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Diseases of Blood Cells. Back to Basics. Blood is a liquid tissue A mixture of cells and water The water contains Protein, glucose, cholesterol, calcium, hormones, metabolic waste and hundreds of other substances

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back to basics
Back to Basics
  • Blood is a liquid tissue
    • A mixture of cells and water
    • The water contains
      • Protein, glucose, cholesterol, calcium, hormones, metabolic waste and hundreds of other substances
    • Plasma is the liquid portion of the blood containing the blood clotting protein Fibrinogen
    • Serum is the fluid remaining after the blood clots
      • Does not contain Fibrinogen
slide3

plasma (55%)

red blood cells

(5-6-million /ml)

white blood cells

(5000/ml)

platelets

slide4

Plasma

liquid part of blood

plasma transports:-

  • soluble food molecules
  • waste products
  • hormones
  • antibodies
production of erythrocytes
Production of Erythrocytes
  • Hematopoiesis – blood cell formation
    • Occurs in the red bone marrow (myeloid tissue)
      • Axial skeleton and girdles
      • Epiphyses of the humerus and femur
      • Marrow contains immature erythrocytes
      • Composed of reticular connective tissue
  • Hemocytoblasts give rise to ALL formed elements
    • Lymphoid stem cells - give rise to lymphocytes
    • Myeloid stem cells - give rise to all other blood cells
production of erythrocytes erythropoiesis1
Production of Erythrocytes: Erythropoiesis
  • A hemocytoblast is transformed into a committed cell called the proerythroblast
  • Proerythroblasts develop into early erythroblasts
  • The developmental pathway consists of three phases
    • Phase 1 – ribosome synthesis in early erythroblasts
    • Phase 2 – hemoglobin accumulation in late erythroblasts and normoblasts
    • Phase 3 – ejection of the nucleus from normoblasts and formation of reticulocytes
  • Reticulocytes then become mature erythrocytes
    • Reticulocytes make up about 1 -2 % of all circulating erythrocytes
regulation and requirements for erythropoiesis
Regulation and Requirements for Erythropoiesis
  • Circulating erythrocytes – the number remains constant and reflects a balance between RBC production and destruction
    • Too few red blood cells leads to tissue hypoxia
    • Too many red blood cells causes an undesirable increase in blood viscosity
  • Erythropoiesis is hormonally controlled and depends on adequate supplies of iron, amino acids, and B vitamins
hormonal control of erythropoiesis
Hormonal Control of Erythropoiesis
  • Erythropoietin (EPO) released by the kidneys is triggered by:
    • Hypoxia due to decreased RBCs
    • Decreased oxygen availability
    • Increased tissue demand for oxygen
  • Enhanced erythropoiesis increases the:
    • RBC count in circulating blood
    • Oxygen carrying ability of the blood
erythropoietin mechanism
Erythropoietin Mechanism

Imbalance

Start

Normal blood oxygen levels

Stimulus: Hypoxia due to decreased RBC count, decreased availability of O2 to blood, or increased tissue demands for O2

Imbalance

Increases O2-carrying ability of blood

Reduces O2 levels in blood

Erythropoietin stimulates red bone marrow

Kidney (and liver to a smaller extent) releases erythropoietin

Enhanced erythropoiesis increases RBC count

dietary requirements of erythropoiesis
Dietary Requirements of Erythropoiesis
  • Erythropoiesis requires:
    • Proteins, lipids, and carbohydrates
    • Iron, vitamin B12, and folic acid
  • The body stores iron in Hb (65%), the liver, spleen, and bone marrow
  • Intracellular iron is stored in protein-iron complexes such as ferritin and hemosiderin
  • Circulating iron is loosely bound to the transport protein transferrin
slide12

Platelets

if you get cut:-

  • platelets produce

tiny fibrin threads

  • these form a web-like

mesh that traps blood

cells.

  • these harden forming a clot, or "scab."
  • 150,000 to 400,000 per mm3
thrombopoiesis
Thrombopoiesis
  • Thrombocytes or platelets
    • Derived from the megakaryocyte
  • Thrombopoietin
    • Formed in the liver and is similar to erythorpoeitin
  • Megakaryocytes fragment to form platelets
    • The spleen takes up about 1/3 of the platelets
      • Forms red plulp
hemostasis
Hemostasis

= Opposite of hemorrhage  stops bleeding

Too little hemostasis too much bleeding

Too much hemostasis thrombi / emboli

Three major steps:

  • Vasoconstriction
  • Platelet plug Temporarily blocks the hole
    • Platelet-derived cytokines further the process
  • Coagulation cascade (= clot formation seals hole until tissues repaired)
    • Two pathways: Extrinsic and Intrinsic
  • After vessel repair, plasmin dissolves the clot
steps of hemostasis
Steps of Hemostasis

Vessel damage exposes collagen fibers

Platelets adhere to collagen & release factors

local vasoconstriction & platelet aggregation

+ feedback loop

decreased blood flow

platelet plug formation

steps of hemostasis cont
Steps of Hemostasis cont.
  • Two coagulation pathways converge onto common pathway
    • Intrinsic Pathway. Collagen exposure. All factors needed are present in blood. Slower.
    • Extrinsic Pathway. Uses Tissue Factors released by injured cells and a shortcut.
  • Usually both pathways are triggered by same tissue damaging events.
  • The different factors can be subject to a variety of problems
    • Hemophilia
    • Hypercoagulable states
the role of the platelet
The Role of the Platelet
  • VIII – Von Willebrand Factor
    • vWF can bind to exposed collagen and also to receptors on the surface of platelets
  • Platelets are delivered to the damage site and bind to vWF = platelet activation
  • Platelet Plug
    • Platelets expose receptors
    • Degranulation – release of ADP to promote platelet activation (pa)
    • Releases Thromboxane A2to promote pa
structure of blood clot
Structure of Blood Clot

Plasmin, trapped in clot,

will dissolve clot by fibrinolysis

Clot formation limited to area of injury: Intact endothelial cells release anticoagulants (heparin, antithrombin III, protein C).

SEM x 4625

clot busters anticoagulants
Dissolve obsolete or unwanted clots

Enhance fibrinolysis

Examples:Urokinase, Streptokinase & t-PA

Prevent coagulation by blocking 1 or more steps in fibrin forming cascade

Inhibit platelet adhesion plug prevention

Examples:

Coumadin (warfarin) blocks Vit K

EDTA chelates Ca2+

Aspirin prevents platelet plug

Clot Busters & Anticoagulants
the fibrinolytic system
The Fibrinolytic System
  • tPA – tissue plasminogen activator
    • Activates plasminogen to become plasmin
    • Plasmin is a proteolytic enzyme
      • Degrades fibrinogen, fibrin and several clotting factors
bleeding disorders terminology
Bleeding Disorders - Terminology
  • Petechiae
    • Pinpoints of hemorrhage seen in the skin, or in a post-mortem organ section, such as the brain
  • Purpura
    • Larger and sometimes less-regular areas of bleeding in the skin
  • Ecchymoses
    • Still larger (over 2cm) areas of bleeding
      • Commonly called bruises
  • Hematoma
    • A large volume of blood trapped in a soft tissue
slide25

Petechial Hemorrhages on the Heart found when a coagulopathy is due to a low platelet count. They can also appear following sudden hypoxia.

platelet disorders thrombocytopenia
Platelet Disorders - Thrombocytopenia
  • The inability to mount an adequate hemostatic response
    • Insufficient platelets
      • Under 100,000 mm3
    • May result from marrow suppression due to:
      • Thiazide diuretics, certain anticibiotics, chronic alcohol abuse, tumor metastases, and dietary deficiencies of folic acid and vitamin B12
  • Idiopathic Thrombocytopenia Purpura
    • Autoimmune disorder
      • Petechiae, purpura, often arises after a viral infection
genetic clotting factor disorders
Genetic Clotting Factor Disorders
  • Von Willebrand’s Disease
    • Interferes with platelet binding to the subendothelial surfaces
      • Autosomal dominant inheritance
      • Recurring bouts of gastric and intestinal bleeding
      • Excessive menstrual hemorrhage
        • Transfusion of vWF
  • Hemophilia
    • Defects of factor VIII – Hemophilia A
    • Defect of factor IX – Hemophilia B
      • Both found on X chromosome
hemophilia and acquired clotting factor disorders
Hemophilia and Acquired Clotting Factor Disorders
  • Hemophiliacs suffer from bleeding into the larger weight-bearing joints
    • Ankylosis
  • Impaired Hepatic Synthesis
    • Deficiency of vitamin K
      • Produced in the colon by e.coli
      • Lipid-soluble and absorbed in the bile
        • Liver damage may decrease vit K in the blood
hemophilia
Hemophilia
  • It is sometimes called Christmas disease after Stephen Christmas, the first patient described with this disease. In addition, the first report of its identification was published in the Christmas edition of the British Medical Journal.
  • In more recent history, royal watchers know that Queen Victoria of Britain's son Leopold had hemophilia, and that two of her daughters, Alice and Beatrice, were carriers of the gene. Through them, hemophilia was passed to the royal families in Spain and Russia, leading to one of the most famous young men with the disease, Tsar Nicholas II's only son Alekei.
erythrocytes rbcs
Erythrocytes (RBCs)
  • Biconcave disc
    • Folding increases surface area (30% more surface area)
    • Plasma membrane contains spectrin
      • Give erythrocytes their flexibility
  • Anucleate, no centrioles, no organelles
    • End result - no cell division
    • No mitochondria means they generate ATP anaerobically
      • Prevents consumption of O2 being transported
  • Filled with hemoglobin (Hb) - 97% of cell contents
    • Hb functions in gas transport
      • Hb + O2 HbO2 (oxyhemoglobin)
  • Most numerous of the formed elements
    • Females: 4.3–5.2 million cells/cubic millimeter
    • Males: 5.2–5.8 million cells/cubic millimeter
erythrocyte function
Erythrocyte Function
  • Erythrocytes are dedicated to respiratory gas transport
  • Hemoglobin reversibly binds with oxygen and most oxygen in the blood is bound to hemoglobin
  • Composition of hemoglobin
    • A protein called globin
      • made up of two alpha and two beta chains
    • A heme molecule
      • Each heme group bears an atom of iron, which can bind to one oxygenmolecule
      • Each hemoglobin molecule thus can transport four molecules of oxygen
hemoglobin
Hemoglobin
  • Oxyhemoglobin – hemoglobin bound to oxygen
    • Oxygen loading takes place in the lungs
  • Deoxyhemoglobin – hemoglobin after oxygen diffuses into tissues (reduced Hb)
  • Carbaminohemoglobin – hemoglobin bound to carbon dioxide
    • Carbon dioxide loading takes place in the tissues
fate and destruction of erythrocytes
Fate and Destruction of Erythrocytes
  • The life span of an erythrocyte is 100–120 days
    • Travels about 750 miles in that time (LA to Albuquerque)
  • Old erythrocytes become rigid and fragile, and their hemoglobin begins to degenerate
  • Dying erythrocytes are engulfed by macrophages
  • Heme and globin are separated
    • Iron is removed from the heme and salvaged for reuse
      • Stored as hemosiderin or ferritinin tissues
      • Transported in plasma by beta-globulins as transferrin
fate and destruction of erythrocytes1
Fate and Destruction of Erythrocytes
  • Heme is degraded to a yellow pigment called bilirubin
    • Liver secretes bilirubin into the intestines as bile
    • Intestines metabolize bilirubin into urobilinogen
    • Urobilinogen leaves the body in feces, in a pigment called stercobilin
  • Globin is metabolized into amino acids which are then released into the circulation
laboratory assessment of blood cells
Laboratory Assessment of Blood Cells
  • Complete Blood Count (CBC) includes
    • White Blood Cell Count (WBC)
    • Red Blood Cell Count (RBC)
    • Percentage of white cells that are neutrophils, eosinophis or basophils (white cell differential count)
    • Amount of hemoglobin
    • Hematocrit
      • Percent of blood volume occupied by red blood cells
erythrocyte disorders1
Erythrocyte Disorders
  • Polycythemia
    • Abnormal excess of erythrocytes
      • Increases viscosity, decreases flow rate of blood
  • Anemia
    • Abnormally low hemoglobin in blood
      • Caused by decreased numbers of RBC’s, decreased amount of hemoglobin in RBC’s, or both
anemia
ANEMIA
  • Hemoglobin level falls below normal range:
    • 14-18 g/dl for males and 12-16 g/dl for females
  • Signs and symptoms of hypoxia
    • Pallor, weakness, lethargy, and exercise intolerance
    • May affect cardiac rhythms and cause hepatic necrosis
red blood cell indices
Red Blood Cell Indices
  • Mean Corpuscular Volume (MCV)
    • Average size of a RBC
  • Mean Cell Hemoglobin (MCH)
    • Average amount of hemoglobin per RBC
  • Mean Corpuscular Hemoglobin Concentration (MCHC)
    • Average concentration of hemoglobin in all RBCs
red cell indices used to diagnose disease
Red Cell Indices Used to Diagnose Disease
  • Macrocytic
    • Red Blood Cells may be too large
  • Microcytic
    • Red Blood Cells may be too small
  • Normocytic
    • Red Blood Cells are normal size
  • Normochromic
    • Normal amount of hemoglobin
  • Hypochromic
    • Too little hemoglobin
slide54

Anemia

?

Production?

Survival/Destruction?

causes of anemia
Causes of Anemia

Decreased erythrocyte production

  • Decreased erythropoietin production
  • Inadequate marrow response to erythropoietin

Erythrocyte loss

  • Hemorrhage
  • Hemolysis
impaired erythocyte production
Impaired Erythocyte Production
  • Iron Deficiency
    • Erythrocytes are small (microcytic) and deficient in hemoglobin (hypochromic)
    • Low MCV and MCHC values
  • Vitamin B12 Deficiency (cobalamin)
    • Vit B12 is required for normal DNA synthesis
    • May be due to decreased intrinsic factor (IF)
    • Mitosis in the marrow progenitor lines is suppressed
      • RBCs are macrocytic, normochromic
      • Increased MCV and normal MCHC
pernicious anemia
Pernicious Anemia
  • Pernicious anemia is a decrease in red blood cells that occurs when the body cannot properly absorb vitamin B12 from the GI Tract
  • Common causes include:
    • Weakened stomach lining (atrophic gastritis)
    • The body's immune system attacking the cells that make intrinsic factor (autoimmunity against gastric parietal cells) or intrinsic factor (IF) itself
symptoms
Symptoms
  • Diarrhea or constipation
  • Fatigue
  • Loss of appetite
  • Pale skin
  • Shortness of breath, mostly during exercise
  • Swollen, red tongue or bleeding gums
  • Neuropathy
folic acid deficiency
Folic Acid Deficiency
  • Produces a megaloblastic anemia similar to cobalamin deficiency
    • No neuropathy
    • Due to poor diet/high-demand states
hemolytic anemia rbc destruction
Hemolytic Anemia – RBC Destruction
  • Hemolytic anemias are either acquired or congenital.
  • Hemolytic anemia is a condition in which there are not enough RBCs in the blood
    • Due to premature RBC destruction-hemolysis
  • Hemolytic anemia can result from:
    • infection
    • certain drugs
    • autoimmune disorders in which the body attacks and destroys its own red blood cells – abnormal amounts of hemoglobin-Hemoglobinopathies
        • Sickle Cell Anemia
        • Thalassemia
symptoms of hemolytic anemia
Symptoms of Hemolytic Anemia
  • Dark Urine
  • Enlarged spleen
  • Fatigue
  • Fever
  • Pale skins color
  • Rapid heart rate
  • Shortness of breath
  • Yellow skin color (jaundice)
  • Chills
sickle cell anemia
Sickle Cell Anemia
  • Normal hemoglobin - HbA
  • Abnormal hemoglobin - HbS
  • Single base pair mutation results in a single amino acid change.
  • Under low oxygen, HgSbecomes insoluble forming long polymers
    • Distorts the cell which becomes less flexible and leads to membrane changes (“sickling”) and vasoocclusion
red blood cells from sickle cell anemia
Red Blood Cells from Sickle Cell Anemia
  • Deoxygenation ofHbSerythrocytes leads to intracellular hemoglobin polymerization, loss of deformability and changes in cell morphology.

OXY-STATE

DEOXY-STATE

sickle cell anemia1
Sickle Cell Anemia
  • Cells get stuck in the microcirculation
    • Obstructs flow and causes ischemic injury
  • Sickle cells have a life span of 20 days
    • Leads to chronic anemia
  • Sickle Cell Crisis:
    • Acute sickling episodes that block flow, pose threat of widespread ischemia and organ damage
    • Pain is due to bone necrosis caused by blood vessel occlusion
thalassemia
Thalassemia
  • Genetic defect in hemoglobin synthesis
    •  synthesis of one of the 2 globin chains ( or )
    • Imbalance of globin chain synthesis leads to depression of hemoglobin production and precipitation of excess globin (toxic)
    • “Ineffective erythropoiesis”
    • Ranges in severity from asymptomatic to incompatible with life (hydrops fetalis)
    • Found in people of African, Asian, and Mediterranean heritage
thalassemias
Thalassemias
  • Dx:
    • Microcytic/Hypochromic, misshapen RBCs
    • -thalassemiawill have an abnormal Hgb electrophoresis (HbA2,HbF)
    • Fe stores are usually elevated
thalassemia1
Thalassemia
  • The oxygen depletion in the body becomes apparent within the first 6 months of life.
  • If left untreated, death usually results within a few years.
  • Note the small, pale (hypochromic), abnormally-shaped red blood cells. The darker cells likely represent normal RBCs from a blood transfusion.
thalassemia2
Thalassemia
  • The only treatments are stem cell transplant and simple transfusion.
  • Chelation therapy to avoid iron overload has to be started early.
polycythemia
Polycythemia
  • Primary absolute polycythemia
    • Marrow stem cell lines proliferate without an increased EPO
      • Benign tumor of the marrow
polycythemia1
Polycythemia
  • Absolute polycythemia (Secondary)
    • Increased red cell concentration in the blood with normal plasma volume
      • Overproduction of erythrocytes by the bone marrow
        • Elevated EPO
          • May be due to elevation, renal tumors, renal hypoxia due to restricted blood flow
polycythemia2
Polycythemia
  • Relative polycythemia
    • Normal RBC numbers suspended in a reduced plasma volume
      • Dehydration
      • Extensive skin burns
      • Diarrhea or diuresis
      • Pregnancy
marrow production myelodysplasia
Marrow Production - Myelodysplasia
  • Used to be referred to as “Preleukemia”
    • Most commonly in the elderly.
  • Occurs when something goes wrong in your bone marrow
signs and symptoms of myelodysplasia
Signs and Symptoms of Myelodysplasia
  • Fatigue
  • Shortness of breath
  • Unusual paleness (pallor) due to anemia
  • Easy or unusual bruising or bleeding
  • Pinpoint-sized red spots just beneath your skin caused by bleeding (petechiae)
  • Frequent infections
causes
Causes
  • Caused by poorly formed or dysfunctional blood cells due to either
    • Unknown causes
    • Chemical exposure
marrow production myelophthisic
Marrow Production - Myelophthisic
  • Myelophthisic anemia is a normocytic-normochromic anemia that occurs when normal marrow space is infiltrated and replaced by nonhematopoietic or abnormal cells.
  • Causes:
    • Most often due to replacement of the bone marrow by metastatic cancers such as breast or prostate; less often, kidney, lung, adrenal, or thyroid.
  • Marrow fibrosis often occurs.
  • Splenomegaly may develop.
marrow production aplastic anemia
Marrow Production - Aplastic Anemia

The body stops producing enough new blood cells.

  • Signs and symptoms may include:
    • Fatigue
    • Shortness of breath with exertion
    • Rapid or irregular heart rate
    • Pale skin
    • Frequent or prolonged infections
    • Unexplained or easy bruising
    • Nosebleeds and bleeding gums
    • Prolonged bleeding from cuts
    • Skin rash
    • Dizziness
    • Headache
slide88
Here we see a sample of bone marrow in a patient with Aplastic Anemia. Notice there are very few cells except for the fat cells
slide89

Factors that can temporarily or permanently injure bone marrow and affect blood cell production include:

Acquired

  • Radiation and chemotherapy treatments
  • Exposure to toxic chemicals.
  • Exposure to benzene
  • Use of certain drugs even some antibiotics.
  • Autoimmune disorders
  • Viral infections
    • Epstein Barr, CMV, Parvovirus B19, HIV
  • Pregnancy.
  • Unknown factors. This is called idiopathic aplastic anemia.
marrow production aplastic anemia1
Marrow Production - Aplastic Anemia

Hereditary

  • Fanconi
    • a rare, inherited blood disorder that leads to bone marrow failure.
  • Diamond-Shwachman
    • a rare autosomal recessive disorder characterized by exocrine pancreatic insufficiency, bone marrow dysfunction
marrow production aplastic anemia2
Marrow Production - Aplastic Anemia

Treatment

  • Most patients require red cell transfusions.
  • Bone MarrowTransplantwhen possible.
  • Stem Cell Transplant
  • Medication: Bone Marrow Stimulants
    • Sargramostim(Leukine)
    • Filgrastim(Neupogen)
    • Pegfilgrastim(Neulasta)
    • Epoetinalfa (Epogen, Procrit)
leukemia
Leukemia
  • Primary malignant tumors of leukocyte precursors in the marrow
  • Proliferating cells in the marrow in varying degrees of differentiation spill over into the blood
  • Signs include:
    • Susceptibility to infection
    • Neutropenia and agranulocytosis
    • Failure of normal hemostasis = blood loss
    • Thrombocytopenia
    • Metasasis to the spleen, liver, meninges and lymph nodes is common
acute lymphocytic leukemia all
Acute Lymphocytic Leukemia (ALL)
  • Predominantly seen in children and adolescents
    • Anemias due to inadequate erythropoiesis
    • Progressive weakness and lethargy
    • Throbocytopenia
    • Bone pain
    • Infection
    • CerivcalLymphadenopathy
  • Treated with chemotherapy and bone marrow transplants
acute myeloblastic leukemia aml
Acute Myeloblastic Leukemia (AML)
  • ALL and AML are clinically similar
    • Prognosis is more optimistic for AML
chronic lymphocytic leukemia cll
Chronic Lymphocytic Leukemia (CLL)
  • The most common of the leukemias
  • Above 50 years of age
  • Onset is gradual
    • Fatigue, weight loss, anorexia
  • B lymphocytes most involved – very high but nonfunctional
    • Deficiency in antibody production
  • Chemotherapy prolongs survivals
chronic myeloblastic leukemia cml
Chronic Myeloblastic Leukemia (CML)
  • 25 to 60 years of age
  • Granulocytes are very high
  • Liver and spleen infiltration – massive splenomegaly
  • Blast Crisis:
    • Large number of leukocytes enter the blood stream
    • Rapid patient deterioration
    • Damaged chromosome 22
      • The Philadelphia chromosome
    • No therapeutic intervention
lymphoma
Lymphoma
  • Solid malignant tumors arising in the cells of lmphoid tissue
  • The tumor replaces marrow and lymphoid tissue
  • Invasive
  • Immune deficiencies…infections
  • Anemia
  • Lymphadema
  • Splenomegaly
lymphomas
Lymphomas
  • Hodgkin’s Lymphoma
    • Most often in young adults
      • Single, painless, cervical lymph node
      • Spreads to adjacent nodes and then to lymphoid organs
      • Reed-Sternberg (RS) cell
        • Large, multinucleate cell
    • Genetics vs Epstein Barr Virus
lymphoma1
Lymphoma
  • Non-Hodgkin’s Lymphoma
    • These tumors arise in B and T lymphocyte lines in particular
    • Lymph nodes are primary site
red cell destruction membrane disorders
Red cell destruction – membrane disorders
  • Hereditary spherocytosis
  • Hereditary elliptocytosis
  • Hereditary pyropoikilocytosis
  • Southeast Asian ovalocytosis
review red blood cell disorders red cell destruction enzymopathies
Review red blood cell disordersRed cell destruction – enzymopathies
  • G6PD deficiency
  • Pyruvate kinase deficiency
  • Other very rare deficiencies
deoxyhemoglobin s polymer structure
Deoxyhemoglobin S Polymer Structure

A) Deoxyhemoglobin S

14-stranded polymer

(electron micrograph)

B) Paired strands of

deoxyhemoglobin S

(crystal structure)

C) Hydrophobic pocket

for 6b Val

D) Charge and size prevent

6bGlu from binding.

Dykes, Nature 1978; JMB 1979

Crepeau, PNAS 1981

Wishner, JMB 1975

transfusion in sickle cell
Transfusion in Sickle Cell
  • In severely anemic patients, simple transfusionsshould be used.
  • Common causes of acute anemia:
  • acute splenic sequestration
  • transient red cell aplasia
  • Hyperhemolysis (infection, acute chest syndrome, malaria).
  • If the patient is stable and the reticulocyte count high, transfusions can (and should) be deferred.
transfusion in sickle cell exchange transfusion
Transfusion in Sickle Cell(exchange transfusion)
  • A comprehensive transfusion protocol should include accurate records of the patient’s red cell phenotype, alloimmunization history, number of units received, serial Hb S percentages, and results of monitoring for infectious diseases and iron overload.
  • Transfusions are used to raise the oxygen-carrying capacity of blood and decrease the proportion of sickle red cells.
transfusion in sickle cell exchange transfusion1
Transfusion in Sickle Cell(exchange transfusion)
  • Transfusions usually fall into two categories:
  • episodic, acute transfusions to stabilize or reverse complications.
  • long-term, prophylactic transfusions to prevent future complications.
transfusion in sickle cell exchange transfusion2
Transfusion in Sickle Cell(exchange transfusion)
  • episodic, acute transfusions to stabilize or reverse complications.
  • Limited studies have shown that aggressive transfusion (get Hgb S < 30%) may help in sudden severe illness.
  • May be useful before general anesthesia.

Vichinsky et al., NEJM 1995

transfusion in sickle cell1
Transfusion in Sickle Cell

Inappropriate uses of transfusion:

  • Chronic steady-state anemia
  • Uncomplicated pain episodes
  • Infection
  • Minor surgery
  • Uncomplicated pregnancies
  • Aseptoic necrosis
transfusion in sickle cell exchange transfusion3
Transfusion in Sickle Cell(exchange transfusion)
  • Except in severe anemia, exchange transfusion offers many benefits and is our first choice
  • Phenotypically matched, leukodepleted packed cells are the blood product of choice.
  • A posttransfusion hematocrit of 36 percent or less is recommended.
  • Avoid hyperviscosity, which is dangerous to sickle cell patients.
iron overload and chelation
Iron overload and chelation
  • Can occur in any patient requiring chronic transfusion therapy or in hemochromatosis.
  • Liver biopsy is the most accurate test though MRI is being investigated.
  • Ferritin is a good starting test.
  • 120 cc of red cells/kg of body weight is an approximate point at which to think about iron overload
iron overload and chelation1
Iron overload and chelation
  • Chelator, deferoxamine
    • 25 mg/kg sq per day over 8 hours.
    • Supplementation with vitamin C may aid excretion.
    • Otooxicity, eye toxicity, allergic reactions.
    • Discontinue during an infection.
  • Oral chelators are in development.
conclusions
Conclusions
  • Transfuse for any severe anemia with physiologic compromise.
  • Decide early whether transfusion will be rare or part of therapy.
  • Avoid long-term complications by working with your blood bank and using chelation theraoy.
anemia insufficient erythrocytes
Anemia: Insufficient Erythrocytes
  • Hemorrhagic anemia – result of acute or chronic loss of blood
  • Hemolytic anemia – prematurely ruptured erythrocytes
  • Aplastic anemia – destruction or inhibition of red bone marrow
slide116

Physical Characteristics of Blood

  • Average volume of blood:
    • 5–6 L for males; 4–5 L for females (Normovolemia)
    • Hypovolemia - low blood volume
    • Hypervolemia - high blood volume
  • Viscosity (thickness) - 4 - 5 (where water = 1)
  • The pH of blood is 7.35–7.45; x = 7.4
  • Osmolarity = 300 mOsm or 0.3 Osm
    • This value reflects the concentration of solutes in the plasma
  • Salinity = 0.85%
    • Reflects the concentration of NaCl in the blood
  • Temperature is 38C, slightly higher than “normal” body temperature
  • Blood accounts for approximately 8% of body weight
slide117

Composition of Blood

  • 2 major components
    • Liquid = plasma (55%)
    • Formed elements (45%)
      • Erythrocytes, or red blood cells (RBCs)
      • Leukocytes, or white blood cells (WBCs)
      • Platelets - fragments of megakaryocytes in marrow
slide119

Blood Plasma

  • Blood plasma components:
    • Water = 90-92%
    • Proteins = 6-8%
      • Albumins; maintain osmotic pressure of the blood
      • Globulins
        • Alpha and beta globulins are used for transport purposes
        • Gamma globulins are the immunoglobulins (IgG, IgA, etc)
      • Fibrinogen; a clotting protein
    • Organic nutrients – glucose, carbohydrates, amino acids
    • Electrolytes – sodium, potassium, calcium, chloride, bicarbonate
    • Nonprotein nitrogenous substances – lactic acid, urea, creatinine
    • Respiratory gases – oxygen and carbon dioxide
anemia1
Anemia
  • Anemia – blood has abnormally low oxygen-carrying capacity
    • It is a symptom rather than a disease itself
      • Due to some underlying condition
    • Blood oxygen levels cannot support normal metabolism
    • Signs/symptoms include fatigue, paleness, shortness of breath, and chills
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Morphological Approach(big versus little)

First, measure the size of the RBCs:

    • Use of volume-sensitive automated blood cell counters, such as the Coulter counter. The red cells pass through a small aperture and generate a signal directly proportional to their volume.
    • Other automated counters measure red blood cell volume by means of techniques that measure refracted, diffracted, or scattered light
    • By calculation from an independently-measured red blood cell count and hematocrit:
  • MCV  (femtoliters) = 10 x HCT(percent) ÷ RBC (millions/µL)
slide122

Diagnosis of Anemia

CBC and Determination of Red Blood Cell Indices

  • Different types of Anemia are generally characterized by red blood cells of a certain size
    • For Example, small (microcytic, low MCV) RBCs occur with iron deficiency
      • RBCs contain less hemoglobin and are pale (hypochromic, low MCHC)
underproduction morphological approach
Underproduction (morphological approach)

MCV>115

  • B12, Folate
  • Drugs that impair DNA synthesis (AZT (Zidovudine, chemo)
  • MDS (myelodysplastic syndromes)
    • Ineffective production (or dysplasia) of the myeloid class of blood cells

MCV = 100 - 115

  • Ditto
  • Endocrinopathy (hypothyroidism)
  • Reticulocytosis
    • Increased number of immature RBCs
underproduction
Underproduction

Normocytic

  • Anemia from a chronic disease
  • Renal failure

Microcytic

  • Iron deficiency
  • Thalassemia trait
    • abnormal form of hemoglobin
  • Anemia due to chronic disease (30-40%)
  • Sideroblastic anemia
    • bone marrow produces ringed sideroblasts rather than healthy RBCs
transfusion in sickle cell controversy
Transfusion in Sickle Cell(Controversy!)
  • Used correctly, transfusion can prevent organ damage and save the lives of sickle cell disease patients.
  • Used unwisely, transfusion therapy can result in serious complications.

http://www.nhlbi.nih.gov/health/prof/blood/sickle/index.htm

transfusion in sickle cell controversy1
Transfusion in Sickle Cell(Controversy!)
  • Simpletransfusion – give blood
  • Partial exchange transfusion - remove blood and give blood
  • Erythrocytapheresis – use apheresis to maximize blood exchange
  • When to use each method?
transfusion in sickle cell2
Transfusion in Sickle Cell
  • In general, patients should be transfused if there is sufficient physiological derangement to result in heart failure, dyspnea, hypotension, or marked fatigue.
  • Tends to occur during an acute illness orwhen hemoglobin falls under 5 g/dL.
transfusion in sickle cell exchange transfusion4
Transfusion in Sickle Cell(exchange transfusion)

Exchange transfusion:

  • Bleed one unit (500 ml), infuse 500 ml of saline
  • Bleed a second unit and infuse two units.
  • Repeat. If the patient has a large blood mass, do it again.
transfusion in sickle cell chronic transfusion therapy
Transfusion in Sickle Cell(chronic transfusion therapy)
  • Stroke
  • Chronic debilitating pain
  • Pulmonary hypertension
  • Setting of renal failure and heart failure
transfusion in sickle cell chronic transfusion therapy1
Transfusion in Sickle Cell(chronic transfusion therapy)

Controversial uses:

  • Prior to contast media exposure
  • Sub-clinical neurological damage
  • Priapism
  • Leg Ulcers
  • Pregnancy
review red blood cell disorders
Marrow production

Thalassemias

Myelodysplasia

Myelophthisic

Aplasticanemia

Nutritional deficiencies

Red cell destruction

Hemoglobinopathies

Enzymopathies

Membrane disorders

Autoimmune

Review red blood cell disorders