Introduction To Hematology

1
Introduction To Hematology

• Brandon West, MS PA-C
• E-mail bdwpac_at_gmail.com

2
Introduction and Objectives

• Hematology
• Study of normal and pathologic aspects of blood
• Be familiar with concepts essential for practice
  of primary care medicine
• Be able to interpret complete blood count (CBC)
  reports
• Recognize and treat common blood disorders
• Know when to request hematology consultation
• Ace your examination

3
Topics

• Hematopoiesis
• Complete blood count (CBC)
• Anemia
• Polycythemia
• Leukopenia
• Leukemia and lymphoma
• Myeloma
• Coagulation
• Transfusion
• Case studies
• Ask questions at any time!

4
Blood

• Suspension of cells in a solute of water,
  proteins, and electrolytes
• Average volume is 5 liters
• 70mL per kg body weight
• Plasma
• Blood from which the cellular components (RBCs,
  WBCs, platelets) have been removed by centrifuge
• Color is yellow
• Contains coagulation proteins (clotting factors)

5
Hematopoiesis

• Development of blood cells and other formed
  elements
• Sites vary throughout development
• Fetal yolk sac, liver, spleen
• Pediatric axial and appendicular skeleton
• Adult axial skeleton (sternum and pelvis)
• Stem cells
• Primitive self-replicate and differentiate to
  become increasingly specialized progenitor cells
  which form mature cells
• Process regulated by growth factors
  (interleukins, erythropoietin, thrombopoietin,
  G-CSF)
• Early lineage division between progenitors for
  lymphoid and myeloid cells

6
Hematopoiesis
7
Complete Blood Count

• White blood cells (WBC)
• Differential
• Neutrophils, lymphocytes, monocytes, eosinophils,
  basophils, bands
• Must specify whether to include with CBC order
• Red blood cells (RBC, HGB, HCT)
• Platelets
• Mean corpuscular volume (MCV)
• Red cell distribution width (RDW)

8
Red Blood Cells

• Transport oxygen via hemoglobin from lungs to
  peripheral tissues and organs
• Normal lifespan 120 days

9
Reticulocyte Count

• Reticulocytes
• Immature red blood cells
• Measurement assists in determining cause of
  anemia
• Normal 1-2
• Must correct for degree of anemia
• Observed retic count (Actual HCT Normal HCT)
  Corrected retic count
• Low suggests decreased production (i.e.
  nutritional or bone marrow problem)
• High suggests bleeding or premature destruction
  of red blood cells (i.e. hemolysis)

10
Red Blood Cells

• Peripheral blood smear
• Normal

11
Red Blood Cells

• Erythropoietin (EPO)
• Growth factor produced by kidneys that is
  essential for RBC production and release
• Sense tissue oxygen content
• EPO increases when oxygen delivery to kidneys
  falls in setting of anemia and hypoxemia
• Response limited or absent in patients with
  kidney disease
• Erythropoietin Stimulating Agents (ESA)
• Procrit and Aranesp
• Specific indications
• Black box warning

12
Anemia

• Condition resulting from decrease in total body
  erythrocyte mass
• Defined by measurement of hemoglobin
  concentration
• Normal range
• Males 14-16 g/dL
• Females 12-14 g/dL
• Almost 1/3 of the world population is anemic!

13
Anemia

• Manifestations related to duration and severity
  of anemia
• Body has physiologic responses to chronic anemia
  such that many patients are asymptomatic until
  hgb lt 8 g/dL
• Symptoms
• Easy fatigue
• Lightheadedness
• Headache
• Tinnitus
• Fainting
• Dyspnea on exertion
• Signs
• Pallor
• Tachycardia
• Systolic ejection murmur
• Orthostatic hypotension

14
Anemia

• Mechanisms
• Blood loss / hemorrhage
• Must be initial consideration in ALL anemic
  patients
• Gastrointestinal tract, menstruation
• Hemolysis
• Shortened RBC survival time not explained by
  bleeding
• Details later
• Decreased production (hypoproliferative)
• Nutritional deficiency (iron, B12, and folate)
• Systemic illness (CKD, cancer, rheumatologic
  disease, etc.)
• Bone marrow disorders
• Determining reticulocyte count and MCV are first
  steps in determining etiology

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Microcytic Anemia

• Microcytosis small cells (MCV lt80)
• Most common type of anemia encountered in primary
  care
• Differential diagnosis
• Hemoglobinopathy (inherited)
• Iron deficiency
• Chronic disease (may also be normocytic)
• Inflammation
• Lead poisoning
• Check iron studies for clarification
• Be familiar with interpretation (see next slide)

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Microcytic Anemia

• Peripheral blood smear
• Microcytosis, Hypochromic

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Microcytic Anemia
RDW is often elevated in iron deficiency anemia
look for this along with low MCV on CBC report
18
Iron Deficiency

• Most common cause of anemia
• Etiology
• Blood loss (GI or GU)
• Rule out cancer (FOBT, colonoscopy?)
• Poor dietary intake
• Malabsorption
• Increased demand
• Pica
• Oral replacement
• 60 mg elemental iron per day response in 2-3
  months
• OTC and Rx formulations
• If no response or poor tolerance, consider
  hematology referral for iron dextran (Infed)

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Thalassemia Basics

• Genetic disorder
• Causes absent or decreased synthesis of the
  affected globin polypeptide chain
• Alpha
• Beta
• Diagnosed by hemoglobin electrophoresis

20
Alpha Thalassemia

• Silent carrier 1 gene inactive
• Alpha thalassemia trait 2 genes inactive
• Asymptomatic mild anemia
• Hgb H disease 3 genes inactive
• Splenomegaly marked microcytic/hypochromic
  anemia
• Hydrops fetalis 4 genes inactive
• No fetal or adult hgb
• Spontaneous abortion or neonatal death not
  compatible with life

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Beta Thalassemia

• Beta Thalassemia Minor
• Asymptomatic microcytosis
• Increased Hgb A2
• Target cells
• Treatment genetic counseling, folate and zinc
  supplementation
• Beta Thalassemia Major
• Diagnosed as infant
• Ineffective erythropoiesis
• Failure to thrive, hepatosplenomegaly, bone
  expansion
• Severe microcytic anemia
• Treatment transfusions, splenectomy, iron
  chelation

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Sideroblastic Anemia

• Mitochondrial defect prevents incorporation of
  iron into hemoglobin ? ineffective erythropoiesis
• Accumulation of iron within red cell nucleus
  forms ringed sideroblasts
• Hereditary or acquired
• Mild or moderate anemia (hgb 8-10 g/dL) usually
  microcytic although MCV may be high if acquired
• Treatment supportive, pyridoxine (vitamin B6)

23
Macrocytic Anemia

• Macrocytosis large cells (MCV gt100)
• Differential diagnosis
• B12 deficiency
• Pernicious anemia
• Folate deficiency
• Myelodysplasia (pre-leukemia)
• ETOH
• Medication effect
• Check vitamin B12, RBC folate, fasting
  homocysteine, and methylmalonic acid (MMA)
• HC and MMA are elevated in subclinical B12 and
  folate deficiency

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Vitamin B12 Deficiency

• Diet is only source absorbed through terminal
  ileum
• Who is at risk?
• Vegans, bariatric surgery, inflammatory bowel
  disease
• Intrinsic factor is required for absorption
• Pernicious anemia (autoimmune)
• Check for intrinsic factor antibody, Schillings
  test
• Key symptoms and signs
• Neuropathy
• Glossitis
• Loss of vibratory sensation
• Dementia
• Management
• Oral replacement not effective
• Cyanocobalamin 1000 mcg IM weekly x 4, then
  monthly (lifelong)
• Nasal spray now available

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Folate Deficiency

• Caused by inadequate intake or poor absorption
• Found in green leafy vegetables absorbed
  through proximal jejunum
• Common in alcoholics
• Only 4 months of stores in human body
• MMA normal but HC elevated
• Management
• Folic acid 1 mg po daily

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Hemolytic Anemia

• History and physical findings
• Review PMH, FH, and medications
• Jaundice
• Abdominal discomfort
• Lab findings
• Elevated reticulocyte count
• Reflects bone marrow compensating for peripheral
  RBC destruction
• Elevated LDH
• Elevated total bilirubin (indirect/unconjugated)
• Decreased haptoglobin
• Abnormal cells on peripheral blood smear
  examination

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Hemolytic Anemia

• Congenital
• Membrane defects
• Hereditary spherocytosis
• Clinical picture variable splenomegaly and
  pigment gallstones common often well-compensated
  anemia
• Spherocytes seen on peripheral smear
• Osmotic fragility test
• Splenectomy is curative
• Hereditary elliptocytosis
• Enzyme defects
• G6PD deficiency
• Affects 10 of world population
• Common in patients of African descent
• Precipitated by stress, infection, drugs, and
  fava beans
• Hemolysis mostly extravascular but may be
  intravascular if severe case

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Hemolytic Anemia

• Congenital
• Sickle cell disease
• RBCs become sickle-shaped ? hemolysis, vascular
  occlusion
• Hgb S gene carried by 8 of African Americans
• 1625 have disease
• Genetic counseling available
• Acute crisis may be triggered by dehydration,
  infection, and physiologic stress last hours to
  days
• Bone pain
• Jaundice
• Priapism
• Chest syndrome
• Complications
• Hemosiderosis
• Skin ulcers
• Renal failure
• Avascular necrosis
• Stroke
• Retinopathy
• Severe infections

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Hemolytic Anemia

• Congenital,
• Sickle cell disease
• Crisis Management
• Hydration
• Pain medication
• Exchange transfusion
• Indications include acute chest syndrome, stroke,
  priapism
• Health maintenance
• Folic acid supplementation
• Highly susceptible to infection with encapsulated
  bacteria
• Pneumococcal vaccination!
• Low threshold for antibiotic therapy prophylaxis
  is standard in children
• Hydroxyurea (Hydrea) may reduce crisis frequency
• Best outcomes when patients are followed by
  specialty center (i.e. Grady)
• Life expectancy only 40-50 years

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Hemolytic Anemia

• Acquired
• Classified according to site of RBC destruction
  and whether mediated by immune system
• Intravascular
• Extravascular
• Autoimmune
• Non-immune
• Many causes be aware of these
• Transfusion of incompatible blood (details later)
• Autoimmune
• Warm (IgG-mediated) most common
• Cold (IgM-mediated)
• Prosthetic valves
• TTP/HUS
• DIC
• Cancer
• Drugs

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Hemolytic Anemia

• Coombs Test (DAT)
• Used to screen for autoimmune hemolytic anemia
• Patient RBCs washed free of plasma and mixed with
  IgG or complement
• Agglutination is a positive result
• Treatment
• Consult hematology
• Folate
• Steroids
• Splenectomy (refractory cases)

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Polycythemia / Erythrocytosis

• Abnormal elevation of hemoglobin
• Rule out relative polcythemia caused by
  contraction of plasma volume, e.g. dehydration
• Primary
• Polycythemia Vera
• RBC production independent of EPO
• EPO level is low / positive JAK-2 is diagnostic
• Uncommon
• May be associated with leukocytosis,
  thrombocytosis, splenomegaly
• Hyperviscosity
• Headache, vertigo, visual changes, mental
  confusion
• Risk of transformation into acute leukemia
• Refer to hematology
• Secondary
• RBC production in response to increased EPO
  production
• EPO level is usually high
• Very common
• Usual etiology is chronic hypoxia (COPD, sleep
  apnea)
• Phlebotomy (250-500 mL) to maintain hct 45-50
  treat underlying problem!

33
White Blood Cells

• Differential
• Neutrophils 45-65
• Segs / Polys
• Lymphocytes 15-40
• Monocytes 2-8
• Eosinophils 0-5
• Basophils 0-3
• Do you remember the physiologic role of each type
  of WBC?

34
Leukopenia

• Neutropenia is most common cause
• Absolute neutrophil count (ANC) lt 1.5 x 109
  cells/L
• Many causes
• Benign racial neutropenia common
• African Americans and Yemenite Jews may have ANC
  as low as 1.0
• Viral infections
• Epstein-Barr, Hepatitis B, HIV
• Drugs
• Careful review of medications be suspicious of
  any medication recently started in patient with
  acute onset neutropenia
• See next slide
• Splenomegaly
• Autoimmune disorders
• SLE (lupus), Rheumatoid Arthritis, etc.
• Bone marrow disorders

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Neutropenia
36
Leukocytosis

• WBC count gt 11,000
• Determine which type of WBC is leading to the
  leukocytosis
• Neutrophilia most common
• Infection
• Connective tissue disorders
• Medications (especially steroids, growth factors)
• Cancer (CML and solid tumors)
• Myeloproliferative disorders
• Cigarette smoking
• Stress (physiologic)
• Pain, seizure, trauma
• Idiopathic

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Leukocytosis

• Patients with acute bacterial infection often
  present with neutrophilia and band formation
  i.e. left shift
• Bands young neutrophils
• Viral infections are usually associated with low
  WBCs leukocytosis may suggest complications
• Ex bacterial pneumonia with underlying influenza
  infection

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Leukocytosis

• Lymphocytosis
• Viral infections
• HBV, HCV, EBV, CMV
• Tuberculosis
• Pertussis
• Drug Reaction
• Stress (physiologic)
• Trauma, MI, cardiac arrest, sickle crisis
• Malignancy
• ALL, CLL, lymphoma

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Chronic Leukemia

• Chronic myelogenous leukemia (CML)
• Translocation between long arms of chromosomes 9
  and 22 Philadelphia Chromosome bcr/abl
  protein
• Patients usually middle-age at diagnosis, average
  age 55 years
• Fatigue, fever, night sweats, abdominal fullness
  (splenomegaly)
• Symptoms of leukostasis may be present if WBC gt
  500,000
• Blurred vision, respiratory distress, priapism
• Three phases of disease
• Early / Chronic phase
• Accelerated
• Blast crisis

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Chronic Leukemia

• CML, continued
• Can you recognize early CML from infection?
• WBC usually lt 50,000 with infection
• WBC average 150,000 at time of diagnosis with CML
• LAP score is decreased with CML
• Splenomegaly NOT present with infection
• Chromosomal abnormality and detection of bcr/abl
  protein by peripheral blood PCR is diagnostic of
  CML
• Treatment
• Refer to hematologist
• Despite very high WBC, not an emergency unless
  leukostasis is suspected
• Imatinib (Gleevec) - released in 2001
• 98 response rate in chronic phase patients
• 80 of patients alive and stable at 7 years
• Allogeneic BMT is only cure
• Reserved for select patients

41
Chronic Leukemia

• Chronic lymphocytic leukemia (CLL)
• Clonal malignancy of B-lymphocytes
• Course usually indolent affects older patients,
  average age at diagnosis is 70 years
• Often found incidentally
• Fatigue, lymphadenopathy common
• Hepatosplenomegaly
• Immunodeficiency is major clinical concern
• Lymphocytes are defective do not make
  antibodies in response to antigens
• Treatment
• Observation
• Indications for therapy include progressive
  fatigue, symptomatic lymphadenopathy, anemia, or
  thrombocytopenia
• Rituximab (Rituxan) and fludarabine /-
  cyclophosphamide is initial approach
• Gamma globulin (IVIG) used in patients with
  recurrent or severe bacterial infections
• Prognosis improving survival is 10-15 years
  with early disease

42
Acute Leukemia

• Acute Myelogenous Leukemia (AML)
• Most common in adults
• Usually no apparent cause
• Exposure to radiation, benzene, and certain
  chemotherapy drugs (alkylators) associated with
  leukemia
• May be de novo or develop as complication of
  underlying myelodysplastic syndrome (MDS)
• Symptoms and signs
• Related to replacement of marrow space by
  malignant WBCs
• Patients often very ill for period of just days
  or weeks
• Skeletal pain
• Bleeding
• Gingival hyperplasia
• Infection
• Pancytopenia with circulating blasts is hallmark
  bone marrow biopsy required
• Auer rods on peripheral smear are pathognomonic

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Acute Leukemia

• AML, continued
• Management
• Immediate referral to hematologist
• Patients often hospitalized for therapy
• Anthracycline (daunorubicin or idarubicin) plus
  cytarabine results in CR in 80 of patients lt 60
  years
• Additional high dose chemotherapy following CR
  leads to cure rate of 35-40
• Acute Lymphocytic Leukemia (ALL)
• More often seen in children

44
Acute Leukemia

• Myeloblast

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Lymphoma

• Hodgkins disease
• Malignancy of B-lymphocytes
• Reed-Sternberg cells
• Various subtypes nodular sclerosing is most
  common
• Bimodal age distribution (20s and 50s)
• Painless lymphadenopathy /-B-symptoms
• Fever, night sweats, weight loss (10 over 6
  months)
• Generalized pruritis
• Ann Arbor staging system based on distribution of
  involved lymph nodes
• Treatment is XRT for very low risk patients
  most will require chemotherapy, i.e. ABVD
• Good prognosis many patients are cured

46
Lymphoma

• Non-Hodgkins Lymphoma (NHL)
• Heterogeneous group of cancers affecting B or T-
  lymphocytes
• Usually classified by histologic grade (low to
  high)
• Follicular lymphoma
• Small lymphocytic lymphoma
• Diffuse large B-cell lymphoma
• Burkitts lymphoma
• Many others
• Painless lymphadenopathy, often involving
  retroperitoneum, mesentery, or pelvis
• Extranodal disease may be present, i.e. skin and
  GI tract
• Diagnosis by tissue biopsy molecular profiling
  assists in classification
• Staging involves CT imaging and sometimes bone
  marrow biopsy
• LDH is important prognostic marker

47
Lymphoma

• NHL, continued
• Treatment
• Observation in select patients
• Chemotherapy
• Immunotherapy (i.e. monoclonal antibodies)
• Rituximab (Rituxan) anti-CD20
• Radiation
• Prognosis
• Low grade lymphoma is often chronic disease with
  remissions and relapses median survival 6-8
  years
• Patients with higher grade lymphoma are often
  treated with curative intention
• International Prognostic Index (IPI) allows for
  risk stratification

48
Myeloma

• Malignancy of plasma cells
• Abnormal paraproteins are created leading to
  systemic problems
• IgG 60
• IgM 20
• Must be able to recognize in primary care setting
• CRAB calcium, renal, anemia, bone
• Primarily disease of elderly (median age 65
  years)
• Males gt Females
• Most common hematologic malignancy among African
  Americans 2 among Caucasians

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Myeloma

• Presentation
• Symptoms usually related to bone pain, anemia, or
  recurrent infections
• Pathologic fractures
• Signs
• Pallor
• Bone tenderness
• Plasmacytoma
• Lab findings
• Anemia
• Rouleaux formation on peripheral smear
• Hypercalcemia
• Total protein elevated with high globulin
  fraction and low albumin
• B2M often elevated important prognostic marker
• Paraprotein (monoclonal gammopathy) detected by
  serum protein electrophoresis
• 15 of cases are non-secretory
• Light chains pass through glomerulus and detected
  in urine detected by urine protein
  electrophoresis

50
Myeloma

• Presentation, continued
• Bone marrow biopsy required
• Shows infiltration of plasma cells into marrow
  space ranging from 20-100
• Chromosomal abnormalities are common
• Diagnosis is made based on specific criteria
  not all monoclocal gammopathies are myeloma
• Skeletal survey shows osteolytic lesions
• Do not confuse with bone scan used for detecting
  skeletal metastases from solid tumors
• Durie-Salmon staging system used to guide initial
  therapy
• Hospitalization indicated for acute renal
  failure, hypercalcemia, or suspicion of spinal
  cord compression
• Disease is not curable although long remissions
  are possible prognosis is improving
• Average survival 6 years

51
Myeloma

• Osteolytic lesions

52
Bleeding Disorders

• Coagulation cascade

53
Bleeding Disorders

• Review coagulation cascade general
  understanding is essential for clinical practice
• Prothrombin time (PT) evaluates extrinsic system
• Factors I, II, V, X, VII
• Activated partial thromboplastin time (PTT)
  evaluates intrinsic system
• Factors I, II, V, X, VIII, IX, XI, XII
• Bleeding time reflects platelet number and
  function

54
Bleeding Disorders

• General approach
• Prolonged PT only
• Warfarin (Coumadin) therapy
• Factor VII deficiency
• Fibrinogen abnormality
• Prolonged PTT only
• Heparin therapy
• Factor VIII deficiency
• Congenital
• Hemophilia A (X-linked)
• 15000 male births
• Male and female carriers no racial predilection
• Acquired
• Factor IX deficiency Hemophilia B / Christmas
  disease
• Lupus anticoagulant
• Antiphospholipid antibodies
• Prolonged PT and PTT
• Usually reflective of general medical condition
  such as DIC, vitamin K deficiency, or liver
  disease
• Disorders of common pathway (rare)

55
Bleeding Disorders

• Approach to patient
• History of trauma? Time between injury and
  bleeding?
• Ask about bleeding at times of life events
• Circumcision
• Tooth eruption
• Dental extraction
• Ear piercing
• Childbirth
• Menstrual cycles
• Family history
• Did you know 30 of patients with hemophilia have
  unremarkable family history?
• Spontaneous mutation of X chromosome

56
Bleeding Disorders

• Patterns of bleeding
• Primary hemostasis platelet and vascular
  function
• Secondary hemostasis clotting factors

57
Bleeding Disorders
Acute hemarthrosis
58
Bleeding Disorders

• von Willebrand Disease
• Most common inherited bleeding disorder
• 1 of population affected
• Deficiency of von Willebrand factor
• Protein that binds platelets together and allows
  for adhesion at site of vascular injury
• Binds to Factor VIII to prolong its half-life in
  circulation
• Bleeding is usually mild to moderate and involves
  skin and mucous membranes
• DDAVP is primary treatment releases vWF and
  factor VIII from storage sites

59
Bleeding Disorders

• Immune Thrombocytopenia (ITP)
• Autoimmune condition antibodies bind platelets
  leading to destruction
• Often found incidentally mild mucosal bleeding,
  petechial rash may be present
• Diagnosis of exclusion must rule out medication
  effect, HIV, and viral hepatitis
• Antiplatelet antibody screening NOT recommended
  due to low sensitivity and specificity
• Bone marrow biopsy NOT required except in elderly
  or refractory cases
• Treatment
• Stop unnecessary medications
• Steroids (Prednisone 1 mg/kg/day x 7-10 days,
  then taper)
• Intravenous immune globulin (IVIG)
• Anti-D (WinRho)
• Splenectomy
• Platelet transfusion used for emergency only as
  may actually exacerbate condition

60
Bleeding Disorders

• Petechiae in patient with acute ITP platelet
  count 10,000

61
Thrombosis

• Venous thromboembolism (VTE)
• DVT and PE are very common in hospital setting
• 20 among general medical patients up to 80 of
  critical care patients
• Be familiar with risk factors
• Obesity
• Oral contraceptives
• Pregnancy
• Tobacco abuse
• Prolonged immobility
• Surgery
• Malignancy
• Consider prophylaxis
• Compression stockings and sequential compression
  devices
• Anticoagulation

62
Thrombosis

• Treatment of VTE
• Parenteral followed by oral (long-term)
  anticoagulation
• LMWH (Lovenox) preferred over UFH for its stable
  pharmacokinetics, ease of dosing, and lower risk
  of allergy
• 1 mg per kg SQ q12h
• Contraindicated in patients with CrCl lt 30
• Consider UFH (short half-life) in patients with
  epidurals or those who are being considered for
  thrombolysis
• Bolus omitted when risk for bleeding is thought
  to be elevated
• Protamine heparin antidote
• Arixtra
• Factor Xa inhibitor
• Easy dosing
• 7.5 mg SQ q24h for patients 50-100 kg weight
• 10 mg SQ q 24h for patients gt 100 kg
• No increased risk in bleeding over LMWH although
  slightly longer half life

63
Thrombosis

• Treatment of VTE, continued
• Warfarin (Coumadin)
• Oral vitamin K antagonist
• Dietary teaching required
• MANY interactions
• Required for minimum of 3 months to reduce risk
  of recurrent thrombosis
• Starting dose usually 5 mg qd but requirements
  lower in elderly, Asian descent, hyperthyroidism,
  CHF, liver disease, malnutrition
• Vitamin K (Mephyton) is antidote for warfarin
  toxicity
• Give 2.5 to 5 mg for INR gt/ 9
• Oral route preferred
• Intravenous infusion must be slow (i.e. over 30
  min) and closely monitored given risk for
  anaphylaxis

64
Thrombosis

• Heparin-Induced Thrombocytopenia (HIT)
• Occurs in 3 of patients exposed to UFH 0.6
  with LMWH
• Drop in platelet count 50 within 5-10 days of
  heparin exposure
• May occur within 48 hours of exposure in those
  previously exposed to drugs
• Thrombosis (NOT bleeding) is of great clinical
  concern
• Thrombotic events detected in about half of HIT
  patients
• Must STOP heparin and consult hematology
• Direct thrombin inhibitor (alternative
  anticoagulant) may be started
• Argatroban
• Refludan

65
Transfusion Medicine

• History
• 19th century experimentation with animal and
  human blood transfusion
• 1900 ABO blood groups first described
• 1936 First US hospital blood bank established
• Blood donation
• Approximately 450 mL whole blood collected
  later processed into RBC, plasma, and platelets
• Apheresis removing whole blood, separating a
  portion, and returning the rest to donor
• Used for plasma and platelet donation
• RBC storage period ranges 35-42 days depending on
  preservative
• Up to 25 of transfused RBCs will be cleared from
  recipient circulation within 24 hours of delivery
  

66
Transfusion Medicine

• Review of physiology
• Anti-A and Anti-B are naturally occurring and
  develop in first months of life in those lacking
  A or B antigens on RBC surface
• Rh factor (D-antigen) absent in 15 of population
• These patients may develop anti-D antibodies
  following pregnancy or transfusion with Rh blood
  leading to severe reactions
• Pretransfusion testing
• ABO and Rh typing
• Antibody screen (Coombs test)
• If positive, further testing required to identify
  specific antibody donor unit is then checked
• Crossmatch
• Donor RBC mixed with recipient serum and
  incubated to check for compatibility
• Type O negative blood may be used in emergency
• Limited supply only 15 of donors

67
Transfusion Medicine

• When to transfuse blood? Use clinical judgment!
• No single hgb/hct rule indications include
• Symptomatic anemia
• Tachypnea, Tachycardia, Cyanosis
• Blood loss (gt15 volume)
• Single unit of PRBC increases hgb by 1.5 g/dL or
  hct by 3-4

68
Transfusion Medicine

• Platelet transfusion
• Platelet count lt 10,000
• Active bleeding in setting of significant
  thrombocytopenia
• Platelet count of 50,000 adequate for most
  surgical procedures
• Single unit will generally raise platelet count
  by 30,000
• Anticipate low yield with splenomegaly, DIC,
  sepsis
• Immune factors may also cause patients to be
  refractory
• Consider ordering HLA-matched platelets
• Relative contraindications
• ITP, TTP, and HIT

69
Transfusion Medicine

• Plasma transfusion
• Indications
• Coagulation factor deficiency
• Consider factor concentrates if available
• Rapid reversal of warfarin effect
• Hemorrhage in patients with liver disease
• DIC (controversial)

70
Transfusion Medicine

• Transfusion Reactions many types!
• Acute hemolytic reaction
• Intravascular hemolysis (hemoglobinuria)
• Fever, chills, pain, nausea, dyspnea, hypotension
• May lead to ARF, DIC, and death
• ABO incompatibility (human error) is most common
  cause
• Proper labeling and patient identification is
  essential for prevention
• STOP transfusion and notify blood bank
  immediately
• Febrile non-hemolytic reaction
• Common in patients with multiple prior
  transfusions
• Caused by cytokines or recipient antibodies to
  donor leukocytes
• Allergic reaction
• May be be related to residual plasma in PRBC
  specimen
• Usually mild pruritis, flushing, urticaria
• Occasional anaphylaxis

71
Transfusion Medicine

• Transfusion reactions
• Hypotensive reaction
• Caused by bradykinin generation
• Patients on ACE inhibitors at higher risk
• Hypotension and tachycardia shortly after
  beginning transfusion BP returns to baseline
  upon interruption
• Usually safe to resume at slower rate upon
  recovery
• Transfusion-related acute lung injury (TRALI)
• Occurs during or shortly after transfusion
• Causes leakage of pulmonary capillaries
  presenting as pulmonary edema in absence of heart
  disease
• Resolves within 48-72 hours
• Mortality rate is 10

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Transfusion Medicine

• What are the risks of infection?
• Hepatitis B
• Risk 1200,000 per unit
• Hepatitis C
• Greatest risk
• Approximately 25 of HCV-infected patients
  worldwide report history of prior blood
  transfusion
• Cytomegalovirus (CMV)
• Very serious in immunocompromised patients
• Specify CMV negative donor in these populations!
• HIV
• Incidence of transfusion-associated disease
  peaked in 1985 now very rare
• Deferral of high risk donors and modern testing
  methods have reduced risk to approximately
  12,000,000 per unit

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References

• Desai, SP. Clinicians Guide to Laboratory
  Medicine. Cleveland Lexi-Comp, 2004.
• McPhee SJ, Papadakis MA. Current Medical
  Diagnosis and Treatment. New York McGraw Hill,
  2010.
• Schmaier AH, Petruzzelli LM. Hematology for the
  Medical Student. Philadelphia Lippincott,
  Williams, and Wilkins, 2003.

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Questions