. • Autologous Donation – Occurs when a person donates his or her own blood for personal use. units positive for hepatitis B (HBsAg) & human immunodeficiency virus (HIV) are not allowed into Blood Bank. -AML in cases complicated by marked elevation(>100. – Use of pt’s own stored blood avoids hazards of donor blood – Useful in pts with multiple RBC antibodies – Pace may be accelerated using erythropoietin(50-150 U/kg SC 3x week in setting of normal iron stores – Since blood is not be used for anyone else. & blood separates into components by gravity along wall of chamber. units positive for infectious agents & units with irregular blood group antibodies are acceptable – If an autologous unit is collected but not used by patient-donor.g. then it is destroyed. – Wait 56 days before giving another donation of whole blood. . • Component to be removed can be selected • Plasmapheresis – Plasma contained antibodies & antigen-antibody complexes present that may contribute to deleterious effects of autoimmune diseases – Removal of plasma (& replacement with saline solution) will help to reduce circulating antibodies & immune complexes. – Also use to enhance platelet yield from blood donors Blood Donation • Whole blood is collected from healthy donors who are required to meet strict criteria concerning – Medical history – Physical health – Possible contact with transfusion-transmissible infectious diseases. ITP)*** – Cold agglutinin disease. – Be on no prescribed medication that would cause donor a problem when donating or that would affect recipient – Have a Hgb level which meets established U. including a history of • Sexual behavior • Drug use • Travel to areas of endemic disease (e. malaria) • Potential donor – Be in good health &feeling well on day of donation. SLE. – Because of potential risk for a clerical error with mistransfusion of an autologous unit in inventory.S. cryoglobulinemia • Leukapharesis – Removal of WBC’s – Most often used in acute leukemia. myasthenia gravis. FDA standard.

000/uL if no platelet antibodies are present as a result of prior transfusions • Efficacy assessed by 1-h & 24-h posttransfusion platelet counts • HLA-matched single donor platelets may be required in pts with platelet antibodies – Most common means for supplying HLA matched platelets to patients who have become HLA sensitized & require platelets from a single donor whose HLA type matches theirs. DIC rapidly reverse warfarin effects & treat TTP – Cryoprecipitate • Source of fibrinogen. Hemochromatosis may develop after 100 U of RBC's in absence of blood loss – Graft-versus-host disease – Alloimmunization • Reduce Risk of Complications – Removal of leukocytes reduces risk of alloimmunization & transmission of CMV – Washing to remove donor plasma reduces risk of allergic reactions – Irridation prevents graft-versus-host disease in immunocompromised patients – Iron chelation therapy with deferoxamine indicated to reduce risk of hemochromatosis in those at risk Platelet Transfusion • Prophylactic transfusions usually for platelet count < 10. & return it with saline to patient. • Blood is collected from cavities & returned through a filter which removes big items like thrombi & tissue fragments. & platelets in an approximate ratio of 3:1:10 units are an adequate replacement for whole blood • Complications RBC Transfusion – Transfusion reaction-immediate or delayed seen in 1-4% of transfusions-IgA-deficient pts at particular risk for severe reaction – Circulatory overload – Iron overload • 1unit contains 200-250 mg iron. & von Willebrand factor • May be used when recombinant factor VIII or factor VIII concentrates are not available – . • Will work as long as the operative field is not contaminated with bacteria or with malignant cells. • Transfusions of Plasma Components – FFP • Source of coagulation factors. – Cell Saver/Wound Drainage • Device is used to collect blood in operative field during surgery. wash it. fibrinogen. FFP .• • • Hemodilution • Patient's blood is collected prior to surgery & replaced with a plasma expander.000/uL(< 20. higher HCT blood can be given back to patient following surgery. but does not remove inflammatory chemical mediators or cytokines Whole Blood Transfusions • Indicated when acute blood loss is sufficient to produce hypovolemia • Provides both oxygen-carrying capacity & volume expansion • In acute blood loss. factor VIII. hematocrit may not accurately reflect degree of blood loss for 48 h until fluid shifts occur RBC Transfusion • Indicated for symptomatic anemia unresponsive to specific therapy or requiring urgent correction • One unit of packed RBC’s raises Hgb by approximately 1 g/dL • May be indicated in pts who are symptomatic from cardiovascular or pulmonary disease when Hgb is between 7 -9 g/dL • If used instead of whole blood in setting of acute hemorrhage packed RBC’s. & protein C & S • Used to correct coagulation factor deficiencies. • Theory is that any bleeding during surgery will lose fewer RBC's.000/uL in acute leukemia) • 1 unit elevates count by about 10. antithrombin. • Previously collected.